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Association Between Migraine and Cardiovascular Disease in WomenAssociation Between Migraine and Cardiovascular Disease in Women

JAMA. 2006;296(22):2677-2678. doi:10.1001/jama.296.22.2677-a
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AUTHOR INFORMATION

Letters Section Editor: Robert M. Golub, MD, Senior Editor.

ASSOCIATION BETWEEN MIGRAINE AND CARDIOVASCULAR DISEASE IN WOMEN

To the Editor: Dr Kurth and colleagues1 reported the results of their study of the association between migraine and risk of cardiovascular disease (CVD). We believe that several factors limit the interpretability of their findings.

While the authors state that exposure misclassification would have led to underestimation of the migraine-CVD association, this is not certain. There were at least 2 types of potential errors in classifying study participants. First, participants were asked whether they had ever experienced a migraine headache or had experienced a migraine headache during the past year. An affirmative response led to further questioning and classification. Women who did not recognize their headaches as being migraines would have been misclassified as having no history of migraine, which may account for the study's low prevalence of active migraine (13.0%). Many patients who believe they have sinus headache actually meet International Headache Society criteria for migraine.2 Second, the question used to identify aura would have been sensitive to premonitory symptoms, which may be present in more than 60% of patients with migraine.3 It is probable that some participants were misclassified as having “active migraine with aura.” The combined effect of these 2 potential classification errors is not obvious.

The issue of residual confounding also deserves careful consideration. The study did not control for psychiatric comorbidities when modeling cardiovascular events. Migraine is positively related to anxiety and depression,4 which, in turn, are positively related to CVD.5 Without adjustment for psychiatric diagnosis, there may be an upward-biased estimate of the association between migraine and CVD. Psychiatric illness could have also influenced the reporting of migraine by study participants. This is problematic since, unlike cardiovascular outcomes, the diagnosis of migraine was not confirmed using medical records. Finally, the use of 5-HT agonists (triptans) should have been adjusted for because their use as treatment for migraine or in patients with psychiatric illness could have contributed to excess cardiovascular morbidity or mortality among those with migraine and aura.6

Financial Disclosures: Dr Young reports that he has served on speakers' bureaus/advisory boards for Allergan (speakers' bureau), Endo (advisory board), GlaxoSmithKline (speakers' bureau), Johnson & Johnson (speakers' bureau), Merck (speakers' bureau), Ortho-McNeil (advisory board and speakers' bureau), and Valeant (advisory board); that he has served as a consultant for GlaxoSmithKline, Merck, Ortho-McNeil, Pfizer, and Winston; and that he has received research support from Abbott, Advanced Bionics, Advanced Neuromodulation Systems, Allergan, AstraZeneca, Capnia, Eisai, Eli Lilly, GlaxoSmithKline, Johnson & Johnson, Medtronic, Merck, Ortho-McNeil, Pfizer, Pozen, Valeant, and Vernalis. Dr Shaw reports that he owns and operates a health outcomes research consulting firm, Shaw Analytics Inc. He has consulting agreements with Integrated Therapeutics Group Inc (a subsidiary of Schering-Plough Corp), Sanofi-Aventis US Inc, and Clinical Advisors LLC. He has not participated in any consulting work related to products that are indicated for the treatment of migraine or cardiovascular disease. None of his clients provides direct financial support for his academic research. He and his immediate family members do not hold any stock in the companies with which Shaw Analytics is contracted.

References
Kurth T, Gaziano JM, Cook NR, Logroscino G, Diener HC, Buring JE. Migraine and risk of cardiovascular disease in women.  JAMA. 2006;296283-291
PubMed
Schreiber CP, Hutchinson S, Webster CJ, Ames M, Richardson MS, Powers C. Prevalence of migraine in patients with a history of self-reported or physician-diagnosed “sinus” headache.  Arch Intern Med. 2004;1641769-1772
PubMed
Isler H. Frequency and time course of premonitory phenomena. In: Amery WK, Wauquier A, eds. The Prelude to the Migraine Attack. London, England: Bailliere Tindall; 1986:44-53
Merikangas KR, Angst J, Isler H. Migraine and psychopathology: results of the Zurich cohort study of young adults.  Arch Gen Psychiatry. 1990;47849-853
PubMed
Rozanski A, Blumenthal JA, Kaplan J. Impact of psychological factors on the pathogenesis of cardiovascular disease and implications for therapy.  Circulation. 1999;992192-2217
PubMed
Dodick DW, Martin VT, Smith T, Silberstein S. Cardiovascular tolerability and safety of triptans: a review of clinical data.  Headache. 2004;44(suppl 1)  S20-S30
PubMed

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Kurth T, Gaziano JM, Cook NR, Logroscino G, Diener HC, Buring JE. Migraine and risk of cardiovascular disease in women.  JAMA. 2006;296283-291
PubMed
Schreiber CP, Hutchinson S, Webster CJ, Ames M, Richardson MS, Powers C. Prevalence of migraine in patients with a history of self-reported or physician-diagnosed “sinus” headache.  Arch Intern Med. 2004;1641769-1772
PubMed
Isler H. Frequency and time course of premonitory phenomena. In: Amery WK, Wauquier A, eds. The Prelude to the Migraine Attack. London, England: Bailliere Tindall; 1986:44-53
Merikangas KR, Angst J, Isler H. Migraine and psychopathology: results of the Zurich cohort study of young adults.  Arch Gen Psychiatry. 1990;47849-853
PubMed
Rozanski A, Blumenthal JA, Kaplan J. Impact of psychological factors on the pathogenesis of cardiovascular disease and implications for therapy.  Circulation. 1999;992192-2217
PubMed
Dodick DW, Martin VT, Smith T, Silberstein S. Cardiovascular tolerability and safety of triptans: a review of clinical data.  Headache. 2004;44(suppl 1)  S20-S30
PubMed
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