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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

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Risk Analysis for Cardiovascular Disease after Spinal Cord Injury

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  1. 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

  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)

  3. 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

  4. 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

  5. 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

  6. Non Traditional or Emerging Risk Factors for CHD • Insulin resistance • Plasma homocysteine • C-reactive protein • Lipoprotein (a) • Small, dense LDL particles • Prothrombic factors

  7. Lipid Profile Oral Glucose Tolerance Blood Pressure Assessment Screening Medical Hx Age, Gender Smoking Obesity Family Hx Physical Activity Stress/lifestyle Risk Factor Assessment

  8. 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.

  9. 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.

  10. 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

  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 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.

  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

  13. 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)

  14. 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.

  15. Spungen et al., J Appl Physiol 95:2398-2407, 2003

  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

  17. Oral Glucose Tolerance in Veterans with or without SCI Bauman WA and Spungen AM. Metabolism. 43: 749-756, 1994

  18. Relationship of Age with Glucose Tolerance in Veterans Bauman WA and Spungen AM. Metabolism. 43: 749-756, 1994

  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 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.

  20. 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.

  21. 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.

  22. 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.

  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)

  24. 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.

  25. 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.

  26. 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.

  27. 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.

  28. *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.

  29. 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

  30. 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

  31. 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

  32. 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

  33. 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

  34. 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

  35. Risk Factor Analysis Study in SCI Bauman WA and Spungen AM. Topics in Spinal Cord Inj Rehabil. 12:35-53, 2007.

  36. Risk Factor Analysis Study in SCI Bauman WA and Spungen AM. Topics in Spinal Cord Inj Rehabil. 12:35-53, 2007.

  37. Risk Factors by LDL Tx Goal Bauman WA and Spungen AM. Topics in Spinal Cord Inj Rehabil. 12:35-53, 2007.

  38. 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

  39. 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.

  40. 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.

  41. 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

  42. 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

  43. 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.

  44. 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

  45. Staff of the VA RR&D Center of Excellence for the Medical Consequences of SCI

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