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(Circulation. 2004;109:726-732.)
© 2004 American Heart Association, Inc.

Clinical Investigation and Reports

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)

B. Delia Johnson, PhD; Kevin E. Kip, PhD; Oscar C. Marroquin, MD; Paul M Ridker, MD; Sheryl F. Kelsey, PhD; Leslee J. Shaw, PhD; Carl J. Pepine, MD; Barry Sharaf, MD; C. Noel Bairey Merz, MD; George Sopko, MD; Marian B. Olson, MS; Steven E. Reis, MD

From the Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pa (B.D.J., K.E.K., S.F.K., M.B.O.); University of Pittsburgh Medical Center, Pittsburgh, Pa (O.C.M., S.E.R.); Brigham and Women’s Hospital, Boston, Mass (P.M.R.); Atlanta Cardiovascular Research Institute, Atlanta, Ga (L.J.S.); University of Florida, Gainesville, Fla (C.J.P.); Rhode Island Hospital, Providence, RI (B.S.); Women’s Health Program, Cedars Sinai Hospital, Los Angeles, Calif (C.N.B.M.); and the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md (G.S.).

Correspondence to B. Delia Johnson, PhD, Graduate School of Public Health, University of Pittsburgh, Parran 127, 130 DeSoto St, Pittsburgh, PA 15261. E-mail djohnson{at}edc.pitt.edu

Received December 17, 2003; accepted December 17, 2003.

Background— Serum amyloid- (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.

Key Words: inflammation • amyloid • proteins • coronary disease • women

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