Background and aims: Circadian disruption and sleep disorders have been shown to increase the risk for many cardiovascular diseases. Their association specifically with valvular heart disease, however, is inconclusive. In this study we test the association between sleep disorders and the future incidence of aortic stenosis using two large electronic health record (EHR) databases datasets (the TriNetX network and the All of Us study). We also explore biochemical data for potential mechanistic insights into that association.
Methods: We fitted Cox proportional hazards models to quantify the risk of future incidence of AS in patients with sleep disorders. We also explored clinical laboratory test datasets for biochemical signals that might explain the association, running mediation analyses.
Results: In our fully adjusted Cox models, we find that having any sleep disorder increases the risk for the future incidence of AS (HR: 1.15 95 % CI: 1.13-1.18). Changes in lipid profile mediate a proportion of that association.
Conclusion: Sleep disorders are associated with an increased risk of AS incidence. That association is independent of classical cardiovascular risk factors even though dyslipidemia plays a large role in mediating this risk.
Keywords: Aortic stenosis; Circadian disruption; Risk factor; Sleep disorders.
© 2025 The Authors. Published by Elsevier B.V.