摘要：
Objective To determine the association of serum fibroblast growth factor-23 concentrations with age-related cardiac diastolic function subclinical state and whether this association differs by sex.Methods Seven hundred sixteen healthy subjects (aged 35-89 years,68.4％ female) were selected from National Basic Research Program of China (973 Program-China Medical University subsection) between January 2014 and February 2015 and assigned into 4 groups according to sex and age:<60 years old male and female group,≥ 60 years old male and female group.Blood biochemical indicators and general clinical data of the subjects were measured.The glomerular filtration rate (eGFR) were estimated using the Modified Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI-ASIA) equation.The fibroblast factor 23 (FGF-23),C-reactive protein (CRP) and interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay (ELISA).Cardiac structure and function parameters including left atrial diameter (LAD),inter-ventricular septum thickness (IVST),left ventricle posterior wall thickness (LVPWT),left ventricle mass index (LVMI),left atrial mass index (LAVI) and the ratio of peak velocity of early filling to the septal early peak diastolic mitral annulus velocity(E/e') were measured by echocardiography.Association between serum FGF-23 and aging-related diastolic function subclinical status was analyzed by binary Logistic regression analysis.Results (1) Serum log-transformed FGF-23 levels were significantly higher in males than in females [(2.0±0.3) ng/L vs (1.9±0.4) ng/L,P＜0.05].(2) Cardiac diastolic function gradually decreased with age,and age related cardiac diastolic function decline of female was significantly higher than males[E/e':＜60 years old male group (7.6±2.6),≥ 60 years old male group (8.6±2.7),P＜0.01;＜60 years old female group (8.3±2.3),≥ 60 years old female group (9.5±3.1),P＜0.01;LAVI:＜60 years old female group (14±5) ml/m2,≥ 60 years old female group (16±5) ml/m2,P＜0.01].(3) Serum FGF-23 was significantly positively correlated with age (r=0.089,P＜0.05) and LAVI (r=0.084,P＜0.05) in total study population while with E/e'(r=0.149,P＜0.05) only in males.There was no significant correlation between serum FGF-23 and cardiac diastolic function parameters in females.(4) Binary Logistic regression analysis showed that median and high FGF-23 were independently associated with age-related cardiac diastolic function decline (OR=2.831,95％ CI:1.144-7.009,P=0.024;OR=2.548,95％ CI:1.053-6.163,P=0.038) in males.Conclusions Serum FGF-23 concentrations are associated with age-related cardiac diastolic function subclinical state in a healthy Chinese population.High levels of FGF-23 are independently associated with age-related cardiac diastolic function decline in males.%目的 探讨健康人群成纤维细胞生长因子23水平与衰老相关心脏舒张功能亚临床状态改变的相关性及二者相关性的性别差异.方法 选取国家973衰老课题组2014年1月至2015年2月中国医科大学研究人群716例,按性别、年龄分为4组:＜60岁男性组、女性组,≥60岁男性组、女性组.检测受试者一般临床资料及血液生化指标,以亚洲人群改良的慢性肾脏疾病流行病学协作组(CKD-EPI-ASIA)公式估算肾小球滤过率(eGFRCKD-EPI-ASIA).测量并记录受试者超声心动图心脏结构及舒张功能指标:左房内径(LAD)、室间隔厚度(IVST)、左室后壁厚度(LVPWT)、左室质量指数(LVMI)、左房质量指数(LAVI)及舒张早期二尖瓣血流峰值速度E与舒张早期二尖瓣瓣环峰值速度e’的比值(E/e').应用酶联免疫吸附试验双抗体夹心法测定成纤维细胞生长因子23(FGF-23)、C反应蛋白(CRP)及白细胞介素6(IL-6).以二元Logistic回归方程按三分位数分层法分析FGF-23水平与衰老相关心脏舒张功能亚临床状态的相关性及二者相关性的性别差异.结果 (1)血清LogFGF-23水平男性与女性相比,差异具有统计学意义[(2.0±0.3) ng/L比(1.9±0.4) ng/L,P＜0.05].(2)心脏舒张功能随年龄增长而逐渐减低,且女性舒张功能随年龄下降较男性显著[E/e’:＜60岁男性组(7.6±2.6),≥60岁男性组(8.6±2.7),P＜0.01;＜60岁女性组(8.3±2.3),≥60岁女性组(9.5±3.1),P＜0.01;LAVI:＜60岁女性组(14±5)m]/m2,≥60岁女性组(16±5) ml/m2,P＜0.01].(3) FGF-23与总体人群中年龄、LAVI存在相关性.FGF-23与男性E/e’呈显著正相关(r=0.149,P＜0.05),而女性无显著相关性.(4)二元Logistic校正混杂变量后显示,男性中位数水平及高位数水平FGF-23与心脏舒张功能增龄性下降独立相关(OR=2.831,95％CI 1.144～7.009,P=0.024;OR=2.548,95％CI 1.053～6.163,P=0.038).结论 健康人群血清FGF-23水平与衰老相关心脏舒张功能亚临床改变有关,高水平FGF-23与男性衰老相关心脏舒张功能减低具有独立相关性.
