Prospective association of vascular endothelial growth factor-A (VEGF-A) with coronary heart disease mortality in Southeastern New England

Background: Autopsy data suggest that plaque neovascularization may be associated with coronary heart disease (CHD) death. Since vascular endothelial growth factor-A (VEGF-A) is upregulated in angiogenesis and therefore neovascularization, we hypothesized that individuals with elevated levels of VEGF-A at baseline would be a greater risk of dying of CHD compared to those with lower levels over time. Methods: We measured VEGF-A levels in 46 CHD death cases and a 14% random sample of 2321 community participants who were free of self-reported CHD at baseline. Traditional CHD risk factors such as age, gender, family history of CHD, cigarette smoking, hypertension, total cholesterol/HDL ratio, diabetes mellitus, were also evaluated at baseline. Mortality follow-up was determined through linkage of baseline data with the National Death Index. Results: During a median of 13 years of follow-up, 46 subjects died of coronary heart disease. Mean VEGF-A levels were significantly higher in the CHD death cases than among the random population sample (400 pg/ml vs. 303 pg/ml, p = 0.0004). In proportional hazards models adjusting for traditional risk factors, the hazard ratios (95%CI) for CHD death associated with increasing tertiles of VEGF-A were 1.0 (referent), 2.12 (0.74, 6.10), and 3.85 (1.37, 10.78), respectively (P_{test for trend} = 0.008). Conclusion: In this population-based prospective, case-cohort study, baseline levels of VEGF-A showed a significant independent association with the risk of CHD death.