We read the report by Aslan et al investigating the association of migraine with coronary microvascular dysfunction using transthoracic Doppler echocardiography in a total of 40 migraineurs and 35 age- and gender-matched healthy subjects. They have found that coronary flow reserve (CFR) was significantly lower in the migraine group (regardless of the aura) than the control group (1.99 ± 0.3 vs 2.90 ± 0.5, p <0.05). Also, CFR was significantly lower in women compared with men (2.32 ± 0.6 vs 2.63 ± 0.6, p <0.05). Although it has not been aimed primarily in this study, migraineurs revealed early diastolic dysfunction compared with healthy controls. After controlling for possible confounding factors, migraine has emerged as the only significant predictor of abnormal CFR (odds ratio 4.62, 95% confidence interval 1.06 to 20.61, p = 0.04).

Migraine carries an increased risk for cardiovascular and cerebrovascular diseases that cannot be explained by traditional cardiovascular risk factors. The mechanisms that link migraine to vascular diseases remain uncertain and are likely to be complex. The circulating endothelial progenitor cell (EPC) number is a surrogate biologic marker of vascular function, and diminished EPC counts are associated with higher cardiovascular risk. In their study, Lee et al showed that circulating EPC numbers and functions are reduced in migraineurs, suggesting that EPCs can be an underlying link between migraine and cardiovascular risk. Also, Yetkin et al showed that migraineurs have decreased endothelium-dependent vasodilatation capacity compared with nonmigraineurs. Additionally, Rodríguez-Osorio et al proposed that patients with migraine show reduced numbers of EPCs and increased levels of calcitonin gene–related peptide, nitric oxide (NOx), and vascular endothelial growth factor than control subjects. No changes were found for flow-mediated dilatation in interictal periods or during headache. Furthermore, EPCs decreased with the time of evolution of migraine (r = −0.592, p <0.0001). These findings suggest altered endothelial function with possible pathophysiological mechanisms in patients with migraine. As a result of all those previous studies, migraine may be a local manifestation of systemic vascular vasomotion abnormalities.

Previous studies evidenced that vascular endothelial function is markedly influenced by estrogen level and improved by hormone replacement therapy in postmenopausal women through the enhancement of NOx production. In an in vitro study, Tsuda et al demonstrated that estrogen deficiency might be involved in the pathophysiology of vascular complications in women. In contrast, it has been shown that endothelial function varied during the menstrual cycle in premenopausal women, suggesting that sex hormone status would have a crucial role in cardiovascular risk and other disease processes in premenopausal women. Therefore, we would like to know whether endogenous estrogen status might be associated with the coronary microvascular dysfunction assessed by CFR and migraine in young women in the study of Aslan et al. It would be important to assess more precisely the relations between estrogen status and endothelial function during the menstrual cycle and their contribution to the pathogenesis of impaired CFR in young women with migraine.

In conclusion, there would be a common pathophysiological pathway of impaired coronary and cerebral endothelial function in which EPC number and estrogen status may play a role.