RESUMO
Study objectives: Objective and subjective measures of excessive daytime sleepiness (EDS) are only weakly associated. No study, however, has examined whether these two measures of EDS differ in terms of underlying mechanisms and prognostic value. Pro-inflammatory cytokines, that is, interleukin-6 (IL-6) appear to promote sleepiness/fatigue, while the stress hormone cortisol promotes vigilance. We hypothesized that objective sleepiness is associated with increased levels of IL-6 and decreased levels of cortisol. Methods: We studied 58 obstructive sleep apnea (OSA) patients with clinical EDS and/or cardiovascular comorbidities who underwent 8-hour in-lab polysomnography for four consecutive nights. Objective and subjective daytime sleepiness were measured by Multiple Sleep Latency Test (MSLT), Epworth Sleepiness Scale (ESS), and Stanford Sleepiness Scale (SSS), respectively. Twenty-four-hour profiles of IL-6 and cortisol levels were assessed on the fourth day. Results: The agreement between objective and subjective EDS in OSA patients was fair (kappa = 0.22). Objective EDS (lower MSLT) in OSA patients was associated with significantly elevated 24-hour (ß = -0.34, p = .01), daytime (ß = -0.30, p = .02) and nighttime (ß = -0.38, p < .01) IL-6 levels, and significantly decreased daytime (ß = 0.35, p = .01) cortisol levels. In contrast, subjective EDS (higher ESS/SSS) was not associated with either elevated IL-6 levels or decreased cortisol levels. Conclusions: Our findings suggest that OSA with objective EDS is the more severe phenotype of the disorder associated with low-grade inflammation, a link to cardiometabolic morbidity and mortality. Compared to subjective EDS, objective EDS is a stronger predictor of OSA severity and may be useful in the clinical management of the disorder.
Assuntos
Distúrbios do Sono por Sonolência Excessiva/fisiopatologia , Hidrocortisona/sangue , Inflamação/etiologia , Interleucina-6/sangue , Apneia Obstrutiva do Sono/fisiopatologia , Adulto , Idoso , Biomarcadores/sangue , Distúrbios do Sono por Sonolência Excessiva/sangue , Distúrbios do Sono por Sonolência Excessiva/complicações , Distúrbios do Sono por Sonolência Excessiva/diagnóstico , Feminino , Humanos , Inflamação/sangue , Inflamação/diagnóstico , Masculino , Pessoa de Meia-Idade , Apneia Obstrutiva do Sono/sangue , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/diagnósticoRESUMO
BACKGROUND: The simultaneous occurrence of metabolic syndrome and excessive daytime sleepiness are very common in obstructive sleep apnea (OSA) patients. Both conditions, if present in OSA, have been reported to be associated with inflammation and disruption of oxidative stress balance that impair the cardiovascular system. To verify the impact of daytime sleepiness on inflammatory and oxidative stress markers, we evaluated OSA patients without significant metabolic disturbance. METHODS: Thirty-five male subjects without diagnostic criteria for metabolic syndrome (Adult Treatment Panel III) were distributed into a control group (n = 10) (43 ± 10.56 years, apnea-hypopnea index - AHI 2.71 ± 1.48/hour), a non-sleepy OSA group (n = 11) (42.36 ± 9.48 years, AHI 29.48 ± 22.83/hour) and a sleepy OSA group (n = 14) (45.43 ± 10.06 years, AHI 38.20 ± 25.54/hour). Excessive daytime sleepiness was considered when Epworth sleepiness scale score was ≥ 10. Levels of high-sensitivity C-reactive protein, homocysteine and cysteine, and paraoxonase-1 activity and arylesterase activity of paraoxonase-1 were evaluated. RESULTS: Patients with OSA and excessive daytime sleepiness presented increased high-sensitivity C-reactive protein levels even after controlling for confounders. No significant differences were found among the groups in paraoxonase-1 activity nor arylesterase activity of paraoxonase-1. AHI was independently associated and excessive daytime sleepiness tended to have an association with high-sensitivity C-reactive protein. CONCLUSIONS: In the absence of metabolic syndrome, increased inflammatory response was associated with AHI and daytime sleepiness, while OSA was not associated with abnormalities in oxidative stress markers.
Assuntos
Proteína C-Reativa/análise , Distúrbios do Sono por Sonolência Excessiva/diagnóstico , Mediadores da Inflamação/sangue , Inflamação/diagnóstico , Estresse Oxidativo , Apneia Obstrutiva do Sono/diagnóstico , Sono , Adulto , Fatores Etários , Biomarcadores/sangue , Estudos de Casos e Controles , Estudos Transversais , Distúrbios do Sono por Sonolência Excessiva/sangue , Distúrbios do Sono por Sonolência Excessiva/fisiopatologia , Humanos , Inflamação/sangue , Masculino , Pessoa de Meia-Idade , Fenótipo , Fatores Sexuais , Apneia Obstrutiva do Sono/sangue , Apneia Obstrutiva do Sono/fisiopatologia , Regulação para CimaRESUMO
INTRODUCTION: Obstructive sleep apnea syndrome (OSAS) is associated with a variety of long-term consequences such as high rates of morbidity and mortality, due to excessive diurnal somnolence as well as cardiovascular and metabolic diseases. Obesity, recurrent episodes of upper airway obstruction, progressive hypoxemia, and sleep fragmentation during sleep cause neural, cardiovascular, and metabolic changes. These changes include activation of peripheral sympathetic nervous system and the hypothalamic-pituitary-adrenal axis, insulin sensitivity, and inflammatory cytokines alterations, which predispose an individual to vascular damage. DISCUSSION: Previous studies proposed that OSAS modulated the expression and secretion of inflammatory cytokines from fat and other tissues. Independent of obesity, patients with OSAS exhibited elevated levels of C-reactive protein, tumor necrosis factor-α and interleukin-6, which are associated with sleepiness, fatigue, and the development of a variety of metabolic and cardiovascular diseases. OSAS and obesity are strongly associated with each other and share many common pathways that induce chronic inflammation. Previous studies suggested that the protective effect of exercise may be partially attributed to the anti-inflammatory effect of regular exercise, and this effect was observed in obese patients. Although some studies assessed the effects of physical exercise on objective and subjective sleep parameters, the quality of life, and mood in patients with OSAS, no study has evaluated the effects of this treatment on inflammatory profiles. In this review, we cited some studies that directed our opinion to believe that since OSAS causes increased inflammation and has excessive daytime sleepiness as a symptom and being that physical exercise improves inflammatory profiles and possibly OSAS symptoms, it must be that physical exercise improves excessive daytime sleepiness due to its improvement in inflammatory profiles.