Abstract
BACKGROUND: Individuals with posttraumatic stress disorder (PTSD) have high rates of cardiovascular disease (CVD) and increased cardiometabolic CVD risk factors (CVDRFs, e.g., hypertension, hyperlipidemia, or diabetes mellitus). Nevertheless, it remains unknown whether PTSD accelerates CVDRF development and how that impacts the development of major adverse cardiovascular events (MACE) in a broad population. Furthermore, the underlying mechanisms remain incompletely characterized. OBJECTIVE: We hypothesized that 1) PTSD accelerates CVDRF development, 2) accelerated CVDRF development mediates the PTSD-MACE relationship, and 3) accelerated CVDRF development is partially explained by alterations in neural, autonomic, and inflammatory intermediaries (e.g., stress-associated neural activity [SNA], ventromedial prefrontal cortex [vmPFC] activity, heart rate variability [HRV], and C-reactive protein [CRP]). METHODS: Subjects (N = 84,343) in the Mass General Brigham Biobank were studied over 10 years. PTSD, CVDRFs, and MACE were identified by diagnostic codes. From participants with available clinical data, neural, autonomic, and inflammatory mediators (e.g., SNA, vmPFC, HRV, and CRP) were assessed. RESULTS: PTSD independently predicted incident CVDRFs (hazard ratio [95 % confidence interval] = (1.432 [1.287, 1.592], p < 0.001) and associated with the accelerated development of a new CVDRF by ∼ 4 months versus those without PTSD. The development of new CVDRFs predicted incident MACE (1.736 [1.652, 1.823, p < 0.001) and mediated the link between PTSD and MACE (p < 0.05) by up to 36.4 %. Additionally, lower vmPFC activity, lower HRV, and higher CRP were associated with the development of CVDRFs. HRV and CRP significantly mediated the PTSD-CVDRF link. CONCLUSIONS: The PTSD-MACE link was partially explained by the accelerated development of CVDRFs. Alterations in neural, autonomic, and inflammatory intermediaries contributed to this association. These findings suggest that greater clinical attention to CVDRFs in individuals with PTSD may attenuate MACE risk.