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Placental Growth Factor as a Predictor of Cardiovascular Events in Patients with CKD from the NARA-CKD Study
Authors:Masaru Matsui  Shiro Uemura  Yukiji Takeda  Ken-ichi Samejima  Takaki Matsumoto  Ayako Hasegawa  Hideo Tsushima  Ei Hoshino  Tomoya Ueda  Katsuhiko Morimoto  Keisuke Okamoto  Sadanori Okada  Kenji Onoue  Satoshi Okayama  Hiroyuki Kawata  Rika Kawakami  Naoki Maruyama  Yasuhiro Akai  Masayuki Iwano  Hideo Shiiki  Yoshihiko Saito  for the NARA-CKD Investigators
Abstract:Placental growth factor (PlGF) contributes to atherogenesis through vascular inflammation and plaque destabilization. High levels of PlGF may be associated with mortality and cardiovascular disease, but the relationship between PlGF level and adverse outcomes in patients with CKD is unclear. We conducted a prospective cohort study of 1351 consecutive participants with CKD enrolled in the Novel Assessment of Risk management for Atherosclerotic diseases in CKD (NARA-CKD) study between April 1, 2004, and December 31, 2011. During a median follow-up of 3 years, 199 participants died and 383 had cardiovascular events, defined as atherosclerotic disease or heart failure requiring hospitalization. In adjusted analyses, mortality and cardiovascular risk increased in each successive quartile of serum PlGF level; hazard ratios (HRs) (95% confidence intervals 95% CIs]) for mortality and cardiovascular risk, respectively, were 1.59 (0.83 to 3.16) and 1.55 (0.92 to 2.66) for the second quartile, 2.97 (1.67 to 5.59) and 3.39 (2.20 to 5.41) for the third quartile, and 3.87 (2.24 to 7.08) and 8.42 (5.54 to 13.3) for the fourth quartile. The composite end point of mortality and cardiovascular events occurred during the study period in 76.4% of patients in both the highest PlGF quartile (≥19.6 pg/ml) and the lowest eGFR tertile (<30 ml/min per 1.73 m2). The association between PlGF and mortality or cardiovascular events was not attenuated when participants were stratified by age, sex, traditional risk factors, and eGFR. These data suggest elevated PlGF is an independent risk factor for all-cause mortality and cardiovascular events in patients with CKD.
Keywords:cardiovascular disease  VEGF  cardiovascular events
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