Effect of CPAP therapy on daytime cardiovascular regulations in patients with obstructive sleep apnea

doi:10.1016/j.compbiomed.2011.09.001

Computers in Biology and Medicine

Volume 42, Issue 3, March 2012, Pages 328-334

https://doi.org/10.1016/j.compbiomed.2011.09.001 Get rights and content

Abstract

Obstructive sleep apnea (OSA) is a sleep disorder with a high prevalence that causes pathological changes in cardiovascular regulation during the night and also during daytime. We investigated whether the treatment of OSA at night by means of continuous positive airway pressure (CPAP) improves the daytime consequences. Twenty-eight patients with OSA, 18 with arterial hypertension, 10 with normal blood pressure, were investigated at baseline and with three months of CPAP treatment. Ten age and sex matched healthy control subjects were investigated for comparisons. We recorded a resting period with 20 min quiet breathing and an exercise stress test during daytime with ECG and blood pressure (Portapres). The bicycle ergometry showed a significant reduction of the diastolic blood pressure at a work load of 50 W and 100 W (p<0.05 and p<0.01, respectively) and a decrease of the heart rate recovery time after the stress test (p<0.05). These results indicate a reduction of vascular resistance and sympathetic activity during daytime. The coupling analysis of the resting periods by means of symbolic coupling traces approach indicated an effect of the CPAP therapy on the baroreflex reaction in hypertensive patients where influences of the systolic blood pressure on the heart rate changed from pathological patterns to adaptive mechanisms of the normotensive patients (p<0.05).

Introduction

Sleep disorders have a high prevalence in the western population. Among sleep disorders obstructive sleep apnea is recognized as a disorder causing severe cardiovascular diseases such as arterial hypertension, which may lead to myocardial infarction and stroke [1]. The early diagnosis and the efficient treatment of obstructive sleep apnea are therefore important tasks in sleep medicine and related disciplines.

Obstructive sleep apnea (OSA) is defined by the occurrence of more than 5 apnea events per hour of sleep (apnea index greater than 5/h) with an obstruction of the upper airways for at least 10 s duration during sleep. Severe sleep apnea is diagnosed if more than 30 apnea events per hour of sleep are found. The consequence of sleep apnea is a severely disturbed sleep, which leads to excessive daytime sleepiness. The combination of obstructive sleep apnea events during the night as diagnosed by cardiorespiratory polysomnography and excessive daytime sleepiness as reported by the patient is called the obstructive sleep apnea syndrome (OSAS). [2].

Treatment of OSAS will first of all reduce the daytime hypersomnolence and the cardiovascular risk. In addition effective treatment will increase the quality of life of the patients. Successful treatment will also decrease costs caused by OSAS, e.g. accidents due to daytime sleepiness as well as therapy cost of developed cardiovascular disorders [3].

The standard treatment of choice for OSA is the continuous positive airway pressure (CPAP), which prevents physically the obstruction of the upper airway by pneumatic stenting [2]. It is assumed that the therapy has positive effects on cardiovascular regulation during daytime [4]. Earlier studies did show a reduction of blood pressure also during daytime [5], [6]. A key role in the pathogenesis of such regulatory dysfunctions is the increased sympathetic activation during night as well as during daytime [4] in patients with OSA, which could be non-invasively diagnosed by the analysis of heart rate and blood pressure variability.

In the last twenty years, different parameter of heart rate and blood pressure dynamics have shown their potential to indicate vegetative changes in developing cardiovascular diseases [7], [8]. These are linear parameters in time and frequency domain [7], [9] as well as non-linear parameters [8]. Their reliability had been criticized, because the underlying mechanism result in rather complex variability [10], [11]. From the viewpoint of physiology, heart rate and blood pressure are strongly interrelated. In addition by mechanical interaction heart rate influences the cardiac output. The cardiac output and resistance of the vessels determine the blood pressure value in the end. Both, heart rate and the vascular resistance are controlled by the vegetative nervous system with its two branches sympathicus and parasympathicus. Afferent signals of blood pressure receptors drive the activity of both subsystems and lead to a closed control loop [12]. This description is rather simple because interrelationships between the vegetative subsystems and different velocity of their acting as well as receptors themselves show non-linear behavior [13]. With this specific regulation, other influences such as the respiratory drive, are also determinants for cardiovascular oscillations [14]. Analyzing the coupling of heart rate and blood pressure, the parameter of baroreflex sensitivity is commonly used, which quantifies the strength of the assumed influence of the blood pressure on the heart rate [15]. A methodological extension has been proposed recently in order to consider the different time delays and origins of the baroreflex [16] but still the non-linear behavior has not been considered. From the areas of statistics and nonlinear dynamics, different methods of coupling analysis in non-linear system were proposed, such as transfer entropy [17], cross-conditional entropy [18] or cross recurrence analysis [19]. Applying these methods to analysis of coupling between heart rate and blood pressure, the mix of intrinsic noise and regular parts in the signals limits their usefulness. Recently new methods based on order pattern analysis and joint symbolic dynamics point to solution of these limitations [19], [20]. These order patterns result from a coarse graining (symbolization) of the data into two states: increasing or decreasing amplitudes. The method of ‘Symbolic Coupling Traces’ (SCT) [21], [22] now is able to detect the nonlinear couplings reliably.

In this study, the SCT is applied to bivariate measures of heart rate and systolic blood pressure in order to quantify differences in the daytime cardiovascular regulation following CPAP therapy in patients with OSA. The method should enlighten the effect of CPAP in these patients with the assumption that the risk for cardiovascular diseases is reduced.

Section snippets

Data

The same study protocol has been applied both in patients with OSA and in healthy controls. The diagnosis of OSA was previously established in a sleep study using attended cardiorespiratory polysomnography. Moderate to severe OSAS was diagnosed if the patients had more than 15 apnea and hypopnea events per hour of sleep (AHI>15/h) and if they had excessive daytime sleepiness quantified by the Epworth Sleepiness Scale (ESS). For the application of our dedicated signal analysis, we considered a

Methods

The bivariate coupling analysis by means of SCT [20] is defined as followed. First, the time series x_i and y_i are transformed into the symbol sequences sx_i and sy_i according to the rule $s z_{i} = {\begin{array}{l} 1, z_{i} \leq z_{i - θ} \\ 0, z_{i} > z_{i - θ} \end{array}$ where z represents x and y. θ is the considered time lag. Second, successive words of length l (wz_i=sz_i, sz_i+1, …, sz_i+k−1) are constructed from sx_i and sy_i, which can form d=2^k different patterns (W_k, k=1,…,d). Third, wx_i and wy_i are used to estimate the joint word distribution (p_mn) _m=1,…,d;

Results

The results of the blood pressure evaluations under the conditions of defined work load during the ergometry stress test are presented in Table 1, Table 2, Table 3. We compared the results and tested them for statistical differences between the three groups, but no statistical significance was found, may be due to a too small sample size.

Nonetheless we could observe several tendencies. Patients with obstructive sleep apnea do show higher systolic blood pressure values than normal controls at

Discussion

Comparing the effects of CPAP therapy on systolic blood pressure and diastolic blood pressure during a daytime physical load stress test and at rest we observe a treatment effect in patients with OSA. First, the diastolic response to physical stress and the heart rate recovery time after work load could be reduced by means of a CPAP therapy over three months, which indicates a reduction of the pathological daytime sympathetic activity in OSA patients. And second, there was a reduction of the

Conflict of interest statement

T. Penzel and I. Fietze own shares of Advanced Sleep Research GmbH and Somnico GmbH. T. Penzel, I. Fietze, and C. Schöbel received institutional grants by Breas, Cephalon, Hoffrichter, MSD, Resmed, UCB, Respironics, Somnomedics, Weinmann.

Acknowledgments

We want to acknowledge the contributions of Dana Buck and Wibke Klaus who participated in the collection of data. We acknowledge the help of the medical technician Franco de Lange when testing the patients. For unrestricted funding we acknowledge DFG project (PE 628/4-1, BR 1303/10-1, KU-837/23-1).

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Events are frequently terminated by subcortical arousals and a drop in blood oxygenation levels (SaO2) by 2% or more, or a drop in blood oxygenation levels (SaO2) by 4% or more without subcortical arousals. Clinical significance is defined at five events or more per hour [6]. Many studies report a 4% and 2% prevalence in men and women, respectively [7]; however, upwards of 20% prevalence in the population is estimated, accounting for underreporting and underdiagnoses cases [8].
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However, when detected off CPAP, a remarkable elevation of HF power accompanied with the declined LHR was revealed. It is previously assumed that long-term CPAP partially reduces sympathetic overactivity and restores the impaired sympathovagal balance in OSA patients40,41, which may be one of the potential mechanisms in preventing the development of cardiovascular diseases, such as hypertension42 and atrial fibrillation.43 However, recently the issue of the impact of CPAP on cardiovascular diseases with OSA is on the debate.
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To investigate the associations between CPAP and HRV in OSA.
Based on literature from five databases published through August 2017, we performed a meta-analysis of cohort studies of OSA treated with CPAP. The change of low-frequency band (LF), high-frequency band (HF) and the ratio between LF and HF (LHR) were analyzed.
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¹: These authors contributed equally to the study.

View full text

Effect of CPAP therapy on daytime cardiovascular regulations in patients with obstructive sleep apnea

Abstract

Introduction

Section snippets

Data

Methods

Results

Discussion

Conflict of interest statement

Acknowledgments

Obstructive sleep apnoea and its cardiovascular consequences

Lancet

Obstructive sleep apnea

N. Engl. J. Med.

The price of obstructive sleep apnea–hypopnea: hypertension and other ill effects

Am. J. Hypertens.

Obstructive sleep apnea and cardiovascular disease: a perspective and future directions

Prog. Cardiovas. Dis.

Ambulatory blood pressure after therapeutic and subtherapeutic nasal continuous positive airway pressure for obstructive sleep apnoea: parallel trial

Lancet

Effect of nasal continuous positive airway pressure treatment on blood pressure in patients with obstructive sleep apnea

Circulation

Heart rate variability: standards of measurement, physiological interpretation, and clinical use

Euro. Heart J.

Introduction: cardiovascular physics

Int. J. Bifurcation Chaos Appl. Sci. Eng.

Spectral analysis of blood pressure and heart rate variability in evaluating cardiovascular regulation: a critical appraisal

Hypertension

Heart rate variability measures: a fresh look at reliability

Clin. Sci.

Assessing nonlinear properties of heart rate variability from short-term recordings: are these measurements reliable?

Physiol. Measur.

Relationships between short-term blood-pressure fluctuations and heart-rate variability in resting subjects II: a simple model

Med. Biol. Eng. Comput.

How should human baroreflexes be tested?

NewsPhysiol. Sci.: an Int. J. Physiol. produced jointly by the Int. Union Physiol. Sci. Am. Physiol. Soc.

Short-term cardiovascular oscillations in man: measuring and modelling the physiologies

J. Physiol.

Comparison of various techniques used to estimate spontaneous baroreflex sensitivity (the EuroBaVar study)

Am. J. Physiol. Regul. Integr. Comput. Physiol.

Advanced analysis of spontaneous baroreflex sensitivity, blood pressure and heart rate variability in patients with dilated cardiomyopathy

Clin. Sci.