Impaired Kidney Function, Subclinical Myocardial Injury, and Their Combined Associations with Cardiovascular Mortality in the General Population

Background: The combined impact of impaired kidney function and subclinical myocardial injury (SCMI) on cardiovascular (CV) mortality has not been well studied. Methods: We analyzed data from 6,057 participants (mean age 57.0 ± 13.0 years) in the U.S. Third National Health and Nutrition Examination Survey. Estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI equation. Electrocardiographic SCMI was defined as a cardiac infarction/injury score ≥10. CV mortality was determined from the National Death Index. Multivariable logistic regression assessed baseline cross-sectional associations between eGFR and SCMI. Cox proportional hazards models were used to examine the individual and combined associations of eGFR and SCMI with CV mortality. Results: At baseline, 1,297 participants (21.4%) had SCMI. In multivariable logistic regression analysis, eGFR <45 mL/min/1.73 m² (vs. ≥45) was not associated with SCMI (OR [95% CI]:1.10[0.84–1.45]). Over a median follow-up of 18.4 years, 690 CV deaths occurred. In separate Cox models, both SCMI (vs. no SCMI) and eGFR <45 (vs. ≥45) were associated with increased CV mortality risk (HR [95% CI]: 1.36[1.16–1.60] and 1.56 [1.24–1.99], respectively). Compared with participants with eGFR ≥45 and no SCMI, those with both eGFR <45 and SCMI had the highest CV mortality risk (HR[95% CI]:2.36[1.65–3.36]), followed by eGFR <45 alone (1.47[1.09–1.96]) and SCMI alone (1.33[1.11–1.58]). Conclusions: Both reduced eGFR and SCMI are independently associated with increased CV mortality. Their combined effect appears synergistic, possibly reflecting distinct underlying mechanisms, as suggested by their lack of significant association with each other at baseline.