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CV Biomarkers Today

Inflammation and Proliferation CRP Lp-PLA2 MCSF PDGF FDF FGF Interleukins (1,6,8,10,12,15) MMPs (1,2,3,9) MIP1 (alpha and beta) TNF alpha Proliferating cell nuclear antigen Hyaluronan receptors SR-A, SR-B1 TGF SM myacin heavy chains CD 11, 18, 36, 40, 68 MCP-1 CCR2 Pentraxin-3

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CV Biomarkers Today

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  1. Inflammation and Proliferation CRP Lp-PLA2 MCSF PDGF FDF FGF Interleukins (1,6,8,10,12,15) MMPs (1,2,3,9) MIP1 (alpha and beta) TNF alpha Proliferating cell nuclear antigen Hyaluronan receptors SR-A, SR-B1 TGF SM myacin heavy chains CD 11, 18, 36, 40, 68 MCP-1 CCR2 Pentraxin-3 C4b binding protein I kappa B-alpha Total sialic acid Osteopontin CV Biomarkers Today Imaging Angiography IVUS 3D reconstruction IVUS Ultrafast CT (coronary) Carotid ultrasound – IMT MRI (carotid, PAD, aortic) PET Aortic CT Scintigraphy (thallium, sestimibe) Intracoronary endo fct (Ach) Brachial ultrasound Plethysmography TEE (aortic) Skin cholesterol Monoclonal antibody imaging Pulsatile flow visualization (aorta) Regional aortic distensibility Aortic stiffness (Doppler) Coronary thermography Coronary elastography Coronary NIR spectroscopy Lipids lipoproteins lipoprotein subfractions (L1-3, V1-6, H1-5) Apolipoproteins (CIII, AII:E, LpB…) Lp(a) Lipid ratios Serum glycoproteins Alpha 1-antitrypsin Alpha 1 acid glycoprotein Alpha 2-macroglobulin Ceruloplasmin haptoglobin Coagulation VWF tPA PAI-1 PF4 D-dimer Tissue factor Fibrinogen Beta thromboglobulin Erythrocyte sed. Rate RBC adhesiveness/aggreg Adhesion molecules s-ICAM s-VCAM P-selectin E-selectin Genetics ACE polymorphism methylenetetrahydrofolate reductase [MTHFR] apolipoprotein E [apo E] paraoxonase [PON] Immunology Anti-oxLDL IgG

  2. Endothelial Dysfunction and CAD MI Sudden death Coronary thrombosis Arrhythmia and loss of muscle Endothelial dysfunction Myocardial ischemia Remodelling Ventricular dilation CAD Atherosclerosis CHF Risk factors  Chol,  BP, DM, insulin resistance), platelets, fibrinogen, etc End-stage heart disease Adapted from Dzau and Braunwald, Am Heart J, 1991.

  3. Endothelium-derived Relaxing Factors Endothelium-derived Contracting Factors Smooth muscle Contraction - TXA Relaxation 2 Tone - PGI - Free radical - 2 + - NO - Ang II - + - EDHF - Endothelin Inhibition of Proliferation Structure Proliferation

  4. BASELINE (3.65 mm) REACTIVE HYPEREMIA (4.02 mm) Flow-Mediated Vasodilation FMD = 10 %

  5. Microvasculature Philpott et al. ATVB 2007;27:2065

  6. Shear stress, hyperemic velocity and Risk Factors FATE – n=1477 , Overall R2 for hyperemic velocity = 0.171

  7. Methods QCA distal to Doppler site for Flow calculation QCA in distal site for vasomotion

  8. Mild Coronary Dilation LAD-D5W LAD- Ach 10-6 Endothelial Function and Atherosclerosis

  9. Methods Coronary flow response to Atrial Pacing Increase in Coronary velocity in normal subject

  10. FATE Prognostic Significance of Markers of Vascular Health:Long-term Results from the Firefighters and their Endothelium (FATE) Study Todd J Anderson, Francois Charbonneau, Lawrence Title, Jean Buithieu, M. Sarah Rose, Heather Conradson, Kathy Hildebrand, Marinda Fung, Subodh Verma, Eva M. Lonn University of Calgary and Libin Cardiovascular Institute McMaster University McGill University University of Toronto Dalhousie University

  11. Methods – Vascular End-points Lumen Intima Media Adventitia Hyperemic VTI CIMT FMD

  12. Results – Cox proportional hazards

  13. Results – Net Clinical Reclassification Index

  14. AB-HEART – Vascular physiology studies • Endothelial dysfunction thought to play an important role in systolic CHF • Role in diastolic CHF has not been as well defined • Ventricular-vascular coupling likely important

  15. AB-HEART – Peripheral arterial studies • Compare peripheral endothelial function in subjects with systolic, diastolic HF with healthy controls • Flow-mediated dilation- conduit vessel function • Hyperemic VTI and PAT – microvascular function • Pulse wave velocity with applanation tonometry • Assess the prognostic implication of these measurements in patients with HF

  16. AB-HEART – Coronary studies • Compare coronary endothelial function in subjects with systolic, diastolic HF with healthy controls • Intracoronary Ach, and adenosine • Measures of Pressure and Flow to calculate microvascular resistance • 25 patients per group • Have not begun these studies as yet

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