Kidney Function, Subclinical Myocardial Injury, and their Joint Association with Cardiovascular Mortality in the General Population

Background: Impaired kidney function and subclinical myocardial injury (SCMI) carry significant mortality risk. However, their interrelationship as well as their combined impact on cardiovascular (CV) mortality remains unexplored. Methods: This analysis included 6057 (Age 57.0±13.0 years; 3296 (54.4%) women; 3029(50.0%) Whites) from NHANES-III who underwent electrocardiogram (ECG) recording, excluding those with estimated glomerular filtration rate (eGFR) <15mL/min/1, history of prior CV disease, or have major ECG abnormality. CKD-Epi equation was used to calculate eGFR which was then categorized as eGFR ≥45 mL/min/1.73 m ₂ and eGFR <45 mL/min/1.73 m ₂ . SCMI was defined as cardiac infarction injury score >=10 from electrocardiogram (ECG) . CV mortality was ascertained from the National Death Index. Multivariable logistic regression assessed baseline cross-sectional association between eGFR and presence of SCMI, while Cox Proportional Hazard models were used to examine the individual and combined associations of eGFR and SCMI with CV mortality. Results: About 21.4% (n=1293) of the participants had SCMI at baseline. In logistic regression model adjusted for sociodemographic and CVD risk factor, eGFR <45 (compared to ≥45) mL/min/1.73 m ₂ was not associated with increased risk of SCMI (OR (95% CI): 1.10 (0.84–1.45)). During a median follow-up of 18.4 years, 690 CV deaths occurred. In separate multivariable Cox models, both SCMI (vs. no SCMI) and eGFR <45 (compared to ≥45) mL/min/1.73 m ₂ were associated with an increased risk of CV mortality ((HR [95% CI]: 1.36 (1.16-1.60) and 1.56(1.24-1.99)), respectively. Compared to participants with eGFR ≥ 45 mL/min/1.73 m ₂ without SCMI (reference group), those with coexistent eGFR <45 mL/min/1.73 m ₂ and SCMI exhibited much higher risk of CV mortality than those with either eGFR <45 mL/min/1.73 m ₂ or SCMI alone ( Table ). Conclusions: Both lower levels of eGFR and SCMI are associated with increased risk of CV mortality, and their combination contribute to increased CV mortality risk in a synergistic manner. Lack of significant association between eGFR and SCMI suggest that their synergistic contribution to the risk of CVD is through different pathways.