Abstract
Background: Obstructive sleep apnoea (OSA) is associated with high cardiovascular morbidity and mortality and is an independent risk factor for hypertension. Novel circulating cardiovascular risk markers enabling a more accurate prediction of cardiovascular risk have been identified. Examination of these markers may clarify the increased risk in OSA and contribute to an analysis of the benefits of treatment.
Methods: Plasma levels of total cholesterol and triglyceride and activated coagulation factors XIIa and VIIa, factors VII, VIII, XII, fibrinogen, thrombin-antithrombin (TAT), von Willebrand factor antigen (vWFAg), soluble P-selectin (sP-sel), and homocysteine were measured before and after treatment for 1 month with therapeutic or subtherapeutic (control) continuous positive airways pressure (CPAP) in 220 patients with OSA.
Results: Levels of activated coagulation factors XIIa, VIIa, TAT and sP-sel were higher in OSA patients at baseline than in unmatched controls, but did not fall with 1 month of therapeutic CPAP treatment. The raised sP-sel levels correlated only with body mass index (p = 0.002). There was a trend towards a significant fall in total cholesterol with therapeutic CPAP (p = 0.06) compared with the control group. In the therapeutic group there was a clinically significant mean fall in total cholesterol of 0.28 mmol/l (95% confidence interval 0.11 to 0.45, p = 0.001) which may reduce cardiovascular risk by about 15%.
Conclusion: A number of activated coagulation factors are increased in untreated OSA patients, potentially contributing to vascular risk, but they do not fall with 1 month of CPAP treatment. Nasal CPAP may produce a clinically relevant fall in total cholesterol level, potentially reducing cardiovascular risk, but this needs to be verified in a larger prospective study.
Full Text
The Full Text of this article is available as a PDF (74.2 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bennett L. S., Langford B. A., Stradling J. R., Davies R. J. Sleep fragmentation indices as predictors of daytime sleepiness and nCPAP response in obstructive sleep apnea. Am J Respir Crit Care Med. 1998 Sep;158(3):778–786. doi: 10.1164/ajrccm.158.3.9711033. [DOI] [PubMed] [Google Scholar]
- Bennett L. S., Stradling J. R., Davies R. J. A behavioural test to assess daytime sleepiness in obstructive sleep apnoea. J Sleep Res. 1997 Jun;6(2):142–145. doi: 10.1046/j.1365-2869.1997.00039.x. [DOI] [PubMed] [Google Scholar]
- Blann A. D., Seigneur M., Steiner M., Miller J. P., McCollum C. N. Circulating ICAM-1 and VCAM-1 in peripheral artery disease and hypercholesterolaemia: relationship to the location of atherosclerotic disease, smoking, and in the prediction of adverse events. Thromb Haemost. 1998 Jun;79(6):1080–1085. [PubMed] [Google Scholar]
- Chin K., Kita H., Noguchi T., Otsuka N., Tsuboi T., Nakamura T., Shimizu K., Mishima M., Ohi M. Improvement of factor VII clotting activity following long-term NCPAP treatment in obstructive sleep apnoea syndrome. QJM. 1998 Sep;91(9):627–633. doi: 10.1093/qjmed/91.9.627. [DOI] [PubMed] [Google Scholar]
- Chin K., Nakamura T., Shimizu K., Mishima M., Nakamura T., Miyasaka M., Ohi M. Effects of nasal continuous positive airway pressure on soluble cell adhesion molecules in patients with obstructive sleep apnea syndrome. Am J Med. 2000 Nov;109(7):562–567. doi: 10.1016/s0002-9343(00)00580-5. [DOI] [PubMed] [Google Scholar]
- Chin K., Ohi M., Kita H., Noguchi T., Otsuka N., Tsuboi T., Mishima M., Kuno K. Effects of NCPAP therapy on fibrinogen levels in obstructive sleep apnea syndrome. Am J Respir Crit Care Med. 1996 Jun;153(6 Pt 1):1972–1976. doi: 10.1164/ajrccm.153.6.8665063. [DOI] [PubMed] [Google Scholar]
- Colhoun Helen M., Zito Francesco, Norman Chan N., Rubens Michael B., Fuller John H., Humphries Steve E. Activated factor XII levels and factor XII 46C>T genotype in relation to coronary artery calcification in patients with type 1 diabetes and healthy subjects. Atherosclerosis. 2002 Aug;163(2):363–369. doi: 10.1016/s0021-9150(02)00022-9. [DOI] [PubMed] [Google Scholar]
- Corsonello Andrea, Malara Alba, Ientile Riccardo, Corica Francesco. Leptin enhances adenosine diphosphate-induced platelet aggregation in healthy subjects. Obes Res. 2002 Apr;10(4):306–306. doi: 10.1038/oby.2002.42. [DOI] [PubMed] [Google Scholar]
- Faccenda J. F., Mackay T. W., Boon N. A., Douglas N. J. Randomized placebo-controlled trial of continuous positive airway pressure on blood pressure in the sleep apnea-hypopnea syndrome. Am J Respir Crit Care Med. 2001 Feb;163(2):344–348. doi: 10.1164/ajrccm.163.2.2005037. [DOI] [PubMed] [Google Scholar]
- Geiser Thomas, Buck Florian, Meyer Beat J., Bassetti Claudio, Haeberli André, Gugger Matthias. In vivo platelet activation is increased during sleep in patients with obstructive sleep apnea syndrome. Respiration. 2002;69(3):229–234. doi: 10.1159/000063625. [DOI] [PubMed] [Google Scholar]
- Grover S. A., Coupal L., Hu X. P. Identifying adults at increased risk of coronary disease. How well do the current cholesterol guidelines work? JAMA. 1995 Sep 13;274(10):801–806. [PubMed] [Google Scholar]
- Henke K. G., Grady J. J., Kuna S. T. Effect of nasal continuous positive airway pressure on neuropsychological function in sleep apnea-hypopnea syndrome. A randomized, placebo-controlled trial. Am J Respir Crit Care Med. 2001 Mar;163(4):911–917. doi: 10.1164/ajrccm.163.4.9910025. [DOI] [PubMed] [Google Scholar]
- Jansson J. H., Nilsson T. K., Johnson O. von Willebrand factor in plasma: a novel risk factor for recurrent myocardial infarction and death. Br Heart J. 1991 Nov;66(5):351–355. doi: 10.1136/hrt.66.5.351. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jenkinson C., Davies R. J., Mullins R., Stradling J. R. Comparison of therapeutic and subtherapeutic nasal continuous positive airway pressure for obstructive sleep apnoea: a randomised prospective parallel trial. Lancet. 1999 Jun 19;353(9170):2100–2105. doi: 10.1016/S0140-6736(98)10532-9. [DOI] [PubMed] [Google Scholar]
- Johns M. W. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep. 1991 Dec;14(6):540–545. doi: 10.1093/sleep/14.6.540. [DOI] [PubMed] [Google Scholar]
- Junker R., Heinrich J., Schulte H., Erren M., Assmann G. Hemostasis in normotensive and hypertensive men: results of the PROCAM study. The prospective cardiovascular Münster study. J Hypertens. 1998 Jul;16(7):917–923. doi: 10.1097/00004872-199816070-00004. [DOI] [PubMed] [Google Scholar]
- Kiely J. L., McNicholas W. T. Cardiovascular risk factors in patients with obstructive sleep apnoea syndrome. Eur Respir J. 2000 Jul;16(1):128–133. doi: 10.1034/j.1399-3003.2000.16a23.x. [DOI] [PubMed] [Google Scholar]
- Lavie L., Perelman A., Lavie P. Plasma homocysteine levels in obstructive sleep apnea: association with cardiovascular morbidity. Chest. 2001 Sep;120(3):900–908. doi: 10.1378/chest.120.3.900. [DOI] [PubMed] [Google Scholar]
- Law M. R., Wald N. J., Rudnicka A. R. Quantifying effect of statins on low density lipoprotein cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis. BMJ. 2003 Jun 28;326(7404):1423–1423. doi: 10.1136/bmj.326.7404.1423. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Maresca G., Di Blasio A., Marchioli R., Di Minno G. Measuring plasma fibrinogen to predict stroke and myocardial infarction: an update. Arterioscler Thromb Vasc Biol. 1999 Jun;19(6):1368–1377. doi: 10.1161/01.atv.19.6.1368. [DOI] [PubMed] [Google Scholar]
- Olson L. G., King M. T., Hensley M. J., Saunders N. A. A community study of snoring and sleep-disordered breathing. Prevalence. Am J Respir Crit Care Med. 1995 Aug;152(2):711–716. doi: 10.1164/ajrccm.152.2.7633731. [DOI] [PubMed] [Google Scholar]
- Peker Yüksel, Hedner Jan, Norum Jeanette, Kraiczi Holger, Carlson Jan. Increased incidence of cardiovascular disease in middle-aged men with obstructive sleep apnea: a 7-year follow-up. Am J Respir Crit Care Med. 2002 Jul 15;166(2):159–165. doi: 10.1164/rccm.2105124. [DOI] [PubMed] [Google Scholar]
- Peppard P. E., Young T., Palta M., Skatrud J. Prospective study of the association between sleep-disordered breathing and hypertension. N Engl J Med. 2000 May 11;342(19):1378–1384. doi: 10.1056/NEJM200005113421901. [DOI] [PubMed] [Google Scholar]
- Pepperell Justin C. T., Ramdassingh-Dow Sharon, Crosthwaite Nicky, Mullins Rebecca, Jenkinson Crispin, Stradling John R., Davies Robert J. O. Ambulatory blood pressure after therapeutic and subtherapeutic nasal continuous positive airway pressure for obstructive sleep apnoea: a randomised parallel trial. Lancet. 2002 Jan 19;359(9302):204–210. doi: 10.1016/S0140-6736(02)07445-7. [DOI] [PubMed] [Google Scholar]
- Phillips Bradley G., Somers Virend K. Sleep disordered breathing and risk factors for cardiovascular disease. Curr Opin Pulm Med. 2002 Nov;8(6):516–520. doi: 10.1097/00063198-200211000-00006. [DOI] [PubMed] [Google Scholar]
- Reiner A. P., Siscovick D. S., Rosendaal F. R. Hemostatic risk factors and arterial thrombotic disease. Thromb Haemost. 2001 Apr;85(4):584–595. [PubMed] [Google Scholar]
- Ridker P. M., Buring J. E., Rifai N. Soluble P-selectin and the risk of future cardiovascular events. Circulation. 2001 Jan 30;103(4):491–495. doi: 10.1161/01.cir.103.4.491. [DOI] [PubMed] [Google Scholar]
- Ridker P. M. Novel risk factors and markers for coronary disease. Adv Intern Med. 2000;45:391–418. [PubMed] [Google Scholar]
- Rubin H. R. Overcoming barriers to preventive care. J Gen Intern Med. 2000 Jun;15(6):434–436. doi: 10.1046/j.1525-1497.2000.115600.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schäfer H., Koehler U., Ewig S., Hasper E., Tasci S., Lüderitz B. Obstructive sleep apnea as a risk marker in coronary artery disease. Cardiology. 1999;92(2):79–84. doi: 10.1159/000006952. [DOI] [PubMed] [Google Scholar]
- Shahar E., Whitney C. W., Redline S., Lee E. T., Newman A. B., Nieto F. J., O'Connor G. T., Boland L. L., Schwartz J. E., Samet J. M. Sleep-disordered breathing and cardiovascular disease: cross-sectional results of the Sleep Heart Health Study. Am J Respir Crit Care Med. 2001 Jan;163(1):19–25. doi: 10.1164/ajrccm.163.1.2001008. [DOI] [PubMed] [Google Scholar]
- Shimizu Mie, Kamio Kazutaka, Haida Munetaka, Ono Yoshiaki, Miyachi Hayato, Yamamoto Masahiro, Shinohara Yukito, Ando Yasuhiko. Platelet activation in patients with obstructive sleep apnea syndrome and effects of nasal-continuous positive airway pressure. Tokai J Exp Clin Med. 2002 Dec;27(4):107–112. [PubMed] [Google Scholar]
- Stradling J. R., Barbour C., Glennon J., Langford B. A., Crosby J. H. Prevalence of sleepiness and its relation to autonomic evidence of arousals and increased inspiratory effort in a community based population of men and women. J Sleep Res. 2000 Dec;9(4):381–388. doi: 10.1046/j.1365-2869.2000.00218.x. [DOI] [PubMed] [Google Scholar]
- Stradling John, Smith Debbie, Radulovacki Miodrag, Carley David. Effect of ondansetron on moderate obstructive sleep apnoea, a single night, placebo-controlled trial. J Sleep Res. 2003 Jun;12(2):169–170. doi: 10.1046/j.1365-2869.2003.00342.x. [DOI] [PubMed] [Google Scholar]
- Young T., Palta M., Dempsey J., Skatrud J., Weber S., Badr S. The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med. 1993 Apr 29;328(17):1230–1235. doi: 10.1056/NEJM199304293281704. [DOI] [PubMed] [Google Scholar]
- von Känel R., Le D. T., Nelesen R. A., Mills P. J., Ancoli-Israel S., Dimsdale J. E. The hypercoagulable state in sleep apnea is related to comorbid hypertension. J Hypertens. 2001 Aug;19(8):1445–1451. doi: 10.1097/00004872-200108000-00013. [DOI] [PubMed] [Google Scholar]