Hypertension and endothelial dysfunction in obstructive sleep apnea (OSA) – Is it related to hypoxia?

Abstract

Introduction OSA is a prevalent disorder causing hypertension. Endothelial dysfunction appears to underlie development of hypertension. It is generally believed that intermittent hypoxemia during sleep is the underlying process leading to hypertension. However, patients with OSA and hypertension have increased sympathetic tone while awake so as patients with OSA without hypertension. We have previously shown that both hypertensive (H-OSA) and normotensive OSA (N-OSA) patients have elevated plasma levels of catecholamines. It is not established whether hypoxia during sleep is necessarily the prerequisite process for endothelial dysfunction and hypertension in OSA. We therefore examined the relationship between endothelial-dependent vasodilatory capacity (using brachial artery flow-mediated method, FMD), arterial oxygen saturation (SaO2) in OSA and non-OSA patients with and without hypertension. We also investigated the role of angiogenic inhibitors that are known to cause endothelial dysfunction and hypertension. Materials and methods We studies 95 subjects with and without OSA and hypertension. Plasma angiogenic inhibitors, endoglin (sEng) and fms-like tyrosine kinase-1 (sFlt-1), were measured using ELISA. Results The apnea–hypopnea indexes were 41 ± 5 and 48 ± 4 /h in N-OSA ( n = 27) and H-OSA ( n = 36), respectively, indicating severe OSA. Asleep SaO2 T ± 8 and 40 ± 9 min, respectively. FMD was markedly impaired in H-OSA (8.0% ± 0.5) compared to N-OSA (13.5% ± 0.5, P ± 0.8, P n = 13), and N-non-OSA (16.1% ± 1.0, P n = 19). There was no correlation between T ± 5.9 and 63.9 ± 4.7 pg/ml) compared to N-non-OSA (32.1 ± 6.5, P = 0.0008 and P = 0.0004, respectively) and H-non-OSA (41.2 ± 7.0, P P = 0.03, respectively). sEng was elevated in H-OSA (4.20 ± 0.17 ng/ml) compared with N-OSA (3.64 ± 0.14, P = 0.01) and N-non-OSA (3.48 ± 0.20, P = 0.01). There was a modest but statistically significant inverse correlation between sEng and FMD in only H-OSA group ( r = −0.38, P Conclusion These data show that patients with OSA and hypertension have marked impairment of FMD independent of hypoxia exposure. FMD is not uniformly affected by exposure to intermittent hypoxia or apnea in patient with OSA. Impaired FMD is associated with increased sFlt-1 and sEng. The differences in sEng concentrations between H-OSA and control groups are comparable to those with target organ damage and hypertension and high risk for cardiovascular adverse outcome.