Changes in Serum Intact Fibroblast Growth Factor 23 Concentrations From Midlife to Late Life and Their Predictors in the Community: The ARIC Study.
Changes in Serum Intact Fibroblast Growth Factor 23 Concentrations From Midlife to Late Life and Their Predictors in the Community: The ARIC Study.
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DOI：
10.1016/j.mayocpiqo.2022.03.002
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发表时间：
2022-06
期刊：
影响因子：
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通讯作者：
Matsushita, Kunihiro
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作者：
Ishigami, Junichi;Honda, Yasuyuki;Karger, Amy B;Coresh, Josef;Selvin, Elizabeth;Lutsey, Pamela L;Matsushita, Kunihiro
研究一般人群从中年到晚年血液中成纤维细胞生长因子23(FGF23)浓度的纵向变化及其主要预测因素。在社区动脉粥样硬化风险研究的14,444名参与者中，我们使用3次就诊(就诊2[N=13,460；平均年龄，57岁]；就诊3[N=12,323；平均年龄，60岁]；就诊5[N=6122；平均年龄，76岁])和线性混合效应模型的数据，分析了31,095项完整血清FGF23测量与年龄的关系。在5804名在第三次访问和第五次访问时都进行了FGF23测量的参与者中，我们使用线性回归模型探索了FGF23从中年到中年变化的预测因素。预先确定的危险因素包括估计的肾小球滤过率、体重指数、曾经吸烟、曾经饮酒、糖尿病、高血压、心血管病史、总胆固醇和高密度脂蛋白胆固醇。FGF23浓度的中位数分别为41.9 pg/m L(四分位间隔[Iqi]，33.9~51.8 pg/m L)，38.3 pg/m l(IqI，30.6~48.3 pg/m l)和55.0 pg/m l(IqI，44.4~70.3 pg/m l)。线性混合效应模型显示，FGF23与年龄呈非线性关系，45-60岁略有下降或无变化，大于或等于65岁的单调增加(FGF23，每10岁儿童+10至15 pg/毫升)。在多变量线性回归模型中，显著更显著地增加了FGF23，中年估计肾小球滤过率小于每1.73m2 60毫升/分钟比大于或等于每1.73平方米60毫升/分钟(ΔFGF23，+4.4pg/mL[95%CI，0.9至8.0])，糖尿病与非糖尿病(ΔFGF23，+6.2pg/mL[95%CI，4.1至8.3])，以及高血压与非高血压(ΔFGF23，+4.1pg/mL[95%CI，2.7至5.4])。FGF23在中年没有表现出任何重大变化，但在晚年呈线性增加。肾功能降低、糖尿病和高血压与FGF23的升高密切相关。需要进一步的研究来了解这些情况与FGF23浓度增加之间的潜在机制。
To investigate longitudinal changes in the blood concentration of fibroblast growth factor 23 (FGF23) from midlife to late life and their major predictors in the general population. In 14,444 participants of the Atherosclerosis Risk in Communities Study, we analyzed the association of 31,095 measurements of serum intact FGF23 with age using data from 3 visits (visit 2 [N=13,460; mean age, 57 years]; visit 3 [N=12,323; mean age, 60 years]; and visit 5 [N=6122; mean age, 76 years]) and a linear mixed-effects model. Among 5804 participants who had FGF23 measurements at both visits 3 and 5, we explored predictors of FGF23 change from midlife to late life using linear regression models. Prespecified risk factors were estimated glomerular filtration rate, body mass index, ever smoking, ever drinker, diabetes, hypertension, history of cardiovascular disease, total cholesterol, and high-density lipoprotein cholesterol. Median FGF23 concentrations were 41.9 pg/mL (interquartile interval [IQI], 33.9 to 51.8 pg/mL) at visit 2, 38.3 pg/mL (IQI, 30.6 to 48.3 pg/mL) at visit 3, and 55.0 pg/mL (IQI, 44.4 to 70.3 pg/mL) at visit 5. A linear mixed-effects model showed that the association of FGF23 with age was nonlinear, with a slight decline or no change in age 45-60 years and a monotonic increase in age greater than or equal to 65 years (FGF23, +10 to 15 pg/mL per 10 years of age). In a multivariable linear regression model, significantly greater increases in FGF23 were noted, with midlife estimated glomerular filtration rate less than 60 mL/min per 1.73 m2 vs more than or equal to 60 mL/min per 1.73 m2 (ΔFGF23, +4.4 pg/mL [95% CI, 0.9 to 8.0]), diabetes vs no diabetes (ΔFGF23, +6.2 pg/mL [95% CI, 4.1 to 8.3]), and hypertension vs no hypertension (ΔFGF23, +4.1 pg/mL [95% CI, 2.7 to 5.4]). FGF23 did not show any major changes in midlife but increased linearly in late life. Reduced kidney function, diabetes, and hypertension were robustly associated with a greater increase in FGF23. Further investigations are needed to understand the potential mechanisms linking these conditions to an increase in FGF23 concentrations.