Prognostic significance of circulating levels of angiogenic cytokines in patients with congestive heart failure

Background Recent experimental studies have suggested that the angiogenic cytokines hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) may play a role in the pathogenesis of congestive heart failure (CHF). The aim of the present study was to test the hypothesis that HGF and VEGF concentrations may vary according to the different markers of CHF severity and to analyze the impact of HGF and VEGF concentrations on the cardiovascular mortality of patients with CHF. Methods We studied 529 consecutive patients who were referred to our center for an evaluation of left ventricular dysfunction. Hepatocyte growth factor and vascular endothelial growth factor levels were determined on blood samples obtained on entry into the study. Clinical follow-up (median 988 days) was obtained for 528 patients. Results Hepatocyte growth factor concentrations were strongly associated with age, diabetes mellitus, and all markers of CHF severity; by contrast, baseline characteristics did not differ among VEGF tertiles. Cardiovascular survival rates at 1, 2, and 3 years were 91%, 87%, and 80%, respectively. The survival curves indicated a worse outcome for patients with high HGF concentrations at baseline (P < .0001); by contrast, cardiovascular survival was similar across the tertiles of VEGF (P = .37). Hepatocyte growth factor concentrations were higher in the 109 patients with a cardiovascular event (1001 [741-1327] pg/mL) than in the 419 patients without (773 [610-1045] pg/mL, P < .0001). By multivariate analysis, a baseline HGF concentration >802 pg/mL was associated with an increased cardiovascular mortality (hazard ratio = 1.85, 95% CI 1.09-3.13, P = .02); other variables retained into the final model were B-type natriuretic peptide (P < .0001), peak oxygen consumption (P = .0002), and ischemic etiology (P = .0005). Conclusions Hepatocyte growth factor levels correlate with CHF severity and are associated with an increased cardiovascular mortality during follow-up.