Comorbidities as risk factors for migraine onset: A systematic review and three-level meta-analysis

Migraine is a debilitating neurological disease with a multifaceted pathophysiology. Pre-existing comorbidities may influence the risk of developing migraine. This review and meta-analysis aim to present a comprehensive overview of the known comorbidities predisposing individuals to new migraine onset, thereby improving our understanding of the respective diseases' interactions.

A systematic search of PubMed and EMBASE identified studies on pre-existing comorbidities as risk factors for new migraine onset. We performed three-level meta-analyses employing restricted maximum likelihood estimation to calculate pooled risk ratios (pRR). Subgroup and sensitivity analyses were conducted to assess the robustness of the data. Risk of bias (RoB) was assessed with the Quality in Prognostic Studies Tool. This review was pre-registered on Prospero (CRD42024501140).

From a total of 17,330 records, we identified 38 studies, encompassing 124 effect sizes from 58 exposures. Most studies (n = 28, 74%) had a low RoB. Heterogeneity was high (>90%), primarily due to within-study differences (>50%), and was not significantly impacted by moderator tests or the exclusion of outliers. We found significantly increased risks for migraine onset associated with prior atopic conditions [pRR = 1.53 (1.15, 2.03)], psychiatric or psychological disorders [pRR = 2.63 (1.79, 3.85)], sleep disorders [pRR = 1.89 (1.26, 2.85)], and cardiovascular conditions [pRR = 1.72 (1.07, 2.76)].

Pre-existing atopic, psychiatric, sleep, and cardiovascular conditions are significantly associated with new migraine onset, likely due to shared genetic predisposition and mediating factors like stress and inflammation. Future research should focus on these associations to advance targeted prevention and treatment strategies.