TBI Linked to 'Striking' Risk for CVD, Endocrine, Brain Disorders

Mild traumatic brain injury (TBI) is linked to a significantly increased risk for a host of subsequent cardiovascular, endocrine, neurologic, and psychiatric disorders, new research shows.

Incidence of hypertension, coronary heart disease, diabetes, stroke, depression, and dementia all began to increase soon after the brain injury and persisted over a decade in both mild and moderate-to-severe TBI.

Researchers found the multisystem comorbidities in all age groups, including in patients as young as 18. They also found that patients who developed multiple post-injury problems had higher mortality during the decade-long follow up.

The findings suggest patients with TBI may require longer follow-up and proactive screening for multisystem disease, regardless of age or injury severity.

Dr Ross Zafonte

"The fact that both patients with mild and moderate-to-severe injuries both had long-term ongoing associations with comorbidities that continued over time and that they are cardiovascular, endocrine, neurologic, and behavioral health-oriented was pretty striking," study author Ross Zafonte, DO, PhD, president of Spaulding Rehab Hospital and professor and chair of physical medicine and rehab at Harvard Medical School, Boston, Massachusetts, told Medscape Medical News.

The study was published online April 28 in JAMA Network Open.

Injury Severity Not a Factor

An estimated 2.8 million individuals in the United States experience TBI every year. Worldwide, the figure may be as high as 74 million.

Studies have long suggested a link between brain injury and subsequent neurologic disorders, but research suggesting a possible link to cardiovascular and endocrine problems has recently gained attention.

Building on a 2021 study that showed increased incidence of cardiovascular issues following a concussion, the researchers examined medical records of previously heathy patients treated for TBI between 2000 to 2015 who also had at least 1 follow-up visit between 6 months and 10 years after the initial injury.

Researchers analyzed data from 13,053 individuals — 4351 with mild injury (mTBI), 4351 with moderate-to-severe injury (msTBI), and 4351 with no TBI. The most common cause of injury was a fall. Patients with sports-related injuries were excluded.

Incidence of hypertension was significantly higher among patients with mTBI (hazard ratio [HR], 2.5; 95% CI, 2.1 - 2.9) and msTBI (HR, 2.4; 95% CI, 2.0 - 2.9) compared with the unaffected group. Risk for other cardiovascular problems, including hyperlipidemia, obesity, and coronary artery disease, were also higher in the affected groups.

TBI patients also reported higher incidence of endocrine diseases, including diabetes (mTBI: HR, 1.9; 95% CI, 1.4 - 2.7; msTBI: HR, 1.9; 95% CI, 1.4 - 2.6). Elevated risk for ischemic stroke or transient ischemic attack was also increased (mTBI: HR, 2.2; 95% CI, 1.4 - 3.3; msTBI: HR, 3.6; 95% CI, 2.4 - 5.3).

Regardless of injury severity, patients with TBI had a higher risk for neurologic and psychiatric diseases, particularly depression, dementia, and psychotic disorders. "This tells us that mild TBI is not clean of events," Zafonte said.

Surprising Rate of Comorbidity in Youth

Investigators found increased risk for posttrauma comorbidities in all age groups, but researchers were struck by the high rates in younger patients, aged 18-40. Compared with age-matched individuals with no TBI history, hypertension risk was nearly six times higher in those with mTBI (HR, 5.9; 95% CI, 3.9 - 9.1) and nearly four times higher in patients with msTBI (HR, 3.9; 95% CI, 2.5 - 6.1).

Rates of hyperlipidemia and diabetes were also higher in younger patients in the mTBI group and posttraumatic seizures and psychiatric disorders were elevated regardless of TBI severity.

Overall, patients with msTBI, but not those with mTBI, were at higher risk for mortality compared with the unexposed group (432 deaths [9.9%] vs 250 deaths [5.7%]; P < .001).

"It's clear that what we may be dealing with is that it holds up even for the younger people," Zafonte said. "We used to think brain injury risk is worse in the severe cases, which it is, and it's worse later on among those who are older, which it is. But our younger folks don't get away either."

While the study offers associations between TBI and multisystem health problems, Zafonte said it's impossible to say at this point whether the brain injury caused the increased risk for cardiovascular or endocrine problems. Other organ injuries sustained in the trauma may be a contributing factor.

"Further data is needed to elucidate the mechanism and the causative relationships, which we do not have here," he said.

Many of the post-injury comorbidities emerged a median of 3.5 years after TBI, regardless of severity. But some of the cardiovascular and psychiatric conditions emerged far sooner than that.

That's important because research suggests less than half of patients with TBI receive follow-up care.

"It does make sense for folks who are interacting with people who've had a TBI to be suspicious of medical comorbidities relatively early on, within the first couple of years," Zafonte said.

In an invited commentary, Vijay Krishnamoorthy, MD, MPH, PhD, Duke University School of Medicine, Durham, North Carolina, and Monica S. Vavilala, MD, University of Washington, Seattle, highlight some of the study's limitations, including a lack of information on comorbidity severity and the lack of a matched group of patients who experienced non-head trauma.

Despite those limitations, the study offers important information on how TBI may affect organs beyond the brain, they note.

"These observations, if replicated in future studies, raise intriguing implications in the future care of patients with TBI, including heightened chronic disease-screening measures and possibly enhanced guidelines for chronic extracranial organ system care for patients who experience TBI," Krishnamoorthy and Vavilala write.

The study received no specific funding. Zafonte reports having received personal fees from Springer/Demos, serving on scientific advisory boards for Myomo and OnCare and has received funding from the Football Players Health Study at Harvard, funded in part by the National Football League Players Association. Krishnamoorthy and Vavilala have disclosed no relevant financial relationships.

JAMA Netw Open. Published online April 28, 2022. Full text, Editorial

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