Association of Migraine With Aura and Other Risk Factors With Cardiovascular Disease in Women | Cardiology | JN Learning | AMA Ed Hub [Skip to Content]
[Skip to Content Landing]

Association of Migraine With Aura and Other Risk Factors With Incident Cardiovascular Disease in Women

Educational Objective
To understand cardiovascular risks associated with migraine.
1 Credit CME
Key Points

Question  Is there an association between migraine with aura and cardiovascular disease (CVD) incidence rates in women, relative to that of other major vascular risk factors?

Findings  In this cohort study that included 27 858 female health professionals aged at least 45 years, the adjusted incidence rate of major CVD was 3.36 per 1000 person-years for women who reported migraine with aura and 2.11 per 1000 person-years for women who reported migraine without aura or no migraine, a difference that was statistically significant.

Meaning  Among female health professionals aged at least 45 years, self-reported migraine with aura was associated with increased incidence rates of CVD, but the clinical importance of this finding remains to be determined.

Abstract

Importance  Migraine with aura is known to increase the risk of cardiovascular disease (CVD). The absolute contribution of migraine with aura to CVD incidence in relation to other CVD risk factors remains unclear.

Objective  To estimate the CVD incidence rate for women with migraine with aura relative to women with other major vascular risk factors.

Design, Setting, and Participants  Female health professionals in the US (the Women’s Health Study cohort) with lipid measurements and no CVD at baseline (1992-1995) were followed up through December 31, 2018.

Exposures  Self-reported migraine with aura compared with migraine without aura or no migraine at baseline.

Main Outcomes and Measures  The primary outcome was major CVD (first myocardial infarction, stroke, or CVD death). Generalized modeling procedures were used to calculate multivariable-adjusted incidence rates for major CVD events by risk factor status that included all women in the cohort.

Results  The study population included 27 858 women (mean [SD] age at baseline, 54.7 [7.1] years), among whom 1435 (5.2%) had migraine with aura and 26 423 (94.8%) did not (2177 [7.8%] had migraine without aura and 24 246 [87.0%] had no migraine in the year prior to baseline). During a mean follow-up of 22.6 years (629 353 person-years), 1666 major CVD events occurred. The adjusted incidence rate of major CVD per 1000 person-years was 3.36 (95% CI, 2.72-3.99) for women with migraine with aura vs 2.11 (95% CI, 1.98-2.24) for women with migraine without aura or no migraine (P < .001). The incidence rate for women with migraine with aura was significantly higher than the adjusted incidence rate among women with obesity (2.29 [95% CI, 2.02-2.56]), high triglycerides (2.67 [95% CI, 2.38-2.95]), or low high-density lipoprotein cholesterol (2.63 [95% CI, 2.33-2.94]), but was not significantly different from the rates among those with elevated systolic blood pressure (3.78 [95% CI, 2.76-4.81]), high total cholesterol (2.85 [95% CI, 2.38-3.32]), or family history of myocardial infarction (2.71 [95% CI, 2.38-3.05]). Incidence rates among women with diabetes (5.76 [95% CI, 4.68-6.84]) or who currently smoked (4.29 [95% CI, 3.79-4.79]) were significantly higher than those with migraine with aura. The incremental increase in the incidence rate for migraine with aura ranged from 1.01 additional cases per 1000 person-years when added to obesity to 2.57 additional cases per 1000 person-years when added to diabetes.

Conclusions and Relevance  In this study of female health professionals aged at least 45 years, women with migraine with aura had a higher adjusted incidence rate of CVD compared with women with migraine without aura or no migraine. The clinical importance of these findings, and whether they are generalizable beyond this study population, require further research.

Sign in to take quiz and track your certificates

Buy This Activity

JN Learning™ is the home for CME and MOC from the JAMA Network. Search by specialty or US state and earn AMA PRA Category 1 CME Credit™ from articles, audio, Clinical Challenges and more. Learn more about CME/MOC

CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.

Article Information

Corresponding Author: Tobias Kurth, MD, ScD, Institute of Public Health, Charité – Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany (tobias.kurth@charite.de).

Accepted for Publication: April 18, 2020.

Author Contributions: Drs Kurth and Bubes had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Kurth.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Kurth, Kotler, Bubes.

Critical revision of the manuscript for important intellectual content: Kurth, Rist, Ridker, Bubes, Buring.

Statistical analysis: Kurth, Kotler, Bubes.

Administrative, technical, or material support: Ridker, Bubes.

Supervision: Kurth, Ridker.

Conflict of Interest Disclosures: Dr Kurth reported receiving personal fees from Eli Lilly, Newsenselab, CoLucid, Total, Novartis, and Daiichi Sankyo and grants from Amgen during the conduct of the study and personal fees from BMJ outside the submitted work. Dr Rist reported receiving grants from the National Heart, Lung, and Blood Institute, Brigham and Women's Hospital, and Biogen during the conduct of the study and personal fees from the American Heart Association outside the submitted work. Dr Ridker reported receiving grants from Novartis and Kowa and personal fees from Inflazome, Corvidia, Johnson & Johnson, and Amarin outside the submitted work. Dr Buring reported receiving grants from the National Institutes of Health during the conduct of the study. No other disclosures were reported.

Funding/Support: The Women’s Health Study is funded by grants from the National Cancer Institute (CA047988 and UM1 CA182913) and the National Heart, Lung, and Blood Institute (HL043851, HL080467, and HL099355). Dr Rist is supported by a Career Development Award from the National Heart, Lung, and Blood Institute (K01 HL128791).

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

References
1.
Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders. 3rd ed. Cephalalgia; 2018.
2.
Charles  A , Hansen  JM .  Migraine aura: new ideas about cause, classification, and clinical significance.   Curr Opin Neurol. 2015;28(3):255-260. doi:10.1097/WCO.0000000000000193PubMedGoogle ScholarCrossref
3.
Mahmoud  AN , Mentias  A , Elgendy  AY ,  et al.  Migraine and the risk of cardiovascular and cerebrovascular events: a meta-analysis of 16 cohort studies including 1 152 407 subjects.   BMJ Open. 2018;8(3):e020498. doi:10.1136/bmjopen-2017-020498PubMedGoogle Scholar
4.
Adelborg  K , Szépligeti  SK , Holland-Bill  L ,  et al.  Migraine and risk of cardiovascular diseases: Danish population based matched cohort study.   BMJ. 2018;360:k96. doi:10.1136/bmj.k96PubMedGoogle ScholarCrossref
5.
Hippisley-Cox  J , Coupland  C , Brindle  P .  Development and validation of QRISK3 risk prediction algorithms to estimate future risk of cardiovascular disease: prospective cohort study.   BMJ. 2017;357:j2099. doi:10.1136/bmj.j2099PubMedGoogle ScholarCrossref
6.
Liman  TG , Neeb  L , Rosinski  J ,  et al.  Peripheral endothelial function and arterial stiffness in women with migraine with aura: a case-control study.   Cephalalgia. 2012;32(6):459-466. doi:10.1177/0333102412444014PubMedGoogle ScholarCrossref
7.
Winsvold  BS , Bettella  F , Witoelar  A ,  et al; International Headache Genetics Consortium.  Shared genetic risk between migraine and coronary artery disease: a genome-wide analysis of common variants.   PLoS One. 2017;12(9):e0185663. doi:10.1371/journal.pone.0185663PubMedGoogle Scholar
8.
Tietjen  GE , Khubchandani  J , Herial  N ,  et al.  Migraine and vascular disease biomarkers: a population-based case-control study.   Cephalalgia. 2018;38(3):511-518. doi:10.1177/0333102417698936PubMedGoogle ScholarCrossref
9.
Sacco  S , Kurth  T .  Migraine and the risk for stroke and cardiovascular disease.   Curr Cardiol Rep. 2014;16(9):524. doi:10.1007/s11886-014-0524-1PubMedGoogle ScholarCrossref
10.
Rist  PM , Winter  AC , Buring  JE , Sesso  HD , Kurth  T .  Migraine and the risk of incident hypertension among women.   Cephalalgia. 2018;38(12):1817-1824. doi:10.1177/0333102418756865PubMedGoogle ScholarCrossref
11.
Hagen  K , Åsberg  AN , Stovner  L ,  et al.  Lifestyle factors and risk of migraine and tension-type headache: follow-up data from the Nord-Trøndelag Health Surveys 1995-1997 and 2006-2008.   Cephalalgia. 2018;38(13):1919-1926. doi:10.1177/0333102418764888PubMedGoogle ScholarCrossref
12.
Rist  PM , Tzourio  C , Kurth  T .  Associations between lipid levels and migraine: cross-sectional analysis in the epidemiology of vascular ageing study.   Cephalalgia. 2011;31(14):1459-1465. doi:10.1177/0333102411421682PubMedGoogle ScholarCrossref
13.
Gelaye  B , Sacco  S , Brown  WJ , Nitchie  HL , Ornello  R , Peterlin  BL .  Body composition status and the risk of migraine: a meta-analysis.   Neurology. 2017;88(19):1795-1804. doi:10.1212/WNL.0000000000003919PubMedGoogle ScholarCrossref
14.
Burch  RC , Rayhill  ML .  Migraine and vascular disease.   BMJ. 2016;353:i2806. doi:10.1136/bmj.i2806PubMedGoogle ScholarCrossref
15.
Ridker  PM , Cook  NR , Lee  I-M ,  et al.  A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women.   N Engl J Med. 2005;352(13):1293-1304. doi:10.1056/NEJMoa050613PubMedGoogle ScholarCrossref
16.
Mora  S , Lee  I-M , Buring  JE , Ridker  PM .  Association of physical activity and body mass index with novel and traditional cardiovascular biomarkers in women.   JAMA. 2006;295(12):1412-1419. doi:10.1001/jama.295.12.1412PubMedGoogle ScholarCrossref
17.
Schürks  M , Buring  JE , Kurth  T .  Agreement of self-reported migraine with ICHD-II criteria in the Women’s Health Study.   Cephalalgia. 2009;29(10):1086-1090. doi:10.1111/j.1468-2982.2008.01835.xPubMedGoogle ScholarCrossref
18.
Kurth  T , Gaziano  JM , Cook  NR , Logroscino  G , Diener  H-C , Buring  JE .  Migraine and risk of cardiovascular disease in women.   JAMA. 2006;296(3):283-291. doi:10.1001/jama.296.3.283PubMedGoogle ScholarCrossref
19.
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. doi:10.1136/bmj.a636PubMedGoogle ScholarCrossref
20.
Atiya  M , Kurth  T , Berger  K , Buring  JE , Kase  CS ; Women’s Health Study.  Interobserver agreement in the classification of stroke in the Women’s Health Study.   Stroke. 2003;34(2):565-567. doi:10.1161/01.STR.0000054159.21017.7CPubMedGoogle ScholarCrossref
21.
Kurth  T , Kase  CS , Schürks  M , Tzourio  C , Buring  JE .  Migraine and risk of haemorrhagic stroke in women: prospective cohort study.   BMJ. 2010;341:c3659. doi:10.1136/bmj.c3659PubMedGoogle ScholarCrossref
22.
Flanders  WD , Kleinbaum  DG .  Basic models for disease occurrence in epidemiology.   Int J Epidemiol. 1995;24(1):1-7. doi:10.1093/ije/24.1.1PubMedGoogle ScholarCrossref
23.
Bender  R .  Introduction to the use of regression models in epidemiology.   Methods Mol Biol. 2009;471:179-195. doi:10.1007/978-1-59745-416-2_9PubMedGoogle ScholarCrossref
24.
Joffe  MM , Greenland  S .  Standardized estimates from categorical regression models.   Stat Med. 1995;14(19):2131-2141. doi:10.1002/sim.4780141907PubMedGoogle ScholarCrossref
25.
Chu  LC , Xie  F . Using SAS to calculate incidence and prevalence rates in a dynamic population. Paper presented at: Western Users of SAS Software Conference; September 5-7, 2012; Long Beach, California.
26.
Chou  NT , Steenhard  D . A flexible count data regression model using SAS PROC NLMIXED. Paper presented at: SAS Global Forum; March 22-25, 2009; Washington, DC.
27.
Kurth  T , Winter  AC , Eliassen  AH ,  et al.  Migraine and risk of cardiovascular disease in women: prospective cohort study.   BMJ. 2016;353:i2610. doi:10.1136/bmj.i2610PubMedGoogle ScholarCrossref
28.
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. doi:10.1136/bmj.b3914PubMedGoogle ScholarCrossref
29.
Liman  TG , Bachelier-Walenta  K , Neeb  L ,  et al.  Circulating endothelial microparticles in female migraineurs with aura.   Cephalalgia. 2015;35(2):88-94. doi:10.1177/0333102414529671PubMedGoogle ScholarCrossref
30.
Magalhães  JE , Barros  IML , Pedrosa  RP , Sampaio Rocha-Filho  PA .  Migraine and markers of carotid atherosclerosis in middle-aged women: a cross-sectional study.   Headache. 2019;59(1):77-85. doi:10.1111/head.13460PubMedGoogle ScholarCrossref
31.
Schmidt  M , Sørensen  HT , Pedersen  L .  Diclofenac use and cardiovascular risks: series of nationwide cohort studies.   BMJ. 2018;362:k3426. doi:10.1136/bmj.k3426PubMedGoogle ScholarCrossref
32.
Dreier  JP .  The role of spreading depression, spreading depolarization and spreading ischemia in neurological disease.   Nat Med. 2011;17(4):439-447. doi:10.1038/nm.2333PubMedGoogle ScholarCrossref
33.
Ripa  P , Ornello  R , Pistoia  F , Carolei  A , Sacco  S .  Spreading depolarization may link migraine, stroke, and other cardiovascular disease.   Headache. 2015;55(1):180-182. doi:10.1111/head.12436PubMedGoogle ScholarCrossref
If you are not a JN Learning subscriber, you can either:
Subscribe to JN Learning for one year
Buy this activity
jn-learning_Modal_Multimedia_LoginSubscribe_Purchase
Close
If you are not a JN Learning subscriber, you can either:
Subscribe to JN Learning for one year
Buy this activity
jn-learning_Modal_Multimedia_LoginSubscribe_Purchase
Close
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right
Close

Name Your Search

Save Search
Close
With a personal account, you can:
  • Track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
jn-learning_Modal_SaveSearch_NoAccess_Purchase
Close

Lookup An Activity

or

Close

My Saved Searches

You currently have no searches saved.

Close

My Saved Courses

You currently have no courses saved.

Close
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right
Close