Migraine associated with increased CVD risk

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Migraine is associated with increased risks of cardiovascular problems, including heart attacks, stroke, blood clots and an irregular heart rate, say researchers. Although the absolute risks were low, the findings suggest that “migraine should be considered a potent and persistent risk factor for most cardiovascular diseases in both men and women,” say the authors.

Around 1bn people worldwide are affected by migraine. It has considerable impact on quality of life and imposes a substantial burden on society.

Previous studies have suggested a link between migraine and stroke and heart attacks, particularly among women, but the link between migraine and other heart problems are less well known. In a bid to rectify this, researchers from Aarhus University Hospital, Denmark and Stanford University, US set out to examine the risks of heart conditions including heart attacks; stroke; peripheral artery disease (narrow arteries which reduce blood flow to limbs); blood clots and fast and irregular heart rates in people who experience migraines compared with people who don’t.

The researchers collected patient data from the Danish National Patient Registry over a 19-year period, from 1995 to 2013. They compared data from over 51,000 people who had been diagnosed with migraine with over 510,000 people who were migraine free. For each person with migraine, they matched 10 people of the same age and gender who were migraine free. The average age for migraine diagnosis was 35 years, and 71% of participants were women.

Over a period of 19 years, the researchers found that migraine was positively associated with heart attack, stroke, blood clots and irregular heart rate. For example, for every 1,000 patients, 25 patients with migraine had a heart attack compared with 17 migraine free patients and 45 patients with migraine had an ischaemic stroke (blood clot in the brain) compared with 25 migraine free patients.

These associations persisted after taking account of body mass index and smoking. No meaningful association was found with peripheral artery disease or heart failure. The associations, particularly for stroke, were stronger in the first year of diagnosis than the long term, in patients with migraine aura (warning signs before a migraine, such as seeing flashing lights) than in those without aura, and in women than in men.

This is an observational study, so no firm conclusions can be drawn about cause and effect, and the authors cannot rule out the possibility that other unknown factors, such as physical activity, may have influenced the results. However, key strengths include the large sample size and long term follow up.

The authors outline reasons why migraine might increase cardiovascular disease risk. For example, people with migraine often use anti-inflammatory drugs, which are associated with increased risks of heart problems, while immobilisation related to migraine attacks may increase the risk of blood clots.

They note that current guidelines do not recommend use of anti-clotting drugs such as aspirin to treat migraine, but call on clinicians to “consider whether patients at particularly high risk of heart disease would benefit from anticoagulant treatment”. “Migraine should be considered a potent and persistent risk factor for most cardiovascular diseases” they say. “Ultimately, it will be important to determine whether prevention strategies in patients with migraine can reduce the burden of cardiovascular disease” they conclude.

“We now have plenty of evidence that migraine should be taken seriously as a strong cardiovascular risk-marker” but “action to reduce risk is long overdue,” argue Professor Tobias Kurth and colleagues at Universitätsmedizin Berlin and the University of Vermont in a linked editorial. “Unfortunately, funding for migraine research has been seriously neglected,” they say, and they call on public research agencies to “act quickly by investing in prospective studies to accomplish this goal.”

Abstract
Objective: To examine the risks of myocardial infarction, stroke (ischaemic and haemorrhagic), peripheral artery disease, venous thromboembolism, atrial fibrillation or atrial flutter, and heart failure in patients with migraine and in a general population comparison cohort.
Design: Nationwide, population based cohort study.
Setting: All Danish hospitals and hospital outpatient clinics from 1995 to 2013.
Participants: 51 032 patients with migraine and 510 320 people from the general population matched on age, sex, and calendar year.
Main outcome measures: Comorbidity adjusted hazard ratios of cardiovascular outcomes based on Cox regression analysis.
Results: Higher absolute risks were observed among patients with incident migraine than in the general population across most outcomes and follow-up periods. After 19 years of follow-up, the cumulative incidences per 1000 people for the migraine cohort compared with the general population were 25 v 17 for myocardial infarction, 45 v 25 for ischaemic stroke, 11 v 6 for haemorrhagic stroke, 13 v 11 for peripheral artery disease, 27 v 18 for venous thromboembolism, 47 v 34 for atrial fibrillation or atrial flutter, and 19 v 18 for heart failure. Correspondingly, migraine was positively associated with myocardial infarction (adjusted hazard ratio 1.49, 95% confidence interval 1.36 to 1.64), ischaemic stroke (2.26, 2.11 to 2.41), and haemorrhagic stroke (1.94, 1.68 to 2.23), as well as venous thromboembolism (1.59, 1.45 to 1.74) and atrial fibrillation or atrial flutter (1.25, 1.16 to 1.36). No meaningful association was found with peripheral artery disease (adjusted hazard ratio 1.12, 0.96 to 1.30) or heart failure (1.04, 0.93 to 1.16). The associations, particularly for stroke outcomes, were stronger during the short term (0-1 years) after diagnosis than the long term (up to 19 years), in patients with aura than in those without aura, and in women than in men. In a subcohort of patients, the associations persisted after additional multivariable adjustment for body mass index and smoking.
Conclusions: Migraine was associated with increased risks of myocardial infarction, ischaemic stroke, haemorrhagic stroke, venous thromboembolism, and atrial fibrillation or atrial flutter. Migraine may be an important risk factor for most cardiovascular diseases.

Authors
Kasper Adelborg, Szimonetta Komjáthiné Szépligeti, Louise Holland-Bill, Vera Ehrenstein, Erzsébet Horváth-Puhó, Victor W Henderson, Henrik Toft Sørensen

BMJ material
BMJ abstract
BMJ editorial


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