Abstract 4125025: Association between Marital Status and Major Adverse Cardiovascular Events: Role of Stress-Related Neural-Immune Mechanisms

Background: Chronic stress is associated with cardiovascular disease (CVD) in part through neural mechanisms that potentiate inflammation. Disrupted social connections are associated with higher chronic stress. As such, we hypothesized that: 1) previously married (divorced, separated) individuals have higher major adverse cardiovascular event (MACE) risk compared to married individuals and 2) that greater activation of stress-related neural-immune mechanisms contributes to this relationship. Methods: Participants (N=75,638) enrolled in the Mass General Brigham Biobank were studied. Marital status and MACE were identified using survey data and ICD-10 codes, respectively. A subset (N=1,121) underwent clinical 18 F-FDG-PET imaging, enabling assessment of stress-related neural activity as the ratio of the amygdala to prefrontal cortex activity (AmygAc). Clinical high-sensitivity C-reactive protein (hs-CRP) levels were assessed in another subset of the cohort (N=10,358). Linear and Cox regression and mediation analyses were used. Results: Among participants (median age 62 years; 53% female), 2,978 subjects developed MACE after Biobank enrollment. Previously married (vs. currently married) individuals had greater MACE risk (HR 1.33 [95% CI: 1.20,1.57], p=<0.001, Figure 1A ) , higher AmygAc (B=0.23 [95% CI: 0.06-0.40], p=0.009) and higher hs-CRP (B=0.19 [95% CI: 0.13-0.25], p=<0.001). MACE risk remained significant after adjustment for key confounders ( Table 1 ), and both the AmygAc and CRP were higher among divorced or separated individuals ( Figure 1B and 1C ). Moreover, increased AmygAc and hs-CRP associated with increased MACE risk (HR=1.24 [1.14-1.36], p=<0.001 and 1.13 [1.09-1.16], p=<0.001, respectively), and both AmygAc and hs-CRP mediated the relationship between marital status and MACE (p<0.05). Conclusions: Our findings suggest that divorced and separated individuals are at an increased risk for MACE. This relationship appears to be driven in part by stress-related neural-immune mechanisms.