Of the 27
860 participating women, 5130 (18%) reported any history of migraine, of whom 3612 (70%) reported active migraine (migraine in the year before the baseline questionnaire) and 1518 (30%) indicated previous migraine. Of the women with active migraine, 1435 (40%) were classified as having migraine with aura. Table 1 summarises the age adjusted baseline characteristics of participants according to migraine and aura status. Compared with women without a history of migraine, those with active migraine with aura were younger, were less likely to have a history of diabetes, smoked fewer cigarettes, and drank less alcohol. Women with migraine with aura were also more likely to be postmenopausal and to use postmenopausal hormones.
Table 1 Age adjusted baseline characteristics according to migraine status in Women’s Health Study (n=27 860). Figures are percentages of women* unless stated otherwise
During a mean of 13.6 years of follow-up (377
711 person years), there were 85 confirmed haemorrhagic strokes (44 intracerebral haemorrhages, 36 subarachnoid haemorrhages, and five without a clear distinction). After adjustment for age, the incidence of haemorrhagic stroke per 10
000 women per year was 2.3 for those without migraine, 2.5 for those with any history of migraine, 6.3 for those with active migraine with aura, 0.8 for those with active migraine without aura, and 1.3 for those who reported previous migraine. Compared with women without migraine, after adjustment for age and an assumption of causality, there were four additional haemorrhagic stroke events associated with migraine with aura per 10
000 women per year.
Table 2 summarises the age and multivariable adjusted hazards ratios for the association between migraine and risk of haemorrhagic stroke. Compared with women who did not report history of migraine, those who reported any history had no increased risk of haemorrhagic stroke (age adjusted hazard ratio 1.04, 95% confidence interval 0.59 to 1.82, P=0.90). When we made a distinction with regard to migraine aura, however, the results differed. After adjustment for age and compared with women without migraine history, women with active migraine with aura had increased risk of haemorrhagic stroke (2.31, 1.15 to 4.64, P=0.019). Adjustment for age, history of hypertension, smoking, BMI, alcohol consumption, and total cholesterol concentration (parsimonious model) yielded similar results. Also, adjustment for a large number of covariates via a regression model weighted for a propensity score did not substantially attenuate this finding (2.25, 1.11 to 4.54, P=0.024). Women who reported active migraine without aura and those who reported previous migraine had no increased risk of haemorrhagic stroke.
Table 2 Hazard ratios (95% confidence intervals) for haemorrhagic strokes adjusted for age, multivariables, and propensity score according to migraine status in Women’s Health Study (n=27 860)
The figure shows the age adjusted incidence rates for haemorrhagic stroke for women without a history of migraine, women with active migraine with aura, and those with active migraine without aura. Compared with women with no history of migraine, the increased rates of haemorrhagic stroke for women with active migraine with aura were more apparent towards later years of follow-up.
Age adjusted cumulative incidence of haemorrhagic stroke according to migraine in women
To evaluate the association of migraine with aura with the few subtypes of haemorrhagic stroke (intracerebral haemorrhage n=44; subarachnoid haemorrhage n=36) as well as with fatal haemorrhagic stroke (n=28), we combined women who did not report migraine, reported migraine without aura, and reported previous migraine to form a reference group. The association between active migraine with aura and haemorrhagic stroke was stronger for intracerebral haemorrhages (hazard ratio adjusted for age 2.78, 1.09 to 7.07, P=0.032) than for subarachnoid haemorrhages (1.73, 0.53 to 5.65, P=0.37) and stronger for fatal (3.56, 1.23 to 10.31, P=0.02) than non-fatal haemorrhagic stroke (1.96, 0.78 to 4.93, P=0.15).
With regard to potential effect modification of the age adjusted association between active migraine with aura and haemorrhagic stroke, we found stronger effect estimates for age 55 and above (3.80, 1.61 to 8.97), no history of hypertension (3.23, 1.45 to 7.20), cholesterol concentrations <6.2 mmol/l (2.86, 1.36 to 6.01), current use of postmenopausal hormones (2.84, 1.19 to 6.76), non-active smokers (2.70, 1.29 to 5.67), Framingham risk score estimates of coronary heart disease of <5% (2.98, 1.41 to 6.30), randomisation to vitamin E (2.87, 1.21 to 6.80), and randomisation to aspirin placebo (3.27, 1.26 to 8.49). We did not, however, find any significant effect modification (smallest P value 0.19 for the interaction by age).
When we ran age adjusted Cox proportional hazards models that controlled for time varying frequency of NSAID use during the trial period and randomised aspirin assignment, there was no attenuation in the hazard ratio for haemorrhagic stroke for women with migraine with aura (2.34, 1.17 to 4.70).