doi: 10.1161/CIRCULATIONAHA.105.611350
(Circulation. 2006;113:2128-2151.)
© 2006 American Heart Association, Inc.
Controversies in Cardiovascular Medicine |
Is C-reactive protein an innocent bystander or proatherogenic culprit?
The Verdict Is Still Out
From the TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham & Women’s Hospital and Harvard Medical School, Boston, Mass (B.S, D.M.); Division of Cardiac Surgery, St. Michael’s Hospital, University of Toronto, Toronto, Canada (S.V.); Laboratory for Artherosclerosis and Metabolic Research, Department of Medical Pathology and Laboratory Medicine (S.D., I.J.), and Division of Endocrinology, Clinical Nutrition and Vascular Medicine, Department of Medicine (I.J.), University of California, Davis Medical Center, Sacramento.
Correspondence to David A. Morrow, MD, MPH, TIMI Study Group, Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis St, Boston, MA 02115 (e-mail dmorrow@partners.org); Dr S. Verma, Division of Cardiac Surgery, St. Michael’s Hospital, 30 Bond St, Toronto, Canada (e-mail subodh.verma@sympatico.ca); or Dr I. Jialal, Laboratory for Artherosclerosis and Metabolic Research, University of California, Davis Medical Center, Sacramento, CA (e-mail ishwarlal.jialal@ucdmc.ucdavis.edu).
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
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Introduction |
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Presence at the scene of a crime is not itself necessarily compelling evidence of guilt.— Mark B. Pepys
The recognition of inflammation as a central contributor to atherothrombosis has engendered a sustained effort to characterize the specific participants and pathways and to identify noninvasive markers that enable detection of underlying inflammatory activation for the purpose of assessing cardiovascular risk. C-reactive protein (CRP), an acute-phase reactant, has been investigated in the pursuit of both of these objectives. Epidemiological studies have demonstrated an increased risk of cardiovascular events in patients with elevated levels of CRP.2–5 When considered together with experimental evidence placing CRP within arterial atheroma6–8 and clinical data revealing lowering of CRP with some preventive therapies, this strong base of epidemiological evidence has led to the hypothesis that CRP is both a marker of and a causal agent in the development of atherosclerosis.9,10 In other words, CRP may be both a "marker" and a "maker" of atherothrombosis.11 This hypothesis carries substantial clinical implications in that it forms the basis for both development of potential therapeutic agents that directly target CRP and consideration of CRP itself as a modifiable cardiovascular risk factor.
This unifying theory regarding CRP, while appealing, is not yet established by the available evidence.1,11 We will review the in vitro and in vivo data that support the assertion that CRP is itself pathogenic and the conflicting findings that render this conclusion premature.
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CRP as a Marker of Clinical Risk |
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To understand the basis for the intense investigation of CRP as a proatherogenic agent, it is
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