Familial hypercholesterolemia arises from a defect in the gene for low-density lipoprotein receptors (LDL-R). Heterozygotes for this defect experience accelerated atherosclerosis and represent about 1 in 500 persons.

Hyperlipidemia may also arise from secondary causes including obesity, diabetes, alcohol abuse, hypothyroidism, glucocorticoid excess, and hepatic or renal dysfunction.

Most cases of hyperlipidemia in adults arise from a combination of secondary causes, genetic predisposition, and environmental factors, including poor diet and a lack of exercise.

It has been recognized for several decades that increased plasma concentrations of total and LDL cholesterol are associated with an increased risk of cardiovascular disease. Conversely, higher high-density lipoprotein (HDL) cholesterol levels appear to reduce the risk of atherosclerosis and cardiovascular events because of the critical role of HDL in reverse cholesterol transport. The safety and efficacy of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) inhibitors, or statins, have been particularly well established (Table 23-2).