Interpreting the study on narcolepsy and cardiovascular outcomes: expanding clinical perspectives

To the Editor, We read with great interest the recent publication titled “Narcolepsy and risk of cardiovascular outcomes beyond stimulant use” by Riaz et al. [1] The narcolepsy – cardiovascular disease (CVD) risk association was investigated in a large population-based study that considered stimulant use as a time-varying covariate. This study, despite sound methodology and large data, leaves scope for more work as some important areas remain unexplored. Firstly, the authors considered stimulant exposure but did not incorporate any multimodal physiological data (e.g., polysomnography-derived features or autonomic markers) which could help shed light on mechanistic pathways linking narcolepsy to cardiovascular disease. Self-supervised or deep learning models trained on multimodal sleep data can be used in future studies to identify hidden cardiovascular risk profiles in narcolepsy patients [2]. These integrative approaches will refine present claims-based proxies and facilitate quantification of subclinical changes in cardiac autonomic regulation. Secondly, there was no examination of dynamic weight change and metabolic parameters which are important intermediators of obesity and metabolic dysfunction with sleep disorder and cardiovascular outcome. The study of gradual changes in body mass index trajectories and related metabolic alterations could shed further light on the timing relationship of narcolepsy symptoms and treatment with CVD risk [3]. The aim of these analyses is to ascertain whether narcolepsy per se or its metabolic comorbidities is primarily responsible for the adverse cardiovascular outcomes.