Hemostasis, inflammation, and fatal and nonfatal coronary heart disease: long-term follow-up of the atherosclerosis risk in communities (ARIC) cohort

Abstract

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.

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

Figure 1

Association of markers of inflammation and hemostasis with the risk of sudden cardiac death, non-sudden cardiac death, and non-fatal MI in the total sample population (A.) and among never smokers (B.). Hazard ratio per one SD difference in exposure. Analysis adjusted for age, gender, race, ARIC center, cigarette years of smoking (total sample only), and cigarette smoking status (total sample only). vwF: von Willebrand factor; WBC: white blood cell count ● sudden cardiac death; ■ non-sudden cardiac death; ▲ non-fatal MI

Figure 2

Kaplan-Meier curves of cumulative survival according to tertiles of von Willebrand factor, Factor VIIIc, fibrinogen, white blood cell count, and albumin. Data adjusted for age and presented for the following outcomes: non-data MI, non-sudden cardiac death, and sudden cardiac death. The ARIC study cohort 1987-2001. 1^st tertile ; 2^nd tertile; 3^rd tertile