Background: Collateral circulation can protect and preserve the myocardium against episodes of ischemia and reduce cardiovascular events. Brain-derived neurotrophic factor (BDNF) is an angiogenic regulator promoting angiogenesis. We compared the association of plasma levels of BDNF and C-reactive protein, an established marker, and risk factors of cardiovascular dysfunction and prognosis in patients with angina pectoris. Methods: We enrolled 885 patients with angina pectoris. Plasma BDNF and CRP were measured by ELISA. Patients were prospectively followed for a median of 48 months (interquartile range 37-59 months), and information on further coronary events and mortality was collected. Results: Multiple risk factors for cardiovascular disease were independent determinants of low plasma BDNF level in patients with angina pectoris. Plasma BDNF was inversely associated with levels of triglycerides and low-density lipoprotein cholesterol, presence of diabetes mellitus, fibrinogen level, male sex and age and positively with high-density lipoprotein cholesterol level and platelet count. During follow-up, 15.2% of patients experienced a major coronary event (MCE), and 10.5% died. The plasma BDNF level was an independent predictor of 4-year MCE (adjusted hazard ratio = 1.25 with 95% confidence interval 1.10-1.41, P < 0.01 for each unit increase in the natural logarithm of the BDNF level) and of 4-year mortality (adjusted hazard ratio = 1.29, 95% confidence interval 1.11-1.47, P < 0.01). Conclusion: Multiple cardiovascular risk factors are associated with plasma BDNF level in patients with angina pectoris, and low plasma BDNI, may be associated with future coronary events and mortality in these patients. (C) 2011 Elsevier Inc. All rights reserved.