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      Migraine and the risk of cardiovascular and cerebrovascular events: a meta-analysis of 16 cohort studies including 1 152 407 subjects

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          Abstract

          Objectives

          To perform an updated meta-analysis to evaluate the long-term cardiovascular and cerebrovascular outcomes among migraineurs.

          Setting

          A meta-analysis of cohort studies performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

          Data sources

          The MEDLINE, Web of Science and Cochrane Central Register of Controlled Trials databases were searched for relevant articles.

          Participants

          A total of 16 cohort studies (18 study records) with 394 942 migraineurs and 757 465 non-migraineurs were analysed.

          Primary and secondary outcome measures

          Major adverse cardiovascular and cerebrovascular events (MACCE), stroke (ie, ischaemic, haemorrhagic or non-specified), myocardial infarction (MI) and all-cause mortality. The outcomes were reported at the longest available follow-up.

          Data analysis

          Summary-adjusted hazard ratios (HR) were calculated by random-effects Der-Simonian and Liard model. The risk of bias was assessed by the Newcastle-Ottawa Scale.

          Results

          Migraine was associated with a higher risk of MACCE (adjusted HR 1.42, 95% confidence interval [CI] 1.26 to 1.60, P<0.001, I 2=40%) driven by a higher risk of stroke (adjusted HR 1.41, 95% CI 1.25 to 1.61, P<0.001, I 2=72%) and MI (adjusted HR 1.23, 95% CI 1.03 to 1.43, P=0.006, I 2=59%). There was no difference in the risk of all-cause mortality (adjusted HR 0.93, 95% CI 0.78 to 1.10, P=0.38, I 2=91%), with a considerable degree of statistical heterogeneity between the studies. The presence of aura was an effect modifier for stroke (adjusted HR aura 1.56, 95% CI 1.30 to 1.87 vs adjusted HR no aura 1.11, 95% CI 0.94 to 1.31, P interaction=0.01) and all-cause mortality (adjusted HR aura 1.20, 95% CI 1.12 to 1.30 vs adjusted HR no aura 0.96, 95% CI 0.86 to 1.07, P interaction<0.001).

          Conclusion

          Migraine headache was associated with an increased long-term risk of cardiovascular and cerebrovascular events. This effect was due to an increased risk of stroke (both ischaemic and haemorrhagic) and MI. There was a moderate to severe degree of heterogeneity for the outcomes, which was partly explained by the presence of aura.

          PROSPERO registration number

          CRD42016052460.

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          Most cited references53

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          Pathophysiology of migraine.

          Daniela Pietrobon, Michael A. Moskowitz (2013)
          Migraine is a collection of perplexing neurological conditions in which the brain and its associated tissues have been implicated as major players during an attack. Once considered exclusively a disorder of blood vessels, compelling evidence has led to the realization that migraine represents a highly choreographed interaction between major inputs from both the peripheral and central nervous systems, with the trigeminovascular system and the cerebral cortex among the main players. Advances in in vivo and in vitro technologies have informed us about the significance to migraine of events such as cortical spreading depression and activation of the trigeminovascular system and its constituent neuropeptides, as well as about the importance of neuronal and glial ion channels and transporters that contribute to the putative cortical excitatory/inhibitory imbalance that renders migraineurs susceptible to an attack. This review focuses on emerging concepts that drive the science of migraine in both a mechanistic direction and a therapeutic direction.
          Article 0 comments Cited 209 times – based on 0 reviews     Review now
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            Migraine and cardiovascular disease: systematic review and meta-analysis

            Markus Schürks, Pamela M Rist, Marcelo E. Bigal … (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.
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              Migraine headache and ischemic stroke risk: an updated meta-analysis.

              June Spector, Susan R. Kahn, Miranda R. Jones … (2010)
              Observational studies, including recent large cohort studies that were unavailable for prior meta-analysis, have suggested an association between migraine headache and ischemic stroke. We performed an updated meta-analysis to quantitatively summarize the strength of association between migraine and ischemic stroke risk. We systematically searched electronic databases, including MEDLINE and EMBASE, through February 2009 for studies of human subjects in the English language. Study selection using a priori selection criteria, data extraction, and assessment of study quality were conducted independently by reviewer pairs using standardized forms. Twenty-one (60%) of 35 studies met the selection criteria, for a total of 622,381 participants (13 case-control, 8 cohort studies) included in the meta-analysis. The pooled adjusted odds ratio of ischemic stroke comparing migraineurs with nonmigraineurs using a random effects model was 2.30 (95% confidence interval [CI], 1.91-2.76). The pooled adjusted effect estimates for studies that reported relative risks and hazard ratios, respectively, were 2.41 (95% CI, 1.81-3.20) and 1.52 (95% CI, 0.99-2.35). The overall pooled effect estimate was 2.04 (95% CI, 1.72-2.43). Results were robust to sensitivity analyses excluding lower quality studies. Migraine is associated with increased ischemic stroke risk. These findings underscore the importance of identifying high-risk migraineurs with other modifiable stroke risk factors. Future studies of the effect of migraine treatment and modifiable risk factor reduction on stroke risk in migraineurs are warranted. Copyright 2010 Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                Journal ID (nlm-ta): BMJ Open
                Journal ID (iso-abbrev): BMJ Open
                Journal ID (hwp): bmjopen
                Journal ID (publisher-id): bmjopen
                Title: BMJ Open
                Publisher: BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                ISSN (Electronic): 2044-6055
                Publication date Collection: 2018
                Publication date (Electronic): 27 March 2018
                Volume: 8
                Issue: 3
                Electronic Location Identifier: e020498
                Affiliations
                [1 ] departmentDepartment of Medicine, Division of Cardiovascular Medicine , University of Florida , Gainesville, Florida, USA
                [2 ] departmentDepartment of Medicine, Division of Cardiovascular Medicine , University of Iowa Carver College of Medicine , Iowa City, Iowa, USA
                [3 ] Heart and Vascular Institute, University of Pittsburgh , Pittsburgh, Pennsylvania, USA
                [4 ] departmentDepartment of Medicine, Division of Cardiovascular Medicine , University of Arkansas for Medical Sciences , Little Rock, Arkansas, USA
                [5 ] departmentDepartment of Cardiovascular Medicine , Jefferson University Hospital/Christiana Care Health System , Newark, Delaware, USA
                [6 ] departmentDepartment of Health Services Research, Management, and Policy , College of Public Health, University of Florida , Gainesville, Florida, USA
                Author notes
                [Correspondence to ] Dr Islam Y Elgendy; iyelgendy@ 123456gmail.com
                Author information
                http://orcid.org/0000-0003-2459-5195
                http://orcid.org/0000-0001-6859-4616
                http://orcid.org/0000-0001-9853-7591
                Article
                Publisher ID: bmjopen-2017-020498
                DOI: 10.1136/bmjopen-2017-020498
                PMC ID: 5875642
                PubMed ID: 29593023
                SO-VID: 52a40fcb-63ff-4dd9-ae1a-5822cd6dcf40
                Copyright © © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
                License:

                This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

                History
                Date received : 07 November 2017
                Date revision received : 20 December 2017
                Date accepted : 23 January 2018
                Categories
                Subject: Cardiovascular Medicine
                Subject: Research
                Subject: 1506
                Subject: 1683
                Custom metadata
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                ScienceOpen disciplines: Medicine
                Keywords: cardiac epidemiology,myocardial infarction,migraine,stroke
                Data availability:
                ScienceOpen disciplines: Medicine
                Keywords: cardiac epidemiology, myocardial infarction, migraine, stroke

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