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Journal of Neurology Research

Original Article

Volume 2, Number 1, February 2012, pages 10-15

Cardiovascular Disease Risk Profile in Japanese Midlife Migraineurs

Migraine is a primary, chronic-intermittent headache disorder that affects a large proportion of the population, predominantly middle-aged women [1, 2]. Migraine is associated with stroke and cardiovascular disease (CVD) [3-19]. Potential mechanisms of increased risk for ischemic stroke and CVD have been postulated in migraineurs [5, 9, 14-16]. Distinct backgrounds of CVD risk profile were highlighted in European and North American migraineurs [10, 13, 17-20]. However, little is known about CVD risk factors in large number of Asian migraineurs. Here, we aimed to evaluate CVD risk profile of midlife migraineurs in Japan.

Migraine was diagnosed according to the criteria of the International Classification of Headache Disorders; 2nd Edition [21]. Migraine was classified into migraine with aura (MA) and migraine without aura (MO). Severity of migraine was scaled using functional disability score of Headache Impact Test-6 (HIT-6) [22]. Migraineurs who had more than one attack in the previous year were selected. Migraine sufferers who never had migraine attacks in the previous year were excluded from the present study. Frequencies of migraine attacks were denoted as < 1 attack per month or ≥ 1 attack per month.

A total of 596 subjects (409 women and 187 men) were diagnosed consecutively as migraine between 2006 and 2009 in two Japanese medical centers: Toho University Omori Medical Center and PL Tokyo Health Care Center. For comparison of CVD risk factors, 599 age- and sex- control subjects without prior history of migraine were prepared. To evaluate spontaneous CVD risk profile, migraineurs and controls who used hormonal contraceptive, antihypertensive, diabetic and dyslipidemic drugs were excluded from this study. The present study was approved by Ethics Committee of Toho University Omori Medical Center and PL Tokyo Health Care Center. The informed consent for this study was obtained from all participants.

CVD risk factors were analyzed on the following 9 items: body mass index (BMI), west circumference/height, smoking index (cigarettes/day X years), blood pressure (BP), serum levels of lipids, fasting blood sugar (FBS), serum levels of hemoglobin A_1C (HbA_1c), serum levelsof high sensitivity C-reactive protein (CRP), and a family history of CVD or stroke. Serological measurement of lipids contained total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG). Fasting blood samples were obtained from the antecubital vein in controls and migraineurs during a headache-free period.

Statistical analyses of migraine frequency and a family history of CVD or stroke used χ²-test. Other CVD risk factors and HIT-6 scores were analyzed by unpaired Student’s t-test and one-way analysis of variance. All statistical significances were set at P < 0.05.

Mean age (SD) of migraineurs was 44.6 (9.4) years, 44.3 (9.4) years in women and 45.2 (9.3) years in men. Mean duration of migraine (SD) was 16.7 (11.4) years, 18.7 (12.2) years in women and 13.3 (9.1) years in men. Frequency of ≥1 attack/month was increased in women more than men (P < 0.01). Female migraineurs had significant higher HIT-6 scores as compared to male migraineurs (P < 0.01). Those results suggested that frequency and severity of migraine attacks were impaired in women more than men (Table 1).

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Table 1. Clinical Background of Migraineurs

CVD risk factors of women and men were listed in Table 2. As compared to controls, systolic and diastolic BP was significantly increased in male and female migraineurs (P < 0.01). Serum levels of lipids differed statistically between migraineurs and controls. TC and LDL-C were increased in sera of female (P < 0.01) and male migraineurs (P < 0.01). Serum levels of HDL-C were decreased in female migraineurs (P < 0.001) and male migraineurs (P < 0.01). Serum levels of TG were increased in male migraineurs (P < 0.01). As compared to controls, frequency of relatives with CVD or stroke was increased approximate 2-fold in female (P < 0.001) and male migraineurs (P < 0.01). There were no significant differences of BMI, west circumference/height, smoking index, FBS, HbA_1c and CRP between migraineurs and controls. Migraine subtypes and CVD risk profiles were expressed in Table 3. A significant elevation of systolic and diastolic BP existed in MA and MO sufferers, in comparison with controls (P < 0.05). Serum levels of TC and LDL-C differed significantly among MA, MO and control subjects (P <0.01). A family history of CVD or stroke was more frequent in MA and MO sufferers than controls (P < 0.01). There were no significant differences of CVD risk factors between MA and MO sufferers.

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Table 2. CVD Risk Factors of Migraineurs and Controls

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Table 3. CVD Risk Factors of MA, MO and Control Subjects

We first reported the CVD risk profile in large number of Japanese midlife migraineurs. Our migraineurs had higher BP, higher serum levels of TC and LDL-C, lower serum levels of HDL-C and higher rates of CVD or stroke relatives in women and men. These unfavorable changes were found in both MA and MO sufferers.

Many previous studies supported the significant relationship between migraine and vascular events, including CVD and ischemic stroke [3-19]. Several cohort studies revealed that MA was associated with CVD or ischemic stroke [10-12]. A recent Icelandic cohort study of midlife migraineurs also has shown that female MA is correlated with latelife cerebellar infarct-like lesions on magnetic resonance imaging [13]. Causative mechanism of those vascular disorders might contribute to prothrombotic actions, CVD risk factors, vascular reactivity, specific gene variants, congenital heart diseases, migraine attack frequency, migraine-specific treatment and pathophysiological involvements of the migraine [5, 9, 14-16]. Major prospective studies evaluated CVD risk factors in large number of migraineurs and non-migraineurs [10, 13, 17, 23]. The Genetic Epidemiology of Migraine study of Netherlands pointed out that MA sufferer increased the frequency of hypercholesterolemia, hypertension, and prior history of early onset CVD and stroke. Those risk factors did not differ statistically between MO sufferers and controls [17]. In the Women’s Health Study of North America, women with MA and MO significantly increased BP and serum levels of TC and LDL-C, and decreased serum levels of HDL-C compared to controls [10]. Those hallmarks of BP and serum lipid levels were in the similar results to female migraineurs in the present study. In contrast, the Physicians’ Health Study of North America suggested no significant linkages of CVD risk factors between male migraineurs and controls [23]. The AGES-Reykjavik long-term study of Iceland exhibited no significant elevation of BP and serum TC levels in midlife MA and MO sufferers. In addition, latelife migraineurs had no statistical changes of BP [13]. Other European studies mentioned the controversial result of CVD risk factors [18-20]. An Italian population-based study (age ≥ 45 years) showed that serum levels of TC and LDL-C were increased significantly in migraineurs (n= 151) more than nonmigraineurs (n = 1658) [18]. Hypercholesterolemia defined as TC ≥ 220 mg/dL was correlated independently with migraine in elderly men [18]. In an Austrian study, migraineurs and controls were divided into normal body weight and obesity. Serum levels of TC, LDL-C and oxidized LDL-C were increased significantly in normal weight migraineurs (n = 43) and obese migraineurs (n = 17) compared to normal weight controls (n = 61). There were no statistical differences of BP, and serum CRP and cytokines levels between migraineurs and controls with normal weight [19]. Those previous reports of serum lipid and CRP levels were mimicking to the present study. In contrast, previous Belgian study addressed that BP and serum levels of TC and LDL-C did not differ in young migraineurs (n = 50) and controls (n = 50) without CVD risk factors. Only high sensitivity CRP was increased in interictal sera of migraineurs [20]. Thus, the present and previous studies advocated that unfavorable serum lipid profile was the most common CVD risk profile of migraineurs among many ethnics, including Europe, North American and Japan. In addition to interracial differences, variable backgrounds of migraineurs may reflect BP values, serum levels of lipid and CRP.

In conclusion, the present study indicated elevation of BP, unfavorable changes of serum lipid levels and high frequency of CVD or stroke relatives in middle-aged women and men with MA or MO. The similar CVD risk profile was first confirmed among Japanese, European and North American population. Further cohort studies are needed to elucidate prevalence of CVD or stroke in Japanese migraineurs.

Conflicts of Interest

All authors report no conflicts of interest.

1. Lipton RB, Bigal ME. The epidemiology of migraine. Am J Med. 2005;118 Suppl 1:3S-10S.
   pubmed
2. Ikeda K, Kashihara H, Hosozawa K, Anan K, Shimoma M, Tamura M, Iwasaki Y, et al. Brain check-up-based study of migraine in Japan. Headache Care. 2005; 2 (2): 75-80.
3. Henrich JB, Horwitz RI. A controlled study of ischemic stroke risk in migraine patients. J Clin Epidemiol. 1989;42(8):773-780.
   pubmed doi
4. Tzourio C, Iglesias S, Hubert JB, Visy JM, Alperovitch A, Tehindrazanarivelo A, Biousse V, et al. Migraine and risk of ischaemic stroke: a case-control study. BMJ. 1993;307(6899):289-292.
   pubmed doi
5. Donaghy M, Chang CL, Poulter N. Duration, frequency, recency, and type of migraine and the risk of ischaemic stroke in women of childbearing age. J Neurol Neurosurg Psychiatry. 2002;73(6):747-750.
   pubmed doi
6. 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(7482):63.
   pubmed doi
7. Kurth T, Slomke MA, Kase CS, Cook NR, Lee IM, Gaziano JM, Diener HC, et al. Migraine, headache, and the risk of stroke in women: a prospective study. Neurology. 2005;64(6):1020-1026.
   pubmed doi
8. Stang PE, Carson AP, Rose KM, Mo J, Ephross SA, Shahar E, Szklo M. Headache, cerebrovascular symptoms, and stroke: the Atherosclerosis Risk in Communities Study. Neurology. 2005;64(9):1573-1577.
   pubmed doi
9. MacClellan LR, Giles W, Cole J, Wozniak M, Stern B, Mitchell BD, Kittner SJ. Probable migraine with visual aura and risk of ischemic stroke: the stroke prevention in young women study. Stroke. 2007;38(9):2438-2445.
   pubmed doi
10. Kurth T, Gaziano JM, Cook NR, Logroscino G, Diener HC, Buring JE. Migraine and risk of cardiovascular disease in women. JAMA. 2006;296(3):283-291.
    pubmed doi
11. Kurth T, Gaziano JM, Cook NR, Bubes V, Logroscino G, Diener HC, Buring JE. Migraine and risk of cardiovascular disease in men. Arch Intern Med. 2007;167(8):795-801.
    pubmed doi
12. Liew G, Wang JJ, Mitchell P. Migraine and coronary heart disease mortality: a prospective cohort study. Cephalalgia. 2007;27(4):368-371.
    pubmed doi
13. Scher AI, Gudmundsson LS, Sigurdsson S, Ghambaryan A, Aspelund T, Eiriksdottir G, van Buchem MA, et al. Migraine headache in middle age and late-life brain infarcts. JAMA. 2009;301(24):2563-2570.
    pubmed doi
14. Tietjen GE. Migraine as a systemic disorder. Neurology. 2007;68(19):1555-1556.
    pubmed doi
15. Vargas BB, Dodick DW, Wingerchuk DM, Demaerschalk BM. Migraine with and without aura and risk for cardiovascular disease. Curr Atheroscler Rep. 2008;10(5):427-433.
    pubmed doi
16. Kurth T, Schurks M, Logroscino G, Buring JE. Migraine frequency and risk of cardiovascular disease in women. Neurology. 2009;73(8):581-588.
    pubmed doi
17. Scher AI, Terwindt GM, Picavet HS, Verschuren WM, Ferrari MD, Launer LJ. Cardiovascular risk factors and migraine: the GEM population-based study. Neurology. 2005;64(4):614-620.
    pubmed doi
18. Monastero R, Pipia C, Cefalu AB, Liveri ET, Rosano R, Camarda R, Camarda C. Association between plasma lipid levels and migraine in subjects aged > or =50 years: preliminary data from the Zabut Aging Project. Neurol Sci. 2008;29 Suppl 1:S179-181.
    pubmed
19. Gruber HJ, Bernecker C, Pailer S, Lechner A, Horejsi R, Moller R, Fazekas F, et al. Lipid profile in normal weight migraineurs - evidence for cardiovascular risk. Eur J Neurol. 2010;17(3):419-425.
    pubmed doi
20. Vanmolkot FH, de Hoon JN. Increased C-reactive protein in young adult patients with migraine. Cephalalgia. 2007;27(7):843-846.
    pubmed doi
21. The International Classification of Headache Disorders: 2nd edition. Cephalalgia. 2004;24 Suppl 1:9-160.
    pubmed
22. Bayliss MS, Dewey JE, Dunlap I, Batenhorst AS, Cady R, Diamond ML, Sheftell F. A study of the feasibility of Internet administration of a computerized health survey: the headache impact test (HIT). Qual Life Res. 2003;12(8):953-961.
    pubmed doi
23. Cook NR, Bensenor IM, Lotufo PA, Lee IM, Skerrett PJ, Chown MJ, Ajani UA, et al. Migraine and coronary heart disease in women and men. Headache. 2002;42(8):715-727.
    pubmed doi

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Journal of Neurology Research is published by Elmer Press Inc.