Migraine and cardiovascular risk in women – a dive into the deep

Migraine is a neurovascular disorder affecting three times more women than men, and is ranked as the 2nd disabler worldwide. Fluctuations in sex hormones, possibly interacting with Calcitonin Gene-Related Peptide (CGRP) seem to be involved in the pathophysiology. Moreover, migraine is a major cardiovascular risk factor of yet unknown origin, seemingly unrelated to currently identified cardiovascular risk factors.

 I will assess the effects of sex hormones on the pathophysiology of migraine by measurements of hormone fluctuations in female migraineurs and by a clinical hormonal intervention study. In mice with different ‘migraine genotypes’, I will investigate the effects of different hormone levels on the trigeminovascular system, a key system in migraine pathophysiology. The increased vascular risk in migraine will be studied by microvascular function measurements in migraine patients. To study vascular function from specific patients in depth in a standardized environment, I will develop a ‘vessel-on-a-chip’ model allowing detailed pharmacological studies, ultimately even including measurements of contraction and relaxation. 

In the final part of my project, I will study how sex hormones and the increased vascular risk in migraine interact with the cardiovascular safety of novel (anti-CGRP) antimigraine treatment. Microvascular endothelial function will be assessed in patients before and after the use of this medication. In pigs, the effect of anti-CGRP medication on cardiac ischemia will be studied. In the ‘vessel-on-a-chip’ model, CGRP receptor and endothelial function will be studied in specific patients. Finally, CGRP receptor function will be studied in detail in human isolated blood vessels. The results of this project will provide more knowledge on the role of sex hormones in the pathophysiology of migraine and possibilities for hormonal treatment, as well as preventive measures to mitigate the cardiovascular risk in migraine. Finally, this knowledge will be applied to identify patients at potential risk after use of anti-CGRP medication.