Belyavskiy, Evgeny

Pieske‐Kraigher, Elisabeth

Tadic, Marijana

English

PubMed

Institutional Repository of the Freie Universität Berlin

J Clin Hypertens. 2019;00:1591–1593.	 	 	 | 	1591wileyonlinelibrary.com/journal/jch DOI: 10.1111/jch.13688  C O M M E N T A R YObstructive sleep apnea, hypertension, and obesity:  A dangerous triadEvgeny Belyavskiy MD, PhD  |   Elisabeth Pieske‐Kraigher MD |   Marijana Tadic MD, PhDDepartment of Internal Medicine and Cardiology, Charité – Universitätsmedizin Berlin, Berlin, GermanyCorrespondenceEvgeny Belyavskiy, Department of Internal Medicine and Cardiology, Charité – Universitätsmedizin Berlin, Campus Virchow‐Klinikum, Augustenburgerplatz 1, 13353 Berlin, Germany.Email: evgeny.belyavskiy@charite.deObstructive sleep apnea (OSA) is the most common type of sleep‐disordered breathing. It is characterized by recurrent partial or com‐plete obstruction of the upper airways during sleep, which leads to repetitive episodes of reduction (hypopnea) or absence of airflow (apnea) and intermittent hypoxia and arousal.1The major risk factors for OSA are obesity, male sex, and ad‐vanced age.2 The prevalence of OSA is continuously increasing in developed countries in conjunction with the epidemic obesity.3,4 The present “gold” standard for evaluation of sleep and sleep‐related breathing is the polysomnography (PSG) with up to 12 recording channels including nasal and oral airflow, respiratory effort trans‐ducers, electroencephalography (EEG), electromyography (EMG), and oximetry.5The severity of obstructive sleep apnea is classified based on the apnea‐hypopnea index (AHI)—number of apneic/hypopneic ep‐isodes per hour: 5‐15, mild; 15‐30, moderate; 30 or more, severe.4The Wisconsin Sleep Cohort study recently reported that the prevalence	of	moderate	to	severe	OSA	(ie,	AHI	≥	15	events	per	hour)	was 10% (95% confidence interval (CI): 7‐12) among 30‐ to 49‐year‐old men; 17% (95% CI: 15‐21) among 50‐ to 70‐year‐old men; 3% (95% CI: 2‐4) among 30‐ to 49‐year‐old women; and 9% (95% CI: 7‐11) among 50‐ to 70‐year‐old women.6 These estimated preva‐lence rates represent a substantial increase over the last 2 decades (relative increase of 14%‐55%, depending on the subgroup).There is overwhelming epidemiologic evidence supporting the causal, bidirectional relationship between OSA and hypertension (HTN). Not only that OSA predisposes patients to HTN development, but also increases an incidence of OSA in hypertensive patients.4,7,8Numerous studies have shown the strong association between OSA and cardiovascular morbidity and mortality, including ischemic heart disease, heart failure, arrhythmias, large vessel disease, and cerebrovascular disease.4,9,10 The main acute changes in OSA are intermittent hypoxia, intrapleural pressure changes, and sleep frag‐mentation, which together induce endothelial dysfunction, sympa‐thetic nervous system and renin‐angiotensin‐aldosterone system activation, and increased oxidative stress.4,11 Another mechanism, that potentially could contribute to the development of HTN in OSA, is increased activity of the renin‐angiotensin‐aldosterone system (RAAS).12Obesity, especially central adiposity, has been recognized as one of the strongest risk factors for OSA for a long time. Due to current pandemic of obesity in the Western countries, the prevalence of OSA is likely to increase.13 In the Sleep Heart Health Study, weight gain of 10 kilograms over a 5‐year period conferred a 5.2‐ and 2.5‐fold increase in the likelihood of increasing the AHI by 15 events per hour in men and women, respectively.14 Obesity and OSA tend to coexist and they are associated with inflammation, insulin resis‐tance, dyslipidemia, and high blood pressure (BP), but the causal re‐lation is still not clear.15While continuous positive airway pressure (CPAP) remains the main therapy for OSA, its effect on blood pressure (BP) reduction has not been established yet due to the multifactorial nature of HTN.4 Moreover, the impact of CPAP treatment on BP is inconsis‐tent: In minimally symptomatic patients, CPAP has a neutral effect on BP,16 whereas in subjects with resistant hypertension, CPAP can decrease the systolic BP by 5‐7 mm Hg.17Although obesity is a risk factor for OSA and an independent risk factor for HTN, the influence of obesity on BP response to CPAP treatment in adults with OSA is unknown. Moreover, data regarding influence of obesity on BP response to CPAP treatment in adults with OSA are still scarce.In this issue of the Journal, Kuna et al assessed the BP re‐sponse to CPAP treatment in obese and non‐obese adults with This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.© 2019 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals, Inc.The copyright line for this article was changed on October 9, 2019 after original  online publication. 1592  |     COMMENTARYOSA.18 This consecutive multicenter study included 188 OSA pa‐tients	with	AHI	≥	15,	which	were	divided	into	two	groups:	obese	and non‐obese subjects. Additionally, they underwent 24‐hour BP monitoring and 24‐hour urinary norepinephrine collection at baseline. Obesity was assessed by waist circumference, body mass index (BMI), and abdominal visceral fat volume (captured with magnetic resonance imaging [MRI]). Participants adherent to CPAP treatment were reassessed after 4 months. Primary out‐comes were 24‐hour mean arterial pressure (MAP) and 24‐hour urinary norepinephrine level.The results indicate that obesity was not the factor that influ‐enced BP response to treatment of adults with OSA and that BP response to CPAP treatment was not related to baseline 24‐hour urinary norepinephrine or change in 24‐hour urinary norepinephrine after treatment. Several previous studies reported that change in sympathetic nervous activity, measured by plasma or urinary cat‐echolamine levels, did not correlate with the BP response to CPAP treatment.19‐21 Although measurement of urinary catecholamine levels did not detect the effect of sympathetic overactivity on BP in adults with OSA, the authors postulate that it might be possible that measuring muscle sympathetic nerve activity could reveal a signifi‐cant relationship because sympathetic overactivity has an important role in OSA‐related cardiovascular remodeling22 and contributes to a cardiovascular morbidity in these patients23While the authors found that the participants with OSA had a significant reduction in 24‐hour mean arterial pressure follow‐ing CPAP treatment, there were no significant correlations be‐tween the three obesity measures (waist circumference, BMI, and abdominal visceral fat) and change in BP measures. In addition, investigators did not find differences in BP responses comparing obese and non‐obese participants. The authors explained neg‐ative results by the limited number of subjects in both groups—obese and non‐obese patients and suggested that larger studies are necessary.Although the results appear negative, this current study defi‐nitely has several important strengths. First, the objective to deter‐mine the BP response after CPAP treatment in obese patients was novel. Second, the authors used several parameters for obesity as‐sessment such as waist circumference, body mass index, and abdom‐inal fat volume and not only body mass index, as it is the case with previous studies.Continuous positive airway pressure is recognized as an effective therapy for OSA, but adherence is still suboptimal despite numerous developments in machine dynamics including quieter pumps, softer masks, and improved portability.24 Adherence to CPAP remains rel‐atively low (30%‐60%), which continues to be the largest problem with this kind of therapy.25The main limitation of the present study, which was also claimed by the authors, was a limited sample size that significantly decreased statistical power to less than 80%. The study did not include indi‐viduals who were non‐adherent to CPAP in order to compare them with those who used CPAP. Additionally, the current investigation involved also normotensive individuals. However, previous studies revealed that patients with higher baseline BP and untreated or re‐sistant HTN had the largest benefit from CPAP therapy.17,26It is well known that obesity represents a major risk factor for OSA.2 Surprisingly, there is still a lack of clinical data on the response (eg, BP reduction) to existing therapies such as CPAP in obese and non‐obese patients with OSA. The detailed phenotyping and phys‐iological characteristics of obese and non‐obese OSA patients and their response to prescribed therapy remain to be clarified in larger, prospective, and randomized studies in the future.CONFLIC T OF INTERE S TNone.ORCIDEvgeny Belyavskiy  https://orcid.org/0000‐0001‐9940‐0829 Marijana Tadic  https://orcid.org/0000‐0002‐6235‐5152 R E FE R E N C E S 1. Sarkar P, Mukherjee S, Chai‐Coetzer CL, McEvoy RD. The epide‐miology of obstructive sleep apnoea and cardiovascular disease. J Thorac Dis. 2018;10(Suppl 34):S4189‐S4200. 2. Young T, Peppard PE, Gottlieb DJ. Epidemiology of obstructive sleep apnea: a population health perspective. Am J Respir Crit Care Med. 2002;165:1217‐1239. 3. Wilson PW, D'Agostino RB, Sullivan L, et al. Overweight and obe‐sity as determinants of cardiovascular risk; the Framingham experi‐ence. Arch Intern Med. 2002;162:1867‐1872. 4. Ahmad M, Makati D, Akbar S. Review of and Updates on Hypertension in Obstructive Sleep Apnea. Int J Hypertens. 2017;2017:1848375. 5. Kushida CA, Littner MR, Morgenthaler T, et al. Practice parameters for the indications for polysomnography and related procedures: an update for 2005. Sleep. 2005;28:499‐521. 6. Peppard PE, Young T, Barnet JH, et al. Increased preva‐lence of sleep‐disordered breathing in adults. Am J Epidemiol. 2013;177:1006‐1014. 7. Nieto FJ, Young TB, Lind BK, et al. Association of sleep‐disordered breathing sleep apnea, and hypertension in a large community‐based study. JAMA. 2000;283:1829‐1836. 8. Lavie P, Herer P, Hoffstein V. Obstructive sleep apnoea syn‐drome as a risk factor for hypertension: population study. BMJ. 2000;320(7233):479‐482. 9. Shah NA, Yaggi HK, Concato J, Mohsenin V. Obstructive sleep apnea as a risk factor for coronary events or cardiovascular death. Sleep Breath. 2010;14:131‐136. 10. Gottlieb DJ, Yenokyan G, Newman AB, et al. Prospective study of obstructive sleep apnea and incident coronary heart dis‐ease and heart failure: the sleep heart health study. Circulation. 2010;122:352‐360. 11. Zhang W. Si LY Obstructive sleep apnea syndrome (OSAS) and hy‐pertension: pathogenic mechanisms and possible therapeutic ap‐proaches. Ups J Med Sci. 2012;117:370‐382. 12. Phillips CL, O'Driscoll DM. Hypertension and obstructive sleep apnea. Nat Sci Sleep. 2013;5:43‐52. 13. Garvey JF, Pengo MF, Drakatos P, Kent BD. Kent Epidemiological aspects of obstructive sleep apnea. J Thorac Dis. 2015;7:920‐929.     |  1593COMMENTARY 14. Newman AB, Foster G, Givelber R, et al. Progression and regression of sleep‐disordered breathing with changes in weight: the Sleep Heart Health Study. Arch Intern Med. 2005;165:2408‐2413. 15. Chirinos JA, Gurubhagavatula I, Teff K, et al. CPAP, weight loss, or both for obstructive sleep apnea. N Engl J Med. 2014;370: 2265‐2275. 16. Bratton DJ, Stradling JR, Barbé F, et al. Effect of CPAP on blood pressure in patients with minimally symptomatic obstructive sleep apnoea: a meta‐analysis using individual patient data from four ran‐domised controlled trials. Thorax. 2014;69:1128‐1135. 17. Iftikhar IH, Valentine CW, Bittencourt L, et al. Effects of continuous positive airway pressure on blood pressure in patients with resis‐tant hypertension and obstructive sleep apnea: a meta‐analysis. J Hypertens. 2014;32:2341‐2350. 18. Kuna ST, Townsend RR, Keenan BT, et al. Blood pressure response to treatment of obese vs non‐obese adults with sleep apnea. J Clin Hypertens. 2019;21:1580–1590. 19. Kushida CA, Chediak A, Berry RB, et al. Clinical guidelines for the manual titration of positive airway pressure in patients with ob‐structive sleep apnea. J Clin Sleep Med. 2008;4:157‐171. 20. Drager LF, Bortolotto LA, Figueiredo AC, et al. Effects of continu‐ous positive airway pressure on early signs of atherosclerosis in ob‐structive sleep apnea. Am J Respir Crit Care Med. 2007;176:706‐712. 21. Pinto P, Barbara C, Montserrat JM, et al. Effects of CPAP on ni‐trate and norepinephrine levels in severe and mild‐moderate sleep apnea. BMC Pulm Med. 2013;13:13. 22. Narkiewicz K, Somers VK. The sympathetic nervous system and obstructive sleep apnea: implications for hypertension. J Hypertens. 1997;15:1613‐1619. 23. Narkiewicz K, Somers VK. Sympathetic nerve activity in obstruc‐tive sleep apnoea. Acta Physiol Scand. 2003;177:385‐390. 24. Rotenberg BW, Murariu D, Pang KP. Trends in CPAP adherence over twenty years of data collection: a flattened curve. J Otolaryngol Head Neck Surg. 2016;45:43. 25. Weaver TE, Sawyer AM. Adherence to continuous positive airway pressure treatment for obstructive sleep apnoea: implications for future interventions. Indian J Med Res. 2010;131:245‐258. 26. Martínez‐García MA, Gomez‐Aldaraví R, Soler‐Cataluña J, et al. Positive effect of CPAP treatment on the control of difficult‐to‐treat hypertension. Eur Respir J. 2007;29:951‐957.

Obstructive sleep apnea, hypertension, and obesity: A dangerous triad

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