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ARTICLES: J. Schwaiger, S. Kiechl, H. Stockner, M. Knoflach, P. Werner, G. Rungger, A. Gasperi, and J. Willeit Burden of atherosclerosis and risk of venous thromboembolism in patients with migraine Neurology 2008; 71: 937-943 [Abstract] [Full text] [PDF]

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Burden of atherosclerosis and risk of venous thromboembolism in patients with migraine

Simona Sacco, Antonio Carolei   (28 October 2008)

Reply from the authors

Stefan Kiechl, Stefan Kiechl and Johann Willeit   (28 October 2008)

Burden of atherosclerosis and risk of venous thromboembolism in patients with migraine 28 October 2008
Simona Sacco, University of L'Aquila Università degli studi di L’Aquila, 67010 L’Aquila, Italy, Antonio Carolei Send Correspondence to journal: Re: Burden of atherosclerosis and risk of venous thromboembolism in patients with migraine a_carolei{at}yahoo.com Simona Sacco, et al.	We read the article by Schwaiger et al. with great interest. [1] Migraine and especially migraine with aura has been associated with an increased risk of cardiovascular events most commonly seen in women. [2] It is vital to identify the factors that may explain the increased cardiovascular risk in migraineurs. One of the possible mechanisms linking migraine and cardiovascular disease is atherosclerosis. However, this mechanism is unlikely since migraine is a risk factor for stroke mostly in young women while atherosclerosis causes stroke in older patients. [3] To rule out this hypothesis, demonstration of the lack of any possible association should be provided. Schwaiger et al. [1] found no association between migraine and atherosclerosis despite a higher proportion of venous thromboembolism in migraineurs versus nonmigraineurs. The authors statement that this “provides solid evidence against the view that migraine predisposes to atherosclerosis” should be taken with caution. Their study does not provide information on the proportion and distribution of patients with ischemic stroke or coronary heart disease among migraineurs and nonmigraineurs. If the prevalence of ischemic stroke and coronary heart disease were unbalanced in the two groups, the results might be biased. While Schwaiger et al. report the proportion of women under hormone replacement treatment, they did not give data on oral contraceptive use. This may increase the risk for ischemic stroke in women with migraine with aura and have a greater than multiplicative effect in the presence of cigarette smoking or high blood pressure. [3,4] We think that further data is needed to counter the authors’ conclusion that atherosclerosis does not represent the mechanism linking migraine to cardiovascular disease. References 1. Schwaiger J, Kiechl S, Stockner H, et al. Burden of atherosclerosis and risk of venous thromboembolism in patients with migraine. Neurology 2008;71:937–943. 2. Sacco S, Cerone D, Carolei A. Comorbid neuropathologies in migraine: an update on cerebrovascular and cardiovascular aspects. J Headache Pain 2008;9:237-248. 3. Carolei A, Marini C, De Matteis G, the Italian National Research Council Study Group of Stroke in the Young. History of migraine and risk of cerebral ischaemia in young adults. Lancet 1996;347:1503–1506. 4. Chang CL, Donaghy M, Poulter N. Migraine and stroke in young women: case-control study. The World Health Organisation Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. BMJ 1999;318:13–18. Disclosure: The authors report no disclosures.
Reply from the authors 28 October 2008
Stefan Kiechl, Medical University Innsbruck Anichstr. 35, A-6020 Innsbruck, Austria, Stefan Kiechl and Johann Willeit Send Correspondence to journal: Re: Reply from the authors stefan.kiechl{at}i-med.ac.at Stefan Kiechl, et al.	We appreciate the comments by Drs. Carolei and Sacco. In the Bruneck study cohort, subjects with migraine were more likely to develop cardiovascular disease than nonmigraineurs with the excess risk being comparable to that estimated in recent large-scale studies and a meta-analysis. [5-7] In these analyses, baseline migraine status was not assessed according to ICHD-1/2 criteria but by judgement of an experienced senior neurologist. [1] Risk estimates were similar when exclusively focusing on stroke (HR [95%CI] = 1.63 [0.86-3.07]; P=0.13). Similar to previous reports, [5] excess vascular risk was more pronounced but not confined to migraine with aura. We agree that a single study cannot definitively refute a pathophysiological concept. However, our findings of a heightened vascular risk along with the tendency toward a lower burden of atherosclerosis renders a mechanistic link between both conditions in migraine patients unlikely. Dr. Carolei and Sacco mention the lack of data on oral contraceptive use. In 2005, all of the women studied had begun or finished menopause. When analysis on lifetime frequency of venous thrombembolism (VTE) according to migraine status was adjusted for current and previous hormone use—including both oral contraceptives and hormone replacement therapy—findings remained unchanged. The same was true for analysis on the association between migraine and cardiovascular disease. References 5. 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;330:63-66. 6. Kurth T, Gaziano JM, Cook NR, Logroscino G, Diener HC, Buring JE. Migraine and risk of cardiovascular disease in women. JAMA 2006;296:283-291. 7. Kurth T, Gaziano JM, Cook NR, et al. Migraine and risk of cardiovascular disease in men. Arch Intern Med 2007; 167:795-801. Disclosure: The authors report no disclosures.