Three-year changes of prothrombotic factors in a cohort of South Africans with a high clinical suspicion of obstructive sleep apnea

Roland von Känel; Nico T. Malan; Mark Hamer; Gavin W. Lambert; Markus Schlaich; Manja Reimann; Leoné Malan

doi:10.1160/TH15-03-0206

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2016; 115(01): 63-72
DOI: 10.1160/TH15-03-0206

Coagulation and Fibrinolysis

Schattauer GmbH Schattauer

Three-year changes of prothrombotic factors in a cohort of South Africans with a high clinical suspicion of obstructive sleep apnea

Authors

Roland von Känel

¹Department of Neurology, Inselspital, Bern University Hospital, and University of Bern, Switzerland

²Department of Clinical Research, University of Bern, Switzerland

³Department of Psychosomatic Medicine, Clinic Barmelweid, Barmelweid, Switzerland
Nico T. Malan

⁴Hypertension in Africa Research Team (HART), Faculty of Health Sciences North West University, Potchefstroom, South Africa
Mark Hamer

⁴Hypertension in Africa Research Team (HART), Faculty of Health Sciences North West University, Potchefstroom, South Africa

⁵Department of Epidemiology and Public Health, University College London, UK
Gavin W. Lambert

⁶Baker IDI Heart & Diabetes Institute and Central Clinical School, Monash University, Melbourne, Victoria, Australia
Markus Schlaich

⁷Dobney Chair Clinical Research, School of Medicine and Pharmacology, Royal Perth Hospital Unit, University of Western Australia, Perth, Western Australia, Australia
Manja Reimann

⁸Autonomic and Neuroendocrinological Laboratory Dresden, University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany
Leoné Malan

⁴Hypertension in Africa Research Team (HART), Faculty of Health Sciences North West University, Potchefstroom, South Africa

⁹Medical Research Council: Research Unit for Hypertension and Cardiovascular Disease, North West University, Potchefstroom, South Africa

Abstract

Summary

A hypercoagulable state might be one important mechanism linking obstructive sleep apnea (OSA) with incident myocardial infarction and stroke. However, previous studies on prothrombotic factors in OSA are not uniform and cross-sectional. We longitudinally studied prothrombotic factors in relation to OSA risk, adjusting for baseline levels of prothrombotic factors, demographics, metabolic parameters, aspirin use, and life style factors. The Berlin Questionnaire and/or neck circumference were used to define high OSA risk in 329 South African teachers (48.0 % male, 44.6 % black) at baseline and at three-year follow-up. Von Willebrand factor (VWF), fibrinogen, D-dimer, plasminogen activator inhibitor-1, clot lysis time (CLT), and soluble urokinase-type plasminogen activator receptor (suPAR) were measured in plasma. At baseline 35.7 % of participants had a high risk of OSA. At follow-up, persistently high OSA risk, persistently low OSA risk, OSA risk remission, and new-onset OSA risk were present in 26.1 %, 53.2 %, 9.4 %, and 11.3 % of participants, respectively. New-onset OSA risk was associated with a significant and longitudinal increase in VWF, fibrinogen, CLT, and suPAR relative to persistently low OSA risk; in VWF, fibrinogen, and suPAR relative to remitted OSA risk; and in VWF relative to persistently high OSA risk. Persistently high OSA risk was associated with an increase in CLT and suPAR relative to persistently low OSA risk and in D-dimer relative to remitted OSA risk. Remitted OSA risk was associated with D-dimer decrease relative to persistently low OSA risk. In OSA, hypercoagulability is a dynamic process with a most prominent three-year increase in individuals with new-onset OSA risk.

Keywords

Blood coagulation - cardiovascular disease - fibrinolysis - longitudinal study - risk factor - sleep disordered breathing

Full Text

References

References
1 Jordan AS, McSharry DG, Malhotra A. Adult obstructive sleep apnoea. Lancet 2014; 383: 736-747.
2 Wang X, Ouyang Y, Wang Z. et al. Obstructive sleep apnea and risk of cardiovascular disease and all-cause mortality: a meta-analysis of prospective cohort studies. Int J Cardiol 2013; 169: 207-214.
3 Dong JY, Zhang YH, Qin LQ. Obstructive sleep apnea and cardiovascular risk: meta-analysis of prospective cohort studies. Atherosclerosis 2013; 229: 489-495.
4 Li D, Liu D, Wang X, He D. Self-reported habitual snoring and risk of cardiovascular disease and all-cause mortality. Atherosclerosis 2014; 235: 189-195.
5 Lippi G, Mattiuzzi C, Franchini M. Sleep apnea and venous thromboembolism. A systematic review. Thromb Haemost. 2015 114: Epub ahead of print.
6 Gunnarsson SI, Peppard PE, Korcarz CE. et al. Obstructive sleep apnea is associated with future subclinical carotid artery disease: thirteen-year follow-up from the Wisconsin sleep cohort. Arterioscler Thromb Vasc Biol 2014; 34: 2338-2342.
7 Salepci B, Fidan A, Ketenci SC. et al. The effect of obstructive sleep apnea syndrome and snoring severity to intima-media thickening of carotid artery. Sleep Breath 2015; 19: 239-246.
8 Nadeem R, Molnar J, Madbouly EM. et al. Serum inflammatory markers in obstructive sleep apnea: a meta-analysis. J Clin Sleep Med 2013; 09: 1003-1012.
9 Fava C, Montagnana M, Favaloro EJ. et al. Obstructive sleep apnea syndrome and cardiovascular diseases. Semin Thromb Haemost 2011; 37: 280-297.
10 von Känel R, Dimsdale JE. Hemostatic alterations in patients with obstructive sleep apnea and the implications for cardiovascular disease. Chest 2003; 124: 1956-1967.
11 Liak C, Fitzpatrick M. Coagulability in obstructive sleep apnea. Can Respir J 2011; 18: 338-348.
12 Steiner S, Jax T, Evers S. et al. Altered blood rheology in obstructive sleep apnea as a mediator of cardiovascular risk. Cardiology 2005; 104: 92-96.
13 Shitrit D, Peled N, Shitrit AB. et al. An association between oxygen desaturation and D-dimer in patients with obstructive sleep apnea syndrome. Thromb Haemost 2005; 94: 544-547.
14 El Solh AA, Akinnusi ME, Berim IG. et al. Hemostatic implications of endothelial cell apoptosis in obstructive sleep apnea. Sleep Breath 2008; 12: 331-337.
15 von Känel R, Loredo JS, Ancoli-Israel S. et al. Elevated plasminogen activator inhibitor 1 in sleep apnea and its relation to the metabolic syndrome: an investigation in 2 different study samples. Metabolism 2007; 56: 969-976.
16 Tosur Z, Green D, De Chavez PJ. et al. The association between sleep characteristics and prothrombotic markers in a population-based sample: Chicago Area Sleep Study. Sleep Med 2014; 15: 973-978.
17 Niżankowska-Jędrzejczyk A, Almeida FR. et al. Modulation of inflammatory and hemostatic markers in obstructive sleep apnea patients treated with mandibular advancement splints: a parallel, controlled trial. J Clin Sleep Med 2014; 10: 255-262.
18 Eapen DJ, Manocha P, Ghasemzedah N. et al. Soluble urokinase plasminogen activator receptor level is an independent predictor of the presence and severity of coronary artery disease and of future adverse events. J Am Heart Assoc 2014; 03: e00111.
19 Jiang X, Yongxiang W, Wei Z. et al. Higher dose of warfarin for patients with pulmonary embolism complicated by obstructive sleep apnea hypopnea syndrome. Heart Lung 2014; 43: 358-362.
20 Dimsdale JE, Coy T, Ziegler MG. et al. The effect of sleep apnea on plasma and urinary catecholamines. Sleep 1995; 18: 377-381.
21 Grassi G, Facchini A, Trevano FQ. et al. Obstructive sleep apnea-dependent and -independent adrenergic activation in obesity. Hypertension 2005; 46: 321-325.
22 Mills PJ, Dimsdale JE, Coy TV. et al. Beta 2-adrenergic receptor characteristics in sleep apnea patients. Sleep 1995; 18: 39-42.
23 Austin AW, Wissmann T, von Kanel R. Stress and hemostasis: an update. Semin Thromb Hemost 2013; 39: 902-912.
24 von Känel R, Mills PJ, Ziegler MG. et al. Effect of beta2-adrenergic receptor functioning and increased norepinephrine on the hypercoagulable state with mental stress. Am Heart J 2002; 144: 68-72.
25 Ancoli-Israel S, Kripke DF, Klauber MR. et al. Natural history of sleep disordered breathing in community dwelling elderly. Sleep 1993; 16 (Suppl. 08) S25-S29.
26 Malan L, Hamer M, Frasure-Smith N. et al. Cohort Profile: Sympathetic activity and Ambulatory Blood Pressure in Africans (SABPA) prospective cohort study. Int J Epidemiol. 2014 Epub ahead of print.
27 Netzer NC, Stoohs RA, Netzer CM. et al. Using the Berlin Questionnaire to identify patients at risk for the sleep apnea syndrome. Ann Intern Med 1999; 131: 485-491.
28 Chung F, Yegneswaran B, Liao P. et al. Validation of the Berlin questionnaire and American Society of Anesthesiologists checklist as screening tools for obstructive sleep apnea in surgical patients. Anesthesiology 2008; 108: 822-830.
29 Davies RJ, Stradling JR. The relationship between neck circumference, radio-graphic pharyngeal anatomy, and the obstructive sleep apnoea syndrome. Eur Respir J 1990; 03: 509-514.
30 Balk EM, Moorthy D, Obadan NO. et al. Diagnosis and treatment of obstructive sleep apnea in adults. Comp Eff Rev 2011; 32 p. ES 17.
31 Chang ET, Yang MC, Wang HM. et al. Snoring in a sitting position and neck circumference are predictors of sleep apnea in Chinese patients. Sleep Breath 2014; 18: 133-136.
32 Lammertyn L, Schutte AE, Pieters M. et al. D-dimer relates positively with increased blood pressure in black South Africans: the SABPA study. Thromb Res 2014; 133: 1152-1157.
33 Schutte AE, Myburgh A, Olsen MH. et al. Exploring soluble urokinase plasminogen activator receptor and its relationship with arterial stiffness in a bi-ethnic population: the SAfrEIC-study. Thromb Res 2012; 130: 273-277.
34 Lisman T, de Groot PG, Meijers JC. et al. Reduced plasma fibrinolytic potential is a risk factor for venous thrombosis. Blood 2005; 105: 1102-1105.
35 Gozdzik W, Adamik B, Gozdzik A. et al. Unchanged plasma levels of the soluble urokinase plasminogen activator receptor in elective coronary artery bypass graft surgery patients and cardiopulmonary bypass use. PLoS One 2014; 09: e98923.
36 van der Heijden GJ, Donders AR, Stijnen T. et al. Imputation of missing values is superior to complete case analysis and the missing-indicator method in multivariable diagnostic research: a clinical example. J Clin Epidemiol 2006; 59: 1102-1109.
37 Lee KW, Lip GY. Effects of lifestyle on hemostasis, fibrinolysis, and platelet reactivity: a systematic review. Arch Intern Med 2003; 163: 2368-2392.
38 Haupt TH, Kallemose T, Ladelund S. et al. Risk factors associated with serum levels of the inflammatory biomarker soluble urokinase plasminogen activator receptor in a general population. Biomark Insights 2014; 09: 91-100.
39 Cohen J. Statistical power for the behavioral sciences. 3rd edition Academic; New York: 1988
40 Reeves SL, Brown DL, Chervin RD. et al. Agreement between stroke patients and family members for ascertaining pre-stroke risk for sleep apnea. Sleep Med 2014; 15: 121-124.
41 Hrubos-Strøm H, Randby A, Namtvedt SK. et al. A Norwegian population-based study on the risk and prevalence of obstructive sleep apnea. The Akershus Sleep Apnea Project (ASAP). J Sleep Res 2011; 20: 162-170.
42 Centers for Disease Control and Prevention (CDC).. Vital signs: awareness and treatment of uncontrolled hypertension among adults--United States, 2003–2010. MMWR Morb Mortal Wkly Rep 2012; 61: 703-709.
43 von Känel R, Natarajan L, Ancoli-Israel S. et al. Day/Night rhythm of hemostatic factors in obstructive sleep apnea. Sleep 2010; 33: 371-377.
44 von Känel R, Dimsdale JE, Adler KA. et al. Effects of nonspecific beta-adrenergic stimulation and blockade on blood coagulation in hypertension. J Appl Physiol 2003; 94: 1455-1459.
45 von Känel R, Loredo JS, Ancoli-Israel S. et al. Association between polysomno-graphic measures of disrupted sleep and prothrombotic factors. Chest 2007; 131: 733-739.
46 Doherty LS, Kiely JL, Swan V. et al. Long-term effects of nasal continuous positive airway pressure therapy on cardiovascular outcomes in sleep apnea syndrome. Chest 2005; 127: 2076-2084.
47 McEwen BJ, Phillips CL, Morel-Kopp MC. et al. Diurnal changes and levels of fibrin generation are not altered by continuous positive airway pressure (CPAP) in obstructive sleep apnoea (OSA). A randomised, placebo-controlled crossover study. Thromb Haemost 2012; 108: 701–709. Erratum in: Thromb Haemost 2013; 110: 1085.
48 Phillips CL, McEwen BJ, Morel-Kopp MC. et al. Effects of continuous positive airway pressure on coagulability in obstructive sleep apnoea: a randomised, placebo-controlled crossover study. Thorax 2012; 67: 639-644.
49 Tuomilehto H, Seppä J, Uusitupa M. et al. The impact of weight reduction in the prevention of the progression of obstructive sleep apnea: an explanatory analysis of a 5-year observational follow-up trial. Sleep Med 2014; 15: 329-335.
50 Barceló A, Llompart E, Barbé F. et al. Plasminogen activator inhibitor-I (PAI-I) polymorphisms in patients with obstructive sleep apnoea. Respir Med 2002; 96: 193-196.