Association of plasma soluble urokinase plasminogen activator receptor concentrations and migraine with aura: a REFORM study

Soluble urokinase plasminogen activator receptor (suPAR) has garnered attention as a potential blood-based biomarker for low-grade chronic inflammation. However, its specific association with migraine, including its subtypes, remains to be elucidated. We sought to examine the association of plasma suPAR levels with migraine and its subtypes. In this single-centre, cross-sectional study, plasma was collected at a single time point in adults with migraine and sex-matched healthy controls from October 2020 to June 2022. The quantification of plasma suPAR levels was performed in a blinded fashion using a validated enzyme-linked immunosorbent assay. Plasma suPAR levels were compared between participants with migraine (including subgroups) and healthy controls. Plasma samples were analysed from 634 eligible participants with migraine [mean (SD) age, 44.0 (12.2) years; 568 (89.6%) females] and 154 healthy controls [mean (SD), 41.3 (11.8%) years; 132 (86%) females]. Plasma suPAR levels were 6.7% higher (95% CI: 0.1-13.6%; <i>P</i> = 0.045, adjusted for age, sex, body mass index and smoking) in participants with migraine <i>with</i> aura, when compared with healthy controls. Further analysis revealed no difference in plasma suPAR levels between the overall migraine group and healthy controls (3.7%; 95% CI: -0.7-8.2%; <i>P</i> = 0.097), as well as between participants with migraine without aura and healthy controls (2.5%; 95% CI: -2.9-8.3%; <i>P</i> = 0.81). Similarly, plasma suPAR levels did not differ across participants with episodic migraine, chronic migraine and healthy controls. Finally, we found no difference when comparing participants with migraine at time of blood sampling with participants with non-migraine headache (1.0%; 95% CI: -5.7-8.2; <i>P</i> > 0.99), participants without headache (1.2%; 95% CI: -4.2-7.0%; <i>P</i> > 0.99) or healthy controls (4.5%; 95% CI: -1.9-11.3%; <i>P</i> = 0.39). Elevated plasma suPAR levels in migraine with aura indicate the presence of low-grade chronic inflammation. Future research should explore the role of suPAR in the neurobiologic underpinnings of migraine with aura.