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on October 22, 2009

Arteriosclerosis, Thrombosis, and Vascular Biology. 2009
Published online before print October 1, 2009, doi: 10.1161/ATVBAHA.109.192740
A more recent version of this article appeared on December 1, 2009
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Submitted on June 8, 2009
Accepted on September 10, 2009

Hemostasis, Inflammation, and Fatal and Nonfatal Coronary Heart Disease. Long-Term Follow-Up of the Atherosclerosis Risk in Communities (ARIC) Cohort

Anna M. Kucharska-Newton *; David J. Couper ; James S. Pankow ; Ronald J. Prineas ; Thomas D. Rea ; Nona Sotoodehnia ; Aravinda Chakravarti ; Aaron R. Folsom ; David S. Siscovick ; and Wayne D. Rosamond

From the University of North Carolina at Chapel Hill (A.M.K.-N., D.J.C., W.D.R.); the University of Minnesota (J.S.P., A.R.F.), Minneapolis; the Wake Forest University (R.J.P.), Winston Salem, NC; the University of Washington (T.D.R., N.S., D.S.S.), Seattle; and the Johns Hopkins University (A.C.), Baltimore, Md.

* To whom correspondence should be addressed. E-mail: Anna_Newton{at}unc.edu.

Objective—This study examines the hypothesis that chronic inflammation is associated with a higher risk of cardiac death compared to the risk of nonfatal myocardial infarction.

Methods and Results—Cardiac death and nonfatal MI events were identified in the ARIC cohort during follow-up from 1987 through 2001. Markers of inflammation and hemostasis were determined at baseline using standardized procedures. Cox proportional hazard regression and polytomous logistic regression were used to estimate associations. We observed a positive gradient in incidence of sudden cardiac death (SCD), nonsudden cardiac death (NSCD), and nonfatal MI in association with decreasing levels of albumin and increasing levels of white blood cell count and of markers of hemostasis (fibrinogen, von Willebrand factor, factor VIIIc). Associations for von Willebrand factor were stronger for fatal relative to nonfatal events (3rd versus 1st tertile hazard ratios: SCD 3.11 [95% CI 2.10, 4.59], NSCD 2.12 [95% CI 1.28, 3.49], nonfatal MI 1.42 [95% CI 1.19, 1.70]). For factor VIIIc those associations were strongest for sudden cardiac death: SCD 3.16 (95% CI 2.18, 4.58), NSCD 1.44 (95% CI 0.93, 2.24), nonfatal MI 1.54 (95% CI 1.29, 1.84). Gradients of association for fibrinogen and white blood cell count, examined over tertiles of distribution and per one SD increase, were similar for the 3 end points. All associations were independent of smoking status.

Conclusion—von Willebrand factor and factor VIIIc are associated with an increased risk of cardiac death as compared to the risk of nonfatal MI.


Key words: hemostasis • inflammation • von Willebrand factor • sudden cardiac death • nonfatal myocardial infarction