Abstract
Introduction: Circadian disruption has been implicated in the development of various cardiovascular diseases in several epidemiological studies. The role of molecular clocks in heart failure and vascular disease has also been extensively studied in animal and human models. However, studies assessing circadian rhythms in aortic valve disorders are lacking. We hypothesize that circadian disruption due to sleep disorders increases the risk for a diagnosis of calcific aortic stenosis (AS). Methods: We requested electronic health record (EHR) data from 8.8 million patients with ICD9 and ICD10 codes for sleep disorders and from 8.8 million patients without these diagnosis codes from the TriNetX Diamond network. We then ran cox proportional hazards models for the incidence of non-rheumatic aortic stenosis (ICD10 codes I35.0 and I35.2) after age 60 for patients diagnosed with sleep disorders (ICD10 G47-, ICD9 327-) before age 60 compared to patients with no sleep disorder diagnosis before age 60. We adjusted the models to include sex, BMI, and ICD codes for hypertension, hyperlipidemia, diabetes, and chronic kidney disease. We excluded patients with congenital aortic valve disorders, and patients with aortic valve procedures but no AS. Results: In our adjusted models, patients with any sleep disorder were at a significantly higher risk for being diagnosed with AS after age 60 (Figure). Analysing each individual sleep disorder we find that sleep apnea, hypersomnia, and narcolepsy are the main drivers for the association compared to other sleep disorders. The differences in adjusted and un-adjusted models indicate that a portion of the effect may be driven by cardiometabolic and renal risk factors. Conclusions: Circadian disruption due to a diagnosis of a sleep disorder increases the risk for developing AS. While some disorders are independent risk factors, in others the higher risk might be driven by the presence of known cardiometabolic and renal risk factors.
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