doi: 10.1161/01.ATV.0000121505.88326.d2
© 2004 American Heart Association, Inc.
Editorials |
High-Density Lipoproteins: A New Potential Therapeutic Target for the Prevention of Cardiovascular Disease
From the Molecular Disease Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.
Correspondence to H. Bryan Brewer, National Heart, Lung, and Blood Institute, National Institutes of Health, Molecular Disease Branch, Building 10 Room 7N115, Bethesda, MD 20892-1666. Email bryan@mdb.nhlbi.nih.gov
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
Epidemiological studies have identified low-density lipoproteins (LDL) and high-density lipoproteins (HDL) as independent risk factors that modulate cardiovascular disease (CVD) risk.1,2 Over the past decade, clinical trials of LDL-lowering drugs have clearly established that reductions in LDL are associated with a 30% to 45% reduction in clinical events.3–7 However, despite lowered LDL, many patients continue to have cardiac events. Low HDL is often present in high-risk patients with CVD.8 As a result, a great deal of research interest recently has been focused on raising plasma HDL levels by dietary, pharmacological, or genetic manipulations as a potential strategy for the treatment of CVD. In addition to epidemiologic studies, other lines of evidence suggest that raising HDL would reduce the risk of CVD. Infusion of HDL in the form of apoA-I/phospholipids complexes was associated with regression of atherosclerosis in cholesterol-fed rabbits.9 Moreover, increased plasma HDL concentrations achieved by overexpressing human apoA-I in transgenic animals protects against the development of diet-induced10 and genetically determined atherosclerosis.11 Recently, 5 weekly infusions of apoA-I Milano/phospholipid complexes were shown to regress total atheroma volume by 4.2% in 36 patients compared with 11 controls after an acute coronary event using intravascular ultrasound to quantitate coronary atheroma.12 These combined results provide support for the concept that raising HDL may represent an additional therapeutic target for prevention of CVD.
See page 490
Although our understanding of how HDL protects against CVD is still incomplete, there is evidence that supports at least 3 major atheroprotective mechanisms of HDL. HDL-mediated efflux of
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