Association between the difference in cystatin C and creatinine-based eGFR and risks of multiple cardiovascular diseases: a prospective cohort study

Background The difference between cystatin C- and creatinine-based estimated glomerular filtration rate (eGFR diff ) is closely associated with various adverse outcomes. This study aims to comprehensively evaluate the association between eGFR diff , all-cause mortality, and the risk of multiple cardiovascular-related diseases. Methods This study analyzed data from 297,140 participants in the UK Biobank to assess the association between eGFR diff , mortality, and the incidence of multiple cardiovascular-related diseases. eGFR diff was classified into three groups: negative (< −15 mL/min/1.73 m 2 ), intermediate (−15 to 15 mL/min/1.73 m 2 ), and positive (≥ 15 mL/min/1.73 m 2 ). Cox proportional hazards regression models were used to evaluate this association, while various sensitivity analyses were performed to assess its robustness. Results During a mean follow-up of 13.1 years, the positive eGFR diff group exhibited significantly lower mortality, cardiovascular disease (CVD) incidence, and the occurrence of CVD-related conditions. In the fully adjusted model, participants in the negative eGFR diff group had a hazard ratio of 1.44 (95% confidence interval [CI], 1.40–1.49) for all-cause mortality, 1.49 (95% CI, 1.41–1.59) for CVD incidence, and 1.25 (95% CI, 1.22–1.27) for CVD mortality. The risk of all 10 CVD-related conditions was also significantly higher in the negative group, whereas the positive group exhibited significantly lower risks. For every 10 mL/min/1.73 m 2 increase in eGFR diff , the incidence of various diseases decreased by approximately 10–19%. Conclusion eGFR diff is significantly associated with increased risks of mortality, CVD incidence, and multiple CVD-related conditions. These findings underscore the critical need for developing targeted prevention strategies, particularly for populations with reduced eGFR diff .