Cardiopulmonary Consequences of Obstructive Sleep Apnea

ABSTRACT

Ongoing research in obstructive sleep apnea (OSA) suggests strong associations with cardiopulmonary disorders. There is an abundance of studies describing physiological pathways in OSA that acutely impact the cardiovascular system. These mechanisms, if proven to carry over into the daytime hours, could form the basis for clinical disease. The challenge remains in disentangling these mechanistic processes from the many comorbid conditions often present in patients with OSA. Examples include male gender, obesity, and diabetes mellitus, all of which exert their own influence on the development of cardiopulmonary disease. This review discusses some of the physiological mechanisms associated with disordered breathing during sleep and explores putative cardiopulmonary disease associations.

KEYWORDS

Obstructive sleep apnea - sleep-disordered breathing - cardiovascular disease - obesity - hypoventilation

REFERENCES

• 1 Redline S, Kapur V K, Sanders M H et al.. Effects of varying approaches for identifying respiratory disturbances on sleep apnea assessment.  Am J Respir Crit Care Med. 2000;  161 369-374
• 1a Somers V, Dyken M, Mark A et al.. Sympathetic-nerve activity during sleep in normal subjects.  N Engl J Med. 1993;  328 303-307
• 2 Virolainen J, Ventila M, Turto H et al.. Effect of negative intrathoracic pressure on left ventricular pressure dynamics and relaxation.  J Appl Physiol. 1995;  79 455-460
• 3 Parker J D, Brooks D, Kozar L F et al.. Acute and chronic effects of airway obstruction on canine left ventricular performance.  Am J Respir Crit Care Med. 1999;  160 1888-1896
• 4 Hall M J, Ando S, Floras J S et al.. Magnitude and time course of hemodynamic responses to Mueller maneuvers in patients with congestive heart failure.  J Appl Physiol. 1998;  85 1476-1484
• 5 Berry R B, Gleeson K et al.. Respiratory arousal from sleep: mechanisms and significance.  Sleep. 1997;  20 654-675
• 6 Remmers J E, deGroot W J, Sauerland E K et al.. Pathogenesis of upper airway occlusion during sleep.  J Appl Physiol. 1978;  44 931-938
• 7 Younes M et al.. Role of arousals in the pathogenesis of obstructive sleep apnea.  Am J Respir Crit Care Med. 2004;  169 623-633
• 8 Brooks D, Horner R L, Kozar L F et al.. Obstructive sleep apnea as a cause of systemic hypertension: evidence from a canine model.  J Clin Invest. 1997;  99 106-109
• 9 Blasi A, Jo J, Valladares E et al.. Cardiovascular variability after arousal from sleep: time-varying spectral analysis.  J Appl Physiol. 2003;  95 1394-1404
• 10 Lesske J FE, Bao G, Unger T. Hypertension caused by chronic intermittent hypoxia-influence of chemoreceptors and sympathetic nervous system.  J Hypertens. 1997;  15(12 Pt 2) 1593-1603
• 11 Narkiewicz K, van de Borne P, Montano N et al.. Contribution of tonic chemoreflex activation to sympathetic activity and blood pressure in patients with obstructive sleep apnea.  Circulation. 1998;  97 943-945
• 12 Narkiewicz K, van de Borne P J, Pesek C A et al.. Selective potentiation of peripheral chemoreflex sensitivity in obstructive sleep apnea.  Circulation. 1999;  99 1183-1189
• 13 Hedner J, Wilcox I, Laks L et al.. A specific and potent pressor effect of hypoxia in patients with sleep apnea.  Am Rev Respir Dis. 1992;  146 1240-1245
• 14 Kimoff R J, Brooks D, Horner R L et al.. Ventilatory and arousal responses to hypoxia and hypercapnia in a canine model of obstructive sleep apnea.  Am J Respir Crit Care Med. 1997;  156 886-894
• 15 Somers V K, Mark A L, Zavala D C et al.. Contrasting effects of hypoxia and hypercapnia on ventilation and sympathetic activity in humans.  J Appl Physiol. 1989;  67 2101-2106
• 16 Narkiewicz K, van de Borne P J, Cooley R L et al.. Sympathetic activity in obese subjects with and without obstructive sleep apnea.  Circulation. 1998;  98 772-776
• 17 Somers V K, Mark A L, Zavala D C et al.. Influence of ventilation and hypocapnia on sympathetic nerve responses to hypoxia in normal humans.  J Appl Physiol. 1989;  67 2095-2100
• 18 Ringler J, Basner R C, Shannon R et al.. Hypoxemia alone does not explain blood pressure elevations after obstructive apneas.  J Appl Physiol. 1990;  69 2143-2148
• 19 O'Donnell C P, Ayuse T, King E D et al.. Airway obstruction during sleep increases blood pressure without arousal.  J Appl Physiol. 1996;  80 773-781
• 19a Somers V K, Dyken M E, Clary M P et al.. Sympathetic neural mechanisms in obstructive sleep apnea.  J Clin Invest. 1995;  96 1897-1904
• 20 Voelkel N. Mechanisms of hypoxic pulmonary vasoconstriction.  Am Rev Respir Dis. 1986;  133 1186-1195
• 21 Sarybaev A S, Usupbaeva D A, Plywaczewski R et al.. Effects of intermittent exposure to high altitude on pulmonary hemodynamics: a prospective study.  High Alt Med Biol. 2003;  4 455-463
• 22 Tilkian A G, Guilleminault C, Schroeder J S et al.. Hemodynamics in sleep-induced apnea: studies during wakefulness and sleep.  Ann Intern Med. 1976;  85 714-719
• 23 Niijima M, Kimura H, Edo H et al.. Manifestation of pulmonary hypertension during REM sleep in obstructive sleep apnea syndrome.  Am J Respir Crit Care Med. 1999;  159 1766-1772
• 24 Faller D V. Endothelial cell responses to hypoxic stress.  Clin Exp Pharmacol Physiol. 1999;  26 74-84
• 25 Bradley T D, Rutherford R, Grossman R F et al.. Role of daytime hypoxemia in the pathogenesis of right heart failure in the obstructive sleep apnea syndrome.  Am Rev Respir Dis. 1985;  131 835-839
• 26 Fletcher E C, Schaaf J W, Miller J et al.. Long-term cardiopulmonary sequelae in patients with sleep apnea and chronic lung disease.  Am Rev Respir Dis. 1987;  135 525-533
• 27 Sajkov D, Cowie R, Thornton A et al.. Pulmonary hypertension and hypoxemia in obstructive sleep apnea syndrome.  Am J Respir Crit Care Med. 1994;  149 416-422
• 28 Bady E, Achkar A, Pascal S et al.. Pulmonary arterial hypertension in patients with sleep apnoea syndrome.  Thorax. 2000;  55 934-939
• 29 McQuillan B M, Picard M H, Leavitt M et al.. Clinical correlates and reference intervals for pulmonary artery systolic pressure among echocardiographically normal subjects.  Circulation. 2001;  104 2797-2802
• 29a Sajkov D, Wang T, Saunders N A et al.. Continuous positive airway pressure treatment improves pulmonary hemodynamics in patients with obstructive sleep apnea.  Am J Respir Crit Care Med. 2002;  165 152-158
• 30 Eisensehr I EB, Noachtar S, Korbett K, Byrne A, McAuley A, Palabrica T. Platelet activation, epinephrine, and blood pressure in obstructive sleep apnea syndrome.  Neurology. 1998;  51 188-195
• 31 von Kanel R, Dimsdale J E. Hemostatic alterations in patients with obstructive sleep apnea and the implications for cardiovascular disease.  Chest. 2003;  124 1956-1967
• 32 Chin K, Ohi M, Kita H et al.. Effects of NCPAP therapy on fibrinogen levels in obstructive sleep apnea syndrome.  Am J Respir Crit Care Med. 1996;  153 1972-1976
• 33 von Kanel R, Le D T, Nelesen R A et al.. The hypercoagulable state in sleep apnea is related to comorbid hypertension.  J Hypertens. 2001;  19 1445-1451
• 34 Rangemark C HJ, Carlson J T, Gleerup G, Winther K. Platelet function and fibrinolytic activity in hypertensive and normotensive sleep apnea patients.  Sleep. 1995;  18 188-194
• 35 Goldhaber S. TV. A prospective registry of 5,451 patients with ultrasound-confirmed deep vein thrombosis.  Am J Cardiol. 2004;  93 259-262
• 36 Heit J A. Risk factors for venous thromboembolism.  Clin Chest Med. 2003;  24 1-12
• 37 Arnulf I, Merino-Andreu M, Perrier A et al.. Obstructive sleep apnea and venous thromboembolism.  JAMA. 2002;  287 2655-2656
• 38 Peppard P E, Young T, Palta M et al.. Prospective study of the association between sleep-disordered breathing and hypertension.  N Engl J Med. 2000;  342 1378-1384
• 39 Pepperell J C, Ramdassingh-Dow S, Crosthwaite N et al.. Ambulatory blood pressure after therapeutic and subtherapeutic nasal continuous positive airway pressure for obstructive sleep apnoea: a randomised parallel trial.  Lancet. 2002;  359 204-210
• 40 Chobanian A V, Bakris G L, Black H R et al.. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report.  JAMA. 2003;  289 2560-2571
• 41 Logan A G, Perlikowski S M, Mente A et al.. High prevalence of unrecognized sleep apnoea in drug-resistant hypertension.  J Hypertens. 2001;  19 2271-2277
• 42 Portaluppi F, Provini F, Cortelli P et al.. Undiagnosed sleep-disordered breathing among male nondippers with essential hypertension.  J Hypertens. 1997;  15 1227-1233
• 43 Sin D D, Fitzgerald F, Parker J D et al.. Risk factors for central and obstructive sleep apnea in 450 men and women with congestive heart failure.  Am J Respir Crit Care Med. 1999;  160 1101-1106
• 44 Javaheri S, Parker T J, Woder L et al.. Occult sleep-disordered breathing in stable congestive heart failure.  Ann Intern Med. 1995;  122 487-492
• 45 Chan J, Sanderson J, Chan W et al.. Prevalence of sleep-disordered breathing in diastolic heart failure.  Chest. 1997;  111 1488-1493
• 46 Kaneko Y, Floras J S, Usui K et al.. Cardiovascular effects of continuous positive airway pressure in patients with heart failure and obstructive sleep apnea.  N Engl J Med. 2003;  348 1233-1241
• 47 Shepard Jr J, Pevernagie D, Stanson A et al.. Effects of changes in central venous pressure on upper airway size in patients with obstructive sleep apnea.  Am J Respir Crit Care Med. 1996;  153 250-254
• 48 Alex C G,  O E, Lopata M. Upper airway occlusion during sleep in patients with Cheyne-Stokes respiration.  Am Rev Respir Dis. 1986;  133 42-45
• 49 Phillips B G, Narkiewicz K, Pesek C A et al.. Effects of obstructive sleep apnea on endothelin-1 and blood pressure.  J Hypertens. 1999;  17 61-66
• 50 Lavie L, Kraiczi H, Hefetz A et al.. Plasma vascular endothelial growth factor in sleep apnea syndrome: effects of nasal continuous positive air pressure treatment.  Am J Respir Crit Care Med. 2002;  165 1624-1628
• 51 Kahler C M, Wechselberger J, Molnar C et al.. Serum levels of vascular endothelial growth factor are elevated in patients with obstructive sleep apnea and severe night time hypoxia.  Am J Respir Crit Care Med. 2003;  167 92-93 , author reply 93
• 52 Shamsuzzaman A S, Winnicki M, Lanfranchi P et al.. Elevated C-reactive protein in patients with obstructive sleep apnea.  Circulation. 2002;  105 2462-2464
• 53 Lavie L. Obstructive sleep apnoea syndrome: an oxidative stress disorder.  Sleep Med Rev. 2003;  7 35-51
• 54 Shahar E, Whitney C W, Redline S et al.. 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
• 55 Peker Y, Hedner J, Kraiczi H et al.. Respiratory disturbance index: an independent predictor of mortality in coronary artery disease.  Am J Respir Crit Care Med. 2000;  162 81-86
• 56 Franklin K A, Nilsson J B, Sahlin C et al.. Sleep apnoea and nocturnal angina.  Lancet. 1995;  345 1085-1087
• 57 Peled N, Abinader E G, Pillar G et al.. Nocturnal ischemic events in patients with obstructive sleep apnea syndrome and ischemic heart disease: effects of continuous positive air pressure treatment.  J Am Coll Cardiol. 1999;  34 1744-1749
• 58 Guilleminault C, Conolly S J, Winkle R A. Cardiac arrhythmia and conduction disturbances during sleep in 400 patients with sleep apnea syndrome.  Am J Cardiol. 1983;  52 490-494
• 59 Zwillich C, Devlin T, White D et al.. Bradycardia during sleep apnea. Characteristics and mechanism.  J Clin Invest. 1982;  69 1286-1292
• 60 Shepard Jr J W, Garrison M W, Grither D A et al.. Relationship of ventricular ectopy to oxyhemoglobin desaturation in patients with obstructive sleep apnea.  Chest. 1985;  88 335-340
• 61 Kanagala R, Murali N S, Friedman P A et al.. Obstructive sleep apnea and the recurrence of atrial fibrillation.  Circulation. 2003;  107 2589-2594
• 62 Zwillich C W, Sutton F D, Pierson D J et al.. Decreased hypoxic ventilatory drive in the obesity-hypoventilation syndrome.  Am J Med. 1975;  59 343-348
• 63 Suratt P M, Wilhoit S C, Hsiao H S et al.. Compliance of chest wall in obese subjects.  J Appl Physiol. 1984;  57 403-407
• 64 Koenig S. Pulmonary complications of obesity.  Am J Med Sci. 2001;  321 249-279
• 65 Zerah F, Harf A, Perlemuter L et al.. Effects of obesity on respiratory resistance.  Chest. 1993;  103 1470-1476
• 66 Jones J B,  W S, Findley L J, Suratt P M et al.. Oxyhemoglobin saturation during sleep in subjects with and without the obesity-hypoventilation syndrome.  Chest. 1985;  88 9-15
• 67 Sullivan C E, Berthon-Jones M, Issa F G. Remission of severe obesity-hypoventilation syndrome after short-term treatment during sleep with nasal continuous positive airway pressure.  Am Rev Respir Dis. 1983;  128 177-181
• 68 O'Donnell C P. Leptin prevents respiratory depression in obesity.  Am J Respir Crit Care Med. 1999;  159(5 Pt 1) 1477-1484
• 69 Phillips B G, Kato M, Narkiewicz K et al.. Increases in leptin levels, sympathetic drive, and weight gain in obstructive sleep apnea.  Am J Physiol Heart Circ Physiol. 2000;  279 H234-H237
• 70 Harsch I A, Konturek P C, Koebnick C et al.. Leptin and ghrelin levels in patients with obstructive sleep apnoea: effect of CPAP treatment.  Eur Respir J. 2003;  22 251-257
• 71 Ahmed Q, Chung-Park M, Tomashefski Jr J F. Cardiopulmonary pathology in patients with sleep apnea/obesity hypoventilation syndrome.  Hum Pathol. 1997;  28 264-269
• 72 Otto M EB, Bijoy K, Gilman G, Svatikova A, Fiesler C, Somers V K. Tissue Doppler echocardiography in obesity: selective changes in right but not left ventricular function.  Circulation. 2003;  108 iv 440