doi: 10.1161/hc4401.098467
(Circulation. 2001;104:2376.)
© 2001 American Heart Association, Inc.
From Bench to Bedside |
Exploiting the Vascular Protective Effects of High-Density Lipoprotein and Its Apolipoproteins
An Idea Whose Time for Testing Is Coming, Part I
From the Atherosclerosis Research Center, Division of Cardiology and Burns and Allen research Institute, Department of Medicine, Cedars Sinai Medical Center and UCLA School of Medicine (P.K.S., S.K., B.C.), Los Angeles, Calif, and the University of Malmo, Lund, Sweden (J.N).
Correspondence to P.K. Shah, MD, Director, Division of Cardiology and Atherosclerosis Research Center, Room 5347, Cedars Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA 90048. E-mail shahp@cshs.org
Key Words: lipoproteins • atherosclerosis • apolipoproteins
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Introduction |
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"An invasion of armies can be resisted but not an idea whose time has come."
—Victor Hugo.
Vaso-occlusive disease resulting from atherosclerosis and thrombosis is the leading cause of death and morbidity in the United States and other industrialized nations. Although the precise cause of atherosclerosis is unclear, an emerging paradigm suggests that atherosclerosis involves multiple pathways in which lipoprotein entry and retention, injury to the vessel wall from diverse stimuli, and an associated long-term inflammatory and immune response seem to play a key role.1–4 Dyslipidemia characterized predominantly by elevated levels of one or more circulating non-HDL cholesterol lipoproteins [LDL, VLDL, lipoprotein(a), triglycerides] and/or reduced HDL cholesterol is one of the key risk factors for atherosclerosis and cardiovascular disease.5–16 Over the past several years, a number of large, prospective, randomized, controlled clinical trials have demonstrated both angiographic and clinical benefits of lipid-lowering therapy, with a significant reduction in fatal and nonfatal cardiovascular events.17–23 These studies have primarily targeted LDL cholesterol through pharmacotherapy (mostly statins), with or without dietary counseling, lifestyle modification, or surgery (intestinal bypass in Program on the Surgical Control of the Hyperlipidemias [POSCH] trial). Overall, a significant and clinically worthwhile relative risk reduction ranging from 20% to 40% in major cardiovascular events has been achieved with these strategies, without significant adverse effects or increased noncardiovascular mortality. These remarkable results prompted Brown and Goldstein24 to predict that heart attacks will be gone with the century. This clearly reflects an overoptimistic point of view, because 60% to 70% of
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