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Levine  GN, Cohen  BE, Commodore-Mensah  Y,  et al.  Psychological health, well-being, and the mind-heart-body connection: a scientific statement from the American Heart Association.  侱ܱپDz. 2021;143(10):e763-e783. doi:
Koenen  KC, Sumner  JA, Gilsanz  P,  et al.  Post-traumatic stress disorder and cardiometabolic disease: improving causal inference to inform practice.   Psychol Med. 2017;47(2):209-225. doi:
Buckley  TC, Kaloupek  DG.  A meta-analytic examination of basal cardiovascular activity in posttraumatic stress disorder.   Psychosom Med. 2001;63(4):585-594. doi:
Kibler  JL, Joshi  K, Ma  M.  Hypertension in relation to posttraumatic stress disorder and depression in the US National Comorbidity Survey.   Behav Med. 2009;34(4):125-132. doi:
Sumner  JA, Kubzansky  LD, Roberts  AL,  et al.  Post-traumatic stress disorder symptoms and risk of hypertension over 22 years in a large cohort of younger and middle-aged women.   Psychol Med. 2016;46(15):3105-3116. doi:
Bartoli  F, Crocamo  C, Alamia  A,  et al.  Posttraumatic stress disorder and risk of obesity: systematic review and meta-analysis.   J Clin Psychiatry. 2015;76(10):e1253-e1261. doi:
Suliman  S, Anthonissen  L, Carr  J,  et al.  Posttraumatic stress disorder, overweight, and obesity: a systematic review and meta-analysis.   Harv Rev Psychiatry. 2016;24(4):271-293. doi:
van den Berk-Clark  C, Secrest  S, Walls  J,  et al.  Association between posttraumatic stress disorder and lack of exercise, poor diet, obesity, and co-occuring smoking: a systematic review and meta-analysis.   Health Psychol. 2018;37(5):407-416. doi:
Vancampfort  D, Rosenbaum  S, Ward  PB,  et al.  Type 2 diabetes among people with posttraumatic stress disorder: systematic review and meta-analysis.   Psychosom Med. 2016;78(4):465-473. doi:
Scherrer  JF, Salas  J, Lustman  PJ,  et al.  The role of obesity in the association between posttraumatic stress disorder and incident diabetes.   JAMA Psychiatry. 2018;75(11):1189-1198. doi:
Dzubur Kulenović  A, Kucukalić  A, Malec  D.  Changes in plasma lipid concentrations and risk of coronary artery disease in army veterans suffering from chronic posttraumatic stress disorder.   Croat Med J. 2008;49(4):506-514. doi:
Von Känel  R, Kraemer  B, Saner  H, Schmid  JP, Abbas  CC, Begré  S.  Posttraumatic stress disorder and dyslipidemia: previous research and novel findings from patients with PTSD caused by myocardial infarction.   World J Biol Psychiatry. 2010;11(2):141-147. doi:
Edmondson  D, Kronish  IM, Shaffer  JA, Falzon  L, Burg  MM.  Posttraumatic stress disorder and risk for coronary heart disease: a meta-analytic review.   Am Heart J. 2013;166(5):806-814. doi:
Song  H, Fang  F, Arnberg  FK,  et al. ٰ related disorders and risk of cardiovascular disease: population based, sibling controlled cohort study.  Ѵ. 2019;365:l1255. doi:
Ebrahimi  R, Lynch  KE, Beckham  JC,  et al.  Association of posttraumatic stress disorder and incident ischemic heart disease in women veterans.   JAMA Cardiol. Published online March 17, 2021. doi:
Akosile  W, Colquhoun  D, Young  R, Lawford  B, Voisey  J.  The association between post-traumatic stress disorder and coronary artery disease: a meta-analysis.   Australas Psychiatry. 2018;26(5):524-530. doi:
Roy  SS, Foraker  RE, Girton  RA, Mansfield  AJ.  Posttraumatic stress disorder and incident heart failure among a community-based sample of US veterans.   Am J Public Health. 2015;105(4):757-763. doi:
Chen  MH, Pan  TL, Li  CT,  et al.  Risk of stroke among patients with post-traumatic stress disorder: nationwide longitudinal study.   Br J Psychiatry. 2015;206(4):302-307. doi:
Jordan  HT, Stellman  SD, Morabia  A,  et al.  Cardiovascular disease hospitalizations in relation to exposure to the September 11, 2001 World Trade Center disaster and posttraumatic stress disorder.   J Am Heart Assoc. 2013;2(5):e000431. doi:
Emdin  CA, Odutayo  A, Wong  CX, Tran  J, Hsiao  AJ, Hunn  BH.  Meta-analysis of anxiety as a risk factor for cardiovascular disease.   Am J Cardiol. 2016;118(4):511-519. doi:
Severance  EG, Dickerson  FB, Viscidi  RP,  et al.  Coronavirus immunoreactivity in individuals with a recent onset of psychotic symptoms.   Schizophr Bull. 2011;37(1):101-107. doi:
Turner  JH, Neylan  TC, Schiller  NB, Li  Y, Cohen  BE.  Objective evidence of myocardial ischemia in patients with posttraumatic stress disorder.   Biol Psychiatry. 2013;74(11):861-866. doi:
Vaccarino  V, Goldberg  J, Rooks  C,  et al.  Post-traumatic stress disorder and incidence of coronary heart disease: a twin study.   J Am Coll Cardiol. 2013;62(11):970-978. doi:
Ahmadi  N, Hajsadeghi  F, Mirshkarlo  HB, Budoff  M, Yehuda  R, Ebrahimi  R.  Post-traumatic stress disorder, coronary atherosclerosis, and mortality.   Am J Cardiol. 2011;108(1):29-33. doi:
Gradus  JL, Farkas  DK, Svensson  E,  et al.  Associations between stress disorders and cardiovascular disease events in the Danish population.  Ѵ Open. 2015;5(12):e009334. doi:
Jordan  HT, Miller-Archie  SA, Cone  JE, Morabia  A, Stellman  SD. 𲹰 disease among adults exposed to the September 11, 2001 World Trade Center disaster: results from the World Trade Center Health Registry.   Prev Med. 2011;53(6):370-376. doi:
Glaesmer  H, Brähler  E, Gündel  H, Riedel-Heller  SG.  The association of traumatic experiences and posttraumatic stress disorder with physical morbidity in old age: a German population-based study.   Psychosom Med. 2011;73(5):401-406. doi:
Dirkzwager  AJ, van der Velden  PG, Grievink  L, Yzermans  CJ.  Disaster-related posttraumatic stress disorder and physical health.   Psychosom Med. 2007;69(5):435-440. doi:
Remch  M, Laskaris  Z, Flory  J, Mora-McLaughlin  C, Morabia  A.  Post-traumatic stress disorder and cardiovascular diseases: a cohort study of men and women involved in cleaning the debris of the World Trade Center complex.   Circ Cardiovasc Qual Outcomes. 2018;11(7):e004572. doi:
Sumner  JA, Kubzansky  LD, Elkind  MS,  et al.  Trauma exposure and posttraumatic stress disorder symptoms predict onset of cardiovascular events in women.  侱ܱپDz. 2015;132(4):251-259. doi:
Gilsanz  P, Winning  A, Koenen  KC,  et al.  Post-traumatic stress disorder symptom duration and remission in relation to cardiovascular disease risk among a large cohort of women.   Psychol Med. 2017;47(8):1370-1378. doi:
Scherrer  JF, Salas  J, Cohen  BE,  et al.  Comorbid conditions explain the association between posttraumatic stress disorder and incident cardiovascular disease.   J Am Heart Assoc. 2019;8(4):e011133. doi:
Maddox  SA, Hartmann  J, Ross  RA, Ressler  KJ.  Deconstructing the gestalt: mechanisms of fear, threat, and trauma memory encoding.  ܰDz. 2019;102(1):60-74. doi:
Wilson  MA, Liberzon  I, Lindsey  ML,  et al.  Common pathways and communication between the brain and heart: connecting post-traumatic stress disorder and heart failure.  ٰ. 2019;22(5):530-547. doi:
Liberzon  I, Abelson  JL.  Context processing and the neurobiology of post-traumatic stress disorder.  ܰDz. 2016;92(1):14-30. doi:
Kraynak  TE, Marsland  AL, Gianaros  PJ.  Neural mechanisms linking emotion with cardiovascular disease.   Curr Cardiol Rep. 2018;20(12):128. doi:
Minassian  A, Maihofer  AX, Baker  DG, Nievergelt  CM, Geyer  MA, Risbrough  VB; Marine Resiliency Study Team.  Association of predeployment heart rate variability with risk of postdeployment posttraumatic stress disorder in active-duty Marines.   JAMA Psychiatry. 2015;72(10):979-986. doi:
Kotecha  D, New  G, Flather  MD, Eccleston  D, Pepper  J, Krum  H.  Five-minute heart rate variability can predict obstructive angiographic coronary disease.  𲹰. 2012;98(5):395-401. doi:
Binici  Z, Mouridsen  MR, Køber  L, Sajadieh  A.  Decreased nighttime heart rate variability is associated with increased stroke risk.  ٰǰ. 2011;42(11):3196-3201. doi:
Kobayashi  I, Lavela  J, Mellman  TA.  Nocturnal autonomic balance and sleep in PTSD and resilience.   J Trauma Stress. 2014;27(6):712-716. doi:
Ulmer  CS, Hall  MH, Dennis  PA, Beckham  JC, Germain  A.  Posttraumatic stress disorder diagnosis is associated with reduced parasympathetic activity during sleep in US veterans and military service members of the Iraq and Afghanistan wars.  . 2018;41(12). doi:
Yoo  JK, Badrov  MB, Huang  M,  et al.  Abnormal sympathetic neural recruitment patterns and hemodynamic responses to cold pressor test in women with post-traumatic stress disorder.   Am J Physiol Heart Circ Physiol. 2020;318(5):H1198-H1207. doi:
Passos  IC, Vasconcelos-Moreno  MP, Costa  LG,  et al.  Inflammatory markers in post-traumatic stress disorder: a systematic review, meta-analysis, and meta-regression.  Գ Psychiatry. 2015;2(11):1002-1012. doi:
Eraly  SA, Nievergelt  CM, Maihofer  AX,  et al; Marine Resiliency Study Team.  Assessment of plasma C-reactive protein as a biomarker of posttraumatic stress disorder risk.   JAMA Psychiatry. 2014;71(4):423-431. doi:
Boscarino  JA.  A prospective study of PTSD and early-age heart disease mortality among Vietnam veterans: implications for surveillance and prevention.   Psychosom Med. 2008;70(6):668-676. doi:
Brudey  C, Park  J, Wiaderkiewicz  J, Kobayashi  I, Mellman  TA, Marvar  PJ.  Autonomic and inflammatory consequences of posttraumatic stress disorder and the link to cardiovascular disease.   Am J Physiol Regul Integr Comp Physiol. 2015;309(4):R315-R321. doi:
Flory  JD, Yehuda  R.  Comorbidity between post-traumatic stress disorder and major depressive disorder: alternative explanations and treatment considerations.   Dialogues Clin Neurosci. 2015;17(2):141-150. doi:
Sumner  JA, Nishimi  KM, Koenen  KC, Roberts  AL, Kubzansky  LD.  Posttraumatic stress disorder and inflammation: untangling issues of bidirectionality.   Biol Psychiatry. 2020;87(10):885-897. doi:
Bowers  ME, Ressler  KJ.  An overview of translationally informed treatments for posttraumatic stress disorder: animal models of Pavlovian fear conditioning to human clinical trials.   Biol Psychiatry. 2015;78(5):E15-E27. doi:
Stein  MB, Rothbaum  BO.  175 Years of progress in PTSD therapeutics: learning from the past.   Am J Psychiatry. 2018;175(6):508-516. doi:
Xue  B, Yu  Y, Wei  SG,  et al. ٰ-induced sensitization of angiotensin II hypertension is reversed by blockade of angiotensin-converting enzyme or tumor necrosis factor-α.   Am J Hypertens. 2019;32(9):909-917. doi:
Yu  Z, Swiercz  AP, Moshfegh  CM,  et al.  Angiotensin II type 2 receptor-expressing neurons in the central amygdala influence fear-related behavior.   Biol Psychiatry. 2019;86(12):899-909. doi:
Hodes  GE, Pfau  ML, Leboeuf  M,  et al.  Individual differences in the peripheral immune system promote resilience versus susceptibility to social stress.   Proc Natl Acad Sci U S A. 2014;111(45):16136-16141. doi:
Wang  Y, Zhu  S, Wei  W,  et al.  Interleukin-6 knockout reverses macrophage differentiation imbalance and alleviates cardiac dysfunction in aging mice.   Aging (Albany NY). 2020;12(20):20184-20197. doi:
Deslauriers  J, Toth  M, Der-Avakian  A, Risbrough  VB.  Current status of animal models of posttraumatic stress disorder: behavioral and biological phenotypes, and future challenges in improving translation.   Biol Psychiatry. 2018;83(10):895-907. doi:
Visscher  PM, Wray  NR, Zhang  Q,  et al.  10 Years of GWAS discovery: biology, function, and translation.   Am J Hum Genet. 2017;101(1):5-22. doi:
Alexander  M, Ramstead  AG, Bauer  KM,  et al.  Rab27-dependent exosome production inhibits chronic inflammation and enables acute responses to inflammatory stimuli.   J Immunol. 2017;199(10):3559-3570. doi:
Nievergelt  CM, Maihofer  AX, Klengel  T,  et al.  International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci.   Nat Commun. 2019;10(1):4558. doi:
Zhang  Y, Qi  G, Park  JH, Chatterjee  N.  Estimation of complex effect-size distributions using summary-level statistics from genome-wide association studies across 32 complex traits.   Nat Genet. 2018;50(9):1318-1326. doi:
van der Harst  P, Verweij  N.  Identification of 64 novel genetic loci provides an expanded view on the genetic architecture of coronary artery disease.   Circ Res. 2018;122(3):433-443. doi:
Stein  MB, Levey  DF, Cheng  Z,  et al; Department of Veterans Affairs Cooperative Studies Program (no. 575B); VA Million Veteran Program.  Genome-wide association analyses of post-traumatic stress disorder and its symptom subdomains in the Million Veteran Program.   Nat Genet. 2021;53(2):174-184. doi:
Smith  GD, Ebrahim  S.  ‘Mendelian randomization’: can genetic epidemiology contribute to understanding environmental determinants of disease?   Int J Epidemiol. 2003;32(1):1-22. doi:
Burgess  S, Small  DS, Thompson  SG.  A review of instrumental variable estimators for mendelian randomization.   Stat Methods Med Res. 2017;26(5):2333-2355. doi:
Watanabe  K, Stringer  S, Frei  O,  et al.  A global overview of pleiotropy and genetic architecture in complex traits.   Nat Genet. 2019;51(9):1339-1348.
Dale  CE, Fatemifar  G, Palmer  TM,  et al; UCLEB Consortium; METASTROKE Consortium.  Causal associations of adiposity and body fat distribution with coronary heart disease, stroke subtypes, and type 2 diabetes mellitus: a mendelian randomization analysis.  侱ܱپDz. 2017;135(24):2373-2388. doi:
Tillmann  T, Vaucher  J, Okbay  A,  et al.  Education and coronary heart disease: mendelian randomisation study.  Ѵ. 2017;358:j3542. doi:
Polimanti  R, Ratanatharathorn  A, Maihofer  AX,  et al; Psychiatric Genomics Consortium Posttraumatic Stress Disorder Working Group.  Association of economic status and educational attainment with posttraumatic stress disorder: a mendelian randomization study.   JAMA Netw Open. 2019;2(5):e193447. doi:
Libby  P, Nahrendorf  M, Swirski  FK.  Leukocytes link local and systemic inflammation in ischemic cardiovascular disease: an expanded “cardiovascular continuum.”   J Am Coll Cardiol. 2016;67(9):1091-1103. doi:
Heidt  T, Sager  HB, Courties  G,  et al.  Chronic variable stress activates hematopoietic stem cells.   Nat Med. 2014;20(7):754-758. doi:
Dutta  P, Courties  G, Wei  Y,  et al.  Myocardial infarction accelerates atherosclerosis.  ٳܰ. 2012;487(7407):325-329. doi:
Emami  H, Singh  P, MacNabb  M,  et al.  Splenic metabolic activity predicts risk of future cardiovascular events: demonstration of a cardiosplenic axis in humans.   JACC Cardiovasc Imaging. 2015;8(2):121-130. doi:
Gianaros  PJ, Marsland  AL, Kuan  DC,  et al.  An inflammatory pathway links atherosclerotic cardiovascular disease risk to neural activity evoked by the cognitive regulation of emotion.   Biol Psychiatry. 2014;75(9):738-745. doi:
Tawakol  A, Ishai  A, Takx  RA,  et al.  Relation between resting amygdalar activity and cardiovascular events: a longitudinal and cohort study.  Գ. 2017;389(10071):834-845. doi:
Lima  BB, Hammadah  M, Wilmot  K,  et al.  Posttraumatic stress disorder is associated with enhanced interleukin-6 response to mental stress in subjects with a recent myocardial infarction.   Brain Behav Immun. 2019;75:26-33. doi:
Lionetti  V, Bollini  S, Coppini  R,  et al.  Understanding the heart-brain axis response in COVID-19 patients: a suggestive perspective for therapeutic development.   Pharmacol Res. 2021;168:105581. doi:
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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.