Urinary metabolomic biomarkers predict early cardiovascular risk in moderate-to-severe obstructive sleep apnea

<bold>Study Objective:</bold> There are currently no ideal biomarkers to predict the cardiovascular risk of obstructive sleep apnea (OSA). This study aimed to employ urinary metabolomics to detect early cardiovascular risk in moderate-to-severe OSA patients. <bold>Methods:</bold> We included 22 moderate-to-severe OSA males and 14 sex-matched controls. Clinical data, polysomnography and urine samples were collected. Untargeted metabolomics analyses of urine were performed. Multivariate analyses and receiver operating characteristic analyses were employed to identify potential biomarkers. Associations between metabolites, clinical indicators and cardiovascular risk were examined through linear regression analyses with interaction and mediation analyses. <bold>Results:</bold> Sixty-five metabolites were found in the study, involving pathways including pyrimidine, androgen, estrogen, Vitamin B6 and sulfate/sulfite metabolism. ROC analyses highlighted epinephrine sulfate with the highest AUC (0.883) to detect moderate-to-severe OSA. It had a statistically significant correlation with OSA severity, hypoxia-related indicators (apnea-hypopnea index: r=0.685; oxygen desaturation index: r=0.743, p<0.0001), arterial stiffness(arterial augmentation index: r=0.361, p=0.031) and long-term cardiovascular risk (Framingham cardiovascular risk: r=0.375, p=0.024). Linear regression analysis showed epinephrine sulfate significantly increased the Framingham cardiovascular risk (β=0.004, 95% CI: 0.000-0.009, p=0.049). <bold>Conclusions:</bold> There are significant metabolic pathway alterations in moderate-to-severe OSA patients. Epinephrine sulfate markedly predicts early cardiovascular risk assessment in OSA patients.