For some patients, a good night’s sleep could mean the difference between life and death.

Interruption of airflow during sleep, whether of central or obstructive origin, triggers a series of pathophysiologic events. Many of these have been well studied and recorded, while others remain fertile areas for clinical and laboratory research. The magnitude of the problem makes it critically important. The neurologist, pulmonologist, or otorhinolaryngologist may see patients with a symptom complex needing their specific involvement and intervention, but the cardiologist has, perhaps, a greater and more direct role in reducing overall morbidity and mortality among these patients.

Obesity, systemic and pulmonary hypertension, cardiac arrhythmias (including complete heart block and sustained ventricular tachycardia), cerebrovascular accident (CVA), respiratory and congestive cardiac failure with edematous states, and sudden death syndromes are commonly seen problems. All have a potential etiologic factor in common that, if unsuspected and therefore missed, will result in patient morbidity-and, in many instances, mortality-due to sleep-disordered breathing (SDB). The most common forms of SDB are central sleep apnea (CSA) and obstructive sleep apnea (OSA).

The authors have treated more than 12,500 patients. Of these, 86 percent have had SDB and more than 80 percent have had upper-airway OSA, either alone or in combination with central episodes. The realization that disorders occurring at night affect daytime physiology and function has led to a revolution in scientific and clinical observation and treatment of sleep pathology since the mid to late 1960s. Interest has never been higher, and psychiatrists, psychologists, pulmonologists, and internists with board certification in sleep disorders medicine have established a large network of accredited laboratories. Hundreds of patients per night are carefully evaluated in every major US city and in a majority of other developed countries.

The Sleep Disorders Center of Alabama, in Birmingham, has served as a national training center since 1987 and has trained some 500 polysomnography technicians and approximately 350 physicians from 48 US states and nine other countries. Fully 50 percent of the patients seen at the center with moderate to severe sleep apnea have exhibited one or more serious, treatable cardiovascular complications.


The sequence and physiology of so-called normal sleep are well documented, with age-related differences recognized via large population studies. Children and young adults experience more deep, non-rapid-eye-movement (non-REM) sleep; stages 3 and 4 (slow-wave or d-wave )sleep; and REM sleep compared with older subjects. They have fewer spontaneous arousals and no appreciable incidence of apnea after infancy.1

In midlife, spontaneous arousals begin to occur (as do nocturnal awakenings), with an attendant decrease in the deeper stages (3 and 4) of slow-wave and REM sleep. Occasional central hypopneas and/or apneas can be seen in otherwise normal subjects, but these are usually brief (< 15 seconds) and number less than 10 per hour, with no associated pathophysiologic or clinical abnormality.

Normally, sleep stages occur in a repetitive pattern night after night, with the initial REM period occurring approximately 90 minutes after sleep onset, occurring two or three times more, and gradually lengthening as the night progresses.1 As sleep deepens from stage 1 (light, drowsy, easily aroused) through stage 2 and into the deep, restorative phases (3 and 4) and REM, many normal physiologic changes occur. Respiration slows and deepens, heart rate and blood pressure fall, airway tone fluctuates, muscle tone decreases, and, if one is supine, the jaw may move posteriorly and the tongue may be pulled back against the palate on inspiration.2 This gives rise to respiratory noise, from a soft purring sound to roof-rattling snores.

With the onset of REM sleep, all of these functions become destabilized. Blood pressure and pulse fluctuate greatly. Coordination is lost between the abdominal muscles and the diaphragm, causing a paradoxical dissociation and impairment of normal respiratory rhythm and the depth of chest excursion. In patients with lung disease, early pulmonary edema, or thoracic cage or spinal abnormalities, sudden and severe desaturations can occur (often as isolated REM-related events), terminating in an arousal and bringing the patient up into stage 1 or, occasionally, causing full awakening. Sleep fragmentation and arousals also occur in patients with diseases affecting autonomic control and may be seen after CVA or head trauma, in Shy-Drager syndrome, and in patients with symptomatic mitral-valve prolapse.

When an arousal or awakening due to SDB occurs during a sleep study, it is counted as a single event; the nightly sum of events makes up the total respiratory disturbance index (RDI). An RDI equal to or greater than 10 disturbances an hour generally results in patient morbidity.


The prototypical SDB patient is male, is 40 or more years old, snores, is 20 percent or more above ideal body weight, has a thick neck, has an elevated diastolic blood pressure, and reports fatigue and excessive daytime somnolence. This patient is most likely to have significant sleep apnea.3-7

Examining the nasal and oropharyngeal areas, and noting tongue size and jaw position, are critical in patients with suspected OSA. If the subject has nasal septal deviation, large boggy turbinates, or allergic nasal polyps, upper-airway resistance is always increased. This is aggravated by the supine sleeping position. Highly significant apnea occurs in very young children (and in adults) with upper-airway allergic symptoms, swollen nasopharyngeal membranes, and tonsillar hypertrophy.8-10

Although obstruction occurs in the nasopharynx in many patients, it also occurs, in most, at the oropharyngeal level as an extensively elongated soft palate; large, “kissing” tonsils and/or a narrow palatal arch; a large, edematous uvula; and, in some cases, macroglossia. A dry, scratchy sore throat may be an early morning complaint of such a patient, and this should never be disregarded. The inability of the patient to make the posterior pharyngeal wall clearly visible by saying “ah” while supine is a strong physical marker of snoring and potential airway obstruction during sleep.

Craniofacial abnormalities are predictive of OSA; this spectrum spans abnormalities ranging from a narrow posterior air space due to a slightly atretic or malpositioned mandible to the more classic Pierre Robin syndrome or Klippel-Feil deformity of the skull.11 Mild micrognathia in a patient with an overbite on dental occlusion may be the only physical clue as to why this thin, perhaps female, patient is in the physician’s office complaining of fatigue.

On facial inspection, a somnolent patient with conjunctival suffusion and facial plethora may not be a heavy drinker (as you suspect), but may have had elevated, vasodilating carbon dioxide levels and hypoxemia repeatedly the night before he/she came to see you for further adjustment of the regimen prescribed for his/her now difficult-to-control hypertension.

In Down syndrome patients, carefully performed polysomnograms are abnormal in almost all cases, with more than half of these patients having OSA and significant nocturnal hypoxemia. In children and young adults with Down syndrome, OSA, desaturation, and primary central hypoventilation are frequently seen but rarely suspected because the incidence rates in this population are unaffected by age, obesity, or congenital heart disease.12 It is speculated that OSA may, in fact, be a major contributing factor in the unexplained pulmonary hypertension seen in patients with Down syndrome.

Some studies have found notable differences in the initial complaints of men and women presenting with SDB. Women are more likely to complain of morning fatigue and headache and are less likely to have been told of observed apneic events or very restless sleep.13 Although excessive daytime somnolence is a complaint in the majority of patients with OSA, fully 8%o 155of women with apnea complain instead of difficulty initiating and maintaining sleep. This presentation may lead one to consider prescribing sedative or hypnotic drugs, which would only add to morbidity. This is a serious risk; we have seen a significant number of patients with severe desaturations and cardiac arrhythmias due to significant SDB who complained mainly of insomnia. Sedative/hypnotic drugs should never be prescribed, or be ordered as part of an admission protocol, for any patient from whom the physician has not personally taken at least a brief screening sleep history. Screening history forms are readily available from most sleep laboratories.


With closure of the glottis and the generation of negative intrathoracic pressure during an obstructive event, predictable hemodynamic changes occur. If the cessation is long enough for hypoxia to result, more changes are seen; when these events recur so frequently that the patient’s sleep is fragmented and disrupted 20 to 40 times an hour, dire additional consequences may be seen. Sleep apnea may, in a large population of patients, lead to both systemic and pulmonary hypertension; right and left ventricular hypertrophy and dysfunction; serious arrhythmias; aggravation of ischemic, valvular, and/or congenital heart disease; CVAs; and, in some patients, sudden death. In addition, SDB with hypoxia can increase plasma catecholamines, platelet-activating factor inhibitors, and the release of vasoconstricting prostanoids, especially thromboxane.

Weiss et al14 summarized the mechanical factors of apnea that affect pulse, peripheral resistance, and ventricular pre- and afterload in a review of the hemodynamic consequences of OSA. Repetitively involving brainstem and vascular baro- and chemoreceptors seems, over time, to lead to a state of altered cardiovascular responsiveness. Sympathetic outflow is higher in sleep apnea patients than in controls, and normal day-night plasma catecholamine fluctuation is apparently blunted by sleep disruption/deprivation cycles. This- coupled with elevated myocardial contractility and down-regulation of b2-adrenergic receptors in apnea patients-may lead to both the increased incidence of systemic hypertension and the ventricular hypertrophy seen in a significant percentage of patients with moderate-to-severe apnea (RDI > 20/hour). Instead of the reduction in blood pressure variability during non-REM sleep seen in normal subjects, apnea patients with and without ischemic heart disease have a continued increase in wide systolic and diastolic swings during the night.15-18

Noda et al19 found both the apnea index and the duration of desaturations below 90 percent to correlate significantly with left ventricular mass/body surface area and 24-hour mean blood pressure. They further showed that plasma norepinephrine levels after waking significantly increased compared with those before sleep and were significantly correlated with the duration of desaturations below 90 percent, but not with the apnea index alone.

Pulmonary hypertension and cor pulmonale have similarly been associated with OSA, but are seen as sustained, measurable findings mainly in those who already have some degree of chronic lung disease or in those who have a primary component of central alveolar hypoventilation (pickwickian syndrome) and/or apnea in which daytime alteration of blood gases is noted. These patients may not be significantly hypoxemic while awake, but they almost always have mild carbon dioxide retention.20-22

When either left ventricular failure or serious arrhythmia occurs in an SDB patient, one is immediately suspicious of underlying valvular or ischemic heart disease. This is not always the case, however, and both cardiomyopathy and complete heart block may occur. Both are treatable and reversible with therapy aimed at relieving SDB.23-26 Arrhythmias are common during sleep in patients with SDB and tend to be present both during cessation of airflow and during simple sleep-stage changes in which respiratory function is not necessarily impaired. Grimm et al27 found normal electrophysiologic parameters for sinus node function in 12 of 15 patients (80 percent) and for atrioventricular (AV) nodal function in seven (47 percent) patients. Almost all of the study subjects’ arrhythmias were reversible through atropine administration, and the His-Purkinje system was normal in 6 (40 percent) of patients, despite nocturnal ventricular asystole averaging 8.5 seconds (range: 5 to 16.8 seconds). As is characteristic, all of these patients were asymptomatic while awake, and it was concluded that the prolonged ventricular asystole occasionally seen during OSA is not caused by fixed or anatomic disease of the sinus node or AV conduction system.

Various arrhythmias have been documented during overnight polysomnography, and the majority have been shown-after treatment of apnea-to have been reversible, requiring no further intervention.28 Arrhythmias were found in twice as many patients (with repeated desaturations to less than 90 percent or an apnea/hypopnea index equal to or greater than 40 per hour) as controls.29 Many patients whose blood pressure levels were difficult to control before treatment of their breathing disorders were easily controlled once treated, and many can be totally withdrawn from antihypertensive, diuretic, and inotropic agents. In fact, most patients with moderate to severe apnea have significant spontaneous diuresis once nocturnal hypoxia is curtailed and the deeper stages of sleep are restored.

Episodes of nocturnal angina unresponsive to long-acting nitrates, diastolic heart failure, morning headaches unresponsive to aspirin or other mild analgesics, and transient ischemic attacks with minor CVAs all occur with surprising frequency in SDB patients, further emphasizing the urgency of recognition and treatment.30-32 Transient cerebral ischemia and CVAs at night have been carefully evaluated in recent years, and documentation in apnea patients of decreased fibrinolytic activity and a lower prostacyclin-to-thromboxane ratio has furthered understanding of these morbidity factors. The final relationship between these changes and the systemic hypertension so prevalent in SDB has not yet been established.33-34

Patients with congestive heart failure often complain of poor sleep, daytime fatigability, repetitive episodes of paroxysmal nocturnal dyspnea, and cough. Many have periodic respiration of the Cheyne-Stokes type, and aggressive therapy with combinations of oxygen, nasal continuous positive airway pressure, and theophylline have all been shown to reverse many of these signs and symptoms while improving exercise capacity and cognitive function.35,36


Supplemental oxygen alone improves Cheyne-Stokes respiration, decreases the associated disruption of sleep, and improves the condition of some patients with pure OSA. In individuals with established chronic obstructive pulmonary disease, nocturnal oxygen improves daytime function and decreases the need for, or frequency of, physician visits. Oxygen use for as few as 16 of 24 hours by patients with daytime and nocturnal hypoxemia also delays the onset of cor pulmonale.37-40

The usefulness of other therapies is determined according to a patient’s specific diagnosis following a thorough evaluation, (including a careful inspection of the upper airway and overnight polysomnography with oximetry). Weight loss combined with some form of positive airway pressure therapy is currently the most widely used and demonstrably effective method of therapy. Whereas a significant number of young individuals may benefit from tonsillectomy, adenoidectomy, and/or uvulopalatopharyngoplasty, only a small group of individuals beyond middle age will experience a total reversal of apnea through facial reconstruction and/or upper-airway corrective surgery.41


SDB affects not only patients but their families, employers, and coworkers. Lost work time and on-the-job injury occur frequently in apnea patients; in certain occupations, such as long-haul trucking, these individuals pose a great risk to themselves and others. Chronic sleep/wake disruption and partial or prolonged sleep deprivation may actually worsen SDB and may significantly affect the daytime alertness and safety performance of truck drivers.42

Retrospective analysis37 of sudden death in 460 consecutive victims in Finland found a cardiovascular cause in 186 cases (40.4 percent). Sudden death was strongly associated with a history of habitual snoring. Almost all of the reported snorers died during sleep (P< 0.05). Habitual snoring was also found to be a risk factor for early morning death (P< 0.01), so OSA as a cause of sudden death must be considered if the deceased is known to have been a snorer.

The clinician who takes a 5-minute sleep history and intervenes to break this chain of events is practicing a very dramatic form of preventive medicine. Every physician has patients who complain of either day or nighttime symptoms that, once investigated, prove to be related to the pathophysiology of sleep. It is critical that all health care professionals become more aware of the varied presentations and manifestations of the pathology that results in troubles ranging from minor concentration problems and personality changes to progressive cardiovascular dysfunction, including sudden death.

Frank D. Sutton, MD, FACP, FCCP, is chairman, division of pulmonary and rehabilitative medicine, at Baptist Health Systems of Alabama, and medical director, Sleep Disorders Center of Alabama, both in Birmingham.


  1. Aserinsky E, Kleiman N. Regularly occurring periods of eye motility and concomitant phenomena during sleep. Science. 1953;118:273-274.
  2. Khatri IM, Freis ED. Hemodynamic changes during sleep. J Appl Physiol. 1967:22:867-873.
  3. Davies RJO, Stranding JR. The relationship between neck circumference, radiographic pharyngeal anatomy, and the obstructive sleep apnea syndrome. Eur Respir J. 1990;3:509-514.
  4. Koskenvuo M, Kaprio J, Partinen M, Langinvainio H, Sarna S, Heikkila K. Snoring as a risk factor for hypertension and angina pectoris. Lancet. 1985;I:893-896.
  5. Koskenvuo M, Kaprio J, Telakivi T, Partinen M, Heikkila K, Sarna S. Snoring as a risk factor for ischaemic heart disease and stroke in men. BMJ. 1987;294:16-19.
  6. Levinson PD, McGravey ST, Carlisle CC, Eveloff SE, Herbert PN, Millman RP. Adiposity and cardiovascular risk factors in men with obstructive sleep apnea. Chest. 1993;103:1336-1342.
  7. Stoohs RA, Gingold J, Cohrs S, Harter R, Finlayson E, Guilleminault C. Sleep- disordered breathing and systemic hypertension in the older male. J Am Geriatr Soc. 1996;44:1295-1300.
  8. Rivlin J, Hoffstein V, Kalbfleisch J, et al. Upper airway morphology in patients with idiopathic obstructive sleep apnea. Am Rev Respir Dis. 1984;129:355-360.
  9. Riley R, Guilleminault C, Herren J, et al. Cephalometric analyses and flow volume loops in obstructive sleep apnea patients. Sleep. 1983;6:304-317.
  10. McColley SA, Carroll JL, Curtis S, Loughlin GM, Sampson HA. High prevalence of allergic sensitization in children with habitual snoring and obstructive sleep apnea. Chest. 1997;111:170-173.
  11. Nelson S, Hans M. Contribution of craniofacial risk factors in increasing apneic activity among obese and nonobese habitual snorers. Chest. 1997;111:154-162.
  12. Marcus CL, Keens TG, Bautista DB, Von Pechmann WS, Ward SLD. Obstructive sleep apnea in children with Down syndrome. Pediatrics. 1991;88:132-139.
  13. Ambrogetti A, Olson LG, Saunders NA. Differences in the symptoms of men and women with obstructive sleep apnea. Aust N Z J Med. 1991;21:863-866.
  14. Weiss JW, Remsburg S, Garpestad E, Ringler J, Sparrow D, Parker JA. Hemodynamic consequences of obstructive sleep apnea. Sleep. 1996;19:388-397.
  15. Carlson JT, Hedner J, Elam M, Ejnell H, Sellgren J, Wallin BG. Augmented resting sympathetic activity in awake patients with obstructive sleep apnea. Chest. 1993; 103:1763-1768.
  16. Bergmann BM,Everson CA, Kushida CA, et al. Sleep deprivation in the rat: V. energy use and mediation. Sleep. 1989; 12:31-41.
  17. Nelesen RA, Dimsdale JE, Mills PJ, Clausen JL, Ziegler MG, Ancoli-Israel S. Altered cardiac contractility in sleep apnea. Sleep. 1996;19:139-144.
  18. Leroy L, Van Surell C, Pilliere R, Hagenmuller MP, Aegerter P, Raffestin B. Short-term variability of blood pressure during sleep in snorers with or without apnea. Hypertension. 1996;28;937-943.
  19. Noda A, Okada T, Yasuma F, Nakashima N, Yokota M. Cardiac hypertrophy in obstructive sleep apnea syndrome. Chest. 1995;107:1538-1544.
  20. Sutton FD, Zwillich CW, Creagh E, Pierson DJ, Weil JV. Progesterone for outpatient treatment of Pickwickian syndrome. Ann Intern Med. 1975;83:476-479.
  21. Zwillich C, Sutton FD, Pierson DJ, Creagh E, Weil JV. Decreased hypoxic ventilatory drive in the obesity-hypoventilation syndrome. Am J Med. 1975;59:343-353.
  22. Nahmias RL, Karetzky M. Right ventricular dysfunction in obstructive sleep apnea: reversal with nasal continuous positive airway pressure. Eur Respir J. 1996;9:945-951.
  23. Thomas RJ. The cardiomyopathy of obstructive sleep apnea. Ann Intern Med. 1996;125:425.
  24. Malone S, Liu PP, Holloway R, Rutherford R, Xie A, Bradley TD. Obstructive sleep apnea in patients with dilated cardiomyopathy: effects of continuous positive airway pressure. Lancet. 1991;338:1480-1484.
  25. Zohar Y, Talmi YP, Frenkel H, et al. Cardiac function in obstructive sleep apnea patients following uvulopalatopharyngoplasty. Otolaryngol Head Neck Surg. 1992;107:390-394.
  26. Naughton MT, Bernard DC, Liu PP, Rutherford R, Rankin F, Bradley TD. Effects of nasal continuous positive airway pressure on sympathetic activity in patients with heart failure and central sleep apnea. Am J Respir Crit Care Med. 1995;152:473-479.
  27. Grimm W, Hoffmann J, Menz V, et al. Electrophysiologic evaluation of sinus node function and atrioventricular conduction in patients with prolonged ventricular asystole during obstructive sleep apnea. Am J Cardiol. 1996;77:1310-1314.
  28. Randazza DN, Winters SL, Schweitzer P. Obstructive sleep apnea-induced supraventricular tachycardia. J Electrocardiol. 1996;29:65-67.
  29. Hoffstein V, Mateika S. Cardiac arrhythmias, snoring and sleep apnea. Chest. 1994;106:466-471.
  30. Sch„fer H, Koehler U, Ploch T, Peter JH. Sleep-related myocardial ischemia and sleep structure in patients with obstructive sleep apnea and coronary heart disease. Chest. 1997;111:387-393.
  31. Dyken ME, Somers VK, Yamada T, Ren ZY, Zimmerman MB. Investigating the relationship between stroke and obstructive sleep apnea. Stroke. 1996;27:401-407.
  32. Pressman MR, Schetman WR, Figueroa WG, Uitert BV, Caplan HJ, Peterson DD. Transient ischemic attacks and minor stroke during sleep. Relationship to obstructive sleep apnea syndrome. Stroke. 1995;26:2361-2365.
  33. R†ngemark C, Hedner JA, Carlson JT, Gleerup G, Winther K. Platelet function and fibrinolytic activity in hypertensive and normotensive sleep apnea patients. Sleep. 1995;18:188-194.
  34. Krieger J, Benzoni D, Sforza E, Sassard J. Urinary excretion of prostanoids during sleep in obstructive sleep apnea patients. Clin Exper Pharmacol Physiol. 1991;18:151-155.
  35. Franklin KA, Eriksson P, Sahlin C, Lundgren R. Reversal of central sleep apnea with oxygen. Chest. 1997;111:163-168.
  36. Javaheri S, Parker TJ, Wexler L, Liming JD, Lindower P, Roselle GA. Effect of theophylline on sleep-disordered breathing in heart failure. N Engl J Med. 1996;335:562-567.
  37. Sepp„l„ M, Pentill„ A, Aspholm R, Tiainen E, Kaukianen A. Sudden death and sleeping history among Finnish men. J Int Med. 1991;229:23-28.
  38. Hanly P, Zuberi KN. Daytime sleepiness with congestive heart failure and Cheyne-Stokes respiration. Chest. 1995;107:952-958.
  39. Naughton MT, Liu PP, Benard DC, Goldstein RS, Bradley TD. Treatment of congestive heart failure and Cheyne-Stokes respiration during sleep by continuous positive airway pressure. Am J Respir Crit Care Med. 1995;151:92-97.
  40. Andreas S, Clemens C, Sandholzer H, Figulla HR, Kreuzer H. Improvement of exercise capacity with treatment of Cheyne-Stokes respiration in patients with congestive heart failure. J Am Coll Cardiol. 1996;27:1486-1490.
  41. Stevenson EW, Turner GT, Sutton FD, Doekel RC, Pegram V, Hernandez J. Prognostic significance of age and tonsillectomy in uvulopalatopharyngoplasty. Laryngoscope. 1990;100:820-823.
  42. Stoohs RA, Bingham L, Itoi A, Guilleminault C, Dement WC. Sleep and sleep-disordered breathing in commercial long-haul truck drivers. Chest. 1995;107:1275-1282.