Creatinine-to-cystatin C ratio and frailty in older adults: a longitudinal cohort study

Creatinine-to-cystatin C ratio (CCR) has been associated with multiple adverse outcomes. However, little is known about its relationship with frailty. We aimed to explore the association between CCR and frailty among older adults. A total of 2599 participants aged ≥ 60 years (mean age 67.9 ± 6.0 years, 50.4% males) were included from the China Health and Retirement Longitudinal Study (2011–2015). Baseline CCR was calculated as plasma creatinine (mg/dL) / cystatin C (mg/L) × 10 and was grouped by quartiles. Frailty was evaluated by the validated physical frailty phenotype (PFP) scale and was defined as PFP score ≥ 3. The generalized estimating equations model was used to explore the relationship between CCR and frailty. The frailty risk decreased gradually with increasing CCR in the quartiles (P for trend = 0.002), and the fourth CCR quartile was associated with a significantly lower risk of frailty compared with the lowest quartile (odds ratio [OR] 0.37, 95% confidence interval [CI] 0.19–0.70). When modeling as a continuous variable, per 1-unit increase in CCR was related to 17% decreased odds of frailty (OR 0.83, 95% CI 0.74–0.93). The association was consistent in male and female participants (P for interaction = 0.41). Poisson models revealed that frailty score was negatively associated with CCR (β= -0.11, 95% CI= -0.19 to -0.04), and sex did not significantly moderate the associations (P for interaction = 0.22). The results were not affected by further adjusting for high-sensitivity C-reactive protein. Similar results were observed by analyses with multiple imputation technique and analyses excluding participants with baseline frailty. Higher CCR was associated with a lower frailty risk. CCR may be a simple marker for predicting frailty in older adults.