Migraine is a prevalent debilitating neurovascular disorder, affecting more than 1 billion people globally. Migraine attack usually consists of four different phases including prodrome, aura, headache, and postdrome phases. The headache phase is associated with several symptoms including photophobia, nausea, vomiting, and fatigue which disturb daily activities and reduce the quality of life of migraineurs (1). The burden of migraine, however, is not restricted to the headache phase and patients may suffer from several symptoms such as hypersensitivity, phonophobia, photophobia, and vestibular disorders in the interictal phase, the phase between migraine attacks (2, 3). Although the exact molecular and cellular mechanisms underlying migraine pathogenesis are not completely understood, several reasonable explanations have been proposed. At the molecular level, the critical role of calcitonin-gene-related peptides (CGRPs) in the pathogenesis of migraine has been documented and CGRP receptor antagonists and monoclonal antibodies against CGRP or its receptors have revealed substantial efficacy in the treatment of migraine attacks (4). In addition to CGRP receptors, numerous studies have indicated the high efficacy and safety of 5-HT1F receptor agonists such as Lasmiditan in the treatment of migraine (5). At the cellular level, prior studies have described the role of mitochondrial dysfunction in the pathogenesis of migraine. The correlation of migraine with mitochondrial genome polymorphisms and biomarkers of oxidative stress are amongst the evidence that indicates the possible contribution of mitochondrial dysfunction to migraine pathology (6). A wide range of risk factors has been identified for migraine. Multiple investigations have concluded the important role of genetic factors in migraine development including familial aggregation of migraine, a high concordance rate of migraine in monozygotic twins, and the association between several genetic polymorphisms with the increased risk of migraine (7). The association of migraine with demographic characteristics such as sex and age have also been described. Women are at a higher risk of migraine development than men which could be related to differences in sex hormone fluctuations or psychological factors. Although migraine can occur at any age, their prevalence rate exhibits an age-dependent manner, increases from early life to middle age, and then gradually declines (8). Clinical and experimental data have revealed the association of migraine with numerous comorbidities including cardiovascular, psychiatric, neurologic, as well as inflammatory disorders. The association with these comorbidities complicates the diagnosis, increases the risk of progression to chronic migraine, limits treatment options, and lowers the quality of life of migraineurs. Therefore, understanding migraine comorbidities is very important because it can help to determine possible common or overlapping pathological mechanisms of diseases and can lead to the development of new diagnostic and therapeutic strategies (9). A growing body of evidence has revealed a significant association between migraines, particularly migraine with aura, with cardiovascular diseases (CVDs) such as ischemic heart disease, myocardial infarction, angina, and arrhythmia (10). Because alteration in blood flow is involved in the pathogenesis of migraines and CVDs, this association can be described by inadequate blood flow to the heart or brain due to genetic factors, endothelial dysfunction, and coagulation abnormalities (11). Cardiac syndrome X (CSX), is a type of ischemic heart disease, that is characterized by angina-like chest pain, and ST segment depression during exercise, without any evidence of significant coronary vascular abnormalities at coronary angiography (12). CSX is more prevalent in postmenopausal women. Although the potential risk factors for CSX have not yet been fully elucidated, several mechanisms may involve including microvascular abnormalities (13) and mitochondrial dysfunction. Because these abnormalities have been proposed in the etiology of migraine, we have suggested a link between migraine and CSX in our previous study (14). In this study, we have extended our previous study to a larger population of CSX patients. Furthermore, the association of several risk factors, notably sex and familial aggregation are evaluated.