Importance Posttraumatic stress disorder (PTSD) is a prevalent mental health problem that increases risk of cardiovascular disease (CVD). It is not known whether gender or comorbidities modify associations between PTSD and CVD.

Objective To assess risk of hypertension and atherosclerotic CVD (ASCVD) associated with PTSD in a predominantly young military population, and determine if gender or PTSD comorbidities modify these associations.

Design, setting, and participants Using administrative medical records, this longitudinal, retrospective cohort study assessed relationships of PTSD, gender, comorbidities (metabolic risk factors [MRF], behavioral risk factors [BRF], depression, and sleep disorders) to subsequent hypertension and ASCVD among 863,993 active-duty U.S. Army enlisted soldiers (86.2% male; 93.7% <age 40). Using discrete-time survival analysis, person-months with an initial hypertension diagnosis (n=49,656) were compared to an equal-probability control sample. Separate analyses compared person-months with ASCVD (n=2,427) to an equal-probability control sample.

Main outcomes and measures ICD-9-CM diagnoses of hypertension, ASCVD (coronary artery disease, myocardial infarction, stroke, heart failure), PTSD, MRF (Type 2 diabetes, obesity), BRF (tobacco/alcohol use disorders), depression, and sleep disorders.

Results PTSD was associated with subsequent hypertension (OR=3.0 [95% CI=2.9-3.1]), and ASCVD (OR=2.7 [95% CI=2.2-3.3]). These associations remained significant but were attenuated after adjusting for comorbidities and sociodemographic/service-related variables (Hypertension: OR=1.9 [95% CI=1.8-2.0]; ASCVD: OR=1.4 [95% CI=1.2-1.8]). For hypertension, gender and each comorbidity were significant explanatory variables in multivariable models, and there were significant PTSD interactions with gender, MRF, depression, and sleep disorders. Stratifying separately by gender and presence of each comorbidity, PTSD-hypertension associations were stronger among men, those without MRF, without depression, and without sleep disorders. Standardized risk estimates indicated that predicted hypertension rates for those with vs. without PTSD were higher for men, and for those with vs. without MRF, depression, and sleep disorders. For ASCVD, comorbidities, but not gender, were independent predictors, and associations between PTSD and ASCVD were not modified by gender or comorbidities.

Conclusions and relevance PTSD and comorbidities are independent risk factors for hypertension and ASVD in younger individuals, and gender and comorbid conditions modify PTSD relationships with hypertension. These findings suggest that CVD preventive interventions address PTSD and medical and behavioral comorbidities.

Dr. Murray Stein received consulting income from Actelion, Acadia Pharmaceuticals, Aptinyx, atai Life Sciences, Boehringer Ingelheim, Bionomics, BioXcel Therapeutics, Clexio, EmpowerPharm, Engrail Therapeutics, GW Pharmaceuticals, Janssen, Jazz Pharmaceuticals, and Roche/Genentech. Dr. Stein has stock options in Oxeia Biopharmaceuticals and EpiVario. He is paid for his editorial work on Depression and Anxiety (Editor-in-Chief), Biological Psychiatry (Deputy Editor), and UpToDate (Co-Editor-in-Chief for Psychiatry). All other authors report no conflicts of interest.

Army STARRS was sponsored by the Department of the Army and funded under cooperative agreement number U01MH087981 (2009-2015) with the National Institute of Mental Health (NIMH). Subsequently, STARRS-LS was sponsored and funded by the Department of Defense (USUHS grant number HU0001-15-2-0004). Dr. Gabbay was supported by the Defense Health Program (DH) Joint Program Committee 5 (JPC-5) Working Group (Psychological Health and Resilience and PTSD) under Award Numbers HU0001-18-2-0003 and HU0001-21-2-0057. Additional support for manuscript preparation was provided by National Heart Lung and Blood Institute Grant RO1HL085730.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The IRB of the Uniformed Services University of the Health Sciences gave ethical approval for this work.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

All data produced in the present study are available upon approval of the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS) and the U.S. Department of Defense. The data are not publicly available due to privacy or ethical restrictions.