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Core Curriculum

• The endothelium: New insights into the origins and treatment of CAD

Participants at recent Vascular Biology Working Group meetings have reviewed and provided significant direction in the development of this slide/lecture program entitled The endothelium: New insights into the origins and treatment of CAD.

These program materials present a complete update of the basic science and clinical trials that are bringing advances in knowledge of the endothelium into the daily practice of medicine. The latest studies on the endothelium, the growing importance of bradykinin, and the prognostic role for endothelial function are included. Important new information is also presented on angiotensin type 1 receptor antagonism, ACE inhibition for the treatment of heart failure, and trials that extend the role of tissue ACE inhibition into new patient populations.

Introduction

The information in this slide/lecture program represents an update on the endothelium and its role in cardiovascular health and disease, probably the most exciting area in cardiology today.

The information covers new data extending the knowledge presented in the first volume of this series and in other programs that have helped characterize the endothelium as the gatekeeper of vascular structure and function. The endothelium has been demonstrated to be critically important in the initiation and progression of atherosclerosis and other vascular conditions. Every risk factor for cardiovascular disease is also associated with impaired endothelial function. As our understanding of the pathophysiology of cardiovascular disease evolves, our treatment algorithms should be updated. This program includes current findings in vascular pathophysiology and clinical trials that are turning the science of vascular biology into clinical practice.




The endothelium: New insights into the origins and treatment of CAD

Download 00CoreS01.ppt (19 slides - 1.0MB)

The endothelium: New insights into the origins and treatment of CAD Program overview The endothelium maintains vascular health Unifying model: Endothelial dysfunction to CVD Physiology of NO in the human coronary and peripheral vasculature Physiology of NO in the human coronary and peripheral vasculature: Mechanisms of NO release Atherosclerosis timeline Therapeutic strategies for the treatment of endothelial function Candidates for therapies to enhance endothelial function Brachial FMD predicts coronary endothelial function Exercise improves coronary endothelial function in CAD Vitamin E and endothelial function in smokers Oral omega-3 fatty acids improve endothelial function in hypercholesterolemia Estrogen and vitamin E effects in postmenopausal women Tissue ACE inhibition and endothelial function Tetrahydrobiopterin supplementation restores endothelial function in smokers Effects of antihypertensive agents on endothelial function in postmenopausal women Spironolactone improves endothelial function in CHF Improving endothelial function: Most compelling data

Components and major actions of the renin angiotensin system

Download 00CoreS02.ppt (18 slides - 0.7MB)

Components and major actions of the renin angiotensin system Vasculoprotective effects of angiotensin-(1-7) ACE metabolizes Ang-(1-7) into Ang-(1-5): Effect with and without ACE inhibition ACE and endothelial function Mechanisms for the effects of ACE inhibition on endothelial dysfunction Potential benefits of suppressing cardiac ACE Mechanisms of cardiac RAS activation in cardiac remodeling Possible mechanisms of endothelial dysfunction in heart failure Effect of experimental heart failure on cardiac ACE activity Genetic evidence that cardiac ACE correlates with experimental infarct size Neointima formation: Correlation with blood pressure and residual serum and tissue ACE after ACE-I ACE inhibitors and fibrinolysis Vasculoprotective effects of tissue ACE inhibition Cardiovascular role of bradykinin as determined by knockout mice ACE inhibition increases vasodilation by a bradykinin mechanism in response to flow-mediated dilation Effects of ACE-I vs other antihypertensive agents on endothelial function in hypertensive patients ACE inhibitors and endothelial function: Evidence for the role of NO and bradykinin ACE inhibitors upregulate b -adrenergic receptors on cardiac myocytes by a bradykinin mechanism

Correlation between endothelial function and hypertension

Download 00CoreS03.ppt (7 slides - 0.3MB)

Correlation between endothelial function and hypertension Correlation between endothelial function and atherosclerosis Severe endothelial dysfunction associated with increased CV risk in patients with mild CAD Endothelial dysfunction predicts cardiovascular events: 5-year follow-up in patients with angina Endothelial function vs clinical outcome in patients with CAD Carotid plaque is a marker of CV risk Carotid atherosclerosis and systolic blood pressure

New treatment approach to hypertension

Download 00CoreS04.ppt (24 slides - 1.1MB)

New treatment approach to hypertension JNC-VI guidelines: Risk stratification and treatment JNC-VI guidelines: Compelling indications Vascular changes and CV risk factors in borderline hypertension (BP > 140/90 mm Hg) Reduction in systolic blood pressure with quinapril by patient age Efficacy of quinapril vs captopril in moderate-to-severe hypertension Combined and distinct vascular effects of ACE-I and statins: Effect on blood pressure Combined and distinct vascular effects of ACE-I and statins: Effect on hemodynamic reactivity Blood pressure control after 8 weeks of quinapril: Effect of age and gender Blood pressure control after 8 weeks of quinapril: Effect of race ACE inhibitor therapy: Effect on vascular and cardiac structure in hypertensive patients Quinapril reduces blood pressure and vascular hypertrophy Effect of quinapril on ST-segment depression in patients with angina Quinapril improves fasting glucose levels in type 2 diabetes Quinapril + HCTZ fixed combinations trials: Design Quinapril 10 mg/HCTZ 12.5 mg study: Results Quinapril 20 mg/HCTZ 12.5 mg study: Efficacy UKPDS: Importance of tight control of both BP and glycemia on risk of diabetes complications Change in vascular ACE density after arterial injury and effect of quinapril to prevent restenosis Quinaprilat improves blood flow in ischemic myocardium Quinaprilat reduces total coronary resistance: Ischemic regions Quinaprilat reduces total coronary resistance: Non-ischemic regions ATIME: Slower dose escalation of quinapril improves blood pressure control Hypercholesterolemia induces AT1 receptor expression

Relative risks for heart failure: Framingham Study

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Relative risks for heart failure: Framingham Study Progression of hypertension to LVH and heart failure Effect of ACE inhibition on mortality and morbidity in heart failure patients: An analysis of 32 trials LVH regression: Changes in left ventricular mass index with 4 drug classes LVH is normalized in most patients with long-term quinapril treatment Effect of ACE inhibition on FMD in patients with heart failure Increasing dosages of enalaprilat did not affect FMD Effect of quinapril on b-receptor function in heart failure Effect of quinapril on b -receptor density ATLAS: High- vs low-dose ACE inhibition in heart failure—study design ATLAS: High-dose ACE-I reduces adverse outcomes in heart failure ACE inhibitors in CHF: Are maximally recommended doses sufficient?

Comparative inhibition of plasma and tissue ACE

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Comparative inhibition of plasma and tissue ACE Relative potency of ACE inhibitors in plasma and tissue Relative potency of ACE inhibitors in human heart and lung Comparative dissociation rates of ACE inhibitors from human atrial membranes ACE inhibition: Pharmacokinetic overview

Differential effects of quinapril and losartan on superoxide production in endothelial cells

Download 00CoreS07.ppt (11 slides - 0.5MB)

Differential effects of quinapril and losartan on superoxide production in endothelial cells ACE inhibitors and ARBs: Comparative effects on postprandial endothelial function Comparative effect of ACE inhibition and AR blockade on fibrinolytic balance Quinapril but not losartan improves survival in cardiomyopathic hamsters ACE inhibitors vs ARBs in heart failure trials: Study characteristics RESOLVD: Clinical results ELITE II: Study design ELITE II: Study results ACE inhibitors vs ARBs in heart failure: Effects on mortality and hospitalization ELITE I substudy compares the effects of ACE inhibition and AR blockade on LV remodeling ACE inhibitors vs ARBs in heart failure: Clinical summary

Tissue ACE trials in patients with CAD and preserved LV function

Download 00CoreS08.ppt (23 slides - 1.0MB)

Tissue ACE trials in patients with CAD and preserved LV function TREND: Endothelial function and ACE inhibition TREND: Influence of smoking status on progression of endothelial dysfunction TREND: Effect of smoking and ACE-I on coronary artery segment diameter BANFF: Effect of ACE inhibitors vs other cardiovascular agents on FMD BANFF: Results by ACE genotype Trials of ACE inhibition effects on outcomes following revascularization APRES: Effect of ramipril on cardiac outcomes QUO VADIS: Effects of quinapril on ischemia QUO VADIS: Chronic ACE inhibition and Ang II formation in internal mammary artery segments New tissue ACE trials: Differences in scope QUIET: Design and methods QUIET: Cardiac death, nonfatal MI, or VT/VF QUIET: Effect of quinapril on CAD progression according to LDL-C level HOPE: Design and methods HOPE: Primary outcome (MI, stroke, CV death) HOPE: Risk reduction with ACE inhibition HOPE: Risk reduction in diabetic cohort HOPE: Baseline SBP vs global endpoint Tissue ACE trials in patients with CAD and preserved LV function: Benefits observed Tissue ACE trials in patients with CAD and preserved LV function: Implications for clinical practice EUROPA: An upcoming tissue ACE trial EUROPA substudies: Confirmation of pathophysiologic concepts
corerefs.pdf (0.1MB)corerefs.pdf (0.1MB)
This slide/lecture program has been developed under the auspices of the Vascular Biology Working Group. The goal of these programs is to educate healthcare professionals on the contemporary role of the endothelium as a key to cardiovascular health, and to spur exploration of therapeutic interventions capable of improving endothelial function and thereby help reduce the incidence of adverse outcomes.

Published by Medical Education Consultants, Inc. (MEDCON), on behalf of the University of Florida College of Medicine. Supported by an unrestricted educational grant from Pfizer Inc.

Copyright © 2000.

The editorial content of this program expresses the views of the individual contributors and does not necessarily reflect the views or recommendations of the University of Florida College of Medicine, Pfizer, or the publisher. The indications and dosages of drugs discussed in this program may vary from those approved by the Food and Drug Administration (FDA). The reader is advised to consult the full prescribing information for each medication prior to use.

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