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Core Curriculum

• Vascular biology for clinical practice: From basic concepts to mainstream medicine

Physicians who participated at recent Vascular Biology Working Group meetings have provided the direction for the development of these materials.

The program offers a comprehensive update of studies that are advancing our understanding of vascular pathobiology and providing new evidence-based treatment approaches for cardiovascular risk reduction.

Introduction

The information in this slide/lecture program has two primary areas of focus:

  1. An update on basic science advances in vascular biology and how this new data may be driving the results of new clinical trials
  2. New clinical trials that have shown that treatment directed to the underlying vascular pathobiology translates into improved clinical outcomes.

This program updates and extends the knowledge presented in the first two volumes of this series and other VBWG programs, and reflects the continued advance of vascular biology into mainstream medicine.

A major focus of this program is on clinical practice issues related to prevention and cardiovascular risk reduction. Emphasis is on management strategies that 1) consider multiple risk factors, 2) employ evidence-based medicine, and 3) use adequate dosing and combination therapies to enhance clinical outcomes. The recent HOPE study, which demonstrates an expanded role for ACE inhibition in high-risk patients to achieve vasculoprotective benefits beyond blood pressure lowering, is discussed, along with new data that demonstrate the benefit of aggressive lipid lowering to reduce cardiovascular risk.




Cardiovascular disease: Leading cause of death

Download 01CoreS01.ppt (11 slides - 0.4MB)

Cardiovascular disease: Leading cause of death A public health crisis: 60.8 million Americans have 1 or more CV diseases Over 1 million Americans will have a heart attack this year A public health crisis: Stroke prevalence is on the rise Stroke morbidity and mortality A public health crisis: CHF hospitalizations have tripled in 25 years A public health crisis: Increasing prevalence of diabetes The global burden of cardiovascular disease CVD deaths worldwide: 1990 to 2020 Atherosclerotic changes in fetal development: Influence of maternal hypercholesterolemia Progression of atherosclerosis in childhood: Influence of maternal hypercholesterolemia

The progression from CV risk factors to endothelial injury and clinical events

Download 01CoreS02.ppt (11 slides - 0.7MB)

The progression from CV risk factors to endothelial injury and clinical events Physiology of NO in the human coronary and peripheral vasculature Atherosclerosis timeline Therapeutic strategies to enhance vascular wall function Candidates for therapies to enhance vascular endothelial function Correlation between vascular function and hypertension Impaired vascular function in diabetes patients Correlation between vascular function and atherosclerosis  Severe vascular dysfunction predicts increased CV risk in patients Vascular dysfunction predicts CV events: 5-year follow-up Effects of ACEI vs other antihypertensive agents on vascular

Section III: The renin-angiotensin system and ACE inhibition

Download 01CoreS03.ppt (12 slides - 0.5MB)

Section III: The renin-angiotensin system and ACE inhibition Influence of the RAS: Circulating vs local ACE Links between angiotensin and atherogenesis Influence of angiotensin II on the blood vessel Influence of angiotensin II on the heart ACE activity is increased in coronary artery specimens from patients ACE inhibition: Two critical pathways Vasculoprotective effects of local ACE inhibition The fibrinolytic system: tPA and PAI-1 Systolic blood pressure predicts plasma PAI-1 PAI-1 is increased in atheroma from diabetic subjects ACE inhibition favorably alters fibrinolytic balance

Section IV: The interaction of the RAS and lipids

Download 01CoreS04.ppt (9 slides - 0.4MB)

Section IV: The interaction of the RAS and lipids Cholesterol lowering reduces blood pressure response to mental stress Angiotensin II induces LOX-1, an endothelial receptor for oxidized LDL ACE inhibition downregulates LOX-1 in mammary artery segments of Antiatherosclerotic effect of ACE inhibition and AT1 receptor blockade AT1 receptor density is upregulated in hypercholesterolemia and Combined and distinct vascular effects of ACE-I and statins: Combined and distinct vascular effects of ACE-I and statins: Hypertension and hypercholesterolemia: Interactions and potential

Section V: Improving outcomes in CAD: Trial updates

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Section V: Improving outcomes in CAD: Trial updates Key clinical trials of ACE inhibition Multitrial analysis: Effect of early ACEI on deaths in acute MI patients Dose-related effects of early ACEI on left ventricular function in acute MI Full-dose ACEI decreases LV remodeling associated with post-AMI  regional Trends in discharge medications of post-AMI patients: 1994-1999 HOPE: Design and methods HOPE: Baseline characteristics of patients HOPE: Primary outcome (MI/stroke/CV death) HOPE: Risk reduction with ramipril 10 mg HOPE: Secondary outcomes HOPE: Reduction in MI/stroke/CV death (subgroup analysis) HOPE: Reduction in MI/stroke/CV death (subgroup analysis, cont’d) HOPE: Concomitant medications HOPE: CV benefits beyond blood pressure reduction HOPE: Significance for clinical practice Clinical implications of HOPE New avenues of research suggested by HOPE SECURE: Design SECURE: Effect of ramipril on carotid atherosclerosis SECURE: Conclusions Trials of ACE inhibitors and atherosclerosis Dose-related effects of ACEI on left ventricular mass and volume QUO VADIS: Effect of ACEI on ischemia in post-CABG patients APRES: Effect of ACEI on cardiac outcomes in post-PTCA/CABG ACE inhibition therapy: Indications and contraindications Comparison of ACE inhibitors in duration of inhibition Inhibition of ACE in various tissues after long-term oral treatment FDA-approved indications for ACE inhibitors ACE inhibitors with cardiovascular benefits documented Changing indications for ACE inhibition The new era in risk reduction therapy Key ongoing trials of ACE inhibition Most hypertension is complicated Multifactorial nature of coronary heart disease: Composite risk analysis Stroke risk according to risk factor levels Classification of blood pressure for adults JNC VI guidelines: Risk stratification and treatment JNC VI: Compelling indications UKPDS: Tight blood pressure control decreases CVD risk in people UKPDS: Comparisons between tight control of BP and glycemia on risk HOT: Greatest benefit at ≤80 mm Hg in diabetic hypertensives ADA and NKF recommendations on treatment of hypertension Average number of antihypertensive agents needed for patients to Summarized results of isolated systolic hypertension treatment Risk reduction in isolated systolic hypertension in older patients AHA cites HOPE among top 10 research advances in 2000 HOPE: Cerebrovascular events Reduction in stroke risk with statin therapy Aspirin and stroke risk End-stage renal disease: An increasing public health concern Summary of studies on nephropathy progression vs blood pressure Microalbuminuria and ischemic heart disease risk Relative risk of developing ischemic heart disease MICRO-HOPE: Long-term effect of ACE inhibition on HOPE: ACE inhibition in patients with mild renal insufficiency REIN: ACE inhibition in nondiabetic nephropathy REIN: Renal survival in patients on ramipril vs conventional therapy REIN: Risk of progression to overt proteinuria REIN core and follow-up studies: Effect of ACE inhibition on GFR in ACE inhibitors in renal disease Cost-effectiveness of ACEI in nondiabetic nephropathy

Section VI: Lipids: New insights into the importance of aggressive treatment

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Section VI: Lipids: New insights into the importance of aggressive treatment Effect of a high-fat meal on vascular activity in normocholesterolemic LDL-C apheresis improves vascular function following hypercholesterolemia Improvement in vascular function with LDL-C 100 mg/dL in patients Mediterranean diet pyramid Postprandial effect of Mediterranean diet components on Components of Mediterranean diet that benefit endothelial function Mediterranean diet associated with long-term CV benefits after first MI Increase in native and oxidized LDL reduce endothelial production of NO Cholesterol levels and thrombogenic potential Effect of statins on thrombolytic balance Statins: Potential mechanisms of benefit in atherosclerosis Natural history of atherosclerosis and postintervention: Complementary effect of major therapies on 3 vital therapeutic goals Pathobiologic responses to intervention Postintervention: Two different pathobiologies Management of atherosclerosis and management of postintervention: Revascularization, plaque pathology, and lipid lowering Percentage of patients receiving drug therapy who met L-TAP: Distance from LDL-C goal in patients with CHD Cardiologists and primary care physicians: Achieving NCEP goals Post-CABG Trial: LDL-C levels achieved with moderate vs aggressive Post-CABG Trial: Angiographic vein graft outcomes with aggressive vs Effects of statins on lipid lowering and clinical events: Primary prevention trials Effect of statins on lipid lowering and clinical events: Secondary prevention trials 4S: Reduction in need for PTCA/CABG with lipid lowering AVERT: Lipid lowering vs revascularization trial – overview of AVERT: Time to first ischemic event Clinical challenge: Aggressively  LDL-C to  CHD events CURVES: Study design CURVES: Comparative efficacy of statins ASAP: Study design ASAP: Effect of treatment on lipid levels ASAP: Primary outcome—change in carotid IMT LIPID: Secondary prevention of CHD events with LIPID: Effect of lipid lowering on CV outcomes in patients with MIRACL: Central hypothesis MIRACL: Study design MIRACL: Primary and secondary outcomes MIRACL: Primary outcome –– time to ischemic event MIRACL: Relative risk of primary outcome events MIRACL: Worsening angina requiring hospitalization MIRACL: Reduction in fatal/nonfatal stroke MIRACL: Blood lipids MIRACL: Conclusions MIRACL: Closes a treatment gap MIRACL: Implications for clinical practice L-CAD: Effect of early lipid lowering in ACS—study design L-CAD: Effects of early intensive lipid lowering on atherosclerosis L-CAD: Major cardiovascular events with lipid lowering vs usual care FLORIDA: Effect of early lipid lowering after acute MI—study design FLORIDA: Results FLORIDA: Possible confounding effects Improvement in survival with early lipid lowering after ACS Reduction in 1-year mortality with early statin treatment following acute MI In-hospital prescribing of statin improved long-term compliance Prescribing of lipid-lowering medications at discharge post-AMI: Predictors of lipid-lowering agent use at hospital discharge Continuum of care

Section VII: Diabetes and the impact of risk factor clustering on CV risk

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Section VII: Diabetes and the impact of risk factor clustering on CV risk CV events in patients with diabetes CV risk similar in patients with type 2 diabetes and no prior MI The Cardiovascular Dysmetabolic Syndrome Clustering of major CV risk factors accelerates atherosclerosis Clustering of risk factors affects fibrinolytic balance Impact of increasing risk factors on CV death rate in diabetic vs Expected vs observed prevalence of “deadly quartet” risk factors Clustering of risk factors increases mortality in post-CABG patients: New criteria for diagnosis of diabetes mellitus Strategies for reducing macrovascular complications MICRO-HOPE: Effects of ACE inhibition on cardiovascular and MICRO-HOPE: Primary outcomes MICRO-HOPE: Secondary outcomes HOPE & MICRO-HOPE: Primary outcomes CAPPP: Relative risk for CV events with ACEI or conventional therapy Survival of diabetic patients after acute MI is increased with ACE inhibition Common pattern of dyslipidemia in type 2 diabetes Treatment decisions based on LDL-C levels in adults with diabetes Order of priorities for treatment of diabetic dyslipidemia in adults Order of priorities for treatment of diabetic dyslipidemia in adults Efficacy of statin therapy in hyperlipidemic patients with type 2 diabetes 4S: Benefits of lipid lowering in diabetic subgroup with CHD CARE: Benefit of lipid lowering in diabetic subgroup with CHD and average CARE: Reduction in CV events (CHD death/nonfatal MI/CABG/PTCA) Key ongoing lipid intervention trials in diabetes: Primary and secondary Current recommendations for diabetes management  Cost-effectiveness of treating dyslipidemia in diabetic patients

Section VIII: Heart failure:

Download 01CoreS08.ppt (26 slides - 1.2MB)

Section VIII: Heart failure: Progression of hypertension to LVH and heart failure Mechanisms of disease progression in heart failure Aims of heart failure management and therapeutic approaches ACE inhibitors in post-MI patients with LV dysfunction or heart failure ACEI benefits post-AMI patients with heart failure: AIRE, TRACE, SAVE AIREX: ACEI benefits long-term survival in patients with post-AMI b-blockers in heart failure: Key clinical trials RALES: Aldosterone receptor blockade improves outcomes in severe heart failure ACE inhibition improves vascular flow in heart failure by ACE inhibition reduces QT dispersion in patients with acute MI LVH regression: Changes in left ventricular mass index ATLAS: High-dose ACEI reduces adverse outcomes in patients with ATLAS: High-dose ACEI is well tolerated ACE inhibitors in heart failure: Conclusions Comparative RAS and fibrinolytic effects of ACE inhibition and ARBs RESOLVD: ARB vs or plus ACEI in heart failure ELITE II: ARB vs ACEI in heart failure ACE inhibitors vs ARBs in heart failure: RESOLVD, ELITE, ELITE II Val-HeFT: ARB vs usual therapy in heart failure – study overview Val-HeFT: Primary outcomes analysis Val-HeFT: Combined morbidity/mortality in subgroups Val-HeFT: Summary ACEI + ARB vs ACEI monotherapy in heart failure ACE inhibitors vs ARBs in heart failure: Clinical summary Ongoing ARB morbidity and mortality trials in patients with HF or LV dysfunction post-MI
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Published by Medical Education Consultants, Inc. (MEDCON), on behalf of the University of Florida College of Medicine.

The editorial content of this program does not necessarily reflect the views or recommendations of the University of Florida College of Medicine, Wyeth-Ayerst Laboratories, Monarch Pharmaceuticals, Pfizer Inc, or the publisher. The reader is advised to consult the full prescribing information of each product prior to use.

This program was prepared and produced by Medical Education Consultants, Inc., Westport, Connecticut, on behalf of the University of Florida College of Medicine through an unrestricted educational grant provided by Wyeth-Ayerst Laboratories, Monarch Pharmaceuticals, and Pfizer Inc.

©2001 Medical Education Consultants, Inc. (MEDCON). All rights reserved.

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