Systemic and cerebral endothelial dysfunction in chronic migraine. A case-control study with an active comparator

Background and objective Unlike migraine and migraine with aura, little information exists regarding chronic migraine (CM) as a risk factor for cardiovascular disease. In this study we aim to determine whether an association between CM and endothelial dysfunction exists. Methods Individuals 18 years and older diagnosed with episodic migraine (EM) and CM according to ICHD criteria were studied. After an overnight fast and abstinence from vasoactive drugs, ultrasound studies were performed and blood samples taken from patients and matched controls according to internationally agreed on protocols. Results A total of 113 individuals were enrolled (35 CM, 37 EM, 41 controls). CM patients had a lower percentage of flow-mediated vasodilation (FMD; difference of means=5.03%; p=1.0E-6) and breath-holding index (BHI; difference of means 0.754; p=2.0E-6), as well as increased carotid intima media thickness (cIMT; difference of means=0.128mm; p=7.0E-5) than controls. The EM patients and controls comparison found similar, but less pronounced, differences: decreased BHI (p=0.031), and increased cIMT (p=0.028). Fibrinogen (r=0.277; p=0.006), C-reactive protein (r=0.288; p=0.003), and erythrocyte rate sedimentation (r=0.298; p=0.002) also correlated with cIMT, and inversely with BHImV and FMD. Conclusions Migraine is associated with systemic and cerebral endothelial dysfunction demonstrated by ultrasound studies and biological markers. The degree of these changes was strongly associated with the severity of migraine. Our data indicate that migraine may be a cerebral disorder with systemic endothelial damage.