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Special Communication
July 14, 2021

Posttraumatic Stress Disorder and Cardiovascular Disease: State of the Science, Knowledge Gaps, and Research Opportunities

Author Affiliations
  • 1Cardiology Section, Department of Medicine, VA Boston Healthcare System, Boston, Massachusetts
  • 2Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts
  • 3Department of Medicine, Harvard Medical School, Boston, Massachusetts
  • 4National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland
  • 5UCSF Department of Medicine, University of California, San Francisco
  • 6Biomedical Engineering and Medical Institute, Icahn Mount Sinai School of Medicine, New York, New York
  • 7Department of Cardiology, Icahn Mount Sinai School of Medicine, New York, New York
  • 8Department of Psychiatry, Emory University, Atlanta, Georgia
  • 9Department of Psychiatry, Texas A&M University, College Station
  • 10Yale University School of Medicine, New Haven, Connecticut
  • 11VA Connecticut Healthcare System, West Haven
  • 12Department of Psychiatry, UC San Diego School of Medicine, University of California, San Diego, La Jolla
  • 13VA Center of Excellence for Stress and Mental Health, San Diego, California
  • 14Department of Psychiatry, Uniformed Services University, Bethesda, Maryland
  • 15Department of Pathology, Louisiana State University Health Science, New Orleans
  • 16Department of Cardiology, Northwestern Medicine, Chicago, Illinois
  • 17Deputy Editor, JAMA Cardiology
  • 18Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia
  • 19Herbert Wertheim School of Public Health and Human Longevity Science, University of California, San Diego, La Jolla
  • 20VA San Diego Healthcare System, San Diego, California
JAMA Cardiol. 2021;6(10):1207-1216. doi:10.1001/jamacardio.2021.2530

Posttraumatic stress disorder (PTSD) is characterized by a persistent maladaptive reaction after exposure to severe psychological trauma. Traumatic events that may precipitate PTSD include violent personal assaults, natural and human-made disasters, and exposure to military combat or warfare. There is a growing body of evidence for associations of PTSD with major risk factors for cardiovascular disease (CVD), such as hypertension and diabetes, as well as with major CVD outcomes, such as myocardial infarction and heart failure. However, it is unclear whether these associations are causal or confounded. Furthermore, the biological and behavioral mechanisms underlying these associations are poorly understood. Here, the available evidence on the association of PTSD with CVD from population, basic, and genomic research as well as from clinical and translational research are reviewed, seeking to identify major research gaps, barriers, and opportunities in knowledge acquisition and technology as well as research tools to support and accelerate critical research for near-term and longer-term translational research directions. Large-scale, well-designed prospective studies, capturing diverse and high-risk populations, are warranted that include uniform phenotyping of PTSD as well as broad assessment of biological and behavioral risk factors and CVD outcomes. Available evidence from functional brain imaging studies demonstrates that PTSD pathophysiology includes changes in specific anatomical brain regions and circuits, and studies of immune system function in individuals with PTSD suggest its association with enhanced immune inflammatory activity. However, establishment of animal models and human tissue biobanks is also warranted to elucidate the potential causal connection of PTSD-induced brain changes and/or inflammation with CVD pathophysiology. Emerging large-scale genome-wide association studies of PTSD will provide an opportunity to conduct mendelian randomization studies that test hypotheses regarding the presence, magnitude, and direction of causal associations between PTSD and CVD outcomes. By identifying research gaps in epidemiology and genomics, animal, and human translational research, opportunities to better justify and design future interventional trials are highlighted that may test whether treatment of PTSD or underlying neurobiological or immune dysregulation may improve or prevent CVD risk or outcomes.

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