Cardiometabolic multimorbidity burden and all-cause mortality after non-ST-segment elevation myocardial infarction: a multi-cohort study

Background Cardiometabolic multimorbidity (CMM), defined as the coexistence of at least two cardiometabolic diseases (CMDs, including myocardial infarction, diabetes, and stroke), has been established as an important risk factor for adverse cardiovascular outcomes [1-2]. However, the differential impact of varying CMM burden on all-cause mortality following non-ST-segment elevation myocardial infarction (NSTEMI) has not been validated across multiple cohorts, and its value for clinical prognostic stratification remains unclear. Purpose This study aimed to investigate the association between different CMM burdens—stratified by the presence of diabetes and/or stroke—and the risk of all-cause mortality in patients with NSTEMI. Methods A total of 16,884 NSTEMI patients from two independent cohorts were included in this study: the TAMI cohort (n=14,880) and the Medical Information Mart for Intensive Care-IV (MIMIC-IV) cohort (n=2,004). Patients were categorized into hierarchical groups based on baseline CMM status: (1) non-CMM (NSTEMI only); (2) overall CMM; (3) NSTEMI with one CMD (diabetes or stroke); and (4) NSTEMI with two CMDs (diabetes and stroke). The primary endpoint was 10-Year all-cause mortality. Kaplan-Meier curves and multivariable Cox proportional hazards models were employed to evaluate the association between CMM burden and all-cause mortality. Results In the TAMI cohort, 1,432 (9.6%) deaths occurred. In the MIMIC-IV cohort, 571 (28.5%) deaths occurred. The Kaplan-Meier curves demonstrated a significant upward trend in all-cause mortality risk for both cohorts as the CMM burden increased (log-rank P < 0.001). In the TAMI cohort, compared to patients with NSTEMI only, CMM was significantly associated with a higher risk of mortality (HR: 1.390; 95% CI: 1.248–1.549). This risk increased incrementally with greater CMM burden: patients with one CMD had an HR of 1.309 (95% CI: 1.166–1.470), while those with both diabetes and stroke faced the highest risk (HR: 1.657; 95% CI: 1.423–1.929). When analyzed separately, diabetes alone conferred a higher risk (HR: 1.369; 95% CI: 1.206–1.555) than stroke alone (HR: 1.185; 95% CI: 1.001–1.403). Consistent trends were observed in the MIMIC-IV cohort, albeit with higher absolute event rates. The concordant findings across both cohorts validate the positive association between CMM burden and all-cause mortality in NSTEMI patients. Conclusion An increasing burden of CMM is associated with a higher risk of all-cause mortality in patients with NSTEMI, with the coexistence of both diabetes and stroke identifying the highest-risk subgroup. In clinical practice, systematic assessment of CMM burden in NSTEMI patients should be prioritized to optimize individualized prognostic stratification and to improve outcomes through comprehensive, multidisciplinary comorbidity management.