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Migraine and subclinical atherosclerosis: endothelial dysfunction biomarkers and carotid intima-media thickness: a case-control study

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Abstract

Background

Migraine is a common neurovascular disease associated with vascular risks, especially in young adult females, but the mechanism underlying these associations remains unknown. This study evaluated the relationships between plasma endothelial dysfunction biomarkers and carotid intima–media thickness (IMT) in young adult females with migraine.

Methods

This case–control study included 148 female patients (age range: 18–50 years). Migraine was diagnosed according to the International Headache Society-IIIb criteria. Endothelial dysfunction biomarkers, such as von Willebrand factor (vWF), C-reactive protein (CRP), homocysteine, total nitrate/nitrite concentration, and thiobarbituric acid-reactive substances (TBARS), were evaluated in plasma. Carotid IMT was measured by a radiologist with sonography.

Results

The CRP, TBARS, vWF, and IMT levels were increased in the migraine compared with the control group (p < 0.001, p = 0.02, p < 0.001, and p < 0.001, respectively). After adjusting for confounders, multiple linear regression analysis revealed that systolic arterial blood pressure, CRP, vWF, TBARS, and right and left internal carotid artery (ICA) IMT were independently positively correlated with migraine (p < 0.01, p = 0.004, p = 0.023, p = 0.024, p = 0.032, and p = 0.048, respectively). Multiple logistic regression analysis revealed that right ICA IMT was independently associated with ergotamine and triptan and left ICA IMT was independently associated with ergotamine (p = 0.013, p = 0.026, and p = 0.017, respectively). In addition, significant correlations were found between LDL lipoprotein and carotid IMT in the migraine group (p < 0.05).

Conclusions

Carotid IMT enhancement and elevated TBARS, vWF, and CRP levels in migraine subjects during a migraine attack could be regarded as consequences of migraine attack pathophysiology. The independent associations between triptan and ergotamine consumption and enhanced carotid IMT suggest that repeated use of these vasoconstrictive antimigraine agents may have additional effects on carotid IMT.

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Abbreviations

BMI:

body mass index

CCA:

common carotid artery

CRP:

C-reactive protein

ICA:

internal carotid artery

ICHD:

International Headache Society

IMT:

intima–media thickness

LDL:

low-density lipoprotein

NSAID:

nonsteroidal anti-inflammatory drug

TBARS:

thiobarbituric acid-reactive substances

VAS:

visual analog score

vWF:

von Willebrand factor

References

  1. Headache Classification Committee of the International Headache Society (2013) The international classification of headache disorders, 3rd edition (beta version). Cephalalgia 33:629–808. https://doi.org/10.1177/0333102413485658

    Article  Google Scholar 

  2. Lipton RB, Stewart WF, Diamond S, Diamond ML, Reed M (2001) Prevalence and burden of migraine in the United States: data from the American migraine study II. Headache 41:646–657

    Article  CAS  PubMed  Google Scholar 

  3. Waeber C, Moskowitz MA (2005) Migraine as an inflammatory disorder. Neurology 64(10 suppl 2):S9–S15

    Article  PubMed  Google Scholar 

  4. Moskowitz MA (2007) Pathophysiology of headache—past and present. Headache 47:558–567

    Article  Google Scholar 

  5. Spector JT, Kahn SR, Jones MR, Jayakumar M, Dalal D, Nazarian S (2010) Migraine headache and ischemic stroke risk: an updated meta-analysis. Am J Med 123:612–624

    Article  PubMed  PubMed Central  Google Scholar 

  6. Kurth T, Schürks M, Logroscino G, Gaziano JM, Buring JE (2008) Migraine, vascular risk, and cardiovascular events in women: prospective cohort study. BMJ 337:1–9. https://doi.org/10.1136/bmj.a636

    Article  Google Scholar 

  7. Rajan R, Kuhrana D, Lal V (2014) Interictal cerebral and systemic endothelial dysfunction in patients with migraine: a case–control study. J Neurol Neurosurg Psychiatry 1–5. https://doi.org/10.1136/jnnp-2014-309571

  8. Avci AY, Lakadamyali H, Arikan S, Benli US, Kilinc M (2015) High sensitivity C-reactive protein and cerebral white matter hyperintensities on magnetic resonance imaging in migraine patients. J Headache Pain 16:9. https://doi.org/10.1186/1129-2377-16-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Hamed SA, Hamed EA, Eldin AME, Mahmoud NM (2010) Vascular risk factors, endothelial function, and carotid thickness in patients with migraine: relationship to atherosclerosis. J Stroke Cerebrovasc Dis 19:92–103. https://doi.org/10.1016/j.jstrokecerebrovasdis.2009.04.007

    Article  PubMed  Google Scholar 

  10. Tietjen GE, Herial NA, White L, Utley C, Kosmyna JM, Khuder SA (2009) Migraine and biomarkers of endothelial activation in young women. Stroke 40:2977–2982. https://doi.org/10.1161/STROKEAHA.109.547901

    Article  CAS  PubMed  Google Scholar 

  11. Yang EY, Nimbi V (2011) Ultrasound imaging of carotid intima–media thickness: an office-based tool to assist physicians in cardiovascular risk assessment. Curr Atheroscler Rep 13:431–436. https://doi.org/10.1007/s11883-011-0200-5

    Article  CAS  PubMed  Google Scholar 

  12. Naqvi TZ, Lee MS (2014) Carotid intima–media thickness and plaque in cardiovascular risk assessment. JACC Cardiovasc Imaging 7(10):1025–1038. https://doi.org/10.1016/j.jcmg.2013.11.014

    Article  PubMed  Google Scholar 

  13. Tietjen GE, Khubchandani J, Herial N, Palm-Meinders IH, Koppen H, Terwindt GM, Buchem MA, Launer LJ, Ferrari MD, Kruit MC (2017) Migraine and vascular disease biomarkers: a population-based case–control study. Cephalalgia 1–8. https://doi.org/10.1177/0333102417698936

  14. Gonzales-Quintanilla V, Toriello M, Palacio E, Gonzalez-Gay MA, Castillo J, Montes S, Martinez-Nieto R, Fernandez J, Rojo A, Gutierrez S, Pons E, Otreino A (2015) Systemic and cerebral endothelial dysfunction in chronic migraine. A case–control study with an active comparator. Cephalalgia 36:552–560. https://doi.org/10.1177/0333102415607857

    Article  Google Scholar 

  15. Stam AH, Weller CM, Janssens ACJW, Aulchenko YS, Oostra BA, Frants RR, Maagdenberg AMJM, Ferrari MD, Dujin CM, Terwindt GM (2012) Migraine is not associated with enhanced atherosclerosis. Cephalalgia 33:228–235. https://doi.org/10.1177/0333102412466966

    Article  PubMed  Google Scholar 

  16. Bassuk SS, Rifai N, Ridker PM (2004) High-sensitivity C-reactive protein: clinical importance. Curr Probl Cardiol 29:439–493

    PubMed  Google Scholar 

  17. Touboul PJ, Hennerici MG, Meairs S, Adams H, Amarenco P, Bornstein N, Csiba L, Desvarieux M, Ebrahim S, Hernandez R, Jaff M, Kownator S, Naqvi T, Prati P, Rundek T, Sitzer M, Schminke U, Tardif JC, Taylor A, Vicaut E, Woo KS (2012) Mannheim carotid intima–media thickness and plaque consensus (2004-2006-2011). Cerebrovasc Dis 34:290–296. https://doi.org/10.1159/000343145

    Article  PubMed  PubMed Central  Google Scholar 

  18. Albieri V, Olsen TS, Andersen KK (2016) Risk of stroke in migraineurs using triptans. Association with age, sex, stroke severity and subtype. EBioMedicine 6:199–205. https://doi.org/10.1016/j.ebiom.2016.02.039

    Article  PubMed  PubMed Central  Google Scholar 

  19. Valentin JP, Bonnafous R, John GW (1996) Influence of the endothelium and nitric oxide on the contractile responses evoked by 5-HT1D receptor agonist in the rabbit isolated saphenous vein. Br J Pharmacol 119:35–42

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Tfelt-Hansen P, Nilsson E, Edvinsson L (2007) Contractile responses to ergotamine and dihydroergotamine in the perfused middle cerebral artery of rat. J Headache Pain 8:83–89. https://doi.org/10.1007/s10194-007-0368-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Vanmolkot FH, Hoon JN (2010) Endothelial function in migraine: a cross-sectional study. BMC Neurol 10:119. https://doi.org/10.1186/1471-2377-10-119

    Article  PubMed  PubMed Central  Google Scholar 

  22. Fischer M, Gaul C, Shanib H, Holle D, Loacker L, Griesmacher A, Lackner P, Broessner G (2014) Markers of endothelial function in migraine patients: results from a bi-center prospective study. Cephalalgia 35:877–885. https://doi.org/10.1177/0333102414564890

    Article  PubMed  Google Scholar 

  23. Tzourio C, Gagniere B, El Amrani E, Alperovitch A, Bousser MG (2003) Relationship between migraine, blood pressure and carotid thickness. A population-based study in the elderly. Cephalalgia 23:914–920. https://doi.org/10.1046/j.1468-2982.2003.00613.x

    Article  CAS  PubMed  Google Scholar 

  24. Neri M, Frustaci A, Millic M, Valdiglesias V, Fini M, Bonassi S, Barbanti P (2015) A meta-analysis of biomarkers related to oxidative stress and nitric oxide pathway in migraine. Cephalalgia 35:931–937. https://doi.org/10.1177/0333102414564888

    Article  PubMed  Google Scholar 

  25. Silva FA, Rueda-Clausen CF, Silva SY, Zarruk JG, Guzman JC, Morillo CA, Vesga B, Pradilla G, Flórez M, López-Jaramillo P (2006) Endothelial function in patients with migraine during the interictal period. Headache 47:45–51. https://doi.org/10.1111/j.1526-4610.2006.00532.x

    Article  Google Scholar 

  26. Heshmat-Ghahdarijani K, Javanmard SH, Sonbolestan SA, Saadatnia M, Sonbolestan SA (2015) Endothelial function in patients with migraine without aura during the interictal period. Int J Prev Med 6(2). https://doi.org/10.4103/2008-7802-151432

  27. Ciancarelli I, Tozzi-Ciancarelli MG, Massimo CD, Marini C, Carolei A (2003) Urinary nitric oxide metabolites and lipid peroxidation by-products in migraine. Cephalalgia 23:39–42. https://doi.org/10.1046/j.1468-2982.2003.00447.x

    Article  CAS  PubMed  Google Scholar 

  28. Lippi G, Mattiuzzi C, Meschi T, Cervellin G, Borghi L (2014) Homocysteine and migraine. A narrative review. Clin Chim Acta 433:5–11. https://doi.org/10.1016/j.cca.2014.02.028

    Article  CAS  PubMed  Google Scholar 

  29. Moschiano F, D’Amico D, Usai S, Grazzi L, Stefano MD, Ciusani E, Erba N, Bussone G (2008) Homocysteine plasma levels in patients with migraine with aura. Neurol Sci 29:173–175. https://doi.org/10.1007/s10072-008-0917-2

    Article  Google Scholar 

  30. Ipcioglu OM, Ozcan O, Gultepe M, Tekeli H, Senol MG (2008) Functional vitamin B12 deficiency represented by elevated urine methylmalonic acid levels in patients with migraine. Turk J Med Sci 38:409–414

    CAS  Google Scholar 

  31. Xiang Y, Hwa J (2016) Regulation of vWF expression, and secretion in health and disease. Curr Opin Hematol 23:288–293. https://doi.org/10.1097/MOH.0000000000000230

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Cesar JM, Garcia-Avello A, Vecino AM, Sastre JL, Alvarez-Cermeno JC (1995) Increased levels of plasma von Willebrand factor in migraine crisis. Acta Neurol Scand 91:412–413

    Article  CAS  PubMed  Google Scholar 

  33. Furie B, Furie BC (1990) Molecular basis of vitamin K-dependent γ-carboxylation. Blood 75:1753–1762

    CAS  PubMed  Google Scholar 

  34. Gudmundsson LS, Aspelund T, Scher AI, Thorgeirsson G, Johannsson M, Launer LJ, Gudnason V (2009) C-reactive protein in migraine sufferers similar to that of non-migraineurs: the Reykjavik study. Cephalalgia 29:1301–1310. https://doi.org/10.1111/j.1468-2982.2009.01865.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Goadsby PJ, Edvinsson L, Ekman R (1990) Vasoactive peptide release in the extracerebral circulation of humans during headache. Ann Neurol 28:183–187

    Article  CAS  PubMed  Google Scholar 

  36. Gudmundsson LS, Thorgeirsson G, Sigfusson N, Sigvaldason H, Johannsson M (2005) Migraine patients have lower systolic but higher diastolic blood pressure compared with controls in a population-based study of 21537 subjects. The Reykjavik study. Cephalalgia 26:436–444. https://doi.org/10.1111/j.1468-2982.2005.01057.x

    Article  Google Scholar 

  37. Agostoni E, Aliprandi A (2008) Migraine and hypertension. Neurol Sci 29:S37–S39. https://doi.org/10.1007/s10072-008-0883-8

    Article  PubMed  Google Scholar 

  38. Finocchi C, Sassos D (2017) Headache and arterial hypertension. Neurol Sci 38(suppl1):s67–s72. https://doi.org/10.1007/s10072-017-2893-x

    Article  Google Scholar 

  39. Folsom AR, Eckfeldt JH, Weitzman S, Ma J, Chambless LE, Barnes RW, Cram KB, Hutchinson RG (1994) Relation of carotid artery wall thickness to diabetes mellitus, fasting glucose and insulin, body size, and physical activity. Atherosclerosis risk in communities (ARIC) study investigators. Stroke 25:66–73

    Article  CAS  PubMed  Google Scholar 

  40. Howard G, Sharrett AR, Heiss G, Evans GW, Chambless LE, Riley WA, Burke GL (1993) Carotid artery intimal–medial thickness distribution in general populations as evaluated by B-mode ultrasound. ARIC investigators. Stroke 24:1297–1304

    Article  CAS  PubMed  Google Scholar 

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Funding

This study was supported by the Baskent University Research Fund.

Author information

Authors and Affiliations

Authors

Contributions

A.Y.A. and M.H.A. conceived and designed the study; E.T. measured the carotid IMT; S.A. acquired and analyzed the laboratory data; M.A.T analyzed the statistics; A.Y.A. acquired and interpreted the data and wrote the paper; A.Y.A. and U.C. critically revised the manuscript for important intellectual content.

Corresponding author

Correspondence to Aynur Yilmaz Avci.

Ethics declarations

The study was approved by the Baskent University Institutional Review Board and Ethics Committee (project no: KA15/133) and conducted in accordance with the Declaration of Helsinki. All M and control subjects gave informed consent for participation in the study and for carotid artery Doppler ultrasound and laboratory tests.

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The study was approved by Baskent University Institutional Review Board and Ethics Committee (project no: KA15/133) and conducted in accordance with the Declaration of Helsinki of 1964.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Cite this article

Yilmaz Avci, A., Akkucuk, M.H., Torun, E. et al. Migraine and subclinical atherosclerosis: endothelial dysfunction biomarkers and carotid intima-media thickness: a case-control study. Neurol Sci 40, 703–711 (2019). https://doi.org/10.1007/s10072-019-3710-5

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