Article In Brief
Post-traumatic stress disorder (PTSD) was associated with a significant increase in risk for early incident transient ischemic attack and ischemic stroke independent of established stroke risk factors and comorbid psychiatric disorders. The study authors suggest that psychological factors, including PTSD, may be important targets for prevention strategies for young adults.
Young and middle-aged adults with post-traumatic stress disorder (PTSD) have an increased risk of developing ischemic stroke and transient ischemic attack (TIA), according to a study of nearly one million veterans serving in Iraq and Afghanistan over a 13-year period. The findings were published in the November issue of Stroke.
The researchers also discovered that the link between PTSD and stroke was stronger in men than in women, and that vets with PTSD were more likely than vets without PTSD to have unhealthy habits—such as smoking and inactivity—that increase stroke risk, according to the study.
“It is important to emphasize that PTSD is not just an issue for veterans,” explained lead author Lindsey Rosman, PhD, assistant professor of medicine in the division of cardiology at the University of North Carolina, in comments to Neurology Today.
“It's a serious public health problem. Clinicians should be aware that PTSD is prevalent among young people and may have major implications for their risk of stroke,” Dr. Rosman said. “While more research is needed to determine the best methods for screening and patient management, a case can be made for health care providers to adopt a more personalized, tailored approach to patient counseling on individual risks in their clinical practice,” she added.
“From a public health perspective, there exists a great opportunity to improve stroke prevention in young adults through the development of targeted screening programs, tailored patient counseling on individual risks, and age-appropriate interventions,” Dr. Rosman and her study coauthors wrote. “Because psychological factors may be potent risk factors for stroke in the young, it will be important to determine whether early identification of PTSD symptoms and treatment mitigates the risk of early stroke. If so, addressing mental health issues, including PTSD, may be an important part of a comprehensive stroke prevention strategy.”
“While more research is needed to determine the best methods for screening and patient management, a case can be made for health care providers to adopt a more personalized, tailored approach to patient counseling on individual risks in their clinical practice.”
—DR. LINDSEY ROSMAN
Study Design, Findings
Dr. Rosman and her colleagues examined health care data from nearly one million US military veterans who had served in Operation Enduring Freedom, Operation Iraqi Freedom, and Operation New Dawn and who had one or two outpatient medical visits at a VA medical facility between 2001 and 2014. Researchers also looked at medical claims data from non-VA care. Patients' diagnoses were determined through ICD-9 codes.
They found that 28 percent of the claims in the sample were diagnosed with PTSD. The average age of veterans was 30, and two-thirds of the sample was white. Nearly 88 percent of the sample was male. At baseline, none had experienced TIA or ischemic stroke.
Over the 13-year study period, 766 veterans (95 women and 671 men) experienced a TIA. After adjusting for stroke risk factors including diabetes, hypertension, obesity, vascular disease, and psychiatric disorders such as depression and anxiety, researchers found that veterans with PTSD were 61 percent more likely to experience a TIA than those without PTSD (HR, 1.61; 95 percent CI,1.27-2.04).
Over the same study period, 1,877 veterans experienced an ischemic stroke. Dr. Rosman and her colleagues found that after adjusting for stroke risk factors and psychiatric comorbidities, veterans with PTSD were 36 percent more likely to experience ischemic stroke than those without PTSD (HR, 1.36; 95 percent CI, 1.22-1.52).
Dr. Rosman and her colleagues reported that the link between PTSD and ischemic stroke was stronger in men, but the same was not true for TIA (p=0.003).
Dr. Rosman noted that young adults in the general population are increasingly exposed to stressful or traumatic life events such as gun violence, natural disaster, sexual abuse, military combat, and other forms of severe adversity in their communities.
“We know that exposure to these types of traumatic events can lead to long-term psychological problems in some people, which may ultimately increase their risk of developing stroke at a young age,” she said.
She speculated that prolonged exposure to intense psychological stress may lead to “chronic inflammation, platelet activation and aggregation, and neuroendocrine dysregulation, all of which could conceivably contribute to development of stroke.”
While stroke is a complex condition that occurs in a diverse patient population, she noted, the causes, characteristics, and consequences of stroke for young patients will likely differ from those for the typical stroke patient who is much older and more likely to have other medical conditions.
“We cannot apply a one-size–fits-all strategy to address this problem,” said Dr. Rosman. “We need more studies to understand risk factors for stroke, specifically in young people, so that we can develop more effective screening and prevention programs.”
Study limitations included the possibility that some ICD-9 codes could have been missed or misclassified, and the authors pointed out that veterans with transient neurological symptoms such as TIA may be less likely to seek medical care when symptoms resolve. In addition, the study may not be generalizable to non-veterans and older adults, the authors acknowledged, since the study population consisted post 9-11 veterans who were primarily young to middle-aged men.
Rohan Arora, MD, director of the stroke program at Long Island Jewish Medical Center in Forest Hills, NY, said there may be a physiological reason for the association. He noted that exposure to psychosocial stress may lead to secretion of pro-inflammatory cytokines in the blood stream, thereby causing injury to the arteries and leading to clot formation. Stress, or PTSD, may also cause inflammation of arteries and promote clumping of blood cells that can increase risk of stroke.
“Stress is [also] known to worsen pre-existing high blood pressure, diabetes, the likelihood of smoking, physical inactivity, and substance abuse that may increase risk of stroke in young adults,” he said. “The important thing to note is that many of the above factors are modifiable, which means that working on stress management can be beneficial in the prevention of a stroke.”
Future research should expand to include a more diverse population of young adults, he noted, especially those who have no clear identifiable cause for stroke despite a thorough medical evaluation. A stress management program should be offered and researched on an ongoing basis for young adults who meet criteria for severe psychological stress or PTSD and at-risk stroke.
Alfredo Morabia, MD, PhD, professor of clinical epidemiology at the Mailman School of Public Health of Columbia University, was the principal investigator of a cohort study, which also found PTSD could increase the long-term risk for stroke. In research published last year in Circulation: Cardiovascular Quality and Outcomes, an American Heart Association journal, he found higher long-term risk for stroke and heart attack in the clean-up crews who worked in the aftermath of the 9-11 attack on the World Trade Center in New York City.
Dr. Morabia, who is also a professor of epidemiology at the Barry Commoner Center for Health and the Environment at Queens College of the City University of New York, noted that longitudinal designs with repeated measures of PTSD and conventional cardiovascular risk factors are needed for observational studies to generate a consensus about a possible causal role of PTSD.
“In cohort studies such as Rosman's, PTSD conventional cardiovascular risk factors are set once for all at baseline. Since pre-existing PTSD may increase weight gain, tobacco use, blood pressure, and possibly cholesterol after the trauma, as well as being a predictor of subsequent PTSD and cardiovascular disease, the PTSD-stroke association may be confounded in a time-dependent way,” Dr. Morabia said. “Until such consensus is reached, screening for PTSD using simple PTSD scales among populations at risk, such as military veterans or workers involved in disaster response and safety, is consistent with what the bulk of the literature shows,” he said.
Janine Flory, PhD, associate professor of psychiatry at Icahn School of Medicine at Mount Sinai, who was also an investigator on the 9-11 study with Dr. Morabia, told Neurology Today that the mechanisms linking PTSD to stroke are thought to be related to dysregulation in what she called the stress axes, consisting of the hypothalamic-pituitary-adrenal axis and sympathetic-adrenal axis.
“Dysregulation in these systems may contribute to stroke risk via chronic inflammation, hypertension, and accelerated atherogenesis,” she said.
Dr. Flory noted that the most common treatment for PTSD is pharmacotherapy with selective serotonin reuptake inhibitors (SSRIs); however, it is unknown whether they may affect risk for stroke. Medications such as prazosin, an antihypertensive medication, is used by some providers to reduce frequency of nightmares and other hyperarousal symptoms in PTSD, but she pointed out that medications are not universally effective in treating PTSD and that people may not want to take SSRIs long term due to side effects.
“Trauma-processing therapies are recommended as the first line treatment of choice. It is not known how and whether these treatments impact stroke risk, including whether there is an indirect effect of successful treatment on lifestyle factors associated with stroke risk like increased physical activity, improved sleep, and decreases in alcohol or tobacco use.
“The bottom line is that PTSD screening and early intervention efforts are needed to alleviate distress associated with the disorder. An unintended and beneficial consequence of more widespread and more effective treatments may be a reduced incidence of stroke,” Dr. Flory said.
She added that the findings also suggest that people who treat PTSD should consider augmenting treatment with behavioral interventions that target classic lifestyle factors that increase risk for stroke such as smoking cessation, increased exercise, and nutritional or dietary interventions.
Drs. Rosman, Arora, Flory, and Morabia disclosed no competing interests. The study was supported by the Department of Veterans Affairs, the National Heart, Lung, and Blood Institute, and the Veterans Administration's Health Services Research and Development Service.