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Atherosclerosis is the leading cause of death in the Western world. Drugs discussed in this chapter prevent the sequelae of atherosclerosis (heart attacks, angina, peripheral arterial disease, ischemic stroke) and decrease mortality in patients with a history of cardiovascular disease and hyperlipidemia. Although the drugs are generally safe and effective, they can cause problems, including drug-drug interactions and toxic reactions in skeletal muscle and the liver.

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LipoproteinsMacromolecular complexes in the blood that transport lipids
ApolipoproteinsProteins on the surface of lipoproteins; they play critical roles in the regulation of lipoprotein metabolism and uptake into cells
Low-density lipoprotein (LDL)Cholesterol-rich lipoprotein whose regulated uptake by hepatocytes and other cells requires functional LDL receptors; an elevated LDL concentration is associated with atherosclerosis
High-density lipoprotein (HDL)Cholesterol-rich lipoprotein that transports cholesterol from the tissues to the liver; a low concentration is associated with atherosclerosis
Very-low-density lipoprotein (VLDL)Triglyceride- and cholesterol-rich lipoprotein secreted by the liver that transports triglycerides to the periphery; precursor of LDL
HMG-CoA reductase3-Hydroxy-3-methylglutaryl-coenzyme A reductase; the enzyme that catalyzes the rate-limiting step in cholesterol biosynthesis
Lipoprotein lipase (LPL)An enzyme found primarily on the surface of endothelial cells that releases free fatty acids from triglycerides in lipoproteins; the free fatty acids are taken up into cells
Proliferator-activated receptor-alpha (PPAR-α)Member of a family of nuclear transcription regulators that participate in the regulation of metabolic processes; target of the fibrate drugs and omega-3 fatty acids
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Pathogenesis

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Premature or accelerated development of atherosclerosis is strongly associated with elevated concentrations of certain plasma lipoproteins, especially the low-density lipoproteins (LDLs) that participate in cholesterol transport. A depressed level of high-density lipoproteins (HDLs) is also associated with increased risk of atherosclerosis. In some families, hypertriglyceridemia is similarly correlated with atherosclerosis. Chylomicronemia, the occurrence of chylomicrons in the serum while fasting, is a recessive trait that is correlated with a high incidence of acute pancreatitis and managed by restriction of total fat intake (Table 35–1).

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Table 35–1 Primary Hyperlipoproteinemias and Their Drug Treatment.

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