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

J Thromb Haemost. 2016 Apr;14(4):655-66. doi: 10.1111/jth.13274. Epub 2016 Mar 14.


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.

Keywords: coronary artery disease; hypercoagulability; laboratory marker; secondary prevention; tissue factor.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anticoagulants / chemistry*
  • Antithrombins / blood
  • Antithrombins / chemistry*
  • Coronary Angiography
  • Coronary Artery Disease / blood*
  • Coronary Artery Disease / mortality*
  • Enzyme-Linked Immunosorbent Assay
  • Factor VIIa / chemistry*
  • Female
  • Follow-Up Studies
  • Glomerular Filtration Rate
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • Prospective Studies
  • Risk Factors
  • Thrombin / chemistry
  • Thromboplastin / metabolism
  • Treatment Outcome


  • Anticoagulants
  • Antithrombins
  • Thromboplastin
  • Factor VIIa
  • Thrombin