(Circulation. 1997;95:1-4.)
© 1997 American Heart Association, Inc.
Articles |
Small LDL, Atherogenic Dyslipidemia, and the Metabolic Syndrome
the University of Texas Southwestern Medical Center at Dallas.
Correspondence to Scott M. Grundy, MD, PhD, University of Texas Southwestern Medical Center at Dallas, Center for Human Nutrition, 5323 Harry Hines Blvd, Dallas, TX 75235.
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Introduction |
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A high serum cholesterol has been increasingly acknowledged as being a major risk factor for coronary heart disease (CHD). Several types of evidence support the cholesterol-CHD link; these encompass research in laboratory animals, epidemiological studies, findings of premature CHD in genetic forms of hypercholesterolemia, laboratory investigations, and clinical trials of cholesterol-lowering therapy. Most people with a high serum cholesterol also have elevated LDL because much of the serum cholesterol is transported in LDL. The concept therefore has emerged that LDL is the predominant atherogenic lipoprotein. The National Cholesterol Education Program (NCEP)1 specifically designated LDL cholesterol as the primary target of cholesterol-lowering therapy. This assignment of priority to LDL cholesterol seems to be fully vindicated by recent clinical trials.2 3 4 These trials tested HMG CoA reductase inhibitors (statins), which mainly lower LDL, for effects on coronary morbidity and mortality. Statin therapy in these trials produced astonishing reductions in new coronary events; these reductions almost certainly were a result of concomitant decreases in LDL levels.
Among the different risk factors for CHD, a raised LDL level appears to be primary. Strong evidence indicates that high LDL concentrations initiate atherogenesis and promote atherosclerosis at every stage. The remarkable finding that LDL-lowering therapy reduces risk for subsequent coronary events even in patients with advanced atherosclerotic disease discloses a role for LDL in late stages of atherogenesis.2 3 4 Moreover, populations devoid of some elevations of LDL levels exhibit relatively low prevalence of CHD even when other coronary risk factors, eg, cigarette smoking, hypertension, and diabetes mellitus, are
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