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Endothelial Dysfunction as a Marker of Cardiovascular Events Robert A. Vogel, M.D.

Endothelial Dysfunction as a Marker of Cardiovascular Events Robert A. Vogel, M.D. “Response-to-Injury” Hypothesis . Genes. Coronary Risk Factors. Endothelial Dysfunction  NO ↑ Inflammation ↑ Thrombosis. Coronary Heart Disease.

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Endothelial Dysfunction as a Marker of Cardiovascular Events Robert A. Vogel, M.D.

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  1. Endothelial Dysfunction as a Marker of Cardiovascular EventsRobert A. Vogel, M.D.

  2. “Response-to-Injury” Hypothesis Genes Coronary Risk Factors Endothelial Dysfunction NO ↑Inflammation ↑Thrombosis Coronary Heart Disease

  3. Regulatory Functions of the EndotheliumNormal Dysfunction Vasodilation Vasoconstriction NO, PGI2, EDHF, BK, C-NP ROS, ET-1, TxA2, A-II, PGH2 Thrombolysis Thrombosis tPA, Protein C, TF-I, vonWF PAI-1, TF, Tx-A2 Platelet Disaggregation NO, PGI2 Adhesion Molecules CAMs, Selectins Antiproliferation NO, PGI2, TGF-, Hep Growth Factors ET-1, A-II, PDGF, bFGF, ILGF, Interleukins Lipolysis Inflammation ROS, NF-B LPL Vogel R

  4. Fichtlscherer S et al, Circulation 2000;102;1000Comparison of Forearm Responses to ACh and C-Reactive Protein in 60 Men with CAD

  5. Cayette et al, Nature 1990; Cooke et al, JCI 1992;90:1168Effect of NO Inhibition and Augmentation on Hypercholesterolemic Rabbit Aortic Atherosclerosis Area at 6 Weeks L-NAME L-Arginine Control

  6. Coronary Arteries Epicardial Artery Diameter  with ACh CBF  with ACh Epicardial Artery Diameter  with Adenosine Forearm Brachial Artery Diameter  with Arterial Occlusion Forearm Blood Flow with ACh Clinical Methods for Assessing Endothelium-Dependent Dilation

  7. Takese B, Am J Cardiol 1998:82:1535Comparison of Brachial and Coronary Flow-Mediated Vasodilation

  8. Furchgott RF & Zawadski JV, Nature 1980 Anderson TJ et al, NEJM 1995;332:488

  9. Schachinger V et al, Circulation 2000;101:1899CVE’s over 7.7 Years in 147 Subjects with CAD According to Coronary Artery Responses to Ach, Cold Pressor, and FMD CVE’s

  10. Halcox JPJ et al, Circulation 2002;106:653CVE’s over 4 Years in 176 Subjects without CAD According to CVR and CA Diameters Changes with ACh

  11. Al Suwaidi J et al. Circulation 2000;101:948Cardiac Events in 157 CAD Patients over 28 Months Stratified by CBF Responses to ACh

  12. Targonski PV et al, Circulation 2003;107:2805Relative Risk of CVA or TIA in 503 Non-Obstructive CAD Subjects over 88 Months According to CBR Responses to ACh Relative Risk of CVA/TIA CBF Increase with ACh

  13. Coronary Arteries Epicardial Artery Diameter  with ACh CBF  with ACh Epicardial Artery Diameter  with Adenosine Forearm Brachial Artery Diameter  with Arterial Occlusion Forearm Blood Flow with ACh Clinical Methods for Assessing Endothelium-Dependent Dilation

  14. Perticone F et al, Circulation 2001;104:191Effect of ACh-Induced Forearm Vasodilation* on 32-Month CVE’s (%) in 225 Never Treated Hypertensive Subjects(* Relative Flow Increase)

  15. Heitzer T et al, Circulation 2001;104:2673CVE’s According to FBF Responses to ACh and I.V. Vitamin C in 281 Subjects with CHD ACh-induced FBF Responses Vitamin C Responses

  16. Brachial Artery Flow-Mediated VasodilationBaseline5 MinutesPost-OcclusionBlood Pressure Cuff Occlusion – 1 Minute Release 3.6 mm 3.1 mm

  17. Neuntfeufl T et al, Am J Cardiol 2000;86:207CHD Events over 5 Years in 76 CAD Patients According to Brachial Artery FMD

  18. Murakami T et al. J Am Coll Cardiol 2001;37:294ACVE’s over 4 Years in 480 Patients with Suspected CAD According to Brachial Artery FMD

  19. Endothelial Dysfunction as a Therapeutic Prognosticator

  20. Gokce N et al, Circulation 2002;105:1567Effect of Preoperative FMD on 30-Day MACE and MACE + Elevated Troponin in 187 Patients Undergoing Vascular Surgery

  21. Sorensen KE et al, Circulation1998:97:1234Effect of HRT on Brachial Artery FMD at 3 Years in 100 Postmenopausal Women Randomized to HRT/Placebo and 30 Premenopausal Women

  22. Modena MG et al. J Am Coll Cardiol 2002;40:5055-Year Outcome in 350 Postmenopausal Hypertensive Women with Controlled BP (<140/90) Based on the Change in Brachial Artery Flow-Mediated Vasodilation during the First 6 Months of Treatment(Similar initial FMD values, treatment, and on-treatment BP)  

  23. FMD and LDL-C at Baseline and 3 Months in the REVERSAL Trial 15% 10% 5% 0% 3 Months Flow-Mediated Dilation Baseline Pravastatin 40 mg Atorvastatin 80 mg 75 100 125 150 175 LDL-C (mg/dl)

  24. % Change in IVUS Atheroma Volume at 18 Months in the REVERSAL Trial Percent Change in Atheroma Volume by IVUS P = 0.02 LDL-C 110 LDL-C 79 Pravastatin 40 mg Atorvastatin 80 mg

  25. Summary: Coronary and brachial artery endothelium-mediated dilation provide significant CVE prognostic information and may be indexes of therapeutic responses.

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