Elizabeth Seng, PhD
(Credit: American Headache Society)
Migraine is a common, disabling condition and represents a leading cause of neurological visits in primary care. Veterans with migraine face unique challenges, with a higher prevalence of the disease and greater risk for comorbidities compared with the general population. Although the underlying mechanisms of migraine may be similar between veterans and nonveterans, factors such as military service and additional health conditions can influence the prevalence, presentation, and management of migraine. Veterans may also encounter barriers to care, including limited access to health services, stigma associated with seeking treatment, and a shortage of specialized headache clinics.1
The burden of migraine among veterans can be substantial, affecting daily functioning, increasing health care utilization, and contributing to both physical and socioeconomic challenges. Despite this impact, research examining the relationship between migraine and comorbid conditions in veterans remains limited, particularly across cardiovascular events. Women veterans also face a higher disease burden of migraine, yet studies on the sex differences in migraine for veterans are limited. Understanding how migraine interacts with comorbidities in both men and women could be essential, as these conditions have been linked to more severe migraine symptoms.
Migraine expert Elizabeth Seng, PhD, recently discussed the association between migraine and cardiovascular events, such as ischemic stroke, in a cohort of veterans treated in the Veterans Health Administration (VHA) system at the 2025 American Headache Society (AHS) Annual Meeting, held June 19-22, in Minneapolis, Minnesota.2 Seng, professor of psychology at Yeshiva University and professor of neurology at Albert Einstein College of Medicine, spoke with NeurologyLive® after the meeting to emphasize that the findings from the veterans cohort highlighted the need to consider factors such as sex, overall health, and treatments when assessing long-term cardiovascular risk in migraine.
NeurologyLive: Provide an overview of your AHS presentation, why was this a topic of interest for you?
Elizabeth Seng, PhD: Migraine is a common, disabling neurologic disease. Because it’s so common and mostly prevalent during midlife, that does make it somewhat unusual compared to a lot of other diseases that are more prevalent as we age. That can give us an indicator of trouble that might happen down the road, or in some cases, sooner than we might like.
Cardiovascular diseases, broadly, are a leading cause of mortality worldwide, so these are really important end points for us to understand any associations with migraine. There have been a number of epidemiologic studies looking at the association between migraine and stroke, as well as migraine and other cardiovascular disease factors like myocardial infarction or heart attack. But a lot of those studies were predominantly women, in part because women are more likely to have migraine, so they’re more well represented in general cohort studies, and also because some of the cohorts were explicitly in women. So only women were collected. There is 1 cohort that was only in men. We do know something about men in this population, but very few cohorts had sufficient N to evaluate both women and men in the same cohort and to really start to understand sex differences.
So that’s why we decided, let’s look at this relationship between migraine and ischemic stroke, which is what we presented at AHS, as well as other cardiovascular outcomes in veterans. In the VHA, which is the largest integrated health care system in the country, serving about 9 million lives annually, about two-thirds of people with migraine are men and one-third are women. That’s a great distribution to interrogate sex differences and to understand what’s going on with men, who in migraine tend to be an understudied population.
We looked at the relationship between migraine and ischemic stroke at cross-section from fiscal years 2008 through 2019, with about 2 million veterans in this sample. That’s 685,000 with migraine, and it was a 2:1 match with the rest who were controls and had no headache codes at all in their medical record. We matched them on age by 5-year band, sex, race and ethnicity, and site of care. So, the person with migraine when they were initially diagnosed showed up at a certain place. We matched them with somebody else who showed up at that place in the same year with matching characteristics, with no headache disorder.
What we found was important, in large part, because it replicated what many meta-analyses have shown which is indeed, migraine is associated with an increased risk of stroke, about double the odds. We also importantly saw that women in this dataset continued to have higher odds of stroke with migraine compared with men. Women with migraine had much higher rates of stroke compared with women without migraine, whereas for men with migraine also had higher odds, still around an odds ratio of 2, but the magnitude was smaller than in women.
Similar to other studies, I think it’s really worth noting that the impact migraine has on stroke risk is much larger earlier in life. As we age, other cardiovascular risk factors also come into play, hypertension, obesity, all of these increase our risk of stroke. But people with migraine are experiencing it during midlife, and that migraine effect is much larger in veterans under the age of 55 years.
Another important finding was a replication, but I put a bit of a different spin on, was migraine with aura. We looked at whether it was particularly associated with stroke, and it was. Compared with migraine without aura, migraine with aura had about 1.5 higher odds of ischemic stroke. As we adjusted, though, that odds ratio went down to about 1.2, so adjustments really attenuated it. But people with migraine without aura were still at about double the odds of ischemic stroke. So yes, migraine with aura was even higher, the odds ratio there was 2.85, but migraine without aura in our dataset was still 2.36. That is not small.
A lot of times providers put migraine with aura in the “risk” bucket and don’t worry so much about stroke in people without aura. But I think these data, as well as other datasets, show that yes, the risk may be higher with aura, but it’s still present without aura, and it’s something we should be considering as clinicians.
What clinical implications do these findings on veterans with migraine have going forward?
Going forward, we really want to understand the treatment context. This dataset is extremely large, and we have fairly complete capture of treatments because it’s an integrated health care system. We really want to understand exogenous hormones of all kinds and their associations with stroke risk and other cardiovascular events in women. But there are also lots of medications people may be given for migraine that could have implications for stroke, and I think it’s important for us to understand that.
I also think it’s important for us to really drill down into these age and sex differences. The difference in the odds ratio between men and women starts off at about 1.0, but it decreases as we adjust, which suggests that adjustments for mental health and cardiovascular comorbidities could be potential mechanisms of that difference. If we can understand why migraine seems to confer more risk of stroke for women than for men, then we may be able to start addressing that disparity.
Are there any other related concluding thoughts you’d like to share?
I had the great privilege of being involved with the AHS research career development mentorship programs and spending time with amazing researchers from across the country who are doing extraordinary work to improve the lives of people with migraine. One of the things I kept bringing up from this presentation and these set of analyses is how difficult it is to ask questions and get answers using electronic health records.
In the VHA, we have a wealth of information and relatively complete capture. But many people are probing their electronic health records and asking questions, and I just want to throw out both encouragement and caution. We should use these data sources to evaluate questions that can improve the lives of people with migraine but even with a PhD and a team of experts on this project, we kept being surprised. For example, if someone has a heart attack, is taken to another hospital, and dies there, we know they died, but we may not know about the heart attack. We have to go to a different data source to get that information.
It takes a lot of thoughtfulness to make sense of what’s happening in an electronic health record. I strongly encourage people, when you have questions, remember your lectronic health record is certainly a source of information but also find colleagues who do this work all the time. They’ll help you understand blind spots and prevent you from making inappropriate inferences from incomplete data.
Transcript edited for clarity. Click here for more coverage of AHS 2025.