Migraine May Increase Smokers’ Risk of Stroke

Among current smokers, migraine may increase the risk of stroke and combined vascular events, according to research published online ahead of print July 22 in Neurology. Migraine may not be associated with these outcomes among nonsmokers, however.

Teshamae S. Monteith, MD, Assistant Professor of Clinical Neurology at University of Miami School of Medicine, and colleagues found that study participants with migraine had twice the risk of silent brain infarctions, but they considered the findings to be consistent with previous data that suggest that migraine is not a significant risk factor for stroke among older subjects. “We thought that factors associated with a greater migraine burden, such as obesity, might put migraineurs more at risk of vascular events, but this was not the case,” said Dr. Monteith.

Cohort Was Ethnically Diverse
Data have suggested that migraine with aura is an independent risk factor for ischemic stroke in women younger than 45. Migraine also has been associated with an unfavorable cardiovascular risk profile. Dr. Monteith and colleagues initiated their study to assess the association between migraine with and without aura and stroke. They examined data from the prospective Northern Manhattan Study, which enrolled an ethnically diverse, older, community-based cohort.

Eligible participants were stroke-free, older than 40, and had lived in northern Manhattan for three months or longer. Dr. Monteith’s group excluded participants with a history of meningitis, head trauma, or radiation to rule out individuals with the potential for secondary headache. They also excluded people with a myocardial infarction before baseline.

Bilingual research assistants collected data through interviews in English or Spanish. Baseline data included demographics, socioeconomic factors, medical history and medication use, vascular risk factors, family history, and migraine history. The investigators adapted standard questions regarding hypertension, diabetes, cigarette smoking, and cardiac conditions using the Centers for Disease Control and Prevention’s Behavioral Risk Factor Surveillance System. Self-reported migraine was assessed with a questionnaire, and additional questions closely adhered to the International Classification of Headache Disorders, second edition criteria for migraine.

Study participants were screened annually by phone for changes in clinical status, and patients who screened positive were invited for an interview and examination by a neurologist. The primary outcome was adjudicated stroke. The secondary outcomes were confirmed combined vascular events (ie, stroke, myocardial infarction, or vascular death), myocardial infarction, and vascular death.

Migraine Tripled Smokers’ Stroke Risk
The researchers had information on migraine status for 1,292 participants. Among this population, 262 participants had migraine (75 with aura, 187 without aura). People with migraine were younger and more likely to be women and have Medicaid or no insurance and several vascular risk factors. Over a mean follow-up of 11 years, the researchers observed 294 combined vascular events, including 114 strokes, 94 myocardial infarctions, and 178 vascular deaths.

Migraine was not associated with risk of combined vascular events including stroke or stroke-only outcomes. When they examined migraine with aura and migraine without aura separately, the investigators found no associations in relation to combined vascular events including stroke or to stroke alone. Age at baseline, sex, race or ethnicity, smoking, moderate alcohol use, moderate to heavy physical activity, BMI, hypertension, hypercholesterolemia, or diabetes did not modify the effect.

The researchers did, however, observe an interaction between current smoking and stroke. They also found an interaction between current smoking and combined vascular events. A stratified analysis yielded a hazard ratio of stroke for migraine versus no migraine among current smokers of 3.17. Among former smokers, the hazard ratio was 0.87, and among participants who had never smoked, the hazard ratio was 0.49 when controlling for socioeconomic and vascular risk factors.

Mechanism of Increased Risk Is Unclear
Previous research has indicated that migraine with aura is an independent risk factor of recurrent ischemic stroke and other vascular events in young patients with ischemic stroke. In addition, stroke risk associated with migraine with aura was greater in younger than in older women in the Women’s Health Study. “Perhaps our participants were too old to display such a relationship between migraine with aura and stroke in both men and women of postmenopausal age,” said Dr. Monteith.

Oxidative stress may be the mechanism by which migraine increases stroke risk among smokers. Oxidative stress may have a role in migraine and may increase susceptibility to vascular events among active smokers. Furthermore, prothrombotic states, decreased platelet hemostasis time, and endothelial dysfunction, which are associated with migraine, are plausible mechanisms that may enhance stroke risk in active smokers. “We suspect that a synergic action may occur between vascular changes of migraine and smoking as an effect modifier, although further work is necessary to elucidate this association,” said Dr. Monteith.