Body mass index and major cardiovascular events after myocardial infarction: A nationwide registry study

AIM: The "obesity paradox" suggests lower cardiovascular risk at higher body mass index (BMI) after myocardial infarction (MI), but whether it reflects true protection or methodological bias is unclear. METHODS: From the nationwide SWEDEHEART registry, patients hospitalised with MI from 2010-2021 were included. BMI at admission was modelled both as a continuous variable using restricted cubic splines and categorised into 6 groups, with 20 to <25 kg/m2 as reference. The primary outcome was major adverse cardiovascular events (MACE), a composite of recurrent MI, stroke, heart failure hospitalisation, or cardiovascular death. Cox regression models estimated the BMI associated with lowest risk and HRs for categorical BMI groups. Adjustments included sociodemographic factors, smoking, and comorbidities not attributed to obesity. Mediation analyses assessed the roles of diabetes, hypertension, and prior cardiovascular disease. RESULTS: In 173 617 patients, the mean age was 71.0 years, 66.7% were men, and mean BMI was 27.1 kg/m2. During a median follow-up of 3.3 years, 36.5% experienced MACE. BMI had a U-shaped association with MACE, with the lowest risk at BMI 25.1 kg/m2. The adjusted HR (95% CI) for MACE was 0.99 (0.97-1.01) for overweight and 1.17 (1.14-1.20) for obesity class I, increasing across higher obesity classes. Excess risk was largely mediated by diabetes, hypertension, and prior cardiovascular disease. CONCLUSIONS: Obesity was associated with increased risk of MACE, partly mediated by obesity-related risk factors. The findings suggest that previously reported "obesity paradoxes" may reflect differences in confounder adjustment, handling of mediators, patient populations, and survivor bias.