Association of serum creatinine-cystatin C ratio with all-cause, cardiovascular and cancer mortality in US adults: a nationwide cohort study

Abstract

Objective: To investigate the association of serum creatinine-cystatin C ratio (Cr/CysC) with long-term all-cause mortality and cause-specific (cardiovascular and cancer) mortality among US general adults.

Methods: This nationally representative cohort study included adults in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2004. Participants were linked to National Death Index data from the survey date through December 31, 2019. Weighted Cox proportional hazards regression models were used to calculate hazard ratios and 95% confidence intervals (CIs), and restricted cubic splines and stratified analyses were also performed.

Results: A total of 12,914 participants were included in this study (mean [SD] age, 45.3 [17.3] years; males, 48.9%). During a median follow-up of 17.9 years (maximum follow-up, 20.8 years), 3439 total deaths occurred, including 1098 cardiovascular deaths and 736 cancer deaths. Cumulative incidence curves revealed that increased Cr/CysC ratio had lower risk of all-cause (P < 0.001), cardiovascular (P < 0.001) and cancer (P < 0.001) mortality. Cox regression an Fine-Gray hazards models demonstrated that the multivariable-adjusted hazard ratios comparing the highest vs. lowest quartile of Cr/CysC ratio were 0.40 (95% CI, 0.34-0.47; P < 0.001) for all-cause mortality, 0.68 (95% CI, 0.52-0.88; P < 0.001) for cardiovascular mortality, and 0.51 (95% CI, 0.36-0.71; P < 0.001) for cancer mortality. Nonlinear association was observed for Cr/CysC ratio and all-cause mortality (P = 0.018 for nonlinearity), and linear associations were observed for Cr/CysC ratio and cardiovascular (P = 0.212 for nonlinearity) and cancer (P = 0.550 for nonlinearity) mortality. Besides, a series of sensitivity analyses ensured the robustness of the results.

Conclusions: In this cohort of US adults, Cr/CysC ratio was negatively associated with all-cause, cardiovascular, and cancer mortality. Our study suggests that Cr/CysC ratio may serve as a simple and effective predictor of long-term health outcomes.

Keywords: Creatinine-cystatin C ratio; Epidemiology; Mortality; Muscle mass; NHANES; Sarcopenia.

Fig. 1

Weighted Kaplan-Meier curves for all-cause mortality by quartiles categories of Cr/CysC ratio in adults. The P value was calculated with the use of the log-rank test

Fig. 2

Hazard ratios (95% CIs) of Cr/CysC ratio with all-cause mortality using a restricted cubic spline regression model. Results were adjusted for age, gender, race/ethnicity, education level, family income-to-poverty ratio, history of hypertension, diabetes, CVD, cancer, smoking, alcohol drinking, BMI, LDL-C, HDL-C, CRP and eGFR (model 3). The solid blue line is multivariable adjusted hazard ratios, and the blue shadows represent the 95% CIs