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PPAR Research
Volume 2008 (2008), Article ID 891425, 13 pages
http://dx.doi.org/10.1155/2008/891425
Review Article

Should We Use PPAR Agonists to Reduce Cardiovascular Risk?

Departments of Epidemiology & Medicine, University of Iowa, Iowa City 52242, IA, USA

Received 2 July 2007; Accepted 9 October 2007

Academic Editor: Giulia Chinetti

Copyright © 2008 Jennifer G. Robinson. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Trials of peroxisome proliferator-activated receptor (PPAR) agonists have shown mixed results for cardiovascular prevention. Fibrates 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 expected, 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 reduction on total cardiovascular events without significant noncardiovascular adverse effects with long-term use.