Portal de Periódicos da CAPES

Continuous Positive Airway Pressure Treatment

2006; Elsevier BV; Volume: 129; Issue: 6 Linguagem: Inglês

10.1378/chest.129.6.1403

1931-3543

Ferdinando Iellamo, Nicola Montano,

Respiratory Support and Mechanisms

Obstructive sleep apnea syndrome (OSAS) is definitely considered one of the major health issues in the Western world. Besides the problems with daily life functioning, such as hypersomnolence, decreased cognitive functions, motor vehicle crashes, and reduced quality of life, the most relevant medical issue is related to the strong association of OSAS with cardiovascular, cerebrovascular, and metabolic diseases.1Caples SM Gami AS Somers VK Obstructive sleep apnea.Ann Intern Med. 2005; 142: 187-197Crossref PubMed Scopus (341) Google Scholar Several studies1Caples SM Gami AS Somers VK Obstructive sleep apnea.Ann Intern Med. 2005; 142: 187-197Crossref PubMed Scopus (341) Google Scholar, 2Peppard PE Young T Palta M et al.Prospective study of the association between sleep-disordered breathing and hypertension.N Engl J Med. 2000; 342: 1378-1384Crossref PubMed Scopus (4050) Google Scholar, 3Garni AS Howard DE Olson EJ et al.Day-night pattern of sudden death in obstructive sleep apnea.N Engl J Med. 2005; 352: 1206-1214Crossref PubMed Scopus (844) Google Scholar have pointed out that OSAS is an independent risk factor for almost all cardiovascular diseases, such as atrial fibrillation, congestive heart failure, coronary atherosclerosis, myocardial infarction, and sudden death. Namely, the last Joint National Committee report4Chobanian AV Bakris GL Black HR et al.Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure.JAMA. 2003; 289: 2560-2572Crossref PubMed Scopus (16852) Google Scholar for prevention and treatment of hypertension considered OSAS as the first identifiable cause of hypertension. Being the prevalence of this syndrome is so high in the general population, correct therapeutic strategies are important. Continuous positive airway pressure (CPAP) ventilation is the treatment of choice for mild-to-severe OSAS.5Giles T Lasserson T Smith B et al.Continuous positive airways pressure for obstructive sleep apnoea in adults.Cochrane Database Syst Rev. 2006; 1: CD001106PubMed Google Scholar Indeed, CPAP treatment is capable not only of reducing OSAS symptoms and its consequences, but it has also been associated with the reduction of several of the so-called "intermediate mechanisms" linking OSAS to cardiovascular diseases, such as nighttime and daytime sympathetic hyperactivity, inflammation, and endothelial and metabolic dysfunction.1Caples SM Gami AS Somers VK Obstructive sleep apnea.Ann Intern Med. 2005; 142: 187-197Crossref PubMed Scopus (341) Google Scholar The ultimate convincing evidence supporting the protective effects of CPAP treatment of OSAS patients on cardiovascular outcomes has been recently published by Marin et al,6Marin JM Carrizo SJ Vicente E 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.Lancet. 2005; 365: 1046-1053Abstract Full Text Full Text PDF PubMed Scopus (2664) Google Scholar who studied snorers, mild OSAS patients, severe OSAS patients without CPAP, and severe OSAS patients under CPAP therapy. After a 10-year follow-up, the patients with severe OSAS without CPAP had a significant increase in fatal and nonfatal cardiovascular events, while the patients with severe OSAS receiving CPAP had a risk of events similar to control subjects. However, in their placebo-controlled trial evaluating the effects of 4 weeks of treatment with CPAP on ambulatory BP in hypertensive OSAS patients, published in this issue of CHEST (see page 1459), Campos-Rodriguez and coworkers7Campos-Rodriguez F Grilo-Reina A Perez-Ronchel J et al.Effect of continuous positive airway pressure on ambulatory blood pressure in patients with sleep apnea and hypertension: a placebo controlled trial.Chest. 2006; 129: 1459-1467Abstract Full Text Full Text PDF PubMed Scopus (182) Google Scholar did not observe significant changes in daytime or nighttime BP. This latter finding may of course raise some concern about the capability of CPAP treatment of reducing BP. To this regard, data present in the literature are often controversial. In addition to the articles quoted by this study reporting an effect or no effect of CPAP on BP, a study by Mills and coworkers8Mills PJ Kennedy BP Loredo JS et al.Effects of nasal continuous positive airway pressure and oxygen Supplementation on norepinephrine kinetics and cardiovascular responses in obstructive sleep apnea.J Appl Physiol. 2006; 100: 343-348Crossref PubMed Scopus (129) Google Scholar has recently reported that 2 weeks of CPAP treatment was able to increase norepinephrine clearance and reduce BP in a group of OSAS patients, half of whom were hypertensive. They did not measure ambulatory BP but only in-hospital daytime values. Moreover, they did withdraw antihypertensive therapy for the 2 weeks of study, at variance with the study of Campos-Rodriguez et al.7Campos-Rodriguez F Grilo-Reina A Perez-Ronchel J et al.Effect of continuous positive airway pressure on ambulatory blood pressure in patients with sleep apnea and hypertension: a placebo controlled trial.Chest. 2006; 129: 1459-1467Abstract Full Text Full Text PDF PubMed Scopus (182) Google Scholar As discussed by the authors,7Campos-Rodriguez F Grilo-Reina A Perez-Ronchel J et al.Effect of continuous positive airway pressure on ambulatory blood pressure in patients with sleep apnea and hypertension: a placebo controlled trial.Chest. 2006; 129: 1459-1467Abstract Full Text Full Text PDF PubMed Scopus (182) Google Scholar this might be a key factor explaining the lack of decrease in BP in a group of well-controlled hypertensive subjects. In support of this hypothesis are the observations that CPAP treatment reduced 24-h ambulatory BP in a group of subjects with uncontrolled resistant hypertension despite therapy9Logan AG Tkacova R Perlikowski SM et al.Refractory hypertension and sleep apnoea: effect of CPAP on blood pressure and baroreflex.Eur Respir J. 2003; 21: 241-247Crossref PubMed Scopus (282) Google Scholar; and that 6-month and 1-year, but not 1-month, CPAP therapy was able to reduce daytime sympathetic nerve activity in obstructive sleep apnea (OSA) normotensive patients without affecting BP and heart rate.10Narkiewicz K Kato M Phillips BA et al.Nocturnal continuous positive airway pressure decreases daytime sympathetic traffic in obstructive sleep apnea.Circulation. 1999; 100: 2332-2335Crossref PubMed Scopus (426) Google Scholar Hence, CPAP may act by normalizing the mechanisms underlying high BP, namely sustained sympathetic activation, without a clear effect on BP (and heart rate as well), which is the result of multiple neural, humoral, and vascular factors. These effects would require longer-term CPAP therapy than 4 weeks as in the study of Campos-Rodriguez,7Campos-Rodriguez F Grilo-Reina A Perez-Ronchel J et al.Effect of continuous positive airway pressure on ambulatory blood pressure in patients with sleep apnea and hypertension: a placebo controlled trial.Chest. 2006; 129: 1459-1467Abstract Full Text Full Text PDF PubMed Scopus (182) Google Scholar as recognized by the authors. Another issue that is not usually taken into account in this kind of trial is the duration of the hypertensive state. Since hypertension has a multifarious origin,11Malliani A Montano N Emerging excitatory role of cardiovascular sympathetic afferents in pathophysiological conditions.Hypertension. 2002; 39: 63-68Crossref PubMed Scopus (126) Google Scholar vascular remodeling is likely to represent the last, and maybe definitive factor that contributes to the maintenance of hypertension despite the reduction of all neurohumoral, inflammatory, endothelial, metabolic, and other promoting factors.12Intengan HD Schiffrin EL Vascular remodeling in hypertension: roles of apoptosis, inflammation, and fibrosis.Hypertension. 2001; 38: 581-587Crossref PubMed Scopus (816) Google Scholar To this regard, we should have to wonder whether a different effect on BP could be obtained starting the CPAP treatment as soon as hypertension is diagnosed in patients with concomitant OSA. Thus, a possible design for future randomized, placebo-controlled trials should include a population of OSA patients with newly diagnosed hypertension, in which CPAP treatment is compared to placebo. Last but not least, we should consider that CPAP is the optimal treatment for OSA, improving symptoms and cardiovascular outcomes, but it is not per se an antihypertensive therapy. It works by improving overall neural cardiovascular regulation, which is rather complex during sleep,13Iellamo F Placidi F Marciani MG et al.Baroreflex buffering of sympathetic activation during sleep: evidence from autonomic assessment of sleep macroarchitecture and microarchitecture.Hypertension. 2004; 43: 814-819Crossref PubMed Scopus (65) Google Scholar through decreasing chemoreflex activation, increasing baroreflex sensitivity, and decreasing peripheral sympathetic drive, in addition to improve endothelial function,1Caples SM Gami AS Somers VK Obstructive sleep apnea.Ann Intern Med. 2005; 142: 187-197Crossref PubMed Scopus (341) Google Scholar, 14Somers VK Dyken ME Clary MP et al.Sympathetic neural mechanism in obstructive sleep apnea.J Clin Invest. 1995; 96: 1897-1904Crossref PubMed Scopus (2108) Google Scholar all factors involved in the progression of the atherosclerotic process and its consequences. In this sense, CPAP acts indirectly by improving the features that concur to the establishment and/or maintenance of arterial hypertension. Therefore, the study by Campos-Rodriguez et al7Campos-Rodriguez F Grilo-Reina A Perez-Ronchel J et al.Effect of continuous positive airway pressure on ambulatory blood pressure in patients with sleep apnea and hypertension: a placebo controlled trial.Chest. 2006; 129: 1459-1467Abstract Full Text Full Text PDF PubMed Scopus (182) Google Scholar has the profound merit of not definitely establishing the potential antihypertensive effects of CPAP, but vice versa of stimulating more extensive trials in order to evaluate the impact of this treatment on BP in OSAS patients.