Inflammatory Biomarkers Link Migraine to Stroke in Young Women

Inflammatory cytokines interleukin 6 (IL-6), tumor necrosis factor alpha (TFNα), and transforming growth factor beta 1 (TGF-β1) are elevated in young women with migraine, and these levels correlate with headache frequency, BMI, and high sensitivity C-reactive protein (CRP).

LOS ANGELES—Inflammatory cytokines interleukin 6 (IL-6), tumor necrosis factor alpha (TFNα), and transforming growth factor beta 1 (TGF-β1) are elevated in young women with migraine, and these levels correlate with headache frequency, BMI, and high sensitivity C-reactive protein (CRP), according to research presented at the 52nd Annual Scientific Meeting of the American Headache Society.

“Migraine is a risk factor for stroke in young women,” reported Gretchen Tietjen, MD, Professor and Chair of Neurology at the University of Toledo in Ohio. She noted that previous research found that “markers of endothelial activation—namely inflammatory and coagulation biomarkers—were elevated in premenopausal migraineurs interictally, compared to a control group, suggesting a role in endothelial dysfunction in migraine-related stroke.”

Dr. Tietjen and colleagues evaluated adiponectin and inflammatory cytokine biomarkers in the blood and urine of 125 premenopausal migraineurs between ages 18 and 50 and 50 case-matched controls. Subjects were subgrouped into migraine with aura (n = 61) and migraine without aura (n = 64). Participants did not have a history of stroke, myocardial infarction, diabetes, and vasculitis, and they were not taking antiplatelet agents, anticoagulants, or NSAIDs.

The average age of migraineurs was 37, and the average age of headache onset was 19. Migraine history spanned an average of 17 years, and headache frequency averaged 12 days per month.

“These were people from a clinic who had very frequent migraines compared to the control group without any history of headaches,” Dr. Tietjen noted.

Interrelated Inflammation Markers

Each cytokine correlated with BMI, and adiponectin was inversely correlated with BMI. The cytokines also correlated with high-sensitivity CRP, and adiponectin was inversely correlated with high-sensitivity CRP as well. IL-6, TFNα, and TGF-β1 were all correlated with one another; however, adiponectin did not correlate with the other biomarkers studied.

“I was surprised to find that adiponectin, which has generated a lot of interest for its possible role in migraine and in stroke (related to endothelial dysfunction), did not seem to be associated with migraine, with migraine frequency, or with the other biomarkers,” Dr. Tietjen told Neurology Reviews.

Differences in Age, Aura Status, and Frequency

In an age-adjusted analysis, the investigators found a significant difference between subjects and controls for TGF-β1 and TFNα. When the results were further stratified by aura status, Dr. Tietjen’s group found a significant difference in TGF-β1 between subjects who experienced migraine with aura and those without aura.

In a logistic regression analysis, which controlled for hypertension, oral contraception pills, BMI, and hyperlipidemia, the results were similar. When the investigators looked at headache frequency, they found a correlation with TGF-β1, TFNα, and IL-6, but not with adiponectin. However, they did find an inverse correlation between adiponectin and age of headache onset.

“Those who were more underweight and had higher adiponectin levels had a younger age of headache onset,” Dr. Tietjen reported.

“The findings suggest that migraine is associated with an inflammatory state that occurs between headaches, but it appears to be related to headache frequency,” she said. “This inflammatory state may be secondary to activation of the vascular endothelium, but it also may be related to weight, [because] all cytokines correlated with BMI. Further understanding of the basis of these findings may lead to improved headache treatment and stroke prevention in the migraine population.

“This work is preliminary but opens up new avenues of research in migraine pathogenesis and migraine-related stroke risk,” Dr. Tietjen concluded.

—Rebecca K. Abma