Endothelial dysfunction and hypertension in obstructive sleep apnea – Is it due to intermittent hypoxia?

Abstract

a b s t r a c tBackground: Obstructive sleep apnea (OSA) is a prevalent disorder causing hypertension. Endothelial dysfunction appears to underlie development of hypertension. It is not known 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, hypoxia and circulating angiogenesis inhibitors in OSA. Methods and results:We studies 95 subjects with and without OSA and hypertension. Endothelialdependent vasodilation was assessed using brachial artery flow-mediated vasodilation method (FMD). Plasma angiogenesis inhibitors, endoglin (sEng) and fms-like tyrosine kinase-1 (sFlt-1), were measured using ELISA. The apneaehypopnea indexes were 41 AE 5 and 48 AE 4 events/hr in normotensive OSA (N-OSA) and hypertensive OSA (H-OSA), respectively, indicating severe OSA. The sleep time spent with SaO 2 < 90% (T < 90%) were 34 AE 8 and 40 AE 9 min, respectively. FMD was markedly impaired in H-OSA (8.0% AE 0.5) compared to N-OSA (13.5% AE 0.5, P < 0.0001), H-non-OSA (10.5% AE 0.8, P < 0.01), and N-non-OSA (16.1% AE 1.0, P < 0.0001). There was no correlation between T < 90% and FMD. Both OSA groups had elevated levels of sFlt-1 (62.4 AE 5.9 and 63.9 AE 4.7 pg/ml) compared to N-non-OSA (32.1 AE 6.5, P ¼ 0.0008 and P ¼ 0.0004, respectively) and H-non-OSA (41.2 AE 7.0, P < 0.05 and P ¼ 0.03, respectively). In contrast, sEng was only elevated in H-OSA (4.20 AE 0.17 ng/ml) compared with N-OSA (3.64 AE 0.14, P ¼ 0.01) and N-non-OSA (3.48 AE 0.20, P ¼ 0.01). There was a modest but statistically significant inverse correlation between sEng and FMD in only H-OSA group (r ¼ À0.38, P < 0.05). Conclusion: These data show that patients with OSA and hypertension have marked impairment of FMD, independent of hypoxia exposure, which is associated with increased sEng.Copyright Ó 2013, SciBioIMed.Org, Published by Reed Elsevier India Pvt. Ltd. All rights reserved. Key MessagesObstructive sleep apnea is a highly prevalent disorder with associated high morbidity and mortality. Obstructive sleep apnea is now considered as one of the causes of systemic hypertension. No all patients with obstructive sleep apnea develop hypertension. There appears to be divergent responses to apnea-associated hypoxia. In this article a group of patients with severe obstructive sleep apnea and hypoxia exposure during sleep had normal blood pressure and relatively preserved endothelial-dependent vasodilatory capacity. A comparable group of patients with similar apnea severity and hypoxia exposure had marked impairment in endothelial-dependent vasodilatory capacity and hypertension. This group had significantly elevated circulating levels of soluble endoglin, an angiogenesis inhibitor, with known effect on endothelial function and development of hypertension. It is conceivable that inflammatory state of obstructive sleep apnea provokes release of angiogenesis inhibitors causing downstream perturbation of endothelial...

The Relation of Polysomnographic Parameters to Carotid and Brachial Artery Intima-media Thickness in Patients with Severe Obstructive Sleep Apnea Syndrome

“…However, no association was documented between CIMT and sleep parameters in our patient population even it was composed entirely of patients with severe OSAS who had moderate rates of concomitant degree of obesity and dyslipidemia.Being able to be measured simultaneously to flow-mediated vasodilation (FMD) assessed in the same brachial artery, BA-IMT was shown to significantly correlate to a cumulative cardiovascular risk index for heart attack as well as to carotid IMT (8). Our findings support that brachial IMT may be a marker of the grade of atherosclerosis and vascular function, providing additive information for stratifying subjects with cardiovascular risk factors and of value in the assessment of atherosclerosis(8,26).Based on the predictive role of apnea duration and arousal index on BA-IMT rather than CIMT, endothelial function may be assumed not to be uniformly affected by exposure to intermittent hypoxia or apnea events in patient with OSA(27). In this regard, given that brachial not carotid IMT was associated with sleep parameters in our patients with severe OSAS, our findings indicate the divergent vascular responses to obstructive apneas and intermittent hypoxia in OSA population(28) and are in agreement with the statement that the thickening process of the intima-media of the carotid artery might be different from the atherosclerotic process that occurs in the coronary artery, whereas the mechanism responsible for endothelial dysfunction of the brachial artery parallels the atherosclerotic process of the coronary artery (29).BA-IMT was demonstrated to be associated with cardiovascular risk factors and coronary artery disease (CAD) and the prognostic value of BA-IMT was shown in terms of late cardiovascular events in patients admitted for stable angina on multivariate Cox regression analysis, BA-IMT >0.37mm (odds ratio=1.96; p=0.03), remained significantly associated with cardiovascular events (30).Accordingly, our findings related to predictive role of apnea duration and arousal index on BA-IMT values should be cautiously interpreted given that average 0.26 (left) and 0.27 (right) mm of BA-IMT in in our patients with severe OSAS.…”

Age, Body Mass Index, and Daytime and Nocturnal Hypoxia as Predictors of Hypertension in Patients With Obstructive Sleep Apnea

“…Nevertheless, there are several studies in which the majority of examined patients were men. 12,37,38,45 Furthermore, hypertensive individuals were defined as patients who were previously diagnosed as hypertensive and were also taking at least one antihypertensive agent. Blood pressure measurements taken in the sleep clinic were not used to diagnose hypertension, as these were single readings obtained in the sitting position, which cannot be used as a reliable indicator for a hypertension definition.…”

An update on cardiovascular effects of obstructive sleep apnoea syndrome

“…The duration of desaturation (SpO 2 <90%) was not associated with flow-mediated vasodilatation. Plasma levels of FMS-like tyrosine kinase 1, which is a type of VEGF receptor, were increased in hypertensive and normotensive patients with OSA 22. Paediatric patients with OSA showed reduced flow-mediated vasodilatation compared with controls and there was a negative correlation between flow-mediated vasodilatation and AHI 23…”