Serum amyloid A as a predictor of coronary artery disease and cardiovascular outcome in women - The National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation (WISE)

Background - Serum amyloid-alpha (SAA) is a sensitive marker of an acute inflammatory state. Like high-sensitivity C-reactive protein (hs-CRP), SAA has been linked to atherosclerosis. However, prior studies have yielded inconsistent results, and the independent predictive value of SAA for coronary artery disease ( CAD) severity and cardiovascular events remains unclear. Methods and Results - A total of 705 women referred for coronary angiography for suspected myocardial ischemia underwent plasma assays for SAA and hs-CRP, quantitative angiographic assessment, and follow-up evaluation. Cardiovascular events were death, myocardial infarction, congestive heart failure, stroke, and other vascular events. The women's mean age was 58 years ( range 21 to 86 years), and 18% were nonwhite. SAA and hs-CRP were associated with a broad range of CAD risk factors. After adjustment for these risk factors, SAA levels were independently but moderately associated with angiographic CAD ( P = 0.004 to 0.04) and highly predictive of 3-year cardiovascular events ( P < 0.0001). By comparison, hs-CRP was not associated with angiographic CAD ( P = 0.08 to 0.35) but, like SAA, was strongly and independently predictive of adverse cardiovascular outcome ( P < 0.0001). Conclusions - Our results show a strong independent relationship between SAA and future cardiovascular events, similar to that found for hs-CRP. Although SAA was independently but moderately associated with angiographic CAD, this association was not found for hs-CRP. These results are consistent with the hypothesis that systemic inflammation, manifested by high SAA or hs-CRP levels, may promote atherosclerotic plaque destabilization, in addition to exerting a possible direct effect on atherogenesis.