Abstract
Purpose
Systemic inflammation is important in the pathogenesis of cardiovascular disease (CVD). We sought to characterize the systemic inflammatory profile associated with obstructive sleep apnea (OSA).
Methods
Adult patients referred for suspected OSA at the University of British Columbia Hospital Sleep Disorders Program were recruited for our study. Patients using HMG CoA inhibitors or a history of CVD were excluded. Fasting serum samples were obtained the morning after their diagnostic polysomnograms. Samples were tested for the following circulating inflammatory mediators: interferon gamma; interleukins 1B, 6, and 8; intercellular and vascular cell adhesion molecules (sICAM-1 and sVCAM-1); and leptin using a multiplex Luminex System.
Results
There were 176 patients; 68% were male, mean age = 50 ± (SD) 11 years, mean apnea/hyponea index (AHI) = 22.9 ± 22/h, mean desaturation (i.e. % of sleep time spent below an oxyhemoglobin saturation of 90%) = 5.4% ± 15, and mean body mass index (BMI) = 32.2 ± 8 kg/m2. In univariate analyses, only leptin, sVCAM-1, and sICAM-1 were significantly associated with indices of OSA severity (i.e. AHI and/or desaturation). In multivariate linear regression analyses that controlled for BMI, gender, age, and current smoking; desaturation persisted as a significant independent predictor for elevated sVCAM-1 and leptin.
Conclusions
We did not find significant associations between OSA and markers of activated innate immunity (IL-1B, 6, and 8). However, OSA severity was independently associated with serum levels of sVCAM-1 and leptin; these may represent mechanisms involved in the pathogenesis of OSA-related CVD.
Similar content being viewed by others
References
Marin JM, Carrizo SJ, Vicente E et al (2005) Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study. Lancet 365:1046–1053
Libby P, Ridker PM, Maseri A (2002) Inflammation and atherosclerosis. Circulation 105:1135–1143. doi:10.1161/hc0902.104353
Lindahl B, Toss H, Siegbahn A, Venge P, Wallentin L (2000) Markers of myocardial damage and inflammation in relation to long-term mortality in unstable coronary artery disease. N Engl J Med 343:1139–1147. doi:10.1056/NEJM200010193431602
Ridker PM, Rifai N, Stampfer MJ, Hennekens CH (2000) Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men. Circulation 101:1767–1772
Khera A, McGuire DK, Murphy SA, Meo Neto Jde P, Morrow DA, de Lemos JA (2004) Association among plasma levels of monocyte chemoattractant protein-1, traditional cardiovascular risk factors, and subclinical atherosclerosis. J Am Coll Cardiol 44:1812–1818. doi:10.1016/j.jacc.2004.07.047
Ballantyne CM (2001) Newer risk markers and surrogate endpoints in atherosclerosis management. Clin Cardiol 24(8 Suppl):III13–III17
Ryan S, Taylor CT, McNicholas WT (2006) Predictors of elevated nuclear factor κB dependent genes in obstructive sleep apnea syndrome. Am J Respir Crit Care Med 174:824–830. doi:10.1164/rccm.200601-066OC
Gozal D, Kheirandish-Gozal L (2008) Cardiovascular morbidity in obstructive sleep apnea: oxidative stress, inflammation, and much more. Am J Respir Crit Care Med 177:369–375. doi:10.1164/rccm.200608-1190PP
Ohga E, Tomita T, Wada H, Yamamoto H, Nagase T, Ouchi Y (2003) Effects of obstructive sleep apnea on circulating ICAM-1, IL-8, and MCP-1. J Appl Physiol 94:179–184
Ohga E, Nagase T, Tomita T, Teramoto S, Matsuse T, Katayama H, Ouchi Y (1999) Increased levels of circulating ICAM-1, VCAM-1, and L-selectin in obstructive sleep apnea syndrome. J Appl Physiol 87:10–14
El-Solh AA, Mador MJ, Sikka P, Dhillon RS, Amsterdam D, Grant BJ (2002) Adhesion molecules in patients with OSA and CAD. Chest 121(5):1541–1547. doi:10.1378/chest.121.5.1541
Yokoe T, Minoguchi K, Matsuo H et al (2003) Elevated levels of C-reactive protein and interleukin-6 in patients with obstructive sleep apnea syndrome are decreased by nasal continuous positive airway pressure. Circulation 107:1129–1134. doi:10.1161/01.CIR.0000052627.99976.18
Schulz R, Hummel C, Heinemann S, Seeger W, Grimminger F (2002) Serum levels of vascular endothelial growth factor are elevated in patients with obstructive sleep apnea and severe nighttime hypoxia. Am J Respir Crit Care Med 165:67–70
Lavie L, Kraiczi H, Hefetz A, Ghandour H, Perelman A, Hedner J, Lavie P (2002) Plasma vascular endothelial growth factor in sleep apnea syndrome effects of nasal continuous positive air pressure treatment. Am J Respir Crit Care Med 165:1624–1628. doi:10.1164/rccm.20110-040OC
Ryan S, Nolan GM, Hannigan E, Cunningham S, Taylor C, McNicholas WT (2007) Cardiovascular risk markers in obstructive sleep apnoea syndrome and correlation with obesity. Thorax 62(6):509–514. doi:10.1136/thx.2006.066720
AASM (1999) Sleep related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in adults. Sleep 22:667–689
McArdle N, Hillman D, Beilin L, Watts G (2007) Metabolic risk factors for vascular disease in obstructive sleep apnea: a matched controlled study. Am J Respir Crit Care Med 175(2):190–195. doi:10.1164/rccm.200602-270OC
Harsch IA, Konturek PC, Koebnick C, Kuehnlein PP, Fuchs FS, Pour Schahin S, Wiest GH, Hahn EG, Lohmann T, Ficker JH (2003) Leptin and ghrelin levels in patients with obstructive sleep apnoea: effect of CPAP treatment. Eur Respir J 22(2):251–257. doi:10.1183/09031936.03.00010103
Ip MS, Lam KS, Ho C, Tsang KW, Lam W (2000) Serum leptin and vascular risk factors in obstructive sleep apnea. Chest 118(3):580–586. doi:10.1378/chest.118.3.580
Schäfer H, Pauleit D, Sudhop T, Gouni-Berthold I, Ewig S, Berthold HK (2002) Body fat distribution, serum leptin, and cardiovascular risk factors in men with obstructive sleep apnea. Chest 122(3):829–839. doi:10.1378/chest.122.3.829
Minoguchi K, Yokoe T, Tazaki T. Increased carotid intima-media thickness and serum inflammatory markers in obstructive sleep apnea
Tam CS, Wong M, Tam K, Aouad L, Waters KA (2007) The effect of acute intermittent hypercapnic hypoxia treatment on IL-6, TNF-alpha, and CRP levels in piglets. Sleep 30(6):723–727
Kohler M, Ayers L, Pepperell JC, Packwood KL, Ferry B, Crosthwaite N, Craig S, Siccoli MM, Davies RJ, Stradling JR (2009) Effects of continuous positive airway pressure on systemic inflammation in patients with moderate to severe obstructive sleep apnoea: a randomised controlled trial. Thorax 64(1):67–73.
Savransky V, Nanayakkara A, Li J, Bevans S, Smith PL, Rodriguez A, Polotsky VY (2007) Chronic intermittent hypoxia induces atherosclerosis. Am J Respir Crit Care Med 175(12):1290–1297. doi:10.1164/rccm.200612-1771OC
Acknowledgements
Dr. Mulgrew was supported by a BC Lung fellowship and by the CIHR/HSFC IMPACT training scheme. Dr. Ayas was supported by a Michael Smith Foundation for Health Research Scholar Award, a CIHR/BC Lung Association New Investigator Award, and a Departmental Scholar Award from the University British Columbia. This research was supported by a Michael Smith Foundation for Health Research Unit Award (Respiratory Sleep Disorders Research Unit) and an operating grant from the BC Lung Association.
Conflicts of interest
Dr. Ayas received a research grant from Respironics, a maker of CPAP equipment. Otherwise, none of the other authors have conflicts to disclose.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Al Lawati, N., Mulgrew, A., Cheema, R. et al. Pro-atherogenic cytokine profile of patients with suspected obstructive sleep apnea. Sleep Breath 13, 391–395 (2009). https://doi.org/10.1007/s11325-009-0259-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11325-009-0259-1