Altered Serum Levels of Renin-Angiotensin System Markers in Migraine

Objective: To compare the serum levels of renin-angiotensin system (RAS) components between patients with migraine and healthy controls, and to evaluate whether these levels are associated with migraine severity. We hypothesized that migraine would be associated with the activation of the inflammatory arm of the RAS, possibly leading to increased levels of angiotensin (Ang) II. Background: Recent studies have proposed the use of drugs that interfere with RAS, a hormonal system primarily implicated in blood pressure regulation, as a prophylactic strategy for migraine. However, no previous studies have directly assessed RAS components in migraine. Methods: This was a cross-sectional study involving 30 patients with episodic migraine who were in the interictal period and 20 healthy controls. This study was conducted at Hospital das Clínicas (Universidade Federal de Minas Gerais, Belo Horizonte, Brazil) outpatient clinic. Headache severity was evaluated using the Headache Impact Test, version 6 (HIT-6) and the Migraine Disability Test (MIDAS) questionnaires. Given that migraine is comorbid with mood disorders, depressive and anxious symptoms were evaluated using the Beck Anxiety and Depression Inventories (BDI and BAI), respectively. Clinical and demographic data were also collected. Serum levels of angiotensin-converting enzyme (ACE), ACE2, Ang II, and Ang (1-7) were measured by enzyme-linked immunosorbent assay. Results: Patients with migraine and controls were comparable in age, body mass index, blood pressure, and depressive and anxious symptoms. Patients with migraine showed lower levels of ACE [85.2 (66.8, 101.2) vs 65.5 (54.2, 77.5); P =.005] and lower ACE/ACE2 ratio [4.3 (3.4, 5.2) vs 3.5 (2.9, 4.1); P =.032] than controls. Conversely, patients with migraine had higher levels of Ang II [309.7 ± 147.4 vs 605.4 ± 200.4; difference: −287.1 (95% CI: −391.4-−182.8), P <.001] and Ang (1-7) [214.4 ± 155.8 vs 397.9 ± 217.9; difference: −184.6 (95% CI: −296.7-−72.6), P =.001] than controls. There were no correlations between RAS serum markers and migraine severity scores (HIT and MIDAS) or depressive and anxious symptoms (BDI and BAI) (P >.05). Conclusions: Altogether, our results suggest the participation of RAS in migraine pathophysiology, but not in its severity.