Background The lymphatic system has been suggested to play an important role in
cholesterol metabolism and
cardiovascular disease. However, the relationships of
vascular endothelial growth factor-C (
VEGF -C), a central player in lymphangiogenesis, with mortality and cardiovascular events in patients with suspected or known
coronary artery disease are unknown. Methods and Results We performed a multicenter, prospective cohort study of 2418 patients with suspected or known
coronary artery disease undergoing elective coronary angiography. The primary predictor was serum levels of
VEGF -C. The primary outcome was all-cause death. The secondary outcomes were cardiovascular death, and major adverse cardiovascular events defined as a composite of cardiovascular death, non-fatal
myocardial infarction, and non-fatal
stroke. During the 3-year follow-up, 254 patients died from any cause, 88 died from
cardiovascular disease, and 165 developed major adverse cardiovascular events. After adjustment for established risk factors,
VEGF -C levels were significantly and inversely associated with all-cause death (hazard ratio for 1- SD increase, 0.69; 95% confidence interval, 0.60-0.80) and cardiovascular death (hazard ratio, 0.67; 95% confidence interval, 0.53-0.87), but not with major adverse cardiovascular events (hazard ratio, 0.85; 95% confidence interval, 0.72-1.01). Even after incorporation of N-terminal pro-
brain natriuretic peptide, contemporary sensitive cardiac
troponin-I, and
high-sensitivity C-reactive protein into a model with established risk factors, the addition of
VEGF -C levels further improved the prediction of all-cause death, but not that of cardiovascular death or major adverse cardiovascular events. Consistent results were observed within 1717 patients with suspected
coronary artery disease. Conclusions In patients with suspected or known
coronary artery disease, a low
VEGF -C value may independently predict all-cause mortality.