Migraine and cardiovascular disease: systematic review and meta-analysisBMJ 2009; 339 doi: https://doi.org/10.1136/bmj.b3914 (Published 27 October 2009) Cite this as: BMJ 2009;339:b3914
- Markus Schürks, instructor19,
- Pamela M Rist, doctoral student12,
- Marcelo E Bigal, director34,
- Julie E Buring, professor12,
- Richard B Lipton, professor356,
- Tobias Kurth, senior researcher1278
- 1Division of Preventive Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, 900 Commonwealth Avenue East, Boston, MA 02215-1204, USA
- 2Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA
- 3Department of Neurology, Albert Einstein College of Medicine, NY, USA
- 4Merck Research Laboratories, Whitehouse Station, NJ, USA
- 5Department of Epidemiology and Population Health, Albert Einstein College of Medicine, NY, USA
- 6Montefiore Headache Center, Bronx, NY, USA
- 7INSERM Unit 708—Neuroepidemiology, Paris, France
- 8Faculty of Medicine, University Pierre et Marie Curie, Paris, France
- 9Department of Neurology, University Hospital Essen, Germany
- Correspondence to: M Schürks
- Accepted 22 June 2009
Objective To evaluate the association between migraine and cardiovascular disease, including stroke, myocardial infarction, and death due to cardiovascular disease.
Design Systematic review and meta-analysis.
Data sources Electronic databases (PubMed, Embase, Cochrane Library) and reference lists of included studies and reviews published until January 2009.
Selection criteria Case-control and cohort studies investigating the association between any migraine or specific migraine subtypes and cardiovascular disease.
Review methods Two investigators independently assessed eligibility of identified studies in a two step approach. Disagreements were resolved by consensus. Studies were grouped according to a priori categories on migraine and cardiovascular disease.
Data extraction Two investigators extracted data. Pooled relative risks and 95% confidence intervals were calculated.
Results Studies were heterogeneous for participant characteristics and definition of cardiovascular disease. Nine studies investigated the association between any migraine and ischaemic stroke (pooled relative risk 1.73, 95% confidence interval 1.31 to 2.29). Additional analyses indicated a significantly higher risk among people who had migraine with aura (2.16, 1.53 to 3.03) compared with people who had migraine without aura (1.23, 0.90 to 1.69; meta-regression for aura status P=0.02). Furthermore, results suggested a greater risk among women (2.08, 1.13 to 3.84) compared with men (1.37, 0.89 to 2.11). Age less than 45 years, smoking, and oral contraceptive use further increased the risk. Eight studies investigated the association between migraine and myocardial infarction (1.12, 0.95 to 1.32) and five between migraine and death due to cardiovascular disease (1.03, 0.79 to 1.34). Only one study investigated the association between women who had migraine with aura and myocardial infarction and death due to cardiovascular disease, showing a twofold increased risk.
Conclusion Migraine is associated with a twofold increased risk of ischaemic stroke, which is only apparent among people who have migraine with aura. Our results also suggest a higher risk among women and risk was further magnified for people with migraine who were aged less than 45, smokers, and women who used oral contraceptives. We did not find an overall association between any migraine and myocardial infarction or death due to cardiovascular disease. Too few studies are available to reliably evaluate the impact of modifying factors, such as migraine aura, on these associations.
Contributors: MS and TK conceived and designed the study, analysed the data, and drafted the manuscript. MS, PMR, and TK acquired the data. All authors had full access to the data, take responsibility for the integrity of the data and the accuracy of the data analysis, interpreted the data, critically revised the draft for important intellectual content, and gave final approval of the version to be published. MS and TK reserved the final decision in writing and in the decision to submit the article for publication. MS and TK are guarantors.
Funding: This study was funded by an investigator initiated (TK) research grant from Merck (IISP-35437). The sponsor played no role in the study design or in the collection and analysis of the data.
Competing interests: MS has received an investigator initiated research grant from the Deutsche Forschungsgemeinschaft and honorariums from LEK Consulting for telephone surveys. MEB is a full time employee of Merck Research Laboratories; he has carried out research, been on the advisory board, or has been in the speaker’s bureau of several pharmaceutical companies that market drugs for migraine. JEB has received investigator initiated research funding and support from the National Institutes of Health and Dow Corning; research support for pills or packaging from Bayer Heath Care and the Natural Source Vitamin E Association; and an honorarium from Bayer for speaking engagements. RBL has consulted for, carried out studies funded by, or received lecture honorariums from Merck and other companies including Allergan, GlaxoSmithKline, Johnson and Johnson, Minster, and Neuralieve. He has stock options in Minster and Neuralieve. TK has received investigator initiated research funding from the National Institutes of Health, McNeil Consumer & Specialty Pharmaceuticals, Merck, and Wyeth Consumer Healthcare; he is a consultant to i3 Drug Safety and World Health Information Science Consultants, LLC, and he has received honorariums from Genzyme, Merck, and Pfizer for educational lectures.
Ethical approval: Not required.
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