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Sleep Medicine 9 (2008) 890–893

Original Article

Comparison of obstructive sleep apnea patientswith and without leg edema q

Imran Iftikhar a, Mansoor Ahmed b, Shannon Tarr c, Stephen J. Zyzanski d,Robert P. Blankfield d,e,*

a Department of Internal Medicine, Fairview Hospital, Cleveland Clinic System, Cleveland, OH, United Statesb Southwest Cleveland Sleep Center, Middleburg Heights, OH, United States

c Department of Surgery, Fairview Hospital, Cleveland Clinic System, Cleveland, OH, United Statesd Department of Family Medicine, Case Western Reserve University School of Medicine, Cleveland, OH, United States

e University Hospitals Medical Practice, Berea, OH, United States

Received 28 April 2007; received in revised form 26 September 2007; accepted 5 October 2007Available online 12 February 2008

Abstract

Background: To determine the proportion of patients with obstructive sleep apnea (OSA) who have leg edema, and to identify dif-ferences between edematous and non-edematous OSA patients.Methods: Retrospective, cross-sectional study of 378 patients with OSA (apnea/hypopnea index [AHI] P15) who had neither heartfailure nor chronic lung disease.Results: Thirty-five percent (133/378) of the subjects with OSA had bilateral leg edema. Eighty-one percent (108/133) of the edem-atous subjects had mild pitting that was 1+. Compared to the non-edematous OSA subjects, the edematous subjects were older(age = 51 ± 13 versus 45 ± 13 years, p = 0.001), more obese (body mass index = 39 ± 9 versus 33 ± 8 kg/m2, p = 0.001), had moresevere OSA (AHI = 46 ± 71 versus 27 ± 29, p = 0.004), spent a greater proportion of sleep time with an oxygen saturation <90%(20 ± 26 versus 11 ± 18%, p = 0.001), and were more likely to have diabetes mellitus (11% versus 3%, p = 0.001) and hypertension(32% versus 10%, p = 0.001). Age, obesity, hypertension and diabetes mellitus correlated significantly with edema status. Afteradjusting for these confounding variables, the AHI means remained different between the edema and non-edema groups (41 ± 5versus 28 ± 3, p = 0.04).Conclusions: Approximately one-third of OSA patients have edema. Edematous OSA patients are older, more obese, more likely tohave diabetes mellitus and hypertension, and have more severe OSA than OSA patients who lack edema.� 2008 Elsevier B.V. All rights reserved.

Keywords: Edema; Obesity; Obstructive sleep apnea

1389-9457/$ - see front matter � 2008 Elsevier B.V. All rights reserved.

doi:10.1016/j.sleep.2007.10.019

q None of the authors has a financial interest or a conflict of interestregarding the subject matter of this study.

* Corresponding author. Address: Berea Health Center, 201 FrontStreet, Suite 101, Berea, OH 44017, United States. Tel.: +1 440 2437299; fax: +1 440 243 0651.

E-mail address: blankfield@roadrunner.com (R.P. Blankfield).

1. Introduction

Leg edema is associated with obstructive sleep apnea(OSA) among ambulatory adult women [1], and there isevidence that OSA can cause edema [2]. Among patientswith OSA, the proportion with edema appears to beone-quarter to one-third, but only two previous studieshave addressed this question, both had small samples,and one of the studies focused upon right-sided heartfailure, not edema [3,4].

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We sought to identify the proportion of OSA patientswho have leg edema in a large sample and to identify dif-ferences between edematous and non-edematous OSApatients.

2. Methods

We conducted a retrospective analysis of 378 patientsreferred to an accredited sleep laboratory, a facility withthree suburban locations near Cleveland, Ohio, whosesleep studies were performed between January 2002and June 2006. Most of the patients had been referredfor a sleep evaluation by their primary care physician.A convenient sample of adults age 18 years or older withconfirmed OSA was selected based upon alphabetizedsurnames.

Prior to enrolling in the study, diagnostic polysom-nography was performed on all subjects in a sleep labo-ratory. Standard electroencephalograms,electrooculograms and submental electromyogramswere used to monitor the sleep stages. Airflow was mon-itored by thermistors at the mouth and by nasal pressuretransduction. Respiratory movements were monitoredby qualitative inductance plethysmography (Respitrace,Sensormedics, Inc., CA). Snoring was detected bymicrophone. Arterial oxygenation was monitored by afinger pulse sensor (Ohmeda model 3700, BoulderCO). Electrocardiograms were monitored by chest wallleads. Tibial electromyography sensors recorded legmovements. Sleep was scored by the method of Rechts-chaffen and Kales [5]. Apneas were defined as anabsence of inspiratory air flow for 10 s or longer, andhypopneas were defined as a reduction of inspiratoryair flow of 50% or more with an associated drop in arte-rial oxygen saturation. A desaturation event was identi-fied when there was a reduction in the oxygen saturationof 4% or more. The average number of episodes of apne-as and hypopneas per hour of sleep (apnea-hypopneaindex, or AHI) was calculated. There are no universallyaccepted criteria for diagnosing OSA [6]. For this study,OSA was defined as an AHI P15 events per hour [7].

A physician obtained a medical history and per-formed a physical examination at the initial consultationevaluation, and a sleep study was subsequently ordered.The physical examination included an estimation of theamount of pre-tibial, pitting edema, and the severity ofthe edema was categorized as being none, trace, 1+,2+ or 3+. Trace edema was defined as being <1 mmof pitting, 1+ edema was defined as 1–2 mm of pitting,2+ edema was defined as 2–4 mm of pitting, and 3+ pit-ting was defined as >4 mm pitting. For the purposes ofthis study, edema was categorized as 1+, 2+ or 3+ pit-ting. Zero to trace pitting was categorized as being non-edematous.

Subjects were excluded if they were <18 years old, iftheir AHI was <15, if they had a history of heart failure,

a history of chronic obstructive lung disease or othernon-reversible pulmonary disease, a history of chronicliver disease, or a history of kidney disease associatedwith proteinuria.

In order to avoid misclassifying subjects whoseedema status might be attributable to medication, edem-atous subjects using antihypertensive or diabetic medi-cations that can cause edema (calcium channelblockers, alpha receptor antagonists, hydralazine orthiazolidinediones) were excluded. Likewise, non-edem-atous subjects using antihypertensive or cardiac medica-tions that can reduce edema (diuretics) were excluded.Non-edematous subjects using antihypertensive or dia-betic medications that can cause edema were included,and edematous subjects using diuretics were included.

Subjects answered the questions comprising theEpworth daytime sleepiness scale (ESS) [8].

The study protocol was approved by the InstitutionalReview Board of the Southwest General Health Center,Middleburg Heights, Ohio.

Categorical variables were compared using chi-square analysis. Continuous variables were comparedusing t-tests with several adjustments for variance viola-tions. An analysis of covariance and multiple regressionwas used to examine whether the AHI was indepen-dently associated with edema status after controllingfor relevant confounding variables.

3. Results

Of the 378 subjects enrolled in the study, 133 (35%)had edema. Of the 133 subjects in the edema group,the edema was 1+ in 81% (108/133) while only 19%(25/133) of the edematous subjects had 2+ or greaterpitting edema.

Compared to the non-edematous OSA subjects, thosewith edema were older (age = 51 ± 13 versus 45 ± 13years, p = 0.001), more obese (body mass index = 39 ± 9versus 33 ± 8 kg/m2, p = 0.001), had more severe OSA(AHI = 46 ± 71 versus 27 ± 29, p = 0.004), spent agreater proportion of sleep time with an oxygen satura-tion <90% (20 ± 26 versus 11 ± 18%, p = 0.001), weremore likely to have diabetes mellitus (11% versus 3%,p = 0.001), and were more likely to have hypertension(32% versus 10%, p = 0.001) (Table 1). The proportionof men and the severity of daytime sleepiness did not differbetween the two groups, and there were no differencesbetween the two groups in terms of proportion withasthma and proportion with coronary artery disease.

Age, BMI, hypertension and diabetes mellitus all cor-related significantly with AHI, and each differed signifi-cantly between the edema and non-edema groups.Adjusting for age, BMI, hypertension and diabetes mel-litus, the adjusted AHI means remained differentbetween the edema and non-edema groups (41 ± 5 ver-sus 28 ± 3, p = 0.04).

Table 1Demographic, medical, and laboratory characteristics of OSA subjectswith and without edema

Edema(N = 133)

No edema(N = 245)

p

Age, mean ± SD, yrs 51 ± 13 45 ± 13 0.001Sex,% Male 61% 68% 0.16Body mass index ± SD, kg/m2 39 ± 9 33 ± 8 0.001Apnea-Hypopnea Index ± SD 46 ± 71 27 ± 29 0.004% Sleep time O2 < 90% 20 ± 26 11 ± 18 0.001Epworth Sleepiness Scale score ± SD 13 ± 7 11 ± 6 0.08Hypertension 32% 10% 0.001Diabetes 11% 3% 0.001

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4. Discussion

In line with previous research [3,4], approximatelyone-third of patients with OSA have leg edema at thetime that the diagnosis is confirmed by polysomnogra-phy. The amount of edema in these patients is typicallymild, usually 1+. Based upon our findings, edematousOSA patients are older, more obese, have a greater pro-portion of hypertension and diabetes mellitus, and havemore severe OSA than non-edematous OSA patients.Furthermore, the relationship between edema and sever-ity of OSA was found to be independent of age, obesity,hypertension and diabetes.

The limitations of this study include the fact thatthere were no laboratory tests available to confirm thehistories provided by subjects. Especially for the edema-tous subjects, echocardiograms, spirometry evaluations,and urinalyses were unavailable to confirm the absenceof heart failure, lung disease, or proteinuric kidney dis-ease. Nonetheless, even though there may have beeninaccuracies in the histories provided by some subjects,there is no reason to believe that this was a widespreadproblem.

Although the study was performed at three separatesites, all the subjects reside in the Cleveland, Ohio, area.Accordingly, it is possible that the subjects enrolled inthe present study are not representative of OSA patientsin general.

Even though this study has limitations, the resultshave implications for understanding the cardiovascu-lar complications of OSA. OSA contributes to a num-ber of cardiovascular diseases, including coronaryartery disease, myocardial infarcts, strokes and heartfailure [9,10]. The explanation for the increased riskof cardiovascular disease among OSA patients isunknown, but a number of hypotheses have been pro-posed. Since OSA is a risk factor for the developmentof hypertension [11–13], the effects of OSA on bloodpressure may explain the increased risk of adversecardiovascular events. Other possible explanationsinclude OSA induced sympathetic hyperactivity [14–16], alterations in cerebral blood flow that precipitate

strokes [17], and atherogenesis due to hypoxemia [18].However, since OSA can cause fluid retention [2],since fluid retention can manifest as increased intra-vascular volume, and since increased intravascularvolume is a risk factor for the first major cardiovascu-lar event, heart failure, strokes and transient ischemicattacks [19], then fluid retention resulting in intravas-cular volume expansion may contribute to the adversecardiovascular events that occur in patients with OSA[20].

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