Association between body mass index and all-cause mortality in patients with non-ST-segment-elevation myocardial infarction

Background Body mass index (BMI) is a modifiable prognostic factor in non-ST-segment elevation myocardial infarction (NSTEMI). Investigating the impact of BMI on short- and long-term prognosis in patients with NSTEMI can inform clinical management and improve patient outcomes[1, 2]. Purpose This study aimed to investigate the association between BMI and both in-hospital and 10-year all-cause mortality in critically ill NSTEMI patients admitted to the coronary care unit, and to evaluate the incremental value of C-reactive protein (CRP) in mortality risk stratification. Methods This multinational, multicohort study included 7,815 critically ill NSTEMI patients from three international cohorts (TAMI, MIMIC-IV, and eICU-CRD). BMI was categorized into normal, overweight, obesity I, and obesity II/III groups, based on WHO and Chinese criteria. CRP levels were dichotomized at 2 mg/L. The primary endpoints were in-hospital and 10-year all-cause mortality. Associations between BMI and mortality were evaluated using multivariable Cox proportional hazards models and restricted cubic splines. Results In-hospital all-cause mortality rates were 2.99%, 7.28%, and 5.57%, while 10-year all-cause mortality rates were 12.67% and 21.52% for TAMI and MIMIC-IV, respectively. A significant U-shaped association was observed between BMI and all-cause mortality in critically ill NSTEMI patients. In the TAMI cohort, severe obesity (obesity II/III) was independently associated with increased risks of in-hospital (hazard radio (HR)=1.84; 95% CI, 1.20–2.81) and 10-year (HR=1.85; 95% CI, 1.49–2.32) all-cause mortality. Conversely, overweight and obesity I conferred protective associations with lower all-cause mortality risk. Furthermore, the coexistence of severe obesity and elevated inflammation (CRP≥2 mg/L) demonstrated a synergistic risk, adjusted HRs of 4.57 (95% CI, 2.58–8.08) for in-hospital and 3.07 (95% CI, 2.33–4.06) for 10-year all-cause mortality. Subgroup analysis showed that combined presence of severe obesity, elevated inflammation, and diabetes was associated with the highest all-cause mortality risk, with adjusted HRs reaching 6.21 (95% CI, 2.77–13.89) for in-hospital and 3.66 (95% CI, 2.43–4.92) for 10-year all-cause mortality. The pooled meta-analysis results of the three databases were consistent. Conclusions BMI shows a U-shaped association with mortality in critically ill NSTEMI patients, with severe obesity as an independent risk factor. It establishes the combination of severe obesity and elevated inflammation as a distinct, high-risk clinical phenotype. In clinical practice, integrated ‘metabolic-inflammatory’ management should be prioritized, and targeted strategies combining long-term weight control with anti-inflammatory therapy should be actively explored to improve short- and long-term prognosis.