Several registry-based studies have reported an increased risk of long-term systemic comorbidities during the chronic phase of recovery from traumatic brain injury (TBI). However, few have been designed to pinpoint whether the diseases were present before the brain injury.

Now, analysis of prospectively collected data has demonstrated that adults who sustain TBI, regardless of age and injury severity, are at higher risk of certain cardiovascular, endocrine, neurologic, and psychiatric disorders. In JAMA Network Open, Saef Izzy, MD, a neurologist in the Division of Stroke and Cerebrovascular Diseases and the Division of Critical Care Neurology at Brigham and Women’s Hospital, Ross Zafonte, DO, chief of the Physical Medicine and Rehabilitation Service at Massachusetts General Hospital and president of Spaulding Rehabilitation Network, and colleagues also report links between certain post-TBI comorbidities and increased mortality risk.

Methods

The team examined data on three groups of adults:

• 4,351 without prior comorbidities who had at least one inpatient or outpatient visit for mild TBI (mTBI) between 2000 and 2015 and at least one inpatient or outpatient follow-up visit (restricted to the period from six months to 10 years after TBI) between 2000 and 2019

• 4,351 with moderate to severe TBI (msTBI) who met the same criteria and were matched by age, sex, and race to the patients with mTBI

• 4,351 without TBI (“unexposed group”) who had inpatient or outpatient visits within the same time frames, also matched by age, sex, and race to the mTBI group

Comorbidities After TBI

The researchers studied 21 comorbidities across four organ systems. Compared with the unexposed group, patients with mTBI or msTBI were at significantly higher risk for nearly all of them:

• Cardiovascular disorders—All risks studied were higher, including hypertension (HR, 2.5 for mTBI and 2.4 for msTBI), hyperlipidemia, obesity, and coronary artery disease

• Endocrine disorders—The HR for diabetes was nearly doubled (1.9 for both mTBI and msTBI), but there was no increased hazard of the other disorders studied (hypothyroidism, pituitary dysfunction, adrenal insufficiency, and erectile dysfunction)

• Neurological disorders—All risks studied were higher, including ischemic stroke or transient ischemic attack (HR, 2.2 for mTBI and 3.6 for msTBI), dementia (HR, 3.8 for mTBI and 4.2 for msTBI), and seizure disorders (HR, 5.0 for mTBI and 7.6 for msTBI)

• Psychiatric disorders—All risks were at least doubled, including depression, anxiety disorder, bipolar disorder, sleep disorder, suicide ideation/intent/attempt, substance misuse, opioid misuse, alcohol misuse, and especially psychosis (HR, 10.0 for mTBI and 8.7 for msTBI)

The HRs for specific comorbidities varied by age. Still, the risk of cardiovascular, neurologic, and psychiatric disorders was higher in both subtypes of TBI, compared with unexposed patients, in all three age groups studied (18–40 years, 41–60 years, and >60 years).

Mortality Risk

Patients with msTBI were at a higher risk of mortality compared with the unexposed group (9.9% vs. 5.7%; P<0.001). Patients with mTBI were not.

Many of the individual comorbidities that developed after TBI were associated with higher mortality, including adrenal insufficiency (HR, 6.2), coronary artery disease (HR, 2.2), hypertension (HR, 1.34), dementia (HR, 3.0), substance misuse (HR, 3.7), and anxiety disorder (HR, 1.4).

Guidance for Patient Monitoring

The increased risk of comorbidities after TBI may represent a combination of direct factors (hormonal and inflammatory changes caused by injury) and indirect factors (psychosocial risk factors such as physical inactivity, unhealthy diet, and social isolation). The indirect factors might themselves be related to the increased propensity for comorbidities such as sleep disorders and depression.

Patients with TBI, regardless of severity and in all age groups, may benefit from proactive screening for chronic systemic diseases, particularly cardiometabolic diseases.