Multifactorial Etiology of Hypercholesterolemia Implications for Prevention of Coronary Heart Disease

High serum cholesterol is a major risk factor for coronary heart disease (CHD), and most cholesterol in serum circulates with low density lipoproteins (LDLs). These lipoproteins are macromolecular complexes containing a core of nonpolar lipids — mainly cholesterol ester—and a surface coat of unesterified cholesterol, phospholipids, and apolipoprotein (apo) B-100. Many investigators believe that the high levels of LDL are mainly responsible for the association between high serum cholesterol and CHD. Apparently, circulating LDL particles filter into the arterial wall where they are chemically or physically modified and are taken up by macrophages. Uptake of LDL transforms macrophages into foam cells, the hallmark of atherosclerotic lesions. Although other lipoproteins-very low density lipoproteins (VLDLs) and high density lipoproteins (HDLs) — undoubtedly participate in atherogenesis, LDL appears to be the primary culprit. This review therefore will focus on the causation of high serum levels of LDL cholesterol, and it will consider the implications of causation for therapeutic control of hypercholesterolemia.