C-reactive protein and migraine. Facts or speculations?

Migraine is a highly prevalent and frequently disabling disorder. Since the pathogenesis of this condition has a strong inflammatory component and migraine is significantly associated with cardiovascular disease, we assess whether C-reactive protein (CRP) may be epidemiologically or casually linked with migraine. An electronic search on Medline, Scopus and Web of Science produced 17 studies reporting original data about the epidemiological association between CRP and migraine (1 retrospective, 1 interventional, 14 cross-sectional and 1 both interventional and cross-sectional). When all studies reporting sufficient data about CRP values were pooled (n = 12; 6980 cases and 38,975 controls), the concentration of CRP was found to be significantly higher in patients with migraine than in controls (weighted mean difference 1.12 mg/L; 95% CI 1.01-1.25 mg/L; p < 0.001). In further analysis of studies containing separate data for migraine with and without aura (n = 7), CRP values remained significantly higher in both migraineur patients with aura (n = 1939; weighted mean difference 0.88 mg/L; 95% CI 0.63-1.14 mg/L; p < 0.001) or without aura (n = 2483; weighted mean difference 1.04 mg/L; 95% CI 0.78-1.30 mg/L; p < 0.001) when compared with controls (n = 29,354). Despite a large inter-study heterogeneity (99.3%), our analysis provides evidence of a potential epidemiological association between increased concentration of CRP and migraine, thus paving the way for further clinical investigations about therapeutic agents that may contextually decrease the risk of cardiovascular disease and reduce the burden of migraine.