SAN DIEGO—Migraine with aura is associated with increased risk of venous thromboembolism, but migraine without aura is not, according to research presented at the 58th Annual Scientific Meeting of the American Headache Society. The investigators plan to identify the mechanism of the increased risk, which they hypothesize could involve hormones, genes, or prothrombotic states.
Many previous studies have focused on the associations between migraine and atherothrombosis, migraine and stroke, and migraine and myocardial infarction. Results generally have indicated that gender and migraine status (ie, migraine with or without aura) modify the risk of these outcomes. Fewer studies have examined the relationship between migraine and venous thromboembolism, however. Most of the published studies of this topic have focused on specific subgroups of patients and lacked data on the general population of migraineurs.
Kuan-Po Peng, MD, a neurologist at Taipei Veterans Hospital in Taiwan, and colleagues sought to evaluate the risk of venous thromboembolism in the general migraine population and to identify the subgroup of patients at greatest risk. They collected data from the Taiwan National Health Insurance Research Database, which includes information for nearly 750,000 patients with migraine. To increase diagnostic accuracy, the researchers identified patients with neurologist-diagnosed migraine. They also used a diagnosis code plus a composite of anticoagulation prescriptions to identify patients with venous thromboembolism.
Kuan-Po Peng, MD
Dr. Peng and colleagues identified a cohort of migraineurs and a cohort of patients without headache. Each cohort included 102,159 patients, and both were matched by sex and propensity score. The researchers followed both cohorts for approximately four years and observed cases of venous thromboembolism. They used Cox proportional hazards regression analyses to calculate adjusted hazard ratios (aHRs) for the two study arms.
In all, 226 migraineurs and 203 patients without headache had venous thromboembolism. “To our surprise, we found that, overall, the risk of venous thromboembolism is not increased in the migraine population,” said Dr. Peng. The aHR of venous thromboembolism was 1.12 among migraineurs. Subgroup analysis by migraine subtype indicated an elevated risk of venous thromboembolism in patients with migraine with aura (aHR, 2.42), but not in patients with migraine without aura (aHR, 0.81). When the investigators analyzed the data by gender, they found a higher risk of venous thromboembolism among female migraineurs with aura, compared with their male counterparts (aHR, 2.81 vs 1.81).
Dr. Peng’s group conducted sensitivity analyses, excluding anticoagulant use, contraceptive use, major surgery, pregnancy, and other risk factors for venous thromboembolism. In these analyses, the risk of venous thromboembolism was similar to that in the primary analysis.
“We are interested in the mechanism behind this specific association,” said Dr. Peng. “There might be a role for estrogen because … all the patients at higher risk are female, and estrogen is a known risk factor for venous thromboembolism.” The investigators, however, saw no difference in the association between migraine with aura and venous thromboembolism when comparing women younger than 50 (an age used to mark the beginning of menopause) and those older than 50. The low number of cases of venous thromboembolism, and consequent lack of power, may explain this result, said Dr. Peng.
—Erik Greb