Brain Injury Increases Risk of Cardiovascular Disease

At a glance:

• Traumatic brain injury is under-recognized as a risk factor for cardiovascular disease.
• Increased risk of cardiovascular and cognitive dysfunction likely important drivers of high levels of disability and early death in people with TBI.
• Screening and preventative care may lessen this harm.

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Traumatic brain injury (TBI) is a leading cause of long-term disability and premature death, especially among military personnel and those playing contact sports. While substantial research has examined acute and chronic neurological consequences of TBI, the surprising associations between TBI and cardiovascular disease and an array of other non-neurological conditions need more study.

People who sustain a brain injury have an increased risk of developing chronic cardiovascular disease than people without a brain injury. A better understanding of the links between brain injuries and long-term cardiovascular health could help prevent significant disability and premature death.

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These are the conclusions reached by a group of investigators from Harvard Medical School, Brigham and Women’s Hospital, Spaulding Rehabilitation Hospital, Massachusetts General Hospital, and elsewhere, whose research focused on the long-term consequences of TBI.

After reviewing more than a dozen recent studies of people who play contact sports, serve in the military, and are in the general population, the researchers’ analysis of the overarching lessons of these studies, published in The Lancet Neurology, emphasizes the need for future cardiovascular research, surveillance, and intervention in TBI survivors.

The authors note that the studies they evaluated offer important clues about the ways that nervous system dysfunction, neuroinflammation, changes in the brain-gut connection, and post-injury comorbidities may elevate the risk of both cardiovascular and cognitive dysfunction in TBI survivors compared to people in the general population.

How to improve outcomes for people with brain injuries

“Despite decades of extensive traumatic brain injury-focused research, surprisingly, there has been minimal progress in mitigating long-term outcomes and mortality following injuries. The cardiovascular effects of TBI may be a missing link in advancing our efforts to improve long-term quality of life and reducing mortality rates in TBI patients,” said first author Saef Izzy, HMS assistant professor of neurology at the Stroke and Cerebrovascular Center of Brigham and Women’s. “We have the opportunity to identify and improve targeted screening for high-risk populations, build preventative care strategies, and improve outcomes for survivors of TBI.”

Existing research has identified a strong link between TBI and neurological conditions such as Alzheimer’s disease and dementia. However, the mechanisms driving neurological disease after TBI remain poorly understood, despite decades of research.

Based on their analysis, Izzy and colleagues suggest that non-neurological effects of TBI, such as cardiovascular, metabolic, and endocrine dysfunction, may act as intermediaries contributing to neurological disease decades after TBI. For example, hypertension, hyperlipidemia, diabetes, and hypopituitarism can negatively affect cognitive function and are established risk factors for dementia. These risk factors were all elevated in people who experienced TBI, according to the meta-analysis.

Unlocking mysteries of the brain-body connection

The authors note that there are many potential links between TBI and cardiovascular and cognitive dysfunction. Neuroinflammatory pathways triggered by TBI could predispose individuals to atherosclerosis. Weight gain and sleep disturbances after an injury could pose independent or additive risks. Disruptions to connections between the nervous and gastrointestinal systems could throw off the balance of microbes in the gut, contributing to cognitive and cardiovascular effects.

It remains unclear how single versus repetitive injuries, age at injury, TBI severity, and other comorbidities impact cardiovascular risk, the researchers noted. This is in part due to methodological limitations to current research, such as retrospective study designs and reliance on self-reported health data. The authors noted that prospective studies could clarify what risk factors and biomarkers may be most relevant to cardiovascular dysfunction post-TBI.

“This review is a clarion call to conduct better assessments and earlier intervention for survivors of TBI who may have increased cardiovascular risk. It calls for new or expanded datasets that capture, over time, changes in biomarkers and targets associated with cardiovascular disease,” said corresponding author Ross Zafonte, the Earle P. and Ida S. Charlton Professor of Physical Medicine and Rehabilitationat HMS and president of Spaulding Rehabilitation Network.

“There is a growing recognition that many systems interact to produce multilevel dysfunction after TBI, with a series of nuanced comorbidities,” said Zafonte, who is also principal investigator of the Football Players Health Study at Harvard. “Clinicians can begin to treat some of these conditions, and in the future, management guidelines can more directly address the cardiovascular health of TBI survivors.”

Authorship, funding, disclosures

Additional authors include Rachel Grashow, Farid Radmanesh, Patrick Chen, Herman Taylor, Rita Formisano, Fiona Wilson, Meagan Wasfy, and Aaron Baggish.

Izzy reports grants from the U.S. National Institutes of Health (NIH) and 2023 Stepping Strong Innovator Award. Zafonte reports receiving grants from the NIH and royalties from Springer and Demos publishing for serving as a co-editor of Brain Injury Medicine. Zafonte has also served as an advisor to Myomo, Oncare.ai, Nanodiagnostics, and Kisbee. He reports evaluating patients in the Massachusetts General Hospital Brain and Body–TRUST Program, which is funded by the NFL Players Association.