Different effects of apnea during rapid eye movement period on peripheral arterial stiffness in obstructive sleep apnea

Highlights

• Obstructive sleep apnea (OSA) is associated with arterial stiffness but is rarely studied. Among 275 patients recruited, 40.7% had rapid eye movement (REM)-predominant OSA.

• We used polysomnography to assess patients' apnea–hypopnea index (AHI) during rapid eye movement (REM) periods (AHI-REM) of sleep.

• AHI-REM was independently correlated with a clinically useful peripheral arterial stiffness index, compliance index (CI).

• An increase in the interquartile range of AHI-REM was associated with a 9.6% decrease in CI.

• AHI-REM may be a suitable surrogate marker for predicting peripheral arterial stiffness in OSA patients.

Abstract

Bakground and aims

Obstructive sleep apnea (OSA) contributes to cardiovascular diseases, including arterial stiffness. The association between OSA and peripheral arterial stiffness indices remains controversial.

Methods

This study recruited 275 patients who were referred for sleep apnea study. Arterial stiffness was assessed by peripheral compliance index (CI) and central pulse wave velocity derived from digital volume pulse (PWV_DVP) by photoplethysmography. Overnight polysomnography and autonomic nerve system function tests were also conducted.

Results

A total of 275 patients (170 men) were recruited. Most were middle-aged and overweight. Most patients (112/275, 40.7%) had rapid eye movement (REM)-predominant OSA. The CI was significantly correlated with the apnea–hypopnea index (AHI) (R = −0.132, p = 0.029) and AHI-REM (R = −0.170, p = 0.005) and AHI non-REM (R = −0.122, p = 0.043). Among models and variable used to predict CI, only male sex (B = −0.708, p = 0.007) and AHI-REM (B = −0.010, p = 0.033) were independent predictors of CI. An increase in the interquartile range of AHI-REM was associated with a 9.6% decrease in CI.

Conclusions

AHI-REM was independently correlated with a peripheral arterial stiffness index, CI. AHI-REM may be a suitable surrogate marker for predicting peripheral arterial stiffness in OSA patients.

Introduction

Obstructive sleep apnea (OSA) is a clinical disorder that is characterized by intermittent hypoxia, arousals, and exaggerated ventilatory efforts with excessive negative intrathoracic pressure fluctuations that result in increased sympathetic nerve activity, oxidative stress, endothelial dysfunction, and vascular stiffness [1,2]. The prevalence of OSA is about 6%–13% in the middle-aged population, with higher values of up to 19%–37% in older individuals [3,4]. OSA is associated with increased risk of cardiovascular disease (CVD) as well as CVD risk factors such as hypertension, dyslipidemia, inflammation, and insulin resistance [5,6]. Abnormal vascular functions such as increased arterial stiffness and endothelial dysfunction have been demonstrated in patients with OSA, and the increase in cardiovascular risk in these patients may be related to these abnormalities [7,8].

Arterial stiffness is a composite indicator of arterial health and is strongly associated with sclerosis at various sites in the arterial tree [9,10]. It is caused by structural changes in the vascular wall, including fibrosis, medial smooth muscle cell necrosis, breaks in elastin fibers, calcifications, and diffusion of macromolecules into the arterial wall [11,12]. Arterial stiffness can be measured by several indices that are obtained in different arterial territories, such as central portions (carotid–femoral pulse wave velocity [PWV_cf]; digital volume pulse–derived pulse wave velocity [PWV_DVP]; cardio–ankle vascular index [CAVI]) [9,13,14] and peripheral portions (carotid–radial pulse wave velocity [PWV_cr]; compliance index [CI]) [2,10,15,16]. We have demonstrated that there is a good correlation (r = 0.669, p < 0.001) between PWV_DVP and PWV_cf in 100 asymptomatic hospital staff members [13]. Furthermore, multivariate analysis showed that subjects with hypertension had higher PWV than those without hypertension as determined by both methods (PWV-DVP odds ratio 2.28, 95% CI 1.19 to 4.37; PWV-AT odds ratio 2.47, 95% CI 1.26 to 4.84)¹³. Meanwhile, PWV_DVP derived from our home made system is advantageous in terms of complete technical independence, and portability. Central arterial stiffness is considered a measure of conduit artery passive (capacitative) stiffness. Central arterial stiffness depends mainly on the elastin/collagen composition of the aorta, as well as its diameter and wall thickness, whereas peripheral arterial stiffness is a measure of the muscular arterial bed's active stiffness and depends on multiple factors but principally on endothelial function and sympathetic resting tone [2]. CI is a well validated peripheral arterial stiffness index in patients with chronic kidney disease [17], nonalcoholic fatty liver disease [18], obesity [19], and pre-diabetes [20].

Many researchers have studied the association between OSA and arterial stiffness. One review found that 19 of 24 cross-sectional studies in adult populations reported a significant difference in arterial stiffness between normal controls and OSA patients [21]. In the vast majority of these studies, arterial stiffness was assessed using aortic PWV. These analyses did not prove causality, but they suggested a potential dose–response association.

OSA can occur in both rapid eye movement (REM) and non-REM (NREM) sleep. However, during REM sleep, cholinergic-mediated inhibition of the hypoglossal nerve results in the suppression of genioglossus muscle tone, which substantially increases the propensity for upper airway collapse [22,23]. This increased propensity for upper airway collapse can lead to OSA that becomes worse during REM sleep [24,25]. Furthermore, compared with non-REM sleep, REM sleep was associated with greater sympathetic activity and cardiovascular instability in patients with OSA [26,27]. REM sleep induced surges in heart rate and coronary blood flow reduction [28]. Longer sleep apneas and greater hypoxemia were found during REM sleep than NREM sleep in patients with OSA [29]. These acute hemodynamic changes could play a part in triggering ischemic events in OSA patients with CVD [30]. Therefore, OSA during REM sleep may have more serious adverse CVD consequences than OSA during NREM sleep.

In the present study, we attempted to identify the central (i.e. elastic artery) and peripheral (i.e. muscular artery) arterial stiffness levels and impact of REM sleep in an OSA study population, and we also determined their potential interdependence in degrees of severity.