Practical Management of Hypercholesterolemia

Consultant Pharmacists Impact on the Treatment of Hypercholesterolemia

 

What is Cholesterol, and Why is it of Concern?

 

Guidelines for Treating Hypercholesterolemia

 

Management of Hypercholesterolemia

 

Management of Hypercholesterolemia By Different Health Care Workers.

 

Practical Management of Hypercholesterolemia

 

Community Pharmacists and the Management of Hypercholesterolemia

 

Economic Impact of Pharmacists’ Treatment of Hypercholesterolemia

 

This paper will look at the impact of consultant pharmacists on the treatment of hypercholesterolemia by physicians. Pharmacists have now assumed responsibilities outside the dispensing counter and have been active in monitoring and treating (under protocol) patients with high cholesterol levels (as well as other disease states).

 

A review of the treatment of hypercholesterolemia by physicians by a group of consultant pharmacists who call on physicians offices, and check physicians progress by reference to the achievement of NCEP cholesterol guidelines, has shown that physicians are doing an overall poor job of getting their patients to national cholesterol treatment standards (NCEP guidelines).

 

This paper is therefore essentially a review of the problem, through an analysis of the fact that many patients are not achieving control of cholesterol despite treatment by their physicians. Some of the suspected reasons behind this will be discussed, through a review of related literature with summary of findings of research already conducted on this topic.

 

Firstly, cholesterol and the problems it presents to health will be discussed, and a short review of the various treatment options that are available will be presented, in order to show that hypercholesterolemia is – fundamentally – treatable, but that the management of this treatment is failing.

 

The thesis will then move on to discussing a review of research on the topic of why and how patients tend not to respond well to treatment of hypercholesterolemia by physicians, in terms of the lifestyle changes necessary to reduce cholesterol levels, and the various psychological and cultural barriers to cholesterol reduction.

 

The paper then moves on to a short review of the most relevant research on this topic, and then looks at the role pharmacists have played in helping physicians to reduce cholesterol levels in individuals, through a review of the relevant literature and a review of two short case studies, of the ImPACT program in the United States, and the SCRIP program in Canada.

 

Chapter 1: What is Cholesterol, and Why is it a Concern?

 

Cholesterol is a soft waxy substance that is a natural component of the fats in the bloodstream and in all the cells of the body, and while cholesterol is an essential part of a healthy body, high levels of cholesterol in the blood (known as hypercholesterolemia) increase a person’s risk for cardiovascular disease, which can lead to stroke or heart attack (Anderson et al., 2001). When there is too much cholesterol circulating in the blood, it can create sticky deposits (plaques) along the artery walls, and plaque can eventually obstruct or even block the flow of blood to the brain, heart, and other organs (Anderson et al., 2001). A recent report indicates that more and more Americans have high cholesterol — the condition is most common among those living in Western cultures (Anderson et al., 2001). While heredity may be a factor for some people, increasingly sedentary lifestyles combined with diets high in saturated fats appear to be the main culprits (Anderson et al., 2001).

 

The normal range for total blood cholesterol is between 140 and 200 mg per decilitre (mg/dL) of blood (Anderson et al., 2001). Levels between 200 and 240 mg/dL indicate moderate risk, and levels surpassing 240 mg/dL indicate high risk (Anderson et al., 2001). While total cholesterol level is important, it does not tell the whole story, as there are two main types of cholesterol: low density lipoproteins (LDL) and high density lipoproteins (HDL): HDL is generally considered to be “good” cholesterol, while LDL is considered “bad” (Anderson et al., 2001). Triglycerides are a third type of fatty material found in the blood, and while their role in heart disease is not entirely clear, it appears that as triglyceride levels rise, levels of “good” cholesterol fall (Anderson et al., 2001). The complex interaction of these three types of lipids is thrown out of balance when a person has hypercholesterolemia (Anderson et al., 2001). High cholesterol is characterized by a combination of elevated levels of LDL cholesterol, normal or low levels of HDL cholesterol, and normal or elevated levels of triglycerides (Anderson et al., 2001).

 

Signs and Symptoms Of Hypercholesterolemia (Anderson et al., 2001)

 

In its preliminary stages, high cholesterol generally occurs without any symptoms; for this reason, screening through routine blood tests is crucial for early detection (Anderson et al., 2001). In its advanced state, however, high cholesterol may result in any of the following: fat deposits in the tendons and skin (called xanthomas); enlarged liver and spleen (which the healthcare provider may feel on exam); severe abdominal pain as a result of pancreatitis (this happens if triglycerides deposit in the pancreas, which may occur when triglyceride levels are 800 mg/dL or higher); chest pain and even a heart attack (this may occur when enough cholesterol has built up in blood vessel walls to block the flow of blood in the heart) (Anderson et al., 2001).

 

Causes Of Hypercholesterolemia (Anderson et al., 2001)

 

In some cases, abnormally high cholesterol may be related to an inherited disorder, and certain genetic causes of abnormal cholesterol and triglycerides, known as hereditary hyperlipidemias, are often very difficult to treat (Anderson et al., 2001). High cholesterol or triglycerides can also be associated with other diseases a person may have, such as diabetes (Anderson et al., 2001). In most cases, however, elevated cholesterol levels are associated with an overly fatty diet coupled with an inactive lifestyle (Anderson et al., 2001). It is also more common in those who are obese, a condition that has now reached epidemic proportions in the United States, affecting as much as half of the adult population (Anderson et al., 2001).

 

Causes of high total and LDL cholesterol levels include: Hereditary hyperlipidemia (Types IIa or IIb); Diets high in saturated fats and cholesterol; Liver diseas; Underactive thyroid; Poorly controlled diabetes; Overactive pituitary gland (a gland in the brain that helps control hormones in the body); A kidney disorder called nephrotic syndrome characterized by elevated cholesterol, loss of protein in the urine leading to low levels of protein in the blood, and excessive fluid retention causing swelling; Anorexia nervosa Medications such as progestogens, cyclosporins, and thiazide diuretics (Anderson et al., 2001).

 

Causes of low HDL cholesterol include: Malnutrition; Obesity; Cigarette smoking; Certain medications such as beta blockers and anabolic steroids; Low levels of physical activity; Polycystic ovarian syndrome (a hormonal disorder caused by multiple cysts in the ovaries accompanied by irregular or no menstruation, acne, obesity, and excessive facial hair) (Anderson et al., 2001).

 

Causes of high triglyceride levels include: Hereditary hyperlipidemia (Types I, IIb, III, IV, or V); Diets high in calories, especially from sugar and refined carbohydrates; Obesity; Poorly controlled diabetes; Insulin resistance (decreased effectiveness of insulin, a hormone that lowers blood sugar levels); Alcohol use; Kidney failure; Stress; Pregnancy; Polycystic ovarian syndrome; Hepatitis; Lupus; Multiple myeloma (a rare disease that occurs more frequently in men than in women and is associated with anemia, bleeding, recurrent infections, and weakness); Lymphoma (tumor of the lymphoid tissue); Certain medications such as estrogens (available in either oral contraceptives or as part of hormone replacement therapy for menopausal women), corticosteroids, a class of cholesterol-lowering medications known as bile acid binding resins (including cholestyramine, colestipol, colesevelam), and isotretinoin (used to treat acne) (Anderson et al., 2001).

 

Risk Factors (Anderson et al., 2001)

 

There are certain factors that put a person at increased risk of having high cholesterol; while some factors cannot be altered by changes in lifestyle, many can be changed (Anderson et al., 2001). The most important risk factors for high cholesterol are: Obesity; Diets high in saturated fat and trans fatty acids (found frequently in processed foods, such as those that have been hydrogenated or fried); Low fiber in the diet; Physical inactivity; Stress; Smoking cigarettes; Living in an industrialized country; Underactive thyroid Diabetes; Polycystic ovary syndrome (Anderson et al., 2001).

 

Diagnosis (Anderson et al., 2001)

 

Since most people have few if any symptoms of hypercholesterolemia (another term for high cholesterol), blood screening is very important (Anderson et al., 2001). An initial blood test is done to check a “random” measurement of total and HDL cholesterols, meaning that the test is performed at any time during the day, regardless of what has been eaten (Anderson et al., 2001). Those with abnormal levels (total cholesterol more than 200 mg/dL or HDL less than 40 mg/dL), will go on to have a test called fasting lipid profile (in which the person being tested refrains from eating for 8 to 12 hours, usually overnight, prior to the test) (Anderson et al., 2001). The fasting test will indicate whether or not total cholesterol levels fall within the normal range (between 140 and 200 mg/dL), are moderately high (between 200 and 240 mg/dL), or if they are in the very high range (240 mg/dL or greater) (Anderson et al., 2001). This blood test also reveals the levels of LDL, HDL, and triglycerides; according to guidelines released by the National Cholesterol Education Program (NCEP), the optimal level for LDL cholesterol depends on whether you have heart disease or not and whether there are other risk factors present for heart disease (such as diabetes and high blood pressure) (Anderson et al., 2001). The optimal level for HDL for all people (healthy or otherwise) is a measurement higher than 60 mg/dL; low levels are 40 mg/dL and below (Anderson et al., 2001).

 

Adults with normal total and HDL cholesterol levels should have their cholesterol checked every 5 years (Anderson et al., 2001). Those being treated for hypercholesterolemia should have their cholesterol levels measured every 2 to 6 months and have liver function tests as well if they are on cholesterol-lowering medication (Anderson et al., 2001).

 

Preventive Care (Anderson et al., 2001)

 

Changing eating habits is key in preventing high cholesterol; other lifestyle changes that can reduce the risk of developing high cholesterol and cardiovascular disease include maintaining a normal weight and increasing physical activity (Anderson et al., 2001).

 

Diet (Anderson et al., 2001)

 

The best ways to lower cholesterol through diet include the following: Reducing the amounts of saturated fat and cholesterol consumed each day; Increasing daily consumption of fruits, vegetables, fish, and whole grains; Supplementing the diet with other protective components such as fiber (Anderson et al., 2001).

 

There are a number of diets designed to keep cholesterol levels in check including the American Heart Association (AHA) diet, the Mediterranean diet, and the Ornish diet. While these three diets vary in some ways, they all emphasize whole grains and include fiber, fresh fruits and vegetables, lean protein, particularly soy and fish, and avoidance of saturated fats and trans fatty acids (Anderson et al., 2001). These diets are outlined below (Anderson et al., 2001):

 

The AHA Step I Diet is considered appropriate for the general population, including those who have normal cholesterol levels and want to prevent the development of high cholesterol (Anderson et al., 2001). This diet calls for up to 55% of daily calories from carbohydrates, 15% from protein, and no more than 30% from fat (Anderson et al., 2001). The diet also outlines quite specific of types of fat and the proportions to include:

 

Between 8% and 10% of fat from saturated fatty acids (saturated fats are found mainly in foods that come from animals such as butter, cheese, milk, cream, and ice cream); Up to 10% from polyunsaturated fatty acids (polyunsaturated fat is highly unsaturated fat that is found in large amounts in foods from plants, including safflower, sunflower, corn, and soybean oils); Up to 15% from monounsaturated fatty acids (monounsaturated fat is a slightly unsaturated fat found in large amounts in foods from plants, including peanut, avocado, canola, and olive oils); Less than 300 mg per day of dietary cholesterol (Anderson et al., 2001).

 

This diet also specifies the level of calories that helps people achieve and maintain a healthy weight, and it is ideal for those who currently include a lot of fat in their diets and have not previously attempted to lower their cholesterol levels through dietary changes (Anderson et al., 2001).

 

The AHA Step II Diet is designed for patients who require greater LDL lowering, and includes the Step I guidelines (above) with two modifications: Less than 7% of calories from saturated fat (instead of 8% to 10%); Less than 200 mg per day of dietary cholesterol (instead of less than 300 mg per day) (Anderson et al., 2001).

 

The Mediterranean Diet is comprised of whole grains, fresh fruits and vegetables, fish, olive oil, garlic, and moderate, daily consumption of red wine (Anderson et al., 2001). Although this diet is not low in fat, it is high in monounsaturated fatty acids and has been shown to increase HDL cholesterol levels and to inhibit the process whereby LDL cholesterol adheres to artery walls (Anderson et al., 2001). One large, well-designed study found that people who had had at least one heart attack were between 50% and 70% less likely to suffer another heart attack if they followed the Mediterranean diet (Anderson et al., 2001). This diet puts a great emphasis on bread, root and green vegetables, and the daily consumption of fruit, fish, and poultry; only olive and rapeseed (canola) oils are used in this eating plan and margarine (with alpha-linolenic acid) is used instead of butter (Anderson et al., 2001). Eating beef and lamb is discouraged (Anderson et al., 2001). This diet is naturally rich in fiber, antioxidants, and omega-3 fatty acids; it contains the same amount of protein as the AHA diet, but the source of protein is primarily fish (Anderson et al., 2001). The Mediterranean diet has less carbohydrates than the AHA or Ornish diets, but places the same emphasis on consuming fruits, vegetables, nuts, legumes, and beans (Anderson et al., 2001).

 

The Ornish Diet is a completely vegetarian diet that has been shown to dramatically reduce cholesterol levels and to actually reverse the risk of heart disease (Anderson et al., 2001). No oils or animal products are allowed in the Ornish diet, except non-fat dairy products and egg whites (Anderson et al., 2001). In this diet, total fat is limited to 10% of daily calories, saturated fats are significantly limited, and carbohydrates generally make up 75% of calories (Anderson et al., 2001). Complex carbohydrates from whole grains and other high-fiber foods and from fresh fruits and vegetables are emphasized (Anderson et al., 2001).

 

Weight Reduction (Anderson et al., 2001)

 

Being overweight increases risk of high cholesterol and heart disease; even small degrees of weight loss can make nutritional changes more effective in lowering LDL — a 5 to 10 pound weight loss can double the LDL reduction achieved by dietary adjustment alone (Anderson et al., 2001). Weight loss is often accompanied by lowered triglycerides and increased HDL levels (Anderson et al., 2001). The goal for weight loss should be a realistic one, rather than a rapid or dramatic loss (Anderson et al., 2001). Very low calorie diets (500 to 800 calories) can be dangerous and are not recommended (Anderson et al., 2001). A reasonable caloric restriction is considered a reduction of 250 to 500 calories per day in the usual diet aimed at achieving a gradual, weekly weight loss of one-half to one pound (Anderson et al., 2001).

 

Physical Activity (Anderson et al., 2001)

 

Regular physical activity by itself both reduces the risk of death from heart disease and enhances the effects of diet on LDL cholesterol levels (Anderson et al., 2001). In a study of 377 people who were divided into four groups (aerobic exercise, the AHA Step II diet, the Step II diet plus exercise, or no intervention), those who only made dietary changes did not show reduced LDL while the group on the Step II diet plus exercise had a significant reduction in LDL cholesterol (Anderson et al., 2001). Moderate exercise three to five times per week (the equivalent of walking 7 to 14 miles per week) can help promote weight loss in overweight individuals, reduce LDL and triglyceride levels, and produce favorable levels of HDL (Anderson et al., 2001). Exercise may also lower blood pressure; for these reasons, everyone with risk factors for heart disease should consider starting a program of regular, aerobic physical activity, individualized to suit physical fitness level, heart health, and exercise preferences (Anderson et al., 2001).

 

Treatment Approach (Anderson et al., 2001)

 

The main goal of treatment is to reduce the risk of cardiovascular diseases, such as heart disease and stroke, by lowering blood cholesterol levels (Anderson et al., 2001). Studies have shown that for every 1% reduction in cholesterol levels there is a 2% reduction in the rate of heart disease (Anderson et al., 2001). People who benefit most from lowering their cholesterol are those who already have heart disease or who have multiple risk factors for the disease (Anderson et al., 2001). In addition to lifestyle changes, specific cholesterol-lowering medications are often prescribed (Anderson et al., 2001).

 

Changes in lifestyle are the most effective means of both preventing and, in less severe cases, treating elevated LDL cholesterol levels (Anderson et al., 2001). The cornerstone of this treatment strategy is dietary modification and exercise (Anderson et al., 2001). In addition to little fat and cholesterol, lean protein (such as soy and fish), and lots of fruits and vegetables, diets should include: Soluble fibers, such as psyllium, which have a cholesterol lowering effect; Soy, which reduces total cholesterol; Antioxidants, which when consumed in high amounts, have been associated with lowered risk of cardiovascular disease. (Vitamin E appears to be of particular value); Omega-3 fatty acids, such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), which may lower the chance of recurrent heart attacks and death from heart disease; Folic acid supplements, which may improve the function of the blood vessels in those with high cholesterol and reduce the risk of heart disease (Anderson et al., 2001). In addition, herbs and supplements may help lower cholesterol levels, and the most promising include: Red Yeast Rice, Fenugreek, and Guggulipid (Anderson et al., 2001).

 

Lifestyle (Anderson et al., 2001)

 

The following changes in life habits have been shown to both prevent high cholesterol and to lower high levels of cholesterol and triglyceride: Dietary changes; Weight reduction; Increased physical activity; Stress reduction; Quitting smoking (because tobacco use lowers HDL cholesterol) (Anderson et al., 2001).

 

Medications (Anderson et al., 2001)

 

According to the National Cholesterol Education Program (NCEP) guidelines, healthcare practitioners should prescribe cholesterol-lowering medication when: LDL cholesterol is higher than 190 mg/dL and the person has no known risk factors for heart disease; LDL cholesterol is higher than 160 mg/dL and the person has two or more risk factors for heart disease; LDL cholesterol exceeds 130 mg/dL and the person has heart disease (Anderson et al., 2001).

 

The following are commonly prescribed medications for high cholesterol (Anderson et al., 2001). Statin drugs or HMG-CoA reductase inhibitors (lovastatin, pravastatin, simvastatin, atorvastatin, and fluvastatin) (Anderson et al., 2001). This class of medications is used to treat elevated LDL and triglyceride levels, and also to raise HDL levels (Anderson et al., 2001). Taking statins reduces the risk of death in those with heart disease and slows the rate of development of both heart disease and stroke when used by those with high cholesterol (Anderson et al., 2001). Healthcare practitioners prefer statin drugs because they are the most effective cholesterol-lowering medication (Anderson et al., 2001). Side effects include myositis (inflammation of the muscles), joint pain, stomach upset, and liver damage (Anderson et al., 2001).

 

Niacin (nicotinic acid), which is used to treat elevated LDL and triglyceride levels and is more effective in increasing HDL levels than other cholesterol-lowering medications (Anderson et al., 2001). Side effects may include redness or flushing of the skin (which can be reduced by taking aspirin 30 minutes before the niacin), stomach upset (which usually subsides in a few weeks), headache, dizziness, blurred vision, and liver damage (Anderson et al., 2001). Starting with low doses of niacin and increasing very gradually helps to reduce the likelihood and severity of side effects (Anderson et al., 2001). Niacin should be avoided by people who have gout, diabetes, low blood pressure, or a history of peptic ulcer (Anderson et al., 2001).

 

Bile acid sequestrants (cholestyramine, colestipol, and colesevelam): these are used to treat elevated LDL levels (Anderson et al., 2001). Common side effects include bloating, constipation, heartburn, and elevated triglycerides (Anderson et al., 2001). These medications may also lead to a deficiency of fat-soluble vitamins and loss of calcium in the urine (Anderson et al., 2001).

 

Fibric acid derivatives (gemfibrozil, fenofibrate, and clofibrate): these medications are used to treat elevated triglycerides and low HDL in people who cannot tolerate niacin (Anderson et al., 2001). Side effects include myositis, stomach upset, sun sensitivity, gallstones, irregular heartbeat, and liver damage (Anderson et al., 2001).

 

Probuchol lowers both LDL and HDL: its use is therefore generally limited to certain types of hereditary high cholesterol and/or to cases in which other cholesterol-lowering medications have been ineffective (Anderson et al., 2001). Side effects include diarrhea, bloating, nausea, and dizziness (Anderson et al., 2001).

 

Nutrition and Dietary Supplements (Anderson et al., 2001)

 

There is considerable evidence that dietary antioxidants, particularly vitamin E, as well as folic acid, fiber, and soy can help to prevent the development of heart disease (Anderson et al., 2001). Substances that have shown promise in lowering cholesterol specifically or that have demonstrated benefit in preventing heart disease in people with high cholesterol are discussed below (Anderson et al., 2001).

 

Fiber and Fiber Sources (Anderson et al., 2001)

 

The American Heart Association (AHA) recommends increased intake of dietary fiber in the form of whole grains, vegetables, fruits, legumes, and nuts because they have been shown to do the following: Reduce total and LDL cholesterol more effectively than a diet low in saturated fat and cholesterol alone; Help control weight and intake of calories by promoting a sense of fullness; and improve cholesterol and triglyceride levels as well as blood sugar in people with diabetes (Anderson et al., 2001).

 

Soluble fibers such as those in psyllium husk, guar gum, and oat bran have a cholesterol-lowering effect when added to a low-fat, cholesterol-lowering diet (Anderson et al., 2001). Studies have shown psyllium, in particular, to be quite effective in lowering total as well as LDL cholesterol levels (Anderson et al., 2001). Oat bran (3 g per day) has also been shown to lower total cholesterol (Anderson et al., 2001).

 

Soy (Anderson et al., 2001)

 

Many studies have shown that replacing some animal protein with soy protein in the diet results in lower blood cholesterol levels, especially when soy is consumed as part of a general low-fat diet (Anderson et al., 2001). One study has shown that as little as 20 g of soy protein per day is effective in reducing total cholesterol, but that 40 to 50 g shows faster effects (in 3 weeks instead of 6) (Anderson et al., 2001). This evidence suggests that soy protein should be included in a healthy diet: in fact, since October of 1999, the FDA has allowed the labels of foods containing 6.25 g or more of soy protein to carry the claim that these foods reduce the risk of heart disease (Anderson et al., 2001). Moreover, the AHA recommends that people with elevated total and LDL cholesterol add soy to their daily diet (Anderson et al., 2001). Ethanol-washed soy preparations should be avoided because this procedure causes the soy to lose its isoflavones (the substances likely responsible for its cholesterol-lowering effects) in the process (Anderson et al., 2001).

 

Omega-3 fatty Acids (Anderson et al., 2001)

 

Numerous studies have reported the benefits of consuming fish oils, rich in the omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), at doses ranging from 850 mg to 4 g per day for those with heart disease (Anderson et al., 2001). Supplementation with DHA, for example, has been shown to reduce triglycerides and LDL levels and raise HDL levels (Anderson et al., 2001).

 

Alpha-Linolenic Acid (Anderson et al., 2001)

 

Walnuts are one of the best sources of the omega-3 fatty acid alpha-linolenic acid (Anderson et al., 2001). Replacing a major portion (35%) of the monounsaturated fat in the Mediterranean diet with walnuts appears to significantly improve cholesterol and triglyceride levels in people with high cholesterol (Anderson et al., 2001). Almonds, although not as well studied as walnuts, appear to have similar effects when used as a substitute for a portion of monounsaturated fats in low-fat diets (Anderson et al., 2001).

 

Vitamin E (Anderson et al., 2001) number of studies conducted over the last 10 years have reported beneficial results from the use of vitamin E supplements for the treatment and prevention of heart disease including for those with elevated cholesterol levels (Anderson et al., 2001).

 

Vitamin C (Anderson et al., 2001)

 

Preliminary evidence suggests that vitamin C (3 glasses of orange juice per day or up to 3 g per day as a supplement) may help decrease total and LDL cholesterol and triglycerides, and increase HDL levels (Anderson et al., 2001).

 

Coenzyme Q10 (CoQ10) (Anderson et al., 2001)

 

Coenzyme Q10 (CoQ10), also known as ubiquinone, is an antioxidant that is essential for energy production (Anderson et al., 2001). Levels of CoQ10 have been found to be lower in people with high cholesterol when they were compared to healthy individuals of the same age; furthermore, when person with high cholesterol take statin drugs, CoQ10 levels appear to decline in direct proportion to the level of decrease in cholesterol (Anderson et al., 2001). This is particularly important to bear this in mind when statin drugs are used for long periods of time (Anderson et al., 2001). Taking CoQ10 supplements, however, can correct the deficiency caused by statin medications without affecting the medication’s positive effects on cholesterol levels (Anderson et al., 2001).

 

Folic Acid (Vitamin B9) (Anderson et al., 2001)

 

High blood levels of homocysteine (an amino acid produced by the body) have been shown to increase the risk of heart attacks (Anderson et al., 2001). Evidence suggests that high homocysteine levels are also related to low folate levels; this means that an adequate supply of folate and other B. vitamins may be important, particularly for those with heart disease (Anderson et al., 2001).

 

Plant Sterols (Anderson et al., 2001)

 

Plant sterols (fats present in fruits, vegetables, seeds, and nuts) appear to interfere with the absorption of cholesterol, thereby lowering the level of cholesterol in the blood (Anderson et al., 2001). A daily intake of 1.6 g of margarine containing plant sterols has been shown to reduce total and LDL cholesterol, with larger intakes not necessarily providing any additional benefit (Anderson et al., 2001). Questions have been raised, however, regarding the possibility that plant sterols interfere with the absorption of certain antioxidants such as alpha- and beta-carotenes, alpha-tocopherol, and lycopene (Anderson et al., 2001). While the significance of this is still unclear, it warrants further investigation, and these micronutrients must be carefully monitored in the blood of those using plant sterols (Anderson et al., 2001).

 

L-Carnitine (Anderson et al., 2001)

 

L-carnitine is produced in the liver and kidneys from the amino acids lysine and methionine; it is stored in skeletal muscles and the heart and may be beneficial in treating conditions such as chest pain, heart attack, heart failure, diabetes, and abnormal cholesterol (Anderson et al., 2001). In several human studies, supplementation with 2 to 3 g per day of L-carnitine led to a significant reduction in total cholesterol and triglycerides, and to increases in HDL cholesterol levels (Anderson et al., 2001).

 

Red wine (Anderson et al., 2001)

 

Red wine contains flavonoids, which inhibit LDL oxidation (the process whereby LDL cholesterol adheres to artery walls) (Anderson et al., 2001). Studies have demonstrated a relationship between flavonoid consumption (from food) and reduced risk of death from coronary heart disease (Anderson et al., 2001). Although non-alcoholic grape products contain flavonoids, red wine contains much higher concentrations of flavonoids; however, the use of alcohol is not advocated by the AHA and other organizations because of the potential for addiction and the other serious repercussions such as motor vehicle accidents and the development of hypertension, liver disease, breast cancer, weight gain (Anderson et al., 2001). If red wine is consumed, it is recommended that men have no more than 2 glasses (20 g ethanol) per day and women, no more than 1 glass (15 g ethanol) (Anderson et al., 2001).

 

Red Yeast Rice (Anderson et al., 2001)

 

Red yeast rice, the fermented product of rice and red yeast, has been used in China since at least 800 AD to make wine and preserve food, and for its medicinal properties, which are believed to include, among other things, improvement in blood circulation (Anderson et al., 2001). Recent well-designed studies have shown that red yeast rice significantly reduces total cholesterol, LDL cholesterol, and triglyceride concentrations (Anderson et al., 2001).

 

Chromium (Anderson et al., 2001)

 

Brewer’s yeast is an important source of chromium; ninety percent of Americans are deficient in this important mineral (Anderson et al., 2001). Chromium has demonstrated the ability to lower LDL levels in the blood and raise HDL levels (Anderson et al., 2001).

 

Calcium (Anderson et al., 2001)

 

Preliminary studies in animals and people suggest that calcium supplements, in the range of 1,500 to 2,000 mg per day, may help to lower cholesterol (Anderson et al., 2001). The information available thus far suggests that keeping cholesterol levels normal or even low by using calcium supplements (along with many other measures such as changing your diet and exercising) is likely to be more beneficial than trying to treat it by adding calcium once you already have elevated cholesterol; more research in this area is needed, however (Anderson et al., 2001).

 

Vitamin B5 (Pantothenic Acid) (Anderson et al., 2001)

 

Research has shown that vitamin B5 lowers cholesterol; studies are currently underway to determine if this vitamin helps prevent heart disease (Anderson et al., 2001).

 

Herbs (Anderson et al., 2001)

 

Hawthorn (Crataegus oxyacantha and monogyna) (Anderson et al., 2001)

 

The flowers and berries of the hawthorn plant have been used in traditional herbal and homeopathic remedies to protect against stroke and to treat chest pain, irregular heartbeat, and heart failure (Anderson et al., 2001). In addition, studies using rats suggest that the tincture of Crataegus (made from the berries) may be a powerful agent for the removal of LDL from the blood stream (Anderson et al., 2001). The tincture of hawthorn berries also reduced the production of cholesterol in the liver of rats who were being fed a high-cholesterol diet (Anderson et al., 2001). Studies to determine if hawthorn will confer the same effects in humans are needed (Anderson et al., 2001).

 

Green Tea (Camellia sinensis) (Anderson et al., 2001)

 

Green tea has been observed to have a variety of beneficial effects, including anticancer and antioxidant effects (Anderson et al., 2001). The tea has also demonstrated an ability to lower total cholesterol and raise HDL cholesterol in both animals and people (Anderson et al., 2001). Although an animal study conducted to determine how green tea effects these changes was not conclusive, results from the study suggest that the catechins in green tea may block intestinal absorption of cholesterol and promote its excretion from the body (Anderson et al., 2001).

 

Garlic (Allium sativum) (Anderson et al., 2001)

 

Long hailed for its beneficial effects, a number of studies have found that garlic reduces elevated total cholesterol levels more effectively than placebo; however, the size of the effect in these studies was small, and study limitations make it difficult to draw any firm conclusions (Anderson et al., 2001). More research with better-designed studies is warranted in order to assess the safety and effectiveness of garlic and to determine the most appropriate dose and form (fresh garlic vs. supplements) (Anderson et al., 2001).

 

Red clover (Trifolium pratense) (Anderson et al., 2001)

 

Preliminary studies suggest that chemicals in red clover known as isoflavones may raise HDL levels, especially in menopausal women (Anderson et al., 2001). Not all studies, however, have shown such positive effects; further studies are needed before a definitive conclusion can be made (Anderson et al., 2001).

 

Bilberry (Vaccinium myrtillus) (Anderson et al., 2001)

 

Animal studies suggest that bilberry may prevent the oxidation of LDL cholesterol, thereby lessening the risk of this bad form of cholesterol contributing to the development of atherosclerotic plaque in the arteries; research in people is needed (Anderson et al., 2001).

 

Massage and Physical Therapy (Anderson et al., 2001)

 

While no studies have examined the effect of massage on cholesterol levels, massage has been shown to reduce cortisol (stress-related hormone) levels and to induce relaxation (Anderson et al., 2001). Massage may therefore have an indirect effect on risk factors that result from or are worsened by stress, such as poor eating habits and obesity, cigarette smoking, or lack of exercise (Anderson et al., 2001). Lowering cortisol levels may also have a positive effect on cholesterol levels (Anderson et al., 2001).

 

Mind/Body Medicine (Anderson et al., 2001)

 

Stress Reduction (Anderson et al., 2001)

 

Emotional and social stress increases the risk for heart disease (Anderson et al., 2001). Stress is thought to promote hardening of the arteries and effective stress reduction techniques can help to reduce high cholesterol levels and other risk factors (Anderson et al., 2001). In several studies of Transcendental Meditation (TM), significant reductions in total cholesterol levels as well as reductions in blood pressure, obesity, and cigarette smoking were seen after 3 to 11 months of practice (Anderson et al., 2001). Although TM appears to be one of the more effective methods for relaxation, other methods that may be considered include: Progressive muscle relaxation (PMR); Biofeedback; Yoga; Stress management classes (Anderson et al., 2001).

 

Ayurveda (Anderson et al., 2001)

 

Guggulipid (Commiphora mukul) (Anderson et al., 2001)

 

Guggulipid, a traditional Ayurvedic medication used to treat high cholesterol, is widely used in India and was first recommended as a treatment for hardening of the arteries in 600 BC (Anderson et al., 2001). It appears to be an effective cholesterol-lowering agent and its healthful effects are thought to be due to its ability to block the production of cholesterol in the liver (Anderson et al., 2001). In a 4-week study of 61 people who were on a fruit and vegetable-rich diet, half were given guggul supplements of 400 mg three times and the other half received placebo (Anderson et al., 2001). The guggulipid group had reductions of total cholesterol, LDL, and triglycerides comparable to that seen with conventional cholesterol-lowering drugs while the placebo group had no improvement (Anderson et al., 2001).

 

Fenugreek (Trigonella foenum graecum) (Anderson et al., 2001)

 

Fenugreek is a legume sold as a dried seed. It is cultivated in India and the Middle East, and used as a condiment in foods like curry and in baked goods (Anderson et al., 2001). In Ayurvedic medicine, spices and herbs are traditionally used to treat a variety of chronic diseases (Anderson et al., 2001). Fenugreek seeds have been shown to decrease LDL cholesterol and triglycerides, and increase HDL cholesterol levels (Anderson et al., 2001). These effects appear to result from reduced intestinal absorption of cholesterol, and may be related to the high fiber content of the seed (Anderson et al., 2001). Consumption of fenugreek may therefore be beneficial in the management of high cholesterol levels (Anderson et al., 2001).

 

Prognosis and Complications (Anderson et al., 2001) number of complications may occur if high cholesterol is left untreated, and these include: Heart disease — the leading cause of death in the United States, and elevated cholesterol levels more than doubles the risk of heart attack, such that lowering cholesterol by 1% reduces the risk of coronary artery disease by 2%; Stroke — low levels of HDL cholesterol have been associated with an increased risk of stroke; Insulin resistance — 88% of people with low HDL and 84% with high triglycerides also have insulin resistance (that is, their bodies are not responsive to insulin, which leads to high blood sugar levels), with many people with insulin resistance go on to develop diabetes (Anderson et al., 2001).

 

It is also important to note that lowering cholesterol too rapidly may contribute to the development of depression, which may be related to low levels of omega-3 fatty acids (Anderson et al., 2001). Maintaining an appropriate weight, eating a low-fat diet, and exercising can have a significant impact on cholesterol levels and improve long-term prognosis (Anderson et al., 2001).

 

Chapter 2: Literature Review

 

Introduction

 

All of the studies identified in this review classify cholesterol screening as a blood test with basic education on lifestyle changes for those who receive a raised blood cholesterol result (Bankhead et al., 2003). The education and counseling involved in the cholesterol screening program are crucial because the onus is on the individual to make lifestyle changes to reduce their risk status (Bankhead et al., 2003). Cholesterol screening is usually offered on an opportunistic or open-access basis; studies reported screening in shopping centers, local pharmacies, worksites, colleges and the healthcare setting (e.g. general practice or hospital); some studies were undertaken in people who had already been identified as being at high risk of CVD (Bankhead et al., 2003).

 

The following results report on studies that observe the subsequent behavior of participants who receive a high or moderately high cholesterol result following blood cholesterol screening; no studies report solely on those who received a desirable result or on those who chose not to attend for cholesterol screening (Bankhead et al., 2003).

 

Description of included studies (Bankhead et al., 2003) total of 55 papers reported the effects of cholesterol screening on health behavior and health beliefs; fifty-six studies are reported, however, as one paper reported two studies (Bankhead et al., 2003). The majority of studies were published after 1990, with 36 studies published between 1990 and 1994, and ten studies between 1995 and 2000; a further ten studies were published between 1985 and 1989 (Bankhead et al., 2003). The timing of the majority of studies follows the introduction of the NCEP in the U.S.A. In 1985 (Bankhead et al., 2003).

 

The review consists of studies carried out in eight different countries, with 35 studies conducted in the U.S.A., seven from Canada, four from the UK, four from Sweden, three in Australia, and one study from each of Germany, Norway and South Africa (Bankhead et al., 2003). In 23 of the studies, cholesterol screening was conducted in an open-access environment such as in a supermarket, at a health fair or at a pharmacy; studies reporting on open-access cholesterol screening were from the U.S.A., Canada or Australia (Bankhead et al., 2003). Fourteen studies were conducted in a workplace environment, two involved both open access and workplace participants, 12 were conducted in a healthcare setting, two were conducted on college students, one surveyed a specific community and two did not report the cholesterol screening setting (Bankhead et al., 2003). The majority of studies aimed to observe changes in health behaviors and health beliefs over time following screening, and for this reason, 43 of the 55 studies used a cohort design, which means that the results are therefore subject to a number of biases inherent in observational studies (Bankhead et al., 2003). A further eight studies used a randomised controlled trial (RCT) design and one study used a nonrandomized intervention design (Bankhead et al., 2003). One study used a cross-sectional design and three used a qualitative design (Bankhead et al., 2003). Thirty-six studies had a follow-up rate of over 70%, 17 had a follow-up rate of below 70% and in three studies the follow-up rate is unclear (Bankhead et al., 2003). Thirty-six studies had a follow-up period of less than 1 year, 11 studies had a follow-up period of 1 year and six studies had a follow-up period of greater than 1 year; the remaining studies did not report a follow-up period (Bankhead et al., 2003).

 

The results reported may have been attributed to the self-selected nature of the screened population, who may be more motivated to change behavior (Bankhead et al., 2003). In addition, the results may have been attributed to the heightened publicity of the risks of high blood cholesterol at the time the studies were conducted (Bankhead et al., 2003). Findings also need to be interpreted in light of the methodological limitations regarding the reliability of the tools used to measure health behaviors and health beliefs, uncertainty of self-reports, recall bias, regression to the mean and study attrition (Bankhead et al., 2003). Few studies investigated the impact of cholesterol screening on those who received desirable blood cholesterol results, such as the ‘certificate of health effect, and few studies investigated the long-term changes in health behaviors and health beliefs; furthermore, the literature lacked appropriate qualitative studies that could assess the subtle impact on health beliefs, and lacked comparisons across cultural and socio-demographic groups (Bankhead et al., 2003). The limitations of the literature and the gaps in the literature are discussed further in the discussion on cholesterol screening (Bankhead et al., 2003).

 

Results

 

Changes in health behaviors following cholesterol screening (Bankhead et al., 2003)

 

Dietary change (Bankhead et al., 2003)

 

Dietary change was assessed in 30 studies: most of the tools used to measure dietary change were survey specific, reporting change by frequency of specific foods consumed, assessing mild, moderate or major improvements, or simply reporting improved diet with lower fat intake vs. not improved diet, and the validity and reliability of these measures were not discussed (Bankhead et al., 2003). Previously validated measures were used in eight studies, including the Block Fat Screener, the Food Habits questionnaire, Rate Your Plate, the Burnette Dietary Item questionnaire and the Sackett Dietary Change questionnaire (Bankhead et al., 2003). Twenty-eight of the 30 studies reported positive changes in diet following cholesterol screening, whereas two reported no change (Bankhead et al., 2003).

 

A dose-response relationship between higher cholesterol levels and magnitude of dietary changes was looked for in seven of the studies: of these, six reported that the higher the cholesterol levels, the greater the dietary changes that were made, and one reported no effect. Four RCTs assessed dietary change (Bankhead et al., 2003). Two RCTs assessed whether ‘knowing your high cholesterol result’ had a greater impact on dietary changes: one reported a greater impact on dietary change for those who knew their high cholesterol result, while the other found no effect for those in the intervention group (Bankhead et al., 2003). The latter study reported that both those in the intervention group and those in the non-intervention group reported dietary improvement; the difference in results observed between these two studies may have been due to the different study settings: the former study was conducted in a healthcare setting, whereas the latter was conducted in a workplace setting (Bankhead et al., 2003). One RCT assessed the difference between participant-orientated goals and doctor reminder for dietary change, while another assessed the difference between enhanced information and routine information giving following cholesterol screening; in both of these studies the intervention had no effect, although positive dietary changes were observed in all groups (Bankhead et al., 2003). It is therefore possible that the dietary change in these studies was due to the effect of screening (Bankhead et al., 2003).

 

In five cohort studies and one nonrandomized intervention study, an intervention (enhanced education either at screening or subsequently from the doctor) was used to improve dietary change (Bankhead et al., 2003). One of these cohort studies showed significant improvement over time in the intervention group compared with the control group, which showed no change, and two studies showed significant improvement over time between baseline and follow-up (Bankhead et al., 2003). Two cohort studies found that those who had previously been screened were more likely to adopt a low-fat diet than newly diagnosed people (Bankhead et al., 2003). Contrary to this, another study reported that participants who had been previously screened with a high cholesterol result found it more difficult to make dietary changes than those who were newly detected with a high cholesterol level (Bankhead et al., 2003). One study found that women were more likely than men to make dietary changes (Bankhead et al., 2003).

 

Exercise change (Bankhead et al., 2003)

 

The impact of cholesterol screening on level of exercise was reported in 15 studies (Bankhead et al., 2003). Eight of the studies reported exercise improvement simply by asking the participants whether they had increased their level of exercise or not, or reported changes in those who exercising regularly (Bankhead et al., 2003). Four studies reported exercise improvement over time using frequency of exercise per week, two studies assessed exercise using a Likert scale of minor, moderate and major improvements, and one study used descriptive methods (Bankhead et al., 2003). An increase in exercise for those with high cholesterol levels was reported in 11 of the studies, three reported no change in exercise after screening, and a case study reported a negative outcome where the patient stopped exercising because he was worried it might lead to a heart attack (Bankhead et al., 2003). A dose-response relationship between higher cholesterol levels and magnitude of exercise changes was reported in two of the studies (Bankhead et al., 2003). An RCT assessed the difference on exercise levels between enhanced and routine information; the intervention was found to have no effect (Bankhead et al., 2003). An intervention (enhanced education) was also used to try and increase the adoption of exercise in two cohort studies, but although exercise adoption increased overall in these studies, the enhanced education intervention was no more effective than routine care (Bankhead et al., 2003). One study compared prior screenees with new screenees, and found no difference in exercise adoption (Bankhead et al., 2003).

 

Weight change (Bankhead et al., 2003)

 

Following cholesterol screening, weight change was investigated in 11 studies: weight reduction was reported in eight of the studies, and three reported no change in weight (Bankhead et al., 2003). An intervention (enhanced education) was used in an RCT and one in a cohort study to try to improve weight reduction; both studies found that although weight reduction was reported overall, this was not as a result of the intervention (Bankhead et al., 2003).

 

Adherence with referral to see a doctor (Bankhead et al., 2003)

 

Twenty-four studies reported on adherence with referral to see a doctor for retesting of cholesterol levels following opportunistic screening (Bankhead et al., 2003). An adherence rate of 30-60% was reported in 16 of the studies, seven reported an adherence rate of over 60%, and one study reported over 60% compliance in the high blood cholesterol group, but under 60% compliance in the moderately high blood cholesterol group (Bankhead et al., 2003). A positive dose-response relationship between higher cholesterol levels and greater adherence to referral was observed in five of the studies (Bankhead et al., 2003). One study observed a negative dose-response relationship between higher cholesterol levels and greater adherence, but this was probably due to the high cholesterol groups having to attend more follow-ups than the desirable cholesterol group (four vs. one) (Bankhead et al., 2003). Two RCTs reported the effects of an intervention (reminder letter) to increase adherence to see a doctor regarding a high cholesterol result: one found this intervention to be successful, whereas the other found the intervention to be ineffective at increasing adherence (Bankhead et al., 2003). One study reported that those who had previously received a high cholesterol result were more likely to adhere to referral than new screenees (Bankhead et al., 2003). Knowledge of prior cholesterol level was associated with a significantly greater adherence with referral to see a doctor (Bankhead et al., 2003). Prior knowledge of cholesterol levels and actual cholesterol levels were independently associated with compliance to follow-up. Increasing age and being female were both shown to increase adherence to referral (Bankhead et al., 2003).

 

Adherence with drug treatment (Bankhead et al., 2003)

 

Five studies reported adherence to drug treatments: of these, two reported poor adherence to drug treatment; one found a dose response relationship where those taking drug treatment reported a greater reduction in cholesterol levels over the study period, one reported that adherence to drug treatment increased over the study period, and one reported that a high proportion of those who took drug treatment for high cholesterol levels remained compliant for at least 6 months (Bankhead et al., 2003).

 

Smoking cessation (Bankhead et al., 2003)

 

Smoking cessation or reduction in number of cigarettes smoked per day was assessed in nine studies (Bankhead et al., 2003). Four of the studies measured change in smoking behavior by reporting whether or not the participants had stopped smoking at follow-up, four studies reported the level of reduction in the number of cigarettes smoked by follow-up, and one study reported smoking behavior by frequency of cigarettes smoked per day (Bankhead et al., 2003). An intervention (enhanced education) was used to encourage smoking cessation in two cohort studies, and one RCT (Bankhead et al., 2003). A reduction in or cessation of smoking was reported in five of the nine studies; where an intervention was used to encourage smoking cessation no additional benefit was observed (Bankhead et al., 2003). One study reported an improvement in smoking cessation in both the control group and the intervention group; one study observed previously screened participants to assess whether they would be more likely to reduce their smoking level than new screenees; no difference was observed between the two groups (Bankhead et al., 2003).

 

Association with attendance for further screening (Bankhead et al., 2003)

 

Three studies reported an association between cholesterol screening and further health screening (Bankhead et al., 2003). Stockbridge and colleagues reported that previous cholesterol screening was the motivation to attend for cholesterol screening again by just over half of all participants (Bankhead et al., 2003). Wynder and colleagues reported that 11% of the participants went for cholesterol screening because of a previous high blood cholesterol result (Bankhead et al., 2003). One cross-sectional study investigated the association between cholesterol screening and use of breast screening; previous cholesterol screening had a positive association with attendance for breast screening (Bankhead et al., 2003).

 

Blood cholesterol change (Bankhead et al., 2003)

 

Blood cholesterol change following cholesterol screening was investigated in 21 studies. Nineteen of these studies reported a cholesterol reduction; two of the studies reported no change in cholesterol level following screening (Bankhead et al., 2003). A dose-response relationship between higher cholesterol levels and greater reduction in cholesterol levels over time was observed in three studies (Bankhead et al., 2003). Three RCTs reported blood cholesterol change; two RCTs reported that ‘knowing your high cholesterol result’ resulted in greater cholesterol reduction (Bankhead et al., 2003). The blood cholesterol reductions reported in these two studies were similar: one RCT reported that those who expected to be followed up after a health check had a greater reduction in blood cholesterol level than those who were not expecting to be followed up; one non-randomised intervention study and three cohort studies also used an intervention (enhanced education) to encourage cholesterol reduction (Bankhead et al., 2003). Cholesterol reduction was observed as a result of the intervention in three of these studies; some reduction in cholesterol levels would be expected because of regression to the mean (Bankhead et al., 2003).

 

Changes in health beliefs following cholesterol screening (Bankhead et al., 2003)

 

Effect of labeling on absenteeism from work, change in well-being and intention to change lifestyle behaviors (Bankhead et al., 2003)

 

Seven studies reported on the impact of labeling people with high or borderline-high cholesterol levels on health beliefs as well as behaviors; only one qualitative case series reported a negative effect of labeling (Bankhead et al., 2003). This study reported that labeling of individuals who were diagnosed with hypercholesterolaemia led to feelings of illness, anxiety and confusion (Bankhead et al., 2003). The other six studies were quantitative studies and reported no effect of labeling; two studies reported that having a high cholesterol result did not increase absenteeism from work; Rastam and colleagues reported an overall increase in sick days, but concluded this was due to the ageing population (Bankhead et al., 2003). Fischer and colleagues reported that although participants reported distress immediately after screening, this did not affect absenteeism from work or perception of their health and well-being (Bankhead et al., 2003). Havas and colleagues used the General Health Perceptions Questionnaire to assess the impact of a high blood cholesterol result on general well-being; it was concluded that labeling participants with high cholesterol levels did not result in negative beliefs about well-being, although the authors suggest that this may have been due to the positive way in which the participants were counselled after the screening test (Bankhead et al., 2003).

 

Elton and co-workers conducted an RCT and reported that those who are more informed about their cholesterol risk made a greater effort to change their lifestyle in order to reduce their cholesterol levels (Bankhead et al., 2003). Two further RCTs found that participants who knew that they had a high cholesterol result increased their intention to alter their lifestyles and to gain more information about the condition; however, this latter study was carried out on university students, and therefore is not generalisable to the general population at risk from a high level of cholesterol (Bankhead et al., 2003).

 

Acceptance of risk status (Bankhead et al., 2003)

 

Seven studies (published in six papers) reported the impact of cholesterol screening on acceptance of risk after cholesterol screening (Bankhead et al., 2003). Negative consequences caused by receipt of a high-risk result were reported in six of the seven studies; two qualitative studies reported that people at high risk found it difficult to make sacrifices to reduce their cholesterol levels (Bankhead et al., 2003). These studies reported that people resisted lifestyle changes as they felt it would impact on their quality of life (Bankhead et al., 2003). Clarke and colleagues reported that fatalism prevented people from taking an active role in changing their health behaviors to reduce their cholesterol level; one study, using the General Well-Being Schedule, concluded that there were no adverse effects of accepting a risk status on general well-being (Bankhead et al., 2003). Four studies reported that people coped with their risk status by denial or threat minimization (Bankhead et al., 2003).

 

Irvine and Logan assessed life satisfaction of deniers and non-deniers using the Rand Corporation Mental Health Index, Spielberger State-Trait Personality Inventory and Campbell’s Life Satisfaction Index; they concluded that denial was a significant barrier to health behavior change (Bankhead et al., 2003). People did not perceive themselves as ill, which made it difficult for them to understand and accept their diagnosis and undertake lifestyle changes (Bankhead et al., 2003). Croyle and colleagues, using an RCT design, assessed threat minimisation of borderline high blood cholesterol participants using Miller’s Monitoring and Blunting questionnaire and self-esteem using the Rosenberg’s Self-Esteem questionnaire (Bankhead et al., 2003). The study concluded that while people in this group were more willing to make lifestyle changes compared with the desirable cholesterol group, they were more likely to deny the seriousness of the raised cholesterol levels and to have lower self-esteem (Bankhead et al., 2003). One study reported that those who had previously received a high cholesterol result and received a second high cholesterol result were less likely to report threat minimization (Bankhead et al., 2003).

 

Knowledge of Cholesterol Levels in Patients (Bankhead et al., 2003)

 

Recall of cholesterol level (Bankhead et al., 2003)

 

Recall of cholesterol levels after screening was reported in nine studies; accurate recall of cholesterol levels was reported in six of these studies, whereas three reported poor recall (Bankhead et al., 2003). Two of the above studies reported on whether socio-demographics had an impact on personal cholesterol knowledge levels, and found that older people, women and those with higher education were more likely to have a greater knowledge of cholesterol issues (Bankhead et al., 2003).

 

General cholesterol knowledge (Bankhead et al., 2003)

 

Accurate recall of knowledge about cholesterol issues (e.g. national recommendations on healthy levels and association with other diseases such as CVD) at follow-up was reported in five studies, and one study reported poor recall of general information about cholesterol (Bankhead et al., 2003).

 

Summary (Bankhead et al., 2003)

 

Evidence suggests that cholesterol screening may have a positive impact on health behaviors: a majority of studies reported an adoption of healthier diets, increase in exercise, reduction in weight and reduction in cholesterol levels for those diagnosed with high or moderately high cholesterol levels (Bankhead et al., 2003). There was inconsistent evidence to suggest that screening had a positive impact on smoking cessation; however, most of the studies were observational studies with inherent biases, and it is difficult to assess the extent to which changes in health behaviors were attributable to other influences such as heightened publicity about the risk of high cholesterol and the self-selected nature of the screened population (Bankhead et al., 2003). Furthermore, methodological limitations should be noted: evidence suggests that follow-up among those identified as possibly having high blood cholesterol is often inadequate, although higher risk levels predict better referral adherence (Bankhead et al., 2003). Evidence from quantitative studies suggests that the impact of labeling the screened population with an at-risk status had little effect on absenteeism from work or negative perceptions of health (Bankhead et al., 2003). One qualitative study suggests that some individuals did experience consequences of their new ‘sick’ label; furthermore, a small number of qualitative studies suggest that some participants experience psychological problems as a consequence of their newly identified at-risk status (Bankhead et al., 2003).

 

Evidence suggests that participants of cholesterol screening have a good general knowledge of cholesterol issues, but there is inconsistent evidence for recall of personal cholesterol levels (Bankhead et al., 2003). Evidence suggests that previous cholesterol screening had a positive impact on health behaviors such as future cholesterol and breast screening, dietary change, smoking cessation and adherence to recommended follow-up (Bankhead et al., 2003). Those who had previously attended cholesterol screening also accepted their risk status better than newly screened participants (Bankhead et al., 2003). Evidence from RCTs suggests that randomizing participants into knowing their high cholesterol status and not knowing their high cholesterol status resulted in an improvement in health behaviors, but had negative effects on health beliefs for those who were aware of their high risk status (Bankhead et al., 2003). There is inconsistent evidence from RCTs for the effectiveness of interventions (e.g. enhanced lifestyle education or reminder letters to increase referral rates) to improve health behaviors (Bankhead et al., 2003).

 

Discussion: benefits of cholesterol screening (Bankhead et al., 2003)

 

Issues arising from Study Design (Bankhead et al., 2003)

 

Design type (Bankhead et al., 2003) majority of the studies followed a cohort design, and the roles of chance, bias and confounding influence should therefore be considered (Bankhead et al., 2003). A striking aspect in the literature reported is the contrast in findings between the small number of studies using a qualitative methodology and the larger number using a quantitative methodology (Bankhead et al., 2003). A negative impact on health beliefs and well-being was evident only in the qualitative studies (Bankhead et al., 2003). The quantitative studies did not report such effects, possibly because they were unable to detect such subtle outcomes, although positive behavioral significant negative consequences on health beliefs are also reported (Bankhead et al., 2003). More qualitative studies are needed to understand this issue (Bankhead et al., 2003).

 

Study groups (Bankhead et al., 2003)

 

All the studies in the review focused on people who had been identified as having moderately high or high cholesterol levels; none aimed solely to examine the ‘certificate of health effect’ on people who were screened and found to have desirable cholesterol levels (Bankhead et al., 2003). The findings of this review therefore cannot comment on, or rule out, an adverse impact on the subsequent health beliefs or behaviors of those who were screened as normal (Bankhead et al., 2003).

 

Self-selection bias (Bankhead et al., 2003)

 

There is concern that the voluntary screening programs described in many of these studies may attract a more health-conscious population than the general population, who are more motivated to make lifestyle changes to improve their health (Bankhead et al., 2003). The inverse care law suggests that those who benefit most from voluntary cholesterol screening are the ones least likely to participate in such a public screening program, as these people may be less motivated to improve their health (Bankhead et al., 2003). Opportunistic screening may also be used to monitor cholesterol levels over time, as those who are at high risk are more likely to be found in the healthcare setting (Bankhead et al., 2003).

 

Recall bias (Bankhead et al., 2003)

 

Recall bias is a problem for the studies in this review, owing to the self-reported nature of behaviors and beliefs (Bankhead et al., 2003). Participants are more likely to report the behavioral change if they know that this is the relationship being investigated (Bankhead et al., 2003). Added to this is the problem of seasonal lifestyle changes that may have affected the study results: many of the studies in the U.S.A. may have had difficulties having matched controlled groups because of the great awareness and publicity of the cholesterol problem (Bankhead et al., 2003). This would particularly have influenced studies assessing the effectiveness of interventions to improve lifestyle behaviors (Bankhead et al., 2003).

 

Generalisability (Bankhead et al., 2003)

 

As reported earlier, the majority of these studies were conducted in the U.S.A., and cultural differences will affect the generalisability of the results in the rest of the world: caution should also be applied to the generalisability of studies with small sample sizes, studies specific to certain small cultures and selection bias (Bankhead et al., 2003).

 

Impact of cholesterol screening on health behaviors (Bankhead et al., 2003)

 

Diet, exercise, weight and smoking changes (Bankhead et al., 2003)

 

The results reported for health behaviors are generally positive, with the majority of studies reporting change in a healthy direction for the outcomes diet, exercise and weight (Bankhead et al., 2003). There was inconsistent evidence for changes in smoking behavior; however, with methodological weaknesses, particularly in the measures used to assess changes, and the limitations of selection bias and attrition, interpretation should be treated with caution (Bankhead et al., 2003). The simplicity and the lack of reliability and validity of tools used to measure behavioral changes should be noted; however, behavioral changes did reflect changes in cholesterol levels, so it is possible that the measures used are acceptable (Bankhead et al., 2003). Accuracy may be improved by logging changes over time; however, with large samples and limited resources in many of these studies, it may not be feasible to record changes over time (Bankhead et al., 2003). Many of the tools used to measure lifestyle change were based on self-report; these self-reports may have been exaggerated to reflect the heightened publicity and pressure to conform to changes in lifestyle to lower CVD risk (Bankhead et al., 2003). Changes in behavior may also have been done just before follow-up appointment for study purposes only, and therefore participants may not have adopted long-term changes (Bankhead et al., 2003). The timing of the studies could have affected the behavioral changes too, owing to seasonal changes in lifestyle behaviors; studies have proven that cholesterol levels may rise in the colder months (Bankhead et al., 2003). It could be argued that those who volunteer for opportunistic cholesterol screening are more health conscious, and are therefore more motivated to make health-related changes (Bankhead et al., 2003). Those with higher cholesterol levels may have been more likely to change their health behaviors owing to unhealthier lifestyles at baseline, and more likely to exaggerate the changes made because they knew the importance of change; however, Klepp and colleagues found that those with the highest cholesterol levels were strongly motivated to change diet to a greater extent than those with lower cholesterol levels because of the perceived seriousness of their condition (Bankhead et al., 2003). Klepp also stated that confidence in a person’s ability to change, and seeing the risk reduction were important in behavioral change; however, few studies in this review took an in-depth look at the motivation for and process of behavioral change (Bankhead et al., 2003).

 

Adherence with follow-up to see a doctor (Bankhead et al., 2003)

 

The majority of studies that assessed adherence with follow-up to see a doctor showed a low adherence rate (? 60%): this may have been due to the lack of perceived seriousness of the condition diagnosed in a non-medical environment (Bankhead et al., 2003). For some participants, the initial test in a non-medical environment may have lessened the perceived seriousness of the test and therefore not motivated participants to seek the necessary retesting in a medical environment (Bankhead et al., 2003). Participants may have perceived themselves healthy with no obvious symptoms of cardiovascular disease, and therefore not understood the importance of having their high blood cholesterol result rechecked (Bankhead et al., 2003). Furthermore, many of the cholesterol screening programs offered free cholesterol checks at convenient places, whereas follow-up with the doctor involved making an appointment, traveling to the clinic and often incurring medical fees (Bankhead et al., 2003). Concern has been expressed that the community screening programs may counteract the medical advice by arming subjects with strategies for attempting to reduce their cholesterol levels on their own, and therefore making them feel that visiting the doctor is unnecessary (Bankhead et al., 2003).

 

Other factors that may have contributed to poor adherence to follow-up are lack of time, procrastination and too short a length of follow-up (Bankhead et al., 2003). Ovhed and colleagues argued that to achieve greater compliance to follow-up, re-invitation and tracking of patients who do not show up is necessary, which would obviously be hard to achieve in a community open-access cholesterol screening program (Bankhead et al., 2003). It could be argued that those who adhered to the recommendations for follow-up were more health conscious and more used to the culture of visiting health centers for health checks (Bankhead et al., 2003). The presence of other health problems (hypertension, diabetes) may have predicted greater follow-up to see the doctor as these individuals are already seeing their doctor regularly about other conditions and will not incur extra time or cost by mentioning cholesterol levels (Bankhead et al., 2003). Gordon and colleagues found that those who had high cholesterol levels were more likely to comply with follow-up to see their physician than those with borderline-high cholesterol levels (Bankhead et al., 2003). This could have been due to the greater perceived seriousness of the condition, but equally could have been due to the greater vigour with which the message to follow-up was delivered at screening for those with very high cholesterol levels (Bankhead et al., 2003).

 

Change in cholesterol levels (Bankhead et al., 2003)

 

Changes in blood cholesterol levels were considered in the review as one potential measure of successful lifestyle change, and the evidence suggests that cholesterol reduction was achieved; however, although 19 studies showed a drop in cholesterol levels on follow-up after screening, only one study measured this in such a way as to rule out a regression to the mean effect (i.e. A greater reduction in cholesterol levels would be expected in participants with the highest cholesterol levels) (Bankhead et al., 2003). Regression to the mean is potentially a problem when interpreting the results owing to the large number of cohort rather than controlled designs; regression to the mean may occur in both these study designs, but if the initial cholesterol levels are randomly distributed between intervention and control groups, then any differential effect is probably due to the intervention (Bankhead et al., 2003). It is therefore not possible to distinguish reduction in cholesterol levels attributable to regression to the mean from reduction attributable to screening; all but one study that reported cholesterol change and behavioral change showed that cholesterol reduction was concomitant with behavioral improvements (Bankhead et al., 2003). This indicates that the decrease in cholesterol change is real and may be associated with improved lifestyle; however, because of the difficulty in measuring change in health behaviors, it would be difficult for any study to measure whether the magnitude of the cholesterol reduction was the same as the magnitude of behavioral change, and therefore does not completely rule out the effect of regression to the mean (Bankhead et al., 2003). Cholesterol levels were measured using clinical assessment, which is a more accurate assessment than self-reported assessments used to measure other behaviors such as diet, exercise and smoking (Bankhead et al., 2003).

 

Effects of previous cholesterol screening on future screening and health behavior (Bankhead et al., 2003)

 

Those who went for cholesterol screening were more likely to return for future cholesterol screening and more likely to attend for other screening such as mammography; it could be argued that those who attend for opportunistic cholesterol screening are more health conscious and are therefore more motivated to attend for health screening (Bankhead et al., 2003). Those who had a history of previous screening reported greater compliance to lifestyle changes; this may also have been due to these individuals having greater motivation and interest in their health or may have been because they are more accustomed to their health status (Bankhead et al., 2003).

 

Impact of cholesterol screening on health beliefs (Bankhead et al., 2003)

 

Effects of labeling screening participants with a ‘sick’ status and risk acceptance (Bankhead et al., 2003)

 

The results with regard to health beliefs were less positive, with several studies reporting denial and harm minimisation and many also reporting that lack of engagement with the lifestyle change agenda was common: only one qualitative study found a significant problem with labeling individuals with a ‘sick’ status, the other six quantitative studies found no effect of labeling (Bankhead et al., 2003). Caution should be noted regarding the self-reported measures used to assess health beliefs in such quantitative studies as they may under-report the negative beliefs and may not elicit subtle outcomes (Bankhead et al., 2003). Qualitative methods may provide a more in-depth description of the effects of labeling and acceptance of risk status; acceptance of an at-risk status was shown to cause stress in some people, and coping mechanisms such as denial and threat minimisation were observed in some participants (Bankhead et al., 2003). The response to an at-risk status varied as these participants sought explanations for their new status and tried to identify the factors that might have caused it (Bankhead et al., 2003).

 

Those who perceived that their personal circumstances or lifestyle were consistent with having a raised cholesterol level had fewer difficulties than those who defined themselves as being within the anomalous group (i.e. At risk according to the test but not appearing to have any of the risk factors) (Bankhead et al., 2003). Denial inhibits the appraisal of risk status and may prevent the adoption of appropriate behavioral actions; Irvine and Logan argued that people who received a raised cholesterol level did not perceive the seriousness of the disease because of the lack of symptoms and the opportunistic nature of screening (Bankhead et al., 2003). Several studies report that good quality information and counselling can assist in overcoming the problem of acceptance of risk and denial (Bankhead et al., 2003). The SCORE (screening, counseling and referral) process in the U.S.A. aims to do this (Bankhead et al., 2003). No research was identified on the negative effects of labeling participants with low cholesterol risk (Bankhead et al., 2003). Screening can falsely reassure people who receive a normal result and therefore no behavioral changes or detrimental behavioral changes are made; this is often referred to as the ‘certificate of health’ effect (Bankhead et al., 2003).

 

Knowledge about cholesterol screening (Bankhead et al., 2003)

 

General knowledge about cholesterol issues was good, and in a majority of studies was associated with changes in behaviors; however, this may have been due to heightened publicity about cholesterol as a risk factor, and not as a direct result of cholesterol screening (Bankhead et al., 2003). There was inconsistent evidence regarding the level of recall of personal cholesterol risk levels (Bankhead et al., 2003). Poor recall of personal cholesterol levels could, again, reflect the lack of perceived seriousness of high cholesterol owing to the lack of symptoms and the non-medical environment in which screening is conducted (Bankhead et al., 2003). Understanding the meaning of having a raised cholesterol level is crucial for behavioral changes to occur; feeling susceptible to the disease and knowing that the disease is severe facilitate patients to act (Bankhead et al., 2003).

 

Cultural and social differences (Bankhead et al., 2003)

 

International differences (Bankhead et al., 2003)

 

In this review a majority of the studies showed some improvements in health behaviors and health beliefs following cholesterol screening; however, the majority of these studies were conducted in the U.S.A. At a time when there was a great public interest in community cholesterol screening, and a culture of health check-ups (Bankhead et al., 2003). Few studies were conducted in Britain, and there are certainly great differences to be noted between the U.S.A. And Britain: in Britain the health-check ritual is less well established and public interest does not appear to be high (Bankhead et al., 2003). It has been suggested that the impact of cholesterol screening is rather limited in the British population and adoption of lifestyle advice is poor (Bankhead et al., 2003). Such opportunistic screening at community centers may therefore not be so effective in changing the health behaviors and health beliefs of the British population as it is in the U.S.A. And elsewhere (Bankhead et al., 2003). Cholesterol screening in Britain is currently mainly provided in a healthcare setting identifying and treating those at greatest risk (Bankhead et al., 2003). The increased use of cholesterol screening in the U.S.A. may be reflected in the heightened publicity of the condition that could have equally influenced the changes in health behaviors and beliefs; certainly, the literature has recognized that a single event such as cholesterol screening is unlikely to secure changes in ingrained lifestyle patterns (Bankhead et al., 2003).

 

Ethnic and social differences (Bankhead et al., 2003)

 

Relatively few studies assessed the impact of cholesterol screening on cultural, gender, age and other socio-demographic groups, yet ultural and social norms can affect the impact of screening on health beliefs and health behaviors (Bankhead et al., 2003). Brunt and Shields explain that the cultural norm for women to be ‘Rubenesque’ in the Hutterite culture makes weight loss particularly resistant to change (Bankhead et al., 2003). Studies indicated that women were more likely to make dietary changes, more likely to adhere to referral to see a doctor, and had a greater general knowledge of cholesterol issues (Bankhead et al., 2003). Brett reported that change in diet may not necessarily lower cholesterol, as there may be a genetic determinant involved (Bankhead et al., 2003), in familial hyperocholesterolemia, for example.

 

Study setting differences: community, workplace and healthcare settings (Bankhead et al., 2003)

 

Although no studies directly compared across cholesterol settings, studies have suggested that workplace screening is more effective at encouraging lifestyle changes than community screening because there is more control over follow-up and more peer pressure to make changes to health behaviors (Bankhead et al., 2003). Studies report that workplace programs allow continued individual and group monitoring, which are necessary components of any program designed to elicit desirable changes to modify health behaviors and beliefs (Bankhead et al., 2003). In a community open-access setting follow-up and continual support after cholesterol screening are harder to achieve (Bankhead et al., 2003). Gemson and colleagues certainly found that those who were followed up more frequently showed greater reduction in cholesterol levels; Strychar and co-workers concluded that if greater dietary changes were required, a more intensive follow-up program may be appropriate; Wang and colleagues argue that community open access screening reaches risk groups who may not otherwise have used the healthcare system, but there is no evidence that these people will then comply to follow-up recommendations or make long-term lifestyle changes (Bankhead et al., 2003). Strychar and colleagues commented that one of the major roles of community cholesterol screening was to raise awareness of the cholesterol problem, as it helps to facilitate changes in health behavior and health beliefs (Bankhead et al., 2003). The healthcare setting is the most controlled environment for cholesterol screening, but currently targets those who are at highest risk (Bankhead et al., 2003).

 

Summary (Bankhead et al., 2003)

 

The questions this section aimed to answer were: 1. What are the effects of opportunistic blood cholesterol screening on future health beliefs and behaviors?; 2. What are the implications for the NHS, including their impact on the cost-effectiveness of screening programs?; and, 3. What are the gaps in the literature and what recommendations can be made as to future research directions, including a description of the framework for further research on this topic, taking into account any important theoretical perspectives identified in the literature search (Bankhead et al., 2003).

 

1. The studies reviewed herein suggest that cholesterol screening had some positive effects on health behaviors; however, these positive findings need to be interpreted in the light of methodological issues; for example, participation was voluntary, and screened participants were possibly more motivated to make changes (Bankhead et al., 2003). These results are therefore not generalisable to the entire population (Bankhead et al., 2003). Caution should also be noted regarding the lack of reliability and validity of tools to measure changes in health behaviors, study attrition and uncertainty of self-reports; furthermore, uncertainty of long-term changes, inaccurate risk assessment (additive rather than multiplicative), perception of cholesterol testing in non-medical environments, perception of seriousness of the risk status owing to lack of symptoms, readiness to accept advice, and convenience and cost of follow-up should all be considered (Bankhead et al., 2003). Reduction in blood cholesterol levels was reported in all but two of the studies that assessed this outcome, suggesting that successful lifestyle changes had been made; however, as most of the studies only reported follow-up of screened participants, some of the reduction will be attributable to regression to the mean (Bankhead et al., 2003). Blood cholesterol screening had a less positive effect on health beliefs, with several qualitative studies reporting denial and threat minimization leading to a lack of engagement in lifestyle changes (Bankhead et al., 2003). Quantitative studies concluded that the effect of labeling did not appear to have adverse affects on absenteeism from work or cause negative perceptions of health and well-being; however, one qualitative study did report negative effects of labeling (Bankhead et al., 2003). There are indications that qualitative methods may be necessary to identify such effects (Bankhead et al., 2003).

 

2. When interpreting the results, there is little evidence about the effect of open-access cholesterol screening programs on health behaviors and health beliefs, at least in the UK (Bankhead et al., 2003). None of the papers provided cost-effectiveness data on cholesterol screening programs; research comparing the different cholesterol screening settings within the UK should be considered (Bankhead et al., 2003).

 

3. There are gaps in this review for the literature on cholesterol screening and recommendations for future research are given below (Bankhead et al., 2003). It will be necessary to: Assess the impact of cholesterol screening on people who have normal results, to answer the question of whether there is a certificate of health effect; Conduct a range of qualitative studies is required to assess the subtle impact of cholesterol screening on health beliefs, on the process of change and on the complexity of individual decisions to change behavior; Assess the long-term impact of screening on health behaviors and health beliefs, as most of the studies in this review only assessed short-term changes to health behaviors and health beliefs, and the conclusions cannot be extended to longer term changes; Assess the elements of the multi-component interventions, individually and in combination, which are most effective in motivating patients to make changes in their behavior; Assess the differences between countries regarding the impact of cholesterol screening on health behaviors and health beliefs; Assess the differences between cholesterol screening settings, in terms of looking at which cholesterol screening setting is the most effective at impacting on long-term changes in behaviors and beliefs; Assess why people who attend for cholesterol screening do not make changes in health behaviors; Assess the relative impact of cholesterol screening on various racial, ethnic and socio-demographic groups, in terms of uncovering if there is a need to develop and evaluate targeted recruitment strategies and more effective follow-up to overcome selection bias? (Bankhead et al., 2003).

 

Chapter 3: Guidelines for Treating Hypercholesterolemia

 

Coronary heart disease (CHD) is a leading cause of morbidity and mortality, and high blood cholesterol is a major risk factor for CHD. In its third report, the Expert Panel on the Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults of the National Cholesterol Education Program guidelines for screening and management of high blood cholesterol have been updated to further identify and treat patients at risk (Chase, 2002). Therapeutic lifestyle changes are stressed as therapy for all patients, and pharmacologic therapy is indicated for all people not meeting low-density lipoprotein target goals (Chase, 2002). Although 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors are well tolerated and the most frequently used hypolipidemic agents, a variety of agents can be used, including nicotinic acid derivatives, bile acid sequestrants, and fibric acid derivatives (Chase, 2002).

 

Introduction (Chase, 2002)

 

Coronary heart disease (CHD) includes the clinical conditions of acute myocardial infarction, angina pectoris, and heart failure (Chase, 2002). It is estimated that CHD affect 12.2 million Americans; in addition, CHD causes more than 466,000 deaths annually in the United States (Chase, 2002). Approximately 1.1 million Americans had a myocardial infarction in the year 2000, and more than 40% died as a result (Chase, 2002). Sixteen percent of men and 35% of women will experience a second myocardial infarction within 6 years of the first (Chase, 2002).

 

The economic impact of CHD is enormous: in 1999, the direct costs of CHD (costs for hospitalization, nursing home care, physician services, medications, home healthcare) in the United States amounted to $55.2 billion; the indirect costs for lost productivity, morbidity, and mortality were $118.2 billion (Chase, 2002). Although 88% of persons younger than 65 years are able to return to work after a myocardial infarction, CHD is the leading cause of early, permanent disability in the U.S. workforce; it accounts for 19% of disability allowances paid by the Social Security Administration (Chase, 2002).

 

High blood levels of cholesterol (particularly low-density lipoprotein cholesterol [LDL-C]) increase the risk of CHD, and lowering total cholesterol and LDL-C levels reduces this risk (Chase, 2002). Clinical management of persons without CHD (eg, interventions to prevent the development of or reduce risk factors for CHD) is referred to as primary prevention; treatment of elevated LDL-C levels in patients with a history of CHD (or other atherosclerotic disease associated with lipid accumulation in the blood vessel walls) is considered secondary prevention; thus, it is of critical importance that our patients with lipid disorders be identified and treated appropriately and aggressively to reduce their risk of CHD (Chase, 2002).

 

Pathophysiology: Cholesterol Metabolism (Chase, 2002)

 

Cholesterol is an essential component of cell membranes and a metabolic precursor of bile acids and steroid hormones (eg, adrenocortical and sex hormones), and is obtained from the diet and synthesized in the liver, intestinal mucosa, and other cells (Chase, 2002). The rate-limiting step in cholesterol synthesis involves the enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, which converts HMG-CoA to mevalonate (Chase, 2002). Cholesterol and other lipids (eg, triglycerides, which are made up of free fatty acids and glycerol) are transported in the systemic circulation as a component of lipoproteins (Chase, 2002).

 

Lipoproteins are particles composed of (1) a hydrophobic lipid core made up of cholesterol esters and triglycerides and (2) a hydrophilic outer coat made up of phospholipids, flee cholesterol, and apolipoproteins (Chase, 2002). Apolipoproteins are proteins that provide structural stability to lipoproteins, bind with cell receptors, and play a vital role in regulating lipid transport and lipoprotein metabolism (Chase, 2002).

 

Lipoproteins are classified on the basis of their density as chylomicrons, very low-density lipoproteins (VLDLs), LDLs, intermediate-density lipoproteins (IDLs), and high-density lipoproteins (HDLs) (Chase, 2002). Most of the cholesterol in the serum (60%-70%) is found in LDL particles; HDL particles contain 20% to 30% of the total serum cholesterol; and VLDL particles contain 10% to 15% (as well as most of the triglycerides during fasting conditions) (Chase, 2002). Chylomicrons transport cholesterol and fatty acids from the intestines (ie, dietary cholesterol and that synthesized locally in the mucosa) to the liver (Chase, 2002).

 

In the liver, cholesterol and triglycerides are synthesized and incorporated into VLDL particles, which deliver cholesterol to the peripheral tissues when the particles are released into the bloodstream (Chase, 2002). The triglyceride content of VLDL particles initially is high and decreases progressively as the result of enzyme activity in the bloodstream (Chase, 2002). This enzyme activity converts the particles sequentially to VLDL remnants, IDL, and LDL (Chase, 2002).

 

The LDL particles are small and high in cholesterol content; the LDL receptors on peripheral and hepatic cells bind with apolipoproteins on the surfaces of LDL, resulting in uptake of cholesterol into the cells (ie, clearance of LDL from the bloodstream), where it is subsequently degraded (Chase, 2002). Low intracellular cholesterol concentrations stimulate the synthesis of LDLreceptors, thereby increasing cellular uptake of LDL (Chase, 2002). The HDL particles transport cholesterol from peripheral cells to the liver, a process known as reverse cholesterol transport; high HDL levels promote clearance of cholesterol from peripheral tissues (Chase, 2002).

 

Lipoprotein (a) (Lp[a])] is similar to LDL, but it contains apolipoprotein (a), a protein similar to plasminogen; Lp (a) is formed when apolipoprotein (a) binds to apolipoprotein B. On LDL (Chase, 2002). Apolipoprotein B. is the only apolipoprotein on LDL particles, whereas other lipoproteins have multiple apolipoproteins on their surfaces (Chase, 2002). High levels of LDL-C, triglycerides, apolipoprotein B, and Lp (a) and low levels of HDL and apolipoprotein A-I (an apolipoprotein associated with HDL synthesis) are associated with high risk of CHD (Chase, 2002).

 

Hypercholesterolemia (Chase, 2002)

 

The cholesterol level in blood is, as we have seen, determined by a combination of factors, including inheritance (ie, genetic abnormalities in lipoprotein metabolism), age, and acquired factors (eg, lifestyle factors such as dietary intake of saturated fat and cholesterol, physical activity) (Chase, 2002). Secondary causes of hypercholesterolemia and lipoprotein abnormalities include poorly controlled diabetes mellitus, hypothyroidism, nephrotic syndrome, dysproteinemia, obstructive liver disease, drug therapy (eg, cyclosporine, glucocorticoids), and alcoholism (Chase, 2002).

 

Atherosclerosis (Chase, 2002)

 

High blood levels of cholesterol play a leading role in atherosclerotic lesion formation in the walls of coronary arteries (Chase, 2002). Atherosclerosis begins with accumulation of lipoproteins (primarily LDL) within the inner layer of the arterial wall, where they no longer come in contact with antioxidants and other constituents in the bloodstream (Chase, 2002). Chemical modification (particularly oxidation) of lipoproteins leads to a local inflammatory reaction involving macrophages, which ingest oxidized lipoproteins and form foam cells (Chase, 2002). Accumulation of foam cells contributes to fatty lesion formation; reverse cholesterol transport out of the tissues mediated by HDL may also occur (Chase, 2002).

 

Over time, fatty lesions progress to fibrous plaques; fissures may develop in a plaque, exposing the underlying tissues to platelets and other constituents of blood (Chase, 2002). Platelet adhesion, activation, and aggregation lead to thrombus (clot) formation, partially or completely occluding the vessel lumen and causing clinical symptoms of CHD (eg, myocardial ischemia or infarction) (Chase, 2002).

 

Diagnosis and Classification (Chase, 2002)

 

It is recommended that a complete fasting lipoprotein profile (as opposed to only total cholesterol and HDL-C) be measured in all adults 20 years and older at least once every 5 years (Chase, 2002). A fasting lipoprotein profile includes total cholesterol, LDL-C, HDL-C, and triglycerides; measurement of the LDL-C on initial screening provides more information for risk assessment (Chase, 2002).

 

Although LDL-C testing is more precise, advantages of testing for total cholesterol over a complete fasting lipoprotein profile include greater availability of the test, lower cost, and lack of a requirement that the patient fast before the test (Chase, 2002). As a result, it may not be practical in all situations to have a full fasting profile performed; if the testing opportunity is non-fasting (fasting defined as nothing by mouth with caloric value in the preceding 9 to 12 hours), only total cholesterol and HDL will be usable and should be measured; however, LDL-C may be calculated from the results of these tests in patients with a total triglyceride level of 400 mg/dL or less using the following equation[2]: LDL-C = total cholesterol – (HDL-C + triglycerides)/5 (Chase, 2002).

 

In patients with total triglyceride levels higher than 400 mg/dL, LDL-C should be measured directly by preparative ultracentrifugation because calculating LDL-C from total cholesterol, total triglyceride, and HDL-C values is inaccurate in this situation (Chase, 2002). In general, LDL-C levels less than 100 mg/dL are optimal; levels of 100 to 120 mg/dL are near optimal; the range 130 to 159 mg/dL is considered borderline high risk; and 160 mg/dL or greater is high risk (Chase, 2002).

 

Cholesterol ratios (total cholesterol/HDL-C and LDL-C / HDL-C) are also strong predictors of CHD (Chase, 2002). Other measures that are not performed routinely but may provide insight into a patient’s risk for CHD include Lp (a) and apolipoproteins B. And A-I (Chase, 2002). Hypercholesterolemia may be isolated or accompanied by hypertriglyceridemia (Chase, 2002). If the triglyceride value is greater than or equal to 200 mg/dL, the non-HDL-C level should be assessed: non-HDL-C = total cholesterol – HDL. Identified as a secondary target of therapy by the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) in patients with high triglyceride levels, non-HDL levels reflect the sum of LDL and VLDL (triglyceride-rich remnant lipoprotein) levels (Chase, 2002).

 

Chapter 4: Management of Hypercholesterolemia (Chase, 2002)

 

Lifestyle modifications, such as smoking cessation, dietary therapy, and physical activity, with or without antilipemic drug therapy, are used to manage hypercholesterolemia and reduce risk of CHD (Chase, 2002). According to the NCEP, the intensity of treatment for hypercholesterolemia should be guided by the patient’s risk, which depends on the LDL-C level, the number of CHD risk factors, and whether CHD is already present (Chase, 2002). More aggressive interventions are recommended for patients at high risk than for patients at lower risk (Chase, 2002).

 

The target LDL-C level is progressively lower as the risk for CHD increases; the measured LDL-C level at which drug therapy should be initiated also is lower as the risk for CHD increases; for example, drug therapy should be considered for patients with CHD if their measured LDL-C level is 130 mg/dL or higher and the target level is 100 mg/dL or less (ie, a reduction of 23% or more is required) (Chase, 2002). By contrast, drug therapy should be considered for a patient without CHD and with fewer than 2 risk factors if the measured LDL-C level is 190 mg/dL or higher and the target level is less than 160 mg/dL (ie, a reduction of 16% or more is needed) (Chase, 2002).

 

The American Diabetes Association recommends aggressive treatment of hypercholesterolemia in patients with diabetes mellitus because diabetes increases the risk of CHD 2-fold to 4-fold (Chase, 2002). Drug therapy should be initiated if the measured LDL-C level is 130 mg/dL or greater in adults with diabetes (100 mg/dL or greater if CHD is also present) and the target LDL-C level is 100 mg/dL or lower (Chase, 2002).

 

Dietary Therapy and Physical Activity (Chase, 2002)

 

The NCEP ATP III recommends a multifaceted lifestyle approach, termed therapeutic lifestyle changes (TLC), to lower LDL levels and reduce risk for CHD (Chase, 2002). Non-pharmacologic approaches considered effective for lipid management include dietary modifications, weight loss or control, aerobic exercise, moderate alcohol consumption, and smoking cessation (Chase, 2002). The objectives of dietary therapy are to reduce elevated serum cholesterol levels and maintain good nutrition (Chase, 2002). The dietary recommendations include reduction of saturated fats to less than 7% of total calories and cholesterol to less than 200 mg/d (Chase, 2002). Therapeutic options for enhancing LDL lowering include increasing consumption of plant stanols/sterols to 2 g/d and increasing intake of viscous (soluble) fiber to 10 to 25 g/d (Chase, 2002).

 

Physical activity is an essential element in managing hypercholesterolemia; in overweight patients, physical activity and dietary therapy promote weight loss (Chase, 2002). Obesity is not listed as a risk factor for CHD because it acts indirectly through other risk factors, such as diabetes mellitus, hyperlipidemia, and hypertension (Chase, 2002). Exercise and weight loss in overweight patients may reduce triglyceride levels, blood pressure, risk for diabetes mellitus, and cholesterol levels (Chase, 2002). Restricting alcohol intake is recommended for patients who are overweight or who have hypertriglyceridemia, because alcohol contributes calories and increases serum triglyceride concentrations in many people (Chase, 2002).

 

If, after at least 6 months of dietary therapy and exercise, the reduction in LDL-C levels is inadequate (or if the LDL-C level rises above the level at which drug therapy is indicated), the addition of drug therapy to dietary therapy should be considered; drug therapy is not, however, a substitute for dietary therapy (Chase, 2002). Potential benefit, adverse effects, and costs enter into the decision to use drug therapy (Chase, 2002).

 

Drug Therapy (Chase, 2002)

 

Hypolipidemic agents to treat hypercholesterolemia include bile acid sequestrants (cholestyramine, colestipol, and colesevelam), niacin (nicotinic acid), fibric acid derivatives (fenofibrate, gemfibrozil), and HMG-CoA reductase inhibitors (simvastatin, pravastatin, and atorvastatin, commonly referred to as statins) (Chase, 2002). When selecting among the available hypolipidemic drug therapies, one should take into consideration the patient’s lipid profile (ie, the presence of hypertriglyceridemia and hypercholesterolemia, low HDL level), contraindications, potential drug interactions, and cost (Chase, 2002).

 

Measurement of LDL-C levels 4 to 6 weeks and 3 months after initiation of antilipemic drug therapy is recommended by the NCEP (Chase, 2002). The target LDL-C level for drug therapy is the same as that for dietary therapy; adjustments in drug dosage may be necessary to achieve the target level or to avoid adverse effects (Chase, 2002). If the response is adequate, checkups should be scheduled at least every 4 months, although measurement of serum total cholesterol concentration suffices at these visits (lipoprotein analysis with LDL-C measurement may take place annually after the 3-month visit) (Chase, 2002). If the response to the initial drug is inadequate despite adjustment, another drug or a combination of 2 drugs should be tried; most patients respond to 1 or 2 drugs (Chase, 2002).

 

Bile acid sequestrants (Chase, 2002): the bile acid sequestrants cholestyramine (Questran), colestipol (Colestid), and colesevelam (Welchol) bind to bile acids in the intestinal tract, interrupting enterohepatic circulation and causing the removal of bile acids from the body when the drug is eliminated in the feces (Chase, 2002). Although hepatic cholesterol synthesis increases to compensate for these losses, the number of LDL receptors on hepatocytes also increases, promoting clearance of LDL from the bloodstream (Chase, 2002). Both VLDL and triglyceride concentrations may increase during bile acid sequestrant therapy, especially if they are elevated before treatment (Chase, 2002).

 

Treatment with bile acid sequestrants should be used in patients who have hypercholesterolemia but not hypertriglyceridemia (Chase, 2002). This group includes patients with polygenic or heterozygous familial hypercholesterolemia and those with the hypercholesterolemic form of familial combined hyperlipidemia (Chase, 2002).

 

Although these agents primarily lower levels of LDL by 15% to 30%, they also can modestly increase HDL by 3% to 5%; a modest, usually transient, 5% to 10% increase in triglyceride level also occurs, however, secondary to increased triglyceride production and increased VLDL triglyceride content and size (Chase, 2002). If triglyceride levels are greater than 250 mg/dL, a variable increase in triglyceride levels is seen (Chase, 2002). In patients with dysbetalipoproteinemia or baseline triglyceride levels higher than 500 mg/d, a marked increase in triglyceride levels usually will occur, thus contraindicating single-drug therapy with resins (Chase, 2002).

 

The ability of both cholestyramine and colestipol to bind bile acids is well documented, but the efficient (95% to 99%) reabsorption of bile acids limits the efficiency of large doses of these drugs; frequent dosing is thus required to trap a substantial amount of the bile acid pool (Chase, 2002). Interactions occur between resins and other substances in the intestine; interference with the absorption of fat-soluble vitamins, for example, vitamin K, can lead to hypoprothrombinemia (Chase, 2002). This does not appear detrimental except in patients with significant problems in bile acid metabolism, such as in those with severe liver or small bowel disease; therefore, multivitamin supplementation is usually not indicated, except in these cases (Chase, 2002).

 

Medication taken with or near the time of resin ingestion may be bound and not absorbed (Chase, 2002). Medications at risk include phenylbutazone, warfarin, thiazide diuretics, propranolol, penicillin G, tetracycline, phenobarbital, thyroxine preparations, and digitalis (Chase, 2002). The effect on absorption of many other drugs has not been well studied; the current recommendation is that other medications be taken at least 1 hour before or 4 to 6 hours after the bile acid-binding resin, which may limit the use of resins in patients taking multiple drugs concomitantly (Chase, 2002).

 

The bile acid sequestrants are not absorbed in the body; therefore, the range of adverse effects is limited (Chase, 2002). These agents can be used in the treatment of hypercholesterolemia in children and pregnant women, although clear-cut data as to the safety of long-term use in children or the use during pregnancy or lactation are not available (Chase, 2002). Most complaints about resins relate to the taste, texture, and bulkiness. Colesevelam offers the advantage of being in capsule form; however, as many as 6 must be taken a day (Chase, 2002). The most frequent adverse effects of the bile acid sequestrants are dose dependent and include nausea, vomiting, heartburn, abdominal pain, belching, bloating, and constipation (Chase, 2002). These adverse effects might be minimized by a gradual increase in dose (Chase, 2002).

 

Nicotinic acid and derivatives (Chase, 2002): the lipid-lowering capacity of nicotinic acid was shown more than 30 years ago, and it has been used successfully in a variety of hyperlipidemic conditions (Chase, 2002). Niacin (Niaspan), a nicotinic acid derivative, reduces hepatic synthesis of VLDL and, as a result, reduces LDL formation; it lowers LDL-C and triglyceride levels and raises HDL-C levels (Chase, 2002).

 

Changes in lipoprotein levels that occur with standard doses of niacin are reductions in plasma triglyceride and total cholesterol levels of 30% to 40% and 15% to 20%, respectively (Chase, 2002). The LDL levels may be reduced by 20% or more (reductions exceeded only by HMG-CoA reductase inhibitors) (Chase, 2002). A significant rise in HDL-C levels (approximately 15%) is generally seen; however, adverse effects may be more common with the higher doses (Chase, 2002). The changes in serum triglyceride and HDL-C concentrations that are induced by niacin are curvilinear, whereas the changes in serum LDL-C concentrations are linear (Chase, 2002). Thus, a daily dose of 1500 to 2000 mg of niacin will substantially change the serum triglyceride and HDL-C concentrations without causing many of the mucocutaneous and hepatic adverse effects seen with higher doses (Chase, 2002).

 

This dose is often ideal for patients with familial combined hyperlipidemia. These patients usually need to take a statin as well, and because it is tolerated better, the statin should be given first (Chase, 2002). The patients may then be more receptive to moderate doses of plain or timed-release nicotinic acid (Chase, 2002). Higher doses (3000 to 4500 mg/d) may be needed to reduce serum LDL-C concentrations substantially in patients with familial hypercholesterolemia even when statins and a bile acid-binding resin are given concomitantly (Chase, 2002).

 

The most common adverse effects from niacin are gastrointestinal upset, loose bowel movements or diarrhea, peripheral vasodilation (flushing of the face and neck), and pruritus (Chase, 2002). Niacin-induced vasodilation appears to be mediated by prostaglandins (eg, prostacyclin) (Chase, 2002). Healthcare practitioners and pharmacists can counsel patients on ways to minimize the adverse effects of niacin (Chase, 2002). Flushing may be reduced by pretreatment with a prostaglandin inhibitor, such as aspirin, 325 mg administered 30 minutes before the niacin dose (Chase, 2002). The aspirin use can often be discontinued after a few days because tachyphylaxis develops in response to the prostaglandin-mediated flush (Chase, 2002). Patients can also minimize flushing by taking niacin at the end of a meal and by not taking it with hot liquids (Chase, 2002).

 

Hepatotoxicity has been reported in patients receiving niacin; it may be dose related (>2000 mg/d) and associated with the use of extended-release preparations (Chase, 2002). The symptoms and time course of niacin-induced hepatitis are similar to those associated with statins (Chase, 2002). Timed-release formulations of nicotinic acid are designed to minimize cutaneous flushing; however, the absence of flushing may indicate poor gastrointestinal absorption (Chase, 2002). Additional drawbacks of such formulations are lesser decreases in serum triglyceride concentrations and lesser increases in serum HDL-C concentrations than are induced with plain nicotinic acid (Chase, 2002). Healthcare professionals can suggest the timed-release formulations for patients who cannot tolerate plain niacin and can be sure to follow up for evaluation of antilipemic effect and effect on aminotransferase levels (Chase, 2002).

 

Less common adverse effects include acanthosis nigricans, vascular-type headaches, orthostatic hypotension (especially in elderly patients), and reversible blurred vision resulting from macular edema (Chase, 2002). Niacin inhibits the tubular excretion of uric acid, predisposing patients to hyperuricemia and gout (Chase, 2002). Elevations in plasma glucose levels, attributed to the rebound in fatty acid concentrations that may occur after each dose of niacin, occur in some individuals, leading to glucose intolerance (Chase, 2002). The elevated free fatty acids may compete with the use of glucose by peripheral tissues (Chase, 2002).

 

Fibric acid derivatives (Chase, 2002). The prototypical fibric acid is clofibrate (which is not used in the United States) (Chase, 2002). Clofibrate and related drugs somewhat resemble short-chain fatty acids and function to increase the oxidation of fatty acids in both liver and muscle (Chase, 2002). The increase in fatty acid oxidation in the liver is associated with increased formation of ketone bodies (an effect that is not clinically important) and decreased secretion of triglyceride-rich lipoproteine (Chase, 2002). Fenofibrate (Tricor) and gemfibrozil (Lopid) are marketed in the United States; bezafibrate and ciprofibrate are available in Europe; these drugs, known as fibrates, reduce VLDL synthesis and VLDL cholesterol levels, and they decrease LDL-C levels in patients with hypercholesterolemia or combined hypercholesterolemia and hypertriglyceridemia and increase HDL-C levels (Chase, 2002).

 

Therapy with the fibrates results in triglyceride reduction of up to 50%, making these first-line agents in primary hypertriglyceridemia (Chase, 2002). The LDL-C reduction averages 10% to 15%, but this effect is variable and some patients may in fact have a mild increase in LDL levels secondary to fibrate treatment (Chase, 2002). If the increase is substantial, a low-dose statin is often added to the regimen (Chase, 2002). Fenofibrate may lower serum LDL-C concentrations more effectively than does clofibrate or gemfibrozil; however, HDL-C levels increase up to 25% (Chase, 2002). Thus, the primary indications for fibrate therapy are serum triglyceride concentrations of more than 1000 mg/dL, remnant removal disease, and low serum HDL-C concentrations; however, they may also be useful in patients with combined hyperlipidemia (Chase, 2002). Rash and dyspepsia are the most common adverse effects from fenofibrate, and gastrointestinal complaints (eg, abdominal or epigastric pain, dyspepsia) are the most common adverse effects from gemfibrozil (Chase, 2002).

 

HMG-CoA reductase inhibitors (Chase, 2002): drugs of the statin class are structurally similar to HMG-CoA, a precursor of cholesterol, and are competitive inhibitors of HMG-CoA reductase, the last regulated step in the synthesis of cholesterol (Chase, 2002). The HMG-CoA reductase inhibitors inhibit the rate-limiting step in the synthesis of cholesterol, resulting in increases in the number of LDL receptors on hepatocytes and clearance of LDL-C from the bloodstream (Chase, 2002). These agents reduce hepatic secretion of VLDL and may also increases HDL-C levels (Chase, 2002). They lower serum LDL-C concentrations by up-regulating LDL receptor activity and reducing the entry of LDL into the circulation (Chase, 2002). Inhibitors of HMG-CoA reductase also may have antiatherogenic effects unrelated to their lipid-lowering effects (eg, improved function of the endothelial cells that line the inner surface of the arterial wall and decreased platelet thrombus formation) (Chase, 2002).

 

Given alone for primary or secondary prevention, these drugs can reduce the incidence of CHD by 25% to 60% and reduce the risk of death from any cause by approximately 30% (Chase, 2002). Therapy with a statin also reduces the risk of angina pectoris and cerebrovascular accidents and decreases the need for coronary artery bypass grafting and angioplasty (Chase, 2002).

 

The dose required to lower serum LDL-C concentrations to a similar degree varies substantially among the statins (Chase, 2002). In addition, the response to increases in the dose is not proportional, because the dose-response relation for all 6 statins is curvilinear (Chase, 2002). In general, a doubling of the dose decreases serum LDL-C concentrations by an additional 6% (Chase, 2002). The maximal reduction in serum LDL-C concentrations induced by treatment with a statin ranges from 24% to 60% (Chase, 2002). Another statin that is currently under review (but not approved for use) at the Food and Drug Administration, rosuvastatin, may have an even greater effect on LDL-C than the ones currently available (Chase, 2002).

 

All the statins lower serum triglyceride concentrations, with atorvastatin and simvastatin having the greatest effect (Chase, 2002). In general, the higher the baseline serum triglyceride concentration, the greater the decrease induced by statin therapy (Chase, 2002). Statins are a useful adjunct in the treatment of moderate hypertriglyceridemia, but they are often insufficient as monotherapy (Chase, 2002). The HMG-COA reductase inhibitors are considered to be the most effectivehypolipidemic agents available for lowering LDL-C levels (Chase, 2002).

 

Statins are useful in treating most of the major types of hyperlipidemia; the classic indication is heterozygous familial or polygenic hypercholesterolemia, in which the LDL receptor activity is reduced (Chase, 2002). Statins increase LDL receptor activity by inhibiting the synthesis of cholesterol; they also reduce the formation of apolipoprotein B-containing lipoproteins and impede their entry into the circulation and can reduce high serum concentrations of triglycerides and remnant lipoproteins (Chase, 2002). As a result, statin therapy is also indicated in patients with combined or familial combined hyperlipidemia, remnant removal disease, and the hyperlipidemia of diabetes and renal failure (Chase, 2002).

 

Patients should be counseled regarding the proper administration and adverse effects of the HMG-CoA reductase inhibitors (Chase, 2002). Since lovastatin (Mevacor) is better absorbed when taken with food, it should be taken with meals; however, pravastatin is best taken on an empty stomach or at bedtime (Chase, 2002). Food has less of an effect on the absorption of the other statins; because the rate of endogenous cholesterol synthesis is higher at night, all the statins are best given in the evening (Chase, 2002).

 

Adverse effects from HMG-CoA reductase inhibitors are uncommon (Chase, 2002). The most common adverse effects of statins are gastrointestinal upset, muscle aches, and hepatitis. Liver enzyme elevations have been reported (Chase, 2002). Rarely, patients may complain of rash, peripheral neuropathy, insomnia, bad or vivid dreams, and difficulty sleeping or concentrating (Chase, 2002). For patients who have central nervous system adverse effects, a statin with no penetration of the central nervous system, such as pravastatin, can be tried (Chase, 2002).

 

Myopathy (muscle aching or weakness accompanied by increases in creatine kinase) and rhabdomyolysis (muscle breakdown sometimes accompanied by myoglobinuria and acute renal failure) are rare complications of HMG-CoA reductase inhibitor therapy (Chase, 2002). The risk of myopathy and rhabdomyolysis is increased when HMG-CoA reductase inhibitors are used with certain other drugs, including other hypolipidemic agents (specifically, fibric acid derivatives and niacin), azole antifungal agents, erythromycin, and immunosuppressants (eg, cyclosporine) (Chase, 2002).

 

Pharmacokinetic differences among individual HMG-CoA reductase inhibitors may translate into differences in their propensity to interact with other drugs, although comparative studies have not been performed (Chase, 2002). Most HMG-CoA reductase inhibitors (pravastatin is an exception) are metabolized by hepatic cytochrome P450 enzymes (particularly the 3A4 isoenzyme) and can interact with drugs that inhibit these enzymes, resulting in accumulation of the HMG-CoA reductase inhibitor (Chase, 2002). All of the HMG-CoA reductase inhibitors are highly protein bound except for pravastatin, which is roughly 50% bound and possibly less likely to interfere with other drugs that are highly protein bound (Chase, 2002).

 

Other Therapies (Chase, 2002)

 

Dietary supplementation with soluble fiber, such as psyllium husk, oat bran, guar gum and pectin, and fruit and vegetable fibers, lowers serum LDL-C concentrations by 5% to 10% (Chase, 2002). Sitostanol, a plant sterol incorporated into a margarine-like spread (Take Control), inhibits gastrointestinal absorption of cholesterol (Chase, 2002). Small amounts of plant stanols are also found in soybeans, wheat, and rice (Chase, 2002). The n-3 fatty acids, also known as omega-3 fatty acids, can lower serum triglyceride concentrations by up to 30% at a daily dose of 3 g and by about 50% at a daily dose of 9 g (Chase, 2002). Eating 9 to 12 oz of salmon a day supplies enough omega-3 fatty acid; however, most people obtain the dosage through fish oil supplements (Chase, 2002).

 

In postmenopausal women, oral estrogen therapy can lower serum LDL-C concentrations by approximately 10% and raise serum HDL-C concentrations by approximately 15%; however, the risk of venous thrombosis doubles or triples, and there is no overall reduction in the risk of recurrence of coronary disease among women (Chase, 2002). Women with serum triglyceride concentrations above 300 mg/dL may be treated with transdermal estrogen to aid in lowering triglyceride levels; rarely, an anabolic steroid such as oxandrolone (Oxandrin) or stanozolol (Winstrol) is used to reduce the hepatic secretion of triglycerides (Chase, 2002).

 

Advanced Practice Nurse and Pharmacist Roles (Chase, 2002)

 

Cardiovascular disease accounts for nearly 50% of all deaths in the United States (Chase, 2002). Clinical trials and pathophysiologic evidence support the use of aggressive therapy in patients with arteriosclerotic vascular disease and in those with several risk factors for the disease (Chase, 2002). Pharmacists and advanced practice nurses can have a large impact on the health of their patients by conducting cholesterol screening programs and obtaining patient histories to determine if the patient is at risk for CHD (Chase, 2002).

 

Patient education is also a vital component of the entire healthcare team for patients with hypercholesterolemia (Chase, 2002). Patients should be counseled on the role of dietary therapy, exercise, and drug therapy (Chase, 2002). Healthcare practitioners must consider hypolipidemic drug therapy to achieve the target LDL-C goal when necessary (Chase, 2002). Conscientious attention to therapeutic lifestyle changes and pharmaceutical care of patients with lipid disorders will improve patient adherence to the treatment plan and the ultimate patient outcomes (Chase, 2002).

 

The next section will focus on the role that pharmacists, in particular, can play in the management of hypercholesterolemia, with particular reference to the fact that hypercholesterolemia is not well managed, in general, by physicians.

 

Chapter 5: Management of Hypercholesterolemia By Different Health Care Workers.

 

Eaton et al. (1998) wanted to compare the frequency of cholesterol testing and treatment of hypercholesterolemia in patients cared for by family physicians, general internists, and cardiologists, and used a continuous cross-sectional survey of 1991 ambulatory office visits using a national probability sample of U.S. physicians’ office practices (National Ambulatory Care Survey) (Eaton et al., 1998). The physicians surveyed self-reported their specialty as family practice, internal medicine, or cardiology (Eaton et al., 1998). Records of 33,795 patient visits to 1354 physicians were reviewed to find out whether the physicians reported cholesterol testing, cholesterol counseling, and charting of patient use of lipid-lowering medication; the results were compared among the three specialist groups (Eaton et al., 1998).

 

The preliminary results of the Eaton et al. (1998) study showed that during an annual health examination (9.77 million office visits), a cholesterol test was reported by 23.5% of family physicians, 43.5% of internists, and 13.1% of cardiologists (P < 0.01) (Eaton et al., 1998). For all hypercholesterolemic patients (23.52 million office visits), the age- and sex-adjusted percentages of reported cholesterol-reduction counseling during office visits were 38.3% for family physicians, 42.4% for internists, and 36.5% by cardiologists (NS), and percentages of reported lipid-lowering medication prescriptions were 13.4% for family physicians, 25.1% for internists, and 28.4% for cardiologists (P < 0.01) (Eaton et al., 1998).

 

In hypercholesterolemic patients with coronary heart disease (3.47 million office visits), the age- and sex-adjusted percentages of cholesterol reduction counseling reported during office visits were 64.4% for family physicians, 47.1% for internists, and 35.9% for cardiologists (NS) and the age- and sex-adjusted percentages of lipid-lowering medication prescriptions reported were 13.9% for family physicians, 62.5% for internists, and 34.7% for cardiologists (P < 0.01) (Eaton et al., 1998).

 

The main conclusions of the Eaton et al. (1998) study were that recommended goals regarding cholesterol testing and management were not reached by any physician group, and that internists tested for hypercholesterolemia during an annual health examination more frequently and had more patients using lipid-lowering medications than did family physicians or cardiologists (Eaton et al., 1998). Understanding the reasons for these specialty differences might lead to improvement in the diagnosis and management of hypercholesterolemia and therefore reduction in cardiovascular disease (Eaton et al., 1998).

 

Cardiovascular disease is the leading cause of death and morbidity in the United States and most Western societies, and hypercholesterolemia is an important modifiable risk factor for cardiovascular disease (Eaton et al., 1998). Appropriate detection, evaluation, and treatment of hypercholesterolemia should lead to a marked reduction in cardiovascular disease death and morbidity (Eaton et al., 1998). In 1988 the National Heart, Lung, and Blood Institute convened an expert panel that developed national guidelines for the detection, evaluation, and treatment of high blood cholesterol in adults — the National Cholesterol Education Program (NCEP) (Eaton et al., 1998). This expert panel recommended cholesterol screening every 5 years in asymptomatic patients and every 1 to 2 years in patients with cardiovascular disease or abnormal lipid profiles (Eaton et al., 1998). All patients with hypercholesterolemia are recommended to be counseled regarding dietary changes, and if an explicit low-density lipoprotein (LDL) cholesterol goal is not reached, then lipid-lowering medication is recommended (Eaton et al., 1998), as we have seen. For patients with established coronary heart disease, recommended thresholds to initiate lipid-lowering drug therapy are lower (Eaton et al., 1998). Based upon the diet response in the Scandinavian Simvastatin Survival Study, an estimated 90% of patients with established coronary heart disease and hypercholesterolemia should be on lipid-lowering therapy (Eaton et al., 1998).

 

Recent studies have suggested that hypercholesterolemia is underdetected and undertreated, and a recent publication by Jollis et al. purported to show that patients with acute myocardial infarctions cared for by cardiologists had better outcomes than patients cared for by family physicians and internists (Eaton et al., 1998). In explaining these apparent differences in outcomes, Jollis et al. speculated that differences in the frequency in the use of medications, such as aspirin, beta-blockers, heparin, and nitroglycerin, could have explained the better outcomes attributed to cardiologists (Eaton et al., 1998). Eaton et al. (1998) speculate that the differences by specialty in the detection, evaluation, and treatment of hypercholesterolemia might be operative as well (Eaton et al., 1998). Although descriptive studies describing the frequency of detection, counseling, and pharmacologic management of hypercholesterolemia by primary care physicians and cardiologists have been published, few, if any, between-specialty comparisons have been reported (Eaton et al., 1998).

 

By better understanding the similarities and differences in the detection, evaluation, and treatment of hypercholesterolemia between specialties, we can develop improved strategies to enhance risk-factor screening, counseling, and treatment of hypercholesterolemia for all physicians (Eaton et al., 1998). The 1991 National Ambulatory Medical Care Survey (NAMCS) allows for a comparison of detection, counseling, and lipid-lowering medication utilization patterns with regard to hypercholesterolemia for representative samples of family physicians, internists, and cardiologists; because this survey occurred 3 years after the release of the original NCEP guidelines, primary care physicians and cardiologists should have had enough time to have incorporated these guidelines into their practice (Eaton et al., 1998).

 

Methods (Eaton et al., 1998)

 

NAMCS is a continuous survey of a nationwide probability sample of health care providers in the United States administered by the National Center for Health Statistics (Eaton et al., 1998). It attempts to capture objective information about ambulatory medical services provided in physicians’ offices; hospital clinics, urgent care centers, and community health centers are not included in the survey, and the services provided by independent nurse practitioners, chiropractors, and homeopaths are also not included (Eaton et al., 1998). One hundred twelve counties or standard metropolitan statistical areas are sampled throughout the United States (Eaton et al., 1998). Physicians representing 15 specialties from the American Medical Association and American Osteopathic Association master files are sampled from each area (Eaton et al., 1998). The total physician sample is divided into 52 sub-samples representing 1 week of patient visits (Eaton et al., 1998).

 

The sampling rate for each office is based upon the size of the practice to insure complete data collection for each patient visit (Eaton et al., 1998). The actual data collection is carried out by the physician and his or her office staff; each physician records approximately 30 office visits per week (Eaton et al., 1998). The nature of the patient’s complaints, diagnosis, diagnostic or screening services provided, therapeutic services, medications, disposition, and time spent with the physician are recorded after each patient visit (Eaton et al., 1998) (Eaton et al., 1998).

 

To provide unbiased national estimates, 33,795 records from 1354 physicians were abstracted and weighted according to standard cluster sampling techniques to estimate 669 million yearly office visits adjusting for sampling probabilities, non-response bias, and ratio adjustment by physician specialty (Eaton et al., 1998).

 

Physician categories available were based upon self-report for family physicians, general practitioners, general internists, obstetrician-gynecologists, cardiologists, and cardiovascular surgeons (Eaton et al., 1998). The hypercholesterolemia treatment practice patterns of family physicians were compared with that of general internists and did not include general practitioners, so that board certification requirements between primary care physicians would be similar (Eaton et al., 1998). The practice patterns of cardiovascular surgeons, since the sample was too small to make any meaningful inferences, and to have representative samples of male and female patients, obstetrician-gynecologists were excluded (Eaton et al., 1998).

 

Diagnoses were coded using the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) (Eaton et al., 1998). ICD-9 codes 410 through 414 for any of three diagnoses coded per patient encounter were used to define coronary heart disease in this analysis (Eaton et al., 1998). Reasons for visits were coded using A Reason for Visit Classification for Ambulatory Care developed by the American Medical Records Associations (Eaton et al., 1998). An annual health examination was based upon physician reports using this code; physician diagnostic and screening services, therapeutic services, and medications were assessed using the NAMCS data instrument (Eaton et al., 1998). Physicians were asked to code after each visit whether the patient had hypercholesterolemia, whether a cholesterol test was ordered or performed, and whether counseling for hypercholesterolemia was performed (Eaton et al., 1998). Use of lipid medications was ascertained from the list of medications recorded during each patient encounter (Eaton et al., 1998). A specific question regarding a prescription for or patient utilization of specific lipid-lowering medications was not asked (Eaton et al., 1998).

 

Statistical analysis was performed using SPSS; the frequency of cholesterol testing is given as a percentage; its calculation was based upon the weighted results determined by the cluster sampling used in the NAMCS survey (Eaton et al., 1998). Analyses adjusted for age and sex differences in the patient populations between specialties used the weighted results and the three specialties’ combined population as the standard population (Eaton et al., 1998). Statistically significant differences between specialties in their frequency of cholesterol counseling and prescribing lipid-lowering medications were determined by performing a logistic regression on unweighted data, comparing internists with family physicians and cardiologists with family physicians, adjusting for age, sex, and where applicable, the diagnosis of coronary heart disease or annual health examination (Eaton et al., 1998).

 

This conservative approach was used because the weighting procedures based upon cluster sampling are meant to be used only to estimate differences in the frequency for pre-specified groups, such as physician specialties (Eaton et al., 1998). Maximum likelihood estimating procedures used in logistic regression to adjust for multiple confounders are not valid when using the weighted results, because the standard errors associated with the weighted estimates for multiple strata of each variable are unknown (Eaton et al., 1998).

 

Results (Eaton et al., 1998)

 

Cholesterol Testing (Eaton et al., 1998)

 

Of the 99 million estimated patient encounters by internists, 10% had cholesterol testing, whereas of the 48.6 million estimated patient encounters by family physicians, 6.1% had cholesterol testing (Eaton et al., 1998). Cardiologists surveyed had an estimated 11.5 million patient encounters, of which 8.7% had cholesterol testing (Eaton et al., 1998). As the reason for visits might differ by specialty and, therefore, the appropriateness to perform cholesterol testing might differ, rates of cholesterol testing were compared during an annual health examination, when the indications for testing would be similar (Eaton et al., 1998). The frequency of cholesterol testing was higher in all specialties during an annual health examination compared with all patient encounters (Eaton et al., 1998). The differences between specialties for cholesterol testing during annual health examinations are as follows: internists measured cholesterol levels in 43.5%, family physicians in 23.5%, and cardiologists in 13.1% of annual health examination encounters (P < 0.01) (Eaton et al., 1998).

 

Comparing the frequency of cholesterol testing for patients with established coronary heart disease regardless of the reason for the visit revealed no significant differences, with 15.8% of family physicians performing cholesterol testing, followed by 14.4% of internists, and then 9.1% of cardiologists (Eaton et al., 1998).

 

The frequency of cholesterol testing varied significantly by age and sex of the patients (Eaton et al., 1998). Family physicians and cardiologists were more likely to measure cholesterol levels in men, whereas internists were more likely to measure cholesterol levels in women (Eaton et al., 1998). This difference is striking for young women aged between 18 and 29 years, with 74% having cholesterol testing performed by internists and only 9.8% having cholesterol testing performed by family physicians (Eaton et al., 1998). Family physicians and cardiologists were also less likely than internists to screen elderly patients (older than 65 years) (Eaton et al., 1998).

 

Adjusting for age, sex, and rates of annual physical examinations, internists were 83.8% more likely to perform cholesterol tests than family physicians (OR = 1.83, P < 0.05), whereas cardiologists did not differ from family physicians in their rates of screening (Eaton et al., 1998).

 

Management of Hypercholesterolemia (Eaton et al., 1998)

 

There was no statistically significant difference in the frequency of cholesterol counseling during office visits between specialty groups for patients with hypercholesterolemia (Eaton et al., 1998). Regarding the use of lipid-lowering medications, however, internists (25.1%) were much more likely than family physicians (13.4%) to have reported patients using lipid-lowering medications (P < 0.01) (Eaton et al., 1998). Cardiologists (28.4%) were also more likely to have reported patients using lipid-lowering medications than family physicians, but this result did not reach statistical significance because of the smaller number of patients seen by cardiologists (Eaton et al., 1998).

 

Family physicians (61.9%) were more likely than internists (46.8%) or cardiologists (38.0%) to perform cholesterol reduction counseling during office patient visits, but these differences are not statistically significant (Eaton et al., 1998). Regarding use of lipid-lowering medications, internists (63.3%) were the most likely, followed by cardiologists (34.7%), and then family physicians (13.9%), to prescribe lipid-lowering medications to hypercholesterolemic patients with coronary heart disease (P < 0.01) (Eaton et al., 1998).

 

Discussion (Eaton et al., 1998)

 

The 1991 NAMCS survey provides a unique means to compare testing for and management of hypercholesterolemia by family physicians, internists, and cardiologists based upon a national probability sample (Eaton et al., 1998). The analysis of Eaton et al. (1998) suggests a significant interspecialty variation in the frequency of cholesterol testing and the frequency of drug therapy in the treatment of hypercholesterolemia (Eaton et al., 1998). Internists were much more likely to order cholesterol testing during annual physical examinations (83% more likely than family physicians) (Eaton et al., 1998). Cholesterol testing is recommended every 5 years in asymptomatic persons and every 1 to 2 years in patients with cardiovascular disease or who have borderline or abnormal lipid levels according to the NCEP guidelines (Eaton et al., 1998).

 

The frequency of cholesterol testing found in this cross-sectional survey needs to be interpreted within this longitudinal framework (Eaton et al., 1998). Accordingly, it is difficult to comment on the appropriateness of cholesterol testing compared with national guidelines from the NAMCS data (Eaton et al., 1998). The marked increase in testing noted by internists during an annual health examination might reflect a practice style of performing most preventive services at one time rather than interspersed within acute care visits, which might be more common in a family practice settings (Eaton et al., 1998). Cardiologists might be seeing patients by referral and assuming that the primary care physicians will be performing cholesterol testing (Eaton et al., 1998).

 

The marked sex differences in cholesterol testing during annual examinations (only 15% of women seen by family physicians compared with 46.7% seen by internists) deserves further investigation (Eaton et al., 1998). These results could reflect competing demands, with family physicians focusing on gynecologic complaints or other women’s health issues, but it does raise concerns about potential sex bias (Eaton et al., 1998).

 

Eaton et al. (1998) found that with the exception of coronary heart disease patients cared for by family physicians, the frequency of cholesterol counseling for patients with diagnosed hypercholesterolemia was less than 50% (Eaton et al., 1998). This frequency clearly reflects a less than optimal management of this important risk factor for coronary heart disease by all specialties (Eaton et al., 1998). It is here, then, that pharmacists can play a vital role in the diagnosis and treatment of hypercholesterolemia, and the next section will discuss this in further detail.

 

Eaton et al. (1998) also found a low rate of pharmacologic therapy for patients with hypercholesterolemia and coronary heart disease (Eaton et al., 1998). Family physicians reported prescribing lipid-lowering medications in less than 15% of patient encounters, compared with 62.5% for internists and 34.7% for cardiologists, after adjusting for age and sex (Eaton et al., 1998). This finding suggests that significant specialty differences exist (Eaton et al., 1998). This lack of an effective counseling or pharmacologic treatment plan for hypercholesterolemia by family physicians, internists, and cardiologists is consistent with reports in the medical literature (Eaton et al., 1998).

 

Eaton et al. (1998) in a small study in one academic family medicine practice, found that for hypercholesterolemic patients with and without cardiovascular disease, between 72 and 74% had cholesterol testing, between 57 and 65% had dietary changes recommended, and between 20 and 26% were offered pharmacologic therapy, but only 2 to 7% had cholesterol levels controlled (Eaton et al., 1998). Nieto et al., in the Atherosclerosis Risk in Communities study of 15,739 persons, showed that only 42% of hypercholesterolemic (total cholesterol levels > 240 mg/dL) patients were aware of their diagnosis compared with 84% of hypertensive patients (Eaton et al., 1998).

 

Only 4% of hypercholesterolemic patients in this community study had their cholesterol treated and controlled (Eaton et al., 1998). National Health and Nutrition Examination Survey III data collected from 1988 to 1991 show that 87% of adults older than 20 years with fewer than two coronary heart disease risk factors have adequately controlled LDL cholesterol levels, whereas only 43% of adults with two or more risk factors have adequately controlled LDL cholesterol levels, and only 15% of adults with coronary heart disease have adequately controlled LDL cholesterol levels (Eaton et al., 1998). Klein et al., in the Beaver Dam Eye Study, found that between 9.8 and 14.6% of hypercholesterolemic patients were on lipid-lowering therapy (Eaton et al., 1998).

 

The differences by specialty in use of lipid-lowering drugs for both primary and secondary prevention of coronary heart disease (P < 0.01), with family physicians prescribing medication less frequently, is not well documented in the medical literature and is worthy of further investigation (Eaton et al., 1998). These specialty differences could reflect a patient-centered negotiating style adopted by family physicians, in which lipid-lowering agents are not prescribed for patients unless they agree to be compliant; therefore, family physicians might counsel hypercholesterolemic patients more, or indeed, as we shall see, there is a role for pharmacists in this arena (Eaton et al., 1998). The differences in prescription patterns by specialty could represent confounding by health insurance status by specialty, as differences in the cost-benefit ratio for lipid-lowering therapy might vary for those patients who do not have a prescription plan covering the cost of lipid-lowering medications (Eaton et al., 1998).

 

All the results of this Eaton et al. (1998) study should be interpreted with caution: the data are self-reported and are prone to misclassification bias (Eaton et al., 1998). Such a bias would be non-differential and therefore bias the results toward the null, making any interspecialty comparisons more difficult to uncover (Eaton et al., 1998). Concerns about difference in the mix of patient diagnoses, age, sex, and severity of illness also make interspecialty comparisons difficult to interpret (Eaton et al., 1998). This issue was dealt with by comparing patients with similar ICD-9 codes relevant to coronary heart disease and by comparing patients seen for an annual health examination (Eaton et al., 1998). When comparing treatment frequency for hypercholesterolemia, adjusted analyses were performed to deal with confounding by age, sex of patients, and coronary heart disease; other potential confounders, such as socioeconomic status, health insurance status, and physician age and sex, were not available for analysis (Eaton et al., 1998).

 

Another potential weakness of the Eaton et al. (1998) study is the time frame of the analysis: the NAMCS data were collected in 1991 and are 6 years old (Eaton et al., 1998). This National Ambulatory Medical Care Survey is the first for which cholesterol testing and treatment data were collected; these data capture practice patterns of physicians 3 years after the release of the original NCEP guidelines (Eaton et al., 1998). While the absolute percentages might be different in 1997 compared with 1991, it is hoped improved, specialty differences analyzed in Eaton et al. (1998) might well be stable; future NAMCS data can be evaluated serially to test this hypothesis (Eaton et al., 1998). The major strength of this Eaton et al. (1998) study comes from its generalizability, as it estimates more than 669 million U.S. physician office visits in 1991 (Eaton et al., 1998).

 

As confirmed by Eaton et al., (1998) and others, hypercholesterolemia is underdetected and undertreated, and it appears to be a universal problem for all specialties analyzed (Eaton et al., 1998). Internists appeared to perform better than family physicians and cardiologists in the detection and drug treatment of hypercholesterolemia (Eaton et al., 1998). Future research to better understand these differences might be helpful for changing physician practice patterns so that the primary and secondary prevention of coronary heart disease can be optimized by devising better methods for the detection and management of hypercholesterolemia (Eaton et al., 1998). More effective use of practice guidelines, office-based systems, pharmacists, nurses, physician extenders, or medical informatics might be needed to reach national goals of optimal cholesterol management (Eaton et al., 1998). The next section will look at this issue in more detail.

 

Chapter 6: Practical Management of Hypercholesterolemia

 

The first indication of the presence of CHD is sudden cardiac death in 50% of men and 63% of women: this statistic illustrates the importance of early detection and treatment of hypercholesterolemia (Olson et al., 2001). An estimated 36-50% of the general population have hypercholesterolemia warranting treatment with, at a minimum, dietary modifications; therefore, screening the population is a crucial first step in the early detection and subsequent management of hypercholesterolemia to prevent the onset and progression of CHD (Olson et al., 2001).

 

Reports from the National Cholesterol Education Panel (NCEP) recommend that all adults aged 20 years or older have their total cholesterol and high-density lipoprotein (HDL) assessed at least once every 5 years (Olson et al., 2001). Depending on initial screening results and an individual’s risk factors, a full lipoprotein analysis may be required; despite wide dissemination of the NCEP guidelines, population-based data indicate that only approximately 8% of the population is screened annually, much lower than the 20% expected if the guidelines were followed (Olson et al., 2001).

 

Since the publication of the NCEP II guidelines, controversy has arisen regarding the rationale and cost-effectiveness of mass cholesterol screening of adults in the general population (Olson et al., 2001). Proponents suggest that mass screening of all adults over 20 years of age is necessary due to evidence that atherosclerosis commences early in childhood (Olson et al., 2001). Screening provides patients with a complete cardiac assessment, identifies individuals who would benefit from lipid-lowering interventions, and promotes public awareness of the role of cholesterol in cardiac risk (Olson et al., 2001). On the other hand, others recommend selectively screening those individuals most likely to benefit from lipid-lowering interventions if they are found to be hypercholesterolemic (Olson et al., 2001). This practice would be consistent with Canadian, European, and British clinical practice recommendations; furthermore, recommendations published since NCEP II suggest limiting screening to men and women over the ages of 35-40 years and 45-50 years, respectively; any individual with more than two risk factors; and persons with a family history of familial hypercholesterolemia (Olson et al., 2001). All recommendations state that any patient with documented CHD should undergo an aggressive screening strategy (i.e., yearly testing), given the great benefit of early detection and management of hypercholesterolemia in patients with established CHD (Olson et al., 2001).

 

Data from numerous retrospective audits of medical records from both inpatients and outpatients with CHD indicate that only 64% (range 28-96%) of these high-risk individuals had cholesterol measurements documented (Olson et al., 2001). Based on these data, approximately 36% (and as many as 72%) of patients with CHD are not screened for hypercholesterolemia (Olson et al., 2001). Two studies did report exceptionally high proportions of patients being screened: 93% and 96% respectively; however, one used protocols and care maps to guide lipid management, and the other included only those physicians who agreed to participate (Olson et al., 2001). Although all of these studies relied on retrospective chart documentation of cholesterol levels as indicators for screening, they nevertheless highlight the possibility of significant missed opportunities for intervention and improvement in patient outcomes (Olson et al., 2001).

 

Although it is evident that the implementation of screening strategies for hypercholesterolemia is suboptimal, the proportion of patients screened seems to have increased over time; furthermore, screening practices appear to increase as patients move from primary to secondary prevention (Olson et al., 2001). Still, improvements are needed to increase screening, at least for patients at the greatest risk for CHD events (Olson et al., 2001). This measure is a crucial first step in the identification and subsequent management of those with hypercholesterolemia (Olson et al., 2001).

 

Implementation of Therapy (Olson et al., 2001)

 

Given the suboptimal rate of screening for cholesterol risk, it is perhaps not surprising that many investigators suspect that patients are undertreated for hypercholesterolemia (Olson et al., 2001). A 1993 study involving a database of 154,735 adults estimated that 72% of those eligible for lipid-lowering therapy with diet or drugs failed to receive either form of treatment (Olson et al., 2001). Although this study was completed before the publication of the NCEP II guidelines and the pivotal statin trials, the rate is consistent with a 1998 survey of 7423 adults, which found that 71% of treatment-eligible patients in the general population received no therapy (Olson et al., 2001).

 

Nonpharmacologic Therapy: General Population (Olson et al., 2001)

 

Published guidelines suggest that non-pharmacologic therapy, including diet, exercise, and smoking cessation, be initiated in all patients requiring treatment for hypercholesterolemia, with the addition of lipid-lowering drugs in select groups of patients; yet, despite these recommendations, data indicate wide variation in the implementation of such therapy (Olson et al., 2001).

 

Data from several studies show that 34% (range 11-79%) of patients receive counseling for nonpharmacologic interventions (Olson et al., 2001). The largest of these studies found that of 85 million physician visits by patients with documented hypercholesterolemia, only 34% of patients received nonpharmacologic counseling for hypercholesterolemia, defined as any counseling (including dietary) related to cholesterol (Olson et al., 2001). This may be an underestimate as non-physician and community services were excluded from the analysis or counseling may not have been documented (Olson et al., 2001). The most optimistic estimate of patients started on dietary therapy was 79% (Olson et al., 2001). The study yielding this estimate was the only prospective assessment of cholesterol management practices (telephone interviews of 154,735 adults in the United States) that has been found, and it is likely an overestimate because the study addressed only a minority (10.3%) of highly selected patients (i.e., those who were aware of having hypercholesterolemia) (Olson et al., 2001).

 

Nonpharmacologic Therapy: Patients with CHD (Olson et al., 2001)

 

Studies that specifically evaluated the use of nonpharmacologic therapy in patients with documented CHD reveal that only 32% (range 11-55%) of patients receive counseling on the therapy (Olson et al., 2001). One would expect this estimate to be much higher, given the well-established benefits of cholesterol reduction in these high-risk patients (Olson et al., 2001). Based on a survey of 7423 patients, the fraction of U.S. adults with CHD eligible for and receiving dietary therapy is only 29% (Olson et al., 2001). This percentage is identical to that estimated in the general population; a related study, a retrospective chart audit of 3304 inpatients with cardiovascular disease, found that only 5% of the patients had documentation of recommendations for lifestyle adjustments and only 22% had recommendations for dietary therapy (Olson et al., 2001).

 

Interpretation of data on nonpharmacologic therapy is difficult, as these interventions are continuous variables (e.g., patients may only partially modify their diet) rather than simple dichotomous outcomes, and various degrees of success in implementation are possible (Olson et al., 2001). Furthermore, counseling and nonpharmacologic therapies may be used more frequently than reported, given that these recommendations may be poorly documented in patients’ medical records (Olson et al., 2001).

 

It is important to note that investigators have found dietary therapy alone may be ineffective at reducing cholesterol levels (Olson et al., 2001). In fact, some suggest that the step I and II diets recommended by the NCEP II guidelines may not be aggressive enough at reducing cholesterol levels, perhaps making documentation of dietary recommendations irrelevant (Olson et al., 2001). Still, lifestyle adjustments are cost-effective when patients are compliant and are healthy initiatives that should be encouraged and reinforced in all patients (Olson et al., 2001).

 

Lipid-lowering Agents: General Population (Olson et al., 2001) large proportion of the population requires lipid-lowering agents to achieve optimal cholesterol levels (Olson et al., 2001). General population surveys evaluating the use of these drugs indicate that only 23% of patients receive drug therapy for hypercholesterolemia; furthermore, these surveys suggest that 65-77% of the general population receive no therapy (drug or nondrug) at all for hypercholesterolemia (Olson et al., 2001).

 

A national survey of randomly selected, office-based physician visits reported the highest rate of prescriptions for lipid-lowering agents at 23% (Olson et al., 2001). This report may overestimate the actual administration because individuals were captured on a per-visit basis rather than a per-patient basis and because patients prescribed drug therapy are more likely to require follow-up with their physician (Olson et al., 2001). Another study reported the use of lipid-lowering agents to be 19% among a select group of patients who were aware of their elevated cholesterol (only 10.3% of the total population surveyed) (Olson et al., 2001). Consistent with data on population screening, the studies suggest that only a minority of patients eligible for lipid-lowering pharmacologic therapy actually receive it (Olson et al., 2001).

 

A limitation of these data is that they do not account for the degree or duration of cholesterol elevation or the appropriateness of lipid-lowering drug therapy (Olson et al., 2001). It is conceivable that some patients surveyed had cholesterol levels for which drug therapy was not indicated and that many may have received nonpharmacologic therapy, such as dietary counselling (Olson et al., 2001).

 

Lipid-lowering Agents: Patients with CHD (Olson et al., 2001)

 

The absolute benefits of lipid-lowering agents are greatest among those patients with established CHD.[4-6] Drug therapy is recommended immediately, in conjunction with diet and nonpharmacologic therapy, in high-risk patients with lipid levels above target (Olson et al., 2001). Published data from 12 studies involving 68,446 patients with established CHD indicate that only 35% (range 6-62%) received therapy with a lipid-lowering agent (Olson et al., 2001).

 

Again, this literature must be interpreted cautiously, given that the majority of studies did not present the cholesterol levels of the patients; therefore, not all patients may have required drug therapy (Olson et al., 2001). A study of 2763 high-risk patients did identify lipid levels and reported that only 39% of patients with low-density lipoprotein (LDL) levels greater than 130 mg/dl (3.4 mmol/L; a level at which drug therapy should be initiated according to guidelines were prescribed drug therapy (Olson et al., 2001).

 

Whereas most of reported studies retrospectively documented the administration of hypolipidemic agents at single time points, it is possible that prescriptions for these drugs may increase over time as physicians become more familiar with clinical trial data and practice guidelines (Olson et al., 2001). Two studies evaluated the prescription of lipid-lowering therapy over time: the first reported that of 95 patients hospitalized for cardiac catheterization, 25.9% with known hypercholesterolemia were treated with drugs before the procedure (Olson et al., 2001). This figure increased to 32.8% between 1 and 2 years after the procedure (Olson et al., 2001). The second study examined trends in cholesterol management over more than 9 years among 1710 patients hospitalized with recurrent acute myocardial infarction (Olson et al., 2001). Significantly more patients received lipid-lowering drugs in 1995 compared with 1986 (0.8% vs. 11.7%, p<.001); still, in 1995, 36% of patients had elevated cholesterol levels and thus many patients remained untreated (Olson et al., 2001). These studies provide encouragement that practice patterns may improve, but it is important to remember that approximately one-third of high-risk patients are untreated with lipid-lowering agents (Olson et al., 2001).

 

Treatment to Cholesterol Targets (Olson et al., 2001)

 

Even when hypercholesterolemia is identified and treatment is instituted, many patients are not treated to target cholesterol levels (Olson et al., 2001). The British, NCEP II, and Canadian guidelines all recommend target LDL cholesterol concentrations in accordance with an individual’s cardiac risk stratification; the greater the risk for cardiovascular events, the lower the LDL target; for example, British guidelines recommend LDL targets of 160 and 130 mg/dl (4.1 and 3.4 mmol/L) or less in patients without and with CHD, respectively (Olson et al., 2001). Guidelines from NCEP II identify LDL targets of 160, 130, and 100 mg/dl (4.1, 3.4, and 2.6 mmol/L) or lower for patients with less than two risk factors, more than two risk factors, and established CHD or diabetes, respectively (Olson et al., 2001). Although the recently published Canadian guidelines are similar, targets of less than 97 mg/dl (2.5 mmol/L) for patients with CHD or diabetes are recommended (Olson et al., 2001).

 

An estimated 83% (range 38-100%) of patients with fewer than two cardiac risk factors, compared with 39% (range 30-52%) of patients with more than two risk factors, reach their cholesterol targets (Olson et al., 2001). Among patients at high risk for cardiovascular events, only 21% (range 9-39%) achieve their cholesterol targets (Olson et al., 2001). A large study of 48,586 patients with CHD (39% of whom were taking lipid-lowering agents) reported that only 25% achieved a target LDL of less than 100 mg/dl (2.6 mmol/L) (Olson et al., 2001). This study may have overestimated the population reaching target because it included physicians who were frequent prescribers of 3-hydroxy-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (Olson et al., 2001). These studies should be interpreted cautiously because they did not specify whether patients were receiving lipid-lowering therapy at time of assessment, which is important given the treatment gaps in screening and implementation of therapy (Olson et al., 2001). Paradoxically, the proportion of patients achieving target appears inversely associated with patients’ risk for cardiovascular events (Olson et al., 2001).

 

Only a few studies specifically evaluated the proportion of patients who achieved target while receiving lipid-lowering therapy; surprisingly, the proportion remained unchanged at 21% (range 18-35%) (Olson et al., 2001). The largest and most recently published study enrolled 4888 patients with CHD: it reported that only 18% of patients achieved their LDL targets, despite receiving lipid-lowering agents for the previous 3 months (Olson et al., 2001).

 

Reasons for Suboptimal Management of Cholesterol (Olson et al., 2001)

 

Although ample evidence suggests that patients are not adequately managed for hypercholesterolemia, few studies explore the reasons (Olson et al., 2001). Insights into the mechanisms of undertreatment of elevated cholesterol would help in the development of interventions to improve patient care (Olson et al., 2001). One study found that patients were more likely to receive therapy if they had an LDL measurement documented; history of acute myocardial infarction, coronary artery bypass grafting, or hypertension; or were followed by cardiologists (Olson et al., 2001). Other studies have shown that younger patients, and men are more likely to receive lipid-lowering agents, as are those patients with a history of revascularization (Olson et al., 2001). Factors significantly associated with the achievement of targets include a lower baseline LDL cholesterol, administration of combination drug therapy, and patient adherence to treatment (Olson et al., 2001). The lower proportion of high-risk patients reaching their target LDL levels simply may indicate that cholesterol management is more difficult in these patients, given that the target is much lower (Olson et al., 2001). Alternatively, such patients may be poorly adherent with their drugs or simply undertreated (Olson et al., 2001). Many patients are either lost to follow-up in the community setting or do not have their lipid-lowering therapy assessed routinely (Olson et al., 2001). Overall, factors contributing to the suboptimal achievement of targets can be broadly classified into three categories: patient related, physician related, and health care system related (Olson et al., 2001).

 

Patient-related Factors (Olson et al., 2001)

 

Patient-related factors include drug adherence, side effects or intolerance to prescribed therapies, and drug costs (Olson et al., 2001). Approximately 50-79% of patients discontinue their lipid-lowering drugs within 12 months of initiation (Olson et al., 2001). Generally, adherence is poorer in patients treated with therapies other than HMG-CoA reductase inhibitors, such as bile acid sequestrants or niacin, likely due to adverse effects (Olson et al., 2001). A few studies evaluated the influence of adherence or drug side effects on the achievement of lipid goals (Olson et al., 2001). One such study found that 31% of patients were nonadherent; 72% of those patients failed to achieve their target cholesterol levels (Olson et al., 2001). Other than drug side effects, the reasons for poor adherence with cholesterol-lowering agents are largely unknown (Olson et al., 2001). It may be secondary to a lack of patient knowledge about the importance of cholesterol reduction or the requirement for lifelong therapy; in addition, the cost associated with lipid-lowering drugs may negatively affect adherence rates, although the clinical significance of this factor is unknown (Olson et al., 2001).

 

Numerous studies show that patients are often unaware of having hypercholesterolemia (Olson et al., 2001). One study assessed 15,800 patients in the general population (aged 45-64 yrs) with regard to awareness of the presence of hypercholesterolemia (total cholesterol > 240 mg/dl [6.2 mmol/L]) during 1987-1989 (Olson et al., 2001). It found that 42% of patients were aware of their condition.[51] A related study reported that 53% of patients with elevated total cholesterol, defined as greater than 220, 240, and 259 mg/dl (5.7, 6.2, and 6.7 mmol/L) for patients aged 22-29, 30-39, and 40 years and over, respectively, had no prior knowledge of these elevations (Olson et al., 2001). A third study reported that public awareness of elevated cholesterol levels increased over time, although more than 80% of those surveyed were still unaware of their own condition (Olson et al., 2001). Patients also may simply fall through the cracks and be lost to monitoring and follow-up; clearly, initiatives are needed to improve public awareness of the need for cholesterol monitoring (Olson et al., 2001).

 

Physician-related Factors (Olson et al., 2001)

 

Numerous physician-related factors may affect the management of patients with hypercholesterolemia (Olson et al., 2001). Reliance on laboratory reports to confirm the presence or absence of hypercholesterolemia may cause some patients with abnormal lipid levels to be missed; for instance, a study reported that physicians were more likely to recognize hypercholesterolemia if it were marked as abnormal on the laboratory report (Olson et al., 2001). Many laboratory reports indicate a range of normal cholesterol values without taking into account the level of risk for individual patients (Olson et al., 2001).

 

Lack of knowledge about guidelines and the clinical trials reporting the efficacy of lipid-lowering drugs may contribute to suboptimal cholesterol management (Olson et al., 2001). A 1998 study reported that only 54% of physicians would prescribe lipid-lowering agents to a patient with documented CHD and an LDL greater than 130 mg/dl (3.36 mmol/L), despite evidence and guideline recommendations to initiate therapy in these patients (Olson et al., 2001). A study published in 1988 reported that only 48% of physicians stated that lowering blood cholesterol reduces coronary disease risk “often” or “always,” but the study was conducted before publication of the major lipid-lowering trials (Olson et al., 2001).

 

Physicians may overestimate the adequacy of treatment in their patients with hypercholesterolemia (Olson et al., 2001). They reported performing lipid panels in 86% of their patients, yet on chart audit, lipid panels were available for only 67% of patients (Olson et al., 2001). Another study reported a prevalence of hypercholesterolemia of 24% in family practice patients, yet the condition was documented in only 13% of cases (Olson et al., 2001). Although the reasons for physician nonadherence with guidelines are largely unknown, one report cited physician time constraints, lack of skills for behavioral modifications, patient inattentiveness, and the urgency of the patients’ concomitant medical problems as potential factors (Olson et al., 2001).

 

Health Care System Factors (Olson et al., 2001)

 

Traditionally, health care systems were driven by illness, not prevention (Olson et al., 2001). A survey of family physicians identified the following two assertions as barriers to the provision of preventive services: “patient is well and does not present” and “priority was given to the presenting complaint” (Olson et al., 2001). Although few trials have evaluated the impact of health care system factors on patients’ achievement of target cholesterol measurement, some evidence suggests that lack of appropriate monitoring and follow-up may contribute to poor response rates (Olson et al., 2001). One study found that 88% of patients treated with lipid-lowering therapy and who had not reached their target had been on the same dose of statin for at least 1 year (Olson et al., 2001). Another study found that 65% of patients not achieving their target goals were taking the starting (low) dosage of their lipid-lowering drug (Olson et al., 2001). These data suggest that more aggressive dosage titrations, the use of combination therapy, and aggressive follow-up may be needed to help patients achieve target measurements (Olson et al., 2001).

 

Limitations of Data (Olson et al., 2001)

 

Most studies in this review by Olson et al. (2001) were conducted in North America, making it difficult to generalize to other settings; there is a potential for publication bias in which only reports of poor cholesterol management practices are published (Olson et al., 2001). Given that data from the population-based studies, which provide estimates for millions of people, are remarkably consistent with most smaller studies, it is likely that the data presented here are representative of general practice patterns (Olson et al., 2001). Most of the studies were retrospectively conducted and are limited in their ability to capture undocumented interventions (i.e., screening and treatment initiation) (Olson et al., 2001). At least two of the studies required physicians to consent to being involved; this may have introduced a volunteer bias because those who agreed to participate may have had a greater interest in hypercholesterolemia than other physicians (Olson et al., 2001). These studies, however, involved small numbers of the total patients in this review and did not greatly affect the calculated weighted average (Olson et al., 2001). Most published papers evaluated events at a single point in time rather than accounting for temporal changes over time (Olson et al., 2001). Practice patterns likely have improved since publication of the major clinical trials and guidelines, but few published studies have evaluated temporal changes to practice patterns (Olson et al., 2001). Many studies evaluating the proportion of patients reaching target did not define the LDL goal (Olson et al., 2001). In addition, cholesterol targets were set by consensus guidelines, even though there is little randomized, controlled trial evidence for screening recommendations or specific numeric goals (Olson et al., 2001). Still, randomized trial evidence does suggest that patient outcomes are improved at lower cholesterol levels, a finding that is consistent with considerable epidemiologic evidence (Olson et al., 2001).

 

Future Directions (Olson et al., 2001)

 

Emphasis must be placed on screening, documenting results, initiating therapy, and following patients to improve the proportion of patients achieving target lipid goals (Olson et al., 2001). Recognition of the gap between evidence and practice in cholesterol risk management is increasing; this awareness is an important first step (Olson et al., 2001). Innovative approaches to the management of patients with or at risk for CHD are required to improve the application of appropriate lipid-lowering interventions to eligible patients (Olson et al., 2001).

 

Multidisciplinary team involvement at the level of the community may improve the proportion of patients screened, started on appropriate therapy, and followed to target lipid goals; for example, dieticians can provide appropriate dietary counseling and community pharmacists can identify patients who would benefit from pharmacologic therapy and work with patients and family physicians to optimize the proportion of patients achieving target lipid goals (Olson et al., 2001). Use of advanced measurement technology, such as point-of-care technology involving fingerstick blood samples, may assist in the identification, monitoring, and follow-up of patients; furthermore, reminder systems for both patients and physicians may help ensure that repeat lipid panels and appropriate monitoring and follow-up are conducted (Olson et al., 2001). Further studies should investigate the reasons why patients are not reaching targets and evaluate ways to optimize therapy (Olson et al., 2001). In light of the enormous public health importance of CHD and the availability of safe and efficacious therapies, our next step must be to improve the process of cholesterol risk management (Olson et al., 2001).

 

The next section will focus in detail on the roles that community pharmacists can play in helping to manage hypercholesterolemia.

 

Chapter 7: Community Pharmacists and the Management of Hypercholesterolemia.

 

Bluml et al. (2000) present a review which aims to demonstrate that pharmacists, working collaboratively with patients and physicians and having immediate access to objective point-of-care patient data, promote patient persistence and compliance with prescribed dyslipidemic therapy that enables patients to achieve their National Cholesterol Education Program (NCEP) goals (Bluml et al., 2000). This review was based on 26 community-based ambulatory care pharmacies: independent, chain-professional, chain-grocery store, home health/home infusion, clinic, health maintenance organization/managed care (Bluml et al., 2000).

 

The main results of the Bluml et al. (2000) study are that in a population of 397 patients over an average period of 24.6 months, observed rates for persistence and compliance with medication therapy were 93.6% and 90.1%, respectively, and 62.5% of patients had reached and were maintained at their NCEP lipid goal at the end of the project (Bluml et al., 2000).

 

The main conclusion of the review of Bluml et al. (2000) is that working collaboratively with patients, physicians, and other health care providers, pharmacists who have ready access to objective clinical data, and who have the necessary knowledge, skills, and resources, can provide an advanced level of care that results in successful management of dyslipidemia (Bluml et al., 2000).

 

Introduction (Bluml et al., 2000)

 

Project ImPACT: Hyperlipidemia, a community pharmacy-based demonstration project, was initiated in March 1996 and was completed in October 1999 (Bluml et al., 2000). ImPACT is an acronym for Improve Persistence And Compliance with Therapy (Bluml et al., 2000). Dyslipidemia (hyperlipidemia) was considered an ideal area in which to demonstrate the value that pharmacists can add to the patient care process for several reasons: Coronary artery disease (CAD) is the leading cause of death in the United States and accounts for an annual expenditure of $100 billion for health care; Dyslipidemia has been shown to be associated with increased risk of CAD in large epidemiologic studies; Reduction in low-density lipoprotein cholesterol (LDL-C) levels has been shown to produce reductions in CAD events and total mortality; Other modifiable CAD risk factors are invariably present in patients with hyperlipidemias, including hypertension, diabetes, obesity, and sedentary lifestyle; Pharmacist services are widely accessible to patients, physicians, and other health care providers and add a unique pharmacotherapy management resource to the health care delivery team; Evidence suggests that pharmacists who provide disease management services can increase patient compliance and improve treatment outcomes; A point-of-care testing device for measuring lipid levels, the Cholestech LDX Analyzer, is available to pharmacists and other health care providers; The availability of reliable patient lipid profile results within 5 minutes of obtaining a blood sample by fingerstick allows the pharmacist to be directly involved in management of lipid-lowering therapies and patient outcomes; The management of cholesterol disorders represents a major benchmark by which quality health care services can be evaluated by accrediting agencies and purchasers of health care (Bluml et al., 2000).

 

Lifestyle modifications combined with improvements in persistence and compliance in the use of lipid-lowering medications will result in a greater number of patients reaching their target lipid goals (Bluml et al., 2000). If patients reach and maintain their National Cholesterol Education Program (NCEP) goals, cardiovascular-related risk will be reduced, resulting in positive health care outcomes (Bluml et al., 2000).

 

Objectives (Bluml et al., 2000)

 

The core objectives of Project ImPACT: Hyperlipidemia were to: Improve patient persistence and compliance with lipid-lowering therapy; Increase communication and the flow of clinical information among patients, pharmacists, and physicians; Improve the cholesterol levels of individual patients over time; and, increase the population of patients who reach and maintain their NCEP lipid goals (Bluml et al., 2000).

 

Methods (Bluml et al., 2000)

 

Site Selection (Bluml et al., 2000)

 

As the result of a competitive application process, 32 community pharmacy practice sites distributed across 15 states were selected to participate in Project ImPACT: Hyperlipidemia (Bluml et al., 2000). Selection was based on criteria that addressed the readiness of the pharmacy to provide basic pharmaceutical care services as evidenced by the availability of certain health care resources and the requisite knowledge and skills to facilitate the delivery of such services: Private or semi-private area for patient consultation; Technician support; Documentation system for recording, tracking, and reporting patient care interventions; Experience with patient-focused disease state management programs; Demonstrated communication skills; Ability to implement point-of-care testing technologies (Bluml et al., 2000).

 

In addition, participating pharmacists from all sites attended a 2.5-day orientation and training program at the project’s inception; the training program was the basis for the APhA certificate program “Pharmaceutical Care forPatients with Dyslipidemias” (Bluml et al., 2000).

 

Of the 32 pharmacies, 2 sites were unable to implement the project (one secondary to regulatory issues, and the other secondary to departmental reorganization), 2 experienced unexpected staffing challenges, 1 moved to another location, and 1 pharmacy was sold and closed; thus, a total of 26 pharmacy practice sites in 12 states completed the study (Bluml et al., 2000).

 

Patient Enrollment (Bluml et al., 2000)

 

Patients enrolled in the project were either newly diagnosed with dyslipidemia (e.g., hypercholesterolemia, mixed hyperlipidemia) or were already receiving lipid-lowering medications but were poorly controlled (i.e., not yet at target lipid goal) (Bluml et al., 2000). Patients were identified through referrals from local physicians or other health care providers, by the project pharmacists, or by patient self-referral (Bluml et al., 2000). In cases of non-physician referral, patients’ physicians were contacted by pharmacists and were involved from that point forward in the patient’s care (Bluml et al., 2000). Patients were informed about the expected effects of their participation in the project (i.e., potential benefits, risks, inconveniences, discomforts), were assured confidentiality (patient privacy was protected by use of an assigned code in all reporting), and told about their right to withdraw at any time (Bluml et al., 2000). Patients gave written informed consent and authorized that medical information from other health care providers could be sent to the pharmacist (Bluml et al., 2000).

 

Process of Care (Bluml et al., 2000)

 

Patients provided the necessary personal and general health information that the pharmacist used to assess their CADrisk (Bluml et al., 2000). From a fingerstick blood sample, a fasting lipid profile was obtained using the Cholestech LDX Analyzer (a point-of-care testing device in the “waived” category under the Clinical Laboratory Improvement Amendments), and results were logged into a clinical activity record at each project visit (Bluml et al., 2000). After the initial visit and consultation with the pharmacist, patients were asked to make follow-up visits every month for the first 3 months and quarterly thereafter (Bluml et al., 2000). In addition to being actively involved in their therapy, treatment plans, and goal setting, patients as well as their physicians were kept informed about clinical progress in these areas: Cholesterol test results; Condition; CAD risk; and NCEP goal achievement (Bluml et al., 2000).

 

Practice Model (Bluml et al., 2000)

 

The practice model designed for the project was sufficiently flexible to accommodate variations in staffing and types of resources available at the practice sites represented in the study (Bluml et al., 2000). The practice model structure: Established a process for the seamless flow of patient care data between and among patients, pharmacists, and physicians; Used point-of-care testing technology to obtain timely, objective information about the patient’s progress in a community practice setting; Organized methods for pharmacists to document, interpret, and report their lipid management interventions (Bluml et al., 2000).

 

Persistence and Compliance Measures (Bluml et al., 2000)

 

The persistence measure used for the project was defined as follows: a patient who started on medication, remained on medication subsequent to drug therapy initiation, and continued to be on medication as of his or her last visit (Bluml et al., 2000). Persistence as a percentage was calculated by dividing the number of persistent patients by the total number of patients who started on medication (Bluml et al., 2000). Compliance was determined through an evaluation based on the number of missed doses for each lipid-lowering medication and refill timing (Bluml et al., 2000). Any patient who missed doses for 5 days or more or who missed a scheduled refill visit by more than 5 days was deemed to be noncompliant at that visit (Bluml et al., 2000). Compliance as a percentage was calculated by dividing the number of visits at which patients were compliant by the total number of patient visits (Bluml et al., 2000).

 

End-of-Project Survey (Bluml et al., 2000) final project survey was conducted with all 26 sites to gain an understanding of what factors were likely responsible for creating the environment that produced the persistence, compliance, and treatment-to-goal results (Bluml et al., 2000). The survey also included queries about the sites’ experiences with obtaining payment for the pharmaceutical care services delivered during this project (Bluml et al., 2000).

 

Results (Bluml et al., 2000) total of 574 patients were enrolled at the 26 sites before July 1, 1997. Of those, 397 patients completed the entire study, and results are presented for those patients in the following section (Bluml et al., 2000). There were 34 patients who completed only 1 visit and had insufficient data to allow reporting of results (Bluml et al., 2000). The remaining 143 patients did complete at least 2 visits to the pharmacy, but did not complete the full 2-year observation period: 29 withdrew in the first 90 days, 30 moved from the area, 33 gave personal reasons, 22 had logistical or medical complications, and 29 were lost to follow-up (Bluml et al., 2000). The results for these 143 patients are reported separately at the end of the Results section (Bluml et al., 2000).

 

Patient Population Characteristics (Bluml et al., 2000)

 

At the beginning of the study, 153 (38.5%) of the 397 patients were either newly diagnosed or had been taking lipid-lowering medications for less than 1 month, and 244 (61.5%) had been on lipid-lowering medications for longer periods but remained poorly controlled (Bluml et al., 2000). This combined population consisted of 51.6% women and 48.4% men, with an average age of 57 years (Bluml et al., 2000). Of these patients, 298 (75.1%) had no history of CAD and were categorized as primary prevention patients (199 with an LDL-C goal < 130 mg/dL and 99 with an LDL-C goal < 160 mg/dL), while the other 99 (24.9%) had previously experienced a coronary event and therefore fell into a secondary prevention category (LDL-C goal <=100 mg/dL) (Bluml et al., 2000). Patient ethnicity was as follows: 24 (6%) African-American, 3 (0.8%) Asian, 337 (84.9%) Caucasian, 1(0.2%) Hispanic, and 32 (8.1%) not specified (Bluml et al., 2000).

 

Persistence and Compliance with Medication Therapy (Bluml et al., 2000)

 

Of the 397 patients who completed the 2-year study, 345 (86.9%) patients were treated with lipid-lowering medications and lifestyle modifications, while 52 (13.1%) continued with lifestyle modifications focused on diet and exercise in an effort to reach target cholesterol goals (Bluml et al., 2000). The distribution of lipid-lowering medication use was as follows: 89% HMG-CoA reductase inhibitors; 5% niacin; 4% fibrates; and 2% bile acid resins (Bluml et al., 2000).

 

Of the 345 patients started on medication, 323 continued with drug therapy, for a resultant patient medication persistence rate of 93.6% (Bluml et al., 2000). Of 2,817 documented visits for patients on medications, 2,539 occurrences of compliance (i.e., within 5 days of expected refills) were reported, for a resulting per-visit medication compliance rate of 90.1% (Bluml et al., 2000).

 

Resultant Lipid Levels (Bluml et al., 2000)

 

Using the two-tailed Student’t test for paired data, statistically significant improvements were found for the 397 study patients using beginning and ending LDL-C measures (mean duration = 24.6 months) (Bluml et al., 2000). Mean (±standard deviation) reductions of 12.8% ± 1.6% and 10.0% ± 6.5% were observed for total cholesterol and triglycerides, respectively, while a mean increase of 14.2% ± 3.9% was observed in high-density lipoprotein levels (Bluml et al., 2000). Overall, a mean reduction of 22.1% ± 2.6% was observed for LDL-C values; in addition, the midpoint measures (mean interval from beginning = 12.1 months; Table 3) demonstrate progressive improvements over time (Bluml et al., 2000).

 

The NCEP Adult Treatment Panel II (ATPII) guidelines recommend LDL-C goals of < 160 mg/dL for patients with less than two CAD risk factors, < 130 mg/dL for patients with two or more CAD risk factors, and <= 100 mg/dLfor patients with a history of CAD (Bluml et al., 2000). Based on these NCEP guidelines, 290 of the 397 patients (73.1%) were at or below goal on two or more visits during the study, and 248 (62.5%) were at or below goal as of their last full lipid profile (Bluml et al., 2000).

 

Pharmacist Interventions (Bluml et al., 2000)

 

Pharmacists intervened with physicians to request a variety of therapeutic changes during the course of the study (Bluml et al., 2000). These interventions were focused on improving NCEP goal achievement through drug therapy optimization and addressed issues that included coordination of care, adverse drug reactions, drug interactions, drug dosing, drug selection, and side effects (Bluml et al., 2000). Physicians accepted the pharmacist recommendations and made changes in 265 (76.6%) of the 346 reported interventions (Bluml et al., 2000).

 

Practice Model Observations (Bluml et al., 2000)

 

While implementation of the Project ImPACT practice model may have varied slightly from site to accommodate practice differences, it consistently produced an environment that resulted in a high level of collaboration through the following: Regular communications between and among all involved parties; Referral of patients by pharmacists to physicians and other providers (family practitioners, internal medicine physicians, cardiologists, dieticians, nurse practitioners, and endocrinologists); Referral of patients to pharmacists by physicians and other providers (family practitioners, internal medicine physicians, cardiologists, and nurse practitioners); Increased availability and use of objective clinical measures; Sharing treatment data and pertinent lifestyle and clinical information, including objective lipid measures obtained in the pharmacy, with patients and physicians; Periodic evaluation of the patient’s progress toward lipid goals, and, if necessary, consultation and intervention with the patient’s physician; Timely adjustments in the patient’s treatment plans (Bluml et al., 2000).

 

Process of Care Observations (Bluml et al., 2000)

 

Eligible “at risk” patients who were enrolled in the project were identified through community screening events (12%), patient self-referrals (13%), physician referrals (15%), and pharmacist identification and referral (60%) (Bluml et al., 2000). Two critical components of the process of care in the pharmacy were scheduling appointments for patients and arranging for adequate personnel to provide the services (Bluml et al., 2000). The end-of-project survey asked about the mechanisms that pharmacists used to accomplish these tasks (Bluml et al., 2000).

 

Because of the time management challenges that pharmaceutical care services can and often do present, the survey asked about the amount of time spent for the initial visit and for scheduled follow-up visits (Bluml et al., 2000). On average, pharmacists spent 30 to 60 minutes (mean = 45 minutes) with patients at their initial visit and 10 to 30 minutes (mean = 22 minutes) with patients during follow-up visits (Bluml et al., 2000).

 

Pharmacists were asked to describe their level of satisfaction with their own role, their relationships with patients and physicians, and their perceptions of how satisfied patients and physicians were with pharmacists’ services provided as a part of the project (Bluml et al., 2000). The percentages of pharmacists responding “very satisfied” and “satisfied” were as follows: With their professional role, 88.5% and 11.5%, respectively; With their relationship with patients, 84.6% and 15.4%, respectively; With their relationship with physicians, 19.2% and 46.2%, respectively (with another 30.8% being “neutral” and 3.8% “dissatisfied”) (Bluml et al., 2000).

 

Pharmacists perceived that 53.8% of their patients were “very satisfied” and 46.2% “satisfied” with the services provided (Bluml et al., 2000). Pharmacists’ perceptions of the physicians’ feelings about the value of their services were not as strong: “very satisfied,” 19.2%; “satisfied,” 46.2%; “neutral,” 26.9%; and “dissatisfied,” 7.7% (Bluml et al., 2000).

 

Pharmacists at 25 of the 26 project sites planned to continue to provide this service (Bluml et al., 2000). Respondents at all sites recommended that other pharmacists implement these same types of services in their practices (Bluml et al., 2000).

 

Payment Observations (Bluml et al., 2000)

 

Although the project was not designed as a payment demonstration, participants were asked about the value of their services and their experiences in obtaining payment (Bluml et al., 2000). Pharmacists indicated an average assigned value of $55 per visit– $28 for counseling services and $27 for lipid profiles (Bluml et al., 2000). With respect to patients paying for these services, pharmacists indicated that, of 232 patients who were asked for payment, 174 (75%) paid an average of $35 per visit (Bluml et al., 2000). Of 121 third party payers billed for services, 64 (53%) paid an average of $30 for each visit billed (Bluml et al., 2000). Of these 64 payers, 30 paid for counseling services and 53 paid for lipid profiles (some paid for both) (Bluml et al., 2000). Two project sites secured contracts with managed care organizations to deliver services to those health plan beneficiaries, one under a fee-for-service arrangement and the other under capitation (Bluml et al., 2000).

 

Patients Not Completing Study (Bluml et al., 2000)

 

The results presented thus far are for the population of patients who continued for the full duration of the project (Group 1) (Bluml et al., 2000). Data for those patients who did not complete the entire project (Group 2) show the following (Table 6): Patient demographics (age, ethnicity, sex, and CAD status) for Group 2 did not vary by more than 3% from Group 1; Average length of participation in the project was 7.2 months for Group 2, compared with 24.6 months for Group 1; Enrollment category distribution, newly diagnosed and poorly controlled, were 47.6% and 52.4%, respectively, inGroup 2, and 38.5% and 61.5%, respectively, in Group 1; There were 20% fewer patients on drug therapy treatment in Group 2 as compared with Group 1; Persistence for Group 2 was 96.8%, compared with 93.6% for Group 1; Compliance for Group 2 was 86.1%, compared with 90.1% for Group 1; Clinical outcomes for lipid level and NCEP goal achievement measures for Group 2 were approximately 50% of those achieved by Group 1 (Bluml et al., 2000).

 

Discussion (Bluml et al., 2000)

 

When evaluating the current state of dyslipidemia management in the existing health care delivery system, a less-than-optimal picture develops (Bluml et al., 2000). Recent studies on the treatment of CAD indicate that the majority of eligible patients go untreated: of those patients who are treated, only 40% remain on their lipid-lowering medication therapy after 12 months (Bluml et al., 2000). Literature from primary care settings indicate that successful treatment-to-goal results range from 8% to 33% (Bluml et al., 2000).

 

The outcomes from Project ImPACT: Hyperlipidemia present a dramatically different picture: in the project, pharmacists demonstrated that they can, in collaboration with patients and physicians, effectively identify patients with lipid disorders who require treatment and support them in their efforts to improve persistence, compliance, and treatment to goal (Bluml et al., 2000). The results presented herein, if compared with the existing health care delivery system, represent a twofold to fourfold improvement (Bluml et al., 2000).

 

Project ImPACT: Hyperlipidemia provides a contemporary view of the capabilities of pharmacists, with the appropriate resources, to empower patients to achieve therapeutic outcomes through the effective application of a process of care to manage dyslipidemia (Bluml et al., 2000). Pharmacists are in a prime position to ensure the success of collaborative practice efforts, because of their accessibility to patients and physicians, their ability to use resources in providing an advanced level of care, and their information management capabilities, motivation to expand care, and education and training in the area of patient-focused disease management services (Bluml et al., 2000). New point-of-care testing and communication technologies provide pharmacists with accurate, objective data to reinforce their counseling and intervention activities relative to persistence and compliance with diet, exercise, and drug therapy (Bluml et al., 2000).

 

The project results suggest that patients receiving pharmaceutical care in a collaborative practice environment can make significant short-term improvements in persistence and compliance; however, longer-term participation in such an environment is required to achieve greater improvements in clinical outcomes (Bluml et al., 2000).

 

Conclusion (Bluml et al., 2000)

 

Working collaboratively with patients, physicians, and other health care providers, pharmacists who have ready access to objective clinical data, and the necessary knowledge, skills, and resources, can provide an advanced level of care that results in successful management of dyslipidemia (Bluml et al., 2000). In the project ImPACT, mean reductions in both total cholesterol and LDL-C exceeded 30 points for a diverse, multicenter patient population that included both treatment-na ve and previously treated patients who had not achieved goals (Bluml et al., 2000). Patients enrolled in this project achieved medication persistence and compliance rates significantly higher than those previously found in the literature from similar ambulatory care settings (Bluml et al., 2000).

 

Project ImPACT therefore offers a sound model for pharmacists to use in empowering patients and improving the quality of consumer health outcomes (Bluml et al., 2000). This approach to health care delivery warrants further investigation and consideration for widespread adoption (Bluml et al., 2000).

 

Chapter 8: Economic Impact of Pharmacists’ Treatment of Hypercholesterolemia

 

The Study of Cardiovascular Risk Intervention by Pharmacists, as discussed by Simpson et al. (2001) is a randomized, controlled trial in over 50 community pharmacies in Alberta and Saskatchewan, Canada, and demonstrated that a pharmacist intervention program improved cholesterol risk management in patients at high risk for cardiovascular disease (Simpson et al., 2001). In a sub-study, costs and consequences were analyzed to describe the economic impact of the program (Simpson et al., 2001). Two perspectives were taken: a government-funded health care system and a pharmacy manager (Simpson et al., 2001). Costs were reported in 1999 Canadian dollars; incremental costs to a government payor and community pharmacy manager were $6.40/patient and $21.76/patient, respectively, during the 4-month follow-up period (Simpson et al., 2001). The community pharmacy manager had an initial investment of $683.50 (Simpson et al., 2001). The change in Framingham risk function for the intervention group from baseline also was reported (Simpson et al., 2001). The 10-year risk of cardiovascular disease decreased from 17.3% to 16.4% (p<.0001) during the 4 months (Simpson et al., 2001). The intervention program in this study led to a significant reduction in cardiovascular risk in the intervention group during the 4-month follow-up period (Simpson et al., 2001). The incremental cost to provide the program appeared minimal from both government and pharmacy manager perspectives; it is therefore hoped that these results could support negotiations for reimbursement of clinical pharmacy services with payors (Simpson et al., 2001).

 

Introduction (Simpson et al., 2001)

 

Cardiovascular disease (CVD), the result of coronary atherosclerosis, is the leading cause of death in developed countries (Simpson et al., 2001). In Canada, CVD accounts for 36% of deaths, primarily from acute myocardial infarction (Simpson et al., 2001). With one in 10 physician visits, and nearly one in 20 hospitalizations attributed to CVD, management of such patients places a significant burden on the Canadian health care system (Simpson et al., 2001). In 1993, the direct and indirect costs of CVD in Canada exceeded $7 billion (Simpson et al., 2001).

 

Elevated serum cholesterol is a well-known risk factor for CVD. Large-scale epidemiologic studies, such as the Framingham, Multiple Risk Factor Intervention Trial, and Seven Countries studies, established a direct relationship between serum cholesterol level and degree of CVD risk (Simpson et al., 2001). Numerous randomized, multicenter clinical trials demonstrated that a reduction of serum cholesterol significantly reduces the risk of CVD morbidity and mortality (Simpson et al., 2001). A survey of the Canadian population aged 18 to 74 years revealed that 46% had a total cholesterol level over 200 mg/dl (5.2 mmol/L) and 15% had low-density lipoprotein (LDL)-cholesterol levels over 160 mg/dl (4.1 mmol/L) (Simpson et al., 2001). Despite the prevalence of this risk factor and the overwhelming evidence to support cholesterol-lowering drugs, management of cholesterol risk remains less than optimal (Simpson et al., 2001).

 

Improving the management of cholesterol risk begins with the recognition of patients at high risk for developing CVD and initiation of a stepped-care approach of individualized therapy (Simpson et al., 2001). Numerous studies demonstrated the efficacy of multidisciplinary programs designed to improve patient outcomes through management of cholesterol risk (Simpson et al., 2001). These studies enrolled patients who were referred to specialty clinics and health centers dedicated to CVD risk factor management; accessibility to these settings for the general population is often limited; therefore alternative strategies are required (Simpson et al., 2001).

 

Community pharmacists are well positioned to identify and follow patients at high risk for CVD (Simpson et al., 2001), as we have seen. The recently completed Study of Cardiovascular Risk Intervention by Pharmacists (SCRIP) examined the efficacy of a community pharmacist intervention program on cholesterol risk management (Simpson et al., 2001). The intervention program consisted of an interview with the community pharmacist to identify cardiovascular risk factors, measurement of total cholesterol and blood pressure, education on risk factor management, and close follow-up (Simpson et al., 2001). The study was stopped early due to striking benefit in the intervention group. A total of 675 patients were randomly assigned to receive either the intervention program or usual care. After 4 months of follow-up, 58% of patients in the intervention group reached the composite primary end point, demonstrating improvements in cholesterol risk management, compared with 30% in usual care (p<.0001).[33]

 

Before implementing an intervention program such as SCRIP into community pharmacies, decision-makers must be able to determine the program’s value (Simpson et al., 2001). To improve the quality of fiscal decision-making, governments and third-party payors are demanding economic evaluations of new health care initiatives (Simpson et al., 2001). These evaluations are intended to provide information to policy makers faced with the difficult decision of resource allocation (Simpson et al., 2001). Guidelines are available for design and conduct of economic evaluations of new health care technologies (Simpson et al., 2001).

 

Given the striking improvement in cholesterol risk management demonstrated by the community pharmacist intervention in SCRIP, it was necessary to evaluate the economic impact of this program (Simpson et al., 2001). A sub-study identified the incremental costs to provide a program of community pharmacy intervention in cholesterol risk management in view of its clinical benefit (Simpson et al., 2001).

 

Methods (Simpson et al., 2001)

 

The SCRIP was a randomized, controlled study involving over 50 community pharmacies in Alberta and Saskatchewan, Canada (Simpson et al., 2001). The objective of the main study was to determine whether a community pharmacist intervention program would improve cholesterol risk management (Simpson et al., 2001). Patients with either established CVD or diabetes with one or more other CVD risk factors and who provided informed consent were randomly assigned to receive either the intervention program or usual pharmacy care (Simpson et al., 2001). The intervention program consisted of screening and identification of CVD risk factors (including a point-of-care cholesterol test), individualized verbal and written education on risk factor management, referral to family physicians, and close follow-up for 16 weeks (Simpson et al., 2001). Patients assigned to usual care received a pamphlet on CVD risk factors, general information only, and minimal follow-up (Simpson et al., 2001). During the final follow-up visit, total cholesterol and blood pressure were measured for all patients (Simpson et al., 2001). The primary end point for the main study was a composite of performance of a fasting cholesterol panel, prescription of a new cholesterol-lowering agent, or dosage increase of an existing cholesterol-lowering agent (Simpson et al., 2001).

 

Given the significant clinical benefit of improved cholesterol risk management observed in the main SCRIP study, it is necessary to report the economic impact of this program (Simpson et al., 2001). A cost-identification analysis was the most appropriate economic evaluation due to the design of the main SCRIP study (Simpson et al., 2001). To provide the information in meaningful terms for resource-allocation decisions, we assumed the improvement in risk factor management would translate into a reduction in cardiovascular risk (Simpson et al., 2001). A change in cardiovascular risk, quantified by the Framingham risk function was used to predict impact of the community pharmacist’s intervention on health outcomes (Simpson et al., 2001).

 

The Framingham risk function is a well-validated tool used to estimate the risk of cardiovascular events in a North American population (Simpson et al., 2001). This risk function measured effectiveness in other studies (Simpson et al., 2001). Sufficient information was available to calculate change in the Framingham risk estimate for the intervention group; however, measurement of total cholesterol and blood pressure (vital components of the Framingham risk function) is not considered part of usual pharmacy care and was not performed during the initial visit for the non-intervention group (Simpson et al., 2001). Therefore it was not possible to calculate change in Framingham risk estimate for the usual-care group; the absence of a control group therefore limited this sub-study to a cost identification study (Simpson et al., 2001).

 

Provincial government and community pharmacy managers are the two primary decision-makers involved in implementing an intervention program; therefore, these two perspectives were adopted to identify resource utilization and costs (Simpson et al., 2001). A decision analysis framework identified possible events occurring as a result of the pharmacist-patient interaction (Simpson et al., 2001). It also identified areas of potential resource consumption, which included visits to family physicians, performance of fasting cholesterol panels, prescription of cholesterol-lowering agents, and treatment of adverse effects of these agents (Simpson et al., 2001).

 

Costs: Government Perspective (Simpson et al., 2001).

 

Pharmacies participating in SCRIP were from both Alberta and Saskatchewan, Canada; because of provincial variations in health care systems, data from each province were treated separately (Simpson et al., 2001). Unit cost estimates were taken from health benefit lists and drug formularies, and all costs were expressed in 1999 Canadian dollars (Simpson et al., 2001).

 

It was assumed that physician fees were for patient’s repeat visits to their general practitioners (Simpson et al., 2001). The assumption was that a patient visiting a physician for CVD risk factor assessment would receive an examination of the relevant body systems and diagnostic tests, described as “limited visit” and “partial assessment” in the provincial medical benefit schedules (Simpson et al., 2001).

 

Drug costs were estimated using market share according to the number of prescriptions for each type and strength of cholesterol-lowering agent (Simpson et al., 2001). Prescriptions for all patients receiving new agents during the SCRIP follow-up period were reviewed and tallied according to active ingredient and strength (Simpson et al., 2001). The median age of patients was 65 years; therefore, to calculate the Alberta Government share of drug cost (70% for those aged 65 years and older), it was assumed that 50% of the patients prescribed a new cholesterol-lowering agent were 65 years or older (Simpson et al., 2001). It was also assumed that each patient prescribed a cholesterol-lowering drug would have a baseline liver function test performed (Simpson et al., 2001). These assumptions were adjusted in a sensitivity analysis to test robustness of the results (Simpson et al., 2001).

 

Resource consumption data were recorded from two sources: case report forms completed by investigators at each visit and surveys completed by patients at the end of 4 months (Simpson et al., 2001). The number of fasting cholesterol panels and prescriptions for cholesterol-lowering agents were reported by the pharmacists and validated with a copy of the laboratory report or prescription (Simpson et al., 2001). The number of physician visits, nature and frequency of adverse drug events, and actions taken to treat the adverse events were reported by the patients on the survey (Simpson et al., 2001).

 

Costs: Community Pharmacy Manager (Simpson et al., 2001).

 

Costs incurred by the community pharmacy manager were divided into fixed costs and variable costs (Simpson et al., 2001). Fixed costs included the purchase of equipment (an Accutrend GC point-of-care cholesterol device and a blood pressure monitor) and training of pharmacists (Simpson et al., 2001). Variable costs included the pharmacists’ time to provide study-related activities for all patients and consumable items used to measure total cholesterol in the intervention group (Simpson et al., 2001). Two investigators were asked to list the consumable items that they used to provide the SCRIP intervention (Simpson et al., 2001). These items included the Accutrend GC cholesterol test strip, gloves, lancet, and bandage (Simpson et al., 2001). It was assumed that each patient in the intervention group would receive two cholesterol measurements during the study (Simpson et al., 2001).

 

The largest resource consumed from the pharmacy manager perspective was pharmacist time (Simpson et al., 2001). Pharmacists recorded the time required to complete each case report form for the main study; all activities related to the main study were divided into segments to evaluate differences between usual care and intervention (Simpson et al., 2001). The segments were as follows: patient recruitment and registration (enrollment), treatment, follow-up, and final visit (Simpson et al., 2001). Differences between usual care and intervention provided an estimate of the additional time necessary to provide the SCRIP intervention program (Simpson et al., 2001). Average pharmacists’ wage rates were then applied to the total time to estimate the cost of pharmacists’ time (Simpson et al., 2001)

 

Change in Cardiovascular Disease Risk (Simpson et al., 2001)

 

The improvement in cholesterol risk management demonstrated in the main study provided some insight into the benefits of the community pharmacy intervention program (Simpson et al., 2001). An improvement in the proportion of patients receiving fasting cholesterol panels and prescriptions for cholesterol-lowering agents translates into a reduction in risk of CVD events (Simpson et al., 2001). To illustrate this reduction, the Framingham risk estimate was calculated from data gathered at baseline and at 4 months for the intervention group (Simpson et al., 2001).

 

Data on age, gender, systolic blood pressure, total cholesterol, presence of diabetes, and smoking status were collected for all intervention-group patients (Simpson et al., 2001). Information on electrocardiograph-verified left ventricular hypertrophy (LVH) or high-density lipoprotein (HDL) cholesterol concentrations were not available to the community pharmacists; therefore, assumptions were made for these two variables (Simpson et al., 2001). First, it was assumed that LVH was absent for all intervention-group patients, that no patient developed LVH during the relatively short follow-up period (Simpson et al., 2001). Second, the HDL cholesterol was assumed to be 40 mg/dl (1.0 mmol/L) for men and 45 mg/dl (1.2 mmol/L) for women, based on epidemiologic data from patients with established cardiovascular disease (Simpson et al., 2001).

 

Statistical Analysis (Simpson et al., 2001)

 

Proportions of groups who visited their family physician, who had a fasting cholesterol panel, and who were prescribed a cholesterol-lowering agent were compared with x2 (Simpson et al., 2001). The difference in frequencies of physician visits between usual-care and intervention groups was compared using the Mann-Whitney U. statistic for nonparametric data (Simpson et al., 2001). The differences in pharmacist time between usual-care and intervention groups were compared using an independent samples t test (Simpson et al., 2001).

 

For each subject in the intervention group, the 10-year risk of coronary heart disease was calculated at baseline and at the final 4-month follow-up (Simpson et al., 2001). The differences in mean values for Framingham risk function, systolic blood pressure, and total cholesterol were compared using a paired t test (Simpson et al., 2001). The proportion of smokers at baseline and at 4 months in the intervention group was compared using McNemar’s test statistic (Simpson et al., 2001). All tests were considered significant if the p value was less than 0.05 (Simpson et al., 2001).

 

Results (Simpson et al., 2001) total of 675 patients were enrolled in the main study between February 1, 1998, and January 31, 2000; 344 patients were randomized to intervention and 331 to usual care (Simpson et al., 2001). During the study, 15 patients withdrew before completing the study, with 6 withdrawing immediately after randomization (Simpson et al., 2001). As these six patients did not contribute any data to the sub-study, data were available for only 669 patients — 340 from the intervention group (232 in Alberta, 108 in Saskatchewan) and 329 from the usual-care group (225 in Alberta, 104 in Saskatchewan) (Simpson et al., 2001). For purposes of analysis, however, all 15 patients were retained in the groups to which they were randomized (Simpson et al., 2001).

 

Resource Use and Costs: Government (Simpson et al., 2001).

 

There were no significant differences in the number of visits to physicians between the usual-care and intervention groups during the study period (Simpson et al., 2001). In Alberta, 99% and 100% of the usual-care and intervention-group patients, respectively, visited a physician at least once during the 4-month follow-up period (Simpson et al., 2001). In Saskatchewan, 98% of both groups visited a physician at least once; the median number of visits was three in all four patient groups (Simpson et al., 2001).

 

The main differences in resource utilization between patients in the intervention and usual-care groups were in the performance of fasting cholesterol panels and prescription of cholesterol-lowering drugs, which were study end points; there were no adverse drug reactions attributed to cholesterol-lowering drugs (Simpson et al., 2001).

 

The total costs to the provincial governments are $6.40/patient over 4 months ($6.27 in Alberta, $6.70 in Saskatchewan) (Simpson et al., 2001). Cost to the government was sensitive to the proportion of patients qualifying for government co-pay for drugs and the amount of co-payment (Simpson et al., 2001). Cost increased by $1/patient for a 4-month period if 75% of the study sample qualified for government co-pay (Simpson et al., 2001). Conversely, if the government did not provide drug cost coverage, cost to the government decreased by $2.32/patient for the 4 months (Simpson et al., 2001).

 

Resource Use and Costs: Community Pharmacy Manager (Simpson et al., 2001).

 

The average time to provide all intervention activities was 102.4 ± 55.1 minutes (Simpson et al., 2001). There were no significant differences in the time to recruit and register a new patient between the usual-care and intervention groups (18.7 ± 14.0 min versus 17.8 ± 13.4 min, respectively, p=0.38) (Simpson et al., 2001). Follow-up visits took slightly longer with intervention patients compared with usual care patients (9.6 ± 6.4 min versus 8.1 ± 6.3 min; p=0.003) (Simpson et al., 2001). The time to provide the SCRIP intervention took 9.3 ± 1.1 minutes (Simpson et al., 2001).

 

The average initial cost to purchase equipment and train pharmacists was $683.50 ($691.59 in Alberta, $675.40 in Saskatchewan) (Simpson et al., 2001). The average incremental cost to a community pharmacy manager to provide the SCRIP intervention was $21.76/patient ($22.02 in Alberta, $21.50 in Saskatchewan) (Simpson et al., 2001). Using the total time to provide the intervention over the 4-month study period, the average cost to a community pharmacy manager was $48.44/patient (Simpson et al., 2001).

 

Change in Cardiovascular Disease Risk (Simpson et al., 2001)

 

The baseline 10-year risk of coronary heart disease was 17.3 ± 8.8% in the intervention group (Simpson et al., 2001). This risk decreased to 16.4 ± 8.1% after 4 months (p<.0001) (Simpson et al., 2001). The reduction in risk was driven primarily by reductions in total cholesterol and systolic blood pressure (Simpson et al., 2001).

 

Discussion (Simpson et al., 2001)

 

In Simpson et al.’s (2001) study, the main study demonstrated a significant improvement in cholesterol risk management through a simple community pharmacist intervention (Simpson et al., 2001). In this sub-study, the improvement was illustrated by a reduction of CVD risk in the intervention group, as calculated by the Framingham risk function (Simpson et al., 2001). This cost-identification analysis suggests that a government-funded health care system would have to increase expenditures by approximately $6.40/patient to provide this program for 4 months (Simpson et al., 2001). A community pharmacy manager would incur an initial cost of approximately $680 to obtain equipment and train pharmacists; from this perspective, the cost to provide this program would be approximately $22/patient for 4 months (Simpson et al., 2001).

 

The cost estimates in this study were based on 4 months of data (Simpson et al., 2001). This short follow-up limited assessment of the true impact of the SCRIP intervention program on a provincial health care budget; however, one can postulate on the potential downstream clinical benefits of this intervention program (Simpson et al., 2001). Given that CVD is the leading cause of hospitalization and mortality for both men and women in Canada, programs to reduce the risk of morbidity and mortality of this disease will likely significantly reduce the burden of illness (Simpson et al., 2001). The percentage of Canadians at high risk for CVD who have elevated cholesterol levels is not known; however, it appears that 46% of the general Canadian population between the ages of 18 and 74 years have a total cholesterol level above 200 mg/dl (5.2 mmol/L) and 15% have an LDL level greater than 160 mg/dl (4.1 mmol/L) (Simpson et al., 2001). Epidemiologic studies suggest that patients with CVD have a total cholesterol level of 208-240 mg/dl (5.38-6.4 mmol/L) and a mean LDL level of 132-140 mg/dl (3.42-3.61 mmol/L): clearly, this places the majority of patients with CVD above the target LDL level of 100 mg/dl (2.5 mmol/L) as outlined in the new Canadian guidelines and therefore eligible for receiving the SCRIP intervention program (Simpson et al., 2001).

 

Interestingly, the intervention program did not lead to an increase in the number of visits to physicians (Simpson et al., 2001). During the initial interview with intervention-group patients, pharmacists identified CVD risk factors, provided patient-specific education, and instructed patients to visit their family physicians for risk factor assessment (Simpson et al., 2001). It was anticipated that this recommendation would lead to at least one extra physician visit during the follow-up period; however, there were no differences between intervention-group and usual-care patients in either the number of patients visiting their physician or the number of physician visits/patient (Simpson et al., 2001). Given that intervention-group patients were more likely to have a fasting cholesterol panel performed and more likely to be prescribed cholesterol-lowering agents, the SCRIP intervention program possibly changed the nature of the physician visit (Simpson et al., 2001). Through recommendations by the pharmacists, it is possible that the intervention-group patients visited their physicians specifically for CVD risk factor assessment (Simpson et al., 2001). The SCRIP intervention program informed patients about cardiovascular risk factors and provided a system to remind patients to see their primary care physician for preventive care, both of which were identified as important barriers to preventive care (Simpson et al., 2001).

 

During the 4-month follow-up period, the 10-year risk of CVD, estimated using the Framingham risk function, decreased by 5.2%, from 17.3% to 16.4%, which is similar in magnitude to previously reported studies (Simpson et al., 2001). The Cost Effectiveness of Lipid Lowering (CELL) study demonstrated a 1% reduction in Framingham risk function, from 14.4% to 14.2%, after 18 months of follow-up (Simpson et al., 2001). The CELL study used existing clinical staff to compare an intervention program of intensive health care advice and/or pravastatin with usual care and/or drug therapy within a multifactorial study design (Simpson et al., 2001). Other investigators found that a specialty clinic designed to manage all CVD risk factors could reduce the Framingham risk function by 24%, from 25% to 19%, after an average 12 months of follow-up (Simpson et al., 2001). Both studies used staff dedicated to the screening, assessment, and management of CVD risk factors (Simpson et al., 2001). The beneficial effect on Framingham risk function seen in SCRIP may be an underestimate of the true potential for the intervention program for two reasons: first, investigators provided the intervention while operating a community pharmacy; therefore, it is not known what the impact of this program would be if it was provided by pharmacy staff who were solely responsible for providing clinical services such as the SCRIP intervention; second, the duration of follow-up likely limits the evaluation of the full impact of the intervention program (Simpson et al., 2001).

 

Framingham risk could not be calculated for the usual-care group patients because baseline data on total cholesterol and systolic blood pressure were not measured (Simpson et al., 2001). Collection of these variables was an integral part of the intervention program but not part of usual pharmacy practice (Simpson et al., 2001). Without knowing the change in Framingham risk function for the usual-care group patients, it was not possible to calculate an incremental change in effectiveness for the SCRIP intervention program; however, the significant reductions in 10-year risk of CVD, total cholesterol, and systolic blood pressure in the intervention group compared with baseline are consistent with the positive impact on the process of cholesterol risk management demonstrated in the main SCRIP study (Simpson et al., 2001).

 

As patients at high risk of CVD with elevated LDL are identified and appropriately started on cholesterol-lowering drugs, their risk of morbidity and mortality decreases significantly (Simpson et al., 2001). Reductions in the burden of illness with cholesterol-lowering drugs are cost-effective (Simpson et al., 2001). Clinical programs such as the pharmacist intervention in SCRIP provide community pharmacists with opportunities to explore alternative funding sources; for example, by charging a nominal fee (e.g., $15/visit) to patients, the provincial health care system, or a third-party payor, the cost of the program could be easily offset (Simpson et al., 2001). Furthermore, by providing an alternative service to clients, pharmacists could see increased customer loyalty, an added sense of professionalism, and potentially increased prescription volume (Simpson et al., 2001).

 

The conclusion to Simpson et al.’s (2001) work is that SCRIP, a randomized, multicenter study, conclusively demonstrated that a community pharmacist intervention program improves cholesterol risk management (Simpson et al., 2001). Patients who received this intervention program significantly reduced their 10-year risk of CVD, their total cholesterol, and their systolic blood pressure from baseline (Simpson et al., 2001). The incremental costs to a government-funded health care system and community pharmacy manager appeared minimal (Simpson et al., 2001). It is hoped that these data, along with the results of the main study, can justify reimbursement for advanced clinical services provided by pharmacists (Simpson et al., 2001).

 

Chapter 9: Conclusions

 

We have seen, throughout this paper, that hypercholesterolemia is a high risk factor in cardiovascular disease, and that CVD is a major killer in the developed world. We have also seen that current management of hypercholesterolemia is inadequate, for many reasons, as pointed out in the review of the literature presented by Bankhead et al. (2003). We then moved on to look at some relevant studies of hypercholesterolemia, and its treatment and management, which showed that pharmacists are well-placed to deal with the management of hypercholesterolemia, particularly in the light of a study by Eaton et al.,(1998) which showed that hypercholesterolemia is poorly managed within the health care sector as a whole, and by physicians in particular. The thesis then moved on to look at two cases studies of cholesterol management by pharmacists: ImPACT (in the U.S.) and SCRIP (in Canada) which showed how effective community pharmacists’ management of hypercholesterolemia can be. This became particularly evident through the economic analysis of the management of hypercholesterolemia by Simpson et al., (2001).

 

In conclusion, then, hypercholesterolemia presents a grave problem to the well-being of citizens in the developed world, especially as obesity and physical inactivity rates are increasing yearly. Evidence has been presented to show that hypercholesterolemia is most effectively – and cost effectively – managed by community pharmacists, through their increased ability to reassure individuals, and to ensure that individual patients continue their medication for the duration of their treatment. The governments of developed countries need to begin to put policies in place which will ensure that community pharmacists have more power in the management of hypercholesterolemia, otherwise a major health problem will develop and will be unmanageable within coming decades.

 

Bibliography

Anderson, RA et al. (2001). Hypercholesterolemia. Available at http://www.healthandage.com/html/res/com/ConsConditions/Hypercholesterolemiacc.html. Accessed on 28th May 2004.

Bankhead, CR et al. (2003). The impact of screening on future health-promoting behaviours and health beliefs: a systematic review. Health Technology Assessment; 7(42).

Bluml, BM et al. (2000). Pharmaceutical Care Servces and Results in Project ImPACT: Hyperlipidemia. J.Am.Pharm.Assoc. 40(2): 157-165.

Chase, S. (2002). New Lipid Guidelines Recommend Tighter Control. Topics in Advanced Practice Nursing eJournal 2(3)

Eaton, CB et al. (1998). Cholesterol Testing and Management: A National Comparison of Family Physicians, Pharmacists and Cardiologists. J.Am.Board.Fam.Pract. 11(3): 180-186.

Olson, KL et al. (2001). Cholesterol risk management: a systematic examination of the gap from evidence to practice. Pharmacotherapy 21(7): 807-817.

Simpson, SH et al. (2001). Economic impact of community pharmacist intervention in cholesterol risk management: an evaluation study of cardiovascular risk intervention by pharmacists. Pharmacotherapy 21(5): 627-635.

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