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Risk Analysis for Cardiovascular Disease after Spinal Cord Injury. The State of the Science Conference July 17, 2007 National Rehabilitation Hospital RRTC on Spinal Cord Injury. Ann M. Spungen, EdD

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risk analysis for cardiovascular disease after spinal cord injury

Risk Analysis for Cardiovascular Disease after Spinal Cord Injury

The State of the Science Conference

July 17, 2007

National Rehabilitation Hospital

RRTC on Spinal Cord Injury

Ann M. Spungen, EdD

Associate Professor of Medicine and Rehabilitation Medicine, Mount Sinai School of Medicine, NY

Associate Director VA RR&D Center of Excellence for the Medical Consequences of SCI

Co-Chair VA CS #535

outline
Outline
  • Risk factor description (AHA, NCEP)
    • Assessments for lipids, DM, IR, HTN
    • Traditional, non traditional or emerging
  • Risk factor treatment goals and guidelines
  • Risk factors in SCI (data)
american heart association aha risk factors for cvd
Non Modifiable

Increasing age

Male gender

Heredity

Other Contributors

Stress

Excess alcohol

Modifiable

Smoking

High cholesterol

High blood pressure

Physical inactivity

Obesity

Diabetes mellitus

American Heart Association (AHA) Risk Factors for CVD
aha modifiable rfs for cvd
Smoking

Independent RF

2-4x >risk of CHD

Persons w/CHD, 2x risk for sudden death

Neg. acts on other RFs (Cholesterol, BP and DM)

Cigar/pipe also have >risk of death

Secondhand smoke exposure  >risk of CHD

High Cholesterol

>Serum cholesterol; >risk for CHD

In presence of HTN or Smk, risk for CHD is amplified

High Blood Pressure

 work of the heart  stiffening

 risk of stroke, heart attack, kidney failure, & CHF

 risk w/obesity, smk, high cholesterol, and/or DM

Physical Inactivity

 PA, >risk of heart and vessel disease

Obesity

>Body fat (waist), >risk of HD

 risk of DM

Diabetes Mellitus

¾ of all DM die of some form of heart or vessel disease

AHA ModifiableRFs for CVD
aha risk factors for cvd
Non Modifiable

Increasing age

83% CHD deaths are in ≥65y

Older ages, women who have heart attacks are more likely to die than men

Gender

Men >risk of heart attack and occur earlier in life

Post menopause Women’s death rate from CHD ↑, not equal to men’s

Heredity (Race/Ethnicity)

>Risk in children of parents w/HD

>Risk in African, Mexican, Native, Hawaiian, and some Asian Americans than in Caucasians

Other Contributors

Stress

Noted relationship w/CHD

May cause worsening of other RFs (i.e.smoking, overeating, etc.)

Excess alcohol

Women (1 drink/d) and Men (2 drinks/d)

Can raise BP

Increase TGs

Irregular HBs

Add to obesity

AHA Risk Factors for CVD
non traditional or emerging risk factors for chd
Non Traditional or Emerging Risk Factors for CHD
  • Insulin resistance
  • Plasma homocysteine
  • C-reactive protein
  • Lipoprotein (a)
  • Small, dense LDL particles
  • Prothrombic factors
risk factor assessment
Lipid Profile

Oral Glucose Tolerance

Blood Pressure Assessment

Screening

Medical Hx

Age, Gender

Smoking

Obesity

Family Hx

Physical Activity

Stress/lifestyle

Risk Factor Assessment
atp iii classification of ldl cholesterol mg dl
ATP III Classification ofLDL Cholesterol (mg/dL)

LDL Cholesterol

<100

100-129

130-159

160-189

≥190

HDL Cholesterol

<40

≥60

Classification

Optimal

Near or above optimal

Borderline high

High

Very high

Low

High

Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285:2486-2497.

slide9

ATP IIIRisk Categories & LDL-C Goals

Risk Category

CHD and CHD risk equivalents or

10-year risk >20%

≥2 risk factors or

10-year risk ≤20%

0-1 risk factor*

LDL Goal (mg/dL)

<100

<130

<160

*Almost all people with 0-1 risk factor have a 10-year risk <10%; thus, Framingham risk calculations are not necessary.

NLEC

2002, www.lipidhealth.org

Expert Panel on Detection, Evaluation, and Treatment of

High Blood Cholesterol in Adults.JAMA. 2001;285:2486-2497.

slide10

Diagnostic Criteria for Disorders of Carbohydrate Metabolism

OGTT

120 min

(mg/dL)

<140

140-199

≥200

Normal (NGT)

Impaired (IGT)

Diabetic (DM)

FPG

(mg/dL)

<100

100*-125

≥126

Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus: Diabetes Care 20:1183-1197, 1997.

*Updated from 110, Diabetes Care 2003

assessment of risk factor analysis
Assessment of Risk Factor Analysis
  • Framingham Point Scores (separate for gender)
    • Age categories
    • Total-C by Age Cat
    • Smoker / Nonsmoker
    • HDL-c categories
    • SBP categories

http://www.nhlbi.nih.gov/guidelines/cholesterol/index.htm

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. 285(19), 2001.

studies in sci
Studies in SCI:
  • Body Comp
    • Spungen AM, et al. J Appl Physiol, 2000.
    • Spungen AM, et al. J Appl Physiol, 2003.
  • Oral Glucose Tolerance
    • Bauman WA and Spungen AM. Metabolism. 1994; 43:749-756.
    • Bauman WA, et al. Spinal Cord. 1999; 37: 765-771.
  • Lipid Profile
    • Bauman WA, et al. Spinal Cord. 1998; 36:13-17.
    • Bauman WA, et al. Spinal Cord. 1999; 37:485-493.
    • La Porte RE et al. Lancet. 1:1212-1213 1983.
  • Homocysteine
    • Bauman WA, et al. J Spinal Cord Medicine. 2001; 24:81-86.
  • C-Reactive Protein
    • Lee MY, et al. JSCM 28:20-25, 2005.
  • Risk Factors for CHD
    • Bauman WA and Spungen AM, Top Spinal Cord Inj Rehabil; 12:35-53.
    • Nash MS Arch Phys Med Rehabil. 88:751-757, 2007
slide13

5

0

-5

-10

-15

-20

R2 = 0.44, P<0.01

Slope = -0.488 ±0.16

-25

-30

0

5

10

15

20

25

30

Total Body Lean Tissue Loss with Duration of Injury in the SCI Twins

Intrapair Diff (kg)

Duration of Injury (y)

body composition in sci

60

100

50

90

80

40

70

30

TOTAL BODY Percent Fat

Control

60

TOTAL BODY Percent Lean

Para

20

50

SCI

Tetra

10

Control

40

0

30

10

15

20

30

35

40

45

25

10

20

30

40

50

60

70

80

AGE (y)

Body Mass Index (kg/m2)

Body Composition in SCI

Spungen AM, Adkins RH, Stewart CA, Wang J, Pierson Jr RN, Waters RL, Bauman WA. Factors influencing body composition in persons with spinal cord injury: A cross-sectional study. J Appl Physiol, 2003.

body composition summary
Body Composition Summary
  • Persons with SCI have:
    • lower amounts of lean body mass
    • higher amounts of percent fat
    • loose lean tissue mass with continued duration of injury
    • loose lean tissue mass at a greater rate over age than the general population
slide17

Oral Glucose Tolerance in Veterans with or without SCI

Bauman WA and Spungen AM. Metabolism. 43: 749-756, 1994

slide18

Relationship of Age with Glucose Tolerance in Veterans

Bauman WA and Spungen AM. Metabolism. 43: 749-756, 1994

oral glucose tolerance in non vets with sci
Oral Glucose Tolerance in Non VETS with SCI
  • 201 SCI
    • 169 Men, 32 Women
    • 114 Latino, 54 White, 28 Afric Amer
    • 56 Comp Tetra, 25 Inc Tetra, 84 Comp Para, 36 Inc Para
  • Total Study Group meanSEM (range)
    • Age (y) 39  0.8 (20 - 73)
    • DOI (y) 13  0.7 (1 - 43)
    • BMI (kg/m2) 25  0.4
    • TB %Fat (%) 34  0.9

Bauman WA, Adkins RH, Spungen AM, Waters RL. The effect of residual neurological deficit on oral glucose tolerance in persons with chronic spinal cord injury. Spinal Cord. 1999; 37: 765-771.

oral glucose tolerance in non vets with sci20

DM

13%

n=27

IGT

Normal

28%

n=56

59%

n=118

Oral Glucose Tolerance inNon VETS with SCI

IGT or DM

Comp Tetra73%*

Inc Tetra 44%

Comp Para 24%

Inc Para 31%

*2(6)=36.9, p<0.0001

Bauman WA, Adkins RH, Spungen AM, Waters RL. The effect of residual neurological deficit on oral glucose tolerance in persons with chronic spinal cord injury. Spinal Cord. 1999; 37: 765-771.

oral glucose tolerance in non vets with sci21
Oral Glucose Tolerance inNon VETS with SCI
  • Percent with hyperinsulinemia during the OGTT
    • 53% Tetra (mostly Complete Tetra)
    • 37% Para
    • 46% Males (*sig. higher peak and  insulin with similar glucose levels)
    • 31% Females

Bauman WA, Adkins RH, Spungen AM, Waters RL. The effect of residual neurological deficit on oral glucose tolerance in persons with chronic spinal cord injury. Spinal Cord. 1999; 37: 765-771.

additional findings in non vets with sci
Additional findings inNon VETS with SCI
  • Peak Glucose correlated with:
    • Highest level of lesion
    • Older age at time of injury
    • Increased TB %fat
  • Peak Insulin correlated with:
    • Male gender
    • Increased TB %fat

Bauman WA, Adkins RH, Spungen AM, Waters RL. The effect of residual neurological deficit on oral glucose tolerance in persons with chronic spinal cord injury. Spinal Cord. 1999; 37: 765-771.

cho metabolism summary
CHO Metabolism Summary
  • Increased prevalence of IGT and DM
  • The greater the ND, the worse the CHO metabolism
  • Peak Glucose is independently related to %fat, ND, age at time of injury, and male gender
  • Hyperinsulinemia: >50% Tetra and >30% Para
  • OGTT ↔ to diagnose early disease (IGT, mild DM, and hyperinsulinemia)
lipid profile
Lipid Profile
  • 541 SCI
    • 247 Tetra, 294 Para
    • 156 ComT, 91 IncT, 206 ComP, 88 IncP
    • 111 Latino, 86 White, 50 Afric Amer
    • 221 Men, 26 Women
  • Total Study Group meanSEM
    • Age (y) 38  0.7
    • DOI (y) 13  0.6
    • BMI (kg/m2) 24.3  0.31

Bauman WA, Adkins RH, Spungen AM, Maloney P, Gambino R, Waters RL. Is immobilization associated with an abnormal lipoprotein profile? Observations in a diverse cohort. Spinal Cord. 1999; 37:485-493.

lipid profile25

50

45

40

35

30

Tetra

Complete

Tetra

Incomplete

Para

Complete

Para

Incomplete

Lipid Profile

In 541 NonVets with SCI, 29% had serum HDL level

<35 mg/dL

Bauman WA, Adkins RH, Spungen AM, Maloney P, Gambino R, Waters RL. Is immobilization associated with an abnormal lipoprotein profile? Observations in a diverse cohort. Spinal Cord. 1999; 37:485-493.

slide26

Additional Lipid Values

LDL 130 (m/dL)

TC/HDL

>4.5

Comp

Tetra

(n=156)

51%

55%

Incomp

Tetra

(n=91)

42%

52%

Comp

Para

(n=206)

49%

48%

Incomp

Para

(n=88)

32%

44%

TC=total cholesterol; HDL=high density lipoprotein cholesterol

Bauman WA, Adkins RH, Spungen AM, Maloney P, Gambino R, Waters RL. Is immobilization associated with an abnormal lipoprotein profile? Observations in a diverse cohort. Spinal Cord. 1999; 37:485-493.

lipid profile27
Lipid Profile

Total

Men

Women

White

Afric Amer

Latino

SCI

320

233

87

149

88

83

Control

303

244

59

169

87

47

Bauman WA, Adkins RH, Spungen AM, Maloney P, Gambino R, Waters RL. Is immobilization associated with an abnormal lipoprotein profile? Observations in a diverse cohort. Spinal Cord. 1999; 37:485-493.

slide28

*P<0.0001

*P<0.05

Comparison of Serum HDL Cholesterol & Triglycerides Among Ethnic Subgroups

Bauman WA, Adkins RH, Spungen AM, Maloney P, Gambino R, Waters RL. Is immobilization associated with an abnormal lipoprotein profile? Observations in a diverse cohort. Spinal Cord. 1999; 37:485-493.

lipid metabolism in sci summary
Lipid Metabolism in SCI Summary
  • Significantly lower HDLs
  • Greater decrease in HDLs with increasing neurological deficit
  • African Americans with SCI have a similar lipid profile to the general population
significance of plasma homcysteine levels
Significance of Plasma Homcysteine levels
  • A vasotoxic amino acid
  • Increased concentrations are caused by genetic mutations, vitamin deficiencies, renal and other diseases, various drugs, and increasing age
  • Increased levels are associated with increased risk of CHD
plasma homocysteine levels in persons with sci n 845
Plasma Homocysteine Levels in Persons with SCI (n=845)

HCYTotalMenWomen

(µmol/L) % (N) % (n) % (n)

≤ 14 56 (474)

> 15-19* 33 (282) 37 (264) 15 (18)

> 20† 11 (89) 12 (87) 2 (2)

Mortality ratios: *2.8; † 4.5

Bauman et al., J Spinal Cord Med. 24:81-86, 2001

significance of c reactive protein crp
Significance of C-reactive Protein (CRP)
  • General marker of inflammation
  • Measures the concentration of a protein in serum that indicates acute inflammation
  • Associated with increased risk of CHD
c reactive protein in sci
RISK

Lowest

Mild

Moderate

High

Highest

Count

16

13

16

15

17

C-Reactive Protein in SCI

mg/L

<0.7

0.7-1.1

1.2-1.9

2.0-3.8

3.9-15.0

21 %

17 %

21 %

19 %

22 %

* Those with fasting insulin resistance were associated with a two-fold increase in CRP levels.

Lee Et al., JSCM 28:20-25, 2005

homocysteine and c reactive protein summary
Homocysteine and C-Reactive Protein Summary
  • 44% of SCI patients studied in a large sample had a homocysteine level associated with an increased mortality ratio
  • 62% of SCI pts studied had moderate to high CRP levels
risk factor analysis study in sci
Risk Factor Analysis Study in SCI

Bauman WA and Spungen AM. Topics in Spinal Cord Inj Rehabil. 12:35-53, 2007.

risk factor analysis study in sci36
Risk Factor Analysis Study in SCI

Bauman WA and Spungen AM. Topics in Spinal Cord Inj Rehabil. 12:35-53, 2007.

risk factors by ldl tx goal
Risk Factors by LDL Tx Goal

Bauman WA and Spungen AM. Topics in Spinal Cord Inj Rehabil. 12:35-53, 2007.

slide38

185±38

196±38

119±34

38±12

121±33

124±83

51±13

148±86

Risk Factors Study: SCI and NonSCI

45

45

40

40

35

35

30

30

25

25

Count

20

20

15

15

10

10

5

5

0

0

20

40

60

80

100

120

140

160

180

200

220

80

100

120

140

160

180

200

220

240

260

280

300

TC

LDL

90

90

80

80

70

70

60

60

50

50

Count

40

40

30

30

20

20

10

10

0

0

0

100

200

300

400

500

600

700

10

20

30

40

50

60

70

80

90

100

110

TG

HDL

slide39

HDL Cholesterol in the Total Group

HDL cholesterol <40 mg/dL: 63%

HDL cholesterol <35 mg/dL: 44%

HDL cholesterol <30 mg/dL: 19%

Mean HDL cholesterol: 38 ±12 mg/dL

Bauman WA and Spungen AM. Topics in Spinal Cord Inj Rehabil. 12:35-53, 2007.

assessment for risk for chd percent of sci subjects needing intervention
Assessment for Risk for CHD:Percent of SCI Subjects Needing Intervention

41 % of the SCI population qualified for intervention by ATP III guidelines.

Bauman WA and Spungen AM. Topics in Spinal Cord Inj Rehabil. 12:35-53, 2007.

summary of risk factor study
Summary of Risk Factor Study
  • Highest Risk LDL goal <100mg/dL(7 of 222 S’s)(10-y risk >20%)
    • 4% by Framingham Point score
    • 9% had CHD dx or vascular disease equivalent
      • BUT, silent disease may missed in asymptomatic/inactive
    • 17% DM (↑IGT?)
      • BUT, higher if included known diabetics
  • Moderate Risk LDL goal <130mg/dL (58 of 222 S’s)
    • 50% 10y risk of 10-20% by Framingham Point score
    • 70% had 2 or more RFs
  • Overall, 41% qualified for intervention
slide42

Risk Factor Analysis in SCI: A guideline driven assessment of need for cardiovascular disease risk intervention in persons with chronic paraplegia

  • Subjects:
    • 41 subjects with paraplegia
      • ASIA A & B: T6 to L1 and Age: 34±11 years
  • Main Outcome Measure:
    • % of subjects qualifying for intervention Based on ATP III guidelines
  • Results:
    • 63% of subjects qualified for intervention
    • 76% had HDL cholesterol <40 mg/dL
    • 1/3 had hypertension
    • 34% had the metabolic syndrome
  • Conclusion: A high percentage of young, healthy persons with SCI are at risk for CVD & qualify for lipid-lowering intervention

Nash MS, et al. Arch Phys Med Rehabil. 88:751-757, 2007

commentary
Commentary
  • HDL cholesterol levels in persons with SCI are frequency depressed and require heightened scrutiny because they may greatly increase risk due to extremely depressed values, requiring more intense intervention.
  • Absence of activity and associated symptoms of CVD in persons with SCI may result in incorrect stratification of CHD risk, resulting in reduced appreciation of risk.
  • Conventional RFs should be identified and treated in persons with SCI according to current standards of care for the general population.
special thanks to
Special thanks to:
  • Department of Veterans Affairs:
    • Rehabilitation, Research and Development Service, Washington, DC
    • James J Peters VA Medical Center, Bronx, NY
  • United Spinal Association (Formerly EPVA), Jackson Heights, NY
  • Rancho Los Amigos National Rehabilitation Center, Downey CA
  • The Kessler Institute of Rehabilitation, West Orange, NJ