Abstract Rationale Prior research suggests increased mortality among patients with narcolepsy compared to the general population, but comparative evidence among patients referred for sleep evaluation remains limited. Understanding mortality and healthcare utilization differences between narcolepsy and other sleep disorders may inform risk management and clinical care. Methods This retrospective cohort study analyzed Veterans Affairs (VA) electronic health records (October 1999 - March 2025). Patients with narcolepsy were identified using validated ICD-9/10 algorithms and categorized as narcolepsy type 1 (NT1). We constructed two propensity-matched control groups: (i) general sleep clinic (GSC; no chronic hypersomnia), matched 1:3 to cases on age, sex, race/ethnicity, and diagnosis year; and (ii) non-NT1 narcolepsy (no NT1 ICD codes), matched 1:1 on the same variables. The primary outcome was all-cause mortality; secondary outcomes included hospitalization and emergency/urgent-care (ED/UC) visits. Logistic regression models estimated adjusted odds ratios (aOR) controlling for body mass index (BMI) and Charlson Comorbidity Index (CCI). Results The study included 12,483 GSC, 4,161 NT1, and 4,161 non-NT1 patients. Mean ages were 43.8, 48.0, and 47.6 years, respectively. Both narcolepsy groups had fewer major comorbidities than GSC controls, including cardiovascular (42-44% vs 48%), metabolic (36-38% vs 45%), psychiatric (43-48% vs 53%), and sleep apnea (33-37% vs 65%). All-cause mortality was 15.0% in GSC, 24.7% in NT1, and 29.1% in non-NT1. Compared with GSC, mortality risk was significantly higher in NT1 (aOR 2.16; 95% CI 1.97-2.36) and non-NT1 (aOR 2.63; 95% CI 2.41-2.88). Total hospitalizations were modestly increased in NT1 (aOR 1.24; 95% CI 1.16-1.34) and non-NT1 (aOR 1.12; 95% CI 1.03-1.20), while ED/UC visits were significantly lower in both NT1 (aOR 0.63; 95% CI 0.58-0.69) and non-NT1 (aOR 0.42; 95% CI 0.38-0.46). Conclusions Among veterans referred for sleep evaluation, patients with narcolepsy—both NT1 and non-NT1—experienced more than twofold higher adjusted mortality compared with matched sleep clinic controls, even after accounting for BMI and comorbidity burden. These findings suggest that narcolepsy confers disease-specific mortality risk, underscoring the need for systematic cardiovascular surveillance, risk-factor management, and longitudinal studies to elucidate underlying mechanisms. This abstract is funded by: Jazz Pharmaceutical
Azarian et al. (Fri,) studied this question.