Obesity is an established cardiovascular risk factor, yet associations across the full BMI spectrum, particularly severe obesity, remain incompletely described. Investigators analyzed 289,875 participants (mean age 60.3 years; 79.2% women) from 21 cohorts enrolled between 1948 and 2015 in the Cross-Cohort Collaboration. Participants had BMI ≥18.5 kg/m² and were followed for a median of 19.2 years. The results were published in the Circulation.

During follow-up, 15,542 myocardial infarctions, 15,467 strokes, 14,172 heart failure events, 9,066 atrial fibrillation diagnoses, and 113,918 deaths occurred (14,647 CHD-related; 28,879 CVD-related). Multivariable Cox models adjusted for demographic and clinical factors.

Compared with normal weight, class 2 and class 3 obesity were associated with the highest risk of heart failure (HR 2.1 [95% CI 2.0–2.3] and 3.0 [2.7–3.2], respectively) and atrial fibrillation (HR 1.8 [1.7–2.0] and 2.8 [2.5–3.1], respectively). Women demonstrated higher relative risk increases for stroke, total CVD, and all-cause mortality with severe obesity (interaction P<0.001, 0.003, <0.001). In men, stroke risk did not increase with higher BMI (P trend=0.49), whereas in women, stroke risk plateaued but remained elevated.

Higher BMI categories were associated with increased risk of most cardiovascular outcomes, particularly heart failure and atrial fibrillation. Observed sex differences were noted in stroke, total CVD, and mortality risks.

Limitations include reliance on BMI without measures of central adiposity, lack of physical activity data, and single baseline BMI assessment. Long enrollment periods, lower obesity prevalence than the general population, potential residual confounding, reverse causation, and lack of stroke and heart failure subtype differentiation may affect findings.