Body mass index modifies cardiovascular risk across blood pressure categories, particularly among underweight adults with hypertension: a 6.3 million‑person nationwide Japanese cohort study.

Co-occurring obesity and hypertension is associated with high cardiovascular risk, whereas the prognostic significance of underweight in the presence of hypertension remains uncertain. We examined whether the association between body mass index category and 10-year risk of major adverse cardiovascular events differed across blood pressure categories. Using the Japan Medical Claims Database from 2005 to 2023, we analyzed 6,262,298 adults without prior cardiovascular disease, chronic renal failure, dialysis, or antihypertensive medication use at baseline. Blood pressure was classified as normal (<120 and <80 mmHg), high-normal (120-129 and <80 mmHg), elevated (130-139 and/or 80-89 mmHg), stage 1 hypertension (140-159 and/or 90-99 mmHg), or stage 2/3 hypertension (≥160 and/or ≥100 mmHg). Body mass index was classified as underweight (<18.5 kg/m²), normal weight (18.5-24.9), overweight (25.0-29.9), or obesity (≥30.0). The primary outcome was major adverse cardiovascular events within 10 years. Multivariable Cox proportional hazards models estimated hazard ratios for combined blood pressure and body mass index categories, using normal blood pressure with normal weight as the reference. During a median follow-up of 1,183 days, 34,034 participants experienced major adverse cardiovascular events. Underweight showed a marked blood pressure-dependent increase in risk, with the hazard ratio rising from 1.14 (95% confidence interval, 1.07-1.22) in normal blood pressure to 5.01 (4.23-5.93) in stage 2/3 hypertension. The interaction between blood pressure category and body mass index category was significant. These findings suggest that higher blood pressure may amplify the adverse prognostic significance of underweight.