Abstract 4144014: Stress-related genetic factors modify the effect of lower socioeconomic status on cardiovascular disease risk through autonomic and immune mechanisms.

Introduction: Lower socioeconomic status (SES) associates with greater MACE risk in part via stress-related mechanisms. Further, a higher polygenic risk score for neuroticism (nPRS), a marker linked to stress sensitivity and chronic stress conditions, is associated with greater MACE risk. Moreover, individuals with higher nPRS are more susceptible to the cardiovascular impacts of lower SES. Yet, it remains unknown whether individuals with higher nPRS experience greater adverse changes in autonomic and inflammatory intermediaries of stress in the setting of lower SES and whether these changes contribute to MACE risk. Accordingly, we tested the hypotheses that: 1) lower SES links to MACE risk via lower heart rate variability (HRV) and higher C-reactive protein (CRP), and 2) lower SES has a greater impact on HRV and CRP among those with higher nPRS. Methods: Individuals (N=18093; median age 64 years; 54% female) with nPRS and SES data were identified in the Mass General Brigham Biobank. SES was assessed as the median income of an individual’s residential zip code with lower income defined as the lowest tertile. Higher nPRS was defined as values ≥ population median. MACE data was collected for 10 years following enrollment using ICD-10 codes. CRP (N=4117) and HRV (N=4412) data were collected from available clinical lab values and electrocardiograms, respectively, with HRV assessed as the standard deviation of all normal RR intervals. Results: In the full cohort, both HRV and CRP mediated the relationship between lower SES and MACE risk (p<0.05 for both). In subgroup analyses, CRP and HRV mediated the link between lower SES and MACE among those with higher (but not lower) nPRS (p<0.05) (Figure 1A). Moreover, lower SES associated with both lower HRV and higher CRP, most notably among those with higher nPRS, while those relationships were attenuated among individuals with lower nPRS (Figure 1B). Conclusions: Alterations in HRV and CRP appear to be heightened among individuals with higher nPRS and may mediate the association between lower SES and MACE. These findings suggest that the adverse health effects of lower SES are greater among those with genetic risk related to stress sensitivity and stress conditions.