Circulation. 2005;111:3481-3488
doi: 10.1161/CIRCULATIONAHA.105.537878
doi: 10.1161/CIRCULATIONAHA.105.537878
(Circulation. 2005;111:3481-3488.)
© 2005 American Heart Association, Inc.
Basic Science for Clinicians |
Pathophysiology of Coronary Artery Disease
From the Donald W. Reynolds Cardiovascular Clinical Research Center (P.L.), Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass, and the Department of Medicine (P.T.), Montreal Heart Institute, University of Montreal, Montreal, Quebec, Canada.
Correspondence to Peter Libby, MD, Brigham and Women’s Hospital, 77 Ave Louis Pasteur, NRB 741, Boston, MA 02115. E-mail plibby{at}rics.bwh.harvard.edu
During the past decade, our understanding of the pathophysiology of coronary artery disease (CAD) has undergone a remarkable evolution. We review here how these advances have altered our concepts of and clinical approaches to both the chronic and acute phases of CAD. Previously considered a cholesterol storage disease, we currently view atherosclerosis as an inflammatory disorder. The appreciation of arterial remodeling (compensatory enlargement) has expanded attention beyond stenoses evident by angiography to encompass the biology of nonstenotic plaques. Revascularization effectively relieves ischemia, but we now recognize the need to attend to nonobstructive lesions as well. Aggressive management of modifiable risk factors reduces cardiovascular events and should accompany appropriate revascularization. We now recognize that disruption of plaques that may not produce critical stenoses causes many acute coronary syndromes (ACS). The disrupted plaque represents a "solid-state" stimulus to thrombosis. Alterations in circulating prothrombotic or antifibrinolytic mediators in the "fluid phase" of the blood can also predispose toward ACS. Recent results have established the multiplicity of "high-risk" plaques and the widespread nature of inflammation in patients prone to develop ACS. These findings challenge our traditional view of coronary atherosclerosis as a segmental or localized disease. Thus, treatment of ACS should involve 2 overlapping phases: first, addressing the culprit lesion, and second, aiming at rapid "stabilization" of other plaques that may produce recurrent events. The concept of "interventional cardiology" must expand beyond mechanical revascularization to embrace preventive interventions that forestall future events.
Key Words: atherogenesis • inflammation • ischemia • plaque • acute coronary syndromes
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|
|
|
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|
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|
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|
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|
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|
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|
|
|
|
|
|
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|
|
|
|
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|
|
|
|
|
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|
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|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
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|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|