Plasma adrenomedullin levels in migraine: A registry for migraine (REFORM) study

Objective To compare plasma adrenomedullin (AM) levels between adults with migraine and healthy controls (HCs), assessing subgroup differences and clinical associations. Methods This cross-sectional, observational single-center study was carried out from September 2020 to June 2022. Adults with migraine and HCs were enrolled and underwent blood sampling. Migraine subgroups included episodic migraine, chronic migraine, migraine without aura and migraine with aura. Plasma AM concentrations were quantified using a validated immunoluminometric assay by trained personnel who were blinded to group status. Results In total, 667 participants with migraine and 147 HCs provided data eligible for analysis. Plasma AM concentrations did not differ significantly between the migraine and HC group (18.2 ± 9.1 pg/ml vs. 18.5 ± 8.4 pg/ml; p = 0.08). However, participants with episodic migraine exhibited lower AM levels than HCs (16.9 ± 7.7 pg/ml vs. 18.5 ± 8.4 pg/ml; p = 0.04). Multivariate regression models showed that plasma AM concentrations are positively associated with body mass index (4.2% increase in AM per kg/m 2 ; 3.6 to 4.8%; p < 0.001) and monthly migraine days (0.6% increase in AM per MMD; 0.2 to 1.0%; p = 0.006). Conclusions Plasma AM concentrations were comparable between participants with migraine and HCs; however, those with episodic migraine exhibited slightly lower levels. Future studies should investigate other candidate blood-based biomarkers for migraine.