Type and severity of migraine determines long-term risk of atrial fibrillation in women: a nationwide population-based study
Authors: Rhee T.-M , Choi E.-K , Han K.-D , Lee S.-R , Oh S 
Published: October 2021

Abstract

Background
Migraine, especially when accompanied by aura, increases the risk of ischemic stroke and has also shown a close relationship with the occurrence of atrial fibrillation (AF). Although the risk of stroke and cardiovascular diseases is higher in women with migraine than in men, there is a lack of evidence for gender differences in the risk of AF in migraineurs.

Purpose
We sought to evaluate the gender-specific risk of AF according to the type and severity of migraine.

Methods
The study population included all national health checkup examinees (2009) without a history of AF from the Korean National Health Insurance Service data. The diagnosis and type or severity of migraine were determined using claims data, including diagnostic, procedural, and medication prescription codes. Newly developed non-valvular AF was identified during 10 years of follow-up. Gender-difference in the effect of migraine on AF occurrence was evaluated according to the type and severity of migraine. A multivariate Cox regression model was used to adjust for baseline differences between comparison groups, including age, smoking status, drinking habit, regular physical activity, income level, diabetes mellitus, hypertension, dyslipidemia, body mass index, and glomerular filtration rate as covariates.

Results
Of a total of 4,020,488 subjects (men, n=2,213,147, women, n=1,807,341) enrolled, 4,986 had migraine with aura (mean age 50.6±14.0, men 29.3%) and 105,029 without aura (mean age 51.6±14.3, men 30.9%). The proportion of migraine with aura among migraine patients was 4% in both gender groups. In the total population, migraine or migraine with aura did not significantly increase the risk of AF. The risk of AF did not increase in a mild degree of migraine, irrespective of gender or the presence of aura. Severe migraine without aura modestly increased the risk of AF in both men and women compared to the control group. (Men, incidence rate [IR] 4.51 per 1,000 person-year, adjusted hazard ratio [HR] 1.21, 95% confidence interval [CI] 1.12–1.31; Female, IR 3.00 per 1,000 person-year, adjusted HR 1.16, 95% CI 1.09–1.22) The increase of AF risk was the most prominent in women who had severe migraine with aura (IR 3.39 per 1,000 person-year, adjusted HR 1.48, 95% CI 1.18–1.85). In contrast, no significant association was observed between AF and migraine with aura in men. (IR 2.28, adjusted HR 0.63, 95% CI 0.39–1.01; P for interaction 0.011)

Conclusions
Mild migraine was not associated with an increase in AF risk regardless of gender or the presence of aura. Severe migraine without aura showed a mild increase in AF risk without gender-difference, while severe migraine with aura significantly increased the risk of AF only in women, not in men. Surveillance for incident AF and prompt stroke prevention would be beneficial, particularly for young-aged women suffering from severe migraine with aura.

Funding Acknowledgement
Type of funding sources: None. Figure 1