To review the pathophysiology of atherosclerosis, the role of the renin—angiotensin system in atherogenesis, and studies supporting the potential beneficial effects of angiotensin-converting enzyme (ACE) inhibitors in reducing cardiovascular events with long-term use.
BACKGROUND:
Through its action in converting angiotensin I to angiotensin II and by degrading bradykinin, local tissue ACE exerts many effects that can contribute to the development of atherosclerosis. Therefore, the use of ACE inhibitors can possibly result in antiatherogenic effects. Possible mechanisms for antiatherogenic effects of ACE inhibitors include: (1) reduction of blood pressure; (2) antiproliferative and antimigratory effects on vascular smooth muscle cells, neutrophils, and monocytes; (3) restoration of endothelial function; (4) stabilization of fatty plaque by preventing vasoconstriction; (5) antiplatelet effects; and (6) enhancement of endogenous fibrinolysis.
DATA SOURCES:
English-language clinical studies, abstracts, and review articles pertaining to the use of ACE inhibitors and atherosclerosis.
STUDY SELECTION AND DATA EXTRACTION:
Relevant human studies examining the role of ACE inhibitors and atherosclerosis.
DATA SYNTHESIS:
Studies evaluating the possible beneficial effects of ACE inhibitors in the development of atherosclerosis are reviewed and critiqued. Design of ongoing studies with clinical and surrogate end points are discussed.
CONCLUSIONS:
Based on current published studies, recommendations are made regarding the use of ACE inhibitors in atherosclerosis. Therapeutic monitoring parameters for efficacy and adverse effects are also reviewed.
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