BACKGROUND: Abnormal indices of angiogenesis have been reported in chronic heart failure (CHF). We tested the hypothesis that circulating angiogenin (a potent inducer of neovascularization in vivo) is higher in CHF patients compared with controls and associated with indices of CHF severity: brain natriuretic peptide (BNP), Simpson's left ventricular ejection fraction (EF), and New York Heart Association (NYHA) class. METHODS: Using a cross-sectional approach, we measured serum angiogenin and BNP levels in 109 consecutive patients with CHF (85 males; mean age 60 (standard deviation (SD) 10 yrs) and 112 asymptomatic controls with normal cardiac function and related levels to echocardiographic parameters. RESULTS: Angiogenin was significantly higher in CHF patients compared to controls (P <0.001). On univariate analysis, angiogenin was positively associated with age, plasma glucose, insulin, and BNP (all P <0.001); and negatively correlated with diastolic blood pressure (P = 0.04) and EF (P = 0.002). Angiogenin levels increased in an ordinal fashion with NYHA class, exaggerated by the presence of diabetes mellitus (pseudo R2 = 0.15, P <0.001). In multivariate analysis, angiogenin levels were only associated with deteriorating NYHA classification (beta = 0.14 (95% confidence interval (CI) 0.09-0.19), P <0.001). Angiogenin was also a modest discriminator for the presence of CHF (area under the curve 0.72; 95% CI 0.62-0.82), P <0.001). CONCLUSION: Angiogenin is related to worsening heart failure severity (NYHA classification), with the highest levels in NYHA class III. Further research is warranted to determine the validity of angiogenin in a diagnostic and prognostic capacity in CHF.