Migraine headache has been suspected as both a risk factor and a precipitating event for stroke in premenopausal women, but the degree of association and the interplay between migraine and other factors, such as hypertension and use of oral contraceptives, has been unclear. The report of a large European study by Chang and colleagues clarifies the data and calls on physicians to actively intervene to reduce risk factors for stroke in young women who suffer from migraine.

The case-controlled study recruited women 20 to 44 years of age who had suffered stroke, acute myocardial infarction or venous throm-boembolic disease; each case was matched with up to three control subjects. Patients were excluded from the study if they had a recent major illness, pregnancy or surgery; had died within 24 hours of admission to hospital; or had a history of stroke, deep venous thrombosis, pulmonary embolism, acute myocardial infarction or menopause. Case subjects and control subjects were interviewed using a standardized questionnaire to collect extensive demographic, medical and other types of information. Data were gathered on 291 women who had strokes and 736 matched control subjects. Most strokes were hemorrhagic (187); 86 ischemic strokes and 18 unclassified stroke were also reported. Within the hemorrhagic group, 150 patients (80 percent) had subarachnoid hemorrhages.

A history of migraine as defined by International Headache Society criteria was given by 74 of the stroke patients (25.4 percent) and 96 of the control patients (13.0 percent). Stroke patients were also more likely to report a history of hypertension, diabetes, heavy smoking, heavy alcohol intake, a family history of early stroke and migraine. Case subjects were also more likely to be current users of oral contraceptives. The overall risk of stroke (odds ratios) in women with a history of migraine was 1.78, but the risk was dramatically different for ischemic stroke (3.54) compared with hemorrhagic stroke (1.1).

The risk for ischemic stroke was multiplied by a history of hypertension (except during pregnancy), use of oral contraception and smoking, but the synergistic effect was significant only for smoking. The risk was lower for women who used low-dose oral contraceptives than for those who used contraceptives containing 50 mg or more of estrogen. More than 80 percent of women with migraine reported no change in their headache patterns in relation to oral contraceptive use. Up to 40 percent of strokes in women with migraine developed directly from a migrainous attack, and around 70 percent reported a headache within the three days before the stroke. Change in the type or pattern of migraine with use of oral contraceptives was not predictive of stroke. Women with classic migraine headaches and women with other migraine types had similar risks of stroke.

The authors stress that ischemic stroke is a rare event in premenopausal women but that the risk is increased in women who have a personal or family history of any type of migraine. This risk is significantly multiplied by smoking. The authors urge that women with migraine headaches be advised to stop smoking and to control blood pressure. The combination of smoking and oral contraceptive use in migrainous women was of considerable concern.