ABSTRACT

Objective:

Obstructive sleep apnea syndrome (OSAS) increases the risk of cardiovascular disease. Autonomic dysfunction and inflammation are thought to play an important role in this increase. Heart rate variability (HRV) analysis provides noninvasive detection of autonomic dysfunction. The number and distribution of blood cells are also considered important markers of inflammation. In this study, HRV and hemogram parameters were examined in patients with OSAS, and the relationship between them was investigated.

Materials and Methods:

The data of all patients who had overnight polysomnography (PSG) recording and hemogram parameters between 2019 and 2021 were reviewed. HRV analysis was performed on all patients included in the study. Along with demographic and clinical characteristics, the relationship between PSG parameters, HRV, and hemogram parameters was statistically analyzed. The patients were divided into two groups as apnea hypopnea index (AHI) ≥15/hr and AHI<15/hr, and the parameters were compared.

Results:

A total of 321 patients (210 men, 111 women) were included in this study. The mean age was 54.8±16.1 years. The white blood cells count, hemoglobin level, hematocrit level, and neutrophil count, which are considered as indicators of inflammation, were significantly higher in the AHI ≥15/hr group (p=0.015; p=0.040; p=0.019 and p=0.012, respectively). Among the HRV parameters, the median low-frequency component power / high-frequency component power (LF/HF) ratio was 3.1 in patients with AHI>15/hr, while it was 2.1 in the AHI<15/hr group and was significantly higher in the moderate-severe OSAS group (p=0.012). A significant correlation was found between the LF/HF ratio and neutrophil count, leukocyte count, and neutrophil/lymphocyte ratio (r=0.201; p=0.005 and r=0.165; p=0.020 and r=0.189; p=0.008).

Conclusion:

In this study, the presence of increased inflammation and deterioration in sympathovagal balance in patients with OSAS has been demonstrated once again. The correlation of autonomic dysfunction with increased inflammation has been noted for the first time, suggesting that inflammation may play a primary role in sympathetic dysfunction, which is an important complication of OSAS.

Keywords: Obstructive sleep apnea syndrome, heart rate variability, inflammation, white blood cells, neutrophil

References

Young T, Peppard P, Palta M, Hla KM, Finn L, Morgan B, Skatrud J. Population-based study of sleep-disordered breathing as a risk factor for hypertension. Arch Intern Med 1997;157:1746-52.

Dyken ME, Somers VK, Yamada T, Ren ZY, Zimmerman MB. Investigating the relationship between stroke and obstructive sleep apnea. Stroke 1996;2:401-7.

Partinen M, Guilleminault C. Daytime sleepiness and vascular morbidity at seven-year follow-up in obstructive sleep apnea patients. Chest 1990;97:27-32.

Hung J, Whitford EG, Parsons RW, Hillman DR. Association of sleep apnoea with myocardial infarction in men. Lancet 1990;336:261-4.

Bliwise DL, Bliwise NG, Partinen M, Pursley AM, Dement WC. Sleep apnea and mortality in an aged cohort. Am J Public Health 1988;78:544-7.

Nicholl DD, Hanly PJ, Poulin MJ, Handley GB, Hemmelgarn BR, Sola DY, Ahmed SB. Evaluation of continuous positive airway pressure therapy on renin-angiotensin system activity in obstructive sleep apnea. Am J Respir Crit Care Med 2014;190:572-80.

Ryan S, Taylor CT, McNicholas WT. Selective activation of inflammatory pathways by intermittent hypoxia in obstructive sleep apnea syndrome. Circulation 2005;112:2660-7.

Aihara K, Oga T, Chihara Y, Harada Y, Tanizawa K, Handa T, Hitomi T, Uno K, Mishima M, Chin K. Analysis of systemic and airway inflammation in obstructive sleep apnea. Sleep Breath 2013;17:597-604.

Lombardi C, Pengo MF, Parati G. Obstructive sleep apnea syndrome and autonomic dysfunction. Auton Neurosci 2019;221:102563.

Uygur F, Tanriverdi H, Aktop Z, Erboy F, Altinsoy B, Damar M, Atalay F. The neutrophil-to-lymphocyte ratio in patients with obstructive sleep apnoea syndrome and its relationship with cardiovascular disease. Heart Lung 2016;45:121-5.

Kirtane AJ, Bui A, Murphy SA, Barron HV, Gibson CM. Association of peripheral neutrophilia with adverse angiographic outcomes in ST-elevation myocardial infarction. Am J Cardiol 2004;93:532-6.

de Jager CP, van Wijk PT, Mathoera RB, de Jongh-Leuvenink J, van der Poll T, Wever PC. Lymphocytopenia and neutrophil-lymphocyte count ratio predict bacteremia better than conventional infection markers in an emergency care unit. Crit Care 2010;14:R192.

Turak O, Özcan F, Işleyen A, Başar FN, Gül M, Yilmaz S, Sökmen E, Yüzgeçer H, Lafçi G, Topaloğlu S, Aydoğdu S. Usefulness of neutrophil-to-lymphocyte ratio to predict in-hospital outcomes in infective endocarditis. Can J Cardiol 2013;29:1672-8.

Gula LJ, Krahn AD, Skanes A, Ferguson KA, George C, Yee R, Klein GJ. Heart rate variability in obstructive sleep apnea: a prospective study and frequency domain analysis. Ann Noninvasive Electrocardiol 2003;8:144-9.

Stein PK, Bosner MS, Kleiger RE, Conger BM. Heart rate variability: a measure of cardiac autonomic tone. Am Heart J 1994;127:1376-81.

von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP; STROBE Initiative. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. PLoS Med 2007;4:e296.

Ewing DJ, Neilson JM, Shapiro CM, Stewart JA, Reid W. Twenty four hour heart rate variability: effects of posture, sleep, and time of day in healthy controls and comparison with bedside tests of autonomic function in diabetic patients. Br Heart J 1991;65:239-44.

Narkiewicz K, Montano N, Cogliati C, van de Borne PJ, Dyken ME, Somers VK. Altered cardiovascular variability in obstructive sleep apnea. Circulation 1998;98:1071-7.

Khoo MC, Kim TS, Berry RB. Spectral indices of cardiac autonomic function in obstructive sleep apnea. Sleep 1999;22:443-51.

Roche F, Gaspoz JM, Court-Fortune I, Minini P, Pichot V, Duverney D, Costes F, Lacour JR, Barthélémy JC. Screening of obstructive sleep apnea syndrome by heart rate variability analysis. Circulation 1999;100:1411-5.

Roche F, Pichot V, Sforza E, Court-Fortune I, Duverney D, Costes F, Garet M, Barthélémy JC. Predicting sleep apnoea syndrome from heart period: a time-frequency wavelet analysis. Eur Respir J 2003;22:937-42.

Hilton MF, Bates RA, Godfrey KR, Chappell MJ, Cayton RM. Evaluation of frequency and time-frequency spectral analysis of heart rate variability as a diagnostic marker of the sleep apnoea syndrome. Med Biol Eng Comput 1999;37:760-9.

Hatipoğlu U, Rubinstein I. Inflammation and obstructive sleep apnea syndrome pathogenesis: a working hypothesis. Respiration 2003;70:665-71.

Zahorec R. Ratio of neutrophil to lymphocyte counts--rapid and simple parameter of systemic inflammation and stress in critically ill. Bratisl Lek Listy 2001;102:5-14.

Vgontzas AN, Papanicolaou DA, Bixler EO, Hopper K, Lotsikas A, Lin HM, Kales A, Chrousos GP. Sleep apnea and daytime sleepiness and fatigue: relation to visceral obesity, insulin resistance, and hypercytokinemia. J Clin Endocrinol Metab 2000;85:1151-8.

Shamsuzzaman AS, Winnicki M, Lanfranchi P, Wolk R, Kara T, Accurso V, Somers VK. Elevated C-reactive protein in patients with obstructive sleep apnea. Circulation 2002;105:2462-4.

Woodson BT, Garancis JC, Toohill RJ. Histopathologic changes in snoring and obstructive sleep apnea syndrome. Laryngoscope 1991;101:1318-22.

Sekosan M, Zakkar M, Wenig BL, Olopade CO, Rubinstein I. Inflammation in the uvula mucosa of patients with obstructive sleep apnea. Laryngoscope 1996;106:1018-20.

Young T, Peppard PE, Gottlieb DJ. Epidemiology of obstructive sleep apnea: a population health perspective. Am J Respir Crit Care Med 2002;165:1217-39.

Bixler EO, Vgontzas AN, Lin HM, Ten Have T, Rein J, Vela-Bueno A, Kales A. Prevalence of sleep-disordered breathing in women: effects of gender. Am J Respir Crit Care Med 2001;163:608-13.

Young T, Finn L. Epidemiological insights into the public health burden of sleep disordered breathing: sex differences in survival among sleep clinic patients. Thorax 1998;53(Suppl 3):S16-9.

Young T, Skatrud J, Peppard PE. Risk factors for obstructive sleep apnea in adults. JAMA 2004;291:2013-6.

Ip MS, Lam B, Tang LC, Lauder IJ, Ip TY, Lam WK. A community study of sleep-disordered breathing in middle-aged Chinese women in Hong Kong: prevalence and gender differences. Chest 2004;125:127-34.

Young T, Shahar E, Nieto FJ, Redline S, Newman AB, Gottlieb DJ, Walsleben JA, Finn L, Enright P, Samet JM; Sleep Heart Health Study Research Group. Predictors of sleep-disordered breathing in community-dwelling adults: the Sleep Heart Health Study. Arch Intern Med 2002;162:893-900.

Autonomic Dysfunction and Inflammation in Obstructive Sleep Apnea Syndrome

ABSTRACT

References