Sex-Specific Impact of Body Weight on Atherosclerotic Cardiovascular Disease Incidence in Individuals With and Without Ideal Cardiovascular Health.

Background The impact of an elevated body mass index (BMI) on atherosclerotic cardiovascular disease (ASCVD) risk in individuals who are metabolically healthy is debated. We investigated the respective contributions of BMI as well as lifestyle and cardiometabolic risk factors combined to ASCVD incidence in 319 866 UK Biobank participants. Methods and Results We developed a cardiovascular health score (CVHS) based on 4 lifestyle and 6 cardiometabolic parameters. The impact of the CVHS on incident ASCVD (15 699 events) alone and in BMI and waist-to-hip ratio categories was assessed using Cox proportional hazards in women and men separately. In participants with a high CVHS (8-10), those with a BMI ≥35.0 kg/m2 had a nonsignificantly higher ASCVD risk (hazard ratio [HR],  1.20 [95% CI, 0.84-1.70]; P=0.32) compared with those with a BMI of 18.5 to 24.9 kg/m2. In participants with a BMI of 18.5 to 24.9 kg/m2, those with a lower CVHS (0-2) had a higher ASCVD risk (HR, 4.06 [95% CI, 3.23-5.10]; P<0.001) compared with those with a higher CVHS (8-10). When we used the waist-to-hip ratio instead of the BMI, a dose-response relationship between the waist-to-hip ratio and ASCVD risk was obtained in healthier participants. Results were similar in women compared with men. Conclusions In women and men in the UK Biobank, the relationship between the BMI and ASCVD incidence in healthy individuals was inconsistent, whereas cardiovascular risk factors strongly predicted ASCVD incidence in all BMI categories. Assessing lifestyle and cardiometabolic risk factors as well as body fat distribution indices may help identify individuals at high ASCVD risk, regardless of body weight.