PTSD increases risk for major adverse cardiovascular events through neural and cardio-inflammatory pathways

Antonia V. Seligowski, Simran S. Grewal, Shady Abohashem, Hadil Zureigat, Iqra Qamar, Wesam Aldosoky, Charbel Gharios, Erin Hanlon, Omar Alani, Sandeep C. Bollepalli, Antonis Armoundas, Zahi A. Fayad, Lisa M. Shin, Michael T. Osborne, Ahmed Tawakol

Research output: Contribution to journalArticlepeer-review


While posttraumatic stress disorder (PTSD) is known to associate with an elevated risk for major adverse cardiovascular events (MACE), few studies have examined mechanisms underlying this link. Recent studies have demonstrated that neuro-immune mechanisms, (manifested by heightened stress-associated neural activity (SNA), autonomic nervous system activity, and inflammation), link common stress syndromes to MACE. However, it is unknown if neuro-immune mechanisms similarly link PTSD to MACE. The current study aimed to test the hypothesis that upregulated neuro-immune mechanisms increase MACE risk among individuals with PTSD. This study included N = 118,827 participants from a large hospital-based biobank. Demographic, diagnostic, and medical history data collected from the biobank. SNA (n = 1,520), heart rate variability (HRV; [n = 11,463]), and high sensitivity C-reactive protein (hs-CRP; [n = 15,164]) were obtained for a subset of participants. PTSD predicted MACE after adjusting for traditional MACE risk factors (hazard ratio (HR) [95 % confidence interval (CI)] = 1.317 [1.098, 1.580], β = 0.276, p = 0.003). The PTSD-to-MACE association was mediated by SNA (CI = 0.005, 0.133, p < 0.05), HRV (CI = 0.024, 0.056, p < 0.05), and hs-CRP (CI = 0.010, 0.040, p < 0.05). This study provides evidence that neuro-immune pathways may play important roles in the mechanisms linking PTSD to MACE. Future studies are needed to determine if these markers are relevant targets for PTSD treatment and if improvements in SNA, HRV, and hs-CRP associate with reduced MACE risk in this patient population.

Original languageEnglish
Pages (from-to)149-154
Number of pages6
JournalBrain, Behavior, and Immunity
StatePublished - Mar 2024


  • Autonomic
  • Cardiovascular
  • Inflammation
  • Neural
  • PTSD


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