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Characteristics and Predictors of Obstructive Sleep Apnea in Patients With Systemic Hypertension

2010; Elsevier BV; Volume: 105; Issue: 8 Linguagem: Inglês

10.1016/j.amjcard.2009.12.017

1879-1913

Luciano F. Drager, Pedro R. Genta, Rodrigo Pinto Pedrosa, Flávia Baggio Nerbass, Carolina Gonzaga, E M Krieger, Geraldo Lorenzi‐Filho,

Heart Rate Variability and Autonomic Control

Obstructive sleep apnea (OSA) is a secondary cause of hypertension and independently associated with target-organ damage in hypertensive patients. However, OSA remains largely underdiagnosed and undertreated. The aim of the present study was to evaluate the characteristics and clinical predictors of OSA in a consecutive series of patients followed up in a hypertension unit. A total of 99 patients (age 46 ± 11 years, body mass index 28.8 kg/m2, range 25.1 to 32.9) underwent polysomnography. The clinical parameters included age, gender, obesity, daytime sleepiness, snoring, Berlin Questionnaire, resistant hypertension, and metabolic syndrome. Of the 99 patients, 55 (56%) had OSA (apnea-hypopnea index >5 events/hour). Patients with OSA were older and more obese, had greater levels of blood pressure, and presented with more diabetes, dyslipidemia, resistant hypertension, and metabolic syndrome than the patients without OSA. Of the patients with OSA, 51% had no excessive daytime sleepiness. The Berlin Questionnaire and patient age revealed a high sensitivity (0.93 and 0.91, respectively) but low specificity (0.59 and 0.48, respectively), and obesity and resistant hypertension revealed a low sensitivity (0.58 and 0.44, respectively) but high specificity (0.75 and 0.91, respectively) for OSA. Metabolic syndrome was associated with high sensitivity and specificity for OSA (0.86 and 0.85, respectively). Multiple regression analysis showed that age of 40 to 70 years (odds ratio 1.09, 95% confidence interval 1.03 to 1.16), a high risk of OSA on the Berlin Questionnaire (odds ratio 8.36, 95% confidence interval 1.67 to 41.85), and metabolic syndrome (odds ratio 19.04, 95% confidence interval 5.25 to 69.03) were independent variables associated with OSA. In conclusion, more important than the typical clinical features that characterize OSA, including snoring and excessive daytime sleepiness, the presence of the metabolic syndrome is as an important marker of OSA among patients with hypertension. Obstructive sleep apnea (OSA) is a secondary cause of hypertension and independently associated with target-organ damage in hypertensive patients. However, OSA remains largely underdiagnosed and undertreated. The aim of the present study was to evaluate the characteristics and clinical predictors of OSA in a consecutive series of patients followed up in a hypertension unit. A total of 99 patients (age 46 ± 11 years, body mass index 28.8 kg/m2, range 25.1 to 32.9) underwent polysomnography. The clinical parameters included age, gender, obesity, daytime sleepiness, snoring, Berlin Questionnaire, resistant hypertension, and metabolic syndrome. Of the 99 patients, 55 (56%) had OSA (apnea-hypopnea index >5 events/hour). Patients with OSA were older and more obese, had greater levels of blood pressure, and presented with more diabetes, dyslipidemia, resistant hypertension, and metabolic syndrome than the patients without OSA. Of the patients with OSA, 51% had no excessive daytime sleepiness. The Berlin Questionnaire and patient age revealed a high sensitivity (0.93 and 0.91, respectively) but low specificity (0.59 and 0.48, respectively), and obesity and resistant hypertension revealed a low sensitivity (0.58 and 0.44, respectively) but high specificity (0.75 and 0.91, respectively) for OSA. Metabolic syndrome was associated with high sensitivity and specificity for OSA (0.86 and 0.85, respectively). Multiple regression analysis showed that age of 40 to 70 years (odds ratio 1.09, 95% confidence interval 1.03 to 1.16), a high risk of OSA on the Berlin Questionnaire (odds ratio 8.36, 95% confidence interval 1.67 to 41.85), and metabolic syndrome (odds ratio 19.04, 95% confidence interval 5.25 to 69.03) were independent variables associated with OSA. In conclusion, more important than the typical clinical features that characterize OSA, including snoring and excessive daytime sleepiness, the presence of the metabolic syndrome is as an important marker of OSA among patients with hypertension. Obstructive sleep apnea (OSA) is a secondary cause of hypertension,1Chobanian A.V. Bakris G.L. Black H.R. Cushman W.C. Green L.A. Izzo Jr, J.L. Jones D.W. Materson B.J. Oparil S. Wright Jr, J.T. Roccella E.J. Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood PressureNational Heart, Lung, and Blood InstituteNational High Blood Pressure Education Program Coordinating CommitteeSeventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.Hypertension. 2003; 42: 1206-1252Crossref PubMed Scopus (10125) Google Scholar highly prevalent (around 38% to 82%)2Sjöström C. Lindberg E. Elmasry A. Hägg A. Svärdsudd K. Janson C. Prevalence of sleep apnoea and snoring in hypertensive men: a population based study.Thorax. 2002; 57: 602-607Crossref PubMed Scopus (102) Google Scholar, 3Logan A.G. Perlikowski S.M. Mente A. Tisler A. Tkacova R. Niroumand M. Leung R.S. Bradley T.D. High prevalence of unrecognized sleep apnoea in drug-resistant hypertension.J Hypertens. 2001; 19: 2271-2277Crossref PubMed Scopus (721) Google Scholar and directly related to target-organ damage and increased markers of atherosclerosis.4Drager L.F. Bortolotto L.A. Figueiredo A.C. Silva B.C. Krieger E.M. Lorenzi-Filho G. Obstructive sleep apnea, hypertension and their interaction on arterial stiffness and heart remodeling.Chest. 2007; 131: 1379-1386Crossref PubMed Scopus (197) Google Scholar, 5Drager L.F. Bortolotto L.A. Krieger E.M. Lorenzi-Filho G. Additive effects of obstructive sleep apnea and hypertension on early markers of carotid atherosclerosis.Hypertension. 2009; 53: 64-69Crossref PubMed Scopus (127) Google Scholar However, OSA remains largely underdiagnosed and, consequently, undertreated in clinical practice.6Bradley T.D. Floras J.S. Obstructive sleep apnoea and its cardiovascular consequences.Lancet. 2009; 373: 82-93Abstract Full Text Full Text PDF PubMed Scopus (908) Google Scholar, 7Silverberg D.S. Oksenberg A. Iaina A. Sleep related breathing disorders are common contributing factors to the production of essential hypertension but are neglected, underdiagnosed, and undertreated.Am J Hypertens. 1997; 10: 1319-1325Crossref PubMed Scopus (77) Google Scholar, 8Kapur V. Strohl K.P. Redline S. Iber C. O'Connor G. Nieto J. Underdiagnosis of sleep apnea syndrome in U.S. communities.Sleep Breath. 2002; 6: 49-54Crossref PubMed Scopus (0) Google Scholar One potential limitation for the diagnosis is that the classic symptoms of snoring, breathing pauses, and daytime sleepiness are frequently subjective.9Young T. Skatrud J. Peppard P.E. Risk factors for obstructive sleep apnea in adults.JAMA. 2004; 291: 2013-2016Crossref PubMed Scopus (714) Google Scholar Furthermore, case-finding using only the typical patient characteristics (middle age, male gender, and obesity) might fail to identify women and overweight or even healthy weight patients with OSA.9Young T. Skatrud J. Peppard P.E. Risk factors for obstructive sleep apnea in adults.JAMA. 2004; 291: 2013-2016Crossref PubMed Scopus (714) Google Scholar In 1999, Netzer et al10Netzer N.C. Stoohs R.A. Netzer C.M. Clark K. Strohl K.P. Using the Berlin Questionnaire to identify patients at risk for the sleep apnea syndrome.Ann Intern Med. 1999; 131: 485-491Crossref PubMed Scopus (1887) Google Scholar validated the Berlin Questionnaire in 100 participants from a general population who simultaneously underwent portable sleep monitoring. However, this questionnaire was validated to screen OSA in a primary care population and might not be useful in other populations. Because one of the domains involves the presence of high blood pressure, the sensitivity of the Berlin Questionnaire might be low in patients with hypertension. In the present study, we explored the predictors of OSA in consecutive patients with hypertension. This population is distinct from that referred to in sleep studies, because such patients have already had sleep complaints and OSA frequency is extremely high. We evaluated the relative importance of the traditional risk factors for OSA,9Young T. Skatrud J. Peppard P.E. Risk factors for obstructive sleep apnea in adults.JAMA. 2004; 291: 2013-2016Crossref PubMed Scopus (714) Google Scholar including age of 40 to 70 years, male gender, and the presence of snoring and obesity, in addition to daytime sleepiness somnolence, Berlin Questionnaire findings, and the presence of resistant hypertension and the metabolic syndrome. We compared these clinical parameters with data obtained from the overnight polysomnographic studies. The local ethics committee approved the protocol, and all participants provided written informed consent. We involved consecutive patients with hypertension and no previous history of OSA recruited from the Hypertension Unit, Heart Institute (InCor) (University of São Paulo Medical School, São Paulo, São Paulo, Brazil). The main reason for excluding patients with a previous diagnosis of OSA was that these patients have frequently been referred from the Sleep Clinic at the Heart Institute. All participants had an established diagnosis of hypertension according to current guidelines.1Chobanian A.V. Bakris G.L. Black H.R. Cushman W.C. Green L.A. Izzo Jr, J.L. Jones D.W. Materson B.J. Oparil S. Wright Jr, J.T. Roccella E.J. Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood PressureNational Heart, Lung, and Blood InstituteNational High Blood Pressure Education Program Coordinating CommitteeSeventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.Hypertension. 2003; 42: 1206-1252Crossref PubMed Scopus (10125) Google Scholar No patient had a history of “white-coat hypertension,” because they had also performed several out-of-office blood pressure measurements. Resistant hypertension was defined as blood pressure that remained greater than the goal of 3 medications.11Calhoun D.A. Jones D. Textor S. Goff D.C. Murphy T.P. Toto R.D. White A. Cushman W.C. White W. Sica D. Ferdinand K. Giles T.D. Falkner B. Carey R.M. Resistant hypertension: diagnosis, evaluation, and treatment A scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research.Hypertension. 2008; 51: 1403-1419Crossref PubMed Scopus (1199) Google Scholar We evaluated subjective daytime sleepiness using the Epworth Sleepiness Scale. In brief, this scale was used to assess the general level of daytime sleepiness by having patients rate the likelihood of dozing during 8 different daytime situations. The scale ranges from 0 to 24, and scores >10 were considered associated with excessive daytime sleepiness.12Johns M.W. A new method for measuring daytime sleepiness: the Epworth sleepiness scale.Sleep. 1991; 14: 540-559Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar As previously described,10Netzer N.C. Stoohs R.A. Netzer C.M. Clark K. Strohl K.P. Using the Berlin Questionnaire to identify patients at risk for the sleep apnea syndrome.Ann Intern Med. 1999; 131: 485-491Crossref PubMed Scopus (1887) Google Scholar predetermination of a high risk and lower risk of OSA using the Berlin Questionnaire was determined on the basis of the responses in 3 symptom categories. In category 1, high risk was defined as persistent symptoms (>3 to 4 times/week) for ≥2 questions about snoring. In category 2, high risk was defined as persistent (>3 to 4 times/week) daytime tiredness or fatigue. In category 3, high risk was defined as a history of high blood pressure or a body mass index >30 kg/m2. To be considered at high risk of OSA, a patient had to qualify for ≥2 symptom categories. Those who denied having persistent symptoms or who qualified for only one symptom category were placed in the lower risk group. All participants underwent standard overnight polysomnography (EMBLA, Flaga hf. Medical Devices, Reykjavík, Iceland), as previously described.13Drager L.F. Bortolotto L.A. Lorenzi M.C. Figueiredo A.C. Krieger E.M. Lorenzi-Filho G. Early signs of atherosclerosis in obstructive sleep apnea.Am J Respir Crit Care Med. 2005; 172: 613-618Crossref PubMed Scopus (449) Google Scholar OSA was considered present when the apnea-hypopnea index was >5 events/hour of sleep. Fasting blood samples were drawn for the determination of glucose, total cholesterol, low-density lipoprotein, high-density lipoprotein, and triglycerides. The metabolic syndrome was diagnosed according to the National Cholesterol Education Program, Adult Treatment Panel III,14Grundy S.M. Cleeman J.I. Daniels S.R. Donato K.A. Eckel R.H. Franklin B.A. Gordon D.J. Krauss R.M. Savage P.J. Smith Jr, S.C. Spertus J.A. Costa F. American Heart AssociationNational Heart, Lung, and Blood InstituteDiagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute scientific statement.Circulation. 2005; 112 (Erratum in: Circulation 2005;112:e297): 2735-2752Crossref PubMed Scopus (8463) Google Scholar if 3 of 5 factors were present as follows: (1) waist circumference (≥102 cm in men and ≥88 cm in women); (2) triglycerides ≥150 mg/dl or patient receiving specific drug treatment; (3) high-density lipoprotein cholesterol <40 mg/dl in men and <50 mg/dl in women or receiving specific drug treatment; (4) arterial blood pressure of ≥130 or 85 mm Hg systolic and diastolic blood pressure, respectively, or receiving antihypertensive drug treatment; and (5) fasting glucose of ≥100 mg/dl or receiving specific drug treatment. The data were analyzed using the Statistical Package for Social Sciences, version 10.0, statistical software (SPSS, Chicago, Illinois). The quantitative variables are expressed as the mean ± SD. The comparison of continuous variables between patients with and without OSA was performed using the Student t test or Wilcoxon test, as appropriate. Categorical variables are expressed as frequency distribution and were compared using the chi-square test or Fisher's exact test. Comparing the clinical factors to the polysomnographic findings, we determined the sensitivity, specificity, positive predictive value, and negative predictive value. The odds ratio of age 40 to 70 years9Young T. Skatrud J. Peppard P.E. Risk factors for obstructive sleep apnea in adults.JAMA. 2004; 291: 2013-2016Crossref PubMed Scopus (714) Google Scholar and for other traditional risk factors for OSA (including male gender, the presence of snoring and obesity, daytime sleepiness somnolence, Berlin Questionnaire, resistant hypertension, and metabolic syndrome) were calculated using univariate logistic regression analysis. Variables with p 80% for each variable). The data listed in Table 4 show that the presence of OSA was associated with an increased abdominal circumference, obesity, excessive daytime sleepiness on the Epworth Sleepiness Scale, a high risk of OSA on the Berlin Questionnaire, resistant hypertension, and the metabolic syndrome. However, on multiple logistic regression analysis, only a high risk of OSA using the Berlin Questionnaire, age from 40 to 70 years old, and, mainly, the presence of the metabolic syndrome were independent predictors of OSA in patients with hypertension (Table 5). Our results have confirmed previous evidence suggesting that OSA is common and underdiagnosed in patients with hypertension,2Sjöström C. Lindberg E. Elmasry A. Hägg A. Svärdsudd K. Janson C. Prevalence of sleep apnoea and snoring in hypertensive men: a population based study.Thorax. 2002; 57: 602-607Crossref PubMed Scopus (102) Google Scholar especially in patients with resistant hypertension.3Logan A.G. Perlikowski S.M. Mente A. Tisler A. Tkacova R. Niroumand M. Leung R.S. Bradley T.D. High prevalence of unrecognized sleep apnoea in drug-resistant hypertension.J Hypertens. 2001; 19: 2271-2277Crossref PubMed Scopus (721) Google Scholar We have extended these findings by showing that among patients with hypertension, the presence of OSA was associated with increased age and a greater frequency of co-morbidities. More importantly, a significant proportion (∼50%) of patients with OSA did not have excessive daytime somnolence. Male gender, a traditional factor associated with OSA in the general population, had a low sensitivity and specificity for OSA in patients with hypertension. In addition, a high risk of OSA from the Berlin Questionnaire findings, age from 40 to 70 years, and, mainly, the presence of the metabolic syndrome were independent predictors of OSA in patients with hypertension. However, the high sensitivity and specificity of the metabolic syndrome for the presence of OSA suggest that the diagnosis of metabolic syndrome should be considered one of the best predictive tools for the suspicion of OSA in patients with hypertension. The present results could contribute to increase the identification of OSA among patients with hypertension. We found that the traditional methods of screening patients with OSA in the general population might not be the best option for patients with hypertension. The low specificity of the Berlin Questionnaire means that 41% of subjects with hypertension without OSA would unnecessarily be referred for a sleep study. Therefore, a high risk of OSA according to the Berlin Questionnaire findings should be interpreted with caution in patients with hypertension. Similarly, the low sensitivity observed for excessive daytime sleepiness, as determined using the Epworth Sleepiness Scale (49%), and the absence of a significant association between excessive daytime sleepiness and OSA on multivariate analysis, limits its utility for screening of OSA among patients with hypertension. Recently, Gus et al15Gus M. Gonçalves S.C. Martinez D. de Abreu Silva E.O. Moreira L.B. Fuchs S.C. Fuchs F.D. Risk for obstructive sleep apnea by Berlin questionnaire, but not daytime sleepiness, is associated with resistant hypertension: a case-control study.Am J Hypertens. 2008; 21: 832-835Crossref PubMed Scopus (81) Google Scholar investigated the accuracy of the Epworth Sleepiness Scale and the Berlin Questionnaire to identify patients with resistant hypertension at high risk of OSA using portable sleep monitors. They found that a clinical suspicion of OSA using an Epworth Sleepiness Scale score of >10 was very low ( 5 events/hour). Second, previous evidence has suggested that OSA has an independent effect on each characteristic of the metabolic syndrome, including insulin resistance,19Harsch I.A. Schahin S.P. Radespiel-Tröger M. Weintz O. Jahreiss H. Fuchs F.S. Wiest G.H. Hahn E.G. Lohmann T. Konturek P.C. Ficker J.H. Continuous positive airway pressure treatment rapidly improves insulin sensitivity in patients with obstructive sleep apnea syndrome.Am J Respir Crit Care Med. 2004; 169: 156-162Crossref PubMed Scopus (487) Google Scholar abdominal obesity,20Chin K. Shimizu K. Nakamura T. Narai N. Masuzaki H. Ogawa Y. Mishima M. Nakamura T. Nakao K. Ohi M. Changes in intra-abdominal visceral fat and serum leptin levels in patients with obstructive sleep apnea syndrome following nasal continuous positive airway pressure therapy.Circulation. 1999; 100: 706-712Crossref PubMed Scopus (404) Google Scholar high blood pressure,21Peppard P.E. Young T. Palta M. Skatrud J. Prospective study of the association between sleep-disordered breathing and hypertension.N Engl J Med. 2000; 342: 1378-1384Crossref PubMed Scopus (3789) Google Scholar and dyslipidemia.22Li J. Savransky V. Nanayakkara A. Smith P.L. O'Donnell C.P. Polotsky V.Y. Hyperlipidemia and lipid peroxidation are dependent on the severity of chronic intermittent hypoxia.J Appl Physiol. 2007; 102: 557-663Crossref PubMed Scopus (196) Google Scholar, 23Tan K.C. Chow W.S. Lam J.C. Lam B. Wong W.K. Tam S. Ip M.S. HDL dysfunction in obstructive sleep apnea.Atherosclerosis. 2006; 184: 377-382Abstract Full Text Full Text PDF PubMed Scopus (156) Google Scholar, 24Dorkova Z. Petrasova D. Molcanyiova A. Popovnakova M. Tkacova R. Effects of continuous positive airway pressure on cardiovascular risk profile in patients with severe obstructive sleep apnea and metabolic syndrome.Chest. 2008; 134: 686-692Crossref PubMed Scopus (232) Google Scholar Therefore, the role of the metabolic syndrome, which is a cluster of several risk factors for cardiovascular risk, might have a more robust effect than each criterion in isolation. This result has potential clinical implications for cardiologists and general practitioners, because the diagnosis of the metabolic syndrome is easy to determine in the clinical setting.