should we use ppar agonists to reduce cardiovascular risk我们应该使用ppar激动剂以减少心血管疾病的风险.pdfVIP

Hindawi Publishing Corporation PPAR Research Volume 2008, Article ID 891425, 13 pages doi:10.1155/2008/891425 Review Article Should We Use PPAR Agonists to Reduce Cardiovascular Risk? Jennifer G. Robinson Departments of Epidemiology Medicine, University of Iowa, Iowa City, IA 52242, USA Correspondence should be addressed to Jennifer G. Robinson, jennifer-g-robinson@ Received 2 July 2007; Accepted 9 October 2007 Recommended by Giulia Chinetti Trials of peroxisome proliferator-activated receptor (PPAR) agonists have shown mixed results for cardiovascular prevention. Fi- brates are PPAR-α agonists that act primarily to improve dyslipidemia. Based on low- and high-density lipoprotein cholesterol (LDL and HDL) effects, gemfibrozil may be of greater cardiovascular benefit than expected, fenofibrate performed about as ex- pected, and bezafibrate performed worse than expected. Increases in both cardiovascular and noncardiovascular serious adverse events have been observed with some fibrates. Thiazolidinediones (TZDs) are PPAR-γ agonists used to improve impaired glucose metabolism but also influence lipids. Pioglitazone reduces atherosclerotic events in diabetic subjects, but has no net cardiovascular benefit due to increased congestive heart failure risk. Rosiglitazone may increase the risk of atherosclerotic events, and has a net harmful effect on the cardiovascular system when congestive heart failure is included. The primary benefit of TZDs appears to be the prevention of diabetic microvascular complications. Dual PPAR-α/γ agonists have had unacceptable adverse effects but more selective agents are in development. PPAR-δ and pan-agonists are also in development. It will be imperative to prove that future PPAR agonists not only prevent atherosclerotic events but also result in a net redu