The inflection point: α-Klotho levels and the risk of all-cause mortality.

IF 3.9 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Frontiers in Endocrinology Pub Date : 2025-03-11 eCollection Date: 2025-01-01 DOI:10.3389/fendo.2025.1405003

Jianling Song, Hong Li, Xiangdong Fang

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引用次数: 0

Abstract

Purpose: The controversial nature of the association between α-Klotho and mortality risk in the general population warrants further investigation. This study aims to examine the correlation between circulating α-Klotho levels and the risk of all-cause mortality.

Methods: A sample size of 13,748 individuals from the NAHNES 2005-2016 cycles was included in this study. The effect of different α-Klotho levels (divided into quartiles) on survival was assessed using Kaplan-Meier (KM) curves. Cox proportional hazards models were used to analyze the linear relationship between log α-Klotho and the risk of all-cause mortality. Restricted cubic spline Cox proportional hazards regression model was used to analyze the non-linear relationship between log α-Klotho and risk of all-cause mortality. Threshold effect analysis was performed to determine the most favorable inflection point for log α-Klotho. Stratification and sensitivity analyses were performed to assess the robustness of the results.

Results: A total of 1,569 deaths were reported during the median follow-up period of 5.33 years (2.83-7.83 years). Among the log α-Klotho quartile groups, quartile 1 had the highest mortality rate compared to quartiles 2, 3, and 4. Multifactorial Cox regression analysis revealed a weak association between log α-Klotho and a 44% reduction in the risk of all-cause mortality (p=0.0473). We also found a U-shaped non-linear association between log α-Klotho and risk of all-cause mortality, with an optimal inflection point identified at 2.89 pg/mL. The stability of the U-shaped association between log α-Klotho and mortality risk was observed in various stratification and sensitivity analyses.

Conclusion: This study identified a U-shaped association between circulating α-Klotho levels and risk of all-cause mortality, with a notable inflection point at 2.89 pg/mL. Further investigation is warranted to fully elucidate the potential mechanisms underlying the association between α-Klotho and risk of all-cause mortality in the broader population.

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拐点：α-Klotho水平与全因死亡风险。

目的：α-Klotho与普通人群死亡风险相关性的争议性值得进一步研究。本研究旨在探讨循环α-Klotho水平与全因死亡风险的相关性。方法：本研究纳入了2005-2016年NAHNES周期的13748例样本。采用Kaplan-Meier （KM）曲线评估不同α-Klotho水平（分四分位数）对生存率的影响。采用Cox比例风险模型分析log α-Klotho与全因死亡风险的线性关系。采用限制性三次样条Cox比例风险回归模型分析log α-Klotho与全因死亡风险之间的非线性关系。通过阈值效应分析确定log α-Klotho的最有利拐点。进行分层和敏感性分析以评估结果的稳健性。结果：在中位随访5.33年（2.83-7.83年）期间，共报告1569例死亡。在log α-Klotho四分位数组中，四分位数1的死亡率高于四分位数2、3和4。多因素Cox回归分析显示，log α-Klotho与全因死亡风险降低44%之间存在弱相关性（p=0.0473）。我们还发现log α-Klotho与全因死亡风险之间呈u型非线性关联，最佳拐点为2.89 pg/mL。在各种分层和敏感性分析中，观察到log α-Klotho与死亡风险之间的u型相关性的稳定性。结论：本研究发现循环α-Klotho水平与全因死亡风险呈u型相关，其显著拐点为2.89 pg/mL。在更广泛的人群中，α-Klotho与全因死亡风险相关的潜在机制有待进一步研究。

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来源期刊

Frontiers in Endocrinology Medicine-Endocrinology, Diabetes and Metabolism

CiteScore

5.70

自引率

9.60%

发文量

3023

审稿时长

14 weeks

期刊介绍： Frontiers in Endocrinology is a field journal of the "Frontiers in" journal series. In today’s world, endocrinology is becoming increasingly important as it underlies many of the challenges societies face - from obesity and diabetes to reproduction, population control and aging. Endocrinology covers a broad field from basic molecular and cellular communication through to clinical care and some of the most crucial public health issues. The journal, thus, welcomes outstanding contributions in any domain of endocrinology. Frontiers in Endocrinology publishes articles on the most outstanding discoveries across a wide research spectrum of Endocrinology. The mission of Frontiers in Endocrinology is to bring all relevant Endocrinology areas together on a single platform.