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Elevated Levels of Neopterin in Sleep-Disordered Breathing^*

^* From the Department of Medicine, Johns Hopkins University, Baltimore, MD.

Correspondence to: Naresh M. Punjabi, MD, PhD, Associate Professor of Medicine and Epidemiology, Johns Hopkins University, Division of Pulmonary and Critical Care Medicine, 5501 Hopkins Bayview Circle, Baltimore, MD 21224; e-mail: npunjabi{at}jhmi.edu

Abstract

Background: Sleep-disordered breathing (SDB) is increasingly being recognized as an independent risk factor for hypertension and cardiovascular disease. Recent evidence suggests that the maladaptive physiologic response to SDB, particularly cardiovascular effects, may result in part from systemic inflammation. Although abnormal cytokine levels have been documented in SDB, data on whether SDB is associated with cellular activation are limited. Thus, this investigation sought to determine whether neopterin, a marker released by activated macrophages, is increased in SDB.

Methods and results: Fifty-five men, free of medical comorbidity, undergoing polysomnography had fasting serum tested for neopterin levels. Multivariable regression methods were used to quantify the association between neopterin and quartiles of the apnea hypopnea index (AHI) while accounting for body mass index, waist circumference, and percentage of body fat. Quartiles of AHI (I: < 3.83 events per hour; II: 3.83 to 11.98 events per hour; III: 11.99 to 36.82 events per hour; IV > 36.82 events per hour) indicated a range from no SDB through severe SDB. Compared to the subjects in the first AHI quartile, serum neopterin levels were higher by 3.0%, 10.9%, and 26.5% in the second, third, and fourth AHI quartiles, respectively (p < 0.001for linear trend). Neopterin levels also were higher in those with greater degree of sleep-related hypoxemia, more stage 1 sleep, and less stage 2 sleep.

Conclusion: The results of this study indicate that severity of SDB independently associates with serum levels of neopterin, a marker for macrophage activation that may play an important role in the pathogenesis of SDB-related cardiovascular disease.

Key Words: neopterin • obstructive sleep apnea • sleep-disordered breathing