Association Between Traumatic Brain Injury and Subsequent Cardiovascular Disease Among Post-9/11–Era Veterans

Abstract

ImportanceTraumatic brain injury (TBI) was common among US service members deployed to Iraq and Afghanistan. Although there is some evidence to suggest that TBI increases the risk of cardiovascular disease (CVD), prior reports were predominantly limited to cerebrovascular outcomes. The potential association of TBI with CVD has not been comprehensively examined in post-9/11–era veterans.ObjectiveTo determine the association between TBI and subsequent CVD in post-9/11–era veterans.Design, Setting, and ParticipantsThis was a retrospective cohort study conducted from October 1, 1999, to September 30, 2016. Participants were followed up until December 31, 2018. Included in the study were administrative data from the US Department of Veterans Affairs and the Department of Defense from the Long-term Impact of Military-Relevant Brain Injury Consortium–Chronic Effects of Neurotrauma Consortium. Participants were excluded if dates did not overlap with the study period. Data analysis was conducted between November 22, 2021, and June 28, 2022.ExposuresHistory of TBI as measured by diagnosis in health care records.Main Outcomes and MeasuresComposite end point of CVD: coronary artery disease, stroke, peripheral artery disease, and cardiovascular death.ResultsOf the 2 530 875 veterans from the consortium, after exclusions, a total of 1 559 928 veterans were included in the analysis. A total of 301 169 veterans (19.3%; median [IQR] age, 27 [23-34] years; 265 217 male participants [88.1]) with a TBI history and 1 258 759 veterans (80.7%; median [IQR] age, 29 [24-39] years; 1 012 159 male participants [80.4%]) without a TBI history were included for analysis. Participants were predominately young (1 058 054 [67.8%] <35 years at index date) and male (1 277 376 [81.9%]). Compared with participants without a history of TBI, diagnoses of mild TBI (hazard ratio [HR], 1.62; 95% CI, 1.58-1.66; P < .001), moderate to severe TBI (HR, 2.63; 95% CI, 2.51-2.76; P < .001), and penetrating TBI (HR, 4.60; 95% CI, 4.26-4.96; P < .001) were associated with CVD in adjusted models. In analyses of secondary outcomes, all severities of TBI were associated with the individual components of the composite outcome except penetrating TBI and CVD death.Conclusions and RelevanceResults of this cohort study suggest that US veterans with a TBI history were more likely to develop CVD compared with veterans without a TBI history. Given the relatively young age of the cohort, these results suggest that there may be an increased burden of CVD as these veterans age and develop other CVD risk factors. Future studies are needed to determine if the increased risk associated with TBI is modifiable.

Traumatic Brain Injury and Long-Term Risk of Stroke Among US Military Veterans

“…[9][10][11][12][13] Many of these prior studies also did not investigate associations of TBI with both ischemic and hemorrhagic stroke risk. [7][8][9][10][11][12][13][14][15][16] The long-term risk of stroke after TBI remains unclear, particularly in populations comprised of diverse race and ethnicity groups. Information on these outcomes is important to better understand risk, burden, and possible mechanisms.…”

Platelet levels and age are determinants of survival after mild–moderate TBI: A prospective study in Spain

“…Evolution and recovery are worse if there is a history of cognitive impairment ( 4 ), mental disorders, or alcohol use disorders ( 5 , 6 ). In addition, recent studies show that TBI may be a predisposing factor for developing cardiovascular disease ( 7 ).…”

“…Mortality is mainly associated with the characteristics of the TBI and its severity and the patient's baseline situation, or the parameters of systemic severity, as described in a previous study (4). Evolution and recovery are worse if there is a history of cognitive impairment (4), mental disorders, or alcohol use disorders (5,6). In addition, recent studies show that TBI may be a predisposing factor for developing cardiovascular disease (7).…”

Cerebral hypoperfusion exacerbates traumatic brain injury in male but not female mice

“…However, the combination of brain injury in individuals with ongoing cardiovascular disease greatly increased the overall risk (4). Since cardiovascular disease, metabolic dysfunction, and associated risk factors such as smoking and hypertension are all common among TBI survivors, there is an urgent need to understand how these variables interact to alter neurodegenerative outcomes (6)(7)(8) Moreover, it is becoming increasingly clear that preexisting disease states can alter both the incidence and consequences of TBI. For instance, both cerebrovascular disease and depression predicted the incidence of TBI in older adults and vascular dysfunction increased the likelihood that injury resulted in death (9).…”