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Abstract Introduction Narcolepsy is a lifelong disabling disorder causing profound daytime sleepiness. Symptoms present as early as childhood and result in marked disturbances in the life course of many persons with narcolepsy (PWN). Further, PWN experience several health conditions, including cardiovascular disease (CVD). Importantly, PWN often present with several co-occurring sleep disorders, including obstructive sleep apnea, which is a prominent risk factor for CVD. This study examined the association between narcolepsy and CVD comprehensively accounting for potential confounders predisposing PWN to CVD. Methods This retrospective cohort study used the 2005-2021 IBM® MarketScan® Commercial and Medicare supplemental databases to identify newly diagnosed PWN from at minimum 2 outpatient claims using the International Classification of Diseases–Clinical Modification (ICD-9/10-CM) diagnosis codes. In addition, we identified a comparison cohort of persons without narcolepsy or other hypersomnolent disorders, using propensity score (PS) matching 1: up to 3 ratios to balance groups based on underlying demographics, the presence of relevant health conditions, including sleep apnea and diabetes, and other confounders. Using Cox proportional hazard regression, we calculated hazard ratios (HR) with 95% confidence intervals (95%CI) to estimate CVD risk outcomes (including major adverse cardiovascular events MACE, heart failure, stroke, atrial fibrillation, and myocardial infarction MI) for PWN compared to non-narcolepsy. Patients were censored at the end of enrollment or up to December 13, 2021. Results Among 134,067 patients included (mean age=40±16.8 years; 62% female), 34,562 were PWN and 100,405 were matched non-narcolepsy patients. Compared to non-narcolepsy patients, PWN were associated with a 77% increased risk of any CVD (HR=1.77, 95%CI=1.65-1.89) and an 82% increased risk of MACE (HR=1.82, 95%CI=1.66-1.99). PWN also were associated with an increased risk of heart failure (HR=1.64, 95%CI=1.47-1.83), any stroke (HR=2.04, 95%CI=1.82-2.29), atrial fibrillation (HR=1.58, 95%CI=1.40-1.77), and MI (HR=1.64, 95%CI=1.37-1.96) compared to non-narcolepsy patients. Conclusion Using a large representative commercial insurance claims database, our study provides evidence that narcolepsy is an independent risk factor of CVD after comprehensive matching and adjustment for relevant confounders, including sleep apnea. Support (if any) This study was supported by the Sleep Research Society Foundation (Grant #: 23-FRA-001).
Kaufmann et al. (Sat,) studied this question.