Prognostic impact of cardiovascular-kidney-metabolic overlap among patients with non-ST-segment elevation myocardial infarction: a multi-cohort study

Background Cardiovascular-kidney-metabolic (CKM) syndrome is a systemic chronic disease state characterized by metabolic dysfunction as the core pathology, culminating in cardiovascular and kidney target organ damage [1]. Stage 4 CKM syndrome is defined by the presence of clinical cardiovascular disease (CVD). Patients with non-ST-segment elevation myocardial infarction (NSTEMI) are already at this highest-risk stage (Stage 4), yet they frequently harbor multiple additional CKM risk conditions, including hypertension, diabetes, chronic kidney disease (CKD), hypertriglyceridemia (HTG), and obesity [2]. The incremental prognostic impact of this CKM multimorbidity burden in the NSTEMI population remains inadequately defined. Purpose This study aimed to evaluate the association between the burden of core CKM components—hypertension, diabetes, CKD, HTG, and obesity—and the risk of all-cause mortality in patients presenting with NSTEMI, and to delineate the differential contributions of these individual components to mortality risk. Methods This multi-cohort study included patients with a confirmed diagnosis of NSTEMI from two independent cohorts: the TAMI cohort (n=14,880) and the MIMIC-IV cohort (n=1,707). Patients were stratified into six groups based on the total number of coexisting CKM conditions at baseline, ranging from 0 to 5. The primary endpoint was 10-Year all-cause mortality. Kaplan-Meier curves and multivariable Cox proportional hazards models were employed to assess the association between CKM burden groups and mortality risk, and to analyze the independent contribution of each CKM component. Results In the TAMI cohort, 1,432 (9.6%) deaths occurred. In the MIMIC-IV cohort, 571 (28.5%) deaths occurred. Kaplan-Meier curves demonstrated a significant graded increase in all-cause mortality risk with escalating CKM multimorbidity burden in both cohorts (log-rank P < 0.001). In adjusted Cox regression models, compared to patients with NSTEMI alone (0 condition), those with a burden of 5 exhibited a substantially higher risk of death in both the TAMI cohort (HR: 2.010; 95% CI: 1.363–2.898; P < 0.001) and the MIMIC-IV cohort (HR: 3.206; 95% CI: 1.245–8.254; P = 0.016). Among the individual components, CKD was associated with the highest mortality risk in both cohorts (TAMI cohort HR: 1.466; MIMIC-IV cohort HR: 1.495), whereas obesity did not demonstrate a statistically significant independent risk effect in either cohort. Conclusions In patients with NSTEMI overlapping with CKM stage 4, a higher burden of concomitant CKM conditions is associated with a significant and dose-dependent increase in all-cause mortality. CKD emerges as the predominant driver of this risk. These findings underscore the importance of comprehensive CKM risk assessment and stratified management strategies to improve outcomes in NSTEMI patients, with particular attention to those with CKD.