LIPOPROTEINS AND CARDIOVASCULAR RISK - FROM GENETICS TO CHD PREVENTION

Increased levels of low density lipoprotein (LDL) cholesterol and trig lyceride, and low levels of high density lipoprotein (HDL) cholesterol , are associated with increased risk of coronary heart disease (CHD). Only a minor part of the variation in lipids can be explained by defec ts in single genes of large effect; the bulk of variation in most case s is due to the interaction of polygenes and environment. This paper d escribes a strategy for unravelling such complex genetic effects in th e population at large. A person's risk of developing CHD is, however, not determined by levels of circulating lipids alone, but by a number of factors which contribute to his or her global risk. Based on the da ta of the Munster Heart Study (PROCAM), a multiple logistic function u sing nine independent variables for the prediction of risk has been de veloped. This function allows an almost 40-fold degree discrimination in risk between persons in the lowest and highest quintiles of the alg orithm. Data from the Munster Heart Study and other prospective studie s indicates a log-linear relationship between LDL cholesterol and CHD risk. The results of recent large scale intervention trials indicate t hat this relationship also holds true for LDL levels which are achieve d by treatment. This indicates that the benefit achieved by cholestero l lowering is greatest at high baseline LDL. cholesterol levels, and t hat at least for LDL cholesterol levels of greater than or equal to 80 mg.dl(-1), there is no theoretical threshold below which lowering of LDL cholesterol cannot be expected to reduce CHD risk. However, at low LDL cholesterol levels the benefits of treatment may be outweighed by side-effects and by practical cost-benefit considerations. These issu es are also discussed in detail in the present report.