Rationale for cholesterol lowering

Article Abstract:

Though much research remains to be done, cholesterol concentration in the blood seems to play a key role in the development of atherosclerosis and its foremost consequence, coronary heart disease. In atherosclerosis, fatty plaques are deposited in the arteries, restricting blood flow and increasing stress on arterial walls. The correlation between elevated levels of cholesterol in the blood and subsequent heart disease is clear. Research has shown that the ratio of cholesterol associated with low-density lipoproteins (LDL) to that associated with high-density lipoproteins (HDL) is more significant than the total cholesterol level. Low-density lipoproteins represent cholesterol which has been synthesized by the liver and packaged for transport to the rest of the body. Conversely, high-density lipoproteins contain cholesterol which is being returned to the liver for recycling or excretion. In principle, the low- to high-density lipoprotein ratio could be reduced either by lowering low-density lipoproteins or raising high-density ones. There are no reliable experimental data which predict the consequences of raising high-density lipoproteins in the blood. Therefore, most efforts are focused on reducing low-density lipoproteins. One way that LDL may be lowered is by restricting the intake not only of cholesterol, but of those fats which the liver can use to synthesize cholesterol. A second method of reducing the LDL concentration in the blood is to inhibit the enzyme beta-hydroxy-methylglutaryl coenzyme A reductase. The inhibition of this enzyme reduces the synthesis of cholesterol, and increases the number of LDL receptors on liver cell membranes. This process resembles that seen in dietary restriction; beta-hydroxy-methylglutaryl coenzyme A reductase inhibitors, like simvastatin, are therefore viewed as a potentially useful complement to dietary restriction. (Consumer Summary produced by Reliance Medical Information, Inc.)

Health aspects, Drug therapy

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Overview of clinical trials of cholesterol lowering in relationship to epidemiologic studies

Article Abstract:

Epidemiologic evidence has indicated a relationship between serum cholesterol and heart disease. A review of several clinical trials completed in recent years confirms experimentally what had been suggested epidemiologically. The Lipid Research Clinics trial and the Helsinki Heart Study together tested over 7,000 men. The Helsinki Heart Study treated hypercholesterolemia in men without elevated high-density lipoproteins (i.e. their elevated cholesterol was of the low- or very-low density lipoprotein type). The total cholesterol reduction achieved was 11 percent, and resulted in a mortality reduction of 34 percent, which was greater than the 22 percent which had been predicted on the basis of pilot studies. In this study, treatment with the drug gemfibrozil achieved a 14 percent reduction of non-high-density lipoprotein, and a 10 percent elevation of high-density lipoprotein. Although some researchers have speculated that an increase in high-density lipoprotein might begin to reduce the size of atherosclerotic plaques which have already formed inside arteries, no experimental evidence has yet been obtained to confirm this hypothesis. Current recommendations suggest that all adults with cholesterol levels over 200 milligrams per deciliter be placed on dietary restrictions and evaluated for possible drug treatment. According to the available data, if men in the highest quintile of hypercholesterolemia could reduce their risk to that of the men in the lowest quintile, a mortality reduction of 71 percent would occur, and this would translate into an overall 25 percent reduction in mortality due to heart disease among adult men. (Consumer Summary produced by Reliance Medical Information, Inc.)

Evaluation, Demographic aspects, Low-cholesterol diet, Low cholesterol diet

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Introduction

Article Abstract:

The symposium, Simvastatin: A Once-a-Day Treatment for Hypercholesterolemia, was held in June 1988 in California. The reduction of cholesterol levels in the blood is the primary means at our disposal reducing atherosclerosis (the blockage of arteries associated with increased deposition of lipids, or fats). Atherosclerosis of the coronary arteries is responsible for diminished blood and oxygen supply to the heart muscle. The combination of dietary restriction of fats and cholesterol and drug intervention seems to be the best strategy for decreasing blood cholesterol levels. Simvastatin is a relatively new cholesterol-reducing drug, and although its efficacy has been demonstrated, and it seems to be well-tolerated by patients, its long-term safety has not been established. The physician must consider the unknowns of extended use with the demonstrated therapeutic value when determining whether to prescribe simvastatin. (Consumer Summary produced by Reliance Medical Information, Inc.)

Research

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