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Core Curriculum

• Endothelial function: Changing the pattern of treating CV disease

The attached slide materials represent the fifth in a series of slide/lecture programs that focus on what continues to be one of the most exciting new fields of emerging data: The endothelium and its role in cardiovascular health and disease.

These materials extend the knowledge presented in the four previous programs that helped define the endothelium as a mediator of cardiovascular function and structure. Endothelial function is now recognized as critically important in the pathogenesis of atherosclerosis and other cardiovascular conditions. The endothelium is also considerably influenced by cardiovascular risk factors, including hypertension, insulin resistance, and lipids. As our understanding of the pathophysiology of cardiovascular disease is revised, our treatment algorithms should also be updated. This program covers current knowledge concerning the pathophysiology and clinical trials assessing treatments based on this knowledge.

The outline that follows is keyed to the slides. For each slide you will find succinct content points:




Endothelial function: Changing the pattern of treating CV disease

Download 99CoreS01.ppt (13 slides - 1.4MB)

Endothelial function: Changing the pattern of treating CV disease Educational objectives Content outline The endothelium The endothelium: A living organ The endothelium maintains vascular health Causes and consequences of endothelial dysfunction Risk factors and endothelial dysfunction: Mediator role of oxidative stress Oxidative stress: The activators Endothelial dysfunction leads to imbalance of factors resulting in vascular disease Spectrum of vascular remodeling Atherosclerosis timeline Unifying model: Endothelial dysfunction to CVD

Endothelial regulation: Understanding RAS

Download 99CoreS02.ppt (8 slides - 0.3MB)

Endothelial regulation: Understanding RAS Circulating vs tissue ACE Circulating and tissue RAS influence cardiovascular system Vasculoprotective effects of tissue ACE inhibition Role of angiotensin II in atherogenesis ACE inhibitors and fibrinolysis The fibrinolytic system Regulation of fibrinolysis: Fundamental contributions of balance between t-PA and PAI-1

Sources of endothelial insult: Hypertension

Download 99CoreS03.ppt (49 slides - 2.0MB)

Sources of endothelial insult: Hypertension Impaired endothelium-dependent vasodilation in essential hypertension Vasodilation impaired in hypertensive patients Endothelium-independent or -dependent vasodilation and systolic BP Link between hypertension and type 2 diabetes Alterations in vascular endothelium associated with diabetes and hypertension Effect of diabetes and hypertension on monocyte-endothelial cell interactions in animal models Superoxide production in diabetes and hypertension models Consequences of endothelial dysfunction: Hypertension Risk of cardiovascular events by hypertensive status Sources of endothelial insult: Diabetes Blood flow in normal individuals with induced hyperglycemia Blood flow in normal individuals with induced hyperglycemia and fixed insulin Decreased vascular responsiveness in people with diabetes Impaired endothelial function in people with type 1 diabetes Alterations in vascular endothelium associated with diabetes mellitus Patients with atherosclerotic risk factors have impaired smooth muscle response Abnormalities of endothelial function in diabetes: NO pathway Modification of endothelial function by hyperglycemia Insulin causes vasodilation via NO-dependent mechanism Interaction between insulin and the NO system Insulin and endothelial dysfunction CV risk factors in diabetics linked with vascular dysfunction Possible model of type 2 diabetes and CAD risk factors Relating atherosclerosis and insulin resistance Sources of insult: Dyslipidemia Effect of high-fat meal on endothelial activity in normocholesterolemic patients Vitamins C & E attenuate reduction in endothelial function caused by high-fat meal Endothelial function in patients with and without dyslipidemia Rapid improvement in endothelial function with LDL-C apheresis Link between dyslipidemia and type 2 diabetes Endothelial independent responses to NTG in patients associated with risk factors Coagulation and lipoprotein abnormalities in patients with hypertension and diabetes Dysfunctional endothelial cells in dyslipidemia and atherosclerosis When LDL-C is oxidized… Oxidized LDL-C: A common initiating factor for cardiac events Acetylated LDL-C increases ACE expression in macrophage-like cells Sources of endothelial insult: Coronary heart disease Central role of endothelium in CVD and heart failure Endothelial function in heart failure: Vasodilatory response Patients with heart disease and differing vascular responsiveness Coronary vascular resistance of patients with heart disease Effect of Ach on normal and atherosclerotic arteries Increase of vascular adhesion molecules in CHF Clinical outcome vs endothelial function Sources of insult: Summary Risk of cardiovascular disease Endothelial-mediated changes in coronary flow: L-NMMA Endothelial-mediated changes in coronary flow: Acetylcholine + L-NMMA

Endothelial function and treatment of cardiovascular disease

Download 99CoreS04.ppt (62 slides - 2.3MB)

Endothelial function and treatment of cardiovascular disease Drugs shown to improve endothelial function in patients Vasculoprotective effects of ACE inhibition Potency of ACE inhibitors in plasma and tissue (RIB studies) ACE inhibition: Effect on angiogenesis Effect of VEGF & ACE inhibition on endothelial responsiveness to acetylcholine Effect of VEGF & ACE inhibition on calf blood pressure Comparisons of angiogram scores and capillary density Traditional treatment approach New treatment approach ACE inhibition: BP-lowering mechanisms Summary: Tissue ACE inhibition in hypertension Hypertension awareness, treatment, and control Compelling indications UKPDS: Tight blood pressure control decreases CVD risk in people with type 2 diabetes ACE inhibition, not calcium antagonism, improves endothelial function in hypertensives FACET: Probability of remaining free of stroke, acute MI, or hospitalized angina in diabetics ABCD trial: Ca2+ antagonist vs ACE inhibitor in diabetic hypertensives ABCD trial: Summary Dyslipidemia: Lowering lipids and improving endothelial function Statins reduce lipids and improve endothelial function Therapy with a statin improves endothelial function in patients with CAD Treatment of endothelial cells with a statin rapidly (in hours) reverses effects of oxidized LDL-C Statins improve endothelial function in 30 days in patients Treatment with a statin and an antioxidant improves endothelial function and reduces LDL-C oxidation Lowering lipids with a statin increases survival in people with angina or MI: 4S 4S: Reduction in risk in people with diabetes after treatment with a statin 1-year LDL-C and subsequent risk Lowering lipids with a statin reduces coronary events in people with MI: CARE study People with diabetes benefit from lipid lowering with a statin AFCAPS/TexCAPS: Reduction in first acute major coronary event with a statin Summary: Consistency of statins’s affect on potential mechanisms influencing plaque stabilization CURVES study: Comparative efficacy of statins Summary: Effect of statins on LDL-C levels Summary: Effect of statins on CHD event reduction Aggressive LDL-C reduction benefits patients with other CV risk factors: Post-CABG trial Ongoing studies: MIRACL Ongoing studies: MIRACL Ongoing studies: Treating to New Targets (TNT) Beneficial effects of ACE inhibition in heart failure Increased mortality associated with LVH in African-Americans Left ventricular mass index decreases with long-term quinapril treatment LVH reversed in most patients with long-term quinapril treatment Prevention of myocardial infarction with ACE inhibitors Multitrial analysis: Effect of ACE inhibition on 30-day mortality Multitrial analysis: ACE inhibition reduces death in acute MI patients Endothelial function and ACE inhibition: TREND results TREND: Endothelium-dependent microvascular response TREND—Predictors of improved endothelial function: Multivariate analysis BANFF trial: Study design BANFF trial: Absolute changes in flow-mediated vasodilation BANFF trial: Summary and conclusions Quo Vadis Quo Vadis Quo Vadis Quo Vadis Quo Vadis Bradykinin and ACE inhibition: Study design Bradykinin and ACE inhibition: Results Long-term ACE inhibition increases forearm blood flow in patients with chronic heart failure Studies of ACE inhibition in endothelial dysfunction Studies of ACE inhibition in endothelial dysfunction (cont’d)

Summary

Download 99CoreS05.ppt (1 slides - 0.1MB)

Summary

Case 1: A 78-year-old white female with hypertension and hyperlipidemia

Download 99CoreS06.ppt (35 slides - 1.2MB)

Case 1: A 78-year-old white female with hypertension and hyperlipidemia Case 1: Discussion slide Case 1: Discussion slide Case 1: Discussion slide Case 1: Discussion slide Case 1: Discussion slide Case 2: A 58-year-old white male s/p CABG Case 2: Discussion slide Case 2: Discussion slide Case 2: Discussion slide Case 2: Discussion slide Case 2: Discussion slide Case 2: Discussion slide Case 3: A 38-year-old white male with a family history of coronary artery disease Case 3: Discussion slide Case 3: Discussion slide Case 3: Discussion slide Case 3: Discussion slide Case 4: A 50-year-old black male with severe hypertension Case 4: Discussion slide Case 4: Discussion slide Case 4: Discussion slide Case 4: Discussion slide Case 4: Discussion slide Case 5: A 52-year-old female with 5-year history of “borderline” hypertension Case 5: Discussion slide Case 5: Discussion slide Case 5: Discussion slide Case 5: Discussion slide Case 5: Discussion slide Case 6: A 43-year-old male s/p acute anterior wall MI Case 6: Discussion slide Case 6: Discussion slide Case 6: Discussion slide Case 6: Discussion slide
CoreRefs.pdf (0.0MB)CoreRefs.pdf (0.0MB)
This slide/lecture program has been created under the auspices of the Vascular Biology Working Group. The overall goal of this program and future programs is to educate healthcare professionals concerning the modern 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 to reduce incidence of adverse outcomes.

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Related at vwbg.org

The vascular endothelium and CAD: New target considerations in treating the cardiovascular dysmetabolic syndrome

The attached slide materials represent the seventh in a series of slide/lecture programs that focus on what continues to be one of the most exciting new fields of emerging data: The endothelium and its role in cardiovascular health and disease.

Focus: Lipids and the Endothelium

The Endothelium: Impact on CAD treatment strategies

These slide materials represent the third in a series of slide/lecture programs that focus on what continues to be one of the most exciting new fields of emerging data: The endothelium and its role in cardiovascular health and disease.

Curriculum Update #1

Overview of clinical trials to improve endothelial function

The contents of the curriculum update represent a concise overview of clinical trials in the emerging field of study relating to the endothelium and its role in cardiovascular health and disease.
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