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      Migraine with aura and risk of cardiovascular and all cause mortality in men and women: prospective cohort study

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          Abstract

          Objective To estimate whether migraine in mid-life is associated with mortality from cardiovascular disease, other causes, and all causes.

          Design Population based cohort study.

          Setting Reykjavik, Iceland.

          Participants 18 725 men and women, born 1907-35 and living in Reykjavik and adjacent communities.

          Main outcome measures Mortality from cardiovascular disease, non-cardiovascular disease, and all causes. Questionnaires and clinical measures were obtained in mid-life (mean age 53, range 33-81) in the Reykjavik Study (1967-91). Headache was classified as migraine without aura, migraine with aura, or non-migraine headache. Median follow-up was 25.9 years (0.1-40.2 years), with 470 990 person years and 10 358 deaths: 4323 from cardiovascular disease and 6035 from other causes. We used Cox regression to estimate risk of death in those with migraine compared with others, after adjusting for baseline risk factors.

          Results People with migraine with aura were at increased risk of all cause mortality (adjusted (for sex and multivariables) hazard ratio 1.21, 95% confidence interval 1.12 to 1.30) and mortality from cardiovascular disease (1.27, 1.13 to 1.43) compared with people with no headache, while those with migraine without aura and non-migraine headache were not. Further examination of mortality from cardiovascular disease shows that people with migraine with aura were at increased risk of mortality from coronary heart disease (1.28, 1.11 to 1.49) and stroke (1.40, 1.10 to 1.78). Women with migraine with aura were also at increased risk of mortality from non-cardiovascular disease (1.19, 1.06 to 1.35).

          Conclusions Migraine with aura is an independent risk factor for cardiovascular and all cause mortality in men and women. The risk of mortality from coronary heart disease and stroke mortality is modestly increased in people with migraine, particularly those with aura.

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          Most cited references26

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          The International Classification of Headache Disorders: 2nd edition.

          (2004)
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            The global burden of headache: a documentation of headache prevalence and disability worldwide.

            This study, which is a part of the initiative 'Lifting The Burden: The Global Campaign to Reduce the Burden of Headache Worldwide', assesses and presents all existing evidence of the world prevalence and burden of headache disorders. Population-based studies applying International Headache Society criteria for migraine and tension-type headache, and also studies on headache in general and 'chronic daily headache', have been included. Globally, the percentages of the adult population with an active headache disorder are 46% for headache in general, 11% for migraine, 42% for tension-type headache and 3% for chronic daily headache. Our calculations indicate that the disability attributable to tension-type headache is larger worldwide than that due to migraine. On the World Health Organization's ranking of causes of disability, this would bring headache disorders into the 10 most disabling conditions for the two genders, and into the five most disabling for women.
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              Migraine and cardiovascular disease: systematic review and meta-analysis

              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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                Author and article information

                Contributors
                Role: doctoral student
                Role: associate professor
                Role: associate professor
                Role: neurologist
                Role: professor
                Role: professor
                Role: senior investigator
                Role: professor
                Journal
                BMJ
                bmj
                BMJ : British Medical Journal
                BMJ Publishing Group Ltd.
                0959-8138
                1468-5833
                2010
                2010
                24 August 2010
                : 341
                : c3966
                Affiliations
                [1 ]Department of Pharmacology and Toxicology, University of Iceland, Hagi Hofsvallagata 53, IS-107 Reykjavik, Iceland
                [2 ]Department of Preventive Medicine and Biometrics, Uniformed Services University, Bethesda, MD, USA
                [3 ]Icelandic Heart Association, Holtasmara 1, IS-201 Kopavogur, Iceland
                [4 ]University of Iceland, Reykjavik, Iceland
                [5 ]Reykjalundur Rehabilitation Centre, Mosfellsbær, Iceland
                [6 ]Landspitali University Hospital, Reykjavik, Iceland
                [7 ]Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, Bethesda, MD, USA
                Author notes
                Correspondence to: L S Gudmundsson lsg@ 123456hi.is , V Gudnason v.gudnason@ 123456hjarta.is
                Article
                gudl760348
                10.1136/bmj.c3966
                2927696
                20736269
                fcb34ba8-762f-4999-8ebe-db48da8efac6
                © Gudmundsson et al 2010

                This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/2.0/ and http://creativecommons.org/licenses/by-nc/2.0/legalcode.

                History
                : 12 July 2010
                Categories
                Research
                Epidemiologic Studies
                Drugs: Cardiovascular System
                Headache (Including Migraine)
                Pain (Neurology)
                Stroke
                Ischaemic Heart Disease

                Medicine
                Medicine

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