Activated factor VII-antithrombin complex predicts mortality in patients with stable coronary artery disease: a cohort study

Essentials Activated factor VII–antithrombin complex (FVIIa-AT) in plasma may reflect tissue factor exposure. FVIIa-AT levels were assessed in an angiographically controlled coronary artery disease (CAD) cohort. High FVIIa-AT levels correlated with an increased thrombin generation. High FVIIa-AT levels were associated with a greater risk of mortality in patients with stable CAD. Summary Background Plasma concentration of activated factor VII (FVIIa)–antithrombin (AT) complex has been proposed as an indicator of intravascular exposure of tissue factor. Objectives The aims of this observational study were to evaluate (i) FVIIa-AT plasma concentration in subjects with or without coronary artery disease (CAD) and (ii) its association with mortality in a prospective cohort of patients with CAD. Methods FVIIa-AT levels were measured by elisa in 686 subjects with (n = 546) or without (n = 140) angiographically proven CAD. Subjects with acute coronary syndromes and those taking anticoagulant drugs at the time of enrollment were excluded. CAD patients were followed for total and cardiovascular mortality. Results There was no difference in FVIIa-AT levels between CAD (84.8 with 95% confidence interval [CI] 80.6–88.2 pmol L–1) and CAD-free subjects (83.9 with 95% CI 76.7–92.8 pmol L–1). Within the CAD population, during a 64-month median follow-up, patients with FVIIa-AT levels higher than the median value at baseline (≥ 79 pmol L–1) had a two-fold greater risk of both total and cardiovascular mortality. Results were confirmed after adjustment for sex, age, the other predictors of mortality (hazard ratio for total mortality: 2.05 with 95% CI 1.22–3.45, hazard ratio for cardiovascular mortality 1.94 with 95% CI 1.01–3.73, with a slight improvement of C-statistic over traditional risk factors), FVIIa levels, drug therapy at discharge, and even patients using all the usual medications for CAD treatment. High FVIIa-AT levels also correlated with increased thrombin generation. Conclusions This preliminary study suggests that plasma concentration of FVIIa-AT is a thrombophilic marker of total and cardiovascular mortality risk in patients with clinically stable CAD.