成纤维细胞生长因子23（FGF23）与死亡率：路德维希港风险与心血管健康研究
Fibroblast growth factor 23 (FGF23) and mortality: the Ludwigshafen Risk and Cardiovascular Health Study.
作者信息
Brandenburg Vincent M, Kleber Marcus E, Vervloet Marc G, Tomaschitz Andreas, Pilz Stefan, Stojakovic Tatjana, Delgado Graciela, Grammer Tanja B, Marx Nikolaus, März Winfried, Scharnagl Hubert
机构信息
Department of Cardiology, University Hospital of the RWTH Aachen, Germany.
Medical Clinic V, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
出版信息
Atherosclerosis. 2014 Nov;237(1):53-9. doi: 10.1016/j.atherosclerosis.2014.08.037. Epub 2014 Aug 28.
BACKGROUND
Fibroblast growth factor 23 (FGF23) is an important regulatory hormone in phosphate and vitamin D metabolism. Here, we investigated the associations of FGF23 with traditional cardiovascular risk factors and with bone metabolism parameters as well as the impact of FGF23 upon long-term mortality in a large cohort of patients referred for coronary angiography.
METHODS
We examined whether c-term FGF23 concentrations at baseline were associated with cardiovascular and total mortality in 2974 patients from the Ludwigshafen Risk and Cardiovascular Health Study (LURIC). We investigated if these associations were independent from established cardiovascular risk factors as well as from other mineral regulating factors and bone biomarkers such as calcium, parathyroid hormone (PTH), alkaline phosphatase (AP), vitamin D, and serum phosphate.
RESULTS
Mean age of participants was 63 ± 10 years; median c-term FGF23 serum levels were 54 (40-78) RU/ml. During a median follow-up of 9.9 years, 884 deaths (30%) occurred, 545 (18%) of which were cardiovascular. FGF23 significantly and inversely correlated with eGFR. AP, phosphate, and PTH increased in parallel with quartiles of FGF23. Age- and sex-adjusted hazard ratios (HRs) in the fourth quartile compared to the first quartile of FGF23 were 2.54 (95%CI, 2.09-3.09; p < 0.001) for all cause and 2.56 (95% CI, 1.99-3.28; p < 0.001) for cardiovascular mortality. These associations remained significant after additional adjustments for cardiovascular risk factors and bone biomarkers (calcium, PTH, AP, vitamin D, and phosphate): Adjusted HRs were 1.38 (95%CI, 1.26-1.52; p < 0.001) for all-cause and 1.35 (95%CI, 1.20-1.52; p < 0.001) for cardiovascular mortality for each increase by one standard deviation of c-term FGF23.
CONCLUSIONS
In patients undergoing coronary angiography baseline c-term FGF23 levels predict the risk for all-cause and cardiovascular mortality over 9.9 years of follow-up. These associations were independent of established cardiovascular risk factors and serum phosphate.
背景
成纤维细胞生长因子23（FGF23）是磷酸盐和维生素D代谢中的一种重要调节激素。在此，我们在一大群接受冠状动脉造影的患者中，研究了FGF23与传统心血管危险因素、骨代谢参数之间的关联，以及FGF23对长期死亡率的影响。
方法
我们在路德维希港风险与心血管健康研究（LURIC）的2974名患者中，研究基线时的C末端FGF23浓度是否与心血管死亡率和全因死亡率相关。我们调查了这些关联是否独立于既定的心血管危险因素以及其他矿物质调节因子和骨生物标志物，如钙、甲状旁腺激素（PTH）、碱性磷酸酶（AP）、维生素D和血清磷酸盐。
结果
参与者的平均年龄为63±10岁；C末端FGF23血清水平中位数为54（40 - 78）RU/ml。在中位随访9.9年期间，发生了884例死亡（30%），其中545例（18%）为心血管死亡。FGF23与估算肾小球滤过率（eGFR）显著负相关。AP、磷酸盐和PTH随FGF23四分位数平行增加。与FGF23第一四分位数相比，第四四分位数的年龄和性别调整风险比（HR）对于全因死亡率为2.54（95%CI，2.09 - 3.09；p < 0.001），对于心血管死亡率为2.56（95%CI，1.99 - 3.28；p < 0.001）。在对心血管危险因素和骨生物标志物（钙、PTH、AP、维生素D和磷酸盐）进行额外调整后，这些关联仍然显著：C末端FGF23每增加一个标准差，全因死亡率的调整后HR为1.38（95%CI，1.26 - 1.52；p < 0.001），心血管死亡率的调整后HR为1.35（95%CI，1.20 - 1.52；p < 0.001）。
结论
在接受冠状动脉造影的患者中，基线C末端FGF23水平可预测9.9年随访期间的全因死亡率和心血管死亡率风险。这些关联独立于既定的心血管危险因素和血清磷酸盐。
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