The cardiovascular consequences of chronic sleep fragmentation: Evidence from experimental models of obstructive sleep apnea.

Sleep fragmentation (SF) and intermittent hypoxia (IH), hallmark features of obstructive sleep apnea (OSA), disrupt restorative processes by inducing sympathetic activation and endothelial dysfunction, contributing to cardiovascular risk. While IH has been extensively studied, the independent effects of SF remain underexplored. This study investigated the cardiovascular impact of chronic SF in a murine model mimicking moderate-to-severe OSA. Male C57BL/6J mice were exposed to chronic SF or control conditions for 12 weeks. Mean blood pressure (MBP), cardiac function, pulse wave velocity (PWV), and coronary flow velocity reserve (CFVR) were assessed. Endothelium-dependent relaxation in aortic and coronary vessels was examined ex vivo, and aortic histological analysis evaluated intima-to-media thickness and collagen content. SF significantly elevated MBP (107 ± 8 mmHg vs. 89 ± 5 mmHg; p = 0.0001) and PWV (4.3 ± 0.6 m/s vs. 3.1 ± 0.2 m/s; p = 0.0001), indicating hypertension and arterial stiffness. Endothelium-dependent relaxation was impaired in coronary (67 ± 9 % vs. 86 ± 5 %; p = 0.0004) and aortic (73 ± 12 % vs. 87 ± 7 %; p = 0.045) vessels. Histology revealed increased intima-to-media thickness (128 ± 9 μm vs. 102 ± 14 μm; p = 0.008) and collagen deposition (56 ± 10 μm vs. 41 ± 7 μm; p = 0.027). Cardiac function and CFVR were unaffected. Chronic SF independently drives cardiovascular dysfunction through hypertension, arterial stiffness, endothelial impairment, and vascular remodeling. These findings emphasize SF as a distinct pathological factor in OSA, necessitating adjunctive interventions to mitigate cardiovascular risks.