Migraine appears to increase the risk for cardiovascular disease (CVD), including myocardial infarction (MI), ischemic and hemorrhagic stroke, venous thromboembolism (VTE), and atrial fibrillation or atrial flutter, new research shows.
During the first year after diagnosis, migraine was associated with an eightfold increased risk for stroke and an approximately twofold increased risk for MI, VTE, and atrial fibrillation or atrial flutter compared with matched general population controls.
The associations remained throughout the follow-up period and were stronger in patients with migraine aura than in those without and stronger in women than in men.
“Now, accumulating evidence supports that migraine should be considered as a risk factor for most cardiovascular disease, in both men and women,” lead author, Kasper Adelborg, MD, PhD, postdoctoral fellow, Department of Clinical Epidemiology, Aarhus University Hospital, Denmark, told Medscape Medical News.
“Although the absolute risk of cardiovascular diseases was low at the individual level, it translates into a substantial risk at the population level because migraine is a very common disease,” he said.
The study was published online January 31 in the BMJ.
Beyond MI and Stroke
“Migraine affects nearly 15% of the population or about one billion people worldwide” and is a “leading cause of disability” with a “considerable impact on qualify of life” and a “substantial burden on society,” the authors write.
“Previous studies have suggested a link between migraine and stroke, and migraine and myocardial infarction, particularly among women, while the link between migraine and other heart problems is less well known,” Adelborg commented.
Biological mechanisms that might account for an association with migraine and CVD are “likely multifactorial and different for the individual cardiovascular outcomes,” he said.
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, while another mechanism may involve migraine-associated immobilization, which in turn increases the risk of venous thromboembolism,” he said.
To improve the understanding of multiple cardiovascular conditions potentially associated with migraine, the authors examined not only the risk for MI and ischemic and hemorrhagic stroke but also the risk for peripheral artery disease (PAD), VTE, heart failure (HF), and atrial fibrillation or atrial flutter in patients with a first-time migraine diagnosis, as compared with the general population.
They also investigated whether the associations varied by aura status or sex.
The investigators conducted a population-based matched cohort study based on data from Danish administrative and medical registries that included all patients with a first-time primary or secondary diagnosis of migraine from January 1, 1995, to November 30, 2013.
They compared patients with migraine to a matched general population cohort (n = 51,032 and 510,320, respectively; median age at diagnosis, 35 years [range, 22 to 47 years]) matched for age, sex, and year of diagnosis. Most of the study population (71%) was female.
The researchers also examined other CVD risk factors, including diabetes, obesity, hyperlipidemia, hypercholesterolemia, hypertension, valvular heard disease, chronic obstructive pulmonary disease, renal failure, liver disease, cancer, alcohol-related disorders, and thyroid diseases.
Long-term Associations
After 19 years of follow-up, the cumulative incidences of MI, ischemic stroke, hemorrhagic stroke, PAD, VTE, atrial fibrillation or atrial flutter, and HF per 1000 were higher for people in the migraine cohort compared with the general population (25 vs 17 for MI, 45 vs 25 for ischemic stroke, 11 vs 6 for hemorrhagic stroke, 13 vs 11 for PAD, 27 vs 18 for VTE, 47 vs 34 for atrial fibrillation or atrial flutter, and 19 vs 18 for HF).
After the researchers adjusted for covariables, they found that migraine was associated with MI (adjusted hazard ratio [HR], 1.49; 95% confidence interval [CI], 1.36 – 1.64), ischemic stroke (HR, 2.26; 95% CI, 2.11 – 2.41), and hemorrhagic stroke (HR, 1.94; 95% CI, 1.68 – 2.23), as well as VTE (HR, 1.59; 95% CI, 1.45 – 1.74) and atrial fibrillation or atrial flutter (HR, 1.25; 95% CI, 1.16 – 1.36).
No association was found with PAD or HF.
The risk for CVD was highest during the first year, with an eightfold increased risk for stroke and an approximately twofold increased risk for MI, VTE, and atrial fibrillation or atrial flutter.
During more than 1 to 5 years as well as more than 5 to 19 years, the association remained with MI (1.5-fold), ischemic stroke (1.6- to 2.1-fold), hemorrhagic stroke (1.4-fold), VTE (1.3- to 2.0-fold), and atrial fibrillation or atrial flutter (1.2-fold).
An analysis of aura status, with data available for 59% of patients with migraine, found that migraine with aura was associated with long-term risks for MI, ischemic and hemorrhagic stroke, and VTE.
Most associations persisted even in nonusers of nonsteroidal anti-inflammatory drugs and in nonusers of migraine-specific drugs.
“Here, we found several interesting findings,” Adelborg reported.
“In general, the associations were strongest in the first year after diagnosis but persisted in the long term, up to 19 years after diagnosis.”
Additionally, “most associations applied both to migraine patients with aura — meaning, warning signs before a migraine, such as seeing flashing lights — and in those without aura, in both women and men.”
He acknowledged being “surprised by the results.”
He cited several strengths of the study, including the “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.”
“First Step”
Commenting on the study for Medscape Medical News, Tobias Kurth, MD, ScD, professor of Public Health and Epidemiology and head of the Institute of Public Health at Charité–Universitätsmediz, Berlin, Germany, who was not involved with the study, said that it “adds to other studies that have linked migraine with cardiovascular disease events.”
In particular, “what this study adds are more outcomes on the cardiovascular and venous sides, especially heart flutter and venous thromboembolism, which have not been linked as clearly before,” said Kurth, coauthor of an accompanying editorial.
This study is a “first step” in taking action to reduce CV risk, he noted.
But “it is always difficult to derive consequences from one prospective study” and “we do not have information regarding what specific action can be taken for patients with migraine to reduce the risk, beyond normal recommendations to reduce other cardiovascular risk factors, such as addressing hypertension, smoking, and high cholesterol.”
Adelborg agreed, adding, “We need data to inform the development of clinical recommendations and strategies that reduce the risk of cardiovascular disease for patients with migraine.”
Aarhus University and the Program for Clinical Research Infrastructure (PROCRIN), established by the Lundbeck Foundation and the Novo Nordisk Foundation, funded the study. The authors have disclosed no relevant financial relationships. Kurth reports he is employed by the Charité–Universitätsmedizin Berlin, Germany. He has provided methodological expertise for CoLucid and Amgen, for which the Charité–Universitätsmedizin has received unrestricted funds. He has received an honorarium from Novartis for a lecture on neuroepidemiology at a neuroscientific meeting and travel support from the International Headache Society to attend board meetings. He has also received honoraria for editorial services to the BMJ. The disclosures of his coauthors are listed on the original editorial.
BMJ. Published online January 31, 2017. Full text, Editorial
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