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Review
. 2025 Aug;14(4):1229-1268.
doi: 10.1007/s40120-025-00785-z. Epub 2025 Jun 20.

From Headache to Heart Health: Investigating the Migraine-Cardiovascular Disease Connection

Claudio Tana  1 , Dilara Onan  2 , Roberta Messina  3 , Marta Waliszewska-Prosół  4 , David Garcia-Azorin  5 , Luis Leal-Vega  5 , Maria Begoña Coco-Martin  5 , Raffaele Ornello  6 , Bianca Raffaelli  7 , Marcio Nattan Portes Souza  8 , William Wells-Gatnik  9 , Paolo Martelletti  9
Affiliations
Review

From Headache to Heart Health: Investigating the Migraine-Cardiovascular Disease Connection

Claudio Tana et al. Neurol Ther. 2025 Aug.

Abstract

Migraine, particularly with aura, has been consistently associated with an increased risk of cardiovascular disease, including ischemic stroke and myocardial infarction. Shared pathophysiological mechanisms such as endothelial dysfunction, platelet aggregation, systemic inflammation, and autonomic imbalance suggest that migraine may act as an early clinical marker of systemic vascular vulnerability. Psychiatric comorbidities, frequently present in chronic migraine, further compound disability and may contribute to long-term cardiovascular risk. This narrative review discusses the evolving understanding of migraine as a multisystem disorder, emphasizing its vascular and neuropsychiatric dimensions. Emerging data on calcitonin gene-related peptide (CGRP)-targeting monoclonal antibodies highlight their efficacy not only in reducing headache burden but also their favorable cardiovascular safety profile. Moreover, preliminary evidence suggests these agents may have a positive effect on mood symptoms in patients with comorbid depression and anxiety. Recognizing migraine as a condition that intersects neurological, cardiovascular, and psychiatric pathways may support earlier risk stratification and guide integrated treatment approaches in complex patient populations.

Keywords: Aura; CGRP-targeted therapy; Cardiovascular disease; Depression; Medication overuse headache; Migraine.

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Conflict of interest statement

Declarations. Ethical Approval: This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors. Conflict of Interest: Claudio Tana is a member of the Editorial Board of The Journal of Headache and Pain and Editor of the Primary Care Section of Annals of Medicine. Dilara Onan has no conflict of interests to declare. Roberta Messina reports personal fees from Eli Lilly, Lunbeck, and Bromatech for participation on advisory boards and for speaker activities. Marta Waliszewska-Prosół is a member of the Editorial Board of The Journal of Headache and Pain; reports personal fees from AbbVie, Pfizer, Polpharma and Teva for speaker activities. David Garcia-Azorin is a member of the Editorial Board of The Journal of Headache and Pain, and has received research funding from the Regional Health Administration (Gerencia Regional de Salud SACYL) in Castilla y Leon, Spain. Speaker/travel grants/ clinical trials from Teva, Abbvie, Amgen, Eli Lilly, Lundbeck, Novartis, Pfizer and Biohaven. Luis Leal-Vega and Maria Begoña Coco-Martin have no conflict of interests to declare. Raffaele Ornello reports personal fees from Novartis, Teva, Lilly, and Pfizer, and non-financial support from AbbVie/Allergan, Lilly, Novartis, and Teva. BR received honoraria for consulting and lectures from Abbvie/Allergan, Lilly, Lundbeck, Novartis, and Teva as well as research funding from the German Research Foundation, the German Migraine and Headache Society and Novartis. Bianca Raffaelli is a member of the Editorial Board of The Journal of Headache and Pain; reports personal fees from AbbVie, Eli Lilly, Lundbeck, Novartis, Organon, Perfood and Teva for participating in advisory boards and/or speaker activities as well as research funding from Lundbeck, Novartis, Else Kröner-Fresenius-Stiftung, German Research Foundation and German Migraine and Headache Society. Marcio Nattan Portes Souza has received honoraria for oral presentations from Teva, Lilly, Novartis, Allergan/AbbVie, Sanofi, Lundbeck and Libbs. William Wells-Gatnik has no conflict of interests to declare. Paolo Martelletti is the Editor-in-Chief of The Journal of Headache and Pain and of SN Comprehensive Clinical Medicine. Paolo Martelletti and Raffaele Ornello are Editorial Board members of Neurology and Therapy. Paolo Martelletti and Raffaele Ornello were not involved in the selection of peer reviewers for the manuscript nor any of the subsequent editorial decisions.

Figures

Fig. 1
Fig. 1
Reported associations between migraine and neuro- or cardiovascular diseases with their potential risk modifiers. Solid lines indicate associations supported by consistent evidence, such as the link between migraine with aura and ischemic stroke, while dashed lines represent relationships that remain controversial or insufficiently substantiated in the literature, including those with atrial fibrillation and hemorrhagic stroke. This visual framework underscores the complexity of migraine as a systemic disorder with multifaceted vascular implications. Figure 1 is original and was created with BioRender.com. Agreement number for use: ML286AME6W
See this image and copyright information in PMC

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