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Elevated Levels of Neopterin in Sleep-disordered Breathing

Johns Hopkins University Baltimore, MD, Department of Medicine

Abstract

BackgroundSleep Disordered Breathing (SDB) is increasingly being recognized as an independent contributor to 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 is limited. Thus, this investigation sought to determine whether neopterin, a marker released by activated macrophages, is increased in SDB.

Methods and ResultsFifty-five men, free of medical comorbidity, undergoing polysomnography had fasting morning 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 BMI, waist circumference, and percent body fat. Quartiles of AHI (I: < 3.83 events/hr, II: 3.83--11.98 events/hr, III: 11.99--36.82, IV > 36.82 events/hr) 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.

ConclusionsThe results of this study suggest 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 • Sleep-disordered breathing • Obstructive sleep apnea