Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease (Nov 2018)

VEGF‐C and Mortality in Patients With Suspected or Known Coronary Artery Disease

  • Hiromichi Wada,
  • Masahiro Suzuki,
  • Morihiro Matsuda,
  • Yoichi Ajiro,
  • Tsuyoshi Shinozaki,
  • Satoru Sakagami,
  • Kazuya Yonezawa,
  • Masatoshi Shimizu,
  • Junichi Funada,
  • Takashi Takenaka,
  • Yukiko Morita,
  • Toshihiro Nakamura,
  • Kazuteru Fujimoto,
  • Hiromi Matsubara,
  • Toru Kato,
  • Takashi Unoki,
  • Daisuke Takagi,
  • Shuichi Ura,
  • Kyohma Wada,
  • Moritake Iguchi,
  • Nobutoyo Masunaga,
  • Mitsuru Ishii,
  • Hajime Yamakage,
  • Akira Shimatsu,
  • Kazuhiko Kotani,
  • Noriko Satoh‐Asahara,
  • Mitsuru Abe,
  • Masaharu Akao,
  • Koji Hasegawa

DOI
https://doi.org/10.1161/JAHA.118.010355
Journal volume & issue
Vol. 7, no. 21

Abstract

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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.

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