The evolving role of statins in the management of atherosclerosis
Carl J. Vaughan, MD, MRCPIa,
Antonio M. Gotto, Jr., MD, DPhil, FACCa and
Craig T. Basson, MD, PhD, FACCa
a Division of Cardiology, Department of Medicine, Weill Medical College of Cornell University, The New York Presbyterian Hospital, Starr 4, 525 East 68th Street, New York, New York 10021.USA
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Figure 1 Regulation of cholesterol synthesis. Inhibition of HMG CoA reductase reduces intracellular cholesterol levels, thus activating a protease, which in turn cleaves sterol regulatory element-binding proteins (SREBPs) from the endoplasmic reticulum. The SREBPs translocate to the nucleus where they upregulate expression of the LDL receptor gene. Enhanced LDL receptor expression increases receptor-mediated endocytosis of LDL and thus lowers serum LDL. Inhibition of HMG CoA reductase also reduces intracellular levels of isoprenoids, which are intermediates in cholesterol biosynthesis.
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Figure 2 LDL lowering in primary and secondary prevention trials of statin therapy. The mean LDL enrollment levels are depicted for major trials testing statin utility in primary prevention (WOSCOPS, AFCAPS) and secondary prevention (4S, CARE, LIPID) of coronary artery disease. Mean LDL levels achieved after statin therapy in each trial are also depicted. The NCEP-recommended goals for LDL lowering are depicted for both primary and secondary CAD prevention. Note that mean LDL levels achieved with statins in the AFCAPS primary prevention trial to determine drug efficacy are lower than the NCEP goals. (*Absolute value extrapolated from a reported 25% reduction in LDL [23]).
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Figure 3 Statins and determinants of acute coronary syndromes. Statins exhibit pleiotropic effects on many components of atherosclerosis that accompany hypercholesterolemia, including platelet coagulation abnormalities, abnormal endothelial function, and determinants of plaque thrombogenicity such as plaque inflammation and proliferation.
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