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Do Migraines Increase a Man's Stroke Risk? Yes, If He is Young at Heart
Abstract & Commentary
By Dara G. Jamieson, MD, Associate Professor, Clinical Neurology, Weill Medical College, Cornell University. Dr. Jamieson is a consultant for Boehringer Ingelheim and Merck, and is on the speaker's bureau for Boehringer Ingelheim, Merck, Ortho-McNeil, and Pfizer.
Synopsis: Men with migraine are at increased risk of myocardial infarction. But, risk of ischemic stroke is increased only in younger male migraineurs.
Source: Kurth T, et al. Migraine and risk of cardiovascular disease in men. Arch Intern Med. 200;167:795-801.
The diagnosis of migraine headaches may portend a more complicated medical course than just years of episodic disabling headaches. Migraine with aura has been associated with an adverse vascular risk profile and prothrombotic factors. Studies of patients with migraine headaches have tended to focus on this common disease in women. The known correlation between migraine and vascular risk was recently analyzed in data from the Women's Health Study (WHS). This study confirmed that women with migraine with aura have a greater risk of cardiovascular, as well as cerebrovascular, disease. Women with active migraine with aura had an increased risk of ischemic stroke, myocardial infarction (MI), myocardial revascularization, angina, and vascular death. Increased risk was noted after approximately 6 years of follow-up. Women with migraine without aura did not have an increased risk of any vascular events.
However, men make up about a quarter of the 28 million Americans with migraine headaches. The vascular risk of male migraineurs is less well characterized than in women with migraine. Kurth et al report the results of a prospective cohort study of participants in the Physicians' Health Study (PHS), a randomized placebo-controlled trial designed to test the benefits and risks of low dose aspirin and beta carotene in the primary prevention of cardiovascular disease and cancer in apparently healthy male physicians. Between 1981 and 1984, over 22,000 men were randomized to receive one of the two therapies or placebo. Questionnaires were used to collect baseline and follow-up data. For this analysis of migraine headaches and vascular risk, information was collected through February 2005 with a mean follow-up of 15.7 years. Men were classified as having migraine if they had a migraine headache in the first 5 years of follow-up, with frequent migraine defined as 4 or more reports of migraine during this period. Non-migraine headaches were reported, but data was not available for the International Headache Society classification or for the determination of migraine with aura versus migraine without aura. The first occurrence of the combined outcome of nonfatal ischemic stroke, nonfatal MI, or cardiovascular death was determined by follow-up questionnaires and examination of medical records. Cox proportional hazard models evaluated the association between migraine and outcomes. Multivariable models adjusted for multiple vascular risk factors.
For the analysis, 20,084 men were free of vascular disease at 5-year follow-up. About 7.2% (1449) of men reported migraine on the 60 month questionnaire, with frequent migraine reported in 434 men. Migraineurs were younger and more likely to have hypertension or elevated cholesterol. Compared with men without migraine, those men who reported migraine were at significantly increased risk of cardiovascular disease and myocardial infarction. The multivariable-adjusted hazard ratios (95% confidence intervals) were 1.24 (1.06-1.46; P = 0.008) for combined major cardiovascular events, 1.12 (0.84-1.50; P = 0.43) for ischemic stroke, 1.42 (1.15-1.77; P < 0.001) for myocardial infarction, and 1.07 (0.80-1.43; P = 0.65) for ischemic cardiovascular death. While there was no association in older age groups, there was an association between migraine and ischemic stroke (age-adjusted HR 1.84; 95% CI, 1.10-3.08; P = 0.03) for migraineurs younger than 55 years old, as compared to men without migraine. Unlike for ischemic stroke, age did not significantly modify the association between migraine and major cardiovascular disease and MI. No statistically significant increase in coronary revascularization or angina was noted in men with migraine. There was no association between men who reported only nonmigraine headaches and vascular outcomes.
In this study of initially healthy men, free from vascular disease at study entry and during the 5 year migraine ascertainment period, migraine was associated with a significantly increased risk of major cardiovascular events, driven by an increased risk of MI. After adjustment for cardiovascular risk factors, men who reported migraine had a 24% increased risk of major cardiovascular disease and a 42% increased risk of MI. Migraine was not statistically associated with increased risk of ischemic stroke, death from ischemic cardiovascular disease, coronary revascularization, or angina. However there was an increased risk of ischemic stroke for men with migraine who were 40 to 54 years of age, as compared to older men with migraine.
In a previous report from the PHS, migraine was not associated with an increased risk of cardiac disease during a mean of 12 years of follow-up. These more recent results, with almost 16 years of follow-up, show increased risk of MI. The duration of follow-up of a disease with relatively low prevalence in men may account for the disparate results. The WHS indicated an ischemic stroke and cardiac risk, but only in women with active migraine with aura. More information was accumulated for the women in the WHS, allowing analysis of vascular risk as a function of headache characteristics. However, the PHS was not designed to assess men with migraine headaches, which limited the ability of the analysis to assign detailed headache characteristics to specific vascular outcomes. While the PHS had many participants prospectively followed for a long period, headaches were self-reported without information on migraine type. Details of migraine drug use and confounding conditions were not reported. The participants in the PHS were healthy, male, middle-aged, mostly white physicians; although the study results are probably applicable to other male groups. There are still unanswered questions about migraines and vascular disease; but, the increased vascular risk of men, and women, with migraine headaches indicates the need for vigilance in managing their other vascular risk factors.
Kurth, et al. Migraine and risk of cardiovascular disease in women. JAMA. 2006;296:283-291.