5 results on '"Preston, Gregory M"'
Search Results
2. Prediction of cardiovascular events in statin-treated stable coronary patients of the treating to new targets randomized controlled trial by lipid and non-lipid biomarkers
- Author
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Arsenault, Benoit J, Barter, Philip, DeMicco, David A, Bao, Weihang, Preston, Gregory M, LaRosa, John C, Grundy, Scott M, Deedwania, Prakash, Greten, Heiner, Wenger, Nanette K, Shepherd, James, Waters, David D, Kastelein, John JP, Treating to New Targets (TNT) Investigators, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, and Berger, Jeffrey S
- Subjects
Male ,Time Factors ,Physiology ,Epidemiology ,Atorvastatin ,lcsh:Medicine ,Coronary Disease ,Coronary Artery Disease ,Cardiovascular Physiology ,Pathology and Laboratory Medicine ,Cardiovascular ,Biochemistry ,Vascular Medicine ,Gastroenterology ,chemistry.chemical_compound ,Medicine and Health Sciences ,Molecular Targeted Therapy ,Myocardial infarction ,lcsh:Science ,Immune Response ,education.field_of_study ,Multidisciplinary ,Neopterin ,Middle Aged ,Prognosis ,Lipids ,Heart Disease ,Research Design ,6.1 Pharmaceuticals ,Blood Circulation ,Female ,lipids (amino acids, peptides, and proteins) ,Anatomy ,Research Article ,medicine.drug ,medicine.medical_specialty ,Drug Research and Development ,Statin ,Clinical Research Design ,General Science & Technology ,medicine.drug_class ,Immunology ,Clinical Trials and Supportive Activities ,Population ,Cardiology ,Research and Analysis Methods ,Treating to New Targets (TNT) Investigators ,Diagnostic Medicine ,Clinical Research ,Diabetes mellitus ,Internal medicine ,medicine ,Humans ,cardiovascular diseases ,education ,Cardiovascular Disease Epidemiology ,Heart Disease - Coronary Heart Disease ,Inflammation ,Pharmacology ,Adiponectin ,Cholesterol ,business.industry ,Pharmacoepidemiology ,Prevention ,lcsh:R ,Immunity ,Biology and Life Sciences ,Evaluation of treatments and therapeutic interventions ,Atherosclerosis ,medicine.disease ,Biomarker Epidemiology ,Endocrinology ,chemistry ,Cardiovascular Anatomy ,Clinical Immunology ,lcsh:Q ,Clinical Medicine ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,business ,Biomarkers - Abstract
Several plasma non-lipid biomarkers have been shown to predict major cardiovascular events (MCVEs) in population studies. Our objective was to investigate the relationship between lipid and non-lipid biomarkers levels achieved during statin therapy and the incidence of MCVEs in patients with stable coronary heart disease (CHD). We conducted a substudy of the TNT (Treating to New Targets) study, which was a randomized trial that compared the efficacy of high (80 mg) versus low (10 mg) dose atorvastatin for the secondary prevention of CHD. Fasting plasma levels of standard lipids and of 18 non-lipid biomarkers were obtained after an 8-week run-in period on atorvastatin 10 mg in 157 patients who experienced MCVEs during the 4.9 years of study follow-up and in 1349 controls. MCVE was defined as CHD death, nonfatal, non-procedure-related myocardial infarction, resuscitated cardiac arrest, and fatal or nonfatal stroke. After adjusting for age, sex and treatment arm, plasma levels of high-density lipoprotein (HDL) cholesterol, triglycerides, high-sensitivity C-reactive protein (hsCRP), insulin, neopterin, N-terminal pro-brain natriuretic peptide (BNP), lipoprotein(a) [Lp(a)], and the soluble receptor for advanced glycation end products (sRAGE) were predictive - 2014 Arsenault et al. This Funding: This study was funded by Pfizer Inc. Benoit J. Arsenault is supported by a post-doctoral fellowship from the Fonds de la recherche en santé du Québec and the Fondation de l9Institut universitaire de cardiologie et de pneumologie de Québec. Two authors are Pfizer employees and may hold stock in the company. As sponsor, Pfizer in cooperation with the steering committee had a role in all aspects of the study. The secondary biomarker analysis was funded by Pfizer. However, the decision to publish and preparation of the manuscript was driven solely by the authors. of recurrent MCVEs (P#0.02 for each doubling of plasma concentration). However, no significant association was observed between the risk of recurrent MCVEs and plasma levels of low-density lipoprotein cholesterol, adiponectin, cystatin C, lipoprotein-associated phospholipase A2, monocyte chemotactic protein-1, matrix metalloproteinase-9, myeloperoxidase, osteopontin, soluble CD40 ligand, soluble intercellular adhesion molecule-1, or soluble vascular cell adhesion molecule-1. After further adjustment for diabetes, hypertension, smoking, and BMI, the relationship between hsCRP, insulin and MCVE were no longer significant, while the relationship between Lp(a), neopterin, NT-proBNP and sRAGE and MCVE remained statistically significant. In conclusion, in patients with CHD treated with atorvastatin, plasma levels of Lp(a), neopterin, NT-proBNP, and sRAGE are associated with the risk of recurrent MCVEs.
- Published
- 2014
3. Prediction of Cardiovascular Events in Statin-Treated Stable Coronary Patients of the Treating to New Targets Randomized Controlled Trial by Lipid and Non-Lipid Biomarkers.
- Author
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Arsenault, Benoit J., Barter, Philip, DeMicco, David A., Bao, Weihang, Preston, Gregory M., LaRosa, John C., Grundy, Scott M., Deedwania, Prakash, Greten, Heiner, Wenger, Nanette K., Shepherd, James, Waters, David D., Kastelein, John J. P., and null, null
- Subjects
CARDIOVASCULAR agents ,CORONARY disease ,STATINS (Cardiovascular agents) ,RANDOMIZED controlled trials ,LIPIDS ,BIOMARKERS ,PATIENTS - Abstract
: Several plasma non-lipid biomarkers have been shown to predict major cardiovascular events (MCVEs) in population studies. Our objective was to investigate the relationship between lipid and non-lipid biomarkers levels achieved during statin therapy and the incidence of MCVEs in patients with stable coronary heart disease (CHD). We conducted a substudy of the TNT (Treating to New Targets) study, which was a randomized trial that compared the efficacy of high (80 mg) versus low (10 mg) dose atorvastatin for the secondary prevention of CHD. Fasting plasma levels of standard lipids and of 18 non-lipid biomarkers were obtained after an 8-week run-in period on atorvastatin 10 mg in 157 patients who experienced MCVEs during the 4.9 years of study follow-up and in 1349 controls. MCVE was defined as CHD death, nonfatal, non-procedure-related myocardial infarction, resuscitated cardiac arrest, and fatal or nonfatal stroke. After adjusting for age, sex and treatment arm, plasma levels of high-density lipoprotein (HDL) cholesterol, triglycerides, high-sensitivity C-reactive protein (hsCRP), insulin, neopterin, N-terminal pro-brain natriuretic peptide (BNP), lipoprotein(a) [Lp(a)], and the soluble receptor for advanced glycation end products (sRAGE) were predictive of recurrent MCVEs (P≤0.02 for each doubling of plasma concentration). However, no significant association was observed between the risk of recurrent MCVEs and plasma levels of low-density lipoprotein cholesterol, adiponectin, cystatin C, lipoprotein-associated phospholipase A2, monocyte chemotactic protein-1, matrix metalloproteinase-9, myeloperoxidase, osteopontin, soluble CD40 ligand, soluble intercellular adhesion molecule-1, or soluble vascular cell adhesion molecule-1. After further adjustment for diabetes, hypertension, smoking, and BMI, the relationship between hsCRP, insulin and MCVE were no longer significant, while the relationship between Lp(a), neopterin, NT-proBNP and sRAGE and MCVE remained statistically significant. In conclusion, in patients with CHD treated with atorvastatin, plasma levels of Lp(a), neopterin, NT-proBNP, and sRAGE are associated with the risk of recurrent MCVEs. Trial Registration: ClinicalTrials.gov . [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
4. Pharmacokinetics, Pharmacodynamics, Tolerability, and Safety of a Novel Sorbitol Dehydrogenase Inhibitor in Healthy Participants.
- Author
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Landau, Zohar, Novotny, Mark J., Preston, Gregory M., Wright, Kathryn, Freeman, Thomas, Dai, Haiqing, Thompson, John, Oates, Peter J., and Calle, Roberto A.
- Subjects
SORBITOL ,PHARMACOKINETICS ,MICROCIRCULATION disorders ,DIABETES complications ,PHARMACODYNAMICS ,OXIDATIVE stress ,PHYSIOLOGY ,DISEASE risk factors - Abstract
Increased glucose flux through the polyol pathway and the resultant oxidative stress is thought to be a major mechanistic contributor to microvascular diabetic complications. Inhibition of flux through this pathway can be blocked through inhibition of either of 2 enzymes, aldose reductase (AR) or sorbitol dehydrogenase (SDH). This report describes the pharmacokinetics, biomarker pharmacodynamics, and safety of CP-642,931, a potent and specific sorbitol dehydrogenase inhibitor (SDI). CP-642,931 was administered for 7 days to 57 healthy volunteers in doses ranging from 1 to 35 mg daily. After the 35-mg dose, CP-642,931 showed a t
½ of 20.1 hours and tmax at 0.5 to 1.25 hours. After a 35-mg dose, maximum inhibition of SDH was 91% (on days 1 and 7), and maximum serum sorbitol increase was 152-fold on day 7 compared to control. Five participants discontinued the study due to adverse events, including myalgia, muscle spasm, and muscle fatigue. All symptoms resolved in all but 1 participant, who continued to report intermittent muscle fasciculations upon follow-up. In conclusion, CP-642,931 is a potent and specific SDI that is rapidly absorbed through the oral route and effectively inhibits SDH. However, the drug is not well tolerated due to adverse neuromuscular effects. [ABSTRACT FROM AUTHOR]- Published
- 2010
- Full Text
- View/download PDF
5. Aquaporin CHIP: The archetypal molecular water channel.
- Author
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Agre, Peter and Preston, Gregory M.
- Subjects
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MEMBRANE proteins , *PHYSIOLOGY - Abstract
Characterizes CHIP, a channel-forming integral membrane protein from human red blood cells. Function of an osmotically driven, water-selective pore; Search for molecular identity of a water channel; CHIP's homology with the major intrinsic protein of mammalian lens, MIP26; Structure of water pathway; Distribution and expression.
- Published
- 1993
- Full Text
- View/download PDF
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