Exercise-based rehabilitation improves skeletal muscle capacity, exercise tolerance, and quality of life in both women and men with chronic heart failure

Journal of Cardiac Failure Vot. 4 No. 1 1998

Exercise-Based Rehabilitation Improves Skeletal Muscle Capacity, Exercise Tolerance, and Quality of Life in Both Women and Men With Chronic Heart Failure RAIJA

TYNI-LENNt~, EEVA

EUROPE,

PT, MSc,* ALLAN

GORDON,

PT,* EVA JANSSON,

CHRISTER

MD, PhD,*

MD, PhD,*

SYLVI~N, MD, PhDt

Huddinge, Sweden

ABSTRACT Background: Data of training effects in chronic heart failure patients are based on findings in men. The purpose of this study was to compare the effects of skeletal muscle endurance training between men and women with chronic heart failure. Methods and Results: Twelve consecutive men (mean [_+ SD] age 58 _+ 9 years, left ventricular ejection fraction 29 _+ 9%) and 12 women (60 +- 10 years, left ventricular ejection fraction 28 _+ 7 %) with moderate, chronic heart failure stratified according to age and inclusion criteria were investigated at baseline and after 8 weeks of knee extensor endurance training. The activity of skeletal muscle citrate synthase and resting heart rate were similar in men and women at baseline and with training improved (P < .0001) similarly in both genders. Peak work rate (P < .0001), peak oxygen uptake (P < .001) and muscle strength (P < .05) at baseline were higher in men than in women. Training improved peak work rate (P < .0001) and muscle strength (P < .0001) similarly in both genders, while improvement in peak oxygen uptake was better in women (P < .001). The distance ambulated during 6 minutes was similar in both genders at baseline and increased after training more in men (P < .004). The overall and physical Sickness Impact Profile indicated similarly reduced health-related quality of life in men and women, while worse psychosocial quality of life was observed in men (P < .05). Both genders improved after exercise training in the overall, physical, and psychosocial Sickness Impact Profile (P < .01). Conclusions: Exercise-based rehabilitation improves skeletal muscle capacity, exercise tolerance, and the health-related quality of life in women as well as in men with moderate, chronic heart failure. Key words: chronic heart failure, exercise, gender, rehabilitation, quality of life.

From the Departments of *Physical Therapy, ~Cardiology, and ~Clinical Physiology, the Karolinska Institute and Huddinge University Hospital, Huddinge, Sweden. Supported by grants from the National Board of Health and Weltare and the Medical Research Council (4494 and 9515), Sweden. Manuscript received October 7, 1997; revised manuscript received December 30, 1997; revised manuscript accepted January 3,1998. Reprint requests: Raija Tyni-LennC PT, MSc, Department of Physical Therapy, Huddinge University Hospital, S-14 186 Huddinge, Sweden, e-mail: [email protected] Copyright © 1998 by Churchill Livingstone ® 1071-9164/98/0401-000358.00/0

D e s p i t e advances in treatment, m e n and w o m e n with s y m p t o m a t i c heart failure continue to have high mortality and m o r b i d i t y (1-3) and these patients suffer from progressively worsening exercise intolerance and quality of life (4-6). A l t h o u g h the incidence of heart failure is higher in m e n than in women, the prevalence is a b o u t the same in all age groups in b o t h genders (2). Exercise training has been r e p o r t e d to improve skeletal muscle capacity, exercise tolerance, and the quality of life in male patients with chronic heart failure ( C H F )

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Journal of Cardiac Failure Vol. 4 No. 1 March 1998

(6-8), and the major training effects have been suggested to be due to peripheral adaptations (7-11). Clinical investigations suggest that survival and response to therapy may differ in men and women with cardiovascular disease (3,12), while similar responses to exercisebased rehabilitation have been reported in male and female patients with coronary artery disease (CAD) (1315). To our knowledge, no data comparing exercise responses in men and women with CHF have been published. The purpose of the present study was to compare the effects of exercise training in men and women with moderate, CHF applying endurance training of leg muscles as an exercise mode.

Materials and Methods Patients Twelve consecutive male and 12 female patients with moderate, C H F stratified according to age and inclusion criteria gave their informed consent to participate in the present trial approved by the local Ethics Committee. The inclusion criteria were stable New York Heart Association (NYHA) functional class II and class III CHF for at least 3 months before the study; an echocardiographically determined ejection fraction at rest of less than 40%; and medication with diuretics, angiotensinconverting enzyme inhibitors, and beta-blockers. The exclusion criteria were angina pectoris, valvular heart disease determined by Doppler echocardiography, intermittent claudication, diabetes mellitus, chronic obstructive pulmonary disease, or any other disorder limiting physical performance other than heart failure. Before the study, all the patients had had ordinary medical care and counseling concerning drug use, diet, alcohol consumption, smoking, and physical activities. The patients were encouraged not to change their lifestyle during the study and were familiarized with the testing and training procedures during two baseline hospital visits. Data were collected under standardized conditions before and after the training period.

Training Protocol Supervised endurance training of knee-extensor muscles with the two legs simultaneously (6) was performed as outpatient activity in a group of men or women for 15 minutes, three times a week for 8 weeks. The intensity during the first 4 weeks was 65 % and during the last 4 weeks 75% of the absolute baseline peak work rate at the accuracy of 5 W. Each training session also included stretching of leg muscles and 6 minutes of walking as a warm-up activity and 3 minutes of walking and stretching as a cool-down activity.

Skeletal Muscle Biopsy Tissue samples were obtained from the lateral portion of the quadriceps femoris muscle using the percutaneous needle biopsy technique (16). The samples were frozen in isopentane, precooled in liquid nitrogen, and stored at -80°C until analyzed. The frozen samples were mounted in an embedding medium (O. C. T. compound Tissue-Tek, Lab-Tek Products, Naperville, IL). Serial transverse sections (10 txm) were cut using a microtome at -20°C, then freeze-dried and inspected under a dissection microscope at a humidity of less than 40% and a temperature of 22°C. Clearly visible areas of blood, fat, or connective tissue were removed. The sections were weighed on a Cahn electrobalance and ultrasonically homogenized in ice-cooled 0.1 mol/L phosphate buffer with 0.05 % bovine serum albumin (300 Ixg dry muscle to 150 txL buffer). The homogenate was analyzed for protein content after adding an aliquot to 0.1

Table 1. B a s e l i n e C h a r a c t e r i s t i c s of M a l e and Female Study Patients Men

Women

(n = 12)

(n = 12)

58 + 9

60 + 10

(56)

(63)

Height (cm)

178 -+ 0.1 (178)

165 --- 0.1" (165)

Weight (kg)

85 ± 16 (84)

74 ± 9* (76)

BMI

27 + 5 (26)

27 ~+ 4 (28)

LVEF (%)

29 _+ 9 (30)

28 -+ 7 (28)

6/6

6/6

48 ± 38 (36)

35 ± 31 (24)

6 6

7 5

11 4

10 5 1 4 11 2 2

Age (yr)

N Y H A II/III Duration of CHF (months) Etiology of CHF Coronary artery disease and hypertension Dilated cardiomyopathy Medication A C E inhibitors Beta-blockers Calcium antagonists Digoxin Diuretics Warfarin Estrogen Occupational status Retired due to age Retired due to illness Employed Housewife

7 12 2

2 4 6

NYHA, New York Heart Association functional class; BMI, body mass index; LVEE left ventricular ejection fraction; ACE, angiotensinconverting enzyme; CHF, chronic heart failure. *P < .05 between the groups. Data presented are mean value ± SD and (median) number of patients.

Exercise Effects in Women and Men With CHF

•

Tyni-Lenne et al.

11

Table 2. Skeletal Muscle Capacity Pretraining

Enzyme activity Citrate synthase 0xkat/g pr) Phosphofructokinase (p&at/g pr) Isokinetic muscle strength Peak torque 90°/s (Nm) Peak torque 180°/s (Nm)

Posttraining

Gender Effect on Training Effect P Value

Men

Women

P Value

Men

Women

Training Effect PValue

0.58 ÷ 0.1 1.54 -+ 0.5

0.57 -+ 0.1 0.89 -+ 0.4

NS <.002

0.78 m 0.1 1.54 -+ 0.4

0.78 -+ 0.2 1 +- 0.3

<.0001 NS

NS NS

126 -+ 48 85 -+ 40

80 -+ 22 58 -+ 14

<.006 <.04

141 +- 41 102 +- 34

93 -+ 27 68 -+ 18

<.0001 <.0001

NS NS

Data presented are mean value _+ SD. Training effect, pretraining to posttraining change; ixkat, ~moi/s; gpr, gram protein.

mol/L potassium hydroxide (17) and analyzed for citrate synthase (18) and phosphofructokinase activity (19).

Muscle Strength Measurements The peak torques (Nm) of concentric knee extensions were measured with a Cybex isokinetic dynamometer (Lumex Inc., Bay Shore, NY) (20). Four maximal voluntary extensions/flexions were carried out at velocities of 90 degrees/s and 180 degrees/s. After calibration of the dynamometer, subjects were seated in the dynamometer chair, and the thigh, pelvis, and chest were stabilized with straps. The input axis of the dynamometer was aligned with the axis of rotation of the knee joint (the lateral femoral epicondyle), and the lower leg was attached to the lever arm by a cuff proximal to the lateral malleolus. The alignment was duplicated in repeated tests by recording the length of the lever arm, elevation of the dynamometer head, and table and seat positions for each subject.The highest peak torque of the four extensions was considered to be a measure of maximal voluntary muscle strength.

Peak Exercise Capacity and Walk Tests A symptom-limited incremental test consisting in bilateral knee-extensor exercise was performed on the knee-extensor ergometer to assess the peak work rate and peak oxygen uptake. Workload was increased by 10 W at 1-minute intervals to exhaustion. A continuous respiratory gas analysis was recorded by calibrated equipments (Oxycon, Minjurd, The Netherlands or Ametek, Thermox Instr. Div., Pittsburgh, PA). The distance ambulated in a standardized 6-minute corridor walk test (21) was measured, and the heart rate (Sport Tester, Polar Electro Oy, Kempele, Finland) and the perceived exertion rated on the Borg Rate of Perceived Exertion Scale (22) at the end of the walk test were recorded.

Blood Measurements Blood samples were taken from an antecubital vein at rest before and after submaximal exercise and during the 15 minutes of exercise on the knee-extensor ergom-

Table 3. Exercise Tolerance Pretraining

Gender Effect on Training Effect P Value

Men

Women

P Value

Men

Women

Training Effect P Value

Knee-extensor exercise test Peak work rate (W) Peak VO2 (L/rain) Peak VO2 (mL/kg/min)

57 -+ 16 1.10 +- 0.3 13.1 -+ 2.9

31 -+ 9 0.69 -+ 0.1 9.2 -+ 2.2

<.0001 <.001 <.001

81 -+ 20 1.13 -+ 0.3 13.4 _+ 2.7

50 -+ 10 0.85 -+ 0.1 11.4 -+ 2.2

<.0001 <.0001 <.0001

NS <.001 F <.007 F

Six-minute walk test Distance (m) Gait velocity (m/s) Borg RPE in gait (score) Heart rate in gait (beats/min) Resting heart rate (beats/min)

471 1.3 12 105 76

466 1.3 15 110 78

NS NS <.001 NS NS

533 1.5 13 124 73

496 1.4 14 116 70

<.0001 <.0001 NS <.0001 <.0001

<.004 M <.004 M NS <.01 M NS

_+ 40 -+ 0.1 -+ 2 _+ 16 -+ 10

_+ 84 -+ 0.2 -+ 2 _+ 22 -+ 11

Posttraining

_+ 45 -+ 0.1 -+ 2 _+ 15 -+ 10

_+ 75 +- 0.2 -+ 2 _+ 21 -+ 8

Data presented are mean value ± SD. Training effect, pretraining to posttraining change; F, women improved but not men; M, men improved but not women; RPE, rate of perceived exertion.

12

Journal of Cardiac Failure Vol. 4 No. 1 March 1998

Men

Women

6.0-

6.0-

5.5-

5.5"

5.0-

5.0-

4.5-

4.5-

4,0"

o E E o -~ -o o o m

._1 o E E o

3.53.02.5-

"5

2.0-

o o nn

1.5-

4.03.53.02.52.01.5-

1.0-

1.0-

0.5-

0.5-

0.0

I

I

0

5

I

10

I

15

l

5 after Exercise time (min)

0.0

I

I ~

pre A post

I

I

0

5

I

10

I

15

I

5 after

Exercise time (min)

Fig. 1. Blood lactate concentrations in men and women during submaximal exercise and at rest before and after exercise at baseline (square) and after the training period (triangle). Training decreased lactate level (P < .0001) in men and women with a trend (P < .07) toward a gende!!re!ated difference in the effect.

eter at a work rate of 65% of the absolute baseline peak work. The blood lactate concentration was determined in neutralized perchloric acid extracts by an enzymatic fluorometric technique (23) and the plasma norepinephfine concentration by electrochemical detection by highperformance liquid chromatography (24).

Quality of Life M e a s u r e m e n t s Self-reported data on the perceived quality of life were collected by means of two questionnaires: the Sickness Impact Profile (SIP) (25) and the Sense of Coherence (SOC) scale (26,27). The validity and reliability of these instruments have been tested in a normal population and in patients with a variety of chronic diseases (28). The SIP is suggested to measure health- or illnessrelated quality 0f life, and the SOC scale assesses prerequisites for:coping capacity and indicates the general quality of life (29). The SIP scores were calculated for each SIP subscale and for the overall as well as physical and psychosocial dimensions of the SIP. Lower SIP scores and higher S O C scores are indicative of a better quality of life.

Subjective data on general training effects were collected by a semistructured interview. The interviews were tape-recorded, transcribed, and analyzed by two independent investigators.

Statistical Analysis Three-factor (training pre/post, time, gender) and/or two-factor (training pre/post, gender) analyses of variance for repeated measures in, two independent groups were used to analyze the physiological responses, and Student's unpaired t test was used to compare baseline characteristics in the groups. For quality of life parameters, the Mann-Whitney rank-sum test and Wilcoxon's signed rank sum test were used, as these parameters are not considered to be normally distributed. Statistical significance was defined as P < .05.

Results Patient characteristics did not differ significantly between men and women other than body height and weight

Exercise Effects in Women and Men With CHF • Tyni-Lenne et al. 13

Women

Men 12.5-

._1 0

12.5-

._1

10.0-

0

E e-

E ee-

x= Q.

10.0-

cS..

e-

7.5-

e-

7.5-

e-

.m

Q.

O

t-

O

r-

5.0-

E ffl

E

ft.

n

5.0-

2.5-

2.5-

0.0-

0.0 1;

1'5

1'0

pre

,L post

Exercise time (min)

1'5

Exercise time (min)

Fig. 2. Plasma n o r e p i n e p h r i n e c o n c e n t r a t i o n s in m e n and w o m e n patients b e f o r e and during submaximal exercise at baseline (square) and after the training p e r i o d (triangle). Training d e c r e a s e d n o r e p i n e p h r i n e c o n c e n t r a t i o n ( P < .0006) similarly in m e n and women.

(Table 1), which did not change during the study period. The pharmacological treatment remained stable during the study period, and all the patients who entered the study completed it. Compliance, assessed as a percentage of the total number of training sessions attended, ranged from 86% to 100% with no gender-related differences. One of the male patients was excluded in the blood analysis because of a blood sample failure.

Skeletal Muscle Capacity

Baseline skeletal muscle oxidative capacity, assessed as the activity of citrate synthase, was similar at baseline in both genders and increased (P < .0001) after the training in both men (35%) and women (37%) with nonsignificant gender-related differences (Table 2). Glycolytic capacity, assessed as phosphofructokinase activ-

T a b l e 4. Quality of Life

Pretraining

Posttraining

Men

Women

(P Value)

Men

Women

(PValue)

Men (P Value)

Women (P Value)

11 (3-39) 5 (0-24) 9 (0-55) 147 (106-175)

10 (0 17) 7 (0-15) 3 (0-16) 158 (122-186)

NS NS <.04 NS

7 (1-27) 3 (0-18) 4 (0-35) 145 (116-190)

5 (0-11) 4 (0-13) 1 (0-9) 162 (126-192)

NS NS <.03 NS

<.002 <.008 <.008 NS

<.005 <.003 <.003 <.03

Gender

SIP Overall (1) Physical (0) Psychosocial (0) SOC (151)

Training Effect Gender

Data presented are median and (range). Normal values (28) are given in parentheses after the category name. SOC, Sense of Coherence; SIP, Sickness Impact Profile.

14 Journalof Cardiac Failure Vol. 4 No. 1 March 1998

Men

Women I

Ambulation

I

~Pre

Post

Body care Mobility

Emotional behaviour Alertness behaviour

m

Social interaction Communication Sleep and rest Eating Home management

Work Recreational pastimes

0

10

20

Score

I

I

30

40

0

10

20

Score

Fig. 3. The Sickness Impact Profile Scales for men and women patients. The bars show the median scores for each SIP scale; the black bars before (pre) and the gray bars after (post) the training period. *P < .05 for difference between pre and post values. A median score of zero has been reported in 11 of 12 scales in the normal population (28).

ity, was higher in men (P < .002) and did not change with training (Table 2). The peak torques of the quadriceps muscle at the velocities of 90 degrees/s and 180 degrees/s were higher (P < .05) in men than in women and increased (P < .0001) after training in both men (13% and 20%, respectively) and women (16% and 18%, respectively) with nonsignificant gender-related differences (Table 2).

Exercise Tolerance The baseline peak work rate (P < .0001) and the peak oxygen uptake (P < .001) in the knee-extensor exercise were higher in men than in women (Table 3). The training improved (P < .0001) the peak work rate in both genders while peak oxygen uptake in the knee-extensor

exercise improved significantly (P < .001) only in women. The distance ambulated during 6 minutes was similar in men and in women at baseline, and improvement (P < .0001) after the training was better in men, whereas women scored higher Borg ratings both at baseline (P < .0001) and after training (P < .06) (Table 3). The resting heart rate at baseline and the improvement (P < .0001) after training were similar in both genders (Table 3). Baseline blood lactate (Fig. 1) and plasma norepinephrine levels (Fig. 2) at rest and during submaximal exercise did not differ between genders. Training decreased blood lactate (P < .0001) (Fig. 1) as well as plasma norepinephrine levels (P < .0006) (Fig. 2) in both genders. The increase of lactate and norepineph-

Exercise Effects in Women and Men With CHF Table 5. Subjective Experience of General Training Effects

Men

Women

n

%

n

%

Experienced training effect Positive No effect Negative Categories of positive effects

8 4 0

67 33 0

11 1 0

92 8 0

Physical

8

67

11

92

2

17

8

67

3

25

7

58

2

17

5

42

Easier to walk Less fatigue in physical activities Better fitness Emotional

Feeling happier Feeling more balanced Dares more/better self-confidence Social

Better tolerance for social life Valuable to meet peer patients Other

Have changed motion habits Days feel more meaningful Data are presented as number and percentage. One patient's answer could be categorized in several subcategories. rine (slope of the curve) was higher (P < .0001) for women both before and after training.

Quality of Life The health-related quality of life, assessed as the SIP, was reduced at baseline in both genders compared to the normal population (Table 4, Fig. 3). The men reported a median score of ->9 on eight, and women on four, of the 12 SIP scales (Fig. 3). The overall and physical dimensions of the SIP did not differ between the two genders, all'hough men scored higher than women in sickness impact on the psychosocial health-related quality of life (P < .04) (Table 4) and on the work scale (P < .02) (Fig. 3). The overall, physical, and psychosocial scores of the SIP improved in both genders (Table 4) as well as the scores of several individual scales (Fig. 3). The S O C scores did not differ between men and w o m e n at baseline, but only w o m e n showed improvement following training (Table 4). General training effects reported verbally by the patients could be classified as physical, emotional, social, and other types, such as changed life habits and existence (Table 5). W o m e n reported a higher ratio of positive training effects (P < .05) than men, and none of the patients reported any negative effects attributable to the training (Table 5).

Discussion Information of exercise-based rehabilitation in C H F is based on data from male patients (30), and previous

•

Tyni-Lenne et al.

15

studies have shown that female cardiac patients are not referred to rehabilitation programs as often as men (14). This condition can appear remarkable as exercise training has been found to cause improvements in women as well as in men in a similar disorder, C A D (13-15), and also in healthy population (31-33). Exercise modes activating a more restricted muscle mass than in conventional cardiac rehabilitation may be preferred, especially during an early phase of exercise-based rehabilitation, since it reduces the demand on cardiac work simultaneously with a more efficient distribution of blood flow to the working muscle group. A direct comparison between the efficacy of local muscle group versus treadmill/bicycle training programs in patients with C H F has so far not been reported. This comparative study of the effects of knee-extensor training in C H F patients showed similar or even better improvement in women than in men in skeletal muscle capacity and exercise tolerance. Lower baseline values of the peak work rate, peak oxygen uptake, and muscle strength in women may partly be gender-typical differences, as similar differences have been found between healthy men and women (31-34). However, the studied women might also have been more deconditioned than men, and men might have performed closer to their maximal capacity at baseline. Elevated norepinephrine and blood lactate levels at baseline, and the posttraining decrease of these concentrations in both genders, are in agreement with the findings of previous studies in C H F (35-37). One important factor for the reduced blood lactate concentration demonstrated after the training in both genders was an improved local oxidative capacity in the trained muscles, as citrate synthase activity increased in both genders. Previous studies (10) have demonstrated a reduced activity of citrate synthase in C H F patients. No difference between men and w o m e n was found in this study, and both genders increased citate synthase activity similarly. The adaptive changes in oxidative enzymes are welldocumented consequences of endurance training in a normal population (31). However, because a significant increase of peak oxygen consumption was also observed in female patients, improvement in the integrated circulation cannot be excluded as a contributing factor to decreased blood lactate production after exercise training. This study showed, in agreement with other investigators (38), similarly reduced overall quality of life in men and women with CHF, compared to the normal agematched population. Also, more reduced psychosocial quality of life in men than in women was found as recently suggested by other investigators (38). The greater working disability reported by men might partly explain the lower psychosocial quality of life. The overall, physical, and psychosocial aspects of the reduced quality of life improved after physical training in both genders.

16

Journal of Cardiac Failure Vol. 4 No. 1 March 1998

The baseline SOC scores assessing prerequisites for coping capacity were in line with the findings in n o r m a l population (28) and increased only in women. W o m e n also verbally expressed a higher ratio of positive training effects than men. A l t h o u g h the SOC scores have b e e n proposed to be relatively stable in individuals throughout life (27), there is an increasing agreement that the capacity to cope with stress in general, and chronic illness in particular, affects the experience of life quality (26,27,29). It is concluded that exercise-based rehabilitation in patients with C H F appears to be safe and is as effective in w o m e n as in m e n in terms of improved skeletal muscle capacity, exercise tolerance, n e u r o h u m o r a l response, and the quality of life.

References 1. Gillum RF: Heart failure in the United States 1970-1985. Am Heart J 1987;113:1043-5 2. Ho KKL, Andersson KM, Kannel WB, Grossman W, Levy D: Survival after the onset of congestive heart failure in the Framingham heart study subjects. Circulation 1993;88:107-15 3. Adams KF, Dunlap SH, Sueta CA: Relation between gender, etiology and survival in patients with symptomatic heart failure. J Am Coll Cardiol 1996;28:1781-8 4. Sullivan MJ, Hawthorne MH: Exercise intolerance in patients with chronic heart failure. Prog Cardiovasc Dis 1995;38:1-22 5. Coats AJS, Clark AL, Piepoli M, Volterrani M, PooleWilson PA: Symptoms and quality of life in heart failure: the muscle hypothesis. Br Heart J 1994;72:36-9 6. Tyni-Lenn6 R, Gordon A, Sylv6n C: Improved quality of life in chronic heart failure patients following local endurance training with leg muscles. J Cardiac Failure 1996; 2:111-7 7. McKelvie TS, Teo KK, McCartney N, Humen D: Effects of exercise training in patients with congestive heart failure: a critical review. J Am Coll Cardiol 1995;25:78996 8. Magnusson G, Gordon A, Kaijser L, Sylv6n C, Isberg B, Karpakka S, Saltin B: High intensity knee extensor training in patients with chronic heart failure: major skeletal muscle improvement. Eur Heart J 1996;17:1048-55 9. Clark AL, Poole-Wilson PA, Coats AJS: Exercise limitation in chronic heart failure: central role of the periphery. J Am Coll Cardiol 1996;28:1092-102 10. Sullivan MJ, Green H J, Cobb FR: Altered skeletal muscle metabolic response to exercise in chronic heart failure. Relation to skeletal muscle aerobic enzyme activity. Circulation 1991;84:1597-607 11. Sylvdn C: Skeletal muscle in heart failure. Cardiologia 1997;42:1139-44 12. Wenger NK: Gender, coronary artery disease, and coronary bypass surgery. Ann Intern Med 1990;112:557-8 13. O'Callaghan WG, Teo KK, O'Riordan J, Webb H, Dolphin T, Horgan JH: Comparative response of male and

14.

15.

16. 17.

t8.

19.

20.

21.

22.

23. 24.

25.

26.

27. 28.

29.

30.

31. 32.

female patients with coronary artery disease to exercise rehabilitation. Eur Heart J 1984;5:649-51 Ades PA, Waldman ML, Polk DM, Coflesky JT: Referral patterns and exercise response in the rehabilitation of female coronary patients aged over 62 years. Am J Cardiol 1992;69:422-5 Lavie CJ, Milani RV: Effects of cardiac rehabilitation and exercise training on exercise tolerance, coronary risk factors, behavioral characteristics, and quality of life in women. Am J Cardiol 1995;75:340-3 Bergstr/Sm J: Muscle electrolytes in man. Scand J Clin Lab Invest 1962;68(suppl 14):1100-5 Lowry OH, Rosebrough HJ, Farr AL, Randall RJ: Protein measurement with the folin phenol reagent. J Biol Chem 1951;193:265-75 Lin L, Sotonyi R Somogyi E, Karlsson J, Folkers K, Nara Y, Sylvdn C, Kajser L, Jansson E: Coenzyme Q10 content in different parts of the normal human heart. Clin Physiol 1988;8:391-8 Ess6n B, Jansson E, Henriksson J, Taylor AW, Saltin B: Metabolic characteristics of the fibre types in human skeletal muscle. Acta Physiol Scand 1975; 95:153-65 Kannus P: Isokinetic evaluation of muscular performance: implications for muscle testing and rehabilitation. Int J Sports Med 1994;15:11-8 Guyatt G: Use of the six-minute walk test as an outcome measure in clinical trials in chronic heart failure. Heart Failure 1987;21:211-7 Sylvan C, Borg G, Holmgren A, Astr6m H: Psychophysical power functions of exercise limiting symptoms in coronary heart disease. Med Sci Sports Exerc 1991;23: 1050-4 Lowry OH, Passoneau JV: A flexible system for enzymatic analysis. Academic Press, New York, 1972 Hjemdahl P: Catecholamine measurements in plasma by high-performance liquid chromatography with electrochemical detection. Methods Enzymol 1987;142:521-34 Bergner M, Bobbitt RA, Carter W, Gilsson B: The sickness impact profile: development and final revision of a health status measure. Med Care 1981;19:787-806 Flannery RB, Flannery GJ: Sense of coherence, life stress, and psychological distress: a prospective methodological inquiry. J Clin Psychol 1990;46:415-20 Antonovsky A: The structure and properties of the sense of coherence scale. Soc Sci Med 1993;36:725-33 Langius A, Bj6rvell H: Coping ability and functional status in a Swedish population sample. Scand J Caring Sci 1993;7:3-10 Underhill Motzer S, Stewart BJ: Sense of coherence as a predictor of quality of life in persons with coronary heart disease surviving cardiac arrest. Res Nurs Health 1996; 19:287-98 Department of Health and Human Services: Clinical practice guidelines: 17. Cardiac rehabilitation. Office of the Forum of Quality and Effectiveness in Health Care, Rockville, MD, 1995 Wilmore JH, Costill DL: Physiology of sport and exercise. Human Kinetics, Champaign, IL, 1994 Coggan AR, Spina RJ, King DS, Rogers KM, Brown M, Nemeth PM, Holloszy JO: Skeletal muscle adaptations to

Exercise Effects in Women and Men With CHF

endurance training in 60- to 70-yr-old men and women. J AppI Physiol 1992;72:1780-6 33. Spina RJ, Ogawa T, Kohrt WM, Martin WH, Holloszy JO, Ehsani AA: Differences in cardiovascular adaptations to endurance exercise training between older men and women. J Appl Physiol 1993;73:849-55 34. Aniansson A, Grimby G, Hedberg M, Krotkiewski M: Muscle morphology, enzyme activity and muscle strength in elderly men and women. Clin Physiol 1981;1:73-86 35. Ferrari R, Anand IS, Ceconi C, De Giuli F, Poole-Wilson PA, Harris P: Neuroendocrine response to standing and mild exercise in patients with untreated severe congestive heart failure and chronic constrictive pericarditis. Heart 1996;76:50-5

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36. Gordon A, Tyni-Lenn6 R, Jansson E, Kaijser L, TheodorssonNorheim E, Sylvdn C: Improved ventilation and decreased sympathetic stress in chronic heart failure patients following local endurance training with leg muscles. J Cardiac Failure 1997;3:3-12 37. Abraham WT, Hensen L Schrier RW: Elevated plasma norepinephrine concentrations in patients with low output cardiac failure: dependence on increased norepinephrine secretion rates. Clin Sci 1990;79:429-35 38. Olds NB, Varvaro FF, Janosko K, Trost M, Zullo TG, Feldman AM, Murali S: Gender differences in the assessment of quality of life in patients with heart failure. Circulation 1997;96(suppl. I):440