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Jay cohn md aha 04 aeha conf

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Jay cohn md aha 04 aeha conf

  1. 1. The Role of Endothelial Function Testing and Arterial Elasticity Jay N. Cohn, M.D. Professor of Medicine University of Minnesota Medical School Minneapolis, Minnesota
  2. 2. Faculty Disclosure Statement I have received honoraria, study grants, consultation fees and/or hold stock options in the following: Novartis Pharmaceuticals Acorn Cardiovascular Abbott Labs Bristol-Myers Squibb Biosite Diagnostics Amgen SmithKline Beecham Medtronic Inc. Intercure Inc. Forest Laboratories NitroMed Inc. Pfizer Hypertension Diagnostics Solvay Guidant AstraZeneca Pharmaceia
  3. 3. Arterial Vascular Bed Capacitive Function (large artery elasticity) Oscillatory/Reflective Function (small artery elasticity) Systemic Vascular Resistance
  4. 4. Femoral Artery
  5. 5. Impaired NO Release – Platelet aggregation – Increased vascular tone (decreased compliance) – VSM hypertrophy / hyperplasia – Atherosclerosis Endothelium Lumen Media NO NO
  6. 6. Vicious Circle of Hypertension ↑SVR Atherosclerotic Events Endothelial Dysfunction ↑ Arterial Pressure
  7. 7. Simple, Non-Invasive, FDA-Cleared, Reimbursable
  8. 8. Blood Pressure Waveform Analysis Methodology
  9. 9. Pre Post
  10. 10. Vascular Effects of L-NAME in 10 Normal Subjects Control L-NAME P •BP mmHg 112/65 122/75 <0.01 •MAP mmHg 80 90 <0.01 •PWV m/sec 8.25 8.98 0.04 •BA@100 mmHg cm2 10.8 11.0 NS •BAC@100 mmHg cm2 /mmHg .0027 .0049 0.07 •FMV% 5.29 4.47 0.06 •C1 ml/mmHg 16.9 18.5 NS •C2 ml/mmHg 9.9 6.9 <0.001 •SVR dynes-sec-cm-5 1200 1487 <0.001
  11. 11. Hi-Normal (n = 1794) 130 – 139/ 85 – 89 Normal* (n = 2185) 120 – 129/ 80 – 84 Optimal (n = 2880) < 120/80 Hazard Ratio *P < 0.001 for trend across categories. 2.5 1.5 1.0 Impact of High-Normal Blood Pressure on the Risk of Cardiovascular Disease CumulativeCVDIncidence,% Time, years Normal Optimal Hi-Normal Women Vasan RS, et al. N Engl J Med. 2001;345:1291–1297.
  12. 12. •ENDOTHELIAL DYSFUNCTION FUNCTION STRUCTURE Small Artery Constriction Large Art Remodeling ↓C1 ↑Pulse Plaques Pressure Clots ↓C2 ↑SVR Small Art Remodeling ↓↓C2 ↓Flow Organ Reserve Dysfunction “HYPERTENSION” HYPERTENSION
  13. 13. C1 and C2 with Age 0 0.5 1 1.5 2 2.5 20 40 60 75 C1 C2 .08 .01 1.6 McVeigh et al Hypertens. 1999;33:1392McVeigh et al Hypertens. 1999;33:1392 C1 and C2 decreased with age,, the slope of C2C1 and C2 decreased with age,, the slope of C2 being greater. The change in BP with agebeing greater. The change in BP with age independently contributed to the decrease in C1 butindependently contributed to the decrease in C1 but not in C2not in C2
  14. 14. MAP ** C2 ** C1 * SVR * Vascular Measurement in Normotensive and Hypertensive Subjects 150 100 – 50 – 0 N Hyp n = 32 n = 38 *P<0.01, **P<0.001 N Hyp N Hyp N Hyp 2000 1000 – 0 dyne•sec •cm-5mm Hg mL/mm Hg mL/mm Hg 2.0 1.0 – 0 .08 .06 – .04 – .02 – 0
  15. 15. Variable C2 Age Odds Ratio 0.07 1.04 Lower 0.5353 1.02 Upper 0.84 1.05 pp ValueValue <0.01<0.01 <0.001<0.001 95% CI Loss of Arterial Elasticity is Predictive of Cardiovascular Events N=419 subjects, C1 - Large Artery Elasticity and C2 - Small Artery Elasticity measured at baseline by radial artery PulseWave Analysis 1 to 7 year follow-up (contacted and returned questionnaires) End points: MI, stroke, TIA, angina, coronary or peripheral angioplasty, coronary artery or peripheral bypass graft, death Occurrence of Events as a Function of Baseline Arterial Compliance*Occurrence of Events as a Function of Baseline Arterial Compliance* Grey E et al. Am J Hypertens. 2000;13 (part 2). Abstract. Presented at the 15th Scientific Meeting of the American Society of Hypertension. *C1 was associated with age but not outcome For each 2 ml/mmHg x 100 of lowered CFor each 2 ml/mmHg x 100 of lowered C22 - Small- Small Artery Elasticity Index, there is a 33% increase in theArtery Elasticity Index, there is a 33% increase in the odds ratio for cardiovascular events.odds ratio for cardiovascular events.
  16. 16. Small Artery Elasticity Predicts Cardiovascular Events Reduced Small Artery Elasticity was predictive of cardiovascular events Events increase as Small Artery Elasticity decreases Large Artery Elasticity related to age, not independently predictive of events Grey et al, Am J Hypertension. In Press
  17. 17. ↑ BP C2 normal C2 low Fundi normal Funduscopic changes No LVH LVH No microalbuminuria Microalbuminuria C2 normal C2 low No sign of vascular disease Signs of vascular disease Follow Treat aggressively
  18. 18. Natural History of Vascular Disease Genes Pressure Lipids Smoking Inflammation Oxidative Stress Aging Endothelial Dysfunction Atherosclerosis Vascular Aging Events Plaques CAC ↓Small artery compliance ↓FM dilation ↑BP ↑IMT Retinopathy Microalbuminuria ↑↑BP ↓Large artery compliance ↑Pulse pressure M.I. Angina Heart failure Sudden death Stroke Renal failure PVD Dementia Health care costs
  19. 19. Natural History of CVD Progression Elevated BP Target Organ Damage More Recent Paradigm A Proposed Future Paradigm Elevated BP Target Organ DamageVascular Dysfunction Elevated BP Target Organ Damage Vascular Dysfunction Endothelial Dysfunction Early Paradigm Angina Pectoris Stroke MIRenal Damage LVH Hypertension: The Disease Continuum
  20. 20. R A S M U S S E N C E N T E R for CARDIOVASCULAR DISEASE PREVENTION
  21. 21. RASMUSSEN CENTER Screening Tests for Early Detection • Arterial Elasticity (Pulse Contour Analysis) - Small Artery (C2) - Large Artery (C1) • Rest and exercise BP (3-minute treadmill) • Retinal digital photograph • Urine for microalbumin/creatinine ratio • Carotid intimal-medial thickness Vascular Evaluation
  22. 22. RASMUSSEN CENTER Screening Tests for Early Detection Cardiac Evaluation • Electrocardiogram • Cardiac ultrasound (LVID, LVWT, mass ) • Plasma BNP (Biosite)
  23. 23. RASMUSSEN CENTER Screening Tests for Early Detection Modifiable Disease Contributors • Fasting lipids (LDL, HDL, Trig) • Fasting blood sugar • hsCRP • Homocysteine
  24. 24. Results of Rasmussen Center Screening 0 20 40 60 80 100 120 140 0 2 4 6 8 10 12 14 16 3- Frequency Rasmussen Score Low Risk 33% Modest Risk 36% High Risk 31%
  25. 25. Age-Dependent Progression of Vascular Disease VascularRemodeling/ Atherosclerosis Death Morbid Events Age 20 40 60 80 100
  26. 26. Therapy to Prevent Progression• Statin drugs • ACE inhibitors/AT1 blockers • Antihypertensive drugs • Beta blockers • Antioxidants (?) • Hormone replacement (?) • Exercise (?) • Potassium (?) • Diet
  27. 27. Risk Factors Biomarkers Cardiac and Vascular Structural Abnormalities Death Non-Fatal Morbid Events Recurrence Progression Primary Prevention Secondary Prevention Tertiary Prevention

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