Sleep Medicine 9 (2008) 890–893

www.elsevier.com/locate/sleep

Original Article

Comparison of obstructive sleep apnea patients

with 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 States
b
Southwest Cleveland Sleep Center, Middleburg Heights, OH, United States
c
Department of Surgery, Fairview Hospital, Cleveland Clinic System, Cleveland, OH, United States
d
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 2007
Available 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 heart
failure 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 more
severe 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. After
adjusting for these confounding variables, the AHI means remained different between the edema and non-edema groups (41 ± 5
versus 28 ± 3, p = 0.04).
Conclusions: Approximately one-third of OSA patients have edema. Edematous OSA patients are older, more obese, more likely to
have diabetes mellitus and hypertension, and have more severe OSA than OSA patients who lack edema.
Ó 2008 Elsevier B.V. All rights reserved.

Keywords: Edema; Obesity; Obstructive sleep apnea

1. Introduction

Leg edema is associated with obstructive sleep apnea

q
None of the authors has a financial interest or a conflict of interest
regarding the subject matter of this study.
*
Corresponding author. Address: Berea Health Center, 201 Front
Street, Suite 101, Berea, OH 44017, United States. Tel.: +1 440 243
7299; fax: +1 440 243 0651.
E-mail address: blankfield@roadrunner.com (R.P. Blankfield).
(OSA) among ambulatory adult women [1], and there is
evidence that OSA can cause edema [2]. Among patients
with OSA, the proportion with edema appears to be
one-quarter to one-third, but only two previous studies
have addressed this question, both had small samples,
and one of the studies focused upon right-sided heart
failure, not edema [3,4].

1389-9457/$ - see front matter Ó 2008 Elsevier B.V. All rights reserved.
doi:10.1016/j.sleep.2007.10.019

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 I. Iftikhar et al. / Sleep Medicine 9 (2008) 890–893
We sought to identify the proportion of OSA patients
who have leg edema in a large sample and to identify dif-
ferences between edematous and non-edematous OSA
patients.
2. Methods
We conducted a retrospective analysis of 378 patients
referred to an accredited sleep laboratory, a facility with
three suburban locations near Cleveland, Ohio, whose
sleep studies were performed between January 2002
and June 2006. Most of the patients had been referred
for a sleep evaluation by their primary care physician.
A convenient sample of adults age 18 years or older with
confirmed OSA was selected based upon alphabetized
surnames.
Prior to enrolling in the study, diagnostic polysom-
nography was performed on all subjects in a sleep labo-
ratory. Standard electroencephalograms,
electrooculograms and submental electromyograms
were used to monitor the sleep stages. Airflow was mon-
itored by thermistors at the mouth and by nasal pressure
transduction. Respiratory movements were monitored
by qualitative inductance plethysmography (Respitrace,
Sensormedics, Inc., CA). Snoring was detected by
microphone. Arterial oxygenation was monitored by a
finger pulse sensor (Ohmeda model 3700, Boulder
CO). Electrocardiograms were monitored by chest wall
leads. Tibial electromyography sensors recorded leg
movements. Sleep was scored by the method of Rechts-
chaffen and Kales [5]. Apneas were defined as an
absence of inspiratory air flow for 10 s or longer, and
hypopneas were defined as a reduction of inspiratory
air 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 saturation
of 4% or more. The average number of episodes of apne-
as and hypopneas per hour of sleep (apnea-hypopnea
index, or AHI) was calculated. There are no universally
accepted 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 consultation
evaluation, and a sleep study was subsequently ordered.
The physical examination included an estimation of the
amount of pre-tibial, pitting edema, and the severity of
the edema was categorized as being none, trace, 1+,
2+ or 3+. Trace edema was defined as being <1 mm
of 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 of
this 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, if
their AHI was <15, if they had a history of heart failure,
Descargado para Miguel Angel Gamarra Tapiero (magamarra@estudiantes.unimetro.edu.co) en Metropolitan University of Health Sciences de ClinicalKey.es por Elsevier
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891
a history of chronic obstructive lung disease or other
non-reversible pulmonary disease, a history of chronic
liver disease, or a history of kidney disease associated
with proteinuria.
In order to avoid misclassifying subjects whose
edema status might be attributable to medication, edem-
atous subjects using antihypertensive or diabetic medi-
cations that can cause edema (calcium channel
blockers, alpha receptor antagonists, hydralazine or
thiazolidinediones) 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 the
Epworth daytime sleepiness scale (ESS) [8].
The study protocol was approved by the Institutional
Review Board of the Southwest General Health Center,
Middleburg Heights, Ohio.
Categorical variables were compared using chi-
square analysis. Continuous variables were compared
using t-tests with several adjustments for variance viola-
tions. An analysis of covariance and multiple regression
was used to examine whether the AHI was indepen-
dently associated with edema status after controlling
for 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 greater
pitting edema.
Compared to the non-edematous OSA subjects, those
with edema 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 more severe OSA
(AHI = 46 ± 71 versus 27 ± 29, p = 0.004), spent a
greater proportion of sleep time with an oxygen satura-
tion <90% (20 ± 26 versus 11 ± 18%, p = 0.001), were
more 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 proportion
of men and the severity of daytime sleepiness did not differ
between the two groups, and there were no differences
between the two groups in terms of proportion with
asthma 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 different
between the edema and non-edema groups (41 ± 5 ver-
sus 28 ± 3, p = 0.04).
892 I. Iftikhar et al. / Sleep Medicine 9 (2008) 890–893
Table 1
Demographic, medical, and laboratory characteristics of OSA subjects
with and without edema
Edema
(N = 133)
Age, mean ± SD, yrs 51 ± 13
Sex,% Male 61%
Body mass index ± SD, kg/m2 39 ± 9
Apnea-Hypopnea Index ± SD 46 ± 71
% Sleep time O2 < 90% 20 ± 26
Epworth Sleepiness Scale score ± SD 13 ± 7
Hypertension 32%
Diabetes 11%
4. Discussion
In line with previous research [3,4], approximately
one-third of patients with OSA have leg edema at the
time that the diagnosis is confirmed by polysomnogra-
phy. The amount of edema in these patients is typically
mild, usually 1+. Based upon our findings, edematous
OSA patients are older, more obese, have a greater pro-
portion of hypertension and diabetes mellitus, and have
more 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 that
there were no laboratory tests available to confirm the
histories provided by subjects. Especially for the edema-
tous subjects, echocardiograms, spirometry evaluations,
and urinalyses were unavailable to confirm the absence
of heart failure, lung disease, or proteinuric kidney dis-
ease. Nonetheless, even though there may have been
inaccuracies in the histories provided by some subjects,
there is no reason to believe that this was a widespread
problem.
Although the study was performed at three separate
sites, all the subjects reside in the Cleveland, Ohio, area.
Accordingly, it is possible that the subjects enrolled in
the present study are not representative of OSA patients
in general.
Even though this study has limitations, the results
have implications for understanding the cardiovascu-
lar complications of OSA. OSA contributes to a num-
ber of cardiovascular diseases, including coronary
artery disease, myocardial infarcts, strokes and heart
failure [9,10]. The explanation for the increased risk
of cardiovascular disease among OSA patients is
unknown, but a number of hypotheses have been pro-
posed. Since OSA is a risk factor for the development
of hypertension [11–13], the effects of OSA on blood
pressure may explain the increased risk of adverse
cardiovascular events. Other possible explanations
include OSA induced sympathetic hyperactivity [14–
16], alterations in cerebral blood flow that precipitate
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strokes [17], and atherogenesis due to hypoxemia [18].
However, since OSA can cause fluid retention [2],
since fluid retention can manifest as increased intra-
No edema p
vascular volume, and since increased intravascular
(N = 245)
volume is a risk factor for the first major cardiovascu-
45 ± 13 0.001
lar event, heart failure, strokes and transient ischemic
68% 0.16
33 ± 8 0.001 attacks [19], then fluid retention resulting in intravas-
27 ± 29 0.004 cular volume expansion may contribute to the adverse
11 ± 18 0.001 cardiovascular events that occur in patients with OSA
11 ± 6 0.08 [20].
10% 0.001
3% 0.001
References
[1] Blankfield RP, Ahmed M, Zyzanski SJ. Idiopathic edema is
associated with obstructive sleep apnea in women. Sleep Med
2004;5(6):583–7.
[2] Blankfield RP, Ahmed M, Zyzanski SJ. Effect of nasal continuous
positive airway pressure on edema in patients with obstructive
sleep apnea. Sleep Med 2004;5(6):589–92.
[3] Bradley TD, Rutherford R, Grossman RF, Lue F, Zamel N,
Moldofsky H. Role of daytime hypoxemia in the pathogenesis of
right heart failure in the obstructive sleep apnea syndrome. Am
Rev Resp Dis 1985;131:835–9.
[4] Whyte KF, Douglas NJ. Peripheral edema in the sleep apnea/
hypopnea syndrome. Sleep 1991;14:354–6.
[5] Rechtschaffen A, Kales A. A manual of standardized terminol-
ogy, techniques and scoring system for sleep stages of human
subjects. Bethesda, MD: US Government Printing Office 1968;
NIH publication no. 204.
[6] Strohl KP, Redline S. Recognition of obstructive sleep apnea. Am
J Resp Crit Care Med 1996;154:279–89.
[7] Wiegand L, Zwillich CW. Obstructive sleep apnea. Dis Mon
1994;40:199–251.
[8] Johns MW. A new method for measuring daytime sleepiness: the
Epworth sleepiness scale. Sleep 1991;14(6):540–5.
[9] Shahar E, Whitney CW, Redline S, et al. Sleep-disordered
breathing and cardiovascular disease: cross-sectional results of
the Sleep Heart Health Study. Am J Resp Crit Care Med
2001;163:19–25.
[10] Marin JM, Carrizo SJ, Vicente E, Agusti AG. Long-term
cardiovascular outcomes in men with obstructive sleep-a5. Strohl
KP, Redline S. Recognition of obstructive sleep apnea. Am J
Resp Crit Care Med 1996;154:279–89.
[11] Nieto FJ, Young TB, Lind BK, et al. Association of sleep-
disordered breathing, sleep apnea, and hypertension in a large
community-based study. JAMA 2000;283(14):1829–36.
[12] Peppard PE, Young T, Paltza M, Skatrud J. Prospective study of
the association between sleep-disordered breathing and hyperten-
sion. N Engl J Med 2000;342:1378–84.
[13] Pepperrell JC, Ramdassingh-Dow S, Crosthwaite N, et al.
Ambulatory blood pressure after therapeutic and subtherapeutic
nasal continuous positive airway pressure for obstructive sleep
apnoea: a randomized parallel trial. Lancet 2001;359:204–10.
[14] Minemura H, Akashiba T, Yamamoto H, Akahoshi T, Kosaka
N, Horie T. Acute effects of nasal continuous positive airway
pressure o 24-hour blood pressure and catecholamines in patients
with obstructive sleep apnea. Intern Med 1998;37(12):1009–13.
[15] Ziegler MG, Nelesen R, Mills P, Ancoli-Israel S, Kennedy B,
Dimsdale JE. Sleep apnea, norepinephrine-release rate, and
daytime hypertension. Sleep 1997;20(3):224–31.
[16] Dimsdale JE, Coy T, Ziegler MG, Ancoli-Israel S, Clausen J. The
effect of sleep apnea on plasma and urinary catecholamines. Sleep
1995;18(5):377–81.
 I. Iftikhar et al. / Sleep Medicine 9 (2008) 890–893 893

[17] Klingelhöfer J, Hajak G, Sander D, Schulz-Varszegi M,
Rüther E, Conrad B. Assessment of intracranial hemo-
dynamics in sleep apnea syndrome. Stroke 1992;23:
1427–33.
[18] Gainer JL. Hypoxia and atherosclerosis: re-evaluation of an old
hypothesis. Athersclerosis 1987;68:263–6.
[19] Wang TJ, Larson MG, Levy D, et al. Plasma natriuretic peptide
levels and the risk of cardiovascular events and death. N Engl J
Med 2004;350:718–20.
[20] Blankfield RP. Implications of calculated intravascular volume
changes upon atherosclerotic cardiovascular disease. Clin Hemo-
rheol Microcirc 2008;38:75–81.

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en abril 14, 2024. Para uso personal exclusivamente. No se permiten otros usos sin autorización. Copyright ©2024. Elsevier Inc. Todos los derechos reservados.