Liu ChunFang, Hu Jin, Zhou Ren, Zhu Jiao, Mao Haoli
Department of Anesthesiology, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
Prev Med Rep. 2025 Jun 5;55:103130. doi: 10.1016/j.pmedr.2025.103130. eCollection 2025 Jul.
Prescription opioids are widely recognized as the most commonly used and effective analgesics for the management of moderate to severe pain. Klotho protein has been indicated to show a nonlinear relationship with mortality, but findings are inconsistent across populations. The present study investigated the association between Klotho levels and mortality in middle-aged and older adults who use prescription opioids, with the aim of identifying potential therapeutic targets.
This study included participants aged ≥40 years from the National Health and Nutrition Examination Survey (2007-2018) with complete data. Mortality data were obtained from the 2019 public use-linked mortality files released by the National Center for Health Statistics in May 2022. Covariates included demographics, lifestyle habits, and disease history. Survey-weighted Cox regression assessed the relationship between Klotho levels and mortality risk.
Among the 898 participants (mean age 56 years; 43.3 % men) followed up for a median of 88 months, 13.5 % died. Participants in the third Klotho quartile had a lower risk of all-cause mortality compared to the first quartile. Higher Klotho levels were associated with lower cancer mortality, but cardiovascular mortality did not differ significantly. Restricted cubic spline analysis revealed a significant nonlinear association between Klotho levels and all-cause mortality (nonlinear < 0.01).
A significant nonlinear relationship exists between Klotho levels and all-cause mortality among middle-aged and older adults taking prescription opioids. Future research should explore mechanisms underlying this relationship and develop Klotho-targeted therapies.
处方阿片类药物被广泛认为是治疗中度至重度疼痛最常用且有效的镇痛药。已有研究表明，klotho蛋白与死亡率呈非线性关系，但不同人群的研究结果并不一致。本研究调查了使用处方阿片类药物的中老年人中klotho水平与死亡率之间的关联，旨在确定潜在的治疗靶点。
本研究纳入了美国国家健康与营养检查调查（2007 - 2018年）中年龄≥40岁且数据完整的参与者。死亡率数据来自美国国家卫生统计中心于2022年5月发布的2019年公共用途关联死亡率文件。协变量包括人口统计学特征、生活习惯和疾病史。采用调查加权的Cox回归评估klotho水平与死亡风险之间的关系。
在898名参与者（平均年龄56岁；43.3%为男性）中，随访时间中位数为88个月，13.5%的参与者死亡。与第一四分位数相比，klotho水平处于第三四分位数的参与者全因死亡风险较低。klotho水平越高，癌症死亡率越低，但心血管死亡率无显著差异。受限立方样条分析显示klotho水平与全因死亡率之间存在显著的非线性关联（非线性P<0.01）。
在使用处方阿片类药物的中老年人中，klotho水平与全因死亡率之间存在显著的非线性关系。未来的研究应探索这种关系的潜在机制，并开发针对klotho的治疗方法。
