Sex-specific associations of social determinants of health and genetic risk factors with atherosclerotic cardiovascular diseases incidence in the general population.

Background and aims: The combined contribution of social determinants of health (SDOH) that includes socioeconomic status, psychosocial factors and living environment and genetic background on atherosclerotic cardiovascular disease (ASCVD) risk remains unknown. We investigated the contribution of a polysocial risk score (PSS) and polygenic risk scores (PRS) on ASCVD incidence. Methods: We developed a PSS using latent class analysis based on socioeconomic factors, psychosocial factors and living environment in 321,016 UK Biobank participants free of ASCVD. Participants were divided into three PSS groups. The impact of the PSS on incident ASCVD was assessed using Cox proportional hazards. The impact of the PSS and coronary artery disease (CAD) PRS and ischemic stroke (IS) PRS on the incidence of CAD and IS, respectively, were also assessed. Results: During a median follow-up of 12.5 years, 17,737 ASCVD events were recorded. Compared to participants with a low PSS, those with a high PSS had a higher risk of ASCVD (HR=1.78 [95% CI, 1.66-1.90], Conclusions: A PSS that takes into account individual and area-level SDOH was associated with incident ASCVD, particularly in females, and may exacerbate genetic susceptibility to both CAD and IS, suggesting that addressing polysocial risk factors is key to implementing preventive ASCVD strategies in the general population.