From the Division of Cardiology (J.S.M., K.K.P.), Division of Nephrology and Kidney Research Institute (J.S.M., M.C.S., R.K., B.K., I.H.d.B.), Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology (S.R.H., D.S.S.), Department of Epidemiology (S.R.H., B.K., I.H.d.B.), and Department of Laboratory Medicine (A.N.H.), University of Washington, Seattle; Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis (A.A.); Division of Renal Diseases and Hypertension, University of Colorado, Denver (M.C.); Division of Cardiology, Electrophysiology Section, University of Pennsylvania, Philadelphia (R.D.); and Division of Nephrology and Hypertension, Department of Medicine, University of California San Diego, and San Diego VA Healthcare System, San Diego (J.H.I.).
Circulation. 2014 Jul 22;130(4):298-307. doi: 10.1161/CIRCULATIONAHA.113.005499. Epub 2014 Jun 11.
Fibroblast growth factor-23 (FGF-23) is a hormone that promotes urinary phosphate excretion and regulates vitamin D metabolism. Circulating FGF-23 concentrations increase markedly in chronic kidney disease and are associated with increased risk of clinical cardiovascular events. FGF-23 may promote atrial fibrillation (AF) by inducing left ventricular hypertrophy and diastolic and left atrial dysfunction.
We tested the associations of circulating FGF-23 concentration with incident AF among 6398 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) and 1350 participants in the Cardiovascular Health Study (CHS), all free of clinical cardiovascular disease at baseline. Over a median of 7.7 and 8.0 years of follow-up, we observed 291 and 229 incident AF events in MESA and CHS, respectively. In multivariable Cox proportional hazards models, each 2-fold-higher FGF-23 concentration was associated with a 41% higher risk of incident AF in MESA (hazard ratio, 1.41; 95% confidence interval, 1.13-1.76; P=0.003) and a 30% higher risk of incident AF in CHS (hazard ratio, 1.30; 95% confidence interval, 1.05-1.61; P=0.016) after adjustment for potential confounding characteristics, including kidney disease. Serum phosphate concentration was significantly associated with incident AF in MESA (hazard ratio, 1.15 per 0.5 mg/dL; 95% confidence interval, 1.02-1.31; P=0.023) but not CHS. In MESA, an association of low estimated glomerular filtration rate with incident AF was partially attenuated by adjustment for FGF-23.
Higher circulating FGF-23 concentration is associated with incident AF and may, in part, explain the link between chronic kidney disease and AF.
成纤维细胞生长因子 23（FGF-23）是一种促进尿磷排泄和调节维生素 D 代谢的激素。在慢性肾脏病中，循环 FGF-23 浓度显著增加，并与临床心血管事件风险增加相关。FGF-23 可能通过诱导左心室肥厚、舒张和左房功能障碍来促进心房颤动（AF）。
我们在动脉粥样硬化多民族研究（MESA）的 6398 名参与者和心血管健康研究（CHS）的 1350 名参与者中测试了循环 FGF-23 浓度与 AF 事件发生的相关性，所有参与者在基线时均无临床心血管疾病。在中位数为 7.7 年和 8.0 年的随访期间，我们分别在 MESA 和 CHS 中观察到 291 例和 229 例新发 AF 事件。在多变量 Cox 比例风险模型中，FGF-23 浓度每增加 2 倍，与 MESA 新发 AF 的风险增加 41%相关（风险比，1.41；95%置信区间，1.13-1.76；P=0.003），与 CHS 新发 AF 的风险增加 30%相关（风险比，1.30；95%置信区间，1.05-1.61；P=0.016），调整了潜在混杂特征，包括肾脏病。血清磷酸盐浓度与 MESA 新发 AF 显著相关（风险比，每 0.5mg/dL 增加 1.15；95%置信区间，1.02-1.31；P=0.023），但在 CHS 中不相关。在 MESA 中，通过调整 FGF-23，估算肾小球滤过率低与新发 AF 的相关性部分减弱。
较高的循环 FGF-23 浓度与新发 AF 相关，可能部分解释了慢性肾脏病与 AF 之间的联系。
