Wang Kai, Liu Jianing
Medical School, Southeast University, Nanjing, China.
Medical Faculty, Ulm University, Ulm, Germany.
Sci Rep. 2025 May 14;15(1):16722. doi: 10.1038/s41598-025-01580-4.
This study investigated the impact of anti-aging protein α-Klotho on cardiometabolic diseases (CMDs) among middle-aged and elderly population. A total of 11,198 participants aged 40-79 years were included in the National Health and Nutrition Examination Survey (NHANES) spanning 2007-2016. Serum α-Klotho levels were quantified via enzyme-linked immunosorbent assays. CMDs comprised cardiovascular disease (CVD), and four metabolic disorders: type 2 diabetes (T2DM), obesity, chronic kidney disease (CKD), and non-alcoholic fatty liver disease (NAFLD). Weighted logistic regression analysis, subgroup analysis, mediation analysis, restricted cubic splines (RCS), and Cox proportional hazards regression analysis were used. α-Klotho exhibited negative associations with each single CMD except T2DM, and RCS showed U-shape and L-shape dose-response relationships of α-Klotho with risk of T2DM and CKD, respectively. Ordered logistic regression analysis revealed that higher levels of Klotho markedly reduced the cumulative number of metabolic comorbidities complicating CVD (OR 0.56 (0.35, 0.91)). Simple mediation analysis showed CKD may explain up to 20.42% of the association between Klotho and CVD. Notably, α-Klotho's association with cardiometabolic comorbidities was particularly evident among individuals who were widowed/divorced/separated, non-Hispanic Black, lower-income, or less educated, with hypertension, current smokers, lower leisure and commuting physical activity, but higher work-related physical activity. Regarding long-term effects, higher α-Klotho levels were associated with lower all-cause mortality among participants with CMDs, but not among those without CMDs. Higher α-Klotho levels were associated with lower CMD prevalence, particularly in high-risk cardiovascular populations with lower socioeconomic status and unfavorable lifestyles and reduced all-cause mortality risk among CMD patients.
本研究调查了抗衰老蛋白α-klotho对中老年人群心脏代谢疾病（CMD）的影响。2007年至2016年的美国国家健康与营养检查调查（NHANES）纳入了总共11198名年龄在40 - 79岁的参与者。通过酶联免疫吸附测定法定量血清α-klotho水平。CMD包括心血管疾病（CVD）以及四种代谢紊乱疾病：2型糖尿病（T2DM）、肥胖症、慢性肾脏病（CKD）和非酒精性脂肪性肝病（NAFLD）。使用了加权逻辑回归分析、亚组分析、中介分析、限制立方样条（RCS）和Cox比例风险回归分析。除T2DM外，α-klotho与每种单一的CMD均呈负相关，并且RCS分别显示α-klotho与T2DM和CKD风险的U形和L形剂量反应关系。有序逻辑回归分析显示，较高水平的klotho显著降低了并发于CVD的代谢合并症的累积数量（比值比0.56（0.35，0.91））。简单中介分析表明，CKD可能解释klotho与CVD之间关联的20.42%。值得注意的是，α-klotho与心脏代谢合并症的关联在丧偶/离婚/分居者、非西班牙裔黑人、低收入或受教育程度较低者、患有高血压者、当前吸烟者、休闲和通勤体力活动较少但工作相关体力活动较多的个体中尤为明显。关于长期影响，较高的α-klotho水平与患有CMD的参与者的全因死亡率较低相关，但与未患有CMD的参与者无关。较高的α-klotho水平与较低的CMD患病率相关，特别是在社会经济地位较低且生活方式不利的高风险心血管人群中，并且降低了CMD患者的全因死亡风险。
