Key dimensions of post-traumatic stress disorder and endothelial dysfunction: a protocol for a mechanism-focused cohort study

Shiloh Cleveland, Kristina Reed, Jordan L Thomas, Olujimi A Ajijola, Ramin Ebrahimi, Tzung Hsiai, Amit Lazarov, Amanda K Montoya, Yuval Neria, Daichi Shimbo, Kate Wolitzky-Taylor, Jennifer A Sumner, Shiloh Cleveland, Kristina Reed, Jordan L Thomas, Olujimi A Ajijola, Ramin Ebrahimi, Tzung Hsiai, Amit Lazarov, Amanda K Montoya, Yuval Neria, Daichi Shimbo, Kate Wolitzky-Taylor, Jennifer A Sumner

Abstract

Introduction: Both trauma exposure and post-traumatic stress disorder (PTSD) are associated with increased risk of cardiovascular disease (CVD), the leading cause of death in the USA. Endothelial dysfunction, a modifiable, early marker of CVD risk, may represent a physiological mechanism underlying this association. This mechanism-focused cohort study aims to investigate the relationship between PTSD (both in terms of diagnosis and underlying symptom dimensions) and endothelial dysfunction in a diverse, community-based sample of adult men and women.

Methods and analysis: Using a cohort design, 160 trauma-exposed participants without a history of CVD are designated to the PTSD group (n=80) or trauma-exposed matched control group (n=80) after a baseline diagnostic interview assessment. Participants in the PTSD group have a current (past month) diagnosis of PTSD, whereas those in the control group have a history of trauma but no current or past psychiatric diagnoses. Endothelial dysfunction is assessed via flow-mediated vasodilation of the brachial artery and circulating levels of endothelial cell-derived microparticles. Two higher order symptom dimensions of PTSD-fear and dysphoria-are measured objectively with a fear conditioning paradigm and attention allocation task, respectively. Autonomic imbalance, inflammation, and oxidative stress are additionally assessed and will be examined as potential pathway variables linking PTSD and its dimensions with endothelial dysfunction. Participants are invited to return for a 2-year follow-up visit to reassess PTSD and its dimensions and endothelial dysfunction in order to investigate longitudinal associations.

Ethics and dissemination: This study is conducted in compliance with the Helsinki Declaration and University of California, Los Angeles Institutional Review Board. The results of this study will be disseminated via articles in peer-reviewed journals and presentations at academic conferences and to community partners.

Trial registration number: NCT03778307; pre-results.

Keywords: adult psychiatry; anxiety disorders; cardiology.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Conceptual model for the study. The aim examining whether PTSD diagnosis is related to endothelial dysfunction is indicated by the dashed arrows. The aim examining associations of post-traumatic fear and dysphoria with endothelial dysfunction is indicated by the solid arrow. Mechanisms examined in exploratory analyses are printed above and below the solid arrow. PTSD, post-traumatic stress disorder.
Figure 2
Figure 2
Study timeline. CAPS-5, Clinician-Administered PTSD Scale for DSM-5; CVD, cardiovascular disease; DSM-5, Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition; FMD, flow-mediated dilation; LEC-5, Life Events Checklist for DSM-5; PCL-5, PTSD Checklist for DSM-5; PTSD, post-traumatic stress disorder; SCID-5, Structured Clinical Interview for DSM-5.

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