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The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 55:B302-B306 (2000)
© 2000 The Gerontological Society of America

Determinants of Peak V.O2 in Peripheral Arterial Occlusive Disease Patients

Alice S. Ryana, Leslie I. Katzela and Andrew W. Gardnera

a Department of Medicine, University of Maryland School of Medicine, and the Geriatric Research, Education and Clinical Center, Baltimore, Maryland

Alice S. Ryan, Division of Gerontology, BT/18/GR, Baltimore Veterans Affairs Medical Center, Baltimore, MD 21201 E-mail: alice{at}grecc.umaryland.edu.

Decision Editor: Jay Roberts, PhD


   Abstract
Top
 Abstract
Methods
 Results
 Discussion
 References
 
Peripheral arterial occlusive disease (PAOD) patients with intermittent claudication are functionally limited and deconditioned. This study examined whether peak aerobic capacity (V.o2 peak) was associated with PAOD severity, muscle mass, and comorbidities in 109 PAOD patients (93 men and 16 women) aged 48–86 years. The V.o2 peak (1.12 ± 0.34 L/min), percentage body fat (30.6 ± 8.3%), lean tissue mass of the total body (51.4 ± 8.4 kg), lean tissue mass of the legs (16.6 ± 3.0 kg), and appendicular skeletal mass (22.8 ± 4.2 kg) were determined. The lean tissue mass of the total body , lean tissue of the legs and resting ankle/brachial systolic pressure index (ABI; ) correlated with peak V.o2 (all p < .001). None of the comorbidity variables (obesity, arthritis, coronary artery disease, hypertension, diabetes, and smoking history) were significantly associated with peak V.o2 except smoking status. The final model for the prediction of peak V.o2 included lean tissue mass of the legs, resting ABI, smoking status, and ABI x smoking status . In older patients with intermittent claudication, lean tissue mass is an important determinant of physical performance independent of PAOD severity and smoking status. Prevention of muscle atrophy may preserve ambulatory function and peak exercise capacity in older PAOD patients.

PERIPHERAL arterial occlusive disease (PAOD) has an age-adjusted prevalence of 12% (1). Patients with PAOD often experience intermittent claudication that impairs their walking ability and curtails physical activities. Thus, PAOD patients lead a sedentary lifestyle that promotes disuse atrophy of the lower extremity muscles. This muscle wasting is compounded by the usual increase in body fat and loss of fat-free mass that occurs in normal aging (2)(3). The reduction in muscle mass with aging is related to the concomitant decrease in maximal aerobic capacity (V.O2) (4).

Patients with PAOD have a 60% lower functional capacity than age-matched individuals without the disease (5). This is a function of disease severity, because resting ankle/brachial systolic pressure index (ABI) is an important predictor of the distance walked to maximal claudication pain during a graded treadmill test (6). In addition, cigarette smoking reduces the exercise capacity of patients with claudication, independent of ABI (7). Although body mass index (BMI) is also an independent predictor of the distance to maximal claudication pain (6) and peak V.O2 (8) in patients with claudication, we believe that lower extremity muscle mass is the major body composition variable that contributes to the reduced aerobic capacity typically observed in these patients. The purpose of the present study was to determine the relationship of peak V.O2 to the severity of PAOD, muscle mass, and smoking status in older PAOD patients with claudication. We hypothesized that lower extremity muscle mass would be a significant independent predictor of peak V.O2 in these patients.


   Methods
Top
 Abstract
 Methods
Results
 Discussion
 References
 
Subjects
One hundred and nine PAOD patients consisting of 93 men and 16 women between the ages of 48 and 86 years participated in the study. The patients consisted of 61 Caucasians, 46 African Americans, and 2 Native Americans. The Institutional Review Board of the University of Maryland approved all methods and procedures, and all patients provided written informed consent. Patients were screened by medical history, physical examination, fasting blood profile, and a graded exercise treadmill test. All patients had a history of claudication pain secondary to PAOD. All patients were limited by claudication pain secondary to PAOD and were not limited by other factors. Patients were excluded from participation for the following medical conditions: (a) leg pain at rest (Fontaine Stage III for PAOD) (9); (b) ST segment depression greater than 2 mm at rest; (c) exercise tolerance limited by factors other than claudication including chest pain, dyspnea, fatigue, dizziness, and arthritis; and (d) exercise-induced leg pain not of vascular origin.

Calf Blood Flow
Patients were instructed to refrain from smoking and from drinking caffeinated beverages during the morning of testing. After the patient rested in the supine position for 10 minutes, calf blood flow was obtained in the more severely diseased leg by venous occlusion strain-gauge plethysmography (10). A mercury strain gauge was placed around the calf at the maximal circumference, and arterial blood flow to the foot was temporarily occluded by an ankle cuff inflated to 300 mm Hg. Calf blood flow was measured by inflating a thigh cuff to a venous occlusion pressure of 50 mm Hg. The ankle and thigh cuffs were deflated immediately after the resting calf blood flow measurement was obtained. For calf blood flow to be assessed under hyperemic conditions, a reactive hyperemic test was performed by inflating a thigh blood pressure cuff to at least 200 mm Hg to induce arterial occlusion for 3 minutes. The postocclusive reactive hyperemic calf blood flow was obtained within the first minute following the 3-minute occlusion.

Ankle/Brachial Index
After the patient rested in the supine position for 10 minutes, ankle systolic pressure was measured with a Parks Medical Electronics, Inc. nondirectional Doppler flow detector (Model 810-A, Aloha, OR), a pencil probe (9.3 MHz), and standard size ankle blood pressure cuffs (10 cm width). Measurements were obtained from the posterior tibial and dorsalis pedis arteries in both legs. The higher of the two arterial pressures from the more severely diseased leg was recorded as the resting ankle systolic pressure. Brachial systolic pressure was measured from both arms with a Critikon Dinamap Vital Signs Monitor (Model 1846-SX, Tampa, FL), using either a standard adult size blood pressure cuff (14 cm width) or a large adult size cuff (17 cm width). Systolic pressure was recorded from the arm yielding the highest pressure. The ABI was obtained before and 1 minute after the maximal treadmill test. The ABI was used to determine a patient's PAOD severity.

Maximal Exercise Test
Patients performed a progressive graded treadmill protocol at 2 mph, 0% grade with a 2% increase every 2 minutes until maximal claudication pain. V.O2, carbon dioxide production (VCO2), and minute ventilation (VE) were obtained every 20 seconds by using a Sensormedics 2900 (Yorba Linda, CA) metabolic measurement cart. Heart rate was continuously monitored during exercise, and values were recorded at the end of each minute. Brachial pressure was taken during the final minute of each 2-minute exercise stage. Peak oxygen consumption, time to onset, and time to maximal claudication pain were determined from the graded exercise test. Patients were allowed to rest their hands on the handrails periodically for balance purposes but were discouraged from using handrail support because of its affect on the reliability of claudication pain measurements (10). The peak V.O2 was defined as the average of the two highest 20-second V.O2 measurements. Reliable treadmill measurements are obtained by using this protocol (11)(12).

Body Composition
All body composition measurements were performed after a 12-hour fast. Fat mass, lean tissue mass and bone mineral content were determined by dual-energy x-ray absorptiometry (DXA; Model DPX-L, LUNAR Radiation Corp., Madison, WI). All DXA scans were analyzed by using the LUNAR 1.3Z DPX-L program for body composition analyses. Regions of interest, including the arms and legs, were analyzed by using the extended analysis of the LUNAR software. Appendicular skeletal mass was calculated as the lean tissue mass of both arms plus both legs.

Statistical Analyses
Pearson correlation coefficients were calculated to determine the relationships among body composition, peripheral hemodynamics, and peak V.O2. Stepwise multiple regression was used to determine the independent factors related to peak V.O2. Data are expressed as mean ± standard deviation (SD), and significance was set at the .05 level. All analyses were performed by utilizing Statistical Analysis System version 6.12 (13).


   Results
Top
 Abstract
 Methods
 Results
Discussion
 References
 
Patient characteristics are presented in Table 1 . Patients were overweight by BMI criteria and had an upper-body fat distribution as reflected by an increased waist-to-hip ratio (WHR). Two thirds of the patients had bilateral leg claudication, whereas the remaining one third of the patients had unilateral claudication. Patients reported onset of claudication pain after walking on average less than two blocks.


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  		Table 1. Patient Characteristics

 
Body composition results are reported in Table 2 . Total body fat percentage ranged from ~7% to 53%, indicating a wide variability in body fat in this patient population. There was no difference between the lean tissue mass of the more affected leg (leg with the lower ABI and greater claudication symptoms) versus the less affected limb.


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  		Table 2. Body Composition

 
The results from the graded exercise treadmill test and the measures of peripheral hemodynamics are presented in Table 3 . There was a large range of physical fitness and claudication time. Values for the resting ABI were typical for patients with PAOD. As expected, the ABI was lower 1 minute after termination of the treadmill test than at rest.


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  		Table 3. Claudication and Peripheral Hemodynamic Measurements

 
Table 4 shows the relationships between peak V.O2 and measures of body composition and peripheral hemodynamics. All measures of body composition correlated with peak V.O2. Lean tissue mass of the total body and lean tissue mass of the less affected leg had the highest correlation with peak V.O2. Interestingly, the correlations between peak V.O2 and calf circumference were similar to the correlations between peak V.O2 and the measures of body composition determined by DXA. The calculation of appendicular skeletal mass did not improve the association with peak V.O2.


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  		Table 4. Univariate Correlations Between Peak V.O2 and Body Composition and Hemodynamic Measures

 
A stepwise regression was performed to determine those variables independently related to peak V.O2. The model included total body lean tissue, lean tissue of both legs, and appendicular skeletal mass, as well as ABI, and calf blood flow measurements. Comorbidities, including obesity, arthritis, coronary artery disease (CAD), hypertension, diabetes, and smoking history, were each added to check for significance to the model. The lean tissue mass of both legs (partial ; Fig. 1) and resting ABI (partial , Fig. 2) were independent predictors of peak V.O2 explaining a combined 32% of the variance ( p < .001). None of the comorbidity variables were significantly associated with peak V.O2 except smoking status. A binary variable was added to the model to indicate smoking status (current smoker or nonsmoker). The addition of smoking status to the model was significant . All three variables had parameter estimates significantly greater than zero ( p < .05). A principal component analysis indicated no significant collinearity among resting ABI and lean tissue mass of the legs, nor was the correlation between resting ABI and lean tissue mass of the legs significant . However, when interaction terms were evaluated, significance was observed between the resting ABI and smoking, indicating that a higher peak V.O2 was obtained in nonsmoking patients with higher ABI values. Therefore, the final model for the prediction of peak V.O2 included the following: lean tissue mass of the legs, resting ABI, smoking status, and ABI x smoking status .



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  		Figure 1. Relationship between lean tissue mass of the legs and peak aerobic capacity (V.O2) in patients with peripheral arterial occlusive disease .

 


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  		Figure 2. Relationship between ankle to brachial index (ABI) and peak aerobic capacity (V.O2) in patients with peripheral arterial occlusive disease .

 
We next conducted a stratified analysis such that separate regression analyses were performed for smokers and nonsmokers. The results of this analysis indicated that there is a higher correlation ( p < .05) between the resting ABI and peak V.O2 among smokers than nonsmokers , whereas the relationship between lean tissue mass of the legs and peak V.O2 were similar between groups . These results suggest that the resting ABI is more strongly related to peak V.O2 in smokers than in nonsmokers. Separate regression models for smokers and nonsmokers indicated that leg lean tissue mass and resting ABI are better predictors of peak V.O2 for smokers than nonsmokers .


   Discussion
Top
 Abstract
 Methods
 Results
 Discussion
References
 
The results of the present study indicate that in older PAOD patients with claudication and multiple CAD risk factors, the best independent predictors of maximal attainable aerobic capacity are lean tissue mass of the legs, the severity of PAOD measured as the resting ABI, and smoking status.

Previous studies report that walking distance to maximal claudication pain and peak V.O2 are correlated with the resting ABI and BMI in patients with PAOD (6)(8)(14), suggesting that exercise capacity is dependent upon the severity of disease and body composition. However, the BMI is a gross measure of body composition because it depends only upon height and weight, and thus its measurement cannot differentiate between individuals with varying degrees of muscle mass. This is important as total body fat-free mass and fat mass contribute to the decline in peak V.O2 with age in healthy men and women (15). Therefore, in the present study, we used DXA to quantify whole body and regional measures of muscle and fat mass to determine the relationship between body composition and exercise capacity in PAOD patients in a more precise manner. Our results indicate that both lean tissue mass and fat mass are related to peak V.O2. Nonetheless, only lean tissue mass of the legs was a significant predictor of peak V.O2 after adjustment for resting ABI and smoking status. The calculation of appendicular skeletal mass did little to improve the prediction of peak aerobic capacity. Our final model suggests that the muscle mass of the legs is an important determinant of exercise capacity in patients with PAOD. For the patient who is limited by leg claudication pain, a reduction in the amount of muscle tissue available in the leg to extract oxygen during peak exercise compounds the other insufficiencies that a PAOD patient faces when walking.

Our results also indicate that smoking status is an independent predictor of peak V.O2, supporting previous investigations that found that PAOD smokers perform worse on the treadmill, as indicated by shorter distances to onset and to maximal pain (7). In the present study, the relationship between lean tissue mass of the legs and peak V.O2 was similar between smokers and nonsmokers, which suggests that muscle mass is a significant determinant of aerobic capacity in patients with PAOD regardless of smoking status. Furthermore, the resting ABI was a better predictor of peak V.O2 in smokers than in nonsmokers, indicating that disease severity has a greater negative impact on physical performance in smokers. We speculate that the harmful effects of cigarette smoking may act synergistically with the severity of PAOD to reduce peak V.O2. For example, smoking may reduce the capacity of blood to carry oxygen (16) and impair endothelial reactivity (17), but these mechanisms require further study in PAOD patients.

Others have reported a significant correlation between peak V.O2 and total skeletal muscle mass by DXA in heart failure patients (18). This relationship was stronger in the patients than in healthy controls, suggesting that skeletal muscle atrophy in heart failure patients contributed to their low peak V.O2. Moreover, an increase in V.O2 max following lower-body resistance training was attributed to an increased muscle area of the thigh (19), suggesting that exercise programs that increase muscle mass may improve aerobic capacity in patients with skeletal atrophy. Other possible explanations for the low aerobic capacity observed in patients with PAOD include the inability to adequately increase skeletal muscle blood flow during exercise as well as a more rapid increase and an excess of lactate concentration suggesting an inadequate oxygen supply to the exercising muscles (20). However, mitochondrial enzyme activities are higher in patients with intermittent claudication than matched controls, suggesting a spontaneous enzymatic adaptation to their insufficiency (21). Other conditions that contribute to the reduction in maximal oxygen uptake in the elderly include a fall in maximal heart rate, impaired myocardial contractability, and increased stiffness of the arteries (22).

In conclusion, lean tissue mass is an important determinant of physical performance independent of PAOD severity and smoking status in older patients with intermittent claudication. Prevention of muscle atrophy may preserve ambulatory function and peak exercise capacity in older PAOD patients.


   Acknowledgments
 
Our appreciation is extended to the participants in the study. We are grateful to the exercise physiologists and the nurses in the Geriatrics Services at the Baltimore VA Medical Center for technical assistance, to Jacqueline Iannuzzi for statistical consultation, and to Andrew P. Goldberg, MD for his insightful comments. This study was supported by funds from the National Institutes of Health/National Institute on Aging through grants KO1-A600747 (Ryan); and KO1-AG-00657 (Gardner); a grant from the Claude D. Pepper Older Americans Independence Center, OIAC–NIH/NIA-P60-AG12583; by the Geriatrics Research, Education and Clinical Center of the Baltimore Veterans Affairs Medical Center and by the Department of Veteran Affairs.

Received July 27, 1999

Accepted November 10, 1999


   References
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 Abstract
 Methods
 Results
 Discussion
 References
 

  1. Criqui MH, Coughlin SS, Fronek A, 1985. Noninvasively diagnosed peripheral arterial disease as a predictor of mortality: results from a prospective study. Circulation 72:768-773. [Abstract/Free Full Text]
  2. Forbes GB, Reina JC, 1970. Adult lean body mass declines with age: some longitudinal observations. Metabolism 19:653-663. [Medline]
  3. Steer B, 1988. Body composition and aging. Nutr Rev 46:45-51. [Medline]
  4. Fleg JL, Lakatta EJ, 1988. Role of muscle loss in the age associated reduction in V.o2 max. J Appl Physiol 65:1147-1151. [Abstract/Free Full Text]
  5. Eldridge JE, Hossack KF, 1987. Patterns of oxygen consumption during exercise testing in peripheral vascular disease. Cardiology 74:236-240. [Medline]
  6. Gardner AW, Ricci MA, Case TD, Pilcher DB, 1996. Practical equations to predict claudication pain distances from a graded treadmill test. Vasc Med. 1:91-96. [Medline]
  7. Gardner AW, 1996. The effects of cigarette smoking on exercise capacity in patients with intermittent claudication. Vasc Med. 1:181-186. [Medline]
  8. Womack CJ, Hyman BA, Gardner AW, 1998. Prediction of peak oxygen consumption in patients with intermittent claudication. Angiology 49:591-598.
  9. Pentecost MJ, Criqui MH, Dorros G, et al. 1994. Guidelines for peripheral percutaneous transluminal angioplasty of the abdominal aorta and lower extremity vessels. Circulation 89:511-531. [Free Full Text]
  10. Gardner AW, Sieminski DJ, Killewich LA, 1997. The effect of cigarette smoking on free-living daily physical activity in older claudication patients. Angiology. 48:947-955.
  11. Gardner AW, Skinner JS, Cantwell BW, Smith LK, 1991. Progressive vs. single-stage treadmill tests for evaluation of claudication. Med Sci Sports Exerc. 23:402-408. [Medline]
  12. Gardner AW, Skinner JS, Cantwell BW, Smith LK, 1991. Effects of handrail support on claudication and hemodynamic responses to single-stage and progressive treadmill protocols in peripheral vascular occlusive disease. Am J Cardiol. 67:99-105. [Medline]
  13. SAS Institute. SAS/STAT User's Guide, Version 6, 4th ed. Cary, NC: SAS Institute Inc., 1989.
  14. Yao ST, Needham TN, Gourmoos C, Irvine WT, 1972. A comparative study of strain-gauge plethysmography and Doppler ultrasound in the assessment of occlusive arterial disease of the lower extremities. Surgery. 71:4-9. [Medline]
  15. Toth MJ, Gardner AW, Ades PA, Poehlman ET, 1994. Contribution of body composition and physical activity to age-related decline in peak V.o2 in men and women. J Appl Physiol. 77:647-652. [Abstract/Free Full Text]
  16. Galea G, Davidson RJL, 1985. Haematological and haemorheological changes associated with cigarette smoking. J Clin Pathol. 38:978-984. [Abstract/Free Full Text]
  17. Celermajer DS, Sorensen KE, Georgakopoulos D, et al. 1993. Cigarette smoking is associated with dose-related and potentially reversible impairment of endothelium-dependent dilation in healthy young adults. Circulation. 88:2149-2155. [Abstract/Free Full Text]
  18. Toth MJ, Gottlieb SS, Fisher ML, Poehlman ET, 1997. Skeletal muscle atrophy and peak oxygen consumption in heart failure. Am J Cardiol. 79:1267-1269. [Medline]
  19. Evans WJ, Cyr-Campbell D, 1997. Nutrition, exercise, and healthy aging. J Am Diet Assoc. 97:632-638. [Medline]
  20. Carlson LA, Pernow B, 1962. Studies on the peripheral circulation and metabolism in man. II. Oxygen utilization and lactate-pyruvate in the legs at rest and during exercise in patients with arteriosclerosis obliterans. Acta Med Scandinavia. 171:311-323. [Medline]
  21. Lundgren F, Dahllof AG, Schersten T, Bylund-Fellenius AC, 1989. Muscle enzyme adaptation in patients with peripheral arterial insufficiency: spontaneous adaptation, effect of different treatments and consequences on walking performance. Clin Sci. 77:485-493. [Medline]
  22. Gerstenblick G, Lakatta EG, Weisfeldt MC, 1977. Age changes in myocardial function and exercise response. Sonnenblick EH, Lesch M, , ed.Exercise and Heart Disease 105-106. Grune & Stratton, New York.



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