POSTMENOPAUSAL HORMONE REPLACEMENT THERAPY AFTER CABG
Pamela Ouyang, Professor Of Medicine
Johns Hopkins University W400 Wyman Park Building Baltimore, Md 212182680
Grant 5M01RR002719-170206 from National Center For Research Resources
Keywords: coronary bypass, estradiol, hormone therapy, human therapy evaluation, medroxyprogesterone, postmenopause, atherosclerosis, clinical trial, drug screening /evaluation, human morbidity, outcomes research, platelet activation, vasomotion, clinical research, female, human subject, placebo, ultrasound imaging /scanning
Project start date: 2001-12-01
Project end date: 2002-11-30
Sponsored Links Excellgen http://Excellgen.com
POSTMENOPAUSAL HRT ON ATHEROSCLEROSIS AFTER CABG
Pamela Ouyang, Professor Of Medicine
Johns Hopkins University W400 Wyman Park Building Baltimore, Md 212182680
Grant 5M01RR002719-150206 from National Center For Research Resources
Abstract: Coronary atherosclerosis is the major cause of death in women in the United States. Coronary artery bypass surgery decreases symptomatic and clinical evidence of cardiac ischemia, but does not alter the underlying process. Patients may develop recurrent symptoms due to closure of the saphenous vein grafts, the development of atherosclerosis in the graft, or progression of underlying coronary disease. Interventions that reduce the failure of vein grafts would significantly benefit women following bypass surgery and possibly benefit all women with atherosclerotic disease. Observational studies in different populations of postmenopausal women suggest that postmenopausal estrogen replacement therapy reduces cardiac morbidity by 30-50%. However, a recently published, randomized, placebo-controlled clinical trial of Prempro in women with known coronary disease showed no overall difference in cardiovascular death or myocardial infarction after 4 years of study. Thus, the benefit of estrogen and progestin co-therapy (HRT) in women with established coronary disease has not been established. This study is a randomized, placebo-controlled trial using HRT started shortly after coronary bypass surgery to determine whether this treatment will delay the development of graft atherosclerosis and reduce the occurrence of graft occlusion. Women will be randomized to receive placebo or HRT with 17-beta estradiol plus medroxyprogesterone acetate for 3.5 years. The treatment will be started within 6 months of bypass surgery that involves placing a saphenous vein graft. The development of vein graft disease will be measured using quantitative coronary angiographic and intravascular ultrasound assessment of disease severity and extent performed at 6 months and compared to another assessment performed 3 years later. We shall determine the influence of HRT on the change in severity and extent of vein graft disease over 3.5 years of therapy. We postulate that the pathophysiologic mechanisms of platelet activation, fibrinogen binding to platelets, vascular reactivity, coagulation and fibrinolytic factors, and lipoprotein composition predict the occurrence of graft occlusion and graft atherosclerosis. The effect of HRT on these factors will be measured. The proposal also tests the hypothesis that HRT exerts its beneficial effects by its effects on these risk factors in addition to more traditional risk factors including lipids and lipoprotein profile. The influence of these risk factors and the effect of HRT on the frequency of early graft closure (identified on a 6-month coronary angiogram) will be assessed.
Keywords: atherosclerosis, coronary bypass, estradiol, hormone therapy, human therapy evaluation, medroxyprogesterone, postmenopause, clinical trial, clinical trial phase I, clinical trial phase II /III /IV, disease /disorder proneness /risk, drug screening /evaluation, human morbidity, outcomes research, pathologic process, platelet activation, vasomotion, clinical research, female, human subject, placebo, ultrasound scanning
Project start date: 1999-12-01
Project end date: 2000-11-30
POSTMENOPAUSAL HORMONE REPLACEMENT THERAPY AFTER CABG
Pamela Ouyang, Professor Of Medicine
Johns Hopkins University W400 Wyman Park Building Baltimore, Md 212182680
Grant 5M01RR002719-140206 from National Center For Research Resources
Abstract: Coronary atherosclerosis is the major cause of death in postmenopausal women in the USA. While coronary artery bypass surgery decreases symptomatic and clinial evidence of cardioischemia, it does not alter the underlying atherosclerotic process. Patients may develop recurrent symptoms due to saphenous vein graft occlusion, graft atherosclerosis, or progression of underlying coronary artery disease. Interventions that reduce the rate of coronary atherosclerosis progression would significantly benefit women following bypass surgery and possibly benefit all women with atherosclerotic disease. Some observational studies suggest that postmenopausal estrogen replacement therapy (HRT) reduces cardiac morbidity by up to 50%. However, the HERS Study published in 1998, showed no benefit in the clinical outcomes of sudden cardiac death or myocardial infarction in postmenopausal women with known coronary disease randomized to combined conjugated equine estrogen and medroxyprogesterone or placebo over 4 years of follow-up. This study also suggested an increase in these endpoints in the first years of treatment with the active drugs and a subsequent decrease in event rates compared to the placebo treatment with the active drugs and a subsequent decrease in event rates compared to the placebo arm. The efficacy of HRT to delay the development of saphenous graft atherosclerosis is unknown. This randomized, double-masked, placebo-controlled trial tests the hypothesis that HRT started shortly after coronary bypass surgery will delay the development of graft atherosclerosis and reduce the occurrence of graft occlusion. Women are randomized to placebo or HRT with 17 beta-estradiol plus medroxyprogesterone acetate (or 17 beta-estradiol alone if post hysterectomy) within 6 months of surgery. The development of vein graft atherosclerosis will be measured using quantitative coronary angiographic and intravascular ultrasound assessment of disease severity and extent. Studies will be performed 6 months and 3.5 years after randomization. We shall determine the influence of HRT on the primary outcome variables of the change in severity and extent of atherosclerosis in vein grafts over the 3.5 years of therapy. We postulate that the pathophysiologic mechanisms of platelet activation, fibrinogen binding to platelets, vascular reactivity, coagulation and fibrinolytic factors and lipoprotein composition predict the occurrence of graft occulsion and graft atherosclerosis. The effect of HRT on these factors will be masured. The proposal also tests the hypothesis that HRT exerts its beneficial effects on these risk factors in addition to more traditional risk factors including lipids and lipoprotein profile. The influence of these risk factors and the effect of HRT on the frequency of early graft closure (identified on a 6 month coronary angiogram) will be assessed. The study is a multicenter trial with the Data Coordinating Center and principal Investigator located at Johns Hopkins. Women are recruited from the University of Maryland Hospital, Johns Hopkins Hospital and followed at Johns Hopkins. The other sites include Wake Forest University School of Medicine, Hartford Hospital, Christiana Hospital, Cleveland Clinic, University Hospitals of Cleveland, Montreal Heart Institute, Ottawa Heart Insititute, Washington Hospital Center, Miriam Hospital in Rhode Island, University of Connecticut, and the Indiana Heart Institute. Additional sites have been added because of the difficulty in recruitment experienced at every site.
Keywords: coronary bypass, estradiol, hormone therapy, human therapy evaluation, medroxyprogesterone, postmenopause, atherosclerosis, clinical trial, drug screening /evaluation, human morbidity, outcomes research, platelet activation, vasomotion, clinical research, female, human subject, placebo, ultrasound scanning
Project start date: 1998-12-01
Project end date: 1999-11-30
WOMEN S ANGIOGRAPHIC VITAMINS AND ESTROOGENS TRIAL
Pamela Ouyang, Professor Of Medicine
Johns Hopkins University W400 Wyman Park Building Baltimore, Md 212182680
Grant 5M01RR002719-140221 from National Center For Research Resources
Abstract: Cardiovascular disease is the leading cause of death in postmenopausal women in the USA. Coronary artery disease differs between men and women in several important aspects. Lipid profiles and their associated cardiovascular risk in women differ from those in men; cigarette smoking may convey even greater risk in white women than in men; increased risk of cardiovascular disease after menopause and the potential role of estrogen replacement therapy in reducing this risk is specific to women. Several lines of evidence support a protective role for antioxidant vitamins against oxidative damage. Several European epidemiologic studies have suggested a relationship between dietary consumption of antioxidants and coronary artery disease. This trial is a 2x2 factorial, randomized, double-masked, placebo-controlled clinical trial. The trial will randomize women to active or placebo hormone replacement therpy (conjugated equine estrogen, and when appropriate, conjugated equine estrogen with medroxyprogesterone) and to active or placebo vitamin combination (1000 mg/day of Vitamin C and 800 IU/day of Vitamin E). Patients are identified at the time of a cardiac catheterization. Women will be followed on randomized therapy and the progression of coronary disease measured using quantitative angiographic comparison between the initial coronary angiogram and one repeated after three years of randomized therapy. This is a multicenter trial with NIH-selected sites being Johns Hopkins Hospital (Pamela Ouyang, MD), Hartford Hospital, University of Alabama, Medlantic Research Institute, and Duke University Medical Center. The protocol details were determined by a steering committee comprised of the principal investigators from the five clinical sites, the NHLBI project officer (Dr. David Gordon), and the principal investigator from the study coordinating center at George Washington University (Dr. Joel I. Verter).
Keywords: coronary disorder, estrogen analog, female, hormone therapy, human therapy evaluation, vitamin therapy, angiography, ascorbate, cardiovascular disorder prevention, clinical trial phase II /III /IV, combination chemotherapy, medroxyprogesterone, tocopherol, clinical research, human subject, women s health
Project start date: 1998-12-01
Project end date: 1999-11-30
PREVENTION OF CARDIAC EVENTS WITH ACE INHIBITORS
Pamela Ouyang, Professor Of Medicine
Johns Hopkins University W400 Wyman Park Building Baltimore, Md 212182680
Grant 5M01RR002719-150259 from National Center For Research Resources IRG: RIRG
Abstract: Angiotensin converting enzyme (ACE) inhibitor therapy is of proven value in the therapy of patients with congestive heart failure. More recently, the clinical effectiveness of ACE inhibition for secondary prevention in patients that experienced a myocardial infarction with associated left ventricular dysfunction has been demonstrated. The results of the previous randomized, placebo-controlled studies in patients with impaired left ventricular function (SOLVD and SAVE trials) demonstrated that the long-term use of ACE inhibitor therapy in patients with left ventricular dysfunction without overt heart failure not only reduced mortality and the manifestations of congestive heart failure, but importantly, resulted in a reduction in the incidence of myocardial infarction and other clinical manifestations of coronary artery disease. The Prevention of Events with Angiotension Converting Enzyme Inhibition (PEACE) trial will test whether the addition of the ACE inhibitor, Trandolapril, to standard therapy will reduce the incidence of cardiovascular mortality or non-fatal myocardial infarction in patients with coronary artery disease, but preserved left ventricular function (EF>40%). This is a large simple trial funded by the NIH. The Johns Hopkins Bayview Medical Center clinical site is subcontracted with the George Washington Biostatistics Center which is the Data Coordinating Center for the study. The goal of the study is to determine whether the addition of Trandolapril, an ACE inhibitor, when added to standard therapy will reduce the incidence of cardiovascular mortality, non-fatal MI, or need for coronary artery procedure for revascularization in patients with coronary heart disease and EF>40%. The secondary goal is to determine if the addition of the ACE inhibitor to standard therapy will reduce the incidence of hospitalization for the management of either unstable angina, congestive heart failure, stroke, or cardiac arrhythmia. The clinical progression of peripheral vascular disease to require a surgical procedure or percutaneous angioplasty procedure will also be considered a manifestation of atherosclerotic cardiovascular disease.
Keywords: ACE inhibitor, cardiovascular disorder prevention, congestive heart failure, coronary disorder, heart disorder chemotherapy, human therapy evaluation, myocardial infarction, atherosclerosis, clinical trial phase II /III /IV, coronary artery, heart function, heart ventricle, human mortality, patient care management, clinical research, human subject, placebo
Project start date: 1985-12-01
Project end date: 2002-11-30
WOMEN S ANGIOGRAPHIC VITAMINS AND ESTROOGENS TRIAL
Pamela Ouyang, Professor Of Medicine
Johns Hopkins University W400 Wyman Park Building Baltimore, Md 212182680
Grant 5M01RR002719-170221 from National Center For Research Resources
Keywords: coronary disorder, estrogen analog, female, hormone therapy, human therapy evaluation, vitamin therapy, angiography, ascorbate, cardiovascular disorder prevention, clinical trial phase II /III /IV, combination chemotherapy, medroxyprogesterone, tocopherol, clinical research, human subject, women s health
Project start date: 2001-12-01
Project end date: 2002-11-30
POSTMENOPAUSAL HORMONE REPLACEMENT THERAPY AFTER CABG
Pamela Ouyang, Professor Of Medicine
Johns Hopkins University W400 Wyman Park Building Baltimore, Md 212182680
Grant 5M01RR002719-160206 from National Center For Research Resources
Keywords: coronary bypass, estradiol, hormone therapy, human therapy evaluation, medroxyprogesterone, postmenopause, atherosclerosis, clinical trial, drug screening /evaluation, human morbidity, outcomes research, platelet activation, vasomotion, clinical research, female, human subject, placebo, ultrasound scanning
Project start date: 2000-12-01
Project end date: 2001-11-30
WOMEN S ANGIOGRAPHIC VITAMINS AND ESTROOGENS TRIAL
Pamela Ouyang, Professor Of Medicine
Johns Hopkins University W400 Wyman Park Building Baltimore, Md 212182680
Grant 5M01RR002719-160221 from National Center For Research Resources
Keywords: coronary disorder, estrogen analog, female, hormone therapy, human therapy evaluation, vitamin therapy, angiography, ascorbate, cardiovascular disorder prevention, clinical trial phase II /III /IV, combination chemotherapy, medroxyprogesterone, tocopherol, clinical research, human subject, women s health
Project start date: 2000-12-01
Project end date: 2001-11-30
POSTMENOPAUSAL HORMONE REPLACEMENT THERAPY AFTER CABG
Pamela Ouyang, Professor Of Medicine
Johns Hopkins University W400 Wyman Park Building Baltimore, Md 212182680
Grant 5M01RR002719-120206 from National Center For Research Resources
Keywords: coronary bypass, estradiol, hormone therapy, human therapy evaluation, medroxyprogesterone, postmenopause, atherosclerosis, clinical trial, drug screening /evaluation, human morbidity, outcomes research, platelet activation, vasomotion, clinical research, female, human subject, placebo, ultrasound scanning
Project start date: 1997-03-17
Project end date: 1998-06-30
Grants awarded to Pamela Ouyang
Serum Sex Hormonoe Levels & Subclinical Atherosclerosis
Pamela Ouyang, Professor Of Medicine
Johns Hopkins University W400 Wyman Park Building Baltimore, Md 212182680
Grant 5R01HL074406-04 from National Heart, Lung, And Blood Institute IRG: EDC
Abstract: Throughout their lifetime, men are at higher risk of coronary heart disease (CHD) than women, however, after menopause this difference is attenuated. This observation suggests that endogenous sex hormones could be associated with CHD risk. There is some evidence indicating that the effect of sex hormones on CHD risk could be mediated, in part, by alterations in lipid levels or other CHD risk factors. However, other evidence supports an independent relationship of circulating hormone levels with CHD risk. For example, we recently reported a significant positive association between serum total testosterone concentration and the presence of subclinical coronary artery calcium (CAC) in young adult men that was independent of other CHD risk factors. Conversely, we showed an independent inverse association between total testosterone concentration and carotid intimal-medial wall thickness (IMT) in women. Overall, these results suggest that the influence of the hormonal milieu on subclinical atherosclerosis may not be the same in men compared to that in women. The overall objective of the proposed project is to examine the associations of serum sex hormone concentrations with the presence and progression of subclinical atherosclerosis in 3,259 male and 2,802 postmenopausal female participants of the Multi-Ethnic Study of Atherosclerosis (MESA). Subclinical atherosclerosis will be identified using both CAC and carotid IMT. Progression will be identified by the change in CAC over 3.5 years. Circulating concentrations of total (and free) testosterone (T), dehydroepiandrosterone (DHEA), 17beta-estradiol (E2), and sex hormone binding globulin (SHBG) in stored serum samples collected at the MESA baseline exam will be assessed. Laboratory results will be merged with existing demographic, anthropometric, lifestyle, CHD risk factor, and subclinical disease data collected in MESA. Cross-sectional and prospective methods of statistical analysis will be used to assess the proposed associations. MESA is particularly well suited for disentangling the effects of hormonal factors and CHD risk factors on subclinical atherosclerosis because of the availability of high-quality data, serum samples, and CAC and IMT measurements in a large multi-ethnic population of men and women.
Keywords: atherosclerosis, beta globulin, cardiovascular disorder risk, dehydroepiandrosterone, estradiol, gender difference, hormone binding protein, testosterone, African American, Chinese American, Hispanic American, acute phase protein, calcium, cardiovascular disorder epidemiology, caucasian American, cell adhesion molecule, fibrinogen, fibrinolysis, hormone therapy, interleukin 6, longitudinal human study, plasminogen activator inhibitor, postmenopause, racial /ethnic difference, human data
Project start date: 2003-07-01
Project end date: 2008-06-30
5R01HL074406-04 (2006): $168315
5R01HL074406-03 (2005): $275500
5R01HL074406-02 (2004): $275250
Serum Sex Hormone Levels And Subclinical Atherosclerosis
Pamela Ouyang, Professor Of Medicine
Johns Hopkins University W400 Wyman Park Building Baltimore, Md 212182680
Grant 1R01HL074406-01 from National Heart, Lung, And Blood Institute IRG: EDC
Abstract: Throughout their lifetime, men are at higher risk of coronary heart disease (CHD) than women, however, after menopause this difference is attenuated. This observation suggests that endogenous sex hormones could be associated with CHD risk. There is some evidence indicating that the effect of sex hormones on CHD risk could be mediated, in part, by alterations in lipid levels or other CHD risk factors. However, other evidence supports an independent relationship of circulating hormone levels with CHD risk. For example, we recently reported a significant positive association between serum total testosterone concentration and the presence of subclinical coronary artery calcium (CAC) in young adult men that was independent of other CHD risk factors. Conversely, we showed an independent inverse association between total testosterone concentration and carotid intimal-medial wall thickness (IMT) in women. Overall, these results suggest that the influence of the hormonal milieu on subclinical atherosclerosis may not be the same in men compared to that in women. The overall objective of the proposed project is to examine the associations of serum sex hormone concentrations with the presence and progression of subclinical atherosclerosis in 3,259 male and 2,802 postmenopausal female participants of the Multi-Ethnic Study of Atherosclerosis (MESA). Subclinical atherosclerosis will be identified using both CAC and carotid IMT. Progression will be identified by the change in CAC over 3.5 years. Circulating concentrations of total (and free) testosterone (T), dehydroepiandrosterone (DHEA), 17beta-estradiol (E2), and sex hormone binding globulin (SHBG) in stored serum samples collected at the MESA baseline exam will be assessed. Laboratory results will be merged with existing demographic, anthropometric, lifestyle, CHD risk factor, and subclinical disease data collected in MESA. Cross-sectional and prospective methods of statistical analysis will be used to assess the proposed associations. MESA is particularly well suited for disentangling the effects of hormonal factors and CHD risk factors on subclinical atherosclerosis because of the availability of high-quality data, serum samples, and CAC and IMT measurements in a large multi-ethnic population of men and women.
Keywords: atherosclerosis, beta globulin, cardiovascular disorder risk, dehydroepiandrosterone, estradiol, gender difference, hormone binding protein, testosterone, African American, Chinese American, Hispanic American, acute phase protein, calcium, cardiovascular disorder epidemiology, caucasian American, cell adhesion molecule, fibrinogen, fibrinolysis, hormone therapy, interleukin 6, longitudinal human study, plasminogen activator inhibitor, postmenopause, racial /ethnic difference, human data
Project start date: 2003-07-01
Project end date: 2007-06-30
1R01HL074406-01 (2003): $281250
DOSE RANGING STUDY OF THE EFFECTS OF ALPHA ACID ON OXIDATIVE STRESS
Pamela Ouyang
Johns Hopkins University, W400 Wyman Park Building, Baltimore, Md 21218
Grant 5R21AT003862-03 from National Center For Complementary & Alternative Medicine
Abstract: This exploratory small clinical study will determine the effect profile of oral alpha lipoic acid to determine the optimum dose to reduce oxidative stress in the metabolic syndrome. There is biological plausibility for an association between oxidative stress levels and vascular dysfunction in the metabolic syndrome. Metabolic syndrome is a cluster of abnormalities that includes obesity, hypertension, hyperlipidemia, and diabetes, and is associated with increased risk for cardiovascular disease. These factors may be linked by insulin resistance. Metabolic syndrome is associated with greater oxidatave stress. This increased oxidative stress affects adipocytes, hepatocytes, and endothelial cells, causing release of inflammatory cytokines and results in impaired vascular function. These changes are associated with an increased atherosclerotic risk. Reducing oxidative stress could result in decreased inflammation and improved vascular function. Alpha lipoic acid is a potent antioxidant and reduces oxidative stress in models of diabetes. Studies in fat cells show lipoic acid stimulates the plasma membrane targeted translocation of GLUT1 and GLUT 4, important intracellular glucose transporters. Lipoic acid also suppresses the endothelial cell NF-kappaB activation and the expression of cell adhesion molecules by advanced glycation end-products. In animal models of diabetes, alpha lipoic acid decreases oxidative stress and improves glucose utilization. In obese rat models with impaired endothelial vasodilator function, alpha lipoic acid activates aortic endothelial AMP-activated protein kinase, a regulator of cellular metabolism, and improves nitric oxide synthesis and vasodilator function. Human data is more limited with no published studies evaluating the antioxidant effects in individuals with metabolic syndrome over a range of alpha lipoic acid doses. We propose a placebo controlled dose ranging study to determine 1) the dose of alpha lipoic acid that reduces levels of oxidative stress markers, 2) whether alpha lipoic acid improves vascular function through effects on oxidative stress, 3) whether micoparticle release is inhibited by alpha lipoic acid and 4) adverse effect profile of the dose range. This study will determine the effective dose that should be studied in future larger studies powered to evaluate whether alpha lipoic acid therapy improves vascular function. The metabolic syndrome, a cluster of factors including obesity, high blood pressure, high cholesterol and diabetes, carries increased risk of cardiovascular disease and is associated with the overproduction of oxygen free radicals that lead to greater inflammation, vascular abnormalities and abnormal glucose handling. This study will measure whether different doses of alpha lipoic acid, a potent antioxidant, will reduce blood markers of oxidative stress and improve vascular function. If alpha lipoic acid is effective, the information from this study could lead to larger trials of the drug to assess whether it can reduce cardiovascular risk in individuals with metabolic syndrome
Keywords: (hydroxymethylglutaryl-CoA reductase (NADPH)) kinase; 1, 2-Dithiolane-3-pentanoic acid; 3-mononitrotyrosine; 3-nitrotyrosine; 5`-AMP-activated protein kinase; AMP-activated kinase; AMP-activated protein kinase; AMPK enzyme; Acids; Active Oxygen; Adhesion Molecule; Adipocytes; Adipose Cell; Advanced Glycosylation End Products; Adverse effects; Affect; After Care; After-Treatment; Aftercare; Animal Model; Animal Models and Related Studies; Antioxidants; Assay; Atheroscleroses; Atherosclerosis; Atherosclerotic Cardiovascular Disease; Autoantibodies; B cell differentiation factor; B cell stimulating factor 2; B-Cell Differentiation Factor-2; B-Cell Stimulatory Factor-2; BCDF; BSF-2; BSF2; BSF2 (B cell stimulating factor 2); Bioassay; Biologic Assays; Biological; Biological Assay; Bizzozero`s corpuscle/cell; Blood; Blood Platelets; Blood Pressure, High; Blood Serum; Blood Vessels; Body Tissues; C-reactive protein; Cardiovascular Diseases; Cause of Death; Cell Adhesion Molecules; Cell membrane; Cholest-5-en-3-ol (3beta)-; Cholesterol; Clinical Research; Clinical Study; Clinical Trials; Clinical Trials, Unspecified; Common Rat Strains; Cytoplasmic Membrane; D-Glucose; Data; Deetjeen`s body; Dextrose; Diabetes Mellitus; Diabetes Mellitus, Adult-Onset; Diabetes Mellitus, Ketosis-Resistant; Diabetes Mellitus, Non-Insulin-Dependent; Diabetes Mellitus, Noninsulin Dependent; Diabetes Mellitus, Slow-Onset; Diabetes Mellitus, Stable; Diabetes Mellitus, Type 2; Diabetes Mellitus, Type II; Differentiation Factor, B-Cell; Dose; Double-Blind Method; Double-Blind Study; Double-Blinded; Double-Masked Method; Double-Masked Study; Drugs; Dysfunction; Endogenous Nitrate Vasodilator; Endothelial Cells; Endothelium; Endothelium-Derived Relaxing Factor; Enzymes; Fasting; Fat Cells; Fats; Fatty acid glycerol esters; Functional disorder; Future; GLUT; GLUT1; GLUT4; GLUT4 gene; GTR1; Glucose; Glucose Binding Protein; Glucose Transporter; Glucose Transporter Type 1 Gene; Glycation End Products, Advanced; Glycosylation End Products, Advanced; HMG CoA reductase (NADPH) kinase; HMG CoA reductase kinase; HMG coenzyme A reductase (NADPH) kinase; HPGF; Hayem`s elementary corpuscle; Hepatic Cells; Hepatic Parenchymal Cell; Hepatocyte; Hepatocyte-Stimulating Factor; Hybridoma Growth Factor; Hyperlipemia; Hyperlipidemia; Hypertension; IFN-beta 2; IFNB2; IL-6; IL6 Protein; INFLM; Immunoglobulin Enhancer-Binding Protein; Individual; Inflammation; Inflammatory; Insulin Resistance; Interleukin 6 (Interferon, Beta 2); Interleukin-6; Intermediary Metabolism; Intervention Studies; Isoprostanes; LDL; LDL oxidation; Lead; Link; Lipocytes; Lipoic Acid; Lipoproteins, LDL; Liver Cells; Low Density Lipoprotein oxidation; Low-Density Lipoproteins; METBL; MGI-2; MODY; Mammals, Rats; Marrow platelet; Mature Lipocyte; Mature fat cell; Maturity-Onset Diabetes Mellitus; Measurement; Measures; Mediating; Medication; Metabolic Processes; Metabolic syndrome; Metabolism; Modeling; Mononitrogen Monoxide; Myeloid Differentiation-Inducing Protein; NF-kB; NF-kappa B; NF-kappaB; NFKB; NIDDM; Nitric Oxide; Nitric Oxide, Endothelium-Derived; Nitrogen Monoxide; Nitrogen Protoxide; Nitrogen oxide; Non-Insulin Dependent Diabetes; Non-Insulin-Dependent Diabetes Mellitus; Nuclear Factor kappa B; Nuclear Transcription Factor NF-kB; Obesity; Oral; Oxidative Stress; Oxygen Radicals; PBO; Pathway interactions; Pb element; Peroxidases; Pharmaceutic Preparations; Pharmaceutical Preparations; Physiopathology; Placebo Control; Placebos; Plasma Membrane; Plasmacytoma Growth Factor; Platelets; Prevalence; Pro-Oxidants; Proteins, specific or class, C-reactive; Publishing; Randomized; Rat; Rattus; Reactive Nitrogen Species; Reactive Oxygen Species; Reporting; Research; Reticuloendothelial System, Blood; Reticuloendothelial System, Platelets; Risk; SLC2A1; SLC2A1 gene; Safety; Serum; Sham Treatment; Stress; T2D; T2DM; TBARs; Testing; Thiobarbituric Acid Reactive Substances; Thioctic Acid; Thrombocytes; Tissues; Transcription Factor NF-kB; Transport Protein, Glucose; Treatment Side Effects; Type 2 diabetes; Type II diabetes; Vascular Hypertensive Disease; Vascular Hypertensive Disorder; Vasodilating Agent; Vasodilator Agents; Vasodilator Drugs; Vasodilators; adiposity; adult onset diabetes; advanced glycation endproduct; alpha-Lipoic Acid; anti-oxidant; antioxidant therapy; atheromatosis; atherosclerotic vascular disease; autoimmune antibody; base; beta-Lipoproteins; biomarker; cardiovascular disease risk; cardiovascular disorder; cardiovascular disorder risk; cardiovascular risk; cardiovascular risk factor; cell adhesion protein; clinical investigation; corpulence; corpulency; corpulentia; cytokine; design; designing; diabetes; diabetic; dosage; drug/agent; endothelial cell derived relaxing factor; fasted; fasts; free radical oxygen; heavy metal Pb; heavy metal lead; human data; hydroxymethylglutaryl-CoA-reductase kinase; hyperpiesia; hyperpiesis; hypertensive disease; improved; indexing; inflammatory marker; insulin resistant; insulin sensitivity; interferon beta 2; kappa B Enhancer Binding Protein; ketosis resistant diabetes; maturity onset diabetes; model organism; nitrotyrosine; nuclear factor kappa beta; obese; obese people; obese person; obese population; oxidation; oxidized lipid; pathophysiology; pathway; plasmalemma; public health relevance; randomisation; randomization; randomized placebo controlled study; randomized placebo controlled trial; randomly assigned; response; self reactive antibody; sham therapy; side effect; therapy adverse effect; thrombocyte/platelet; treatment adverse effect; treatment effect; urinary; vascular; vascular inflammation
Project start date: 2008-08-01
Project end date: 2011-07-31
Budget start date: 1-AUG-2010
Budget end date: 31-JUL-2011
PFA/PA: PA-06-510
5R21AT003862-03 (2010): $124740
5R21AT003862-02 (2009): $189000
1R21AT003862-01A2 (2008): $189000
CLINICAL UNIT FOR ASYMPTOMATIC CARDIAC ISCHEMIA PILOT
Pamela Ouyang, Professor Of Medicine
Johns Hopkins University W400 Wyman Park Building Baltimore, Md 212182680
Grant 5N01HV018118-00491 from Division Of Heart And Vascular Diseases
Abstract: The purpose of this program is to conduct a multicenter trial as a pilot study to assess the feasibility of and test the methodology required for a full scale clinical trial of asymptomatic cardiac ischemia therapies. The primary objective is to determine the relative efficacy of usual care, stepped medical therapy, and mechanical revascularization to provide freedom from myocardial ischemia. Other objectives are to confirm the frequency of asymptomatic cardiac ischemia in the target patient subgroups, validate current detection and as the availability of patients for randomization and compliance with assigned prescription. The study population will consist of a total of 600 patients with coronary artery disease (CAD), documented by angiographic and radionuclide studies, who have been identified by both exercise stress testing and 48 hour ambulatory ECG monitoring 300 patients with CAD and exertional angina and 300 patients with asymptomatic CAD. Within each stratum, patients will be randomized to three treatment strategies usual, symptom-guided care; maximal medical, ambulatory ECG-directed, stepped care therapy; and mechanical revascularization. The primary endpoint will be a reduction of total and asymptomatic cardiac ischemia detected by ambulatory ECG monitoring. This contract is for a Clinical Unit for patient accession, intervention, and data collection.
Project start date: 1990-12-10
Project end date: 1994-03-31
CLINICAL UNIT FOR THE ANGIOGRAPHIC TRIAL IN WOMEN
Pamela Ouyang, Professor Of Medicine
Medicinejohns Hopkins University
w400 Wyman Park Building
baltimore, Md 212182680
Grant 5N01HV068170-006 from Division Of Heart And Vascular Diseases
Abstract: The purpose of this program is to assess whether hormonal replacement therapy and/or antioxidant treatment will stabilize or inhibit progression, and induce regression of coronary plaques in women. Phase 1(8 months) comprises planning and organizing the Study Protocols, Manual of Operations, and data forms. Protocol Development will take approximately 6 months. After Protocol Development, there will be an approximate 2 month hiatus in activity on the study. During this time, the participating centers will prepare and submit revised cost proposals based on the actual protocol. Phase 11(4 years) will be for patient recruitment and patient follow-up. Phase 111(6 months) is for data analysis
Keywords: angiography, antioxidant, atherosclerotic plaque, cardiovascular disorder chemotherapy, coronary disorder, female, hormone therapy, human therapy evaluation clinical trial phase II /III /IV bioimaging /biomedical imaging, clinical research, human subject
Project start date: 1996-08-30
Project end date: 2002-05-31
5N01HV068170-006 (2000): $362897
5N01HV068170-005 (1999): $231285
Sponsored Links Excellgen http://Excellgen.com
5N01HV068170-004 (1998): $68000
HORMONE REPLACEMENT THERAPY EFFECTS ON PROGRESSION OF ARTHEROSCLEROSIS
Pamela Ouyang, Professor Of Medicine
Johns Hopkins University W400 Wyman Park Building Baltimore, Md 212182680
Grant 5M01RR000052-420531 from National Center For Research Resources
Abstract: Coronary atherosclerosis is the major cause of death in women in the USA. While coronary artery bypass surgery decreases symptomatic and clinical evidence of cardiac ischemia it does not alter the underlying process. Patients may develop recurrent symptoms due to saphenous vein graft occlusion, graft atherosclerosis, or progression of underlying coronary disease. Interventions that reduce the rate of coronary atherosclerosis progression would significantly benefit women following bypass surgery and possibly benefit all women with atherosclerotic disease. Some observational studies suggest that postmenopausal estrogen replacement therapy reduces cardiac morbidity by up to 50%. The benefit of estrogen and progestin therapy (HRT) in women with established coronary disease has not been studied. The efficacy of HRT to delay the development of saphenous graft atherosclerosis is unknown. This randomized, double-masked, placebo- controlled trial tests the hypothesis that HRT started shortly after coronary bypass surgery will delay the development of graft atherosclerosis and reduce the occurrence of graft occlusion. Women will be randomized to placebo or HRT with 17b-estradiol plus medroxyprogesterone acetate (or 17 -estradiol if post hysterectomy) within 4 months of surgery. The development of vein graft atherosclerosis will be measured using quantitative coronary angiographic and intravascular ultrasound assessment of disease severity and extent. Studies will be performed 6 months and 3.5 years after randomization. We shall determine the influence of HRT on the primary outcome variables of the change in severity and extent of atherosclerosis in vein grafts over 3.5 years of therapy. We postulate that the pathophysiologic mechanisms of platelet activation, fibrinogen binding to platelets, vascular reactivity, coagulation and fibrinolytic factors and lipoprotein composition predict the occurrence of graft occlusion and graft atherosclerosis. The effect of HRT on these factors will be measured. The proposal also tests the hypothesis that HRT exerts its beneficial effects by its effects on these risk factors in addition to more traditional risk factors including lipids and lipoprotein profile. The influence of these risk factors and the effect of HRT on the frequency of early graft closure (identified on a 6 month coronary angiogram) will be assessed.
Keywords: atherosclerosis, coronary bypass, hormone therapy, human therapy evaluation, longitudinal human study, pathologic process, postoperative state, biomarker, blood coagulation, blood lipoprotein, clinical trial, female, fibrinolysis, outcomes research, platelet activation, vasomotion, angiography, clinical research, human subject, interview, ultrasound imaging /scanning
HRt & ATHEROSCLEROSIS AFTER CORONARY BYPASS & MENOPAUSE
Pamela Ouyang, Professor Of Medicine
Johns Hopkins University W400 Wyman Park Building Baltimore, Md 212182680
Grant 5M01RR000052-420735 from National Center For Research Resources IRG: ZRR1
Abstract: Coronary atherosclerosis is the major cause of death in postmenopausal women in the USA. While coronary artery bypass surgery decreases symptomatic and clinical evidence of cardiac ischemia it does not alter the underlying artherosclerotic process. Observational studies suggest that postmenopausal estrogen replacement therapy (HRT) reduces cardiac morbidity by up to 50%. However, the HERS study, published in 1998, showed no overall benefit in the clinical outcomes of sudden cardiac death or myocardial infarction in postmenopausal women with known coronary disease randomized to combined conjugated equine estrogen and medroxyprogesterone or placebo over 4 years of follow-up. This study also suggested an increase in these endpoints in the first year of treatment with the active drugs and a subsequent decrease in event rates compared to the placebo arm. The efficacy of HRT to delay the development of saphenous graft atherosclerosis is unknown. The trial of Postmenopausal HRT after CABG is a randomized, double-masked, placebo-controlled trial that tests the hypothesis that HRT started within months of coronary bypass surgery will delay the development of graft atherosclerosis and reduce the occurrence of graft occlusion. Women are randomezed to placebo or HRT with 17 beta-estradiol plus medroxyprogesterone acetate (or 17 beta-estradiol alone if post hysterectomy) within 6 months of surgery. The development of vein graft atherosclerosis will be measured using quantitative coronary angiographic and intravascular ultrasound assessment of disease severity and extent. Studies will be performed 6 months and 3.5 years after randomization. We shall determine the influence of HRT on the primary outcome variables of the change in severity and extent of atherosclerosis in vein grafts over 3.5 years of therapy. We postulate that the pathophysiologic mechanisms of platelet activation, fibrinogen binding to platelets, vascular reactivity, coagulation and fibrinolytic factors and lipoprotein composition predict the occurrence of graft occlusion and graft atherosclerosis. The effect of HRT on these factors will be measured. The proposal also tests the hypothesis that HRT exerts its beneficial effects on these risk factors in addition to more traditional risk factors including lipids and lipoprotein profile. The influence these risk factors and the effect of HRT on the frequency of early graft closure (identified on a 6 month coronary angiogram) will be assessed.
Keywords: atherosclerosis, coronary bypass, estrogen, female, hormone therapy, human therapy evaluation, pathologic process, postmenopause, clinical trial phase I, drug screening /evaluation, longitudinal human study, postoperative state, women s health, angiography, clinical research, human subject, ultrasonography
POSTMENOPAUSAL HORMONE REPLACEMENT THERAPY AFTER CABG
Pamela Ouyang, Professor Of Medicine
Medicinejohns Hopkins University
w400 Wyman Park Building
baltimore, Md 212182680
Grant 5U01HL050840-05 from National Heart, Lung, And Blood Institute IRG: ZRG4
Abstract: Coronary atherosclerosis is a major cause of death in women in the USA. Although coronary artery bypass surgery decreases symptomatic and clinical evidence of ischemia, it does not alter the underlying process. Patients may present several years later with recurrent symptoms that may be a result of occlusion of saphenous vein grafts, development of atherosclerotic disease in the vein grafts, or progression of underlying disease. Any intervention that can reduce the rate of progression of coronary atherosclerosis following bypass surgery would provide significant benefit for women following bypass surgery and possibly for other women with atherosclerotic disease. Observational studies suggest that postmenopausal estrogen replacement therapy is associated with a reduction in cardiac morbidity. However the benefit for hormone replacement therapy in women with established coronary disease has not been demonstrated. This randomized, double-blind controlled trial tests the hypothesis that postmenopausal hormone replacement therapy in women following coronary bypass surgery will reduce the occurrence of graft occlusion and delay the development of graft atherosclerosis. Women will be randomized to esnadiol with daily medroxyprogesterone or placebo within 4 weeks of bypass surgery. Graft occlusion and development of vein graft atherosclerosis will be measured by comparing quantitative coronary angiographic and intravascular ultrasonographic assessment of disease severity and extent performed at 6 months and 3.5 years after randomization. The primary outcome variables will be the occurrence of graft occlusion at 6 months and the change in severity and extent of atherosclerosis in the saphenous vein grafts over 3 years. The proposal will determine th influence of hormone replacement therapy on the primary outcome variables. The pathophysiologic mechanisms of interest in this proposal are platelet activation, fibrinogen binding to platelets, vascular reactivity, coagulation and fibrinolytic factors and lipoprotein composition. The proposal will test the hypothesis that these variables predict the occurrence of graft occlusion and rate o development of graft atherosclerosis. The proposal also tests the hypothesis that hormone replacement therapy exerts its beneficial effects by its effects on those risk factors in addition to more traditional risk factors including the lipids and lipoprotein profile
Keywords: atherosclerosis, chemoprevention, coronary bypass, estrogen, female, hormone therapy, postmenopause, postoperative state blood lipoprotein, body composition, clinical trial, cooperative study, disease /disorder proneness /risk, heart disorder chemotherapy, hypertension, longitudinal human study, myocardial infarction, pathologic process, women`s health angiography, cardiovascular stress test, clinical research, heart catheterization, human subject, photon absorptiometry, statistics /biometry, ultrasonography
Project start date: 1996-08-15
Project end date: 2004-07-31
5U01HL050840-05 (2001): $370606
5U01HL050840-04 (2000): $361422
5U01HL050840-03 (1998): $305432
5U01HL050840-02 (1997): $487960
Sponsored Links Excellgen http://Excellgen.com
1U01HL050840-01A2 (1996): $475913
CLINICAL UNIT FOR THE ANGIOGRAPHIC TRIAL IN WOMEN
Pamela Ouyang, Professor Of Medicine
Johns Hopkins University W400 Wyman Park Building Baltimore, Md 212182680
Grant 1N01HV068170-00096 from Division Of Heart And Vascular Diseases
Project start date: 1996-08-30
Project end date: 2001-10-30