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Published in: BMC Neurology 1/2024

Open Access 01-12-2024 | Migraine | Research

Calcitonin gene-related peptide: a possible biomarker in migraine patients with patent foramen ovale

Authors: Chaojie Li, Yu Yu, Ningning Li, Ya-Na Yin, Lianjun Zhang, Kehang Xie, Donghui Huang

Published in: BMC Neurology | Issue 1/2024

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Abstract

Background

Serum CGRP has been found to increase during migraine attack. However, whether CGRP can identify MA with PFO subtypes in MA remains unknown. This study aimed to investigate the differential expression of calcitonin gene-related peptide (CGRP) between migraine (MA) patients with and without patent foramen ovale (PFO), and to evaluate the predictive value of CGRP for MA with PFO.

Methods

A total of 153 patients with MA, 51 patients with PFO and 102 patients without. Venous blood was drawn and HIT-6 score was calculated during the onset of MA, and blood routine, inflammatory indexes and serum CGRP were detected. The differences in serum markers and HIT-6 scores were compared between the two groups, and the risk factors of MA with PFO were determined by univariate and multivariate logistics regression. Furthermore, the correlation between CGRP level with right-to-left shunt (RLS) grades and headache impact test-6 (HIT-6) score in MA patients with PFO were assessed. Independent risk factors were screened out by multivariate Logistic regression analysis. We used the receiver operating characteristic (ROC) curve to analyze the diagnostic value of these risk factors in MA complicated with PFO.

Results

The serum CGRP level and HIT-6 scores in the MA with PFO group were significantly higher than those in the MA group (P < 0.001). Multivariate regression analysis showed that CGRP was an independent risk factor for MA with PFO (OR = 1.698, 95% CI = 1.325–2.179, P < 0.001). CGRP values ​​increased with the increase of RLS grade(Spearmen rho = 0.703, P < 0.001). Furthermore, a positive correlation between CGRP and HIT-6 scores was found (Spearmen rho = 0.227; P = 0.016). ROC curve showed that the optimal cut-off value for diagnosing MA with PFO was 79 pg/mL, the area under the curve (AUC) for predicting MA with PFO was 0.845, with 72.55% sensitivity and 78.43% specificity.

Conclusions

MA patients with PFO have higher serum CGRP level. elevated CGRP concentration was associated with higher RLS grade and increased HIT-6 score. Higher serum CGRP level has certain clinical value in predicting PFO in MA patients.

Trial registration

This study was approved by the Ethics Committee of Zhuhai Hospital of Integrated Traditional Chinese and Western Medicine (Ethics batch number: 20,201,215,005).
Literature
1.
go back to reference Tepper SJ, Cirillo J, Kim E, L’Italien G, Tweedie JM, Lodaya K, Riley D, Pathan F, Antaki N, Nathanson BH, et al. The temporal trend of placebo response in migraine prevention from 1990 to 2021: a systematic literature review and meta-analysis with regression. J Headache Pain. 2023;24(1):54.CrossRefPubMedPubMedCentral Tepper SJ, Cirillo J, Kim E, L’Italien G, Tweedie JM, Lodaya K, Riley D, Pathan F, Antaki N, Nathanson BH, et al. The temporal trend of placebo response in migraine prevention from 1990 to 2021: a systematic literature review and meta-analysis with regression. J Headache Pain. 2023;24(1):54.CrossRefPubMedPubMedCentral
2.
go back to reference Agboola F, Atlas SJ, Touchette DR, Borrelli EP, Rind DM, Pearson SD. The effectiveness and value of novel acute treatments for migraine. J Manag Care Spec Pharm. 2020;26(11):1456–62.PubMed Agboola F, Atlas SJ, Touchette DR, Borrelli EP, Rind DM, Pearson SD. The effectiveness and value of novel acute treatments for migraine. J Manag Care Spec Pharm. 2020;26(11):1456–62.PubMed
3.
go back to reference Zhang QQ, Lu JJ, Yan MY, Hu XW, Qin YR, Wang DP, Jiang JH, Fang Q, Zhao HR. The Efficacy of Percutaneous Patent Foramen Ovale Closure on Migraine: a Meta-Analysis of Randomized Controlled Trials and Observational Studies. Biomed Res Int 2021, 2021:6643266. Zhang QQ, Lu JJ, Yan MY, Hu XW, Qin YR, Wang DP, Jiang JH, Fang Q, Zhao HR. The Efficacy of Percutaneous Patent Foramen Ovale Closure on Migraine: a Meta-Analysis of Randomized Controlled Trials and Observational Studies. Biomed Res Int 2021, 2021:6643266.
4.
go back to reference Tariq N, Tepper SJ, Kriegler JS. Patent Foramen Ovale and Migraine: closing the Debate–A review. Headache. 2016;56(3):462–78.CrossRefPubMed Tariq N, Tepper SJ, Kriegler JS. Patent Foramen Ovale and Migraine: closing the Debate–A review. Headache. 2016;56(3):462–78.CrossRefPubMed
5.
go back to reference Kumar P, Kijima Y, West BH, Tobis JM. The connection between patent Foramen Ovale and Migraine. Neuroimaging Clin N Am. 2019;29(2):261–70.CrossRefPubMed Kumar P, Kijima Y, West BH, Tobis JM. The connection between patent Foramen Ovale and Migraine. Neuroimaging Clin N Am. 2019;29(2):261–70.CrossRefPubMed
6.
go back to reference Ramachandran R. Neurogenic inflammation and its role in migraine. Semin Immunopathol. 2018;40(3):301–14.CrossRefPubMed Ramachandran R. Neurogenic inflammation and its role in migraine. Semin Immunopathol. 2018;40(3):301–14.CrossRefPubMed
7.
go back to reference Kilinc E, Tore F, Dagistan Y, Bugdayci G. Thymoquinone inhibits neurogenic inflammation underlying migraine through modulation of calcitonin gene-related peptide release and Stabilization of Meningeal Mast Cells in Glyceryltrinitrate-Induced Migraine Model in rats. Inflammation. 2020;43(1):264–73.CrossRefPubMed Kilinc E, Tore F, Dagistan Y, Bugdayci G. Thymoquinone inhibits neurogenic inflammation underlying migraine through modulation of calcitonin gene-related peptide release and Stabilization of Meningeal Mast Cells in Glyceryltrinitrate-Induced Migraine Model in rats. Inflammation. 2020;43(1):264–73.CrossRefPubMed
8.
go back to reference Cho S, Chu MK. Serological biomarkers of chronic migraine. Curr Pain Headache Rep; 2023. Cho S, Chu MK. Serological biomarkers of chronic migraine. Curr Pain Headache Rep; 2023.
9.
go back to reference Edvinsson L. The Trigeminovascular pathway: role of CGRP and CGRP receptors in Migraine. Headache. 2017;57(Suppl 2):47–55.CrossRefPubMed Edvinsson L. The Trigeminovascular pathway: role of CGRP and CGRP receptors in Migraine. Headache. 2017;57(Suppl 2):47–55.CrossRefPubMed
10.
go back to reference Iljazi A, Ashina H, Zhuang ZA, Lopez Lopez C, Snellman J, Ashina M, Schytz HW. Hypersensitivity to calcitonin gene-related peptide in chronic migraine. Cephalalgia. 2021;41(6):701–10.CrossRefPubMed Iljazi A, Ashina H, Zhuang ZA, Lopez Lopez C, Snellman J, Ashina M, Schytz HW. Hypersensitivity to calcitonin gene-related peptide in chronic migraine. Cephalalgia. 2021;41(6):701–10.CrossRefPubMed
11.
go back to reference Paredes S, Cantillo S, Candido KD, Knezevic NN. An Association of Serotonin with Pain disorders and its modulation by Estrogens. Int J Mol Sci 2019, 20(22). Paredes S, Cantillo S, Candido KD, Knezevic NN. An Association of Serotonin with Pain disorders and its modulation by Estrogens. Int J Mol Sci 2019, 20(22).
12.
go back to reference Wang HL. The Clinical Curative Effect and Safety of Percutaneous Closure of Patent Foramen Ovale. Master’s Thesis, Jilin University, Changchun, China, 2016. Wang HL. The Clinical Curative Effect and Safety of Percutaneous Closure of Patent Foramen Ovale. Master’s Thesis, Jilin University, Changchun, China, 2016.
14.
go back to reference Headache Classification Committee of the International Headache Society (IHS). The International classification of Headache disorders, 3rd edition. Cephalalgia. 2018;38(1):1–211.CrossRef Headache Classification Committee of the International Headache Society (IHS). The International classification of Headache disorders, 3rd edition. Cephalalgia. 2018;38(1):1–211.CrossRef
15.
go back to reference Liu F, Kong Q, Zhang X, Li Y, Liang S, Han S, Li G. Comparative analysis of the diagnostic value of several methods for the diagnosis of patent foramen ovale. Echocardiography. 2021;38(5):790–7.CrossRefPubMed Liu F, Kong Q, Zhang X, Li Y, Liang S, Han S, Li G. Comparative analysis of the diagnostic value of several methods for the diagnosis of patent foramen ovale. Echocardiography. 2021;38(5):790–7.CrossRefPubMed
16.
go back to reference Houts CR, Wirth RJ, McGinley JS, Cady R, Lipton RB. Determining thresholds for meaningful change for the Headache Impact Test (HIT-6) total and item-specific scores in Chronic Migraine. Headache. 2020;60(9):2003–13.CrossRefPubMedPubMedCentral Houts CR, Wirth RJ, McGinley JS, Cady R, Lipton RB. Determining thresholds for meaningful change for the Headache Impact Test (HIT-6) total and item-specific scores in Chronic Migraine. Headache. 2020;60(9):2003–13.CrossRefPubMedPubMedCentral
17.
go back to reference Takizawa T, Ayata C, Chen SP. Therapeutic implications of cortical spreading depression models in migraine. Prog Brain Res. 2020;255:29–67.CrossRefPubMed Takizawa T, Ayata C, Chen SP. Therapeutic implications of cortical spreading depression models in migraine. Prog Brain Res. 2020;255:29–67.CrossRefPubMed
18.
go back to reference Schwerzmann M, Nedeltchev K, Lagger F, Mattle HP, Windecker S, Meier B, Seiler C. Prevalence and size of directly detected patent foramen ovale in migraine with aura. Neurology. 2005;65(9):1415–8.CrossRefPubMed Schwerzmann M, Nedeltchev K, Lagger F, Mattle HP, Windecker S, Meier B, Seiler C. Prevalence and size of directly detected patent foramen ovale in migraine with aura. Neurology. 2005;65(9):1415–8.CrossRefPubMed
19.
go back to reference Alpert JS. Strange bedfellows: Migraine Headache and Patent Foramen Ovale. Am J Med. 2021;134(11):1307–8.CrossRefPubMed Alpert JS. Strange bedfellows: Migraine Headache and Patent Foramen Ovale. Am J Med. 2021;134(11):1307–8.CrossRefPubMed
20.
go back to reference Close LN, Eftekhari S, Wang M, Charles AC, Russo AF. Cortical spreading depression as a site of origin for migraine: role of CGRP. Cephalalgia. 2019;39(3):428–34.CrossRefPubMed Close LN, Eftekhari S, Wang M, Charles AC, Russo AF. Cortical spreading depression as a site of origin for migraine: role of CGRP. Cephalalgia. 2019;39(3):428–34.CrossRefPubMed
21.
go back to reference Cao W, Shen Y, Zhong J, Chen Z, Wang N, Yang J. The patent Foramen Ovale and Migraine: Associated mechanisms and perspectives from MRI evidence. Brain Sci 2022, 12(7). Cao W, Shen Y, Zhong J, Chen Z, Wang N, Yang J. The patent Foramen Ovale and Migraine: Associated mechanisms and perspectives from MRI evidence. Brain Sci 2022, 12(7).
22.
go back to reference Ji Y, Rizk A, Voulalas P, Aljohani H, Akerman S, Dussor G, Keller A, Masri R. Sex differences in the expression of calcitonin gene-related peptide receptor components in the spinal trigeminal nucleus. Neurobiol Pain. 2019;6:100031.CrossRefPubMedPubMedCentral Ji Y, Rizk A, Voulalas P, Aljohani H, Akerman S, Dussor G, Keller A, Masri R. Sex differences in the expression of calcitonin gene-related peptide receptor components in the spinal trigeminal nucleus. Neurobiol Pain. 2019;6:100031.CrossRefPubMedPubMedCentral
23.
go back to reference Hansen JM, Hauge AW, Olesen J, Ashina M. Calcitonin gene-related peptide triggers migraine-like attacks in patients with migraine with aura. Cephalalgia. 2010;30(10):1179–86.CrossRefPubMed Hansen JM, Hauge AW, Olesen J, Ashina M. Calcitonin gene-related peptide triggers migraine-like attacks in patients with migraine with aura. Cephalalgia. 2010;30(10):1179–86.CrossRefPubMed
24.
go back to reference Sun W, Cheng H, Xia B, Liu X, Li Y, Wang X, Liu C. Comparative efficacy and safety of five anti-calcitonin gene-related peptide agents for Migraine Prevention: A Network Meta-analysis. Clin J Pain. 2023;39(10):560–9.CrossRefPubMed Sun W, Cheng H, Xia B, Liu X, Li Y, Wang X, Liu C. Comparative efficacy and safety of five anti-calcitonin gene-related peptide agents for Migraine Prevention: A Network Meta-analysis. Clin J Pain. 2023;39(10):560–9.CrossRefPubMed
26.
go back to reference Ashina M, Hansen JM, Do TP, Melo-Carrillo A, Burstein R, Moskowitz MA. Migraine and the trigeminovascular system-40 years and counting. Lancet Neurol. 2019;18(8):795–804.CrossRefPubMedPubMedCentral Ashina M, Hansen JM, Do TP, Melo-Carrillo A, Burstein R, Moskowitz MA. Migraine and the trigeminovascular system-40 years and counting. Lancet Neurol. 2019;18(8):795–804.CrossRefPubMedPubMedCentral
27.
go back to reference Al-Khazali HM, Ashina H, Wiggers A, Rose K, Iljazi A, Christensen RH, Schytz HW, Amin FM, Ashina M. Calcitonin gene-related peptide causes migraine aura. J Headache Pain. 2023;24(1):124.CrossRefPubMedPubMedCentral Al-Khazali HM, Ashina H, Wiggers A, Rose K, Iljazi A, Christensen RH, Schytz HW, Amin FM, Ashina M. Calcitonin gene-related peptide causes migraine aura. J Headache Pain. 2023;24(1):124.CrossRefPubMedPubMedCentral
28.
29.
go back to reference Sarchielli P, Alberti A, Coppola F, Baldi A, Gallai B, Floridi A, Floridi A, Capocchi G, Gallai V. Platelet-activating factor (PAF) in internal jugular venous blood of migraine without aura patients assessed during migraine attacks. Cephalalgia. 2004;24(8):623–30.CrossRefPubMed Sarchielli P, Alberti A, Coppola F, Baldi A, Gallai B, Floridi A, Floridi A, Capocchi G, Gallai V. Platelet-activating factor (PAF) in internal jugular venous blood of migraine without aura patients assessed during migraine attacks. Cephalalgia. 2004;24(8):623–30.CrossRefPubMed
30.
go back to reference Turan E, Kilic SS. Retrospective view of primary Raynaud’s phenomenon in childhood. Reumatol Clin (Engl Ed). 2019;15(6):e92–5.CrossRefPubMed Turan E, Kilic SS. Retrospective view of primary Raynaud’s phenomenon in childhood. Reumatol Clin (Engl Ed). 2019;15(6):e92–5.CrossRefPubMed
31.
go back to reference Korniluk A, Koper-Lenkiewicz OM, Kaminska J, Kemona H, Dymicka-Piekarska V. Mean platelet volume (MPV): New perspectives for an old marker in the course and prognosis of inflammatory conditions. Mediators Inflamm. 2019;2019:9213074.CrossRefPubMedPubMedCentral Korniluk A, Koper-Lenkiewicz OM, Kaminska J, Kemona H, Dymicka-Piekarska V. Mean platelet volume (MPV): New perspectives for an old marker in the course and prognosis of inflammatory conditions. Mediators Inflamm. 2019;2019:9213074.CrossRefPubMedPubMedCentral
32.
go back to reference Ranucci M, Ranucci M, Laddomada T, Baryshnikova E, Nano G, Trimarchi S. Plasma viscosity, functional fibrinogen, and platelet reactivity in vascular surgery patients. Clin Hemorheol Microcirc. 2015;61(3):417–27.CrossRefPubMed Ranucci M, Ranucci M, Laddomada T, Baryshnikova E, Nano G, Trimarchi S. Plasma viscosity, functional fibrinogen, and platelet reactivity in vascular surgery patients. Clin Hemorheol Microcirc. 2015;61(3):417–27.CrossRefPubMed
33.
go back to reference Khasiyev F, Arsava EM, Topcuoglu MA. Cerebral vasomotor reactivity in migraine: effect of patent foramen ovale and aerogenic microembolism. Neurol Res. 2020;42(9):795–804.CrossRefPubMed Khasiyev F, Arsava EM, Topcuoglu MA. Cerebral vasomotor reactivity in migraine: effect of patent foramen ovale and aerogenic microembolism. Neurol Res. 2020;42(9):795–804.CrossRefPubMed
Metadata
Title
Calcitonin gene-related peptide: a possible biomarker in migraine patients with patent foramen ovale
Authors
Chaojie Li
Yu Yu
Ningning Li
Ya-Na Yin
Lianjun Zhang
Kehang Xie
Donghui Huang
Publication date
01-12-2024
Publisher
BioMed Central
Keywords
Migraine
Headache
Published in
BMC Neurology / Issue 1/2024
Electronic ISSN: 1471-2377
DOI
https://doi.org/10.1186/s12883-024-03615-1

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