Summary.  Atherosclerosis is a chronic inflammatory disease and the complement system plays a central role in innate immunity. Increasing evidence exists that the complement system is activated within atherosclerotic plaques. However, the role of complement in atherogenesis is not fully understood. Whereas complement activation by the classic and lectin pathway may be protective by removing apoptotic cells and cell debris from atherosclerotic plaques, activation of the complement cascade by the alternative pathway and beyond the C3 convertase with formation of anaphylatoxins and the terminal complement complex may be proatherogenic and may play a role in plaque destabilization leading to its rupture and the onset of acute cardiovascular events. In this review article we present evidence for complement activation within atherosclerotic plaques and we discuss recent data derived from experimental animal models that suggest a dual role of complement in the development of the disease. In addition, we summarize the role of complement components as biomarkers for cardiovascular disease.

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Complement activation, indicated by the elevation of C5a, seems to be associated with increased cardiovascular risk in patients with advanced atherosclerosis. Clinically, determination of C5a may add to the predictive value of other non-specific inflammatory parameters.

Background-␤-Blockers improve clinical outcome when administered early after acute myocardial infarction. However, whether ␤-blockers actually reduce the myocardial infarction size is still in dispute. Cardiac magnetic resonance imaging can accurately depict the left ventricular (LV) ischemic myocardium at risk (T2-weighted hyperintense region) early after myocardial infarction, as well as the extent of necrosis (delayed gadolinium enhancement). The aim of this study was to determine whether early administration of metoprolol could increase myocardial salvage, measured as the difference between the extent of myocardium at risk and myocardial necrosis. Methods and Results-Twelve Yorkshire pigs underwent a 90-minute left anterior descending coronary occlusion, followed by reperfusion. They were randomized to metoprolol (7.5 mg during myocardial infarction) or placebo. Global and regional LV function, extent of myocardium at risk, and myocardial necrosis were quantified by cardiac magnetic resonance imaging studies performed 4 and 22 days after reperfusion in 10 survivors. Despite similar extent of myocardium at risk in metoprolol-and placebo-treated pigs (30.9% of LV versus 30.6%; PϭNS), metoprolol resulted in 5-fold-larger salvaged myocardium (32.4% versus 6.2% of myocardium at risk; Pϭ0.015). The LV ejection fraction significantly improved in metoprolol-treated pigs between days 4 and 22 (37.2% versus 43.0%; Pϭ0.037), whereas it remained unchanged in pigs treated with placebo (35.1% versus 35.0%; PϭNS). The extent of myocardial salvage was related directly to LV ejection fraction improvement (Pϭ0.031) and regional LV wall motion recovery (Pϭ0.039) at day 22. Conclusions-Early metoprolol administration during acute coronary occlusion increases myocardial salvage. The extent of myocardial salvage, measured as the difference between myocardium at risk and myocardial necrosis, was associated with regional and global LV motion improvement. (Circulation. 2007;115:2909-2916.)