Abstract
Numerous data have pointed to an association between migraine and cardiovascular diseases. The majority of the available data have indicated that migraine with aura can be considered a risk factor for ischemic stroke, whereas migraine without aura cannot be reliably considered as such. High frequency of attacks and a recent onset of migraine have been related to an increased ischemic stroke risk. In addition, in young subjects with ischemic stroke migraine with aura represents an independent risk factor of overall recurrent vascular events and of recurrent ischemic stroke. Also the risk of transient ischemic attack seems to be increased in migraineurs, although this issue has not been extensively investigated. Several studies have also addressed the possible association between migraine and hemorrhagic stroke. Although the results of these individual studies were conflicting, their meta-analysis showed that migraine is associated with a 1.5-fold increase in the risk of hemorrhagic stroke (including intracerebral and subarachnoid hemorrhage). Some studies have identified migraine also as a possible risk factor for cardiac vascular events while others have yielded negative results. A meta-analysis did not show an increased risk of myocardial infarction in subjects with any migraine vs no migraine but subsequently, data has pointed to an association between any migraine with cardiac ischemic disease. Migraine has also been associated by some studies with vascular mortality and with vascular diseases in regions other than the brain and the heart. Several studies have also indicated that compared with nonmigraineurs, migraineurs have a higher burden of asymptomatic white matter brain lesions and, according to some studies, also infarct-like lesions at brain magnetic resonance. The mechanisms underlying the relationship between migraine and cardiovascular disease are still unclear. The possible explanation may rely on a peculiar vascular vulnerability of migraineurs that may contribute to the pathogenesis of migraine and, in the presence of some other unknown factors may also contribute, over time, to the development of cardiovascular disease. At the moment, there are no reliable features that may indicate which subjects, across the overall migraine population, will develop vascular events and so far, no drugs are recommended for the vascular prevention in migraineurs unless other clear indications are present. In general, the acute treatment and the secondary prevention measures of a patient with stroke who has a history of migraine do not differ from that of other stroke patients. There is currently no direct evidence to support that a migraine prophylactic treatment will reduce future stroke risk in secondary prevention.
Similar content being viewed by others
References
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
Collaborative Group for the Study of Stroke in Young Women. Oral contraceptives and stroke in young women: associated risk factors. JAMA. 1975;231:718–22.
Bigal ME, Kurth T, Santanello N, Buse D, Golden W, Robbins M, et al. Migraine and cardiovascular disease: a population-based study. Neurology. 2010;74:628–35.
Buring JE, Hebert P, Romero J, Kittross A, Cook N, Manson J, et al. Migraine and subsequent risk of stroke in the Physicians' Health Study. Arch Neurol. 1995;52:129–34.
Carolei A, Marini C, De Matteis G. History of migraine and risk of cerebral ischaemia in young adults. The Italian National Research Council Study Group on Stroke in the Young. Lancet. 1996;347:1503–6.
Chang CL, Donaghy M, Poulter N. Migraine and stroke in young women: case-control study. The World Health Organization Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. BMJ. 1999;318:13–8.
Donaghy M, Chang CL, Poulter N. On behalf of the European Collaborators of The World Health Organisation Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. Duration, frequency, recency, and type of migraine and the risk of ischaemic stroke in women of childbearing age. J Neurol Neurosurg Psychiatry. 2002;73:747–50.
Hall GC, Brown MM, Mo J, MacRae KD. Triptans in migraine: the risks of stroke, cardiovascular disease, and death in practice. Neurology. 2004;62:563–8.
Henrich JB, Horwitz RI. A controlled study of ischemic stroke risk in migraine patients. J Clin Epidemiol. 1989;42:773–80.
Kurth T, Slomke MA, Kase CS, Cook NR, Lee IM, Gaziano JM, et al. Migraine, headache, and the risk of stroke in women: a prospective study. Neurology. 2005;64:1020–6.
MacClellan LR, Giles W, Cole J, et al. Probable migraine with visual aura and risk of ischemic stroke: the Stroke Prevention in Young Women Study. Stroke. 2007;38:2438–45.
Tzourio C, Iglesias S, Hubert JB, et al. Migraine and risk of ischaemic stroke: a case-control study. BMJ. 1993;307:289–92.
Tzourio C, Tehindrazanarivelo A, Iglésias S, et al. Case-control study of migraine and risk of ischaemic stroke in young women. BMJ. 1995;310:830–3.
Stang PE, Carson AP, Rose KM, Mo J, Ephross SA, Shahar E, et al. Headache, cerebrovascular symptoms, and stroke: the Atherosclerosis Risk in Communities Study. Neurology. 2005;64:1573–7.
Etminan M, Takkouche B, Isorna FC, Samii A. Risk of ischaemic stroke in people with migraine: systematic review and meta-analysis of observational studies. BMJ. 2005;330:63.
Schürks M, Rist PM, Bigal ME, Buring JE, Lipton RB, Kurth T. Migraine and cardiovascular disease: systematic review and meta-analysis. BMJ. 2009;339:b3914.
Spector JT, Kahn SR, Jones MR, Jayakumar M, Dalal D, Nazarian S. Migraine headache and ischemic stroke risk: an updated meta-analysis. Am J Med. 2010;123:612–24.
Kurth T, Schürks M, Logroscino G, Buring JE. Migraine frequency and risk of cardiovascular disease in women. Neurology. 2009;73:581–8.
Kurth T, Gaziano JM, Cook NR, Bubes V, Logroscino G, Diener HC, et al. Migraine and risk of cardiovascular disease in men. Arch Intern Med. 2007;167:795–801.
Kurth T, Schürks M, Logroscino G, Gaziano JM, Buring JE. Migraine, vascular risk, and cardiovascular events in women: prospective cohort study. BMJ. 2008;337:a636.
Rist PM, Buring JE, Kase CS, Schürks M, Kurth T. Migraine and functional outcome from ischemic cerebral events in women. Circulation. 2010;122:2551–7.
Pezzini A, Grassi M, Lodigiani C, Patella R, Gandolfo C, Zini A, et al. on behalf of the Italian Project on Stroke in Young Adults (IPSYS) Investigators. Predictors of long-term recurrent vascular events after ischemic stroke at young age: the Italian Project on Stroke in Young Adults. Circulation. 2014; [In press]. This study addresses predictors of recurrent vascular events in young subjects with stroke and shows that migraine with aura is an independent predictor of vascular recurrences.
Carter KN, Anderson N, Jamrozik K, Hankey G, Anderson CS. Australasian co-operative research on subarachnoid haemorrhage study (ACROSS) group. Migraine and risk of subarachnoid haemorrhage: a population-based case-control study. J Clin Neurosci. 2005;12:534–7.
Schwartz SM, Petitti DB, Siscovick DS, Longstreth Jr WT, Sidney S, Raghunathan TE, et al. Stroke and use of low-dose oral contraceptives in young women: a pooled analysis of two US studies. Stroke. 1998;29:2277–84.
Kuo CY, Yen MF, Chen LS, et al. Increased risk of hemorrhagic stroke in patients with migraine: a population-based cohort study. PLoS One. 2013;8:e55253.
Kurth T, Kase CS, Schürks M, Tzourio C, Buring JE. Migraine and risk of haemorragic stroke in women: prospective cohort study. BMJ. 2010;341:c3659.
Sacco S, Ornello R, Ripa P, Pistoia F, Carolei A. Migraine and hemorrhagic stroke: a meta-analysis. Stroke. 2013;44:3032–8. This meta-analysis provides a summary of studies addressing the relationship between migraine with hemorrhagic stroke.
Mitchell P, Wang JJ, Currie J, Cumming RG, Smith W. Prevalence and vascular associations with migraine in older Australians. Aust N Z J Med. 1998;28:627–32.
Kurth T, Gaziano JM, Cook NR, Logroscino G, Diener HC, Buring JE. Migraine and risk of cardiovascular disease in women. JAMA. 2006;296:283–91.
Sternfeld B, Stang P, Sidney S. Relationship of migraine headaches to experience of chest pain and subsequent risk for myocardial infarction. Neurology. 1995;45:2135–42.
Velentgas P, Cole JA, Mo J, Sikes CR, Walker AM. Severe vascular events in migraine patients. Headache. 2004;44:642–51.
Wang YC, Lin CW, Ho YT, Huang YP, Pan SL. Increased risk of ischemic heart disease in young patients with migraine: a population-based, propensity score-matched, longitudinal follow-up study. Int J Cardiol. 2014;172:213–6.
Schürks M, Rist PM, Shapiro RE, Kurth T. Migraine and mortality: a systematic review and meta-analysis. Cephalalgia. 2011;31:1301–14.
Gudmundsson LS, Scher AI, Aspelund T, Eliasson JH, Johannsson M, Thorgeirsson G, et al. Migraine with aura and risk of cardiovascular and all-cause mortality in men and women: prospective cohort study. BMJ. 2010;341:c3966.
Rose KM, Carson AP, Sanford CP, et al. Migraine and other headaches: associations with Rose angina and coronary heart disease. Neurology. 2004;63:2233–9.
Ikeda K, Hirayama T, Iwamoto K, Takazawa T, Kawase Y, Yoshii Y, et al. Pulse wave velocity study in middle-aged migraineurs at low cardiovascular disease risk. Headache. 2011;51:1239–44.
Jurno ME, Chevtchouk L, Nunes AA, de Rezende DF, Jevoux Cda C, de Souza JA, et al. Ankle-brachial index, a screening for peripheral obstructive arterial disease, and migraine—a controlled study. Headache. 2010;50:626–30.
Rose KM, Wong TY, Carson AP, Couper DJ, Klein R, Sharrett AR. Migraine and retinal microvascular abnormalities: the Atherosclerosis Risk in Communities Study. Neurology. 2007;68:1694–700.
O’Keeffe S, Tsapatsaris N, Beetham Jr W. Association between Raynaud’s phenomenon and migraine in a random population of hospital employees. J Rheumatol. 1993;20:1187–8.
Pal B, Gibson C, Passmore J, Griffiths ID, Dick WC. A study of headaches and migraine in Sjogren’s syndrome and other rheumatic disorders. Ann Rheum Dis. 1989;48:312–6.
Tietjen GE, Gottwald L, Al-Qasmi MM, Gunda P, Khuder SA. Migraine is associated with livedo reticularis: a prospective study. Headache. 2002;42:263–7.
Appenzeller S, Costallat LT. Clinical implications of migraine in systemic lupus erythematosus: relation to cumulative organ damage. Cephalalgia. 2004;24:1024–30.
Bushnell CD, Jamison M, James AH. Migraines during pregnancy linked to stroke and vascular diseases: US population based case-control study. BMJ. 2009;338:b664.
Facchinetti F, Allais G, Nappi RE, D'Amico R, Marozio L, Bertozzi L, et al. Migraine is a risk factor for hypertensive disorders in pregnancy: a prospective cohort study. Cephalalgia. 2009;29:286–92.
Bashir A, Lipton RB, Ashina S, Ashina M. Migraine and structural changes in the brain. A systematic review and meta-analysis. Neurology. 2013;81:1260–8.
Hamedani AG, Rose KM, Peterlin BL, Mosley TH, Coker LH, Jack CR, et al. Migraine and white matter hyperintensities. The ARIC MRI study. Neurology. 2013;81:1308–13.
Kurth T, Mohamed S, Maillard P, Zhu YC, Chabriat H, Mazoyer B, et al. Headache, migraine, and structural brain lesions and function: population based Epidemiology of Vascular Ageing-MRI study. BMJ. 2011;342:c7357.
Monteith T, Gardener H, Rundek T, Dong C, Yoshita M, Elkind M, et al. Migraine, white matter hyperintensities, and subclinical brain infarction in a diverse community. Stroke: The Northern Manhattan Study; 2014 [In press].
Kruit MC, van Buchem MA, Hofman PA, Bakkers JT, Terwindt GM, Ferrari MD, et al. Migraine as a risk factor for subclinical brain lesions. JAMA. 2004;291:427–34.
Palm-Meinders IH, Koppen H, Terwindt GM, Launer LJ, Konishi J, Moonen JM, et al. Structural brain changes in migraine. JAMA. 2012;308:1889–97.
Rist PM, Dufouil C, Glymour MM, Tzourio C, Kurth T. Migraine and cognitive decline in the population-based EVA study. Cephalalgia. 2011;31:1291–300.
Kruit MC, Launer LJ, Ferrari MD, van Buchem MA. Infarcts in the posterior circulation territory in migraine: the population-based MRI CAMERA study. Brain. 2005;128:2068–77.
Scher AI, Gudmundsson LS, Sigurdsson S, Ghambaryan A, Aspelund T, Eiriksdottir G, et al. Migraine headache in middle age and late-life brain infarct. JAMA. 2009;301:2563–70.
Bogousslavsky J, Regli F, Van Melle G, Payot M, Uske A. Migraine stroke. Neurology. 1988;38:223–7.
Broderick JP, Swanson JW. Migraine-related strokes: clinical profile and prognosis in 20 patients. Arch Neurol. 1987;44:868–71.
Caplan LR. Migraine and vertebrobasilar ischemia. Neurology. 1991;41:55–61.
Milhaud D, Bogousslavsky J, van Melle G, Liot P. Ischemic stroke and active migraine. Neurology. 2001;57:1805–11.
Bigal ME, Kurth T, Hu H, Santanello N, Lipton RB. Migraine and cardiovascular disease: possible mechanisms of interaction. Neurology. 2009;72:1864–71.
Kurth T, Chabriat H, Bousser MG. Migraine and stroke: a complex association with clinical implications. Lancet Neurol. 2012;11:92–100.
Sacco S, Olivieri L, Bastianello S, Carolei A. Comorbid neuropathologies in migraine. J Headache Pain. 2006;7:222–30.
Sacco S, Cerone D, Carolei A. Comorbid neuropathologies in migraine: an update on cerebrovascular and cardiovascular aspects. J Headache Pain. 2008;9:237–48.
Pietrobon D, Moskowitz MA. Pathophysiology of migraine. Annu Rev Physiol. 2013;75:365–91.
Attwell D, Buchan AM, Charpak S, Lauritzen M, Macvicar BA, Newman EA. Glial and neuronal control of brain blood flow. Nature. 2010;468:232–43.
Lauritzen M, Skyhoj Olsen T, Lassen NA, Paulson OB. Changes in regional cerebral blood flow during the course of classic migraine attacks. Ann Neurol. 1983;13:633–41.
Dreier JP, Kleeberg J, Petzold G, Priller J, Windmüller O, Orzechowski HD, et al. Endothelin-1 potently induces Leão’s cortical spreading depression in vivo in the rat: a model for an endothelial trigger of migrainous aura? Brain. 2002;125:102–12.
Nozari A, Dilekoz E, Sukhotinsky I, Stein T, Eikermann-Haerter K, Liu C, et al. Microemboli may link spreading depression, migraine aura, and patent foramen ovale. Ann Neurol. 2010;67:221–9.
Sacco S, Ripa P, Grassi D, Pistoia F, Ornello R, Carolei A, et al. Peripheral vascular dysfunction in migraine: a review. J Headache Pain. 2013;14:80.
Sacco S, Degan D, Carolei A. Diagnostic criteria for CADASIL in the International Classification of Headache Disorders (ICHDII): are they appropriate? J Headache Pain. 2010;11:181–6.
Sacco S, Ripa P, Carolei A. Migraine attributed to genetic disorder: proposal of a new category. Cephalalgia. 2011;31:760–2.
Wessman M, Terwindt GM, Kaunisto MA, Palotie A, Ophoff RA. Migraine: a complex genetic disorder. Lancet Neurol. 2007;6:521–32.
Lacombe P, Oligo C, Domenga V, Tournier-Lasserve E, Joutel A. Impaired cerebral vasoreactivity in a transgenic mouse model of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy arteriopathy. Stroke. 2005;36:1053–8.
Lee JH, Eikermann-Haerter K, Joutel A, Moskowitz MA, Ayata C. Enlarged infarcts in mice expressing the archetypal NOTCH3 R90C CADASIL mutation. J Cereb Blood Flow Metab. 2009;29:S253–4.
Eikermann-Haerter K, Lee JH, Yuzawa I, et al. Migraine mutations increase stroke vulnerability by facilitating ischemic depolarizations. Circulation. 2012;125:335–45.
Chen TC, Leviton A, Edelstein S, Ellenberg JH. Migraine and other diseases in women of reproductive age. The influence of smoking on observed associations. Arch Neurol. 1987;44:1024–8.
Sacco S, Ricci S, Carolei A. Migraine and vascular diseases: potential implications for management. Cephalalgia. 2012;32:785–95.
Davis D, Gregson J, Willeit P, Stephan B, Al-Shahi Salman R, et al. Patent foramen ovale, ischemic stroke and migraine: systematic review and stratified meta-analysis of association studies. Neuroepidemiology. 2013;40:56–67.
Kurth T, Diener HC. Migraine and stroke: perspectives for stroke physicians. Stroke. 2012;43:3421–6.
Sacco S, Carolei A. Is migraine a modifiable risk factor for ischemic stroke? Potentially not. Am J Med. 2011;124:e9.
Diener HC, Gendolla A, Feuersenger A, Evers S, Straube A, Schumacher H, et al. Telmisartan in migraine prophylaxis: a randomized, placebo-controlled trial. Cephalalgia. 2009;29:921–7.
Schrader H, Stovner LJ, Helde G, Sand T, Bovim G. Prophylactic treatment of migraine with angiotensin converting enzyme inhibitor (lisinopril): randomised, placebo controlled, crossover study. BMJ. 2001;322:19–22.
Stovner LJ, Linde M, Gravdahl GB, Tronvik E, Aamodt AH, Sand T, et al. A comparative study of candesartan vs propranolol for migraine prophylaxis: a randomized, triple-blind, placebo- controlled, double cross-over study. Cephalalgia. 2014; [In press].
Tronvik E, Stovner LJ, Helde G, Sand T, Bovim G. Prophylactic treatment of migraine with an angiotensin II receptor blocker: a randomized controlled trial. JAMA. 2003;289:65–9.
Dahlöf B, Devereux RB, Kjeldsen SE, Julius S, Beevers G, de Faire U, et al. LIFE Study Group. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomized trial against atenolol. Lancet. 2002;359:995–1003.
Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med. 2000;342:145–53.
der Wammes-van Heijden EA, Rahimtoola H, Leufkens HG, Tijssen CC, Egberts AC. Risk of ischemic complications related to the intensity of triptan and ergotamine use. Neurology. 2006;67:1128–34.
Compliance with Ethics Guidelines
Conflict of Interest
Simona Sacco and Tobias Kurth declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Author information
Authors and Affiliations
Corresponding author
Additional information
This article is part of the Topical Collection on Stroke
Rights and permissions
About this article
Cite this article
Sacco, S., Kurth, T. Migraine and the Risk for Stroke and Cardiovascular Disease. Curr Cardiol Rep 16, 524 (2014). https://doi.org/10.1007/s11886-014-0524-1
Published:
DOI: https://doi.org/10.1007/s11886-014-0524-1