Archives of Physical Medicine and Rehabilitation
Volume 86, Issue 6 , Pages 1176-1181, June 2005

Fitness, Inflammation, and the Metabolic Syndrome in Men With Paraplegia

  • Patricia J. Manns, PhD

      Affiliations

    • College of Health and Human Sciences, Department of Exercise and Sport Science, Oregon State University, Corvallis, OR
    • Corresponding Author InformationCorrespondence to Patricia J. Manns, PhD, PT, 2-50 Corbett Hall, Dept of Physical Therapy, Faculty of Rehabilitation Medicine, University of Alberta, Edmonton, AB T6G 2G4, Canada, Reprints are not available from the author
    • ,
  • Jeffrey A. McCubbin, PhD

      Affiliations

    • College of Health and Human Sciences, Department of Exercise and Sport Science, Oregon State University, Corvallis, OR
    • ,
  • Daniel P. Williams, PhD

      Affiliations

    • College of Health, Department of Exercise and Sport Science, University of Utah, Salt Lake City, UT

Article Outline

Abstract 

Manns PJ, McCubbin JA, Williams DP. Fitness, inflammation, and the metabolic syndrome in men with paraplegia. Arch Phys Med Rehabil 2005;86:1176–81.

Objective

To determine the relations among peak aerobic capacity, physical activity, functional ability, components of the metabolic syndrome (high-density lipoprotein cholesterol [HDL-C], triglycerides [TG], glucose, insulin, abdominal obesity, high blood pressure), and inflammatory factors (interleukin-6 [IL-6], C-reactive protein [CRP]) in men with paraplegia.

Design

Cross-sectional exploratory design.

Setting

University research laboratory.

Participants

Twenty-two men (age, 39±9y; duration of injury, 17±9y; level of injury, T2-L2) with functionally complete paraplegia volunteered to participate.

Interventions

Not applicable.

Main Outcome Measures

Peak aerobic capacity was measured using a graded peak exercise test with an arm ergometer, and physical activity was assessed by the Physical Activity and Disability Scale. Functional ability was assessed by the Self-Report Functional Measure. Circulating glucose, insulin, HDL-C, TG, total cholesterol, IL-6, and CRP levels were determined by specific enzyme or immunologic assays. Body fat was determined by dual-energy x-ray absorptiometry, and central obesity was estimated from abdominal sagittal diameters.

Results

Lower peak aerobic capacities were associated with lower HDL-C and lower physical activity levels (P<.014). Lower physical activity levels were associated with higher fasting glucose, lower HDL-C level, and larger abdominal sagittal diameters (P<.036). Larger abdominal sagittal diameters were associated with higher fasting glucose, higher fasting and postload insulin, lower HDL-C, higher TG, and higher CRP levels (P<.05).

Conclusions

Diet and exercise trials are needed to determine the efficacy and effectiveness of lifestyle interventions aimed at slowing the progression of the metabolic syndrome in people with spinal cord injury.

Key Words:  C-reactive protein , Insulin resistance , Interleukin-6 , Rehabilitation , Spinal cord injuries

 

SUBCLINICAL INFLAMMATION IS both a cause and a consequence of cardiovascular disease1 and type II diabetes mellitus (T2D).2 Interleukin-6 (IL-6) and C-reactive protein (CRP) are important inflammatory risk factors for heart disease and T2D, and modest subclinical elevations in IL-6 and CRP levels increase the risk of developing heart disease3, 4 and T2D5 in previously healthy people. Moreover, in nondisabled people, elevated levels of IL-6 and CRP are significantly associated with components of the metabolic syndrome,6, 7 which is characterized by low levels of high-density lipoprotein cholesterol (HDL-C), elevated levels of fasting glucose and triglycerides (TG), abdominal obesity, and high blood pressure.8

Unfavorable levels of several of the above-listed components within the metabolic syndrome are prevalent in people with spinal cord injury (SCI). For example, low levels of HDL-C in people with SCI are well documented.9, 10 In addition, insulin resistance and high circulating levels of insulin, which are integral to the metabolic syndrome,11 are prevalent in people with SCI.12 Moreover, SCI may accelerate age-related body fat gains. In identical twin pairs discordant for paraplegia, the twin with SCI has been shown to have greater amounts of body fat than the nondisabled twin.13 Thus, SCI-related body fat gains likely contribute to the HDL-C and insulin abnormalities. Furthermore, circulating IL-6 and CRP levels may be elevated in persons with SCI.14, 15 The combination of these metabolic, anthropometric, and inflammatory risk factors may help to explain why heart disease16 and T2D12 are more prevalent in people with SCI than in people without SCI. The high prevalence of heart disease and T2D also suggests that healthy lifestyles, like regular physical activity, could have a substantial public health impact on people with SCI.

Higher aerobic capacity and higher levels of physical activity are associated with more favorable inflammatory17, 18 and lipid19 risk factor profiles in nondisabled persons. Moreover, studies with elderly populations have shown that better functional ability and physical performance are associated with lower circulating IL-6 and CRP levels.20, 21 In people with SCI, information about the prevalence of elevated inflammatory factors is limited,15 and the relations among aerobic capacity, physical activity, functional ability, inflammatory factors (IL-6, CRP), and components within the metabolic syndrome are not known. Therefore, the purpose of our study was to examine the associations among aerobic capacity, physical activity, functional ability, inflammatory factors, and components of the metabolic syndrome in a sample of men with paraplegia.

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Methods 

Participants 

Twenty-two male volunteers with functionally complete paraplegia (ie, they use a wheelchair as their only mode of locomotion) of at least 3 years in duration participated. Participants with diabetes and coronary heart disease were excluded. All participants stated that they had no acute infections. The level of SCI ranged from T2 to L2, and 5 participants had injuries at or above T6. Participants were asked to maintain a consistent medication schedule during the course of the study.

Testing 

A 75-g oral glucose tolerance test was completed to assess each participant’s glucose and insulin responses to an oral glucose load. Participants arrived at the laboratory between 8:00 and 10:00 am in a 12-hour fasted state. A fasting blood sample was drawn, and immediately thereafter, participants consumed 75g of an orange-flavored glucose drinka in 5 minutes or less. Two hours after the oral glucose load, a second blood sample was drawn. In the 2 hours between blood draws, participants refrained from exercise. A medical history questionnaire and a comprehensive physical activity questionnaire designed for people with disabilities22 were completed. A physical therapist determined the level of SCI using the American Spinal Injury Association procedures.23 Functional ability was determined using the Self-Reported Functional Measure (SRFM), which is a valid24, 25 and reliable measure that assesses mobility, all types of transfers, and eating and grooming.26 Clinical experience with men with paraplegia suggests that the majority of our sample would score near the ceiling on the SRFM. Therefore, to improve the sensitivity of the scale, 2 items that tested higher-level functional skills were added: (1) the ability to go up and down 6-in curbs and (2) the ability to get up and down off the floor. Participants had 4 response choices to the question, “How much help do you need?”: “No extra time or help,” “Extra time or special tool,” “Some help,” “Total help or never do.” The maximum score was 60, and higher scores equated with greater independence in functional activities.

Weight was measured to the nearest 0.1kg on a Detecto balance beam scaleb that was modified to allow participants to transfer onto a seat on the scale. Height was measured while the subject was supine, to the nearest 0.1cm. With the participant’s head flush against a wall, the distance from the wall to the bottom of the participant’s heel was measured.27 Two people completed the measurement, with 1 person manually straightening the legs and pulling the ankle into neutral dorsiflexion, as necessary. If the participant had fixed knee or hip contractures, self-reported height was used. Abdominal sagittal diameter (ASD)28 measurements were done in triplicate in the supine position, with the average measurement reported.

On a separate day, at least 3 days after the oral glucose tolerance test, participants reported to the laboratory for aerobic capacity and additional body composition testing. Peak aerobic capacity (Vo2peak) was determined using indirect open circuit spirometry,c with an arm ergometer.d Participants were asked to fast for 4 hours before the exercise test. Each incremental stage of the graded exercise test was 2 minutes long, and resistance started at 5W and was increased by 5W every 2 minutes.29 Participants maintained a speed of 60 revolutions per minute, with the assistance of a metronome and verbal cueing. Vo2peak represented the highest value, averaged over 20 seconds, during the test. Total and regional body compositions were determined using dual-energy x-ray absorptiometry (DXA).e If participants had contractures or spasticity that made it difficult for the lower extremities to remain still during the scanning procedures, a cloth strap was used to stabilize them. We report only total body fat from DXA measurements, not muscle mass or fat-free soft tissue. Therefore, no corrections were made to account for potential differences in the ratio of muscle mass to total fat-free soft tissue in people with SCI compared with people without SCI.30

Biochemical procedures 

Venous blood samples were collected in plasma edetic acid tubes for insulin and in serum vacutainer tubes with gel clot activator for lipids, lipoproteins, glucose, IL-6, and CRP. Serum vacutainera tubes were allowed to clot at room temperature for 30 minutes, and within 2 hours of blood collection, chilled serum and plasma were isolated by centrifugation at 1500g for 15 minutes. Samples were subsequently aliquoted and frozen at −80°C. This study was part of an acute exercise experiment, and the values reported for IL-6, CRP, total cholesterol (TC), TG, and HDL-C are the mean of two 12-hour fasted blood samples drawn a minimum of 1 week apart. Because there were duplicate samples from the same subject, it was important to eliminate between-assay measurement errors. Thus, all assays were done after data collection was complete, and each subject’s duplicate blood samples for the above circulating outcomes were assessed in the same assay.

Serum TC, TG, and HDL-C levels were determined using enzymatic techniques.31, 32 Measurement errors, expressed as coefficients for variation (CVs) (standard deviation/mean × 100) were 1.8% for TC, 2.1% for TG, and 3.5% for HDL-C. A colorimetric glucose oxidase method33 was used to assess serum glucose, and a human insulin-specific radioimmunoassayf was used to assess plasma insulin levels. CVs were 1.7% for glucose and ranged from 4.5% for the low plasma insulin control to 5.6% for the high plasma insulin control. An estimate of insulin resistance was calculated using the homeostasis model assessment (HOMA). The formula to calculate HOMA is (fasting insulin [μU/mL] × fasting glucose [mmol/L])/22.5.34

IL-6 was measured in duplicate using a high-sensitivity enzyme-linked immunosorbent assayg with a detectable limit between 0.378 and 10.1pg/mL. Interassay CVs were determined using known control samples and were 14.7% for the low control, 8.3% for the mid control, and 9.4% for the high control. Serum CRP levels were measured in duplicate with a highly sensitive enzyme-linked immunosorbent assay.h The serum dilution protocol recommended by the manufacturer is 1:500, which cannot detect serum CRP levels below 5mg/L. Because we were interested in detecting and quantifying more modest and possibly more chronic degrees of subclinical vascular inflammation, we modified the dilution protocol to extend the detectable range of the assay from 0.5 to 250mg/L.35 Our interassay CV was 6.6% for a low-level serum CRP control that ranged from 1.2 to 1.4mg/L and 11.7% for a high-level serum CRP control that ranged from 9.1 to 12.6mg/L.

Statistical Analysis 

Statistical analysis was completed using SPSS, version 11.5.i Data were examined for normality before the analysis, and the distributions of IL-6 and CRP were positively skewed. Therefore, those values were log-transformed to allow use of parametric statistics. For descriptive purposes, untransformed values are reported. Partial correlation analysis was used to determine the associations of aerobic capacity, physical activity, and functional ability with inflammatory factors and components of the metabolic syndrome (HDL-C, TG, fasting and 2-h postload glucose and insulin levels; ASD; total body fat; systolic blood pressure [SBP]) while statistically adjusting for differences in age, duration of injury, and medication use. Medication users included those taking antibacterial agents (6/22 participants), angiotensin-converting enzyme inhibitors (2/22 participants), nonsteroidal anti-inflammatory medications (3/22 participants), and a statin drug (1/22 participants). Participants were either coded as “medication users” or as “nonmedication users.” All medication users were taking stable daily doses of their medications (ie, they were not taking medications on an as-needed basis). All statistical tests were considered significant at the level of P less than .05.

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Results 

Twenty-two men with paraplegia participated in the study. Subject characteristics are presented in table 1. All participants were completely independent with horizontal transfers and mobility, and all participants used a manual wheelchair. On average, participants were overweight, had low HDL-C levels, and had subclinical inflammation, as indicated by elevated levels of IL-6 and CRP. Older age was associated with lower peak aerobic capacity (P=.031) and higher 2-hour postload insulin levels (P=.027). Additionally, there was a trend toward both older age (P=.055) and longer duration of injury (P=.051) being associated with greater amounts of total body fat, as measured by DXA.

Table 1. Subject Characteristics for Total Sample
CharacteristicsTotal Sample (N=22)
Age (y)39±9
Duration of injury (y)17±9
Weight (kg)82±18
Height (cm)178.4±8.0
ASD (cm)22.6±4.4
DXA total body fat (%)26.7±6.7
Total body fat (kg)22.9±10.2
Oral glucose tolerance
Fasting glucose (mmol/L)5.2±0.5
2-hour glucose (mmol/L)5.1±1.5
Fasting insulin (pmol/L)101±66
2-hour insulin (pmol/L)407±278
HOMA3.3±2.3
IL-6 (pg/mL)2.5 (1.5–3.6)
CRP (mg/L)3.0 (1.8–9.3)
Physical activity88.7±80.6
Peak aerobic capacity (mg·kg−1·min−1)24.0±8.5
Peak aerobic capacity (L/min)1.90±0.60
Function50.6±2.4
HDL-C (mmol/L)0.99±0.19
TG (mmol/L)1.8±1.4
TC (mmol/L)4.9±1.2

NOTE. Data are mean ± standard deviation, except CRP and IL-6, which are median (interquartile range). Physical activity and Function have arbitrary units. Maximum score for function is 60, which would indicate no deficits in functional ability.

The partial correlation coefficients of peak aerobic capacity (both relative in mL·kg−1·min−1 and absolute in L/min), physical activity, and physical function with the components of the metabolic syndrome with statistical adjustments for differences in age, duration of injury, and medication use are shown in table 2. Lower peak relative aerobic capacity (in mL·kg−1·min−1) was associated with lower HDL-C levels and with lower physical activity levels. Lower levels of self-reported physical activity were associated with higher fasting glucose and lower HDL-C levels and larger ASD. There were also trends for lower peak relative aerobic capacity being associated with higher TG (P=.056), greater amounts of total body fat (P=.071), and larger ASD (P=.070). Neither peak absolute aerobic capacity (in L/min) nor functional ability was associated with any of the metabolic or anthropometric outcomes.

Table 2. Partial Correlation Coefficients Between Vo2peak (absolute and relative), Physical Activity, and Function, and Metabolic and Anthropometric Outcomes, With Adjustment of Medication Use, Age, and Duration of Injury
OutcomesVo2peak (mL·kg−1·min−1)Vo2peak (L/min)Physical ActivityFunction
Fasting glucose−.185.124−.525⁎.082
Fasting insulin−.321−.073−.397.256
2-hour glucose−.340−.239−.344−.226
2-hour insulin−.234−.056−.155−.151
HOMA−.315−.058−.429.250
HDL-C.555⁎.218.625†.006
TG−.445−.076−.256.058
IL-6−.093−.158−.267.170
CRP−.111.219−.142−.093
SBP.431.425.044.060
ASD−.425.055−.483⁎−.339
Total body fat−.424.077−.365−.353
Function.416.280.268NA
Physical activity.636†.447NANA

Abbreviation: NA, not applicable.

⁎ P<.05.

† P<.01.

The partial correlations of total body fat and ASD with the components of the metabolic syndrome, with statistical adjustments for differences in age, duration of injury, and medication use, are shown in table 3. Greater amounts of total body fat and larger ASD were strongly associated with higher fasting and 2-hour postload insulin levels, higher HOMA-derived estimates of insulin resistance, lower HDL-C, higher TG, and higher CRP (see table 3). ASD explained 77% of the variance in total body fat as measured by DXA.

Table 3. Partial Correlation Coefficients Between Total Body Fat and ASD and Metabolic Outcomes, With Adjustment of Medication Use, Age, and Duration of Injury
OutcomesTotal Body FatASD
Fasting glucose.378.562⁎
Fasting insulin.516⁎.650†
2-hour glucose.171.385
2-hour insulin.512⁎.539⁎
HOMA.517⁎.656†
HDL-C−.625†−.635†
TG.752†.707†
SBP.112.175
IL-6−.010.098
CRP.605†.565⁎
ASD.878†NA

⁎ P<.05.

† P<.01.

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Discussion 

We found that lower physical activity levels were associated with higher fasting glucose levels, lower HDL-C levels, and larger ASDs in men with a paraplegic SCI (see table 2). We also found that larger ASDs were associated with higher fasting glucose, higher fasting and postload insulin, higher HOMA-derived estimates of insulin resistance, lower HDL-C, higher TG, and higher CRP levels in men with a paraplegic SCI (see table 3). Other studies have reported associations between aerobic capacity and insulin sensitivity,12 between physical activity and serum lipoproteins,36, 37 and between body composition and serum lipoproteins36, 38 in people with SCI. Our study extends those findings by assessing aerobic capacity, physical activity, physical function, body composition, glucose tolerance, insulin resistance, serum lipoproteins, circulating inflammatory factors, and blood pressure in a single sample of men with paraplegia. Other unique aspects of our study include the use of an average of duplicate blood collections for the circulating outcomes and the use of a multivariate data analysis. Our use of an average of duplicate blood collections is particularly important for IL-6 and CRP levels, because their day-to-day variability can range from 44% to 60%.39, 40 Our statistical control for such potential confounding factors as older ages, longer injury durations, and medication use helps to establish the independence of the association between physical activity and the metabolic syndrome in men with paraplegia (see table 2).

Our inability to detect significant correlations between either physical activity or peak aerobic capacity and circulating inflammatory factors was somewhat unexpected (see table 2). We and others have reported that lower physical activity levels are associated with higher circulating IL-621 and CRP21, 35 levels in nondisabled samples of older adult women and men. In addition, lower aerobic capacity levels are associated with higher circulating CRP levels in nondisabled samples of middle-aged and older adult women41 and men.42 The reported associations between lower aerobic capacity levels and higher circulating CRP levels were independent of the higher body mass indexes (BMIs)41 and the larger waist circumferences41, 42 of the least fit subjects. By contrast, some but not all43 of the reported associations between lower physical activity levels and higher circulating CRP levels were dependent on the higher BMIs44 or on the higher body fat levels35 of the least active subjects. However, neither the cross-sectional reports of nondisabled adults21, 35, 41, 42, 43, 44 nor our cross-sectional report of men with paraplegia can determine whether physical activity is either causally or independently linked with circulating inflammatory factors. Thus, controlled exercise experiments are needed to determine whether regular physical activity can ameliorate age- or injury-related increases in circulating inflammatory factors and whether activity-related reductions in circulating inflammatory factors are mediated by reductions in body fat. In addition, a direct measure of physical activity, as opposed to the self-report measure we used, may help to characterize more fully the relation between physical activity and inflammatory factors in future studies with the SCI population.

Our findings suggest that circulating IL-6 and CRP levels are elevated in men with SCI who are free of pressure ulcers and acute symptomatic infections. Other reports of elevated IL-6 and CRP levels in subjects with SCI have included participants with pressure ulcers14 and coexisting infections.15, 45 Our male participants with paraplegia (average age, 39y) had median IL-6 values that were 42% higher and median CRP values that were 62% higher than healthy, 59-year-old, nondisabled men who remained free of chronic diseases after 6 years of follow-up.4, 46

Both medication use and bladder management techniques need to be considered as potential explanations of the elevated IL-6 and CRP levels in our participants. IL-6 and CRP levels were elevated in our sample of men with paraplegia, even though 6 of 22 of our participants were taking long-term low doses of antibacterial medications, reportedly as a strategy to prevent urinary tract infections. Nevertheless, it is notable that circulating CRP levels were higher in medication users than in nonmedication users (7.2mg/L vs 3.4mg/L, P=.022), which is counterintuitive to what we expected. This finding may be an artifact of the small sample size or may be explained by the characteristics of our medication users, who were older (43y vs 36y, P=.052) and had a higher percentage of body fat (28.7% vs 24.4%, P=.130) than nonmedication users. In addition, although we did not collect information about bladder management techniques (ie, intermittent catheterization, indwelling catheter, condom catheter), it is likely that the large majority (>80%) of our male paraplegic participants were using either intermittent catheterization or condom drainage, and not an indwelling catheter.47, 48 Use of an indwelling catheter is associated with bacteriuria in men with SCI to a greater extent than are other bladder management techniques.49 Although IL-6 and CRP levels were clearly elevated in our participants, future studies are needed to determine the relations between body fat, age, medication use, bladder management techniques, and circulating inflammatory factors in men with SCI.

Chronic low-grade inflammation (as indicated by elevated IL-6 and CRP levels) in people with SCI is a concern because of the increased risks for T2D and heart disease that are associated with chronic low-grade inflammation.50 Circulating IL-6 is the primary cytokine mediator of inflammation.51 CRP is an acute-phase reactant and a marker of systemic inflammation that is synthesized in the liver in response to elevations in circulating IL-6. CRP also mediates and amplifies systemic inflammation by activating the complement pathway. Even though IL-6 is the primary cytokine mediator of inflammation, CRP is a better indicator of chronic systemic inflammation, because it has a longer half-life in the circulation. Accordingly, recent investigations have implicated chronic low-grade elevations in CRP in all phases of atherosclerosis, including plaque initiation,1 plaque progression,52 and plaque instability,53 which may ultimately precipitate an acute coronary event. In addition, elevated levels of IL-6 and CRP are associated with higher circulating insulin levels and with an increased risk for T2D in nondisabled people.6 Thus, chronic inflammation is a plausible contributor to diabetogenesis.50 As a result, chronic low-grade inflammation in people with SCI may help to explain their increased risks for heart disease16 and T2D.12 Future studies should determine which combinations of pharmacologic and nonpharmacologic therapies may be most effective for reducing systemic inflammation in people with SCI.

Our finding that functional ability did not correlate significantly with peak aerobic capacity or with circulating IL-6 and CRP levels is somewhat contrary to previous reports.21, 54, 55 Functional ability is an integration of physiologic capacity and physical performance, and it is mediated by psychologic factors like pain and confidence.56 Lower levels of functional ability are associated with lower peak relative aerobic capacity (in mL·kg−1·min−1) and with lower strength in larger samples (N range, 63–123) of people with quadriplegia and paraplegia.55 Thus, our finding of a moderate yet statistically nonsignificant correlation between functional ability and peak aerobic capacity (r=.416, P=.077) likely reflects a true association that was undetectable in our small sample size of paraplegic men (N=22). We also found that functional ability did not correlate significantly with circulating IL-6 and CRP levels. By contrast, lower levels of functional ability were associated with higher circulating IL-6 and CRP levels in nondisabled elderly people.21 The discrepant findings between the earlier report21 and our study may be explained by differences in study samples (elderly ambulatory participants vs middle-aged nonambulatory participants), the assessment of functional ability (walking speed vs past year of physical activity), and sample sizes (N=880 vs N=22).

Our finding that functional ability did not correlate significantly with either abdominal or total body fat agrees with an earlier report of a nonsignificant correlation between functional ability and BMI, in a sample of 123 men and women with paraplegia or quadriplegia.54 Although functional gains in lifting and wheeling activities may be expected at lower body weights, perhaps those who gain more weight over time work against progressive increases in resistance, thereby compensating for their weight gain with greater gains in upper-body strength. Alternatively, the SRFM, even with the addition of 2 higher-level functional tasks, may not be sensitive enough to detect subtle differences in functional ability in a group of men with paraplegia who are largely independent. Further study using more sensitive functional ability instruments, such as those designed to assess higher-level wheelchair skills,57 and more specific assessments of upper-body strength would help to determine the extent to which body weight or body fat affects functional ability in people with SCI.

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Conclusions 

We found that lower physical activity levels were associated with higher fasting glucose, lower HDL-C, and larger ASDs. Larger ASDs, in turn, were associated with higher fasting glucose, higher fasting and postload insulin, lower HDL-C, higher TG, and higher CRP levels. These findings suggest that the metabolic syndrome is prevalent in people with SCI and that diet and exercise trials are needed to determine the efficacy and effectiveness of lifestyle interventions aimed at slowing the progression of the metabolic syndrome in people with SCI. Moreover, it is difficult for people with SCI to lose weight once it is gained. Thus, the findings also highlight the potential importance of long-term obesity treatment and prevention programs, to reduce the risk for T2D and heart disease in people with SCI.

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References 

  1. Ross R . Atherosclerosis—an inflammatory disease . N Engl J Med . 1999;340:115–126
  2. Pickup JC , Mattock MB , Chusney GD , Burt D . NIDDM as a disease of the innate immune system (association of acute-phase reactants and interleukin-6 with metabolic syndrome X) . Diabetologia . 1997;40:1286–1292
  3. Koenig W , Sund M , Frohlich M , et al.   C-reactive protein, a sensitive marker of inflammation, predicts future risk of coronary heart disease in initially healthy middle-aged men (results from the MONICA (Monitoring Trends and Determinants in Cardiovascular Disease) Augsburg Cohort Study, 1984 to 1992) . Circulation . 1999;99:237–242
  4. Ridker PM , Cushman M , Stampfer MJ , Tracy RP , Hennekens CH . Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men . N Engl J Med . 1997;336:973–979
  5. Pradhan AD , Manson JE , Rifai N , Buring JE , Ridker PM . C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus . JAMA . 2001;286:327–334
  6. Yudkin JS , Stehouwer CD , Emeis JJ , Coppack SW . C-reactive protein in healthy subjects: associations with obesity, insulin resistance, and endothelial dysfunction: a potential role for cytokines originating from adipose tissue? . Arterioscler Thromb Vasc Biol . 1999;19:972–978
  7. Festa A , D’Agostino R , Howard G , Mykkanen L , Tracy RP , Haffner SM . Chronic subclinical inflammation as part of the insulin resistance syndrome (the insulin resistance atherosclerosis study (IRAS)) . Circulation . 2000;102:42–47
  8. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults . Executive summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) . JAMA . 2001;285:2486–2497
  9. LaPorte RE , Brenes G , Dearwater S , et al.   HDL cholesterol across a spectrum of physical activity from quadriplegia to marathon running . Lancet . 1983;1:1212–1213
  10. Washburn RA , Figoni SF . High density lipoprotein cholesterol in individuals with spinal cord injury (the potential role of physical activity) . Spinal Cord . 1999;37:685–695
  11. Reaven G . Metabolic syndrome (pathophysiology and implications for management of cardiovascular disease) . Circulation . 2002;106:286–288
  12. Bauman WA , Spungen AM . Disorders of carbohydrate and lipid metabolism in veterans with paraplegia or quadriplegia (a model of premature aging) . Metabolism . 1994;43:749–756
  13. Spungen AM , Wang J , Pierson RN , Bauman WA . Soft tissue body composition differences in monozygotic twins discordant for spinal cord injury . J Appl Physiol . 2000;88:1310–1315
  14. Segal JL , Gonzales E , Yousefi S , Jamshidipour L , Brunnemann SR . Circulating levels of IL-2r, ICAM-1, and IL-6 in spinal cord injuries . Arch Phys Med Rehabil . 1997;78:44–47
  15. Rebhun J , Madorsky JG , Glovsky MM . Proteins of the complement system and acute phase reactants in sera of patients with spinal cord injury . Ann Allergy . 1991;66:335–338
  16. Yekutiel M , Brooks ME , Ohry A , Yarom J , Carel R . The prevalence of hypertension, ischaemic heart disease and diabetes in traumatic spinal cord injured patients and amputees . Paraplegia . 1989;27:58–62
  17. Mattusch F , Dufaux B , Heine O , Mertens I , Rost R . Reduction of the plasma concentration of C-reactive protein following nine months of endurance training . Int J Sports Med . 2000;21:21–24
  18. Smith JK , Dykes R , Douglas JE , Krishnaswamy G , Berk S . Long-term exercise and atherogenic activity of blood mononuclear cells in persons at risk of developing ischemic heart disease . JAMA . 1999;281:1722–1727
  19. Kraus WE , Houmard JA , Duscha BD , et al.   Effects of the amount and intensity of exercise on plasma lipoproteins . N Engl J Med . 2002;347:1483–1492
  20. Cohen HJ , Pieper CF , Harris T , Rao KM , Currie MS . The association of plasma IL-6 levels with functional disability in community-dwelling elderly . J Gerontol A Biol Sci Med Sci . 1997;52:M201–M208
  21. Taaffe DR , Harris TB , Ferrucci L , Rowe J , Seeman TE . Cross-sectional and prospective relationships of interleukin-6 and C-reactive protein with physical performance in elderly persons (Macarthur studies of successful aging) . J Gerontol A Biol Sci Med Sci . 2000;55:M709–M715
  22. Rimmer JH , Riley BB , Rubin SM . A new measure for assessing the physical activity behaviors of persons with disabilities and chronic health conditions (the physical activity and disability survey) . Am J Health Promot . 2001;16:34–45
  23. Maynard FM , Bracken MB , Creasey G , et al.   International standards for neurological and functional classification of spinal cord injury. American Spinal Injury Association . Spinal Cord . 1997;35:266–274
  24. Hoenig H , Branch LG , McIntyre L , Hoff J , Horner RD . The validity in persons with spinal cord injury of a self-reported functional measure derived from the functional independence measure . Spine . 1999;24:539–543 discussion 543-4
  25. Hoenig H , Hoff J , McIntyre L , Branch LG . The self-reported functional measure (predictive validity for health care utilization in multiple sclerosis and spinal cord injury) . Arch Phys Med Rehabil . 2001;82:613–618
  26. Hoenig H , McIntyre L , Sloane R , Branch LG , Truncali A , Horner RD . The reliability of a self-reported measure of disease, impairment, and function in persons with spinal cord dysfunction . Arch Phys Med Rehabil . 1998;79:378–387
  27. Garschick E , Ashba J , Tun C , Lieberman S , Brown R . Assessment of stature in spinal cord injury . J Spinal Cord Med . 1997;20:36–42
  28. Kahn HS , Austin H , Williamson DF , Arensberg D . Simple anthropometric indices associated with ischemic heart disease . J Clin Epidemiol . 1996;49:1017–1024
  29. Van Loan MD , McCluer S , Loftin JM , Boileau RA . Comparison of physiological responses to maximal arm exercise among able-bodied, paraplegics and quadriplegics . Paraplegia . 1987;25:397–405
  30. Modlesky CM , Bickel CS , Slade JM , Meyer RA , Cureton KJ , Dudley GA . Assessment of skeletal muscle mass in men with spinal cord injury using dual-energy x-ray absorptiometry and magnetic resonance imaging . J Appl Physiol . 2004;96:561–565
  31. Allain CC , Poon LS , Chan CS , Richmond W , Fu PC . Enzymatic determination of total serum cholesterol . Clin Chem . 1974;20:470–475
  32. McGowan MW , Artiss JD , Strandbergh DR , Zak B . A peroxidase-coupled method for the colorimetric determination of serum triglycerides . Clin Chem . 1983;29:538–542
  33. Trinder P . Determination of glucose in blood using glucose oxidase with an alternative oxygen acceptor . Ann Clin Biochem . 1969;6:24–27
  34. Haffner SM , Miettinen H , Stern MP . The homeostasis model in the San Antonio Heart Study . Diabetes Care . 1997;20:1087–1092
  35. Manns PJ , Williams DP , Snow CM , Wander RC . Physical activity, body fat, and serum c-reactive protein in postmenopausal women with and without hormone replacement . Am J Human Biol . 2003;15:91–100
  36. Janssen TW , van Oers CA , van Kamp GJ , TenVoorde BJ , van der Woude LH , Hollander AP . Coronary heart disease risk indicators, aerobic power, and physical activity in men with spinal cord injuries . Arch Phys Med Rehabil . 1997;78:697–705
  37. Dallmeijer AJ , Hopman MT , van der Woude LH . Lipid, lipoprotein, and apolipoprotein profiles in active and sedentary men with tetraplegia . Arch Phys Med Rehabil . 1997;78:1173–1176
  38. Maki KC , Briones ER , Langbein WE , et al.   Associations between serum lipids and indicators of adiposity in men with spinal cord injury . Paraplegia . 1995;33:102–109
  39. Dibbs Z , Thornby J , White BG , Mann DL . Natural variability of circulating levels of cytokines and cytokine receptors in patients with heart failure (implications for clinical trials) . J Am Coll Cardiol . 1999;33:1935–1942
  40. Ockene IS , Matthews CE , Rifai N , Ridker PM , Reed G , Stanek E . Variability and classification accuracy of serial high-sensitivity C-reactive protein measurements in healthy adults . Clin Chem . 2001;47:444–450
  41. LaMonte MJ , Durstine JL , Yanowitz FG , et al.   Cardiorespiratory fitness and C-reactive protein among a tri-ethnic sample of women . Circulation . 2002;106:403–406
  42. Church TS , Barlow CE , Earnest CP , Kampert JB , Priest EL , Blair SN . Associations between cardiorespiratory fitness and C-reactive protein in men . Arterioscler Thromb Vasc Biol . 2002;22:1869–1876
  43. Geffken DF , Cushman M , Burke GL , Polak JF , Sakkinen PA , Tracy RP . Association between physical activity and markers of inflammation in a healthy elderly population . Am J Epidemiol . 2001;153:242–250
  44. Rawson ES , Freedson PS , Osganian SK , Matthews CE , Reed G , Ockene IS . Body mass index, but not physical activity, is associated with C-reactive protein . Med Sci Sports Exerc . 2003;35:1160–1166
  45. Galloway A , Green HT , Windsor JJ , Menon KK , Gardner BP , Krishnan KR . Serial concentrations of C-reactive protein as an indicator of urinary tract infection in patients with spinal injury . J Clin Pathol . 1986;39:851–855
  46. Ridker PM , Rifai N , Stampfer MJ , Hennekens CH . Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men . Circulation . 2000;101:1767–1772
  47. McKinley WO , Jackson AB , Cardenas DD , DeVivo MJ . Long-term medical complications after traumatic spinal cord injury (a regional model systems analysis) . Arch Phys Med Rehabil . 1999;80:1402–1410
  48. Gallien P , Nicolas B , Robineau S , Le Bot MP , Durufle A , Brissot R . Influence of urinary management on urologic complications in a cohort of spinal cord injury patients . Arch Phys Med Rehabil . 1998;79:1206–1209
  49. Esclarin De Ruz A , Garcia Leoni E , Herruzo Cabrera R . Epidemiology and risk factors for urinary tract infection in patients with spinal cord injury . J Urol . 2000;164:1285–1289
  50. Pradhan AD , Ridker PM . Do atherosclerosis and type 2 diabetes share a common inflammatory basis? . Eur Heart J . 2002;23:831–834
  51. Heinrich PC , Castell JV , Andus T . Interleukin-6 and the acute phase response . Biochem J . 1990;265:621–636
  52. Torzewski M , Rist C , Mortensen RF , et al.   C-reactive protein in the arterial intima (role of C-reactive protein receptor-dependent monocyte recruitment in atherogenesis) . Arterioscler Thromb Vasc Biol . 2000;20:2094–2099
  53. Kobayashi S , Inoue N , Ohashi Y , et al.   Interaction of oxidative stress and inflammatory response in coronary plaque instability. Important role of C-reactive protein . Arterioscler Thromb Vasc Biol . 2003;23:1398–1404
  54. Noreau L , Shephard RJ , Simard C , Pare G , Pomerleau P . Relationship of impairment and functional ability to habitual activity and fitness following spinal cord injury . Int J Rehabil Res . 1993;16:265–275
  55. Hjeltnes N , Jansen T . Physical endurance capacity, functional status and medical complications in spinal cord injured subjects with long-standing lesions . Paraplegia . 1990;28:428–432
  56. Cress ME , Buchner DM , Questad KA , Esselman PC , deLateur BJ , Schwartz RS . Continuous-scale physical functional performance in healthy older adults (a validation study) . Arch Phys Med Rehabil . 1996;77:1243–1250
  57. Kilkens OJ , Post MW , van der Woude LH , Dallmeijer AJ , van den Heuvel WJ . The wheelchair circuit (reliability of a test to assess mobility in persons with spinal cord injuries) . Arch Phys Med Rehabil . 2002;83:1783–1788
  • a Fisher Scientific International Inc, Liberty Ln, Hampton, NH 03842.
  • b Metro Equipment Corp, Sunnyvale, CA 94085.
  • c SensorMedics, 22705 Savi Ranch Pkwy, Yorba Linda, CA 92887.
  • d Monarch Rehab Trainer, model 881E; Monarch Exercise AB, 43282 Varberg, Sweden.
  • e QDR 4500A; Hologic, 35 Crosby Dr, Bedford, MA 01730.
  • f Linco Research, 6 Research Park Dr, St. Charles, MO 63304.
  • g R&D Systems Inc, 614 McKinley Pl NE, Minneapolis, MN 55413.
  • h Diagnostic Systems Laboratories, 445 Medical Center Blvd, Webster, TX 77598.
  • i SPSS Inc, 233 S Wacker Dr, 11th Fl, Chicago, IL 60606.

 Supported by the Christopher Reeve Paralysis Foundation.

 No commercial party having a direct financial interest in the results of the research supporting this article has or will confer a benefit on the author(s) or on any organization with which the author(s) is/are associated.

PII: S0003-9993(05)00070-5

doi:10.1016/j.apmr.2004.11.020

Archives of Physical Medicine and Rehabilitation
Volume 86, Issue 6 , Pages 1176-1181, June 2005

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