Markers of hypercoagulability and inflammation predict mortality in patients with heart failure

Background and aims: Plasma levels of inflammatory markers are increased in chronic heart failure (HF) and are also subclinical indicators of future HF. Inflammation is strictly correlated with clotting activation, but the association between inflammation, hypercoagulability and prognosis in HF has not been previously reported. Methods and results: Markers of inflammation (interleukin-6; IL-6, and C-reactive protein; CRP) and hypercoagulability (D-dimer; DD, and thrombinantithrombin III complex; TAT) were prospectively assessed in 214 subjects with New York Heart Association (NYHA) functional class II-IV HF. During a median follow-up of 8.5 months, 32 patients had an event: 13 died and 19 were hospitalized because of worsening of HF. IL-6, DD and TAT levels were all significantly associated with increased risk of death after adjustment for other known HF prognostic factors (age, gender, traditional cardiovascular risk factors, NYHA class, systolic left ventricular function, renal failure, hemoglobin, serum sodium) in a Cox multivariate proportional hazard model (P = 0.003, P = 0.01 and P = 0.02, respectively). When these markers were added simultaneously to the known prognostic factors in a new Cox multivariate model, only DD levels were significant predictors of mortality (hazard ratio [95% confidence interval; CI]: 11 [2.7-45.1], P = 0.001). The Kaplan-Meier curve revealed a significantly better outcome in patients with DD below 450 ng mL^-1. NT-pro-BNP was the only significant predictor of rehospitalization (HR[95% CI]: 5.3 [2.0-13.8], P <0.001). Conclusion: Hypercoagulability and inflammation, as assessed by DD, TAT and IL-6 levels, are associated with an increased mortality risk in HF.