Sleep Apnea and Hypertension: Interactions and Implications for Management
2008; Lippincott Williams & Wilkins; Volume: 51; Issue: 3 Linguagem: Inglês
10.1161/hypertensionaha.106.076190
ISSN1524-4563
AutoresSuraj Kapa, Fatima H. Sert Kuniyoshi, Virend K. Somers,
Tópico(s)Sleep and Wakefulness Research
ResumoHomeHypertensionVol. 51, No. 3Sleep Apnea and Hypertension: Interactions and Implications for Management Free AccessReview ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessReview ArticlePDF/EPUBSleep Apnea and Hypertension: Interactions and Implications for Management Suraj Kapa, Fatima H. Sert Kuniyoshi and Virend K. Somers Suraj KapaSuraj Kapa From the Department of Internal Medicine (S.K.) and Division of Cardiovascular Diseases (F.H.S.K., V.K.S.), Mayo Clinic and Mayo Foundation, Rochester, Minn. , Fatima H. Sert KuniyoshiFatima H. Sert Kuniyoshi From the Department of Internal Medicine (S.K.) and Division of Cardiovascular Diseases (F.H.S.K., V.K.S.), Mayo Clinic and Mayo Foundation, Rochester, Minn. and Virend K. SomersVirend K. Somers From the Department of Internal Medicine (S.K.) and Division of Cardiovascular Diseases (F.H.S.K., V.K.S.), Mayo Clinic and Mayo Foundation, Rochester, Minn. Originally published28 Jan 2008https://doi.org/10.1161/HYPERTENSIONAHA.106.076190Hypertension. 2008;51:605–608Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: January 28, 2008: Previous Version 1 Obstructive sleep apnea (OSA) is highly prevalent in the United States, with an estimated 1 in 4 Americans at risk for OSA. In recent years, there has been a large body of work assessing the role of OSA as an independent risk factor for hypertension. Certain patient characteristics, such as age and the type of elevated blood pressure, may confer increased likelihood that the hypertension is secondary to underlying sleep apnea. Furthermore, early diagnosis and treatment of OSA may be beneficial in the management of hypertensive patients, particularly in those with poorly controlled hypertension. The focus of this brief review is on recent developments in the characteristics and treatment of sleep apnea-associated hypertension. Because of space limitations, only limited references are provided.Interdependence Between OSA and HypertensionThe seventh report of the Joint National Committee identified OSA as an important identifiable cause of hypertension. As many as half of all patients with sleep apnea may have underlying hypertension, and many patients with hypertension, particularly resistant hypertension, may have OSA. In fact, there seems to be an interaction between OSA severity and resistance to antihypertensive medications.1 Elevated nocturnal blood pressure and reduced blood pressure "dipping" during sleep also suggest a higher likelihood of underlying sleep apnea, even in normotensive patients. Whether hypertension contributes to OSA remains unknown.Systolic and Diastolic HypertensionOSA patients may not always exhibit elevated systolic pressures but may have a high prevalence of isolated diastolic hypertension.2–4 One study suggested that there was a significant association between the incidence of combined systolic and diastolic hypertension and the presence of sleep apnea in younger patients (<60 years of age) but not in older patients,5 and no significant association was seen between isolated systolic hypertension and sleep apnea in either age group. These studies suggest that the type of hypertension may need to be considered when studying epidemiologic interactions, pathophysiologic trends, and therapeutic options in sleep apnea-associated hypertension.Effects of GenderSex differences in blood pressure responses to OSA remain to be fully elucidated. Population-based studies have not revealed any differential effect of gender on sleep apnea-associated hypertension prevalence in middle-aged subjects.6,7 The majority of studies have been limited primarily to men with OSA, but there is some evidence in rat models for a sex-dependent difference in response to intermittent hypoxic insults.8 Female rats subjected to intermittent hypoxic insults were less at risk for developing elevated blood pressure than their male or ovariectomized female counterparts. However, a recent study by Drager et al9 suggested that increasing age, body mass index, a family history of hypertension, and female gender independent of menopause and obesity may be risk factors for hypertension in patients with OSA. The apnea-hypopnea index has also been suggested to be associated more closely with impaired conduit and resistance vessel function in women than in men.10 Thus, whereas animal models suggest an attenuated hypertensive response to intermittent hypoxia in females, human studies regarding any association between female gender and sleep apnea-induced hypertension remains inconclusive.AgeAge may also modulate the OSA-hypertension interaction. In a subgroup analysis of the Sleep Heart Health Study, patients <60 years of age with sleep apnea were more likely to demonstrate a significant relationship between minimum oxygen saturation and the development of hypertension.5 This particular study further demonstrated that it was only in younger patients that any significant association existed between blood pressure elevations and sleep-disordered breathing. Children with sleep apnea have higher daytime diastolic pressure and less nocturnal dipping of blood pressure than body mass-matched controls.11 Thus, younger patients with OSA may be more susceptible to consequent hypertension than the elderly.Nocturnal Nondipping Blood Pressure PatternsOne of the characteristics of OSA is a nondipping nocturnal blood pressure profile. This likely results from heightened sympathetic drive during sleep, which is because of 4 main stimuli: (1) hypoxemia; (2) hypercapnia; (3) absence of lung inflation; and (4) microarousals at the end of apneic episodes. The cumulative effect of excess sympathetic activation, along with other vasoactive factors released in response to hypoxia (such as endothelin), may result in the daytime hypertension seen in these patients. However, even in the absence of daytime hypertension, sleep apnea patients may not exhibit the normal nocturnal dip in blood pressure during sleep because of apnea-induced sympathetic activation. Higher nocturnal blood pressure, independent of daytime hypertension, may play a significant role in the development of cardiovascular complications.12 Thus, even in normotensive patients, a nocturnal nondipping blood pressure profile may suggest increased cardiovascular risk. Further studies are needed to establish the prognostic role of elevated nocturnal blood pressures in sleep apnea.Subclinical OSA and PrehypertensionCriteria for identification of early or subclinical manifestations of OSA and of hypertension have contributed to understanding their interaction. The seventh Joint National Committee report established guidelines for classification of patients as "prehypertensive." These patients do not meet the clinical criteria for hypertension but are at higher risk of developing established hypertension and other cardiovascular disease. Similarly, subclinical syndromes suggestive of OSA but not meeting criteria have been identified, including snoring and upper airway resistance syndrome.13 Population-based studies have suggested an interaction between snoring and hypertension, although further investigation is needed to define the relationship.14,15 Thus, the relationship between OSA and hypertension could extend beyond OSA alone and may reflect a broader interaction between disturbed sleep and blood pressure.Only in recent years have studies systematically explored any potential causal relationship between these conditions. One of these studies demonstrated a direct correlation between the severity of sleep-disordered breathing and the presence of incident hypertension 4 years later, independent of other factors.6 Although treatment of OSA may improve blood pressure control, whether early identification and treatment of OSA or sleep-disordered breathing contributes to long-term prevention of hypertension and other cardiovascular complications remains to be determined.Sleep Duration and HypertensionIn patients with sleep apnea, sleep quality is decreased secondary to frequent nocturnal arousals. The effects of sleep duration on hypertension have been described recently in a large cohort of patients from the First National Health and Nutrition Examination Survey.16 Sleep duration of <5 hours per night was shown to significantly increase risk for hypertension in patients 50% in the apnea-hypopnea index may be needed to decrease blood pressure.29 Furthermore, CPAP may improve blood pressure by mechanisms other than improving oxyhemoglobin saturation, as suggested in 1 study comparing nocturnal supplemental oxygen therapy with CPAP31 (Figure 1). The data regarding the antihypertensive effect of CPAP therapy, however, are not entirely consistent, with some studies not showing any antihypertensive effect.32,33 Several recent meta-analyses suggested that CPAP has only very modest effects, lowering blood pressure by ≈2 mm Hg, although certain subgroups may have more robust responses.34–36 Blood pressure was reduced more in those patients with more severe OSA and better effective nightly CPAP use35 (Figure 2). Thus, further study is needed into the role of CPAP therapy and the effectiveness of different devices in treatment of OSA-associated hypertension, as well as to determine the clinical significance of this magnitude of blood pressure reduction in the context of OSA. Clinical PerspectivesAlthough OSA has been associated with a range of cardiovascular diseases, it has been etiologically linked most convincingly to hypertension. There is also considerable evidence that treatment of sleep apnea lowers blood pressure acutely and in the long-term, both at night and during the day. These effects of blood pressure lowering seem to be most marked in more severe hypertensive subjects. Resistant hypertensive patients seem to have a high prevalence of sleep apnea, and their OSA should be treated along with the treatment of hypertension.It would be reasonable to expect that attenuation of nocturnal hypoxemia, along with blood pressure lowering, both of which could be expected to result from treatment of sleep apnea, would decrease cardiac and vascular events. Nevertheless, definitive evidence based on longitudinal randomized control studies clarifying whether treatment of OSA is accompanied by decreased cardiac and vascular events is lacking. Whether treatment of obstructive apnea decreases cardiovascular events secondary to blood pressure lowering also remains to be determined.Download figureDownload PowerPointFigure 1. Effect of CPAP vs supplemental oxygen on 24-hour ambulatory blood pressure. Use of CPAP was associated with a significant decrease in blood pressure compared with patients treated with placebo or supplemental oxygen. The change was measured from the mean pretreatment minus posttreatment values. *Significant change over time, P<0.05. (From Norman et al,31 copyright 2006. American Heart Association. All rights reserved. Reproduced with permission.)Download figureDownload PowerPointFigure 2. Effect of CPAP usage on change in blood pressure. Shown is the relationship between the mean net change in systolic blood pressure (SBP) and the corresponding mean nocturnal CPAP usage based on a meta-analysis of CPAP trials by Bazzano et al.36 This suggests that longer nightly CPAP use may offer greater benefit in reducing SBP (r2=0.40; P=0.13). (From Bazzano et al,36 copyright 2007. American Heart Association. All rights reserved. Reproduced with permission.)Sources of FundingF.H.S.K. is supported by an American Physiological Society Perkins Memorial Award, an American Heart Association predoctoral fellowship and Fundacao de Apoio a Ciencia e Tecnologia do Espirito Santo. V.K.S. is supported by National Institutes of Health grant HL61560, HL65176, HL73211, and M01-RR00585 and the Mayo Clinic College of Medicine.DisclosuresV.K.S. is a consultant for Respironics, Sepracor, Res Med, and Cardiac Concepts and is an investigator on grants from the Res Med Foundation and the Respironics Sleep and Breathing Foundation. The remaining authors report no conflicts.FootnotesCorrespondence to Virend K. Somers, Mayo Clinic, Division of Cardiovascular Diseases, 200 First St, SW, Rochester, MN 55905. E-mail somers. [email protected] References 1 Lavie P, Hoffstein V. Sleep apnea syndrome: a possibly contributing factor to resistant hypertension. Sleep. 2001; 24: 721–725.CrossrefMedlineGoogle Scholar2 Baguet JP, Hammer L, Levy P, Pierre H, Rossini E, Mouret S, Ormezzano O, Mallion JM, Pepin JL. Night-time and diastolic hypertension are common and underestimated conditions in newly diagnosed apnoeic patients. J Hypertens. 2005; 23: 521–527.CrossrefMedlineGoogle Scholar3 Grote J, Hedner J, Peter JH. Mean blood pressure, pulse pressure and grade of hypertension in untreated hypertensive patients with sleep-related breathing disorder. J Hypertens. 2001; 19: 683–690.CrossrefMedlineGoogle Scholar4 Sharabi Y, Scope A, Chorney N, Grotto I, Dagan Y. Diastolic blood pressure is the first to rise in association with early subclinical obstructive sleep apnea: Lessons from periodic examination screening. Am J Hypertens. 2003; 16: 236–239.CrossrefMedlineGoogle Scholar5 Haas DC, Foster GL, Nieto FJ, Redline S, Resnick HE, Robbins JA, Young T, Pickering TG. Age-dependent associations between sleep-disordered breathing and hypertension. Circulation. 2005; 111: 614–621.LinkGoogle Scholar6 Peppard P, Young T, Palta M, Skatrud J. Prospective study of the association between sleep-disordered breathing and hypertension. N Engl J Med. 2000; 342: 1378–1384.CrossrefMedlineGoogle Scholar7 Nieto F, Young T, Lind B, Shahar E, Samet J, Redline S, D'Agostino RB, Newman AB, Lebowitz MD, Pickering TG. Association of sleep-disordered breathing, sleep apnea, and hypertension in a large community-based study. JAMA. 2000; 283: 1829–1836.CrossrefMedlineGoogle Scholar8 Hinojosa-Laborde C, Mifflin SW. Sex differences in blood pressure response to intermittent hypoxia in rats. Hypertension. 2005; 46: 1016–1021.LinkGoogle Scholar9 Drager LF, Pereira AC, Barreto-Filho JA, Figueiredo AC, Krieger JE, Krieger EM, Lorenzi-Filho G. Phenotypic characteristics associated with hypertension in patients with obstructive sleep apnea. J Hum Hypertens. 2006; 20: 523–528.CrossrefMedlineGoogle Scholar10 Faulx MD, Larkin EK, Hoit BD, Aylor JE, Wright AT, Redline S. Sex influences endothelial dysfunction in sleep-disordered breathing. Sleep. 2004; 27: 1113–1120.CrossrefMedlineGoogle Scholar11 Amin RS, Carroll JL, Jeffries JL, Grone C, Bean JA, Chini B, Bokulic R, Daniels SR. Twenty-four hour ambulatory blood pressure in children with sleep-disordered breathing. Am J Respir Crit Care Med. 2004; 169: 950–956.CrossrefMedlineGoogle Scholar12 Pickering TG, Kario K. Nocturnal non-dipping: what does it augur? Curr Opin Nephrol Hypertens. 2001: 10; 611–616.CrossrefMedlineGoogle Scholar13 Guilleminault C, Stoohs R, Shiomi T, Kushida C, Schnittger I. Upper airway resistance syndrome, nocturnal blood pressure monitoring, and borderline hypertension. Chest. 1996: 109; 901–908.CrossrefMedlineGoogle Scholar14 Lindberg E, Janson C, Gislason T, Svardsudd K, Hetta J, Boman G. Snoring and hypertension: a 10-year follow-up. Eur Respir J. 1998; 11: 884–889.CrossrefMedlineGoogle Scholar15 Hu FB, Willett WC, Colditz GA, Ascherio A, Speizer FE, Rosner B, Hennekens CH, Stampfer MJ. Prospective study of snoring and risk of hypertension in women. Am J Epidemiol. 1999; 150: 806–816.CrossrefMedlineGoogle Scholar16 Gangwisch JE, Heymsfield SB, Boden-Albala B, Buijs RM, Kreier F, Pickering TG, Rundle AG, Zammit GK, Malaspina D. Short sleep duration as a risk factor for hypertension: analyses of the First National Health and Nutrition Examination Survey. Hypertension. 2006; 47: 833–839.LinkGoogle Scholar17 Gottlieb DJ, Redline S, Nieto FJ, Baldwin CM, Newman AB, Resnick HE, Punjabi JM. Association of usual sleep duration with hypertension: the Sleep Heart Health Study. Sleep. 2006; 29: 1009–1014.CrossrefMedlineGoogle Scholar18 Shamsuzzaman AS, Gersh BJ, Somers VK. Obstructive sleep apnea: implications for cardiac and vascular disease. JAMA. 2003; 290: 1906–1914.CrossrefMedlineGoogle Scholar19 Sukhija R, Aronow WS, Sandhu R, Kakar P, Maguire GP, Ahn C, Lehrman SG. Prevalence of left ventricular hypertrophy in persons with and without obstructive sleep apnea. Cardiol Rev. 2006; 14: 170–172.CrossrefMedlineGoogle Scholar20 Otto ME, Belohlavek M, Romero-Corral A, Gami AS, Gilman G, Svatikova A, Amin RS, Lopez-Jimenez F, Khandheria BK, Somers VK. Comparison of cardiac structural and functional changes in obese otherwise healthy adults with versus without obstructive sleep apnea. Am J Cardiol. 2007; 99: 1298–1302.CrossrefMedlineGoogle Scholar21 Tavil Y, Kanbay A, Sen N, Ciftci TU, Abaci A, Yalcin MR, Kokturk O, Cengel A. Comparison of right ventricular functions by tissue Doppler imaging in patients with obstructive sleep apnea with or without hypertension. Int J Cardiovasc Imaging. 2007; 23: 469–477.CrossrefMedlineGoogle Scholar22 Amin RS, Kimball TR, Kalra M, Jeffries JL, Carroll JL, Bean JA, Witt SA, Glascock BJ, Daniels SR. Left ventricular function in children with sleep-disordered breathing. Am J Cardiol. 2005; 95: 801–804.CrossrefMedlineGoogle Scholar23 Arias MA, Garcia-Rio F, Alonso-Fernandez A, Mediano O, Martinez I, Villamor J. Obstructive sleep apnea syndrome affects left ventricular diastolic function: effects of nasal continuous positive airway pressure in men. Circulation. 2005; 112: 373–383.Google Scholar24 Berger M, Oksenberg A, Silverberg DS, Arons E, Radwan H, Iaina A. Avoiding the supine position during sleep lowers 24 h blood pressure in obstructive sleep apnea (OSA) patients. J Hum Hypertens. 1997; 11: 657–664.CrossrefMedlineGoogle Scholar25 Otsuka R, Ribeiro de Almeida F, Lowe AA, Linden W, Ryan F. The effect of oral appliance therapy on blood pressure in patients with obstructive sleep apnea. Sleep Breath. 2006; 10: 29–36.CrossrefMedlineGoogle Scholar26 Gotsopoulos H, Kelly JJ, Cistulli PA. Oral appliance therapy reduces blood pressure in obstructive sleep apnea: a randomized, controlled trial. Sleep. 2004; 27: 934–941.CrossrefMedlineGoogle Scholar27 Buchwald H, Avidor Y, Braunwald E, Jensen MD, Pories W, Fahrbach K, Schoelles K. Bariatric surgery: a systematic review and meta-analysis. JAMA. 2004; 292: 1724–1737.CrossrefMedlineGoogle Scholar28 Pepperell JC, Ramdassingh-Dow S, Crosthwaite N, Mullins R, Jenkinson C, Stradling JR, Davies RJ. Ambulatory blood pressure after therapeutic and subtherapeutic nasal continuous positive airway pressure for obstructive sleep apnoea: a randomized parallel trial. Lancet. 2002; 359: 204–210.CrossrefMedlineGoogle Scholar29 Becker HF, Jerrentrup A, Ploch T, Grote L, Penzel T, Sullivan CE, Peter JH. Effect of nasal continuous positive airway pressure treatment on blood pressure in patients with obstructive sleep apnea. Circulation. 2003; 107: 68–73.LinkGoogle Scholar30 Patruno V, Aiolfi S, Costantino G, Murgia R, Selmi C, Malliani A, Montano N. Fixed and autoadjusting continuous positive airway pressure treatments are not similar in reducing cardiovascular risk factors in patients with obstructive sleep apnea. Chest. 2007; 131: 1393–1399.CrossrefMedlineGoogle Scholar31 Norman D, Loredo JS, Nelesen RA, Ancoli-Israel S, Mills PJ, Ziegler MG, Dimsdale JE. Effects of continuous positive airway pressure versus supplemental oxygen on 24-hour ambulatory blood pressure. Hypertension. 2006; 47: 840–845.LinkGoogle Scholar32 Campos-Rodriguez F, Grilo-Reina A, Perez-Ronchel J, Merino-Sanchez M, Gonzalez-Benitez MA, Beltran-Robles M, Almeida-Gonzalez C. Effect of continuous positive airway pressure on ambulatory BP in patients with sleep apnea and hypertension: a placebo-controlled trial. Chest. 2006; 129: 1459–1467.CrossrefMedlineGoogle Scholar33 Iellamo F, Montano N. Continuous positive airway pressure treatment: good for obstructive sleep apnea syndrome, maybe not for hypertension? Chest. 2006; 129: 1403–1405.CrossrefMedlineGoogle Scholar34 Alajmi M, Mulgrew AT, Fox J, Davidson W, Schulzer M, Mak E, Ryan CF, Fleetham J, Choi P, Ayas NT. Impact of continuous positive airway pressure therapy on blood pressure in patients with obstructive sleep apnea hypopnea: a meta-analysis of randomized controlled trials. Lung. 2007; 185: 67–72.CrossrefMedlineGoogle Scholar35 Haentjens P, Van Meerhaeghe A, Moscariello A, De Weerdt S, Poppe K, Dupont A, Velkeniers B. 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. Arch Intern Med. 2007; 167: 757–764.CrossrefMedlineGoogle Scholar36 Bazzano LA, Khan Z, Reynolds K, He J. Effect of nocturnal nasal continuous positive airway pressure on blood pressure in obstructive sleep apnea. Hypertension. 2007; 50: 417–423.LinkGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Sá Gomes e Farias A, de Lima Cavalcanti M, de Passos Junior M and Vechio Koike B (2022) The association between sleep deprivation and arterial pressure variations: a systematic literature review, Sleep Medicine: X, 10.1016/j.sleepx.2022.100042, 4, (100042), Online publication date: 1-Dec-2022. Al-Sadawi M, Saeidifard F, Kort S, Cao K, Capric V, Salciccioli L, Al-Ajam M and Budzikowski A (2021) Treatment of Sleep Apnea with Positive Airway Pressure and Its Association with Diastolic Dysfunction: A Systematic Review and Meta-Analysis, Respiration, 10.1159/000519406, 101:3, (334-344), . Maier L, Matenchuk B, Vucenovic A, Sivak A, Davenport M and Steinback C (2022) Influence of Obstructive Sleep Apnea Severity on Muscle Sympathetic Nerve Activity and Blood Pressure: a Systematic Review and Meta-Analysis, Hypertension, 79:9, (2091-2104), Online publication date: 1-Sep-2022. Segsarnviriya C, Chumthong R and Mahakit P (2020) Effects of intranasal steroids on continuous positive airway pressure compliance among patients with obstructive sleep apnea, Sleep and Breathing, 10.1007/s11325-020-02236-5, 25:3, (1293-1299), Online publication date: 1-Sep-2021. Damaskos C, Litos A, Dimitroulis D, Antoniou E, Mantas D, Kontzoglou K and Garmpis N Cardiovascular Effects of Metabolic Surgery on Type 2 Diabetes, Current Cardiology Reviews, 10.2174/1573403X16666200220120226, 16:4, (275-284) Kim D, Lee E, Kim J, Park P and Cho S A Sleep Apnea Monitoring IC for Respiration, Heart-Rate, SpO 2 and Pulse-Transit Time Measurement Using Thermistor, PPG and Body-Channel Communication , IEEE Sensors Journal, 10.1109/JSEN.2019.2950367, 20:4, (1997-2007) Baboli M, Singh A, Soll B, Boric-Lubecke O and Lubecke V Wireless Sleep Apnea Detection Using Continuous Wave Quadrature Doppler Radar, IEEE Sensors Journal, 10.1109/JSEN.2019.2941198, 20:1, (538-545) Han S, Kim H and Lee S (2019) The effect of high evening blood pressure on obstructive sleep apnea–related morning blood pressure elevation: does sex modify this interaction effect?, Sleep and Breathing, 10.1007/s11325-019-01869-5, 23:4, (1255-1263), Online publication date: 1-Dec-2019. Seetho I and Wilding J (2019) Obesity and Obstructive Sleep Apnea Syndrome Obesity, 10.1007/978-3-319-46933-1_24, (243-271), . Harada G, Takeuchi D, Inai K, Shinohara T and Nakanishi T (2018) Prevalence and risk factors of sleep apnoea in adult patients with CHD, Cardiology in the Young, 10.1017/S1047951118001853, 29:1, (71-77), Online publication date: 1-Jan-2019. Sapiña-Beltrán E, Santamaria-Martos F, Benítez I, Torres G, Masa J, Sánchez-de-la-Torre M, Barbé F and Dalmases M (2019) Normotensive patients with obstructive sleep apnoea, Journal of Hypertension, 10.1097/HJH.0000000000001934, 37:4, (720-727), Online publication date: 1-Apr-2019. Harada G, Takeuchi D, Inai K, Shinohara T and Nakanishi T (2019) Prevalence and risk factors of sleep apnea in adult patients with congenital heart disease, Cardiology in the Young, 10.1017/S1047951119000179, 29:5, (576-582), Online publication date: 1-May-2019. Wu Q, Cunningham J and Mifflin S (2018) Transcription factor ΔFosB acts within the nucleus of the solitary tract to increase mean arterial pressure during exposures to intermittent hypoxia, American Journal of Physiology-Heart and Circulatory Physiology, 10.1152/ajpheart.00268.2017, 314:2, (H270-H277), Online publication date: 1-Feb-2018. Bozkus F, Dikmen N and Demir L (2018) Gamma-glutamyl transferase activity as a predictive marker for severity of obstructive sleep apnea syndrome and concomitant hypertension, The Clinical Respiratory Journal, 10.1111/crj.12765, 12:5, (1964-1973), Online publication date: 1-May-2018. Reckelhoff J (2018) Gender differences in hypertension, Current Opinion in Nephrology and Hypertension, 10.1097/MNH.0000000000000404, 27:3, (176-181), Online publication date: 1-May-2018. Seetho I and Wilding J (2018) Obesity and Obstructive Sleep Apnea Syndrome Thyroid Diseases, 10.1007/978-3-319-47685-8_24-1, (1-30), . Ren H and Hu K (2017)(2017) Inflammatory and oxidative stress-associated factors in chronic intermittent hypoxia in Chinese patients, rats, lymphocytes and endotheliocytes, Molecular Medicine Reports, 10.3892/mmr.2017.7632, 16:6, (8092-8102), Online publication date: 1-Dec-2017. Feldstein C (2016) Blood pressure effects of CPAP in nonresistant and resistant hypertension associated with OSA: A systematic review of randomized clinical trials, Clinical an
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