Slide 1
Risk Analysis for Cardiovascular Disease after 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
Slide 2
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)
Slide 3
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
Slide 4 
AHA Modifiable RFs for CVD
• 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
– Ύ of all DM die of some form of heart or vessel disease
• 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
Slide 5
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
Slide 6
Non Traditional or Emerging Risk Factors for CHD
• Insulin resistance
• Plasma homocysteine
• C-reactive protein
• Lipoprotein (a) 
• Small, dense LDL particles 
• Prothrombic factors
Slide 7
 Risk Factor Assessment
• Lipid Profile
• Oral Glucose Tolerance
• Blood Pressure Assessment
• Screening
– Medical Hx
– Age, Gender
– Smoking
– Obesity
– Family Hx
– Physical Activity
– Stress/lifestyle
Slide 8
ATP III Classification of
LDL Cholesterol (mg/dL)
Slide 9
ATP III Risk Categories

Slide 11
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
Slide 12
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
Slide 13
Total Body Lean Tissue Loss with Duration of Injury in the SCI Twins

Slide 14
Body Composition in SCI
Graph scale of Age ranging from 10 to 80 yrs old 
vs total body percent lean from 30 to 100 percent
Slide 16
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 
Slide 17
Slide 18
Relationship of Age with Glucose Tolerance in Veterans

Slide 19
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
Slide 20
Oral Glucose Tolerance in
Non VETS with SCI

Slide 21
• 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
Slide 22
Additional findings in
Non 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
Slide 23
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)
Slide 24
Lipid Profile
541 SCI- Age, BMI, etc.
Slide 25
Additional Lipid Values

Slide 28
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
Slide 29
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
Slide 30
Plasma Homocysteine Levels in Persons with SCI (n=845)
HCY 		  Total	 Men		Women
(΅mol/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
Slide 31
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
• 
Slide 32
C-Reactive Protein in SCI
RISK
Lowest
Mild
Moderate
High
Highest
Count
16
13
16
15
17

Slide 33
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
Slide 34
Risk Factor Analysis Study in SCI
Slide 35
Risk Factors by LDL Tx Goal

Slide 39
Assessment for Risk for CHD:
Percent of SCI Subjects Needing Intervention

Slide 40
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

Slide 41
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
Slide 42
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.
Slide 43
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
Slide 44
Group photo of Staff of the 
VA RR&D Center of Excellence for the Medical Consequences of SCI