ELEVATED CHOLESTEROL LEVELS

Nondrug Lowering of Cholesterol

In addition to exercise to lower cholesterol, another safe and less costly measure is to eat a low-fat diet, using mostly polyunsaturated fats (such as canola, corn, safflower, and sunflower oils) or monounsaturated fats (such as olive oil). A change from animal to vegetable proteins often corrects high cholesterol. However, it is inadvisable to go on a very low-fat diet. The main focus on cholesterol-lowering diets has been on saturated fat and cholesterol content, not soluble fiber. (When added to the diet, psyllium or oat bran is a safe, effective way of lowering cholesterol.) Exercise and weight reduction are also recommended. Conditions that aggravate high cholesterol, such as dependence on alcohol or tobacco, diabetes, high blood pressure, low magnesium or potassium, and thyroid disease, should be corrected before adding a cholesterol-reducing drug. If cholesterol remains high despite diet, add 10 grams of psyllium (METAMUCIL, PERDIEM) a day. Numerous studies have shown that psyllium, for example five grams twice a day, can significantly lower total cholesterol and LDL cholesterol.[1] Psyllium, a naturally occurring vegetable fiber, is clearly safer than any of the cholesterol-lowering drugs.

Cholesterol-Lowering[2] Drugs for People 70 and Older

It is clear that the relationship between moderately elevated cholesterol levels and increased risk of heart disease is not as clear as people get older.[2] As geriatricians Fran Kaiser and John Morely have written:

Given the uncertainty of the effects of cholesterol manipulation in older individuals, what should be the approach of the prudent geriatrician to hypercholesterolemia (elevated blood cholesterol levels)? In persons over 70 years of age, life-long dietary habits are often difficult to change and overzealous dietary manipulation may lead to failure to eat and subsequent malnutrition. Thus in this group minor dietary manipulations such as the addition of some oatmeal (or other sources of oat bran or soluble fiber) and beans and modest increases in the amount of fish eaten, may represent a rational approach. Recommending a modest increase in exercise would also seem appropriate. Beyond this, it would seem best to remember that the geriatrician’s dictum is to use no drug for which there is not a clear indication.[3]

The use of cholesterol-lowering drugs in people 70 or older should be limited to patients with very high cholesterol levels (greater than 300 milligrams) and those who manifest cardiovascular disease (previous history of heart attack or angina).[4]

The only large clinical trial looking exclusively at the effect of statins on people over the age of 70 provides clear evidence for avoiding these drugs for use in primary prevention of cardiovascular disease in older people who have not had a previous heart attack, stroke, angina, or other cardiovascular diseases or family history. Five thousand eight hundred and four people aged 70 through 82 were randomized to get a statin or a placebo and were followed for an average of 3.2 years. For the more than 3,200 people in this study without prior cardiovascular disease, the statin had no beneficial effect in preventing subsequent cardiovascular disease. There was, however, a significant 25% increased amount of cancer in those getting the statin, particularly gastrointestinal cancers, the cancer predicted in the animal studies of these drugs (see below). The increase was larger the greater the number of years the drug was being used. No other study analyzing cancer exclusively in large numbers of older patients getting statins has refuted this finding of increased gastrointestinal cancer.[5]

In summary, people over 70 using statins for primary prevention of cardiovascular disease have no benefit, compared to a placebo, but an increased risk of muscle damage (rhabdomyolysis), liver damage, and, as found in the study described above, an increased risk of cancer. It needs to be emphasized, however, that for those over 70 who have had previous cardiovascular disease, the use of statins may be beneficial.

There are even questions as to whether elderly people who are hypertensive should have their cholesterol lowered by drugs. One review concluded, “Further trials are required before routinely suggesting that it is advantageous to lower cholesterol in an elderly hypertensive who does not have pre-existing evidence of coronary heart disease.”[6]

Cholesterol-Lowering Drugs and Cancer

Researchers from the University of California[7] have raised questions about the correlation between an increased risk of cancer and lifelong use of cholesterol-lowering drugs by millions of people who have no signs of illness other than an elevated blood cholesterol level. This research is based on animal studies and is sure to be controversial.

Animal studies consistently show a cancer-causing effect for the two most popular classes of cholesterol-lowering drugs, the fibrates or fibric acid derivatives, which include clofibrate (ATROMID-S) and gemfibrozil (LOPID), and the widely used statin drugs, fluvastatin (LESCOL), lovastatin (MEVACOR), pravastatin (PRAVACHOL), and simvastatin (ZOCOR). Evidence of a cancer-causing effect from these drugs based on clinical trials in humans is inconclusive because of inconsistent results and a follow-up period that, to date, is too short to detect some cancers that can take years to develop. The ultimate effect of cholesterol-lowering drugs in humans may not be known for decades.

As part of the Food and Drug Administration’s requirements for getting a new drug approved, companies are required to report the result of cancer experiments on rodents (rats and mice). The most common technique is to give three groups of rodents different doses of a new drug for two years and then compare the incidence of cancer among these groups as well as with a fourth group that received a dummy drug called a placebo. Rats and mice are used because almost all known agents that cause cancer in humans have been found to cause it in these animals. The results of rodent studies are generally published in scientific journals, but are summarized in a product information sheet, or “package insert,” distributed to the pharmacist with each prescription drug. You can get a package insert for any drug you are taking by asking your pharmacist for one.

Researchers have taken the rodent cancer data from the 1992 and 1994 editions of the Physicians’ Desk Reference (PDR, a compilation of package inserts available in many public libraries). The package inserts for cholesterol-lowering drugs show that all the fibrates and statins cause cancer in rats and mice. In most instances, cancer-causing dose levels corresponded to maximums recommended for humans.

How should consumers weigh the worrisome but uncertain risk of cancer based on animal studies against the demonstrated benefits of lowering cholesterol? With some caution.

On the one hand, the study’s authors clearly state that they do not know whether treatment with these cholesterol-lowering drugs will lead to an increased rate of cancer in coming decades. They believe that, for patients with known heart disease, the recent studies suggest that benefits of cholesterol-lowering drugs exceed their risks, at least in men and in the short term (five years). Given the strength of this evidence, it is reasonable to treat high blood cholesterol with drugs in patients with heart or other atherosclerotic disease. On the other hand, for patients not at high short-term risk of heart disease (especially patients with life expectancies of more than 10 to 20 years), drug treatment should probably be avoided. For this group, the benefits of treatment are smaller and the potential risk of increased cancer in the decades after treatment is of greater concern. The authors suggest that cholesterol-lowering drug treatment should be avoided except in patients at high short-term risk of coronary heart disease.

This question of whether the risks of cancer may outweigh the benefits has been answered, at least for older people, in a study published six years after the above-mentioned review of animal evidence of carcinogenicity was published. For those over 70 without previous cardiovascular disease, there was no benefit but there was an increased risk of cancer, especially gastrointestinal cancer as discussed in the section on cholesterol-lowering drugs for people 70 or older.

When Is Drug Treatment Necessary?

Several factors should be taken into account when considering whether people with elevated cholesterol levels should be treated. One is the benefits of the treatment, which vary significantly depending on how abnormal the levels are. Other factors include your age and whether you have other risk factors such as high blood pressure, smoking, or diabetes, and whether you have had a heart attack, heart failure, a stroke, or have kidney damage. The other consideration is the risks or the adverse effects of the treatment, which will vary depending on what is being considered.

Although there is clear evidence that certain of the statin drugs not only lower total cholesterol and LDL cholesterol (the “bad” cholesterol) but also decrease the risk of heart attacks and strokes, this evidence is strongest for people who are at much higher risk of these diseases because they have already had a heart attack, angina, bypass surgery or angioplasty, or a stroke. The treatment of such people to reduce the chance of further cardiovascular disease is known as secondary prevention.

The evidence for treatment, especially with cholesterol-lowering drugs, is much weaker for people who have not yet had the cardiovascular disease described above, known as primary prevention. This is especially so for those people who do not have more than one of the following risk factors: hypertension, diabetes, smoking, obesity, or a close family history of premature heart attacks or strokes. Other predisposing risk factors include a sedentary lifestyle and a high-fat diet. It is likely that millions of people being given cholesterol-lowering drugs such as statins for primary prevention do not have more than one of these risk factors and are only being treated because of their total cholesterol or LDH cholesterol levels.

The following examples are applicable to people who do not have cardiovascular diseases such as heart attack, angina, heart failure, or stroke and who are between the ages of 30 and 74.

Example A: Ben is a 55-year-old man with a total cholesterol of 240 and an HDL of 50. However, his blood pressure is a normal 120/90 and he is neither a diabetic nor does he smoke. Ben turns out to have a 5-year risk of having a cardiovascular event (heart attack, stroke, etc.) of only 5.1%[8], about one-half of the 5-year risk of over 10% that might merit drug treatment.[9] It would be a good idea for Ben—or most people, for that matter—to adopt the nondrug approaches to lowering his cholesterol discussed above, but since his global risk is as low as it is, drug treatment is not indicated even if his total cholesterol and HDL cholesterol stay the same.

Example B: Sally is a 65-year-old woman who, like Ben above, has a total cholesterol of 240, an HDL of 50, a normal blood pressure of 120/90 and is neither a diabetic nor smokes. She turns out to have a 5-year risk of having a cardiovascular event (heart attack, stroke, etc.) of only 5.0%[8], similar to Ben’s even though she is 10 years older, and she also has one-half of the 5-year risk of over 10% that might merit drug treatment.[9]

There is little doubt that many Sallys and Bens are being treated with drugs to lower their cholesterol even though their global risk of having a heart attack or stroke over the next five years is as low as it is. This is because most doctors focus on just one risk factor—in this case cholesterol—instead of examining the total picture including blood pressure and other factors.

Example C: David is a 55-year-old man who, like Ben above, has a total cholesterol of 240, but a lower HDL of 30, a slightly higher blood pressure of 130/90, and does not smoke but is a diabetic. David turns out to have a 5-year risk of having a cardiovascular event (heart attack, stroke, etc.) of 16.1%, more than three times higher than that of either Ben or Sally and well above the 5-year risk of over 10% that might merit drug treatment.[9] If this has not already been done in the context of treating his diabetes, David should start a program of exercise and diet to see if his total cholesterol can be lowered (and HDL—the “good cholesterol”—increased), and then, if total cholesterol still remains elevated, a drug to lower cholesterol, such as niacin-containing drugs or statins  should be tried. It is likely that an exercise and diet program would also lower his mildly elevated blood pressure.