{"title":"The inflection point: α-Klotho levels and the risk of all-cause mortality.","authors":"Jianling Song, Hong Li, Xiangdong Fang","doi":"10.3389/fendo.2025.1405003","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"16 ","pages":"1405003"},"PeriodicalIF":3.9000,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11932894/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Endocrinology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3389/fendo.2025.1405003","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
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.
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.