Marino's Clinical Reports

The purpose of this site is to provide a brief overview of selected medical topics, with emphasis on topics that are either controversial or not readily appreciated by the general public.

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Tuesday, May 29, 2007

What You Should Know About Cholesterol

The association between cholesterol and cardiovascular disease (the leading cause of death in the United States) has created a national obsession with cholesterol, and a multibillion dollar industry for cholesterol-lowering drugs. Unfortunately, the public perception about cholesterol is rooted in as much fancy as fact, and this has created some unsound practices for the control of blood cholesterol. The following information about cholesterol will help to correct this situation, and will help you make well-informed decisions about the cholesterol in your bloodstream.

The Cholesterol Hypothesis
The "cholesterol hypothesis" claims that excess cholesterol in blood will damage the inner lining of blood vessels and promote cardiovascular diseases such as coronary heart disease and stroke. This hypothesis is almost universally accepted by the general public, but is debated by researchers in the field. One of the problems with the cholesterol hypothesis is the inconsistent relationship between blood cholesterol levels and the risk of cardiovascular disease. For example, one of the largest studies of cardiovascular risk factors in the United States (The Framingham Study) showed that elevated blood cholesterol is associated with an increased risk of death from coronary heart disease in people who are under the age of 50, but in people who are over the age of 50, elevated blood cholesterol is associated with a lower risk of death from coronary heart disease.
There are several studies that show no correlation, or a negative correlation, between elevated blood cholesterol and the risk of coronary heart disease. One observation that is particularly interesting comes from a small Italian village named Stocarredo located about a half-mile north of Venice, where residents have excessively high blood levels of cholesterol despite having a much lower incidence of coronary heart disease than the average American. Over 90% of the population of this village shares the same surname, indicating that the tolerance to high cholesterol in these people may be genetic in origin. This observation points to the relative importance of genetic factors over cholesterol (and all other risk factors) in determining the predisposition to coronary heart disease.

Cholesterol in Blood
Cholesterol does not readily dissolve in plasma, and a series of carrier proteins is needed to transport the cholesterol in blood. The cholesterol-protein complexes are called lipoproteins, and there are several lipoproteins identified by their optical density. The lower-density lipoproteins (LDL) are capable of damaging blood vessels and promoting cardiovascular disease, while the higher-density lipoproteins (HDL) have the opposite effect, and can protect blood vessels and prevent cardiovascular disease. As a result of these opposing effects, the risk of cardiovascular disease is determined by the balance between low-density and high-density cholesterol fractions in blood, and not by the total amount of cholesterol in blood. In fact, the total cholesterol level can be misleading because it can be normal despite an elevated LDL-cholesterol ("bad" cholesterol).
Despite the limited value of the total cholesterol level, the routine assay for blood cholesterol (the one used in "screening cholesterol" programs promoted in many health fairs) measures only total cholesterol. This is an unacceptable practice, particularly for health awareness programs that are dedicated to lowering the risk of cardiovascular disease. Remember to ask for a lipoprotein profile to ensure a meaningful evaluation of the cholesterol in your blood.
The most recent recommendations of the National Cholesterol Education Program identifies only LDL-cholesterol as the target of cholesterol-lowering interventions. The desirable level of LDL-cholesterol is determined by the number of other risk factors for cardiovascular disease present in each patient. The other risk factors include age (above 45 years for males or above 55 years for females), smoking, diabetes, hypertension, obesity, HDL-cholesterol less than 40 mg/dL, and a family history of premature coronary heart disease. The target LDL-cholesterol is 160 mg/dL or lower for those with no other risk factors, 130 mg/dL or lower for those with 2 or more additional risk factors, and 100 mg/dL or lower for those with multiple risk factors that include a strong family history of coronary heart disease. (These guidelines are available at

Dietary Restriction
About 85% of the cholesterol in the human body is manufactured by cells in the body (in the liver, intestines, and reproductive organs), while dietary intake contributes only 15% of total body cholesterol. This small contribution of dietary cholesterol means that cholesterol-restricted diets will have little impact on the cholesterol concentration in blood). In fact, when there is a decrease in the dietary intake of cholesterol, the body compensates by increasing the rate of cholesterol production, and this serves to further minimize the effect of cholesterol intake on blood cholesterol levels. Clinical studies have confirmed that dietary restriction of cholesterol has small and inconsistent effects on both total cholesterol and LDL-cholesterol levels in blood. Those "cholesterol free" food labels that are so inviting are more likely to increase sales of the product than lower your blood cholesterol levels.
The dietary factors that will reduce LDL-cholesterol levels include restriction of saturated fatty acids (found in whole milk, cheese, ice cream, and red meat), restriction of trans-fatty acids (present in bread, doughnuts, crackers, cookies, and french fries) and, most importantly, restriction of total calories. Weight reduction through dietary restriction and exercise is the most effective way to reduce LDL-cholesterol levels and avoid the use of cholesterol-lowering drugs.

Cholesterol-Lowering Drugs
When lifestyle modifications (diet, exercise, and weight reduction) do not achieve the desired LDL-cholesterol, then cholesterol-lowering drugs are usually started. The drugs that are most effective are called statins, and they block the metabolic production of cholesterol in the body. These drugs are capable of reducing LDL-cholesterol levels by as much as 50%.
The important question regarding the use of cholesterol-lowering drugs is not their ability to lower LDL-cholesterol levels, but whether this effect is accompanied by a decrease in cardiovascular disease. The evidence from clinical trials shows that these drugs do indeed reduce the incidence of coronary heart disease and stroke, but only in people who have 3 or more risk factors for cardiovascular disease or a strong family history of premature cardiovascular disease. Statins are also not recommended for people who are 70 years of age or older (because the risks from these drugs exceeds the benefits of cholesterol reduction in the elderly).
Are cholesterol-lowering drugs overused? Probably, considering that physicians show a tendency to use these drugs in all adults with an elevated cholesterol or LDL-cholesterol level. The appropriate use of these drugs would limit their use to people with all of the following: 1) an LDL-cholesterol above the target level despite lifestyle modification, 2) three or more risk factors for coronary heart disease, or a strong family history for premature coronary


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