Elevated D-dimer levels are associated with coronary artery disease and cardiovascular death in an angiographically-studied population

Background: Thrombosis superimposed on a ruptured or unstable atherosclerotic plaque is the leading cause of most ischemic cardiovascular events. D-dimer, a hemostasis biomarker reflecting activation of the blood coagulation has been recently associated with coronary artery disease (CAD). Using a quantitative, highly sensitive, D-dimer assay, we investigated its association with cardiovascular risk and outcome in a subset of patients from the angiography-based Verona Heart Study (VHS). Methods: A total number of 824 subjects not assuming anticoagulants at enrolment in the VHS were included in this study. Out of them, 510 were part of a case-control setting (349 CAD versus 161 CAD-free). The remaining (n = 314) were part of an independent cohort of CAD patients prospectively followed for a median follow-up of 56 months. D-dimer levels were measured using the INNOVANCE D-Dimer assay (Siemens Healthcare Diagnostics Products GmbH, Marburg, Germany). Results: D-dimer levels were significantly higher in CAD patients as compared to CAD-free (0.62 mg/L with 95% CI: 0.57–0.68 vs. 0.46 mg/L with 95% CI 0.41–0.52; P < 0.001 by test). D-dimer levels in the highest tertile (> 0.61 mg/L) were independently associated with CAD after adjustment for age and gender (OR 1.89 with 95% CI: 1.13–4.14). In the prospective evaluation, 39 patients (12.4%) had died during follow-up; of them, 27 (69.2%) died because of cardiovascular events. After adjustment for age, gender and high sensitivity C-reactive protein levels, elevated D-dimer levels (> 0.61 mg/L) significantly predicted both total and cardiovascular mortality (HR for total mortality 2.43 with 95% CI: 1.16–5.31; HR for cardiovascular mortality 2.74 with 95% CI: 1.07–7.04, respectively). Conclusions: Elevated D-dimer levels are significant prognostic markers in patients with angiographically confirmed CAD.