Nocturnal intermittent hypoxia predicts prevalent hypertension in the European Sleep Apnoea Database cohort study

Systemic hypertension is associated with obstructive sleep apnoea syndrome (OSAS) but the pathophysiological mechanisms are incompletely understood. A collaborative European network of 24 sleep centres established a European Sleep Apnoea Database to evaluate cardiovascular morbidity associated with OSAS. 11 911 adults referred with suspected OSAS between March 2007 and September 2013 underwent overnight sleep studies, either cardiorespiratory polygraphy or polysomnography. We compared the predictive value of the apnoea–hypopnoea index (AHI) and 4% oxygen desaturation index (ODI) for prevalent hypertension, adjusting for relevant covariates including age, smoking, obesity, dyslipidaemia and diabetes. Among patients (70% male, mean±sd age 52±12 years), 78% had AHI >5 events·h−1 and 41% systemic hypertension. Both AHI and ODI independently related to prevalent hypertension after adjustment for relevant covariates (p<0.0001 for linear trend across quartiles (Q) of severity for both variables). However, in multiple regression analysis with both ODI and AHI in the model, ODI was, whereas AHI was not, independently associated with prevalent hypertension: odds ratios (95% CI) for Q4 versus Q1 regarding ODI were 2.01 (1.61–2.51) and regarding AHI were 0.92 (0.74–1.15) (p<0.0001 and p=0.3054, respectively). This cross sectional study suggests that chronic intermittent hypoxia plays an important role in OSAS-related hypertension. These findings indicate that ODI is superior to AHI in the prediction of hypertension in patients with OSAS http://ow.ly/xFn6R

[1]  E. Fletcher,et al.  highlighted topics Physiological and Genomic Consequences of Intermittent Hypoxia Invited Review: Physiological consequences of intermittent hypoxia: systemic blood pressure , 2001 .

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

[3]  J Sellgren,et al.  Augmented resting sympathetic activity in awake patients with obstructive sleep apnea. , 1993, Chest.

[4]  A. Chesson,et al.  The American Academy of Sleep Medicine (AASM) Manual for the Scoring of Sleep and Associated Events: Rules, Terminology and Technical Specifications , 2007 .

[5]  W. McNicholas,et al.  Selective Activation of Inflammatory Pathways by Intermittent Hypoxia in Obstructive Sleep Apnea Syndrome , 2005, Circulation.

[6]  W. McNicholas,et al.  Pathophysiology of obstructive sleep apnoea. , 1995, The European respiratory journal.

[7]  Oliver Senn,et al.  Effects of continuous positive airway pressure therapy withdrawal in patients with obstructive sleep apnea: a randomized controlled trial. , 2011, American journal of respiratory and critical care medicine.

[8]  J. Pépin,et al.  At 68 years, unrecognised sleep apnoea is associated with elevated ambulatory blood pressure , 2012, European Respiratory Journal.

[9]  Yutaka Imai,et al.  European Society of Hypertension guidelines for blood pressure monitoring at home: a summary report of the Second International Consensus Conference on Home Blood Pressure Monitoring , 2008, Journal of hypertension.

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

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

[12]  Daniel W. Jones,et al.  Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. , 2003, Hypertension.

[13]  K M Hla,et al.  Population-based study of sleep-disordered breathing as a risk factor for hypertension. , 1997, Archives of internal medicine.

[14]  F. Barbé,et al.  Obstructive sleep apnea and systemic hypertension: longitudinal study in the general population: the Vitoria Sleep Cohort. , 2011, American journal of respiratory and critical care medicine.

[15]  G. Semenza,et al.  Adaptive and maladaptive cardiorespiratory responses to continuous and intermittent hypoxia mediated by hypoxia-inducible factors 1 and 2. , 2012, Physiological reviews.

[16]  G. Parati,et al.  Why Is Out-of-Office Blood Pressure Measurement Needed?: Home Blood Pressure Measurements Will Increasingly Replace Ambulatory Blood Pressure Monitoring in the Diagnosis and Management of Hypertension , 2009, Hypertension.

[17]  Crispin Jenkinson,et al.  Ambulatory blood pressure after therapeutic and subtherapeutic nasal continuous positive airway pressure for obstructive sleep apnoea: a randomised parallel trial , 2002, The Lancet.

[18]  M. Poulin,et al.  Cardiovascular and cerebrovascular responses to acute hypoxia following exposure to intermittent hypoxia in healthy humans , 2009, The Journal of physiology.

[19]  J. Stradling,et al.  Effects of continuous positive airway pressure on systemic inflammation in patients with moderate to severe obstructive sleep apnoea: a randomised controlled trial , 2008, Thorax.

[20]  B. A. Phillips.  Long-term Cardiovascular Outcomes in Men With Obstructive Sleep Apnoea-Hypopnoea With or Without Treatment With Continuous Positive Airway Pressure: An Observational Study , 2007 .

[21]  W. McNicholas,et al.  Long-term effects of nasal continuous positive airway pressure therapy on cardiovascular outcomes in sleep apnea syndrome. , 2005, Chest.

[22]  W. T. McNicholas,et al.  Sleep apnoea as an independent risk factor for cardiovascular disease: current evidence, basic mechanisms and research priorities , 2006, European Respiratory Journal.

[23]  Andrew E. Beaudin,et al.  Intermittent Hypoxia Increases Arterial Blood Pressure in Humans Through a Renin-Angiotensin System–Dependent Mechanism , 2010, HYPERTENSION.

[24]  J. Fleetham,et al.  Portable recording in the assessment of obstructive sleep apnea. ASDA standards of practice. , 1994, Sleep.

[25]  T. Young,et al.  Epidemiology of obstructive sleep apnea: a population health perspective. , 2002, American journal of respiratory and critical care medicine.

[26]  L. Lavie,et al.  Obstructive sleep apnoea syndrome--an oxidative stress disorder. , 2003, Sleep medicine reviews.

[27]  Stanley Lemeshow,et al.  Standardizing the power of the Hosmer–Lemeshow goodness of fit test in large data sets , 2013, Statistics in medicine.

[28]  Peretz Lavie,et al.  Obstructive sleep apnoea syndrome as a risk factor for hypertension: population study , 2000, BMJ : British Medical Journal.

[29]  Organización Mundial de la Salud.  Guidelines for ATC classification and DDD assignment , 1996 .

[30]  A. Chesson,et al.  The AASM Manual for the Scoring of Sleep and Associated Events: Rules, Terminology, and Techinical Specifications , 2007 .

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

[32]  G. Plazzi,et al.  Undiagnosed sleep‐disordered breathing among male nondippers with essential hypertension , 1997, Journal of hypertension.

[33]  J Sellgren,et al.  Is high and fluctuating muscle nerve sympathetic activity in the sleep apnoea syndrome of pathogenetic importance for the development of hypertension? , 1988, Journal of hypertension. Supplement : official journal of the International Society of Hypertension.

[34]  M. Johns,et al.  A new method for measuring daytime sleepiness: the Epworth sleepiness scale. , 1991, Sleep.

[35]  G Parati,et al.  The European Sleep Apnoea Database (ESADA): report from 22 European sleep laboratories , 2011, European Respiratory Journal.

[36]  C. Zwillich,et al.  Surges of muscle sympathetic nerve activity during obstructive apnea are linked to hypoxemia. , 1995, Journal of applied physiology.

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

[38]  S. Takagi,et al.  Effects of incomplete ionization of impurities in poly-Si gate and band gap narrowing on direct tunneling gate leakage current , 2001 .

[39]  Brian Caffo,et al.  Prospective Study of Sleep-disordered Breathing and Hypertension the Sleep Heart Health Study at a Glance Commentary , 2022 .

[40]  R. Tamisier,et al.  Chronic intermittent hypoxia in humans during 28 nights results in blood pressure elevation and increased muscle sympathetic nerve activity. , 2010, American journal of physiology. Heart and circulatory physiology.

[41]  T. Douglas Bradley,et al.  High prevalence of unrecognized sleep apnoea in drug-resistant hypertension , 2001, Journal of hypertension.

[42]  T Penzel,et al.  Sleep-related breathing disorder is an independent risk factor for systemic hypertension. , 1999, American journal of respiratory and critical care medicine.

[43]  Gianfranco Parati,et al.  Sleep apnea: epidemiology, pathophysiology, and relation to cardiovascular risk. , 2007, American journal of physiology. Regulatory, integrative and comparative physiology.

[44]  Jose M Marin,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.

[45]  M. Mosteiro,et al.  Effect of CPAP on blood pressure in patients with obstructive sleep apnea and resistant hypertension: the HIPARCO randomized clinical trial. , 2013, JAMA.

[46]  J. Stradling,et al.  Case-control study of 24 hour ambulatory blood pressure in patients with obstructive sleep apnoea and normal matched control subjects , 2000, Thorax.

[47]  G. Parati,et al.  Recommendations for the management of patients with obstructive sleep apnoea and hypertension , 2013, European Respiratory Journal.

[48]  C. Heneghan,et al.  Predictors of decreased spontaneous baroreflex sensitivity in obstructive sleep apnea syndrome. , 2007, Chest.