Cardiopulmonary responses to exercise in moderate-to-severe obstructive sleep apnea

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Yazışma Adresi (Address for Correspondence):

Dr. Levent ÖZTÜRK, Trakya Üniversitesi Tıp Fakültesi, Fizyoloji Anabilim Dalı, Güllapoğlu Yerleşkesi 22030 EDİRNE - TURKEY

moderate-to-severe obstructive sleep apnea

Levent ÖZTÜRK¹, Gökhan METİN², Çağlar ÇUHADAROĞLU³, Ayfer UTKUSAVAŞ³, Bülent TUTLUOĞLU⁴

1Trakya Üniversitesi Tıp Fakültesi, Fizyoloji Anabilim Dalı, Edirne, 2İstanbul Üniversitesi Cerrahpaşa Tıp Fakültesi, Fizyoloji Anabilim Dalı, 3İstanbul Üniversitesi İstanbul Tıp Fakültesi, Göğüs Hastalıkları Anabilim Dalı,

4İstanbul Üniversitesi Cerrahpaşa Tıp Fakültesi, Göğüs Hastalıkları Anabilim Dalı, İstanbul.

ÖZET

Orta ve ileri derece obstrüktif uyku apne sendromunda egzersize kardiyopulmoner yanıtlar

Obstrüktif uyku apne (OSA) hastalarında egzersiz kısıtlılığının mekanizmaları ve maksimal kardiyopulmoner egzersiz tes- ti (KPET)’nin güvenilirliği konusunda mevcut bilgi oldukça sınırlıdır. Bu çalışmada, orta-ileri derece OSA hastalarında eg- zersiz kapasitesinin değerlendirilmesi amaçlanmıştır. Ondokuz OSA hastası (üç kadın, 16 erkek) ile yaş ve vücut kitle in- deksi bakımından benzer 11 gönüllü kontrol grubu (dört kadın, yedi erkek) egzersiz öncesi istirahat döneminde solunum fonksiyon testi ve daha sonra bisiklet ergometresinde maksimal KPET’ye alındı. Tüm çalışma grubu KPET’yi komplikas- yonsuz tamamladı. Kontrol grubunda kondisyon eksikliğine bağlı egzersiz sınırlanması saptandı. Hasta grubunda egzer- siz süresince ventilasyonda mekanik sınırlanma ya da kardiyak iskemi lehine bulgu saptanmadı. Beş hastada egzersiz sınırlanması yoktu; altı hastada ventrikül disfonksiyonu ile uyumlu olduğu düşünülen düşük VO_2peak, düşük anaero- bik eşik ve düşük oksijen nabzı gözlendi. Diğer altı hastada ise periferik damar hastalığını düşündüren düşük VO_2peak, düşük anaerobik eşik ve hesaplanan maksimum kalp tepe atımının %85’inden daha düşük kalp tepe atımı saptandı. İki hastada ise kondisyon düşüklüğü ile uyumlu olarak düşük VO_2peak, düşük anaerobik eşik ve maksimal egzersiz düze- yinde normal sınırlarda oksijen nabzı ve kalp tepe atımı gözlendi. Orta-ileri derece OSA hastalarında egzersiz kapasitesi düşüklüğünün daha sıklıkla ventrikül disfonksiyonu ya da periferik damar hastalığı gibi kardiyovasküler nedenlerden kaynaklanabileceği ve bu hasta grubunda maksimum KPET’nin ciddi komplikasyonlara neden olmadan tolere edilebile- ceği sonucuna varıldı.

Anahtar Kelimeler: Egzersiz testi, maksimum oksijen tüketimi, bisiklet ergometresi, uyku apnesi.

SUMMARY

Cardiopulmonary responses to exercise in moderate-to-severe obstructive sleep apnea

Ozturk L, Metin G, Cuhadaroglu C, Utkusavas A, Tutluoglu B

Department of Physiology, Faculty of Medicine, Trakya University, Edirne, Turkey.

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Obstructive sleep apnea (OSA) refers to the oc- curence of recurring complete or partial inter- ruptions of breathing during sleep. OSA is associated with increased risk for cardiovascular diseases including hypertension, myocardial isc- hemia and left ventricular hypertrophy (1-3).

Untreated OSA patients may have increased mortality rates (4). The two most commonly accepted interventions in the management of OSA include nasal continuous positive airway pressure (CPAP) usage during sleep and surgery. More recently the long-term efficacy and therapeutic effectiveness of these approaches have been questionned, but remain the best options ava- ilable today (5). Hence, there is a clear need for alternative or adjunct treatment strategies. The effects of exercise or fitness on sleep have been studied extensively and it may be important in improving perception of energy and vitality in OSA population (6,7). A recent study demonstrated beneficial effects of exercise conditioning programs in treatment of OSA (8). Some others reported that effective treatment with CPAP imp- roved exercise performance and cardiopulmonary indices in OSA patients (9,10). However, information concerning exercise characteristics of OSA patients is fairly limited in the published literature. Interest in the exercise responses in OSA is both clinically relevant to discerning pre- diction of the mortality from cardiovascular disease and physiologically relevant to understanding the adaptive changes that occur in respon-

se to hypoxia-reoxygenation episodes during sleep. Furthermore, better understanding of OSA-associated decrements in exercise capacity is important as weight management is a cri- tical issue for sleep apnea patients.

In the present study, we assessed the cardiopulmonary responses to exercise in moderate-to- severe OSA patients. We addressed the questi- ons whether exercise capacity is decreased among these patients; whether there is a cardiovascular or pulmonary limitation to exercise;

and whether these patient group can tolerate a maximal exercise test without complications.

MATERIALS and METHODS Subjects

Subjects were 19 non-consecutive OSA patients (three female, 16 male) referred for polysom- nographic evaluation to the Sleep Disorders Unit, Istanbul University Istanbul Faculty of Me- dicine, Istanbul. After an overnight polygraphic sleep study, patients with apnea-hypopnea index (AHI) > 5 were asked to undergo maximal cardiopulmonary exercise testing (CPET). Exc- lusion criteria were a history of regular sportive activities, previous treatment for sleep apnea, and previously diagnosed cardiopulmonary disease. Patients with a limitation in range of mo- tion in ankle, knee, and hip joints were also exc- luded. Prior to testing, all subjects were given written informed consent. None of the patients were on β-blockade or any other drug treatment.

Information regarding the safety of maximal cardiopulmonary exercise testing (CPET) or the mechanisms of exercise limi- tation in obstructive sleep apnea (OSA) patients is fairly limited. In the present study, we addressed the problem of exerci- se capacity in moderate-to-severe OSA patients. Nineteen non-consecutive patients (three female, 16 male) with moderate- to-severe OSA and 11 age and body mass index matched control subjects (four female, seven male) underwent respiratory function tests during pre-exercise resting period and volitionally limited cardiopulmonary exercise testing on an electroni- cally braked cycle ergometer. All participants completed CPET without any complication. Control subjects were exercise li- mited due to deconditioning. None of the patients revealed mechanical ventilatory limitation to exercise or had evidence of cardiac ischaemia. Five patients had no limitation to exercise. Six patients had low VO_2peak, low anaerobic treshold (AT), and low peak O₂pulse, a pattern consistent with ventricular dysfunction. Six patients had low VO_2peak, low AT, and pe- ak heart rate less than 85% predicted. This pattern is consistent with exercise limitation due to peripheral vascular disease.

Two patients had low VO_2peak, low AT without peak oxygen pulse and peak heart rate abnormalities consistent with de- conditioning. We concluded that moderate-to-severe OSA patients have impaired exercise capacity. Exercise limitation se- ems to originate from cardiovascular reasons namely left ventricular dysfunction and/or peripheral vascular impairment;

and finally, maximal CPET can be tolerated by these patient group without serious complications.

Key Words: Exercise testing, maximal oxygen consumption, cycle ergometer, sleep apnea.

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Eleven untrained healthy volunteers (four female, seven male) without a history of snoring, wit- nessed apneas and excessive daytime sleepiness were recruited as a control group for exercise testing. Sleep studies were not performed for the control subjects; none were thought to have cardiorespiratory disorders and any symp- toms indicating sleep disturbance.

The activity levels in the patient and control groups were determined by self report. Participants were asked whether they did any regular exerci- ses, sports or physically active hobbies previously and for each activity, the number of times and minutes of duration. All patients and cont- rols were considered sedentary; exercising less than three times per week for at least 30 minute per session according to the U.S. Surgeon Gene- ral’s Report Guidelines (11).

Sleep Study

Overnight sleep studies were performed by using computerized polysomnography system (Somnologica Embla, Iceland) in all patients with a clinical suspicion of OSA. Polygraphic re- cordings were included 2-channel electroencep- halography (C4-A1, C3-A2), left and right elect- rooculography, chin electromyography. Thora- coabdominal movements were monitored with thoracic and abdominal strain gauges. Airflow was monitored with an oro-nasal thermistor. Ar- terial oxyhaemoglobin saturation was recorded using a pulse oximeter. Sleep staging was ma- nually performed in 30-second epochs following the standard guidelines (12). An episode of obstructive apnea was defined as the absence of airflow for at least 10 seconds in the presence of rib-cage and abdominal excursions. Hypopnea was defined as a 50% reduction in airflow with respect to baseline lasting 10 seconds or more and associated with at least a 4% decrease in arterial oxyhaemoglobin saturation, an electroen- cephalographic arousal or both (13). The number of episodes of apnea and hypopnea per hour was referred to as the apnea-hypopnea index (AHI). Individuals with an AHI greater than 5 were defined as having OSAS. An AHI between 5- 20 indicated mild OSAS, 21-30 moderate OSA and over 30 severe OSAS.

Exercise Testing

The physician who performed the CPETs was not aware of the sleep status of the patient. Each subject first underwent a comprehensive physical examination which included a 12 lead elect- rocardiogram (ECG) recording and blood pressure measurement at rest. Subjects had a light breakfast 2 hours before exercise and abstained from strenuous exercise for a week prior to CPET. They performed pulmonary function tests before exercise test. All tests were performed in an air-conditioned laboratory room at 20-22°C and 40% relative humidity air to minimize ther- mal stress.

The subjects exercised on an electronically braked cycle ergometer (ercometrics 800, ergoline, Germany) at an initial work-rate of 20 watts, which was increased by 20 watts, at the end of each step lasting for 2 minutes. Prior to testing the subjects were acclimated to the cycle ergometer with a 2-min warm up period. The pedal rate was maintained constant at 70 rpm throug- hout the test. Each test was terminated by subject fatigue or maximal exercise level. It was considered maximal level if the subject achieved two of three following test criteria:

1. A respiratory exchange ratio (RER) of 1.10 or higher,

2. Heart rate reaching 80% of age-predicted maximal heart rate, and

3. Plateau of oxygen consumption with increasing work load.

Predicted maximal heart rate (HRmax) was calculated by using the following formula (HRmax

= 220 - age). Age and gender specific maximal predicted values of remaining exercise parameters were calculated according to American Thoracic Society (ATS)/American College of Chest Physicians (ACCP) statement on CPET, and are reported as percent predicted (14). Du- ring CPET, continuous six-lead ECG and heart rate were monitored. Blood pressure was measured every two minutes using standard cuff manometry (ERKA, Germany) at a measurement accuracy of 2 mmHg.

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Direct Measurements of Maximal Oxygen Uptake

Peak VO₂was determined from expired gas measurements during test. O₂and CO₂were analyzed breath-by-breath on a metabolic cart (Vmax 29c, Sensormedics Corporation, Anaheim, US).

The system was calibrated before each test with standard gases of known O₂ and CO₂concent- rations. The most elevated VO₂ measured over 10 seconds during the last minute of the exercise was considered as the VO_2peak. In order to determine anaerobic threshold (AT), we plotted ventilatory equivalents (V_E) for O₂ and CO₂ against VO₂. The point at which V_E/VO₂increased without an increase in V_E/VCO₂ was accepted as the AT (15).

Statistical Analysis

All data analyzed in SPSS 11.0 for Windows. Va- lues are given as means ± Standard Deviation

(SD). Unpaired t-tests were used to compare results from OSA and control subjects. Paired t-tests were performed to compare measured CPET parameters with predicted normal values.

A probability value of 0.05 was accepted as sta- tistically significant.

RESULTS

Study group included three female and sixteen male patients in OSA group and four female and seven male subjects in the control group. Patient and control groups were age (46.9 ± 8.6 years and 40.6 ± 8.4 respectively; p> 0.05) and body-mass index (BMI) (30.7 ± 4.6 and 28.9 ± 3.0 respectively; p> 0.05) matched. The AHI averaged 46 ± 19 hour^-1for OSA patients (range 19-78 hour^-1).

Pulmonary Function Tests

Results from pulmonary function testing are given in Table 1. Five patients had evidence for an obstructive impairment (Patient 2, 8, 10, 17,

Table 1. Results of pulmonary function tests in OSA patients.

Patient no FEV₁(L) FVC (L) FEV₁/FVC (%) FEF_25-75% (L/sec) VC (L) MVV (L)

1 3.17 (99) 3.53 (92) 90 4.36 4.15 (104) 165

2 2.82 (80) 4.08 (93) 69 1.81 4.20 (92) 96

3 3.48 (107) 4.70 (116) 74 2.67 4.98 (118) 140

4* 2.34 (93) 3.00 (103) 78 2.24 3.04 (102) 105

5 4.14 (88) 4.76 (85) 87 4.82 5.04 (86) 172

6 2.91 (94) 3.55 (95) 82 3.51 3.73 (96) 93

7* 2.15 (86) 2.67 (91) 81 2.38 2.94 (97) 107

8 2.58 (67) 3.52 (76) 73 1.86 3.98 (82) 66

9 3.46 (102) 4.76 (110) 73 2.49 5.05 (112) 153

10 2.64 (83) 3.82 (98) 69 1.62 4.01 (99) 90

11 2.92 (101) 3.77 (107) 77 2.60 4.05 (111) 114

12 3.95 (103) 5.10 (107) 77 3.72 5.42 (108) 165

13 2.80 (88) 3.38 (87) 83 3.42 3.66 (90) 119

14 2.91 (72) 3.63 (74) 80 2.81 3.80 (74) 98

15 4.16 (101) 4.70 (96) 89 4.81 4.73 (92) 181

16* 2.36 (85) 2.91 (91) 81 2.46 3.01 (92) 103

17 3.16 (100) 4.36 (112) 73 2.32 4.36 (108) 124

18 2.26 (79) 2.96 (85) 76 1.96 2.96 (82) 71

19 3.57 (107) 4.24 (104) 84 4.74 4.44 (104) 134

Values in parentheses are percent of predicted maximal value calculated according to age and gender.

FEV₁: Forced expiratory volume in one second, FVC: Forced vital capacity, FEF: Forced expiratory flow rate, VC: Vital capacity, MVV:

Maximal voluntary ventilation.

* Female patients.

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and 18) whereas one patient (Patient 14) sho- wed restrictive ventilatory impairment. Patients 8, 17 and 18 had obstruction only in small air- ways, whereas Patient 2 and Patient 10 had both small and large airway obstruction.

Cardiopulmonary Responses to Exercise All participants completed the CPET without complications. Results of control subjects were less than predicted and consistent with deconditioning. Comparisons between OSA and control group were shown in Table 2. Detailed results of OSA patients were as follows. None of the patients developed ischemic changes and significant dysrhythmias on ECG. Specific measurements obtained from CPET for each individual are listed in Table 3. Peak exercise heart rate averaged 153 ± 11 beats per minute compared with the average predicted peak heart rate of 179 ± 5 beats per minute. Five of 19 patients re- ached their predicted peak heart rate with a percent predicted less than 10. In thirteen of the remaining patients, a RER value higher than 1.10 was obtained, suggesting that despite an increase in the heart rate reserve (HRR= Predicted heart rate - peak heart rate), the study was maximal. Patient 10 did not meet the criteria for a maximal study.

Results of peak VO₂ measurements are shown in Figure 1. Five patients (1, 3, 4, 10, and 12) were not exercise-limited. Fourteen patients developed abnormal VO₂responses defined by peak VO₂less than 80% predicted. Results of peak VO₂/HR (oxygen pulse) measurements are shown in Figure 2. Only seven patients (see also Table 3) had peak oxygen pulse levels less than 80% of the predicted values. In all patients, measurement of VO₂at anaerobic treshold was

above 40% of the predicted value which is quite normal. VO₂ at anaerobic treshold averaged 1.27 ± 0.34 L/minute, which is 72 ± 9% of predicted values.

Peak minute ventilation averaged 68.1 ± 14.3 L/minute while the calculated breathing reserve [maximal voluntary ventilation (MVV) - peak V_E] averaged 57.9 ± 23.9 L/minute, indicating that none of the patients had a mechanical ventilatory limitation to exercise.

DISCUSSION

The results of this study show that volitionally limited CPET can be safely performed in patients with moderate-to-severe OSA. None of the patients developed ischemic changes and dysrhythmias on ECG, although most of the patients had an AHI above 30 indicating severe OSA. In a previous study, Aguillard et al. reported that 32 OSA patients participated in a maximal exercise test and twenty-nine of the tests were terminated because of fatigue (16). Two tests were terminated because of respiratory difficulty and one test was terminated due to abnormally elevated blood pressure. None of their patients developed ischemic events. Most of their patients had also moderate-to-severe OSA. They reported that subjective fatigue was not correlated with disease severity. Our data together with the latter result may suggest that disease severity in OSA is not a limiting factor for CPET.

This study confirmed previous findings that in moderate-to-severe OSA patients, exercise capacity is limited as shown by reduced VO_2peak levels. However, this was made for the first time in an attemp to identify the possible limiting mechanisms. Before making firm conclusions, it should be noted that exercise limitation is most-

Table 2. Comparisons of CPET results between OSA and control groups.

OSA group (n= 19) Control group (n= 11) Significance (unpaired t-test)

Endurance time, minute 688 ± 153 747 ± 307 p> 0.05

O₂pulse, mL/beat 11.3 ± 2.5 11.2 ± 2.8 p> 0.05

VO₂max, mL/kg/minute 19.8 ± 3.1 21.8 ± 5.9 p> 0.05

VO₂max, L/minute 1.73 ± 0.37 1.76 ± 0.59 p> 0.05

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Table 3. Results of cardiopulmonary exercise tests in OSA patients.

Patient HRR Peak VO₂ VO₂at AT O₂pulse PETCO₂

no (beats) (L/minute) (L/minute) RER (mL/beat, peak) (mmHg, peak) BR (L)

1 10 2.11 (92) 1.48 (70) 0.98 12.4 (97) 34.9 94.2

2 32 1.85 (77) 1.52 (82) 1.09 12.9 (94) 42.6 34.4

3 26 1.81 (80) 1.54 (85) 1.14 12.1 (94) 30.1 42.7

4* 30 1.54 (97) 1.15 (74) 1.13 10.0 (116) 37.8 45.1

5 17 2.25 (64) 1.61 (71) 1.13 12.8 (70) 33.8 77.7

6 32 1.47 (65) 1.18 (80) 1.14 9.8 (79) 36.7 28.9

7* 15 1.05 (72) 0.82 (78) 1.03 6.5 (79) 32.7 61.0

8 35 1.90 (69) 1.35 (71) 1.19 12.8 (85) 36.0 83.6

9 27 1.59 (76) 0.91 (57) 1.11 11.1 (90) 35.9 91.4

10 33 2.07 (92) 1.65 (79) 1.06 14.3 (112) 44.4 28.6

11 25 1.39 (66) 0.80 (57) 1.16 9.1 (77) 33.8 49.1

12 32 2.33 (90) 1.63 (69) 1.18 16.3 (110) 40.7 85.9

13 26 1.77 (78) 1.44 (81) 1.11 11.6 (91) 34.9 51.4

14 8 1.97 (68) 1.38 (70) 1.11 11.1 (70) 45.0 38.3

15 39 2.23 (73) 1.89 (84) 1.18 14.7 (91) 38.5 98.0

16* 12 1.09 (65) 0.62 (56) 1.26 6.4 (70) 35.1 53.4

17 26 1.45 (66) 1.10 (75) 1.24 9.7 (77) 35.3 60.0

18 33 1.37 (67) 1.04 (75) 1.11 9.6 (82) 39.2 22.0

19 29 1.79 (75) 1.12 (62) 1.19 11.9 (90) 34.0 55.5

Values in parentheses are percent of predicted maximal value calculated according to age and gender. HRR: Heart rate reserve, VO₂: Oxygen uptake, AT: Anaerobic treshold, ETCO₂: End-tidal carbon dioxide.

* Female patients.

Figure 1. (A) Peak VO₂was low and averaged 1.742 ± 0.378 L/minute which was 75 ± 10% of the predicted normal values based on age, sex, and weight, p< 0.001. (B) Measured peak VO₂versus predicted peak VO₂. The solid line represents the line of identity (i.e. values which fall on or above the line would indicate normal pe- ak VO₂). As shown, measured peak VO₂values in 14 of 19 patients with OSA fell below the line of identity in- dicating that these patients had a pathologically low peak VO₂.

A

Peak VO2(L/minute)

Measured Predicted 0.0 1.0 2.0 3.0 4.0

Predicted Peak VO₂(L/minute) 3

2.5

2

1.5

1

0.5

0 Measured Peak VO(L/minute)2

4.0

3.0

2.0

1.0

0.0 B

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ly multifactorial. Consequently, we attempted to determine the potential relative importance of each of the factors involved in the exercise response in these group of OSA patients rather than the single limiting factor. All patients demonstrated either normal or elevated ventilatory reserve at peak exercise, indicating that none had a pulmonary mechanical ventilation limitation to exercise. These findings, together with resting pulmonary function tests, show that pri- mary parenchymal disease cannot explain the reduced exercise capacity in these patients. On the other hand, we observed the following abnormal parameters in most of our patients:

1. A low peak VO₂, 2. A low AT.

In addition, seven patients had a low oxygen pulse below 80% predicted. These abnormalities suggest that exercise limitation might be due to cardiovascular system. Differential diagnosis for these physiologic abnormalities includes ischemic cardiac disease, cardiomyopathy, peripheral vascular disease, and deconditioning. None of the patients had ECG changes suggestive of myocardial ischaemia during exercise. Therefore, it is unlikely that exercise limitation was due to an ischemic cardiac process in any of our patients.

Repetitive obstructive apneas and hypopneas lead to increased negative intrathoracic pressu-

re which increase left ventricular (LV) transmu- ral pressure by increasing the difference between extracardiac and intracardiac pressures, and hence afterload (17). It also increases venous return to the right ventricle. The resulting left- ward shift of the interventricular septum can im- pede LV diastolic filling. Both increased afterload and reduced preload of LV may reduce stroke volume during obstructive apneas (3,18).

However, Parker et al. reported that exaggerated negative intrathoracic pressure does not acutely impair LV contractility when underlying LV function is normal (19). Furthermore, LV systolic dysfunction is a rare complication of OSA with no associated cardiac disease (20). An important limitation of our study is lack of echocardi- ographic evaluation of the patients. This would help to clarify the presence of left ventricular dysfunction and any stroke volume abnormalities of our patients. Nevertheless, peak O₂pulse may be used as a surrogate measure of stroke volume and a low O₂ pulse is consistent with inability to increase the stroke volume during exercise (15). Seven patients (Patients 5, 6, 7, 11, 14, 16, and 17) revealed reduced peak O₂ pulse. A detailed examination of CPET data sho- wed that of the seven patients six had an unchan- ging and flattened O₂pulse response at the ma- ximum work rates suggestive of stroke volume abnormalities besides low VO_2peak, and low AT.

Patient 5 was classified as deconditioned despite low O₂ pulse response. The remaining 12 pati- Figure 2. (A) Peak oxygen pulse measurements averaged 11.3 ± 2.5 mL/beat or 88 ± 13% of the predicted va- lues, p< 0.002. (B) Predicted peak O₂pulse versus measured peak O₂pulse. Peak O₂pulse values of fourteen patients fell below the line of identity, indicating these patients had reduced O₂pulse.

A B

Peak O2(mL/beat)

Measured Predicted 6 8 10 12 14 16 18

Predicted Peak O₂Pulse (mL/beat) 18

16 14 12 10 8 6 4 2

0 Measured Peak OPulse (mL/beat)2

18

16

14

12

10

8

6

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ents had peak O₂pulse levels above 80% of their predicted values indicating exercise limitation in these patients was unlikely due to reduced stroke volume or left ventricular dysfunction. This group of patients revealed two types of patterns:

1. Normal peak VO₂(n= 5); and

2. Low peak VO₂, low AT, a high ventilatory reserve and high heart rate reserve (n= 7).

In patients with peripheral vascular disease, an inappropriately high heart rate reserve rather than low HRR is expected. Therefore, it seems possible that these latter seven patients were exercise-limited due to peripheral vascular disease (Table 4). What are the potential mechanisms of peripheral vascular disease in patients with OSA? There is a strong linkage between hypertension and sleep apnea (1). On the other hand, increased sympathetic nerve activity which accompany OSA may be independently implicated in atherosclerotic vascular disease (21). Remarkably, the high sympathetic drive is

present even during daytime wakefulness when subjects are breathing normally and both arterial oxygen saturation and carbon dioxide levels are also normal (22). Combination of the effects of hypertension and increased sympathetic drive may be responsible for peripheral vascular disease. It is further suggested that chronic hypoxic stress may contribute to development of peripheral vascular disease by inducing endothelial dysfunction and irreversible remode- ling of the vasculature and surrounding tissues (23,24). A recent study demonstrated attenu- ated endothelium-dependent vasodilation of re- sistance vessels in OSA patients in the absence of overt cardiovascular disease (23).

The present study has several limitations that deserve comment. Unfortunately, we did not perform arterial blood gas measurements. This would obtain important evidence on gas exchange and ventilation-perfusion mismatching.

Thus, we could eliminate pulmonary vascular diseases as a potential factor for exercise limita-

Table 4. Summary of interpretation of CPET in OSA.

Patient Maximal Peak VO₂ VO₂at AT Peak O₂pulse Peak HR Possible reason no effort* < 80% pred. < 80% pred. < 80% pred. < 85% pred. for limitation

1 + - + - - No limitation

2 + + + - + Peripheral vascular

3 + - + - - No limitation

4 + - + - + No limitation

5 + + + + - Deconditioning

6 + + + + + Impaired SV

7 + + + + - Impaired SV

10 - - + - + No limitation

12 + - + - + No limitation

13 + + + - - Deconditioning

* Defined in results section.

AT: Anaerobic treshold, HR: Heart rate, SV: Stroke volume.

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tion. The limited number of patients may avoid extrapolation of the results. It can be questioned whether these data are applicable to large mem- ber of OSA patients. Our study group consisted of moderate-to-severe OSA patients. It is obvi- ous that mild OSA patients with AHI < 20 may have better exercise capacity.

Conclusions

The findings from the present study suggest that 1. Moderate-to-severe OSA patients have impaired exercise capacity;

2. The reasons for exercise limitation seems to be cardiovascular diseases namely left ventricular dysfunction and/or peripheral vascular disease; and

3. Moderate-to-severe OSA patients can tolerate maximal CPET without serious complications (2,3).

ACKNOWLEDGEMENTS

Special thanks to Dr. Carl Mottram for careful re- view of and comments on the manuscript.

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