SAN DIEGO — Researchers are unraveling the complex relationship between cardiovascular (CV)- and stroke-related outcomes in migraine with, and without, aura.
Early results of one study suggests aura increases the risk for major adverse cerebrovascular and CV events (MACE) in those with migraine, and that this risk is particularly high in men.
"We confirmed that aura increases the risk for these cerebrovascular and cardiovascular outcomes in people with migraine and that there's an increased risk of these MACE events in men with migraine," study investigator Gina Dumkrieger, PhD, principal data science analyst and assistant professor of neurology, Mayo Clinic, Phoenix, Arizona, told Medscape Medical News.
The findings were presented on June 15, 2024, at the American Headache Society (AHS) 2024 annual meeting.
Few Data on Migraine and Stroke Risk
The extent to which migraine increases the risk for stroke CV outcomes has not been extensively studied.
"We're trying to find out whether migraine-related factors make it more likely that you're going to have one of these events," said Dumkrieger. "Knowing a particular factor increases the risk is something patients and medical providers would want to know."
Using Mayo Clinic electronic health records, which covers all three sites (Florida, Minnesota, and Arizona), researchers identified individuals with migraine using diagnostic codes. They also data on sex, race, and the presence of aura.
They investigated whether a history of MACE risk factors — including atrial fibrillation, diabetes, hyperlipidemia, hypertension, and tobacco use — affected risk and the potential interaction of aura with these risk factors.
MACE events included cerebral infarction, intracerebral hemorrhage, and acute myocardial infarction.
The analysis included 130,126 participants (80% women, 95% White individuals). Of these, 6% experienced a MACE event, and 94% did not.
"We confirmed that aura does increase the risk for a MACE event, and all of the known risk factors that we included were also significant," said Dumkrieger.
Odds ratios (ORs) were 3.82 for atrial fibrillation, 3.11 for hypertension, and 3.06 for hyperlipidemia.
It was surprising, said Dumkrieger, that male sex was tied to an increased risk for a MACE event (OR, 1.40). "This is not something that was known before," said Dumkrieger.
The link between migraine and ischemic stroke, particularly with aura, was stronger in women — particularly young women.
Investigators also found an interaction between male sex and aura, when it comes to MACE outcomes, said Dumkrieger. "Males in general are at higher risk, and people with aura are at higher risk. Males with aura are also at higher risk, but maybe not as much as you would think they would be. It's not a purely additive thing. This is something we need to look into more," she said.
The study also revealed an interaction between aura and hypertension as well as aura and tobacco use, but here too, it was not an additive risk, said Dumkrieger. However, she added, the presence of aura does not moderate the risk for hyperlipidemia, diabetes, or atrial fibrillation.
The research also showed a significant interaction between male sex and Black race which was additive. "There's apparently increased risk if you are male and Black or African American that's greater than what you would expect. We should be especially concerned about these individuals," she said.
Unanswered Questions
The current analysis is part of a larger study that will more closely examine these relationships. "We want to learn, for example, why aura moderates some of the risk factors but not others," said Dumkrieger.
The researchers also plan to investigate other migraine features, including headache frequency, and headache sensations such as pulsating or throbbing.
Dumkrieger was an investigator of another study, also presented at the AHS meeting, that's investigating the role of migraine-specific features and imaging results in the complex interrelationship between migraine and MACE risk.
That study, which also used the Mayo Clinic electronic health record data, included 60,454 migraine patients diagnosed with migraine after 2010.
Researchers divided participants into those with a MACE outcome (1107) and those without such an outcome (59,347) after at least 2 years of follow-up. They created a propensity cohort of individuals matched for age and risk factors for MACE outcome.
The final cohort consisted of 575 patients with and 652 patients without MACE outcome.
One of the most interesting early results from this study was that those with a MACE outcome had significantly more white matter hyperintensities than those with no MACE outcome, at 64% vs 51%, respectively.
This and other findings need to be validated in a different cohort with an electronic health records database from another institution. In future, the team plans to focus on identifying specific migraine features and medications and their relative contributions to MACE risk in migraine patients.
Yet another study featured at the AHS meeting confirmed the increased risk for stroke among migraine patients using a large database with over 410,000 subjects.
Results showed stroke was more than three times more common in those with a migraine diagnosis than in those without (risk ratio, [RR] 3.23; P < .001). The RR for hemorrhagic stroke (3.15) was comparable with that of ischemic stroke (3.20).
The overall stroke RR for chronic migraine vs controls without migraine was 3.68 (P < .001). The RR for migraine with aura vs migraine without aura was 1.37 (P < .001).
Useful Data
Commenting on the research for Medscape Medical News, Juliana VanderPluym, MD, a headache specialist at the Mayo Clinic, Phoenix, Arizona, described this new information "very useful."
The fact that there are more white matter lesions on MRI scans in migraine patients with MACE needs further exploration, said VanderPluym.
"Understanding how much of that relates to migraine, how much relates to other comorbid conditions, and what this all means together, is very important," particularly because MACE can be life-threatening and life-altering," she added.
Learning how migraine medications may impact MACE risk is also something that needs to be examined in greater depth, she said. "I would think that migraines that are controlled might have a different MACE risk for MACE than uncontrolled migraine," she said.
The investigators reported no relevant financial conflicts of interest.