Edematous obstructive sleep apnea patients have low normal serum albumin levels.

To the Editor: Previous research has shown that unexplained edema is associated with obstructive sleep apnea (OSA) in women. (1) Moreover, OSA has been shown to cause edema, for nasal continuous positive airway pressure reduces the amount of edema in OSA patients. (2) It is unclear why only some individuals with OSA develop edema. Since a low colloid oncotic pressure promotes edema formation in patients with renal and liver disease, and since the main component of the colloid oncotic pressure is albumin, we conducted a study to determine if OSA patients with edema have lower serum albumin levels than OSA patients without edema.

A convenience sample of subjects with OSA, some with and some without bilateral edema, were enrolled from an inner city family practice in Cleveland, Ohio, and from a suburban family practice near Cleveland, Ohio, from July 1994 to March 2005. Diagnostic polysomnography was performed on all subjects in a sleep laboratory before enrollment. OSA was defined by an apneahypopnea index (AHI) [greater than or equal to]15. Edema was defined as bilateral, pitting, pretibial swelling that was at least 1+. Subjects with edema were eligible to participate if they had no evidence of left ventricular systolic or diastolic dysfunction, and no evidence of any other cardiac pathology, based upon echocardiographic evaluation. Subjects were excluded if they had hypoalbuminemia (serum albumin <3.2 g/dL), proteinuria (more than 1 + protein on dipstick urinalysis), chronic obstructive pulmonary disease, if they were pregnant, nonambulatory, or if they had abnormal liver function tests or thyroid stimulating hormone level. Subjects were excluded from the edema group if they had trace edema or less, if they were currently using dihydropyridine calcium antagonists, or if they had unilateral edema, myxedema, or idiopathic cyclic edema.

Sixty-two subjects with OSA enrolled in the study, 34 with, and 28 without edema. There were 32 female enrollees and 30 men. For most of the subjects with edema, the edema was mild, usually 1 + or 2+ pitting, and typically presented as an incidental examination finding. There were no differences between the two groups in age, sex, or race. Almost all the enrollees were white. Compared with the nonedematous subjects, the subjects with edema were more obese (mean BMI = 42 [+ or -] 9.6 kg/[m.sup.2] versus 33 [+ or -] 7.5 kg/[m.sup.2] P = 0.001). There were no differences between the two groups in terms of AHI and oxygen saturation while awake, nor were there differences between the two groups in frequency of hypertension or diabetes mellitus. Compared with the nonedematous subjects, more of the subjects with edema tended to use nonsteroidal anti-inflammatory drugs (NSAIDs) (24% versus 7%, P = 0.08). The serum albumin levels were lower in the edematous group than in the nonedematous group (mean serum albumin = 4.0 [+ or -] 0.54 versus 4.3 [+ or -] 0.36 g/dL, P = 0.03). The mean values for serum total protein, serum sodium, serum potassium, and serum creatinine did not differ between the two groups. In addition, the mean serum albumin level was lower in women with OSA compared with men with OSA (3.9 [+ or -] 0.52 versus 4.3 [+ or -] 0.33 g/dL, P < 0.001).

To our knowledge, no previous study has demonstrated that differences in serum albumin levels are associated with different physiologic sequelae, even when serum albumin levels are normal. Our data does not explain why some subjects have relatively low albumin levels, nor does it explain why men with OSA have higher serum albumin levels than women with OSA. However, it may be that there are physiologic differences between the sexes in terms of albumin synthesis or metabolism. While the norms for some laboratory tests differ between men and women, (hemoglobin levels being a prime example), the current norms for serum albumin are the same for both sexes.

This study has a number of limitations: the sample is small, the study did not control for severity of obesity or NSAID use, and only edematous subjects underwent echocardiography. In addition, the generalizibility of the findings may be limited because the data was obtained at only two sites.

Nonetheless, if the results of this study are generalizable, then both severity of obesity and a normal but relatively lower serum albumin level are associated with, and may contribute to, edema formation in OSA patients. Moreover, the finding that women with OSA have relatively lower serum albumin levels than men with OSA offers some insight as to why idiopathic edema primarily affects obese women. (3)

Robert P. Blankfield, MD, MS

Mansoor Ahmed, MD

Stephen J. Zyzanski, PhD

Case Western Reserve University School of Medicine

Cleveland, Ohio

Southwest Cleveland Sleep Center

Middleburg Heights, Ohio

References

1. Blankfield RP, Ahmed M, Zyzanski SJ. Idiopathic edema is associated with obstructive sleep apnea in women. Sleep Med 2004;5:583-587.

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;5:589-592.

3. Streeten DH. Idiopathic edema. Pathogenesis, clinical features, and treatment. Endiocrinol Metab Clin North Am 1995;24:531-547.