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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.

These materials extend the knowledge presented in the six 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 that are common in people with diabetes. The endothelium is considerably influenced by components of the cardiovascular dysmetabolic syndrome, including insulin resistance, hypertension 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:




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

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The vascular endothelium and CAD: New target considerations in treating the cardiovascular dysmetabolic syndrome Content Educational objectives Section I: The cardiovascular dysmetabolic syndrome The cardiovascular dysmetabolic syndrome (CDS)

Section II: A primer on the endothelium

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Section II: A primer on the endothelium Oxidative stress Factors in endothelial dysfunction—early stage plaque Factors in endothelial dysfunction—late stage plaque Regulation of the endothelium: Classic understanding of the RAS Regulation of the endothelium: Circulating vs tissue ACE Regulatory function of ACE Options for regulating the angiotensin system Some contrasts between angiotensin receptor blockade and ACE inhibition Drugs shown to improve endothelial function in patients

Section III: Obesity, diabetes and insulin resistance

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Section III: Obesity, diabetes and insulin resistance Contribution of obesity to insulin resistance Natural history of patients with type 2 diabetes...Problems before you see them Relationship of fasting insulin levels to relative risk for multiple metabolic San Antonio Heart Study: Adjusted risk ratios for CVD mortality in people with type 2 diabetes San Antonio Heart Study: Adjusted risk ratios for CVD mortality by glucose quartile CV risk factors in diabetics linked with vascular dysfunction CAD mortality rates related to glucose tolerance Risk of major CHD event associated with high insulin levels in nondiabetics Quebec Cardiovascular Study Vascular endothelium: Alterations in diabetes mellitus Impaired endothelial function in diabetes Points of intervention in type 2 diabetes: Targeting insulin resistance Monotherapy for type 2 diabetes: Effects on CDS components Comparison of serious adverse event profiles for oral antidiabetic therapies Mechanism of action for oral diabetic agents Effect of troglitazone on glucose disposal Effect of 3 months of metformin or troglitazone on glucose production and uptake Insulin requirements are lower in patients taking troglitazone vs metformin Insulin sensitivity higher in patients taking troglitazone vs metformin Change in intimal-medial thickness with therapy in type 2 diabetes Improving endothelial function in patients with insulin resistance Improvment of coronary blood flow with treatment Increase in NO synthesis in vascular SMC with troglitazone Angina reduced and endothelial function improved in diabetics with treatment

Section IV: Dyslipidemia:

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Section IV: Dyslipidemia: Cardiovascular dysmetabolic syndrome Common pattern of dyslipidemia in type 2 diabetes When LDL-C is oxidized… Oxidized LDL-C: A common initiating factor for cardiac events Rapid improvement in endothelial function with LDL apheresis Effect of high-fat meal on brachial artery flow-mediated vasoactivity in Effects of lipid lowering on endothelial function in hypercholesterolemic patients Summary: Effect of statins on plaque parameters Treatment decisions based on LDL-C levels in adults with diabetes Benefits of aggressive LDL-C lowering Effects of LDL-C and total cholesterol lowering on myocardial ischemia CURVES: LDL-C reductions with statins Effect of troglitazone or glyburide on lipid levels in patients with type 2 diabetes Effect of troglitazone on LDL-C particle size Effect of troglitazone on LDL-C oxidation Fasting TG and risk for CHD death: Paris Prospective Study Targets for triglyceride therapy Atorvastatin’s effect on lipids in patients with hypertriglyceridemia TG and LDL-C-lowering effects of statins in subjects with hypertriglyceridemia Quebec Cardiovascular Study: CHD risks Comparison of traditional vs nontraditional risk factors: Study design Prevalence of traditional and nontraditional risk factors and associated IHD risk Risk of IHD according to cumulative number of risk factors 4S: Benefits of lipid lowering 4S: Benefits of lipid lowering in diabetics Lowering lipids with a statin reduces coronary events in people with MI: CARE study Primary prevention: Statin trials Secondary prevention: Statin trials Future clinical challenge: ↓ LDL-C to ↓ CHD risk

Section V: Cardiovascular disease in women: HRT

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Section V: Cardiovascular disease in women: HRT NEW treatment guideline modifications for reducing heart disease risk in women Impact of estrogen and progestin on cholesterol concentrations HERS: Dyslipidemia reduced with HRT Effects of HRT and simvastatin compared in hypercholesterolemic postmenopausal women Effects of estrogen, simvastatin or combined therapy on brachial FMD Effects of estrogen, simvastatin or combined therapy on fibrinolysis Effects of estrogen, simvastatin or combined therapy on E-selectin Impact of atorvastatin and estradiol on lipids in postmenopausal women ICA intimal thickness and HRT Effect of HRT on carbohydrate metabolism in postmenopausal women Effects of estrogen therapy Women’s Ischemia Syndrome Evaluation (WISE): Study objectives WISE: Study design

Section VI: The endothelium:

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Section VI: The endothelium:Cardiovascular dysmetabolic syndrome Risk of cardiovascular disease Impaired endothelium-dependent vasodilation in essential hypertension Consequences of endothelial dysfunction: Hypertension Risk of cardiovascular events by hypertensive status Hypertension awareness, treatment and control Goal of hypertension prevention and management Classification of blood pressure for adults A treatment approach: Hypertension and diabetes Compelling indications Likely mechanisms of ACE inhibition: Beneficial effects in hypertensive patients with diabetes Vasculoprotective effects of tissue ACE inhibition Potency of ACE inhibitors in plasma and tissue (RIB studies) 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 Low-dose diuretics vs placebo: Meta-analysis of long-term trials Atherosclerotic lesion area reduced with ACE inhibition ACE inhibition: Effect on angiogenesis Probability of death from CHD in diabetic and nondiabetic people with and without prior MI Survival of diabetic patients after acute MI is increased with ACE inhibition UKPDS: Tight blood pressure control decreases CVD risk in people with type 2 diabetes FACET: Probability of remaining free of stroke, acute MI or hospitalized angina ABCD trial: Ca2+ blockade vs ACE inhibition in diabetic hypertensives Interpretation of the findings of FACET and ABCD Hazard ratio for CV events in isradipine/HCTZ treated patients with high or low glucose levels Relative risk of CV events in hypertensive patients with diabetes or IGM in randomized controlled trials Clinical decisions based on clinical trial data Summary: Tissue ACE inhibition in hypertension

Section VII: Summary

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Section VII: SummaryOver past 2 decades mortality has increased in people with diabetes CDS: Taking the treatment challenge to the next level
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.

Published by Medical Education Consultants, Inc. (MEDCON), on behalf of the University of Florida College of Medicine. Supported by an unrestricted educational grant from Parke-Davis, a Division of Warner-Lambert Company. Copyright © 1999.

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, Parke-Davis, 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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