Original ArticleRelationship of left atrial size to obstructive sleep apnea severity in end-stage renal disease
Introduction
Patients with end-stage renal disease (ESRD) have an annual mortality rate between 10% and 20%, mainly due to cardiovascular causes [1], [2], [3]. Increased left atrial (LA) size contributes to cardiovascular mortality in both the general population and in patients with ESRD [4], [5]. In ESRD, the prevalence of obstructive sleep apnea (OSA), characterized by repetitive upper airway collapse during sleep, is at least 50% and is much higher than in the general population [6], [7] with men having a higher prevalence than women [8]. In ESRD patients on peritoneal dialysis, the presence of OSA has been shown to be an independent predictor of cardiovascular morbidity and death [9]. It has also been shown that the severity of OSA is directly related to the degree of overnight fluid shift from the legs in ESRD [10]. Given that ESRD causes fluid retention, that OSA is very common in ESRD, and that OSA increases cardiovascular risk [2], [3], [11], it is important to examine potential mechanisms through which fluid retention, nocturnal rostral fluid shift, and OSA may contribute to potentially reversible changes in cardiac structure in ESRD patients.
The left atrium plays a crucial role in maintaining optimal cardiac function. It modulates left ventricular (LV) filling by acting as a reservoir during ventricular systole, a conduit during early diastole, and as an active pump in late diastole [12]. Its thin-walled structure means that it is more distensible than the left ventricle in response to increases in pressure or volume of pulmonary venous inflow [13]. The most common causes of an enlarged left atrium are LV dysfunction or hypertrophy, mitral valve disease, and fluid overload [13], [14]. The relationship with fluid overload is of particular relevance in ESRD, given that fluid overload is a hallmark of this condition and predicts increased mortality [15].
The high prevalence of OSA in ESRD and in heart failure [16], both pathological states characterized by fluid overload, has led to an interest in the role of fluid retention and fluid shift from the legs in the pathogenesis of OSA in these conditions. In ESRD, the increased prevalence of OSA is not explained solely by comorbidities or increased body mass index (BMI) [17]. Indeed, OSA patients with ESRD tend to have a lower mean BMI than OSA patients with normal renal function [2], [17], [18]. The severity of OSA has been shown to be directly related to the degree of overnight rostral fluid shift from the legs in both heart failure [19] and ESRD patients [10]. In ESRD patients, the volume of fluid accumulating in the legs during the day is likely to be greater than in the general population. Consequently, it is likely that fluid overload and increased overnight fluid shift from the legs play important roles in the pathogenesis of OSA in this population. As fluid overload and rostral fluid shift might distend the LA and increase fluid accumulation in the neck, we postulated that in ESRD patients, LA size would be related to the degree of overnight rostral fluid shift and that, in turn, OSA severity would be related to LA size. To test this hypothesis, we examined LA size determined by echocardiography in relation to OSA severity as determined by polysomnography (PSG) in patients with ESRD.
Section snippets
Subjects
Inclusion criteria were patients with ESRD at least 18 years of age undergoing thrice-weekly hemodialysis at the University Health Network Toronto General Hospital. Patients were recruited consecutively irrespective of symptoms of sleep apnea. Exclusion criteria were patients who were already treated for OSA or had an LV ejection fraction (LVEF) of <45%.
Echocardiography
As part of routine clinical care in the hemodialysis unit, all patients with ESRD undergo echocardiography yearly. Transthoracic
Characteristics of the patients
Forty ERSD patients underwent PSG and an echocardiogram was performed. Their characteristics are shown in Table 1. The study population was receiving adequate dialysis, as indicated by a percent reduction of urea >65% in all. The great majority of apneas and hypopneas were obstructive. A subset of the last 21 patients underwent LFV assessment.
Polysomnographic and echocardiographic data
Among the 40 patients, there was a significant correlation between AHI and LA size (r = 0.626, p < 0.001). In men, this relationship persisted (r = 0.617,
Discussion
This study provides novel insights into potential mechanisms linking fluid retention and overnight rostral fluid shift with cardiac structure and OSA severity in ESRD patients on conventional hemodialysis. We found, in men, that there was a strong, direct relationship between severity of OSA, assessed by the AHI, and LA size. We also showed in men that there were strong relationships between the Δ LFV and both the LA size and the severity of OSA. Furthermore, in men, there was a relationship
Conflict of interest
The ICMJE Uniform Disclosure Form for Potential Conflicts of Interest associated with this article can be viewed by clicking on the following link: http://dx.doi.org/10.1016/j.sleep.2014.07.001.
Acknowledgments
This work was supported by operating grant MOP-82731 from the Canadian Institutes of Health Research. OD Lyons is supported by a joint Canadian Thoracic Society/European Respiratory Society Peter Macklem Research Fellowship, CT Chan by the R. Fraser Elliot Chair in Home Dialysis, RM Elias by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Brazil, Toronto Rehabilitation Institute and Toronto General Hospital, and TD Bradley by the Clifford Nordal Chair in Sleep Apnea and
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