Abstract
Obstructive sleep apnea syndrome (OSAS) is an important risk factor in cardiovascular disorders. Although the precise mechanism remains to be described, hypercoagulability seems to be involved. To test the presence of decreased fibrinolysis, we measured plasma levels of plasminogen activator inhibitor-1 (PAI-1) in 96 male subjects (32 subjects with OSAS, 32 subjects with both OSAS and hypertension, and a 32 subjects in the control group). All subjects completed a sleep questionnaire and underwent a general physical examination, biochemistry test, and polysomnography study. Patients and control subjects had similar baseline clinical characteristics for age, gender, smoking habit, and levels of cholesterol and triglycerides. Patients with OSAS presented significantly higher circulating levels of PAI-1 compared with the control group, and the difference was even more marked in patients with both OSAS and hypertension. OSAS patients presented a significant inverse correlation between PAI-1 levels and apnea-hypopnea index (r = −0.71, p < 0.001). In conclusion, OSAS patients presented higher circulating levels of PAI than the control group, which was even greater when patients had associated hypertension.
Similar content being viewed by others
References
Remmers JE, deGroot WJ, Sauerland EK, Anch AM (1978) Pathogenesis of upper airway occlusion during sleep. J Appl Physiol 44:931–938
Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S (1993) The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med 328:1230–1235
Pichel F, Zamarron C, Magán F, del Campo F, Alfarez-Sala R, Suarez JR (2004) Health-related quality of life in patients with obstructive sleep apnea: effects of long-term positive airway pressure treatment. Respir Med 98:968–976
Teran-Santos J, Jimenez-Gomez A, Cordero-Guevara J (1999) The association between sleep apnea and the risk of traffic accidents. Cooperative Group Burgos-Santander. N Engl J Med 340:847–851
Coccagna G, Pollini A, Provini F (2006) Cardiovascular disorders and obstructive sleep apnea syndrome. Clin Exp Hypertens 28:217–224
Lavie L (2005) Sleep-disordered breathing and cerebrovascular disease: a mechanistic approach. Neurol Clin 23:1059–1075
Suzuki YJ, Jain V, Park AM, Day RM (2006) Oxidative stress and oxidant signaling in obstructive sleep apnea and associated cardiovascular diseases. Free Radic Biol Med 40:1683–1692
Schulz R (2005) The vascular micromilieu in obstructive sleep apnoea. Eur Respir J 25:780–782
Juhan-Vague I, Alessi MC, Vague P (1996) Thrombogenic and fibrinolytic factors and cardiovascular risk in non-insulin-dependent diabetes mellitus. Ann Med 28:371–380
Saigo M, Hsue PY, Waters DD (2004) Role of thrombotic and fibrinolytic factors in acute coronary syndromes. Prog Cardiovasc Dis 46:524–538
Badimon L, Martinez-Gonzalez J, Llorente-Cortes V, Rodriguez C, Padró T (2006) Cell biology and lipoproteins in atherosclerosis. Curr Mol Med 6:439–456
Wessendorf TE, Thilmann AF, Wang YM, Schreiber A, Konietzko N, Teschler H (2000) Fibrinogen levels and obstructive sleep apnea in ischemic stroke. Am J Respir Crit Care Med 162:2039–2042
Sanner BM, Konermann M, Tepel M, Groetz J, Mummenhoff C, Zidek W (2000) Platelet function in patients with obstructive sleep apnoea syndrome. Eur Respir J 16:648–652
Geiser T, Buck F, Meyer BJ, Bassetti C, Haeberli A, Gugger M (2002) In vivo platelet activation is increased during sleep in patients with obstructive sleep apnea syndrome. Respiration 69:229–234
Hui DS, Ko FW, Fok JP, Chan MC, Li TS, Tomlinson B, Cheng G (2004) The effects of nasal continuous positive airway pressure on platelet activation in obstructive sleep apnea syndrome. Chest 125:1768–1775
Guardiola JJ, Matheson PJ, Clavijo LC, Wilson MA, Fletcher EC (2001) Hypercoagulability in patients with obstructive sleep apnea. Sleep Med 2:517–523
Von Kanel R, Dimsdale JE (2003) Hemostatic alterations in patients with obstructive sleep apnea and the implications for cardiovascular disease. Chest 124:1956–1967
Chmielewska J, Ranby M, Wiman B (1983) Evidence for a rapid inhibitor to tPA in plasma. Thromb Res 31:427–436
Cines DB, Pollak ES, Buck CA, Loscalzo J, Zimmerman GA, McEver RP, Pober JS, Wick TM, Konkle BA, Schwartz BS, Barnathan ES, McCrae KR, Hug BA, Schmidt AM, Stern DM (1998) Endothelial cells in physiology and in the pathophysiology of vascular disorders. Blood 91:3527–3561
Rossignol P, Luttun A, Martin-Ventura JL, Lupu F, Carmeliet P, Collen D, Anglès-Cano E, Lijnen HR (2006) Plasminogen activation: a mediator of vascular smooth muscle cell apoptosis in atherosclerotic plaques. J Thromb Haemost 4:664–670
Naya M, Tsukamoto T, Inubushi M, Morita K, Katoh C, Furumoto T, Fujii S, Tsutsui H, Tamaki N (2007) Elevated plasma plasminogen activator inhibitor type-1 is an independent predictor of coronary microvascular dysfunction in hypertension. Circ J 71:348–353
Von Känel R, Loredo JS, Ancoli-Israel S, Dimsdale JE (2007) Association between polysomnographic measures of disrupted sleep and prothrombotic factors. Chest 131:733–739
Mannucci PM, Gringeri A, Peyvandi F, Di Paolantonio T, Mariani G (2002) Short-term exposure to high altitude causes coagulation activation and inhibits fibrinolysis. Thromb Haemost 87:342–343
Toff WD, Jones CI, Ford I, Pearse RJ, Watson HG, Watt SJ, Ross JA, Gradwell DR, Batchelor AJ, Abrams KR, Jeijers JC, Goodall AH, Greaves M (2006) Effect of hypobaric hypoxia, simulating conditions during long-haul air travel, on coagulation, fibrinolysis, platelet function, and endothelial activation. JAMA 295:2251–2261
Gertler JP, Weibe DA, Ocasio VH, Abbott WM (1991) Hypoxia induces procoagulant activity in cultured human venous endothelium. J Vasc Surg 13:428–433
Liao H, Hyman MC, Lawrence DA, Pinsky DJ (2007) Molecular regulation of the PAI-1 gene by hypoxia: contributions of Egr-1, HIF-1alpha, and C/EBPalpha. FASEB J 21:935–949
Rangemark C, Hedner JA, Carlson JT, Gleerup G, Winther K (1995) Platelet function and fibrinolytic activity in hypertensive and normotensive sleep apnea patients. Sleep 18:188–194
Barcelo A, Llompart E, Barbe F, Morlá M, Vila M, Agusti AG (2002) Plasminogen activator inhibitor-I (PAI-I) polymorphisms in patients with obstructive sleep apnoea. Respir Med 96:193–196
Chomiki N, Henry M, Alessi MC, Anfosso F, Juhan-Vague J (1994) Plasminogen activator inhibitor-1 expression in human liver and healthy or atherosclerotic vessel walls. Thromb Haemost 72:44–53
Venugopal B, Sharon R, Abramovitz R, Khasin A, Miskin R (2001) Plasminogen activator inhibitor-1 in cardiovascular cells: rapid induction alter injecting mice with kainate or adrenergic agents. Cardiovasc Res 49:476–483
Mills PJ, Kennedy BP, Loredo JS, Dimsdale JE, Ziegler MG (2006) Effects of nasal continuous positive airway pressure and oxygen supplementation on norepinephrine kinetics and cardiovascular responses in obstructive sleep apnea. J Appl Physiol 100:343–348
Von Kanel R, Loredo JS, Ancoli-Israel S, Dimsdale JE (2006) Association between sleep apnea severity and blood coagulability: treatment effects of nasal continuous positive airway pressure. Sleep Breath 10:139–146
Shatos MA, Doherty JM, Stump DC, Thompson EA, Collen D (1990) Oxygen radicals generated during anoxia followed by reoxygenation reduce the synthesis of tissue-type plasminogen activator and plasminogen activator inhibitor-1 in human endothelial cell culture. J Biol Chem 265:20443–20448
Juhan-Vague I, Alessi MC, Mavri A, Morange PE (2003) Plasminogen activator inhibitor-1, inflammation, obesity, insulin resistance and vascular risk. J Thromb Haemost 1:1575–1579
Mertens I, Van der Planken M, Corthouts B, Van Gaal LF (2001) Visceral fat is a determinant of PAI-1 activity in diabetic and non-diabetic overweight and obese women. Horm Metab Res 33:602–607
Sundell IB, Dahlen GH, Ranby M (1991) Diet-induced changes in glucose and triglycerides are associated with changes in plasminogen activator inhibitor levels. Haemostasis 21:175–180
Fogari R, Zoppi A (2006) Antihypertensive drugs and fibrinolytic function. Am J Hypertens 19:1293–1299
Acknowledgment
This study was supported by grants FIS (01/0634, RD06/0018) and TIN200715460C0402.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Zamarrón, C., Ricoy, J., Riveiro, A. et al. Plasminogen Activator Inhibitor-1 in Obstructive Sleep Apnea Patients with and without Hypertension. Lung 186, 151–156 (2008). https://doi.org/10.1007/s00408-008-9076-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00408-008-9076-8