Migraine and the vascular system: much has been learned but still a long way to go.

Abstract

The link between migraine and the vascular system has been the focus of attention for decades, specifically the association between migraine and ischemic stroke (1). While basic science, clinical medicine, and populationbased studies have provided an abundance of new data, several aspects of the migraine-cardiovascular association remain unclear. In particular, pathophysiologic mechanisms and their translational implications within specific clinical situations often remain speculative. In this special issue of Cephalalgia, we have assembled reviews, viewpoints, and original data covering various aspects of the migraine-cardiovascular association. The experts have covered important pathophysiologic mechanisms, the potential influence of traditional and novel vascular risk factors, issues related to specific migraine treatment choices in patients with elevated vascular risk, and the influence of pregnancy on the migraine-cardiovascular association. In an extensive review, Mawet and colleagues look at current pathophysiological and clinical models linking migraine and stroke (2). In particular, they shed light on potential shared mechanisms that could explain the increased risk of stroke for some patients with migraine, as well as the potential clinical consequences. Liman and colleagues add new data linking migraine with aura with increased levels of endothelial microparticles and arterial stiffness (3). This further supports evidence that endothelial (dys)function may be an important mechanism that contributes to the increased risk of stroke in patients with migraine with aura. This mechanism is further discussed in detail in a commentary by Gretchen Tietjen (4). Labruijere and colleagues add new experimental data testing the effect of dihydroergotamine and sumatriptan in the isolated human coronary artery, middle meningeal artery, and saphenous vein (5). They demonstrate that in concentrations from dosages used in clinical practice, both medications induce only slight contraction of the distal coronary arteries but both induced larger contractions in meningeal arteries. Dihydroergotamine also had effects on the saphenous vein that were larger than the observed effects on arteries. These experimental data underscore the differential interaction of these two migraine-specific drugs with specific arterial and venous systems. Roberto and colleagues review the available data from observational studies to determine whether triptans and ergotamines increase the risk of cardiovascular events in the clinical setting (6). They conclude that the few available data suggest that, at least in recommended doses, these drugs do not appear to be associated with increased risk of adverse vascular outcomes but that firm conclusions cannot be drawn because of limited available data and other potential biases in the data sets available. Because of the potential vasoconstrictive properties of ergotamines and triptans, these drug classes are contraindicated in most of these patients. Diener and colleagues walk us through the dilemma that many physicians are left with when considering migraine-specific drug treatment choices among patients with elevated cardiovascular risk or with established cardiovascular disease (7), and provide some recommendations on how to balance risk-benefit decisions for such patients who need a reduction in headacherelated burden. The relationships of conventional vascular risk factors and vascular biomarkers are reviewed by Sacco and colleagues (8) and Tietjen and Khubchandani (9), respectively. Their data clearly show the tight link between migraine and various vascular risk factors that may contribute to the complex links between migraine and cardiovascular events. Wabnitz and Bushnell review for us the available data on the risk of various adverse vascular outcomes during pregnancy in women with a history of migraine