Editorials |
From the University of Pennsylvania School of Medicine, Philadelphia.
Correspondence to Daniel J. Rader, MD, University of Pennsylvania Medical Center, 654 BRBII/III, Philadelphia, PA 19104-6160. E-mail rader@mail.med.upenn.edu
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
Disorders of plasma lipoprotein metabolism ("dyslipidemia") play a major role in the initiation and progression of atherosclerotic cardiovascular disease (ASCVD). Low-density lipoproteins (LDL), as well as other atherogenic apoB-containing lipoproteins, are known to promote cholesterol accumulation in macrophages as well as inflammatory responses within the vessel wall, leading to atherosclerosis progression. In addition, high-density lipoproteins (HDL) and their major apolipoprotein, apoA-I, promote the efflux of cholesterol from macrophages, the first step in the process of reverse cholesterol transport, and have other antiinflammatory and antioxidant effects that may contribute to inhibition of atherosclerosis. Pharmacological treatment to reduce levels of atherogenic lipoproteins, particularly the use of 3-hydroxy-3-methylglutaryl (HMG) coenzyme A (CoA) reductase inhibitors, or statins, has been proven in multiple large clinical outcome trials to significantly reduce the risk of cardiovascular events, generally by about one-third over five years. Indeed, the reduction of cardiovascular risk with statin therapy has been one of the greatest advances in medicine over the last two decades, and the expanding use of statin therapy will undoubtedly contribute to an important reduction in atherosclerotic cardiovascular disease over the next several decades.
See page 482
However, the success of statin therapy has not eliminated the importance of continuing to develop new therapeutic approaches to the treatment of dyslipidemia. First, as the targets for lipid lowering therapy become ever more aggressive, it becomes more and more difficult for a substantial number of patients to achieve these aggressive targets using statins alone. Approximately only one-half of high risk patients with established
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