Plasma lipoproteins, antihypertensive drugs and coronary heart disease.

There is now a large body of evidence that susceptibility to coronary atherosclerosis is inversely related to the plasma high-density lipoprotein (HDL) cholesterol concentration, in addition to being directly related to blood pressure and the plasma low-density lipoprotein (LDL) level. Studies of the effects of drugs on coronary disease in humans and on experimental atherosclerosis in animals have provided evidence that the associations with HDL and LDL are causal, reflecting an atherogenic effect of one lipoprotein and a protective effect of the other. Interest in the effects of antihypertensive drugs on plasma lipoproteins was stimulated by the failure of these drugs in several clinical trials to reduce the incidence of coronary heart disease in hypertensive subjects, even though the incidence of other complications of high blood pressure were reduced. Many beta-blocking drugs and thiazides have now been shown to have a theoretically adverse effect on the plasma lipoprotein profile, measured in the terms of the ratio of HDL cholesterol to LDL. Although the consequences of these changes and their mechanisms remain to be established, they may explain the negative outcome of the prevention trials, the protection against coronary disease offered by the reduction of blood pressure being offset by the associated changes in lipoprotein metabolism.