Beyond LDL Cholesterol: the Role of LDL Particles and HDL

Abstract

Currently available hypolipidemic treatments aim at reducing low density lipoprotein (LDL)-cholesterol. Unfortunately, cardiovascular events continue to occur despite LDL-lowering therapy with use of statins. Recent evidence has revealed that having increased concentrations of small LDL particles, though common, is an unhealthy pattern; high concentrations of small LDL particles correlate with much faster growth of atheroma, progression of atherosclerosis and earlier and more severe cardiovascular events and death. In addition, at any given level of total cholesterol, the relative risk of coronary artery disease increases with decreasing levels of high density lipoprotein (HDL)-cholesterol. Thus, the target for new interventions would be to reduce small LDL particles and increase HDL and/or its apolipoproteins, which are recognized to have major vascular protective effects ranging from prevention to stabilization and regression of atherosclerosis. L D L C H O L E S T E R O L A N D L D L P A R T I C L E S Atherosclerotic cardiovascular disease is the worldwide leading cause of death, which involves multiple pathways in which lipoprotein entry and retention, injury to the vessel wall from several stimuli, and inflammation seem to play a key role. Currently available treatments are aimed at reducing the high plasma lipid concentrations, most particularly low density lipoprotein (LDL)-cholesterol. Increasing evidence has revealed that the concentration and size of the LDL particles are powerfully related to the degree of atherosclerosis progression than the concentration of cholesterol contained within all the LDL particles. The LDL particles actually vary in size and density, and studies have shown that a pattern that has more small dense LDL particles—called “Pattern B”—equates to a higher risk factor for coronary heart disease (CHD) than does a pattern with more of the larger and less dense LDL particles (“Pattern A”). This is because the smaller particles are more easily able to penetrate the endothelium. “Pattern I,” meaning “intermediate,” indicates that most LDL particles are very close in size to the normal gaps in the endothelium (26 nm). The healthiest pattern, though relatively rare, is to have small numbers of large LDL particles and no small particles. Having small LDL particles, though common, is an unhealthy pattern; high concentrations of small LDL particles (even though potentially carrying the same total EDITORIAL First Department of Cardiology, Hippokratio University Hospital, Athens, Greece HOSPITAL CHRONICLES 2009, 4(3): 102–104 Correspondence to: Christos Pitsavos, MD, FESC, FACC Associate Professor of Cardiology Hippokratio University Hospital Athens, Greece E-mail: cpitsavo@med.uoa.gr KEy WORDS: LDL cholesterol; LDL particles; HDL cholesterol; coronary heart disease; statins; niacin; fibrates;