Comprehensive Metabolomics and Machine Learning Identify Profound Oxidative Stress and Inflammation Signatures in Hypertensive Patients with Obstructive Sleep Apnea

Obstructive sleep apnea (OSA) can aggravate blood pressure and increase the risk of cardiovascular diseases in hypertensive individuals, yet the underlying pathophysiological process is still incompletely understood. More importantly, OSA remains a significantly undiagnosed condition. In this study, a total of 559 hypertensive patients with and without OSA were included. Metabolome and lipidome-wide analyses were performed to explore the pathophysiological processes of hypertension comorbid OSA and derive potential biomarkers for diagnosing OSA in hypertensive subjects. Compared to non-OSA hypertensive patients (discovery set = 120; validation set = 116), patients with OSA (discovery set = 165; validation set = 158) demonstrated a unique sera metabolic phenotype dominated by abnormalities in biological processes of oxidative stress and inflammation. By integrating three machine learning algorithms, six discriminatory metabolites (including 5-hydroxyeicosatetraenoic acid, taurine, histidine, lysophosphatidic acid 16:0, lysophosphatidylcholine 18:0, and dihydrosphingosine) were selected for constructing diagnostic and classified model. Notably, the established multivariate-model could accurately identify OSA subjects. The corresponding area under the curve values and the correct classification rates were 0.995 and 96.8% for discovery sets, 0.997 and 99.1% for validation sets. This work updates the molecular insights of hypertension comorbid OSA and paves the way for the use of metabolomics for the diagnosis of OSA in hypertensive individuals.