By Seema Gupta, MD, MSPH

Clinical Assistant Professor, Department of Family and Community Health, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV

Dr. Gupta reports no financial relationships relevant to this field of study.

SYNOPSIS: A large, prospective cohort study in women with more than two decades of follow-up indicated a consistent link between migraine and cardiovascular disease events, including cardiovascular mortality.

SOURCE: Kurth T, Winter AC, Eliassen AH, et al. Migraine and risk of cardiovascular disease in women: Prospective cohort study. BMJ 2016;353:i2610.

Migraine is a widely prevalent and disabling primary headache disorder. Globally, it is ranked as the third most common disorder and seventh highest specific cause of disability.1 In the United States, migraine headaches affect roughly one out of every seven Americans annually, with more than twice the prevalence in women.2 Current evidence supports an association between migraine, specifically migraine with aura, and ischemic, as well as, to a lesser extent, hemorrhagic stroke risk.3 The risk is higher for women, young people, and those who suffer from frequent headaches. Smoking habits and oral contraceptives, especially together, also increase stroke risk. However, while potential pathways for a cardiovascular disease event in migraine sufferers can be hypothesized, none of the postulated mechanisms has been confirmed as a pathophysiological explanation linking stroke and migraine. Nevertheless, it is possible that in migraineurs, the same underlying mechanism(s) may be responsible for other types of cardiovascular events, including ischemic heart disease and cardiovascular death.4 Because of its high socioeconomic and personal effects, such an association could present significant global public health implications.

Kurth et al conducted a large, prospective cohort study among Nurses’ Health Study II participants. They analyzed data from 115,541 enrolled women who were 25-42 years of age and free from angina and cardiovascular disease. Researchers followed participants from 1989-2011. The primary outcome of the study was major cardiovascular disease, a combined endpoint of myocardial infarction, stroke, or fatal cardiovascular disease.

Researchers observed that 17,531 participants reported a physician’s diagnosis of migraine at baseline in 1989. An additional 6,389 women newly reported a physician’s diagnosis on subsequent questionnaires and were classified as experiencing migraine during follow-up. During 20 years of follow-up, 1,329 major cardiovascular disease events occurred, and 223 women died from cardiovascular disease. After adjustment for potential confounding factors, researchers found that migraine was associated with an increased risk for major cardiovascular disease (hazard ratio [HR], 1.50; 95% confidence interval [CI], 1.33-1.69), myocardial infarction (HR, 1.39; CI, 1.18-1.64), stroke (HR, 1.62; CI, 1.37-1.92), and angina/coronary revascularization procedures (HR, 1.73; CI, 1.29-2.32) compared with women without migraine. Furthermore, migraine was found to be associated with a significantly increased risk for cardiovascular disease mortality (HR, 1.37; CI, 1.02-1.83). This association was similar across subgroups of women, including subgroups defined by age, smoking status, hypertension, postmenopausal hormone therapy, and oral contraceptive use.

COMMENTARY

When compared to women who did not suffer from migraines, study results demonstrated that women who reported a migraine were at greater risk for major cardiovascular disease, including heart attacks, strokes, and angina/coronary revascularization procedures. Although all the findings may not be new, they certainly strengthen the evidence supporting migraine as a risk factor for vascular disorders beyond the brain. Migraine already has been known to be associated with a roughly twofold increase in the risk of ischemic stroke and a 1.5-fold increase in the risk of hemorrhagic stroke.5 With the presence of other risk factors, such as smoking, hyperlipidemia, or the use of oral contraceptives, this risk is further elevated in women experiencing migraines. Although Kurth et al did not ask if participants experienced an aura, these findings, which included a higher risk for cardiovascular mortality, are noteworthy. While the risk may be small at the level of the individual patient, it is significant at a population level because of the wide prevalence of migraines.

Therefore, these findings really should make clinicians consider adding migraine as perhaps an important risk marker for cardiovascular disease, at least in women. Since some patients presenting with migraines may be subject to lifelong preventive pharmacological therapy, it also is important to consider the role of cardiovascular disease in such patients and how that may interact with other risk factors. Furthermore, future research should evaluate the complex relationship of migraine with other cardiovascular risk factors as well as the role of preventive therapies in possible reduction of cardiovascular events in migraine sufferers.

The prudent clinical next step may be to understand that migraine could be a potential risk factor for cardiovascular disease. Optimizing management of existing cardiovascular risk factors remains the most judicious approach until investigators conduct more research.

REFERENCES

  1. Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia 2013;33:629-808.
  2. Burch RC, Loder S, Loder E, Smitherman TA. The prevalence and burden of migraine and severe headache in the United States: Updated statistics from government health surveillance studies. Headache 2015;55:21-34.
  3. de Falco FA, de Falco A. Migraine with aura: Which patients are most at risk of stroke? Neurol Sci 2015;36(Suppl 1):57-60.
  4. Kurth T, Gaziano JM, Cook NR, et al. Migraine and risk of cardiovascular disease in women. JAMA 2006;296:283-291.
  5. Lee MJ, Lee C, Chung CS. The migraine-stroke connection. J Stroke 2016;18:146-156.