Role of Plasma Proteins in the Association Between Socioeconomic Status and Cardiovascular Disease Events: Results From Trans‐Omics for Precision Medicine Cohorts

Background Socioeconomic status (SES) is strongly associated with cardiovascular disease burden and risk. Plasma proteins may elucidate a biological mechanism through which low SES increases the risk of cardiovascular disease. Methods Participants from the following 3 cohorts were included: the Multi‐Ethnic Study of Atherosclerosis (n=2139), Jackson Heart Study (n=967), and Women's Health Initiative (n=1104). SES was approximated using a cumulative score (range 0–3) across education, income, and employment status. A meta‐analysis of Cox proportional hazards ratios was used to assess the association between SES and incident events for coronary heart disease (CHD) and stroke. Linear regression was used within each cohort to determine associations between SES and Olink proteins (n=1270 proteins) and the results were meta‐analyzed across cohorts. Regression‐based mediation analysis was used to determine whether the identified proteins were statistical mediators of the association of SES and incident events. Results Higher SES scores were associated with a lower risk of CHD (hazard ratio [HR], 0.74 [95% CI, 0.63–0.87]) and stroke (HR, 0.81 [95% CI, 0.66–1.00]). After correcting for multiple testing ( P <3.937×10 −5 ), 233 proteins were associated with SES in the meta‐analysis. Of these 233 proteins, 21 had a significant indirect effect on SES and CHD. Because the SES‐stroke association was not statistically significant, proteins were not tested as mediators. Conclusions Our analysis of multiple cohorts identified evidence of different proteomic pathways associated with SES and cardiovascular disease. This work suggests that exogenous social factors (eg, SES) may influence cardiovascular disease via proteomic profiles.