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 (eGFRdiff) is closely associated with various adverse outcomes. This study aims to comprehensively evaluate the association between eGFRdiff, 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 eGFRdiff, mortality, and the incidence of multiple cardiovascular-related diseases. eGFRdiff was classified into three groups: negative (< -15 mL/min/1.73 m2), intermediate (-15 to 15 mL/min/1.73 m2), and positive (≥ 15 mL/min/1.73 m2). 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 eGFRdiff 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 eGFRdiff 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 m2 increase in eGFRdiff, the incidence of various diseases decreased by approximately 10-19%. Conclusion: eGFRdiff 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 eGFRdiff.