Narcolepsy and cardiovascular disease: A two-sample Mendelian randomization study

Background: Observational findings suggest that patients with narcolepsy are at higher risk for cardiovascular diseases (CVDs), but the potential causal relationship between narcolepsy and CVDs is unclear. Therefore, Mendelian randomization (MR) was used to explore the association between narcolepsy and CVDs. Methods: Summary statistics related to narcolepsy, coronary artery disease (CAD), myocardial infarction (MI), heart failure (HF), any stroke (AS), and any ischemic stroke (AIS) were extracted from the public database of relevant published genome-wide association studies (GWAS). Independent single nucleotide polymorphisms were selected as instrumental variables under strict quality control criteria. Inverse variance-weighted (IVW) was the main analytical method to assess causal effects. In addition, we conducted MR pleiotropy residual sum and outlier (MR-PRESSO), weighted median, MR -Egger, and leave-one-out sensitivity analysis to verify the robustness and reliability of the results. Results: The results of the MR study revealed that narcolepsy was significantly associated with an increased risk of HF (OR = 1.714; 95%CI [1.031-2.849]; P = 0.037), CAD (OR = 1.702; 95%CI [1.011-2.864]; P = 0.045). There was no statistically significant causal association between narcolepsy and MI, AS, and AIS. In addition, further sensitivity analysis showed robust results. Conclusions: The results of the two-sample MR study reveal a potential causal relationship between the increased risk of HF and CAD in narcolepsy. These findings emphasize the importance of early monitoring and assessment of cardiovascular risk in patients with narcolepsy.