18-year change in serum intact fibroblast growth factor 23 from midlife to late life and risk of mortality: the ARIC Study.
18-year change in serum intact fibroblast growth factor 23 from midlife to late life and risk of mortality: the ARIC Study.
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DOI：
10.1530/eje-21-0891
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发表时间：
2022-05-12
影响因子：
5.8
通讯作者：
Matsushita, Kunihiro
中科院分区：
文献类型：
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作者：
Ishigami, Junichi;Honda, Yasuyuki;Karger, Amy B.;Coresh, Josef;Selvin, Elizabeth;Lutsey, Pamela L.;Matsushita, Kunihiro
成纤维细胞生长因子23（FGF 23）浓度增加，以响应肾功能下降，以保持正常的磷酸盐浓度。然而，尚未在一般人群中研究FGF 23浓度变化与死亡率的病因学关联。我们分析了5，458名社区动脉粥样硬化风险研究的参与者，他们在中年期间评估了完整的FGF 23和估计的肾小球滤过率（eGFR）（访视3，1993-1995年，平均年龄58岁）和晚年（访视5，2011-2013，76岁），以使用考克斯回归模型检查从中年到晚年的18年间FGF 23变化与随后的晚年死亡风险的关联。完整FGF 23的中位18年变化为+17.3 pg/mL。在第5次访视后中位随访7.2年期间，1，176名参与者死亡。在多变量考克斯模型中，与最低四分位数[≤6.4 pg/mL]相比，在FGF 23变化的最高四分位数（Δ FGF 23，≥31.3 pg/mL）中观察到死亡率升高（校正的风险比[aHR]，1.61 [95%CI，1.36 - 1.90]或1.37 [1.15 - 1.64]，在额外校正eGFR变化后）。当FGF 23变化和晚年的FGF 23同时进入考克斯模型时，晚年的FGF 23，而不是FGF 23变化，是死亡率的独立预测因子;然而，我们观察到从中年到晚年的FGF 23变化和晚年的FGF 23之间的高度相关性（r=0.77）。从中年到晚年的血清完整FGF 23变化与随后的死亡风险相关，与肾功能下降无关。我们的研究结果进一步支持FGF 23的意义超出了其与肾功能的关联。
Fibroblast growth factor 23 (FGF23) concentration increases in response to declining kidney function to preserve normal phosphate concentrations. However, the etiological association of change in FGF23 concentration with mortality has not been examined in the general population. We analyzed 5,458 participants of the Atherosclerosis Risk in Communities Study who had intact FGF23 and estimated glomerular filtration rate (eGFR) assessed during midlife (visit 3, 1993–1995, mean age 58 years) and late-life (visit 5, 2011–2013, 76 years) to examine the association of FGF23 change over 18 years from mid-life to late-life with the subsequent risk of mortality in late-life using Cox regression models. The median 18-year change in intact FGF23 was +17.3 pg/mL. During a median follow-up of 7.2 years following visit 5, 1,176 participants died. In multivariable Cox models, elevated mortality was seen in the highest quartile of FGF23 change (ΔFGF23, ≥31.3 pg/mL) (adjusted hazard ratio [aHR], 1.61 [95%CI, 1.36 to 1.90], or 1.37 [1.15 to 1.64] after additionally adjusting for eGFR change, compared with the lowest quartile [≤6.4 pg/mL]). When both FGF23 change and FGF23 in late-life were simultaneously entered into the Cox model, FGF23 in late-life, but not FGF23 change, was an independent predictor of mortality; however, we observed a high correlation between FGF23 change from midlife to late-life and FGF23 in late-life (r=0.77). Serum intact FGF23 change from midlife to late-life was associated with subsequent risk of mortality independent of decline in kidney function. Our findings further support the implications of FGF23 beyond its association with kidney function.