Lipoproteins and cardiovascular risk--from genetics to CHD prevention.

Increased levels of low density lipoprotein (LDL) cholesterol and triglyceride, 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 defects in single genes of large effect; the bulk of variation in most cases is due to the interaction of polygenes and environment. This paper describes a strategy for unravelling such complex genetic effects in the 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 data of the Münster Heart Study (PROCAM), a multiple logistic function using nine independent variables for the prediction of risk has been developed. This function allows an almost 40-fold degree discrimination in risk between persons in the lowest and highest quintiles of the algorithm. Data from the Münster Heart Study and other prospective studies indicates a log-linear relationship between LDL cholesterol and CHD risk. The results of recent large scale intervention trials indicate that this relationship also holds true for LDL levels which are achieved by treatment. This indicates that the benefit achieved by cholesterol lowering is greatest at high baseline LDL cholesterol levels, and that at least for LDL cholesterol levels of > or = 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 issues are also discussed in detail in the present report.