26 Chapter 1 CARDIOVASCULAR RISK IN WOMEN WITH MIGRAINE Migraine is associated with an increased risk of myocardial infarction (OR 2.2, 95% CI 1.7-2.8) and stroke (OR 1.5, 95% CI 1.2-2.1).67-69 Especially women with migraine with aura exhibit a higher incidence of cardio- or cerebrovascular diseases (CVD), and the relative risk of stroke increases to a 35-fold elevated risk when a young woman with migraine with aura also smokes and uses the oral contraceptive pill.62, 63, 70-72 Migraine poses a greater risk factor than an unfavourable cholesterol profile, overweight, or familial predisposition to CVD.67, 69 Therefore, it is important to monitor the CVD risk in patients, especially in young women. The hypothesis is that this increased risk is the result of a shared pathophysiological mechanism, where both the cardiovascular risk and migraine are manifestations of the same predisposition to vascular dysfunction of small blood vessels, in which endothelial dysfunction may play a role.73 Genetic factors likely play an important role, since genome-wide association studies have identified vascular risk factors and observed associations between migraine and vascular diseases.74 This association is stronger for migraine with aura compared to migraine without aura, suggesting that the underlying mechanisms may differ between the two migraine subtypes, with migraine with aura potentially involving more pronounced vascular abnormalities or endothelial dysfunction. Important to note is that after an ischemic event, elevated levels of CGRP are observed, which likely play a protective role in regulating vascular tone after an infarct.75 Since CGRP is elevated during a migraine attack and thus treatment is now focused on inhibiting CGRP, clinicians should carefully evaluate the safety of CGRP inhibitors for women with migraine, particularly concerning potential ischemic events.76, 77 OUTLINE OF THE THESIS The aim of this thesis is to provide a deeper understanding of the clinical aspects of migraine, particularly in women, and to explore the impact of emerging anti-CGRP treatments, including potential cerebro- and cardiovascular risks. Various clinical and pathophysiological factors that influence the threshold for upcoming migraine attacks will be studied.
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