Aging Table 2 Cardiovascular and Endocrine Systems

Author Year; Country
Score
Research Design
Total Sample Size

Methods

Outcome

Leaf et al. 1993;
USA
Downs & Black = 15
Longitudinal
N SCI = 47

Population: 22 persons with tetraplegia (mean age 39.0 + 16.7, 15 – 80 yrs); 25 persons with paraplegia, (mean age 42.0 + 18.8, 19– 82 yrs); YPI range for both groups 35-3605 days.
Methodology: Characterize the risk of cardiac dysrhythmias via 24 hrs Holter monitoring, and to determine if significant cardiac event occurred at 2 yrs post-baseline.
Outcome Measures: Holter monitoring.

  1. Despite the theoretical basis for↑ incidence of cardiac dysrhythmias following SCI, no significant cardiac events occurred for sample at 2 yr follow-up.

Cheville & Kirshblum 1995;

USA

Cross-sectional with AB controls

Downs & Black = 15

N SCI = 30

N controls = 30

Population: 29 males and 1 female; mean age 59 (range 22-82 yrs); mean YPI 24 (range 2-50 yrs); age and gender-matched AB controls

Methodology: Comparison of thyroid function and to determine the incidence and clinical prevalence of low T3 symdrome

Outcome Measures: Serum levels of triiodothyronine (T3) and thyroxin (T4)

  1. Mean triiodothyronine (T3) levels (p=0.0001) and thyroxin (T4) levels (p=0.02) were  in group with SCI.
  2. T3 resin uptake levels were ↑ (p=0.0001) in group with SCI.

Bauman et al. 1999;

USA

Downs & Black = 14

Cross-sectional with AB controls

N SCI= 320

N controls = 303

Population: 234 males and 86 females with SCI, mean age 41 ± 0.62 yrs (range 20 - 77), mean YPI 15 ± 0.52 (range 1-57 yrs); 303 age-, gender-, ethnicity-, and activity level- matched AB controls

Methodology: Comparison of serum lipid profiles between SCi and control

Outcome Measures: Serum levels of: total cholesterol (TC), triglycerides (TG), HDL-cholesterol (HDL-c), LDL-cholesterol (LDL-c), body mass index (BMI)

  1. Group with SCI had  TC (p < 0.0001), TG (p < 0.05), HDL-c (p < 0.0005), LDL-c (p <0.0001), and  TC/HDL-c ratio (p <0.01) than the AB control group.
  2. The AB control group had  BMI compared to the group with SCI (p < 0.0001), but the estimated per cent body fat was  in the group with SCI (p < 0.0001).

LaVela et al. 2006

USA

Downs & Black = 14

Cross-sectional with AB controls 

N SCI = 3708

N controls = 18018

Population: 741 veterans (98.2% male) with SCI/D and diabetes, mean age 64.1 (range < 40 to 70+ yrs); mean YPI 23.9 yrs; 2967 veterans with SCI/D (96.8%) and no diabetes; mean age 59.2 yrs, mean YPI 23.8 yrs; 1342 veteran AB controls (age range <40 to 70+ yrs) and 16676 general population AB controls (age range < 40 to 70+ yrs)

Methodology: Comparison of prevalence rates of diabetes mellitus

Outcome Measures: Prevalence of diabetes

  1. Diabetes prevalence  among veterans with SCI/D compared to general population (p < 0.0001), but similar to other veterans.
  2. For those 45 to 59 yrs of age, diabetes prevalence was  in veterans with an SCI/D.

Huang et al. 1993;

China

Downs & Black = 14

Cross-sectional with AB controls

N SCI = 30

N controls = 30

Population: 30 males with SCI, ages 17.4 - 43.9 yrs, mean 31.4 yrs; 30 healthy males, ages 21.0-38.7 yrs, mean 29.6 yrs

Methodology: Comparison of pituitary-testicular and pituitary-thyroid axes with age matched, sexually active control population

Outcome Measures: Endocrinologic studies, Radioimmunoassay methods

  1. 4 persons with SCI had low levels of T3, 1 with  serum follicle-stimulating hormone, 8 with  serum testosterone levels, and 11 with  serum prolactin levels.
  2. Compared to AB controls, persons with SCI had  LH responses, with 8 having exaggerated or prolonged LH responses.

Apstein & George 1998;
USA
Downs & Black = 13
Longitudinal with AB controls
N SCI = 100
N controls = 80

Population: 100 male SCI, mean age 45; 80 age- and gender-matched AB controls
Methodology: Evaluate changes in serum lipids at 4, 16, 36 and 52 weeks post-injury, and compared at 52 weeks compared to AB controls
Outcome Measures: Serum levels of total cholesterol (TC), LDL, HDL

  1. Total serum cholesterol (TC) levels were always ↓ (p < 0.05) in males with tetraplegia compared to males with paraplegia.
  2. No differences in triglycerides between SCI groups at any time.
  3. At 4 weeks after injury, low-density lipoprotein-cholesterol (LDL) were ↓ (p < 0.05) in males with tetraplegia compared to males with paraplegia, but were equivalent at 1 YPI.
  4. Serum high-density lipoprotein cholesterol (HDL) were ↓ (p < 0.05) in group with tetraplegia compared to group with paraplegia at 4 weeks, but ↑ to AB levels at 1 YPI.
  5. LDL/HDL ratio ↓ (p < 0.05) at 4 weeks to 1 YPI in group with tetraplegia compared to group with paraplegia, whose LDL/HDL was comparable to AB controls.

Bauman et al. 2001;
USA
Downs & Black = 13
Cross-sectional with AB controls
N SCI = 835
N controls = 14.838

Population: 723 males and 122 females with SCI; mean age 38 + 11 yrs, mean YPI 12 + 9 yrs
Methodology: Comparison of levels of plasma homocysteine to AB reference population
Outcome Measures: Plasma homocysteine (PH)

  1. Older group with SCI ( > 50 years) had ↑ mean PH (p < 0.05) than the younger age group.
  2. Group with SCI had ↑ levels of PH than control group.

Petrofsky & Laymon 2002;
USA
Downs & Black = 13
Cross-sectional with AB controls
N SCI = 50
N controls = 50

Population: All males with complete paraplegia, divided into four age groups (20 – 30 yrs, 31 – 40 yrs, 41 – 50 yrs, 51 – 65 yrs); YPI range 3 – 10 yrs; age-, gender-, and height-matched AB controls
Methodology: Comparison of blood pressure and heart rate during isometric exercise and at rest (leg and arms)
Outcome Measures: Heart rate, blood pressure

  1. Group with SCI had a larger change in blood pressures both at rest and during leg exercise (p < 0.05).
  2. Heart rate during handgrip exercise was normal for both SCI and AB groups, but was absent in the SCI group during the leg exercise.

Tsitouras et al. 1995
Downs & Black = 13
Cross-sectional with AB controls
N SCI =20
N controls = 16

Population: 20 males with SCI, ages 42 + 2, 15 + 2 YPI; 16 healthy males, ages 39+4.
Methodology: Comparison of serum growth hormone and testosterone between the 2 groups.
Outcome Measures:  Serum testosterone (T), human growth hormone (hGH) and insulin-like growth factor 1 (IGF-I).

  1. SCI is associated with impaired secretion of both T and hGH (not the result of aging).
  2. Duration of injury appears to have an adverse effect on serum T.

Bauman & Spungen 1994; USA
Downs & Black =12
Cross-sectional with AB controls
N SCI = 100
N controls = 50

Population: 50 males with paraplegia (mean age 51±2, 19±2 YPI) and 50 with tetraplegia (mean age 47±2, 17±2 years post-injury); 50 male controls (mean age 51±2 yrs). Age- and Body Mass Index (BMI)-matched. 
Methodology: Comparison of responses from oral glucose tolerance test (OGTT).
Outcome Measures: Mean plasma glucose and insulin values, serum lipid levels.

  1. 82% of controls had normal oral glucose tolerance vs. 38% of those with tetraplegia and 50% with paraplegia.
  2. 22% of SCI group were diabetic vs. 6% of controls.
  3. Those with SCI develop carbohydrate disorders at younger ages.
  4. Subjects with SCI had significantly higher mean glucose and insulin values during the OGTT when compared to controls.
  5. Serum lipid levels in subjects with SCI showed a decreased HDL cholesterol level (38±1 mg/dL).

Wang et al. 2007;
Taiwan
Downs & Black = 12
Cross-sectional with AB controls
N SCI = 62
N controls = 29

Population: All males with complete SCI; mean age 28.0 + 9.7 (range 16.2–59.1 yrs); mean YPI 11.8 + 7.0 (1.2–27.7 yrs); age- and gender-matched AB controls
Methodology: Comparison of serum levels of markers of inflammation and endothelial activation between SCI and controls
Outcome Measures: Body weight, BMI, serum levels of albumin, creatinine, LDL, HDL, insulin, C-reactive proteins (CRP), interleukin-6, endothelin-1, and sVCAm-1

  1. Compared to AB controls, group with SCI had ↓ body weight (p = 0.017), BMI (p = 0.044), and serum albumin and creatinine levels (p < 0.001).
  2. Group with SCI had ↓ density lipoprotein-cholesterol (LDL; p = 0.048), ↓ high-density lipoprotein-cholesterol (HDL; p < 0.001), and ↑ total cholesterol/HDL cholesterol ratio (p < 0.001), and a trend toward ↑ insulin levels than AB controls.
  3. Group with SCI had ↑ serum levels of CRP (p < 0.001), interleukin-6 (p < 0.001), endothelin-1 (p < 0.001), and sVCAm-1 (p < 0.001) than AB group.

Demirel et al. 2001;
Turkey
Downs & Black = 12
Cross-sectional with AB controls
N SCI = 69
N controls = 52

Population: 53 males and 16 females with SCI; mean age 33.9 + 11.37 (range 10–70 yrs); mean YPI 16 + 10 (range 1–41 yrs); age- and gender-matched AB controls
Methodology: Comparison of standard risk factors for coronary heart disease (CHD)
Outcome Measures: BMI, blood pressure, diabetes mellitus, HDL, LDL, total cholesterol

  1. Impaired fasting glucose (p < 0.001), diabetes mellitus (p = 0.04), hyperuricemia (p = 0.001), high total cholesterol (TC; p < 0.001), low density lipoprotein-cholesterol (LDL; p < 0.001), low high-density lipoprotein-cholesterol (HDL; p < 0.001), high TC/HDL (p < 0.001), LDL/HDL ratios were more common in persons with SCI (p < 0.001) than in the AB group, while positive family history was more common in the AB control group (p < 0.001). 

Shetty et al. 1993;
USA
Downs & Black = 12
Cross-sectional with AB controls
N SCI = 41
N controls = 119

Population: 41 men with tetraplegia, ages 24 – 66 yrs, mean age 41 yrs; 119 AB control, ages 30 – 70 yrs
Methodology: Comparison of growth hormone (GH) and Somatomedin C (SmC) concentrations in the two groups
Outcome Measures: Radioimmunoassay of SmC

  1. SmC was ↓ (p < 0.007) in group with SCI than AB controls. Inverse relationship between SmC level, and ↑ age in both groups.
  2. Severe inactivity or SCI may cause hyposomatomedinemia, which could contribute to ↓ lean body mass and muscle atrophy, ↑ risk for pressure sore formation and osteoporosis post-SCI.

Zlotolow et al. 1992;
USA
Downs & Black = 11
Cross-sectional with AB controls
N SCI = 28
N controls = 52

Population: 28 males with paraplegia, mean age 48 + 2 (25 – 65 yrs); time since injury ≥1.5 yrs; 52 age- and gender-matched AB controls
Methodology: Comparison of diet, BMI, and serum lipid levels between SCI and AB control groups
Outcome Measures: Serum levels of total cholesterol, HDL, and triglycerides; total caloric and cholesterol intake from diet; BMI

  1. No differences in BMI, total caloric or cholesterol intake between SCI and AB control groups.
  2. Serum HDL cholesterol ↓ (p < 0.0001) compared to AB controls.
  3. Total caloric intake ↓ with age (p < 0.0005) in AB controls but not SCI group.

Liang et al. 2007;
USA
Downs & Black = 11
Cross-sectional with AB controls
N SCI = 185
N controls = 185

Population: All males with SCI, mean age 39 + 10.4 yrs; mean YPI 11.7 (range 1-40.4 yrs); 185 age, gender, and race-matched AB controls
Methodology: Comparison of prevalence rates of metabolic syndrome
Outcome Measures: Total cholesterol (TC), HDL and LDL; Elevated glucose; Triglyceride (TG)

  1. Group with SCI had ↓ HDL (p < 0.01), TG (p < 0.05), glucose (p < 0.001), TC (p < 0.001), and LDL (p < 0.001).

Bauman et al. 2004;
USA
Downs & Black = 11
Cross-sectional with AB controls
N SCI = 13
N controls = 13

Population: 13 SCI males mean age 37 + 8 yrs; mean YPI 15 + 9 yrs; AB identical twins of subjects were control
Methodology: Comparison of energy expenditure and fat-free mass (FMM) with monozygotic twin
Outcome Measures: Basal energy expenditure (BEE) and resting energy expenditure (REE) by indirect calorimetry;
Fat-free mass (FFM) and fat mass (FM) assessed by dual-energy X-ray absorptiometry; Total body potassium (TBK)

  1. Twin with SCI had ↓ BEE (p < 0.005) and REE (p < 0.05) than AB twin.
  2. Fat mass was equivalent between groups, but ratios of FM to FMM and FM to TBK were ↓ (p < 0.05) in twins with SCI.

Jones et al. 2003;
New Zealand
Downs & Black = 11
Cross-sectional with AB controls
N SCI = 19
N controls = 19

Population: All males with SCI; mean age 34 + 8 (16 – 52 yrs); mean YPI > 1 yr; age, gender, height, and weight-matched AB controls
Methodology: Comparison of BMI and adiposity
Outcome Measures: BMI; Total body and regional lean tissue and fat mass

  1. BMI was similar in both groups but total body lean tissue mass was ↓ (p < 0.001) whereas total body fat mass was ↑ (p <0.05) in group with SCI.
  2. Body fat percentage was ↑ (p <0.01) in group with SCI.

Nuhlicek et al 1988;
China
Downs & Black =10
Cross-sectional with AB controls
N SCI = 37
N controls = 10

Population: All males, 19 with tetraplegia; 18 with paraplegia; age range 19 – 49 yrs; age and gender matched AB controls
Methodology: Comparison of body composition between control and groups of different SCI injury levels
Outcome Measures: Anthropometry; Total body water (TBW); Predicted extracellular water (ECW); Lean body mass (LBM) and body cell mass (BCM); Extracellular mass (ECM) and extracellular water (ECW)

  1. Diminishing TBW, ICW, LBM, BCM, and muscle cell mass, and ↑ fat mass with higher spinal lesions.
  2. No change in total body weight, ECM or ECW.

Orazaki et al. 2007;
USA
Downs & Black = 10
Cross-sectional with AB controls
N SCI = 82
N controls = 273

Population: 67 males and 15 females with SCI, mean age 49.7+12 (range 20-90 yrs), mean time since injury 19.7+10 yrs; 273 age, gender, ethnicity, and risk factor-matched AB controls (n=273)
Methodology: Comparison of the burden of atherosclerosis between SCI and control groups
Outcome Measures: Coronary artery calcium (CAC) scores, mean calcium scores

  1. Mean calcium score of the SCI group was ↑ (p <0.0001) than AB controls.
  2. Prevalence of coronary artery calcium (CAC) was greater in persons with SCI (p < 0.05) than in AB controls. CAC score was also greater (p < 0.01).

Yamamoto et al. 1999;
Japan
Downs & Black = 10
Cross-sectional with AB controls
N SCI = 7
N controls = 7

Population: 7 males with complete tetraplegia; mean age 41 + 10.0 (range 33–58 yrs); mean YPI 13.7 + 3.4 (range 9–18 yrs); age- and gender matched AB controls (n=7)
Methodology: Comparison of blood pressure, heart rate, and hormonal changes during 2 minutes of sustained contraction
Outcome Measures: Heart rate, blood pressure

  1. Group with SCI had no changes in heart rate during exercise, whereas AB controls did change (p < 0.05).
  2. Blood pressure ↑ (p < 0.05) in both groups.

Huang et al. 1998;
China
Downs & Black =10
Cross-sectional with AB controls
N SCI = 25
N controls = 25

Population: All males with SCI; mean age 35.4 (range 18 – 55 yrs); mean YPI 7.5 (range 1.1 – 15.8 yrs); age and gender matched AB controls
Methodology: Comparison of hypothalamus-pituitary-adrenal axis
Outcome Measures: Radioimmunoassay methods, corticotropin-releasing hormone levels

  1. Cortisol response to corticotropin-releasing hormone was ↓ (p < 0.01) in SCI group, but differences disappeared if correction was made for baseline values.

Bauman et al. 1996;
USA
Downs & Black = 9
Cross-sectional with AB controls
N SCI = 34
N controls = 48

Population: 34 males with SCI, mean age 50+2 yrs, mean time since injury 11+2 yrs; 48 age- and gender-matched AB controls
Methodology: Comparison of Body Mass Index (BMI) and plasma leptin  (PL) between SCI and control groups
Outcome Measures: Plasma leptin levels, BMI

  1. Group with SCI had ↑ levels of PL (p < 0.005) than the control group.
  2. No significant differences in BMI between SCI and control groups.

Bauman et al. 1994; USA
Downs & Black = 9
Cross-sectional with AB controls
N SCI = 16
N controls = 16

Population: 16 males with SCI mean age 45±3 yrs, mean 19±3 YPI; 16 controls mean age 39±4 yrs
Methodology: Comparison of growth hormone response to intravenous infusion of arginine hydrochloride (30 g/subject over 30 minutes).
Outcome Measures: Plasma human growth hormone (hGH) release and plasma insulin-like growth factor (IGF-I) levels; Body Mass Index (BMI).

  1. Mean hGH responses at 30 and 60 minutes were significantly ↓in the group with SCI than in the control group (3.4±0.7 vs. 10.7±2.5 ng/ml, p <0.01; and 5.2±1.5 vs. 12.5±2.7 ng/ml, p <0.05), even when controlled for age and BMI.
  2. Mean plasma IGF-I levels were ↓in SCI subjects <45 years old than in AB counterparts (202±19 vs. 324±27 ng/ml, p<0.05). Comparison of those >45 years old revealed no differences.
  3. ↓daily physical activity depresses hGH/IGF-I axis in younger individuals with SCI and may be considered a state of premature aging.

Jones et al. 2004;
New Zealand
Downs & Black = 9
Cross-sectional with AB controls
N SCI = 20
N controls = 20

Population: 20 males with SCI, mean age 33 + 2 (range 16 – 52 yrs); mean YPI 10.3 + 1.8 yrs; 20 age, gender, height, weight, and activity level-matched AB controls
Methodology: Comparison of prevalence of metabolic syndrome
Outcome Measures: Lean and fat mass; Plasma glucose and insulin; Total cholesterol; HDL; Oral glucose tolerance test (OGTT)          

  1. 55% of the group with SCI met the criteria for metabolic syndrome, whereas none of the controls did.

Wang et al. 1992;
China
Downs & Black = 9
Cross-sectional with AB reference population
N SCI = 63

Population: All males with SCI; mean age 31.2 (range 18 – 44 yrs); mean YPI 6.2 (range 8 mos – 20 yrs); AB reference population.
Methodology: Comparison of hormone patterns of gonadotropin and testosterone
Outcome Measures: Serum levels of triiodothyronine, testosterone, serumfollicle-stimulating hormone, luteinizing hormone

  1. 7 persons with SCI had ↓ serum triiodothyronine below reference level, and 8 cases had low serum testosterone.
  2. 17 persons with SCI had hyperprolactinemia, and 9 cases had elevated serum testosterone level.  6 persons with SCI had elevated serumfollicle-stimulating hormone and 4 cases had elevated luteinizing hormone.

Spungen et al. 2000; USA
Downs & Black = 8
Cross-sectional with AB controls
N SCI = 8
N controls = 8

Population: Able-bodied (AB) twins of 8 males with SCI with complete paraplegia ages 40.4 + 10, 16 + 9 years post-injury.
Methodology: SCI subjects were compared with twin on total and regional lean tissue and fat mass.
Outcome Measures: Body composition.

  1. Group with SCI had significant ↓ of total body lean mass compared to AB twin group, independent of age.
  2. Group with SCI had significantly ↑ total body fat mass compared to AB twin group.