Hypercholesterolemia and Metabolic Syndrome: Mischievous Partners

Abstract

Elevations of two lipoproteins contribute to atherogenic hypercholesterolemia: low density lipoprotein (LDL) and very low density lipoprotein (VLDL). Their atherogenic potential is identified by their cholesterol (C) content. Together they constitute non-HDL-C. In populations and individuals having very low levels of non-HDL-C, atherosclerotic cardiovascular disease (ASCVD) is rare. In persons with severe elevations of non-HDL-C, these lipoproteins can initiate atherogenesis and precipitate ASCVD in the absence of other risk factors. The importance of non-HDL-C for development of ASCVD is dramatically shown by the reduction in risk accompanying cholesterol-lowering therapy. This does not negate the importance of other risk factors. The most common aggregation of these risk factors occurs in a condition called the metabolic syndrome. The prevalence of the metabolic syndrome increases in parallel with the increasing obesity in the population. This condition is characterized by abdominal obesity, insulin resistance and increased risk for type 2 diabetes, elevations in triglycerides, reduction in HDL, elevations in blood pressure, and prothrombotic and proinflammatory states. Epidemiological studies shown that the presence of the metabolic syndrome doubles the risk for ASCVD and carries a 5-fold increase in risk for type 2 diabetes. Most of the metabolic syndrome can be attributed to lifestyle factors, notably, over nutrition and decreased physical activity. Future advances on prevention of ASCVD will depend on new approaches to controlling hypercholesterolemia and to reducing the prevalence of the metabolic syndrome.