Negative association of C-reactive protein-albumin-lymphocyte index (CALLY index) with all-cause and cardiovascular mortality in population with CKD: the mediating role of biological age acceleration

This study investigated the association between the C-reactive protein-albumin-lymphocyte (CALLY) index and all-cause mortality and cardiovascular disease (CVD) mortality in patients with chronic kidney disease(CKD) while exploring biological aging as a potential mediator. This study included 4,515 patients with CKD from the National Health and Nutrition Examination Survey (NHANES) conducted between 1999 and 2010. The CALLY index was assessed only at baseline. The association between the CALLY index and all-cause and cardiovascular mortality was analyzed using Cox proportional hazards models. Additionally, Kaplan–Meier curves, smooth curve fitting, segmented linear regression, and various subgroup and sensitivity analyses were performed. Finally, the mediating role of biological age acceleration was explored. Among 4,515 participants, with a median follow-up of 127 months and 2,264 recorded deaths, a higher Ln-CALLY was associated with a lower risk of all-cause mortality (HR = 0.845, 95% CI: 0.817, 0.874) and cardiovascular disease (CVD) mortality (HR = 0.860, 95% CI: 0.809, 0.915). Smoothed curve fitting and threshold effect analyses indicated that the effect was more pronounced when Ln-CALLY was lower than 4.96. Mediation analyses further revealed that biological age acceleration (BioAgeAccel) mediated 14.168% of the association between CALLY and all-cause mortality and 27.442% associated with CVD mortality. In the CKD population, CALLY values were negatively associated with all-cause and cardiovascular mortality, with BioAgeAccel significantly mediating this relationship.

本研究探讨了C反应蛋白-白蛋白-淋巴细胞（CALLY）指数与慢性肾脏病（CKD）患者全因死亡率及心血管疾病（CVD）死亡率的关联，并探索生物学衰老作为潜在中介变量的作用。本研究纳入1999-2010年美国国家健康与营养检查调查（NHANES）中的4515名CKD患者，仅在基线时评估CALLY指数。采用Cox比例风险模型分析CALLY指数与全因死亡率及心血管死亡率的关联；此外，还开展了Kaplan-Meier曲线、平滑曲线拟合、分段线性回归及多组亚组与敏感性分析。最后，探究了生物学年龄加速度（BioAgeAccel）的中介作用。在4515名参与者中，中位随访时间为127个月，共记录2264例死亡。结果显示，对数转换后的CALLY（Ln-CALLY）水平越高，全因死亡率风险越低（风险比HR=0.845，95%置信区间：0.817~0.874），心血管疾病死亡率风险亦更低（HR=0.860，95%置信区间：0.809~0.915）。平滑曲线拟合与阈值效应分析表明，当Ln-CALLY低于4.96时，该保护效应更为显著。中介分析进一步显示，生物学年龄加速度（BioAgeAccel）介导了CALLY指数与全因死亡率之间14.168%的关联，以及其与CVD死亡率之间27.442%的关联。在慢性肾脏病人群中，CALLY指数与全因死亡率及心血管死亡率呈负相关，且生物学年龄加速度可显著介导这一关联。