Treatment of obstructive sleep apnea reduces arterial stiffness

PurposeA close relationship between obstructive sleep apnea (OSA) and atherosclerosis has been reported, but it is still discussed controversially whether OSA affects vascular function and structure independently. Therefore, we prospectively investigated the independent impact of OSA and its treatment on arterial stiffness.MethodsOne hundred seventy-two patients with suspected OSA were prospectively enrolled in a non-randomized 6-month study to determine whether effective treatment (respiratory events sufficiently reduced and proven compliance) of OSA with continuous positive airway pressure (CPAP) would affect vascular function as measured by augmentation index (Aix) and pulse wave velocity (PWV). Additionally, using a nested case–control, we matched 45 pairs of patients with and without OSA for gender, age, and hypertension.ResultsOverall, OSA (n = 117) was associated with increased Aix (23.6 ± 13.5 vs. 8.9 ± 13.7, p < 0.001) and PWV (9.1 ± 1.6 vs. 7.8 ± 1.6 m/s, p < 0.001) as compared with that in controls without OSA (n = 55). Multivariable analysis and results from the nested case–control cohort showed that OSA was associated with increased Aix and PWV independently from hypertension, age, gender, body mass index, and antihypertensive medications. In 49 effectively treated OSA patients, Aix (baseline 22.0 ± 13.4, follow-up 20.1 ± 12.9, p < 0.01) and PWV (baseline 9.6 ± 1.5, follow-up 8.7 ± 1.4, p < 0.05) had improved. In contrast, ineffectively treated OSA patients (n = 39) showed no change in Aix and PWV.ConclusionsThis prospective controlled study suggests that OSA is independently associated with increased arterial stiffness. Furthermore, treatment with CPAP significantly reduced arterial stiffness. These findings extend our understanding of the recently shown cardiovascular burden in OSA and help to explain why CPAP treatment proved to ameliorate cardiovascular outcome even in patients without preexisting cardiovascular disease.

[1]  H. Yaggi,et al.  Obstructive sleep apnoea and stroke , 2004, The Lancet Neurology.

[2]  Alvar Agusti,et al.  Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study , 2005, The Lancet.

[3]  L. Bortolotto,et al.  Early signs of atherosclerosis in obstructive sleep apnea. , 2005, American journal of respiratory and critical care medicine.

[4]  T. Young,et al.  Sleep apnea and cardiovascular disease: an American Heart Association/American College of Cardiology Foundation Scientific Statement from the American Heart Association Council for High Blood Pressure Research Professional Education Committee, Council on Clinical Cardiology, Stroke Council, and Coun , 2008, Journal of the American College of Cardiology.

[5]  B. Sanner,et al.  Continuous positive airway pressure treatment of mild to moderate obstructive sleep apnea reduces cardiovascular risk. , 2007, American journal of respiratory and critical care medicine.

[6]  D. Webb,et al.  Non-invasive measures of pulse wave velocity correlate with coronary arterial plaque load in humans , 2004, Journal of hypertension.

[7]  T. Young,et al.  Prospective study of the association between sleep-disordered breathing and hypertension. , 2000, The New England journal of medicine.

[8]  Kozo Hirata,et al.  Pulse wave analysis and pulse wave velocity: a review of blood pressure interpretation 100 years after Korotkov. , 2006, Circulation journal : official journal of the Japanese Circulation Society.

[9]  C. Hayward,et al.  Noninvasive determination of age-related changes in the human arterial pulse. , 1989, Circulation.

[10]  K. D. Hopkins,et al.  A Family History of NIDDM Is Associated With Decreased Aortic Distensibility in Normal Healthy Young Adult Subjects , 1996, Diabetes Care.

[11]  M E Safar,et al.  Arterial Wave Reflections and Survival in End-Stage Renal Failure , 2001, Hypertension.

[12]  Adelaide M. Arruda-Olson,et al.  Sleep Apnea and Cardiovascular Disease , 2003, Herz.

[13]  C. Bulpitt,et al.  The aging of elastic and muscular arteries: a comparison of diabetic and nondiabetic subjects. , 2003, Diabetes care.

[14]  J. Blacher,et al.  Impact of aortic stiffness on survival in end-stage renal disease. , 1999, Circulation.

[15]  Bonnie K. Lind,et al.  Association of Sleep-Disordered Breathing, Sleep Apnea, and Hypertension in a Large Community-Based Study , 2000 .

[16]  E. Fletcher,et al.  Blood pressure response to chronic episodic hypoxia: the renin-angiotensin system. , 2002, Journal of applied physiology.

[17]  D. Newby,et al.  Endothelial Function Is Associated With Pulse Pressure, Pulse Wave Velocity, and Augmentation Index in Healthy Humans , 2006, Hypertension.

[18]  Jan Hedner,et al.  Increased incidence of cardiovascular disease in middle-aged men with obstructive sleep apnea: a 7-year follow-up. , 2002, American journal of respiratory and critical care medicine.

[19]  J. Hedner,et al.  Attenuated endothelium-dependent vascular relaxation in patients with sleep apnoea. , 1996, Journal of hypertension.

[20]  H. Struijker‐Boudier,et al.  Expert consensus document on arterial stiffness: methodological issues and clinical applications. , 2006, European heart journal.

[21]  A. Dupont,et al.  The impact of continuous positive airway pressure on blood pressure in patients with obstructive sleep apnea syndrome: evidence from a meta-analysis of placebo-controlled randomized trials. , 2007, Archives of internal medicine.

[22]  B. Morgan,et al.  Chronic intermittent hypoxia alters NE reactivity and mechanics of skeletal muscle resistance arteries. , 2006, Journal of applied physiology.

[23]  北原 良洋.  Effect of CPAP on brachial-ankle pulse wave velocity in patients with OSAHS : an open-labelled study , 2006 .

[24]  I. Fietze,et al.  Sleep apnoea in heart failure , 2007, European Respiratory Journal.

[25]  Daniel J Buysse,et al.  Sleep–Related Breathing Disorders in Adults: Recommendations for Syndrome Definition and Measurement Techniques in Clinical Research , 2000 .

[26]  M. E. Safar,et al.  Aortic Pulse Wave Velocity Predicts Cardiovascular Mortality in Subjects >70 Years of Age , 2001, Arteriosclerosis, thrombosis, and vascular biology.

[27]  L. Bortolotto,et al.  Obstructive sleep apnea, hypertension, and their interaction on arterial stiffness and heart remodeling. , 2007, Chest.

[28]  S. Strandgaard,et al.  Pulse‐wave morphology and pulse‐wave velocity in healthy human volunteers: Examination conditions , 2006, Scandinavian journal of clinical and laboratory investigation.

[29]  K. Ehlenz.  Regulation of blood volume—implications for cardiovascular pathophysiology in sleep apnoea , 1995, Journal of sleep research.

[30]  T. Young,et al.  Sleep disordered breathing and mortality: eighteen-year follow-up of the Wisconsin sleep cohort. , 2008, Sleep.

[31]  Thomas Penzel,et al.  Effect of Nasal Continuous Positive Airway Pressure Treatment on Blood Pressure in Patients With Obstructive Sleep Apnea , 2003, Circulation.

[32]  D. Liao,et al.  Arterial stiffness and the development of hypertension , 2000, Annals of medicine.

[33]  Yasmin,et al.  Isolated Systolic Hypertension Is Characterized by Increased Aortic Stiffness and Endothelial Dysfunction , 2007, Hypertension.

[34]  N. Marshall,et al.  Sleep apnea as an independent risk factor for all-cause mortality: the Busselton Health Study. , 2008, Sleep.

[35]  M. Kähönen,et al.  Letter by Nieminen et al regarding article, "Differential impact of blood pressure-lowering drugs on central aortic pressure and clinical outcomes: principal results of the Conduit Artery Function Evaluation (CAFE) study". , 2006, Circulation.

[36]  J. Hedner,et al.  Diurnal and obstructive sleep apnea influences on arterial stiffness and central blood pressure in men. , 2005, Sleep.

[37]  P Lavie,et al.  Mortality in sleep apnea patients: a multivariate analysis of risk factors. , 1995, Sleep.

[38]  H. Tse,et al.  Endothelial function in obstructive sleep apnea and response to treatment. , 2004, American journal of respiratory and critical care medicine.

[39]  L. Chambless,et al.  Arterial stiffness and the development of hypertension. The ARIC study. , 1999, Hypertension.

[40]  D. Celermajer,et al.  Treatment of obstructive sleep apnoea leads to improved microvascular endothelial function in the systemic circulation , 2006, Thorax.

[41]  K. Reynolds,et al.  Effect of Nocturnal Nasal Continuous Positive Airway Pressure on Blood Pressure in Obstructive Sleep Apnea , 2007, Hypertension.

[42]  J. Mateika,et al.  Arterial stiffness increases during obstructive sleep apneas. , 2002, Sleep.

[43]  S. Anderson,et al.  Aortic Pulse-Wave Velocity and Its Relationship to Mortality in Diabetes and Glucose Intolerance: An Integrated Index of Vascular Function? , 2002, Circulation.

[44]  J. Fleetham,et al.  Impact of Continuous Positive Airway Pressure Therapy on Blood Pressure in Patients with Obstructive Sleep Apnea Hypopnea: A Meta-analysis of Randomized Controlled Trials , 2007, Lung.

[45]  J. Hedner,et al.  Effects of continuous positive airway pressure treatment and withdrawal in patients with obstructive sleep apnea on arterial stiffness and central BP. , 2008, Chest.

[46]  J. Stradling,et al.  CPAP and measures of cardiovascular risk in males with OSAS , 2008, European Respiratory Journal.

[47]  Christodoulos Stefanadis,et al.  Prediction of cardiovascular events and all-cause mortality with central haemodynamics: a systematic review and meta-analysis. , 2010, European heart journal.

[48]  V. Somers,et al.  Impairment of Endothelium-Dependent Vasodilation of Resistance Vessels in Patients With Obstructive Sleep Apnea , 2000, Circulation.

[49]  J. Stradling,et al.  Endothelial function and arterial stiffness in minimally symptomatic obstructive sleep apnea. , 2008, American journal of respiratory and critical care medicine.

[50]  L. Bortolotto,et al.  Effects of continuous positive airway pressure on early signs of atherosclerosis in obstructive sleep apnea. , 2007, American journal of respiratory and critical care medicine.

[51]  Alice Stanton,et al.  Differential Impact of Blood Pressure–Lowering Drugs on Central Aortic Pressure and Clinical Outcomes: Principal Results of the Conduit Artery Function Evaluation (CAFE) Study , 2006, Circulation.

[52]  S. Javaheri,et al.  Sleep apnea in 81 ambulatory male patients with stable heart failure. Types and their prevalences, consequences, and presentations. , 1998, Circulation.

[53]  I. Kallikazaros,et al.  The incremental effect of obstructive sleep apnoea syndrome on arterial stiffness in newly diagnosed essential hypertensive subjects , 2007, Journal of hypertension.

[54]  Daniel J Buysse,et al.  Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. The Report of an American Academy of Sleep Medicine Task Force. , 1999, Sleep.

[55]  D. Levy,et al.  Changes in Arterial Stiffness and Wave Reflection With Advancing Age in Healthy Men and Women: The Framingham Heart Study , 2004, Hypertension.

[56]  Tine Willum Hansen,et al.  Prognostic Value of Aortic Pulse Wave Velocity as Index of Arterial Stiffness in the General Population , 2006, Circulation.

[57]  C W Whitney,et al.  Sleep-disordered breathing and cardiovascular disease: cross-sectional results of the Sleep Heart Health Study. , 2001, American journal of respiratory and critical care medicine.

[58]  B. Caffo,et al.  Sleep-Disordered Breathing and Mortality: A Prospective Cohort Study , 2009, PLoS medicine.

[59]  K. Clark,et al.  Association of Sleep-Disordered Breathing, Sleep Apnea, and Hypertension in a Large Community- Based Study , 2000 .

[60]  C. Vlachopoulos,et al.  Prediction of Cardiovascular Events and All-Cause Mortality With Arterial Stiffness , 2011 .

[61]  P. Ducimetiere,et al.  Aortic Stiffness Is an Independent Predictor of All-Cause and Cardiovascular Mortality in Hypertensive Patients , 2001, Hypertension.