In the first year after diagnosis, migraine headaches may be an important risk factor for several cardiovascular diseases, particularly stroke, and these associations may be stronger in patients with migraine with auras and women, according to a study recently published in The BMJ.
The associations between migraine and ischemic stroke (IS) and myocardial infarction (MI) are well documented. Less is known about the possible associations between migraine and other cardiovascular diseases.
“Around one billion people worldwide are affected by migraine. Migraine has considerable impact on quality of life and imposes a substantial burden on society. Migraine is primarily a headache disorder, but previous studies have suggested a link between migraine and stroke and MI, particularly among women, while the link between migraine and other heart problems is less well known,” lead author Kasper Adelborg, MD, PhD, postdoctoral fellow, Department of Clinical Epidemiology, Aarhus University Hospital, Denmark, told MDLinx.
“In this large, register-based Danish study published in The BMJ, we confirmed that migraine is associated with increased risks of stroke and MI, but we also found that migraine was associated with increased risks of other cardiovascular diseases (specifically, venous thromboembolism [VT] and atrial fibrillation [AF]). Migraine was not associated with increased risks of heart failure (HF) or peripheral artery disease (PAD),” he added.
In this nationwide, population-based cohort study, Dr. Adelborg and colleagues included 51,032 patients with a first-time primary or secondary diagnosis of migraine from the Danish National Patient Registry (median age at diagnosis: 35 years; 71% women) between 1995 and 2013. The researchers compared the patients with 510,320 subjects from the general population who were matched in age, sex, and calendar year.
Researchers assessed cardiovascular risk factors in all patients, including diabetes, obesity, hyperlipidemia, hypercholesterolemia, hypertension, valvular heart disease, chronic obstructive pulmonary disease, renal failure, liver disease, cancer, alcoholism-related disorders, and thyroid disease.
They found that cardiovascular risk factors and comorbidity at index date were slightly higher in patients with migraine, and that patients with migraine had higher absolute risks for most of these outcomes.
After 19 years of follow-up, the cumulative incidences (per 1,000 people) in the migraine cohort compared with the general population were:
- MI: 25 vs 17
- IS: 45 vs 25
- Hemorrhagic stroke (HS): 11 vs 6
- PAD: 13 vs 11
- VT: 27 vs 18
- AF or atrial flutter: 47 vs 34
- HF: 19 vs 18
Dr. Adelborg and colleagues also found a positive association between migraine and MI (adjusted HR: 1.49; 95% CI: 1.36-1.64), IS (adjusted HR: 2.26; 95% CI: 2.11-2.41), HS (adjusted HR: 1.94; 95% CI: 1.68-2.23), VT (adjusted HR: 1.59; 95% CI: 1.45-1.74), and AF or atrial flutter (adjusted HR: 1.25; 95% CI: 1.16-1.36).
They found no meaningful associations, however, between migraine and PAD (adjusted HR: 1.12; 95% CI: 0.96-1.30) or HF (adjusted HR: 1.04; 95% CI: 0.93-1.16).
In patients with aura, these associations were stronger in the short-term after diagnosis (years 0-1) than in the long-term (up to 19 years) compared with those without aura, and in women compared with men.
The risk of cardiovascular disease was highest in the first year, with an 8-fold increase risk of both IS and HS, and an approximately 2-fold increased risk of MI, VT, and AF or atrial flutter.
“In general, the associations were strongest in the first year after diagnosis but persisted in the long term (up to 19 years after diagnosis). Most associations applied to both migraine patients with aura (warning signs before a migraine, such as seeing flashing lights) and in those without aura, and in both women and in men,” said Dr. Adelborg.
Why are migraine and cardiovascular disease seemingly so closely linked?
According to Dr. Adelborg, “The underlying mechanisms are likely multifactorial and different for the individual cardiovascular outcomes. For example, one potential mechanism may involve vasospasm in the cerebral arteries leading to migraine, which at the same time may increase the risk of stroke. Another mechanism may involve migraine-associated immobilization, which in turn increases the risk of VT.”
This recent study stands out for several reasons, noted Dr. Adelborg.
“In contrast to most previous studies, our study had a very large sample size and an age- and sex- matched comparison cohort from the general population, which allowed us to put migraine in a population context and to perform several subgroup analyses,” he said.
For clinicians, the message is clear, he added.
“Now, accumulating evidence supports that migraine should be considered as a risk factor for most cardiovascular diseases in both men and women. Although the absolute risks of cardiovascular diseases were low at the individual level, it translates into a substantial increase in risk at the population level, because migraine is a very common disease.
“Establishing the link between migraine and cardiovascular risk was an important first step. Now, we need data to inform the development of clinical recommendations and strategies that reduce the risk of cardiovascular disease for patients with migraine. For example, current migraine guidelines do not recommend use of anticoagulant treatment with aspirin and clopidogrel in the prophylaxis of migraine, but future studies should address whether patients at particularly high risk of cardiovascular diseases would benefit from anticoagulant treatment. Additionally, it will be important to determine whether prevention strategies in patients with migraine can reduce the burden of cardiovascular disease in patients with this common disorder,” Dr. Adelborg concluded.
This study was funded by Aarhus University and the Program for Clinical Research Infrastructure (PROCRIN), established by the Lundbeck Foundation and the Novo Nordisk Foundation.