Clinical, diagnostic, and therapeutic aspects of familial hypercholesterolemia.

Heterozygous familial hypercholesterolemia (FH) is a common inherited disorder of lipoprotein metabolism. FH is characterized by elevated levels of low-density lipoprotein cholesterol, the presence of tendon xanthomas, and premature cardiovascular disease. The underlying molecular defect of FH consists of mutations in the gene coding for the low-density-lipoprotein-receptor protein, detection of which provides the only unequivocal diagnosis. Although the cause of FH is monogenic, there is wide variation in the onset and severity of atherosclerotic disease in these patients. Additional atherogenic risk factors of environmental, metabolic, and genetic origin are presumed to influence the clinical phenotype in FH. Criteria used to identify individuals with FH include a combination of clinical characteristics, personal and family history of early coronary artery disease, and biochemical parameters. Since the introduction in 1989 of statins, which have been shown to be effective and to delay or prevent the onset of cardiovascular disease, drug treatment of FH has greatly improved. New lipid-lowering agents are presently being developed for clinical use. This review provides an update on the clinical, diagnostic, and therapeutic aspects of heterozygous familial hypercholesterolemia.