What does this research mean for the field?

A high polysocial risk score increases atherosclerotic cardiovascular disease risk by 46% overall, with a greater effect in females, and combined high polysocial and genetic risk quadruples coronary artery disease risk. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

The research aims to explore how social determinants and genetic risk factors influence the incidence of atherosclerotic cardiovascular diseases (ASCVD).

February 27, 2026Open Access

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

Key Result

High polysocial risk score raised ASCVD risk by 46% overall, with greater effect in females; combined high polysocial and genetic risk quadrupled CAD risk (HR=4.24).

Key Points

The research aims to explore how social determinants and genetic risk factors influence the incidence of atherosclerotic cardiovascular diseases (ASCVD).
Developed a polysocial risk score (PSS) through latent class analysis using socioeconomic, psychosocial, and environmental factors.
Divided participants into three PSS groups based on their scores.
Applied Cox proportional hazards analysis to assess the impact of PSS on ASCVD incidence over a median follow-up of 12.5 years.
Recorded 17,737 ASCVD events during follow-up.
Participants with a high PSS showed a significantly higher ASCVD risk (HR=1.46), especially among females.
Those with a high PSS in the top tertile of CAD polygenic risk scores had a markedly increased CAD risk (HR=4.24).

Structured PICO

Does a high polysocial risk score increase the incidence of ASCVD in a general population free of baseline ASCVD?

Population

321,016 UK Biobank participants free of atherosclerotic cardiovascular disease (ASCVD) at baseline

Intervention

High polysocial risk score (PSS) based on socioeconomic factors, psychosocial factors, and living environment

Comparator

Low polysocial risk score (PSS)

Outcome

Incident atherosclerotic cardiovascular disease (ASCVD)hard clinical

A high polysocial risk score is significantly associated with increased incident ASCVD, particularly in females, and exacerbates genetic susceptibility to CAD and ischemic stroke.

Main Result

Absolute Event Rate: 0% vs 0%

Abstract

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. 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. 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. 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.