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 diseases (ASCVD) risk in individuals who are “metabolically healthy” is debated. Our objective was to investigate the respective contributions of BMI as well as lifestyle and cardiometabolic risk factors combined to ASCVD incidence in 319,866 UK Biobank participants. Methods We developed a cardiovascular health score (CVHS) based on four lifestyle and six 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. Results In participants with a high CVHS (8-10), those with a BMI ≥ 35.0 kg/m 2 had a nonsignificant higher ASCVD risk (HR=1.20 [95% CI, 0.84-1.70], p=0.32) compared to those with a BMI of 18.5-24.9 kg/m 2 . In participants with a BMI 18.5-24.9 kg/m 2 , 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 to 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 WHR and ASCVD risk was obtained in healthier participants. Results were similar in women compared to men. Conclusions In participants of 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. Weight inclusive interventions targeting lifestyle-related and metabolic risk factors are likely to prevent cardiovascular outcomes, regardless of their impact on body weight.