Young Woman — Do Not Visualize Your Migraine Aura Through Cigarette Smoke!

Abstract & Commentary

By Dara G. Jamieson, MD, Associate Professor, Clinical Neurology, Weill Medical College, Cornell University. Dr. Jamieson is a consultant for Boehringer Ingelheim and Merck, and is on the speaker's bureau for Boehringer Ingelheim, Merck, Ortho-McNeil, and Pfizer.

Synopsis: Young women with recent probable migraine with visual aura are at increased risk of ischemic stroke, especially if they both smoke and use oral contraceptives. Even though their absolute risk of stroke is low, these patients should be encouraged to stop smoking.

Sources: MacClellan LR, Giles W, Cole J, Wozniak M, Stern B, Mitchell BD, Kittner S. Probable migraine with visual aura and risk of ischemic stroke: The Stroke Prevention in Young Women Study. Stroke 2007; 38:2438-2445. Kurth T. Migraine with aura and ischemic stroke. Which additional factors matter? Stroke 2007;38:2407-2408.

The association between migraine and ischemic stroke has been noted in multiple clinical trials of both men and women. The correlation seems greatest in young women with migraine with aura, as noted in the Women's Health Study (WHS) (Kurth JAMA 2006). The confounding effect of patent foramen ovale (PFO), a risk factor for ischemic stroke in young people that is present in approximately half of all migraineurs with aura, is unclear. The additional risk conferred by other factors, such as hypertension, diabetes, smoking, and oral contraceptive use, awaits elucidation.

The Stroke Prevention in Young Women Study (SPYW) is a population-based, case-control study initiated to examine risk factors for ischemic stroke in young women. Case data from women aged 15 to 49 years, who were hospitalized with a first ischemic stroke in hospitals in the Greater Baltimore-Washington area, was accumulated between 1992 and 1996 and between 2001 and 2003. Age and geographically matched control subjects were recruited by random digit dialing. The presence of symptoms of migraine headaches was assessed retrospectively in the controls and the stroke cases. The symptom criteria in the questionnaire used to define the headaches was less specific than the International Headache Society (IHS) criteria, without reference to phonophobia, duration of the migraine, or timing of the aura. Because the migraine diagnosis did not strictly adhere to the IHS diagnostic criteria for migraine, the headaches in the SPYW were called probable migraine with or without aura. The duration of exposure to probable migraine was divided into first probable migraine either within one year, within 1 to 12 years, and greater than 12 years before ischemic stroke onset. Probable migraine frequency and severity were assessed by patient interview. Traditional stroke risk factors, demographic characteristics and history of probable migraine were assessed in 386 young women who had a stroke and 614 non-stroke controls. Clinical and neuroimaging data was used to classify location of the stroke. Statistical analysis compared risk factor distribution between cases and controls.

The women in the study with a stroke were older on average and more likely to be African-American. Cases were more likely than controls to report a history of traditional risk factors such as hypertension, diabetes, and myocardial infarction and were more likely to be current smokers and current oral contraceptive users. Stroke patients reported a statistically significant increase in history of probable migraine with visual aura (PMVA), as compared to controls. But, there was no significant difference in history of probable migraine without aura between stroke cases and controls. PMVA was a significant risk factor for stroke among women without traditional vascular risk factors, as compared to either non-migraineurs or women with migraine without aura. PMVA was a significant risk factor for stroke among smokers (odds ratio 1.5; 95% CI, 1.1 to 2.3) with an increased risk in migraineurs with aura who smoked and who also use oral contraceptives. Women with PMVA who smoked and used oral contraceptives had increased stroke risk as compared to either women with PMVA (7.0 OR; 95% CI, 1.4 to 22.8) or nonmigraineurs (10.0 OR; 95% CI, 1.4 to 73.7) who were nonsmokers and did not use oral contraceptives. The vascular risk increased with chronological proximity between the woman's first episode of PMVA and the time of her stroke. There was no correlation between probable migraine and stroke location. The study did not show an association between migraine with aura, ischemic stroke risk and PFO, but echocardiography with air contrast was performed in only 163 stroke patients.

Commentary

The SPYW, a population-based, case-control study of young women with stroke, found that PMVA was associated with an increased risk of ischemic stroke, particularly stroke of undetermined origin. The risk of ischemic stroke associated with recent PMVA, which was independent of a history of hypertension, diabetes, and myocardial infarction, correlated with the findings of other studies of women with migraine including the WHS. The presence of a PFO has been implicated in the association between migraine with aura and ischemic stroke in young women, but this does not explain the increased risk of myocardial infarction in women with migraine with aura noted in WHS. While neither smoking nor oral contraceptive use independently modified the effect of PMVA on stroke risk in the SPYW, these 2 factors had a multiplicative effect on the risk of stroke.

The article was published with an editorial by Tobias Kurth, MD, ScD, who emphasized that, despite the results of the SPYW and other studies linking migraine with aura and ischemic stroke, the risk of stroke for these women is still very small. He noted methodological considerations in the SPYW: the prevalence of PMVA was high among the controls (29%) with potential underestimation of effect, and the retrospective information about migraines was ascertained after the stroke, with potential recall bias or linkage between the 2 events. However, consistent evidence that smoking substantially increases the risk of ischemic stroke in young women with migraine with aura reiterates the need to continue to encourage smoking cessation in migraineurs, especially those women whose headache is associated with an aura.

Additional Reading:

Kurth T, Gaziano JM, Cook NR, Logroscino G, Diener H-C, Bering JE. Migraine and risk of cardiovascular disease in women JAMA 2006; 296:283-291.