Background: Mortality in end-stage renal disease (ESRD) occurs predominantly from cardiovascular disease (CVD) and sudden cardiac death (SCD). Obstructive sleep apnea (OSA) is characterized by periodic airflow limitation associated with sleep arousal and oxygen desaturation and is prevalent in patients with ESRD. Whether OSA increases the risk for SCD, cardiovascular and all-cause mortality among hemodialysis patients remains unknown. Methods: In a prospective cohort of 558 incident hemodialysis patients, we examined the association of OSA with all-cause mortality, cardiovascular mortality, and SCD using Cox proportional hazards models controlling for traditional CVD risk factors. Results: Sixty-six incident hemodialysis patients (12%) had OSA. Mean age (56 years) and percentage of males (56%) were identical in OSA and no-OSA groups. Fewer African Americans had OSA than non-African Americans (9 vs. 18%, respectively). Participants with OSA had higher body-mass index, Charlson comorbidity score, and left ventricular mass index and greater prevalence of diabetes and coronary artery disease. During 1,080 person-years of follow-up, 104 deaths occurred, 29% of which were cardiovascular. OSA was associated with a higher risk of all-cause mortality (HR 1.90 [95% CI 1.04–3.46]) and cardiovascular mortality (HR 3.62 [95% CI 1.36–9.66]) after adjusting for demographics and body-mass index. OSA was associated with a higher risk of SCD after adjusting for demographics (HR 3.28 [95% CI 1.12–9.57]) and multiple cardiovascular risk factors. Conclusions: Incident hemodialysis patients with OSA are at increased risk of all-cause and cardiovascular mortality and SCD. Future studies should assess the impact of screening for OSA and OSA-targeted interventions on mortality in ESRD.

Keywords:
Hemodialysis, Obstructive sleep apnea, Sudden cardiac death, Cardiovascular death, Cardiovascular disease
1.
Herzog CA: Cardiac arrest in dialysis patients: approaches to alter an abysmal outcome. Kidney Int Suppl 2003; 84:S197–S200.
2.
Ritz E, Wanner C: The challenge of sudden death in dialysis patients. Clin J Am Soc Nephrol 2008; 3: 920–929.
3.
Parekh RS, Meoni LA, Jaar BG, Sozio SM, Shafi T, Tomaselli GF, Lima JA, Tereshchenko LG, Estrella MM, Kao WH: Rationale and design for the Predictors of Arrhythmic and Cardiovascular Risk in End Stage Renal Disease (PACE) study. BMC Nephrol 2015; 16: 63.
4.
Green D, Roberts PR, New DI, Kalra PA: Sudden cardiac death in hemodialysis patients: an in-depth review. Am J Kidney Dis 2011; 57: 921–929.
5.
United States Renal Data System: 2015 USRDS Annual Data Report. Volume 2: ESRD in the United States. Chapter 9: Cardiovascular Disease in Patients with ESRD. https://http://www.usrds.org/2015/download/vol2_USRDS_ESRD_15.pdf (accessed July 29, 2017).
6.
Shamseddin MK, Parfrey PS: Sudden cardiac death in chronic kidney disease: epidemiology and prevention. Nat Rev Nephrol 2011; 7: 145–154.
7.
Somers VK, Dyken ME, Clary MP, Abboud FM: Sympathetic neural mechanisms in obstructive sleep apnea. J Clin Invest 1995; 96: 1897–1904.
8.
Lavie L: Obstructive sleep apnoea syndrome – an oxidative stress disorder. Sleep Med Rev 2003; 7: 35–51.
9.
Ciccone MM, Scicchitano P, Zito A, Cortese F, Boninfante B, Falcone VA, Quaranta VN, Ventura VA, Zucano A, Di Serio F, Damiani MF, Resta O: Correlation between inflammatory markers of atherosclerosis and carotid intima-media thickness in Obstructive Sleep Apnea. Molecules 2014; 19: 1651–1662.
10.
Wang J, Yu W, Gao M, Zhang F, Gu C, Yu Y, Wei Y: Impact of obstructive sleep apnea syndrome on endothelial function, arterial stiffening, and serum inflammatory markers: an updated meta-analysis and metaregression of 18 studies. J Am Heart Assoc 2015; 4:e002454.
11.
Nieto FJ, Young TB, Lind BK, Shahar E, Samet JM, 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. Sleep Heart Health Study. JAMA 2000; 283: 1829–1836.
12.
Peppard PE, 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.
13.
Wang AY: Sleep-disordered breathing and resistant hypertension. Semin Nephrol 2014; 34: 520–531.
14.
Gupta S, Cepeda-Valery B, Romero-Corral A, Shamsuzzaman A, Somers VK, Pressman GS: Association between QRS duration and obstructive sleep apnea. J Clin Sleep Med 2012; 8: 649–654.
15.
Mehra R, Benjamin EJ, Shahar E, Gottlieb DJ, Nawabit R, Kirchner HL, Sahadevan J, Redline S: Association of nocturnal arrhythmias with sleep-disordered breathing: the Sleep Heart Health Study. Am J Respir Crit Care Med 2006; 173: 910–916.
16.
Shahar E, Whitney CW, Redline S, Lee ET, Newman AB, Nieto FJ, O'Connor GT, Boland LL, Schwartz JE, Samet JM: Sleep-disordered breathing and cardiovascular disease: cross-sectional results of the Sleep Heart Health Study. Am J Respir Crit Care Med 2001; 163: 19–25.
17.
Gami AS, Olson EJ, Shen WK, Wright RS, Ballman KV, Hodge DO, Herges RM, Howard DE, Somers VK: Obstructive sleep apnea and the risk of sudden cardiac death: a longitudinal study of 10,701 adults. J Am Coll Cardiol 2013; 62: 610–616.
18.
Holley JL, Nespor S, Rault R: A comparison of reported sleep disorders in patients on chronic hemodialysis and continuous peritoneal dialysis. Am J Kidney Dis 1992; 19: 156–161.
19.
Hallett M, Burden S, Stewart D, Mahony J, Farrell P: Sleep apnea in end-stage renal disease patients on hemodialysis and continuous ambulatory peritoneal dialysis. ASAIO J 1995; 41:M435–M441.
20.
Unruh ML: Sleep apnea and dialysis therapies: things that go bump in the night? Hemodial Int 2007; 11: 369–378.
21.
Abuyassin B, Sharma K, Ayas NT, Laher I: Obstructive sleep apnea and kidney disease: a potential bidirectional relationship? J Clin Sleep Med 2015; 11: 915–924.
22.
Hanly PJ, Ahmed SB: Sleep apnea and the kidney: is sleep apnea a risk factor for chronic kidney disease? Chest 2014; 146: 1114–1122.
23.
Jhamb M, Unruh M: Bidirectional relationship of hypertension with obstructive sleep apnea. Curr Opin Pulm Med 2014; 20: 558–564.
24.
Zoccali C, Mallamaci F, Tripepi G: Nocturnal hypoxemia predicts incident cardiovascular complications in dialysis patients. J Am Soc Nephrol 2002; 13: 729–733.
25.
Tang SC, Lam B, Yao TJ, Leung WS, Chu CM, Ho YW, Ip MS, Lai KN: Sleep apnea is a novel risk predictor of cardiovascular morbidity and death in patients receiving peritoneal dialysis. Kidney Int 2010; 77: 1031–1038.
26.
Jung HH, Lee JH, Baek HJ, Kim SJ, Lee JJ: Nocturnal hypoxemia and periodic limb movement predict mortality in patients on maintenance hemodialysis. Clin J Am Soc Nephrol 2010; 5: 1607–1613.
27.
Masuda T, Murata M, Honma S, Iwazu Y, Sasaki N, Ogura M, Onishi A, Ando Y, Muto S, Shimada K, Kario K, Kusano E, Asano Y: Sleep-disordered breathing predicts cardiovascular events and mortality in hemodialysis patients. Nephrol Dial Transplant 2011; 26: 2289–2295.
28.
White IR, Royston P, Wood AM: Multiple imputation using chained equations: issues and guidance for practice. Stat Med 2011; 30: 377–399.
29.
Dharia SM, Unruh ML, Brown LK: Central sleep apnea in kidney disease. Semin Nephrol 2015; 35: 335–346.
30.
Tuohy CV, Montez-Rath ME, Turakhia M, Chang TI, Winkelman JW, Winkelmayer WC: Sleep disordered breathing and cardiovascular risk in older patients initiating dialysis in the United States: a retrospective observational study using medicare data. BMC Nephrol 2016; 17: 16.
31.
McIsaac DI, Gershon A, Wijeysundera D, Bryson GL, Badner N, van Walraven C: Identifying obstructive sleep apnea in administrative data: a study of diagnostic accuracy. Anesthesiology 2015; 123: 253–263.
32.
Leavey SF, McCullough K, Hecking E, Goodkin D, Port FK, Young EW: Body mass index and mortality in 'healthier' as compared with “sicker” haemodialysis patients: results from the Dialysis Outcomes and Practice Patterns Study (DOPPS). Nephrol Dial Transplant 2001; 16: 2386–2394.
33.
Friedman O, Bradley TD, Logan AG: Influence of lower body positive pressure on upper airway cross-sectional area in drug-resistant hypertension. Hypertension 2013; 61: 240–245.
34.
Su MC, Chiu KL, Ruttanaumpawan P, Shiota S, Yumino D, Redolfi S, Haight JS, Yau B, Lam J, Bradley TD: Difference in upper airway collapsibility during wakefulness between men and women in response to lower-body positive pressure. Clin Sci (Lond) 2009; 116: 713–720.
35.
White LH, Motwani S, Kasai T, Yumino D, Amirthalingam V, Bradley TD: Effect of rostral fluid shift on pharyngeal resistance in men with and without obstructive sleep apnea. Respir Physiol Neurobiol 2014; 192: 17–22.
36.
Redolfi S, Yumino D, Ruttanaumpawan P, Yau B, Su MC, Lam J, Bradley TD: Relationship between overnight rostral fluid shift and Obstructive Sleep Apnea in nonobese men. Am J Respir Crit Care Med 2009; 179: 241–246.
37.
Lyons OD, Chan CT, Yadollahi A, Bradley TD: Effect of ultrafiltration on sleep apnea and sleep structure in patients with end-stage renal disease. Am J Respir Crit Care Med 2015; 191: 1287–1294.
38.
Raghuram A, Clay R, Kumbam A, Tereshchenko LG, Khan A: A systematic review of the association between obstructive sleep apnea and ventricular arrhythmias. J Clin Sleep Med 2014; 10: 1155–1160.
39.
Shah RV, Abbasi SA, Heydari B, Farhad H, Dodson JA, Bakker JP, John RM, Veves A, Malhotra A, Blankstein R, Jerosch-Herold M, Kwong RY, Neilan TG: Obesity and sleep apnea are independently associated with adverse left ventricular remodeling and clinical outcome in patients with atrial fibrillation and preserved ventricular function. Am Heart J 2014; 167: 620–626.
40.
Gillis AM, Stoohs R, Guilleminault C: Changes in the QT interval during obstructive sleep apnea. Sleep 1991; 14: 346–350.
41.
Fava C, Dorigoni S, Dalle Vedove F, Danese E, Montagnana M, Guidi GC, Narkiewicz K, Minuz P: Effect of CPAP on blood pressure in patients with OSA/hypopnea a systematic review and meta-analysis. Chest 2014; 145: 762–771.
42.
Pedrosa RP, Drager LF, de Paula LKG, Amaro ACS, Bortolotto LA, Lorenzi-Filho G: Effects of OSA treatment on BP in patients with resistant hypertension: a randomized trial. Chest 2013; 144: 1487–1494.
43.
Liu L, Cao Q, Guo Z, Dai Q: Continuous positive airway pressure in patients with obstructive sleep apnea and resistant hypertension: a meta-analysis of randomized controlled trials. J Clin Hypertens (Greenwich) 2016; 18: 153–158.
44.
Patel D, Mohanty P, Di Biase L, Shaheen M, Lewis WR, Quan K, Cummings JE, Wang P, Al-Ahmad A, Venkatraman P, Nashawati E, Lakkireddy D, Schweikert R, Horton R, Sanchez J, Gallinghouse J, Hao S, Beheiry S, Cardinal DS, Zagrodzky J, Canby R, Bailey S, Burkhardt JD, Natale A: Safety and efficacy of pulmonary vein antral isolation in patients with obstructive sleep apnea: the impact of continuous positive airway pressure. Circ Arrhythm Electrophysiol 2010; 3: 445–451.
45.
Fein AS, Shvilkin A, Shah D, Haffajee CI, Das S, Kumar K, Kramer DB, Zimetbaum PJ, Buxton AE, Josephson ME, Anter E: Treatment of obstructive sleep apnea reduces the risk of atrial fibrillation recurrence after catheter ablation. J Am Coll Cardiol 2013; 62: 300–305.
46.
Jiang N, Zhou A, Prasad B, Zhou L, Doumit J, Shi G, Imran H, Kaseer B, Millman R, Dudley SC Jr: Obstructive sleep apnea and circulating potassium channel levels. J Am Heart Assoc 2016; 5:e003666.
47.
Longenecker JC, Coresh J, Klag MJ, Levey AS, Martin AA, Fink NE, Powe NR: Validation of comorbid conditions on the end-stage renal disease medical evidence report: the CHOICE study. Choices for Healthy Outcomes in Caring for ESRD. J Am Soc Nephrol 2000; 11: 520–529.
48.
Heinzer R, Vat S, Marques-Vidal P, Marti-Soler H, Andries D, Tobback N, Mooser V, Preisig M, Malhotra A, Waeber G, Vollenweider P, Tafti M, Haba-Rubio J: Prevalence of sleep-disordered breathing in the general population: the HypnoLaus study. Lancet Respir Med 2015; 3: 310–318.
49.
Peppard PE, Young T, Barnet JH, Palta M, Hagen EW, Hla KM: Increased prevalence of sleep-disordered breathing in adults. Am J Epidemiol 2013; 177: 1006–1014.
50.
Deegan PC, McNicholas WT: Predictive value of clinical features for the obstructive sleep apnoea syndrome. Eur Respir J 1996; 9: 117–124.
51.
Netzer N, Eliasson AH, Netzer C, Kristo DA: Overnight pulse oximetry for sleep-disordered breathing in adults: a review. Chest 2001; 120: 625–633.
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