Abstract
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=1.46 [95% CI, 1.40-1.52], p<0.001). Risk associated with an elevated PSS was higher for females compared to males. Compared to participants with a low PSS in the bottom tertile of CAD PRS, those with a high PSS in the top tertile of CAD PSS were at higher CAD risk (HR=4.24 [95% CI, 3.94-4.55], p<0.001). Similar results were obtained for IS. 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.</p>