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/m2 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/m2. In participants with a BMI 18.5-24.9 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 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. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement No funding was received for this analysis. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committee of British National Health Service, Northwest-Haydock gave ethical approval for this work I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes The individual-level data can be obtained via the UK Biobank.