Effects of antihypertensives on plasma lipids and lipoprotein metabolism

Abstract

There is good epidemiologic evidence that hypertension is associated with a high risk of cardiovascular disease. However, primary intervention trials have failed to demonstrate that a reduction in blood pressure in hypertensive patients reduces morbidity and mortality from cardiac events. Since various antihypertensive drugs adversely affect lipoprotein metabolism, these drugs may increase associated coronary risk and offset the beneficial effects of lowering blood pressure. This article reviews the effects of various antihypertensive drugs on plasma lipids, lipoproteins, and apolipoproteins. They can be summarized as follows: thiazide-type diuretics cause a marked elevation of plasma triglycerides and very low-density lipoprotein (VLDL) and minor increases in total cholesterol and low-density lipoprotein (LDL), but have little effects on high-density lipoprotein (HDL). The nonselective β-blockers do not significantly affect total cholesterol and LDL, but increase total triglycerides and VLDL and decrease HDL. The changes in plasma lipids and lipoproteins caused by cardioselective β-blockers and β-blockers with intrinsic sympathomimetic activity are qualitatively similar but less pronounced. Calcium antagonists and angiotensin-converting enzyme inhibitors appear to have no significant effects on plasma lipids. α 1-inhibitors reduce total triglycerides, total cholesterol, VLDL, and LDL and increase HDL. The possible mechanisms by which antihypertensive drugs affect cellular lipid metabolism (e.g., LDL receptor, lipid synthesis, lipoprotein lipase, lecithin cholesteryl acyltransferase, acylcholesteryl acyltransferase, and cholesteryl ester hydrolase) are described. The clinical significance of changes in blood lipids and cellular lipid metabolism caused by antihypertensive drugs is not yet totally clear. Nevertheless, before antihypertensive drug treatment is initiated, blood lipid levels should be measured to identify preexisting hyperlipidemia. Blood lipoprotein levels should be monitored during long-term antihypertensive therapy to reconsider the therapeutic regimen if adverse lipid changes are observed.