Genetic Epidemiology and Lipids: A Pattern So Grand and Complex

Intensive research over the course of the last several decades led to dramatic improvements in understanding, treating, and preventing cardiovascular disease. Despite this progress, cardiovascular disease remains the leading cause of mortality in both high- and low-income countries, and the leading source of morbidity in high-income countries. Lipids are well known determinants of cardiovascular disease risk; epidemiological evidence was published long ago. Total cholesterol and low-density lipoprotein cholesterol (LDL), which tend to be strongly correlated, are associated with increased disease risk. LDL can be readily oxidized, which causes inflammation and atherosclerosis to occur, and small, dense LDL particles are considered the most atherogenic lipid particles. High-density lipoprotein cholesterol (HDL), by contrast, is associated with beneficial effects, in terms of cardiovascular disease risk. Several mechanisms are likely to account for the protective consequences of increased HDL concentrations. HDL exhibits anti-inflammatory properties. Additionally, it is thought to be an anti-oxidant, helping to offset the deleterious effects of oxidized LDL. HDL is also involved in reverse cholesterol transport (i.e. the sequestration of cholesterol to the liver for metabolism), which helps to reduce the amount of circulating lipid.

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