Skip to main content
SpringerLink
Log in

Lower extremity edema and pulmonary hypertension in morbidly obese patients with obstructive sleep apnea

  • Original Article
  • Published:
Sleep and Breathing Aims and scope Submit manuscript

Abstract

Introduction

In 70 consecutive male patients with obstructive sleep apnea (OSA) diagnosed at the Northport VA Medical Center Sleep Disorders Center, we have characterized the association between obesity, OSA, and pulmonary hypertension (PH).

Materials and methods

By including anthropometric, pulmonary function, and sleep study parameters in a multivariate logistic regression model, we found that a BMI of >40 kg/m2 and the minimum oxygen saturation in non-rapid eye movement (NREM) sleep predicted the presence of pretibial edema in this sleep apnea population. We then characterized the hemodynamics of those OSA patients that had lower extremity edema. Twenty-nine of the 70 consecutive patients with sleep apnea (41%) had pretibial edema, and right heart catheterization data was obtained for 28 (97%) of these patients.

Results and discussion

Ninety-three percent (26/28) of the patients had right heart failure (mean RAP > 5 mm Hg; RAP range = 0–32 mmHg) and PH (PA mean ≥ 20 mm Hg) was present in 86% (24/28.) The OSA patients with lower extremity edema had an increased cardiac output (7.0 + 1.4 l/min) with a normal cardiac index (2.9 + 0.5 l/min/m2) in the setting of an elevated pulmonary capillary wedge pressure (PCWP 17 ± 7 mmHg) and a normal pulmonary vascular resistance (122 + 70 dynes s cm−5). While PCWP, FEV1% predicted, and the minimum oxygen saturation in NREM sleep all independently predicted PH, PCWP was the most important predictor of PH.

Conclusion

We conclude that pulmonary hypertension is commonly seen in patients with OSA with pretibial edema and that pretibial edema is a highly specific sign of PH in OSA patients. Pulmonary hypertension appears to result from an elevated back pressure and diastolic dysfunction with contributions from lung function and nocturnal oxygen saturation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Motta J, Guilleminault C, Schroeder JS, Dement WC (1978) Tracheostomy and hemodynamic changes in sleep-inducing apnea. Ann Intern Med 89(4):454–458

    CAS  PubMed  Google Scholar 

  2. Tilkian AG, Guilleminault C, Schroeder JS, Lehrman KL, Simmons FB, Dement WC (1976) Hemodynamics in sleep-induced apnea. Studies during wakefulness and sleep. Ann Intern Med 85(6):714–719

    CAS  PubMed  Google Scholar 

  3. Marrone O, Bellia V, Ferrara G, Milone F, Romano L, Salvaggio A, Stallone A, Bonsignore G (1989) Transmural pressure measurements. Importance in the assessment of pulmonary hypertension in obstructive sleep apneas. Chest 95(2):338–342

    Article  CAS  PubMed  Google Scholar 

  4. Tarasiuk A, Chen L, Scharf SM (1997) Effects of periodic obstructive apnoeas on superior and inferior venous return in dogs. Acta Physiol Scand 161(2):187–194

    Article  CAS  PubMed  Google Scholar 

  5. Podszus TE, Greenberg H, Scharf SM (1993) Influence of sleep state and sleep-disordered breathing on cardiovascular function. In: Sullivan CE (ed) Sleep and breathing. Marcel Dekker, New York, pp 257–310

    Google Scholar 

  6. Salejee I, Tarasiuk A, Reder I, Scharf SM (1993) Chronic upper airway obstruction produces right but not left ventricular hypertrophy in rats. Am Rev Respir Dis 148(5):1346–1350

    CAS  PubMed  Google Scholar 

  7. Sajkov D, Cowie RJ, Thornton AT, Espinoza HA, McEvoy RD (1994) Pulmonary hypertension and hypoxemia in obstructive sleep apnea syndrome. Am J Respir Crit Care Med 149(2 Pt 1):416–422

    CAS  PubMed  Google Scholar 

  8. Laks L (1993) Pulmonary arterial pressure in sleep apnea. Sleep 16(8 Suppl):S41–S43

    CAS  PubMed  Google Scholar 

  9. Bradley TD, Rutherford R, Grossman RF, Lue F, Zamel N, Moldofsky H, Phillipson EA (1985) Role of daytime hypoxemia in the pathogenesis of right heart failure in the obstructive sleep apnea syndrome. Am Rev Respir Dis 131(6):835–839

    CAS  PubMed  Google Scholar 

  10. Bady E, Achkar A, Pascal S, Orvoen-Frija E, Laaban JP (2000) Pulmonary arterial hypertension in patients with sleep apnoea syndrome. Thorax 55(11):934–939

    Article  CAS  PubMed  Google Scholar 

  11. Davidson WR (1995) Ventricular hypertrophy in sleep apnoea. J Sleep Res 4(S1):176–181

    Article  PubMed  Google Scholar 

  12. Schoen FJ (2005) The heart. In: Vinay K, Abbas AK, Fausto N (eds) Robbins and cotran pathologic basis of disease, Chapter 12. Saunders, Philadelphia

    Google Scholar 

  13. Milic-Emili J, Mead J, Turner JM, Glauser EM (1964) Improved technique for estimating pleural pressure from esophageal balloons. J Appl Physiol 19:207–211

    CAS  PubMed  Google Scholar 

  14. Milic-Emili J, Mead J, Turner JM (1964) Topography of esophageal pressure as a function of posture in man. J Appl Physiol 19:212–216

    CAS  PubMed  Google Scholar 

  15. Collucci WS, Braunwald E (1997) Pathophysiology of heart failure. In: Braunwald E (ed) Heart disease: a textbook of cardiovascular medicine. Saunders, Philadelphia, pp 394–420

    Google Scholar 

  16. Alexander JK, Amad KH, Cole VW (1962) Observations on some clinical features of extreme obesity, with particular reference to cardiorespiratory effects. Am J Med 32(4):512–524

    Article  Google Scholar 

  17. Davidson CJ, Fishman RF, Bonow RO (1997) Cardiac catheterization. In: Braunwald E (ed) Heart disease: a textbook of cardiovascular medicine. Saunders, Philadelphia, pp 177–203

    Google Scholar 

  18. Branthwaite MA, Bradley RD (1968) Measurement of cardiac output by thermal dilution in man. J Appl Physiol 24(3):434–438

    CAS  PubMed  Google Scholar 

  19. Hillis LD, Firth BG, Winniford MD (1985) Analysis of factors affecting the variability of Fick versus indicator dilution measurements of cardiac output. Am J Cardiol 56(12):764–768

    Article  CAS  PubMed  Google Scholar 

  20. Asbell TN (1973) Giant panniculus adiposus abdominis. Arch Surg 107(6):901–902

    CAS  PubMed  Google Scholar 

  21. Guidry UC, Mendes LA, Evans JC, Levy D, O’Connor GT, Larson MG, Gottlieb DJ, Benjamin EJ (2001) Echocardiographic features of the right heart in sleep-disordered breathing: the Framingham Heart Study. Am J Respir Crit Care Med 164(6):933–938

    CAS  PubMed  Google Scholar 

  22. Whyte KF, Douglas NJ (1991) Peripheral edema in the sleep apnea/hypopnea syndrome. Sleep 14(4):354–356

    CAS  PubMed  Google Scholar 

  23. Chaouat A, Weitzenblum E, Krieger J, Oswald M, Kessler R (1996) Pulmonary hemodynamics in the obstructive sleep apnea syndrome. Results in 220 consecutive patients. Chest 109(2):380–386

    Article  CAS  PubMed  Google Scholar 

  24. Weitzenblum E, Krieger J, Apprill M, Vallee E, Ehrhart M, Ratomaharo J, Oswald M, Kurtz D (1988) Daytime pulmonary hypertension in patients with obstructive sleep apnea syndrome. Am Rev Respir Dis 138(2):345–349

    CAS  PubMed  Google Scholar 

  25. Krieger J, Sforza E, Apprill M, Lampert E, Weitzenblum E, Ratomaharo J (1989) Pulmonary hypertension, hypoxemia, and hypercapnia in obstructive sleep apnea patients. Chest 96(4):729–737

    Article  CAS  PubMed  Google Scholar 

  26. Laks L, Lehrhaft B, Grunstein RR, Sullivan CE (1995) Pulmonary hypertension in obstructive sleep apnoea. Eur Respir J 8(4):537–541

    CAS  PubMed  Google Scholar 

  27. Zielinski J (2005) Effects of intermittent hypoxia on pulmonary haemodynamics: animal models versus studies in humans. Eur Respir J 25(1):173–180

    Article  CAS  PubMed  Google Scholar 

  28. Laks L, Lehrhaft B, Grunstein RR, Sullivan CE (1997) Pulmonary artery pressure response to hypoxia in sleep apnea. Am J Respir Crit Care Med 155(1):193–198

    CAS  PubMed  Google Scholar 

  29. Sajkov D, Wang T, Saunders NA, Bune AJ, Neill AM, McEvoy RD (1999) Daytime pulmonary hemodynamics in patients with obstructive sleep apnea without lung disease. Am J Respir Crit Care Med 159(5 Pt 1):1518–1526

    CAS  PubMed  Google Scholar 

  30. Laaban JP, Cassuto D, Orvoen-Frija E, Iliou MC, Mundler O, Leger D, Oppert JM (1998) Cardiorespiratory consequences of sleep apnoea syndrome in patients with massive obesity. Eur Respir J 11(1):20–27

    Article  CAS  PubMed  Google Scholar 

  31. McQuillan BM, Picard MH, Leavitt M, Weyman AE (2001) Clinical correlates and reference intervals for pulmonary artery systolic pressure among echocardiographically normal subjects. Circulation 104(23):2797–2802

    Article  CAS  PubMed  Google Scholar 

  32. Sanchez NC, Tenofsky PL, Dort JM, Shen LY, Helmer SD, Smith RS (2001) What is normal intra-abdominal pressure. Am Surg 67(3):243–248

    CAS  PubMed  Google Scholar 

  33. Alexander JK, Dennis EW, Smith WG, Amad KH, Duncan WC, Austin RC (1962) Blood volume, cardiac output, and distribution of systemic blood flow in extreme obesity. Cardiovasc Res Cent Bull 1:39–44

    PubMed  Google Scholar 

  34. Poirier P, Giles TD, Bray GA, Hong Y, Stern JS, Pi-Sunyer FX, Eckel RH (2006) Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss. Arterioscler Thromb Vasc Biol 26(5):968–976

    Article  CAS  PubMed  Google Scholar 

  35. Sanner BM, Konermann M, Sturm A, Muller HJ, Zidek W (1997) Right ventricular dysfunction in patients with obstructive sleep apnoea syndrome. Eur Respir J 10(9):2079–2083

    Article  CAS  PubMed  Google Scholar 

  36. Nahmias J, Lao R, Karetzky M (1996) Right ventricular dysfunction in obstructive sleep apnoea: reversal with nasal continuous positive airway pressure. Eur Respir J 9(5):945–9451

    Article  CAS  PubMed  Google Scholar 

  37. McMurray JJ, Ostergren J, Swedberg K, Granger CB, Held P, Michelson EL, Olofsson B, Yusuf S, Pfeffer MA (2003) Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensin-converting-enzyme inhibitors: the CHARM-Added trial. Lancet 362(9386):767–771

    Article  CAS  PubMed  Google Scholar 

  38. Parker JD, Brooks D, Kozar LF, Render-Teixeira CL, Horner RL, Bradley TD, Phillipson EA (1999) Acute and chronic effects of airway obstruction on canine left ventricular performance. Am J Respir Crit Care Med 160(6):1888–1896

    CAS  PubMed  Google Scholar 

  39. Hanly P, Sasson Z, Zuberi N, Alderson M (1992) Ventricular function in snorers and patients with obstructive sleep apnea. Chest 102(1):100–105

    Article  CAS  PubMed  Google Scholar 

  40. Hedner J, Ejnell H, Caidahl K (1990) Left ventricular hypertrophy independent of hypertension in patients with obstructive sleep apnoea. J Hypertens 8(10):941–946

    Article  CAS  PubMed  Google Scholar 

  41. Laaban JP, Pascal-Sebaoun S, Bloch E, Orvoen-Frija E, Oppert JM, Huchon G (2002) Left ventricular systolic dysfunction in patients with obstructive sleep apnea syndrome. Chest 122(4):1133–1138

    Article  PubMed  Google Scholar 

  42. Hetzel M, Kochs M, Marx N, Woehrle H, Mobarak I, Hombach V, Hetzel J (2003) Pulmonary hemodynamics in obstructive sleep apnea: frequency and causes of pulmonary hypertension. Lung 181(3):157–166

    Article  CAS  PubMed  Google Scholar 

  43. Sanner BM, Doberauer C, Konermann M, Sturm A, Zidek W (1997) Pulmonary hypertension in patients with obstructive sleep apnea syndrome. Arch Intern Med 157(21):2483–2487

    Article  CAS  PubMed  Google Scholar 

  44. Dursunoglu D, Dursunoglu N, Evrengul H, Ozkurt S, Kuru O, Kilic M, Fisekci F (2005) Impact of obstructive sleep apnoea on left ventricular mass and global function. Eur Respir J 26(2):283–288

    Article  CAS  PubMed  Google Scholar 

  45. Cloward TV, Walker JM, Farney RJ, Anderson JL (2003) Left ventricular hypertrophy is a common echocardiographic abnormality in severe obstructive sleep apnea and reverses with nasal continuous positive airway pressure. Chest 124(2):594–601

    Article  PubMed  Google Scholar 

  46. Sukhija R, Aronow WS, Sandhu R, Kakar P, Maguire GP, Ahn C, Lehrman SG (2006) Prevalence of left ventricular hypertrophy in persons with and without obstructive sleep apnea. Cardiol Rev 14(4):170–172

    Article  PubMed  Google Scholar 

  47. Wiedemann HP, Matthay RA (1997) Cor pulmonale. In: Braunwald E (ed) Heart disease: a textbook of cardiovascular medicine. Saunders, Philadelphia, pp 1604–1625

    Google Scholar 

  48. Parker JO, Ashekian PB, Di Giorgi S, West RO (1967) Hemodynamic effects of aminophylline in chronic obstructive pulmonary disease. Circulation 35(2):365–72

    CAS  PubMed  Google Scholar 

  49. Parker JO, Kelkar K, West RO (1966) Hemodynamic effects of aminophylline in cor pulmonale. Circulation 33(1):17–25

    CAS  PubMed  Google Scholar 

  50. Burrows B, Kettel LJ, Niden AH, Rabinowitz M, Diener CF (1972) Patterns of cardiovascular dysfunction in chronic obstructive lung disease. N Engl J Med 286(17):912–918

    Article  CAS  PubMed  Google Scholar 

  51. Moss AJ, Harper WH, Dooley RR, Murray JF, Mack JF (1965) Cor pulmonale in cystic fibrosis of the pancreas. J Pediatr 67(5):797–807

    Article  CAS  PubMed  Google Scholar 

  52. Stern RC, Borkat G, Hirschfeld SS, Boat TF, Matthews LW, Liebman J, Doershuk CF (1980) Heart failure in cystic fibrosis. Treatment and prognosis of cor pulmonale with failure of the right side of the heart. Am J Dis Child 134(3):267–272

    CAS  PubMed  Google Scholar 

  53. Moser KM, Spragg RG, Utley J, Daily PO (1983) Chronic thrombotic obstruction of major pulmonary arteries. Results of thromboendarterectomy in 15 patients. Ann Intern Med 99(3):299–304

    CAS  PubMed  Google Scholar 

  54. Heilman RS, Tabakin BS, Hanson JS, Naeye RL (1962) Alterations of circulatory and ventilatory dynamics in pulmonary vascular obstruction secondary to recurrent pulmonary emboli. Case report, with studies of pulmonary physiology. Am J Med 32:298–303

    Article  CAS  PubMed  Google Scholar 

  55. Burchell HB, Edwards JE, Shepherd JT, Swan HJ, Wood EH (1957) Clinical, physiological, and pathological considerations in patients with idiopathic pulmonary hypertension. Br Heart J 19(1):70–82

    Article  CAS  PubMed  Google Scholar 

  56. Sleeper JC, Orgain ES, Mc Intosh HD (1962) Primary pulmonary hypertension. Review of clinical features and pathologic physiology with a report of pulmonary hemodynamics derived from repeated catheterization. Circulation 26:1358–1369

    CAS  PubMed  Google Scholar 

  57. Barratt-Boyes BG, Wood EH (1958) Cardiac output and related measurements and pressure values in the right heart and associated vessels, together with an analysis of the hemo-dynamic response to the inhalation of high oxygen mixtures in healthy subjects. J Lab Clin Med 51(1):72–90

    CAS  PubMed  Google Scholar 

  58. de Divitiis O, Fazio S, Petitto M, Maddalena G, Contaldo F, Mancini M (1981) Obesity and cardiac function. Circulation 64(3):477–482

    PubMed  Google Scholar 

  59. Fletcher EC, Schaaf JW, Miller J, Fletcher JG (1987) Long-term cardiopulmonary sequelae in patients with sleep apnea and chronic lung disease. Am Rev Respir Dis 135(3):525–533

    CAS  PubMed  Google Scholar 

  60. Rochester DF, Enson Y (1974) Current concepts in the pathogenesis of the obesity-hypoventilation syndrome. Mechanical and circulatory factors. Am J Med 57(3):402–420

    Article  CAS  PubMed  Google Scholar 

  61. Naimark A, Cherniack RM (1960) Compliance of the respiratory system and its components in health and obesity. J Appl Physiol 15:377–382

    CAS  PubMed  Google Scholar 

  62. Sharp JT, Henry JP, Sweany SK, Meadows WR, Pietras RJ (1964) The total work of breathing in normal and obese men. J Clin Invest 43:728–739

    Article  CAS  PubMed  Google Scholar 

  63. Permutt S, Wise R, Sylvester J (1986) Interaction between the ventilatory and circulatory pumps. In: Roussos C (ed) The thorax. Marcel Dekker, New York, pp 701–735

    Google Scholar 

  64. Amad KH, Brennan JC, Alexander JK (1965) The cardiac pathology of chronic exogenous obesity. Circulation 32(5):740–745

    CAS  PubMed  Google Scholar 

  65. Bove AA, Santamore WP (1981) Ventricular interdependence. Prog Cardiovasc Dis 23(5):365–388

    Article  CAS  PubMed  Google Scholar 

  66. Janicki JS, Shroff SG, Weber KT (1989) Ventricular interdependence, heart-lung interactions in health and disease. Marcel Dekker, Inc, New York

    Google Scholar 

  67. Laks MM, Garner D, Swan HJ (1967) Volumes and compliances measured simultaneously in the right and left ventricles of the dog. Circ Res 20(5):565–569

    CAS  PubMed  Google Scholar 

  68. Taylor RR, Covell JW, Sonnenblick EH, Ross Jr J (1967) Dependence of ventricular distensibility on filling of the opposite ventricle. Am J Physiol 213(3):711–718

    CAS  PubMed  Google Scholar 

  69. Warnes CA, Roberts WC (1984) The heart in massive (more than 300 pounds or 136 kilograms) obesity: analysis of 12 patients studied at necropsy. Am J Cardiol 54(8):1087–1091

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgment

The authors wish to acknowledge Dr. John P. Dervan and the many attending physicians and fellows of the Cardiology Division of SUNY-Stony Brook School of Medicine who diligently obtained the catheterization data that made this study possible. The authors have no conflicts of interest to report. The work performed by Morris Gold was not connected to his position at Novartis Consumer Health.

Author information

Authors and Affiliations

  1. Department of Medicine, Portland VA Medical Center, Oregon Health & Science University, P3-PULM, P.O. Box 1034, Portland, OR, 97239, USA

    Daniel J. O’Hearn

  2. Department of Medicine, Northport VA Medical Center (NY), Northport, NY, USA

    Avram R. Gold & Paul Diggs

  3. School of Medicine, SUNY-Stony Brook, Stony Brook, NY, USA

    Avram R. Gold & Paul Diggs

  4. Novartis Consumer Health, Summit, NJ, USA

    Morris S. Gold

  5. Department of Medicine, University of Maryland, Baltimore, MD, USA

    Steven M. Scharf

Authors
  1. Daniel J. O’Hearn
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Avram R. Gold
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Morris S. Gold
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Paul Diggs
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Steven M. Scharf
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Daniel J. O’Hearn.

Rights and permissions

Reprints and permissions

About this article

Cite this article

O’Hearn, D.J., Gold, A.R., Gold, M.S. et al. Lower extremity edema and pulmonary hypertension in morbidly obese patients with obstructive sleep apnea. Sleep Breath 13, 25–34 (2009). https://doi.org/10.1007/s11325-008-0200-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11325-008-0200-z

Keywords

Search

Navigation