Hemorrhagic stroke risk in armed forces veterans, the role of post-traumatic stress disorder and its treatment

Substantial strides have been made over the last several decades with regards to stroke incidence, prevalence, and case fatality, leading to more stroke survivors compared to prior decades thanks in part to improvements in prevention and acute stroke therapeutics. For stroke survivors, the long-term effects may be both physical and psychological. Work on acute coronary syndrome (ACS) events (e.g. myocardial infarction), has found that depression during and after hospitalization is a well established contributor to morbidity and mortality,¹ with recent work increasingly establishing this relationship in stroke as well.² Major depression is common and a modifiable risk factor for poor recovery after stroke, as well as for stroke incidence; treatment with psychopharmacology or psychotherapy are effective at treating post-stroke depression.³

In addition to depressive symptoms, anxiety symptoms/disorders also play a prominent feature in the recovery of cardiovascular disease and stroke survivors. For some patients, recovery following a medically significant event, such a stroke or myocardial infarction, may be marked by a persistent fear of a future recurrent medical event, paralleling many features of post-stroke traumatic stress disorder (PTSD).⁴ Past work has found that following an ACS event, 1 in 8 survivors reported clinically significant PTSD symptoms, which in turn is associated with a doubling of risk for 1-year all-cause mortality and/or ACS recurrence.⁵ In stroke, these findings are even more concerning. A meta-analysis of 9 studies and 1138 participants, found nearly 1 in 4 (23%) stroke survivors reported PTSD symptoms following stroke or TIA.⁶ The relationship between PTSD following ACS events and increased recurrent ACS risk has been thought to occur through a variety of proposed mechanisms that are relevant stroke, including medication and follow up care adherence, autonomic dysfunction, and immune dysregulation. To what degree these same processes may impact the risk of first stroke in the context of PTSD is less known, but an increasingly urgent question as the prevalence of PTSD has been increasing, particularly amongst veterans of the armed forces. The report in this issue of Stroke adds important information for all providers about the long-term consequences in contemporary populations of PTSD on subsequent cardiovascular disease, and in particular for hemorrhagic stroke which is associated with high mortality. ⁷ The authors examined a large cohort of United States veterans with a mean age of 30 who had served in Iraq and Afghanistan and followed them for up to 13 years, finding a low absolute incidence of hemorrhagic stroke with PTSD, though there was an overall increased relative risk in adjusted models. The authors further explored the question of whether selective serotonin and serotonin norepinephrine reuptake inhibitors also increase the risk of hemorrhagic stroke and their results parallel those of other large cohort studies and meta-analyses with small absolute risk increases.⁸ In multi-variable models however adjusted for important confounders such as hypertension and drug use, the association of PTSD and serotonin norepinephrine reuptake inhibitors with stroke was no longer statistically significant providing a potential explanation that is mediated through traditional cardiovascular disease risk factors. The authors have found that there was still an association in adjusted models between selective serotonin reuptake inhibitors use and subsequent hemorrhagic stroke, though the overall absolute risk was low. The study results are not generalizable to the broader population, as the baseline demographics in this relatively younger cohort found high rates of hypertension, substance and tobacco use which may have influenced the results. Furthermore, there is likely residual confounding from measures of severity of hypertension and other cardiovascular disease risk factors with PTSD and the medications examined. The authors included an adjustment for health care utilization to partly addresses this limitation, though the c-statistic shows only marginal improvements in model fit showing residual confounding. Given these limitations, the results of this should not discourage the use of pharmacological treatment in PTSD if they are effective in the broader patient population, particularly given the body of evidence detailing the adverse impact of quality of life associated with comorbid depression and other anxiety disorders in this high-risk population. The study however highlights the importance of remaining vigilant on managing risk factors for hemorrhagic stroke, especially in high risk younger population and emphasizes the importance of future research on cardiovascular disease in this population cohort of armed forces veterans.

Non-standard abbreviations:

ACS

acute coronary syndrome

PTSD

post-traumatic stress disorder