0000000000482126

AUTHOR

John E. Deanfield

showing 5 related works from this author

Separating the Mechanism-Based and Off-Target Actions of Cholesteryl Ester Transfer Protein Inhibitors With CETP Gene Polymorphisms

2010

Background— Cholesteryl ester transfer protein (CETP) inhibitors raise high-density lipoprotein (HDL) cholesterol, but torcetrapib, the first-in-class inhibitor tested in a large outcome trial, caused an unexpected blood pressure elevation and increased cardiovascular events. Whether the hypertensive effect resulted from CETP inhibition or an off-target action of torcetrapib has been debated. We hypothesized that common single-nucleotide polymorphisms in the CETP gene could help distinguish mechanism-based from off-target actions of CETP inhibitors to inform on the validity of CETP as a therapeutic target. Methods and Results— We compared the effect of CETP single-nucleotide polymorphisms …

high-density lipoproteinsEpidemiologyBLOOD-PRESSUREPharmacologyDISEASEchemistry.chemical_compoundDOUBLE-BLINDHigh-density lipoprotein:CIENCIAS MÉDICAS ::Medicina interna [UNESCO]Polymorphism (computer science)Physiology (medical)Cholesterylester transfer proteinGeneticsMedicinegeneticsHigh-density lipoproteinsGENOME-WIDE ASSOCIATIONUNESCO::CIENCIAS MÉDICAS ::Medicina internaPharmacologyHDL CHOLESTEROLbiologybusiness.industryCholesterolTorcetrapib:CIENCIAS MÉDICAS [UNESCO]Genetics ; Pharmacology ; Epidemiology ; High-density lipoproteinsDose–response relationshipBlood pressurechemistryATHEROSCLEROSISUNESCO::CIENCIAS MÉDICASbiology.proteinMENDELIAN RANDOMIZATIONepidemiology; genetics; high-density lipoproteins; pharmacologylipids (amino acids peptides and proteins)epidemiologyTORCETRAPIBpharmacologyCardiology and Cardiovascular MedicinebusinessHIGH-DENSITY-LIPOPROTEINLIPID-LEVELSLipoproteinCirculation
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Effects of tobacco cigarettes, e-cigarettes, and waterpipe smoking on endothelial function and clinical outcomes

2020

Abstract Tobacco smoking is a leading cause of non-communicable disease globally and is a major risk factor for cardiovascular disease (CVD) and lung disease. Importantly, recent data by the World Health Organizations (WHO) indicate that in the last two decades global tobacco use has significantly dropped, which was largely driven by decreased numbers of female smokers. Despite such advances, the use of e-cigarettes and waterpipes (shisha, hookah, narghile) is an emerging trend, especially among younger generations. There is growing body of evidence that e-cigarettes are not a harm-free alternative to tobacco cigarettes and there is considerable debate as to whether e-cigarettes are saving …

Clinical ReviewCoronavirus disease 2019 (COVID-19)media_common.quotation_subjectWater Pipe SmokingDisease030204 cardiovascular system & hematologyElectronic Nicotine Delivery Systems03 medical and health sciences0302 clinical medicineEnvironmental healthMedicineHumans030212 general & internal medicineRisk factorAdverse effectSubclinical infectionmedia_commonInflammationbusiness.industryAddictionEndothelial functionEpigenomeE-cigarette vapingTobacco ProductsTobacco smokingOxidative stressCardiovascular DiseasesBiomarker (medicine)Shisha/waterpipe smokingEndothelium VascularbusinessCardiology and Cardiovascular MedicineEuropean Heart Journal
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Effects of gaseous and solid constituents of air pollution on endothelial function

2018

Abstract Ambient air pollution is a leading cause of non-communicable disease globally. The largest proportion of deaths and morbidity due to air pollution is now known to be due to cardiovascular disorders. Several particulate and gaseous air pollutants can trigger acute events (e.g. myocardial infarction, stroke, heart failure). While the mechanisms by which air pollutants cause cardiovascular events is undergoing continual refinement, the preponderant evidence support rapid effects of a diversity of pollutants including all particulate pollutants (e.g. course, fine, ultrafine particles) and gaseous pollutants such as ozone, on vascular function. Indeed alterations in endothelial function…

0301 basic medicineClinical ReviewFine particulateAir pollutionAir pollution030204 cardiovascular system & hematologymedicine.disease_cause03 medical and health sciencesGreenhouse Gases0302 clinical medicineOzoneRisk FactorsEnvironmental healthMedicineAnimalsHumansEndothelial dysfunctionNitrogen dioxidePollutantInflammationAir PollutantsHuman studiesAmbient air pollutionbusiness.industryEnvironmental ExposureParticulates3. Good healthEditor's Choice030104 developmental biology13. Climate actionCardiovascular DiseasesOxidative stressEndothelium VascularCurrent (fluid)Cardiology and Cardiovascular MedicinebusinessVascular functionParticulate matterTranslational MedicineEuropean Heart Journal
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Rationale and design of dal-VESSEL: a study to assess the safety and efficacy of dalcetrapib on endothelial function using brachial artery flow-media…

2011

Dalcetrapib increases high-density lipoprotein cholesterol (HDL-C) levels through effects on cholesteryl ester transfer protein (CETP). As part of the dalcetrapib dal-HEART clinical trial programme, the efficacy and safety of dalcetrapib is assessed in coronary heart disease (CHD) patients in the dal-VESSEL study (ClinicalTrials.gov identifier: NCT00655538), the design and methods of which are presented here. RESEARCH DESIGN AND STUDY METHOD: Men and women with CHD or CHD risk equivalent, with HDL-C levels50  mg/dL were recruited for a 36-week, double-blinded, placebo-controlled trial. After a pre-randomisation phase of up to 8 weeks, patients received dalcetrapib 600  mg/day or placebo in …

AdultMalemedicine.medical_specialtyAdolescentBrachial ArteryDalcetrapibCoronary DiseaseAtherosclerosis CETP inhibition Endothelial function Flow-mediated dilatation ester transfer protein density-lipoprotein cholesterol off-target toxicity cardiovascular-disease dependent vasodilation coronary risk nitric-oxide torcetrapib atherosclerosis cetpModels BiologicalPlaceboschemistry.chemical_compoundYoung AdultDouble-Blind Methodmedicine.arteryInternal medicineCholesterylester transfer proteinmedicineHumansSulfhydryl CompoundsBrachial arteryLipoprotein cholesterolFlow mediated vasodilatationAgedRationalizationbiologybusiness.industryAnticholesteremic AgentsEstersGeneral MedicineCetp inhibitionMiddle AgedAmidesCoronary heart diseaseClinical trialVasodilationTreatment OutcomechemistryRegional Blood FlowResearch DesignCardiologybiology.proteinlipids (amino acids peptides and proteins)FemaleEndothelium VascularbusinessAlgorithms
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High Intestinal Cholesterol Absorption Is Associated With Cardiovascular Disease and Risk Alleles in ABCG8 and ABO

2013

Objectives This study sought to determine whether high intestinal cholesterol absorption represents a cardiovascular risk factor and to link ABCG8 and ABO variants to cardiovascular disease (CVD). Background Plant sterol–enriched functional foods are widely used for cholesterol lowering. Their regular intake yields a 2-fold increase in circulating plant sterol levels that equally represent markers of cholesterol absorption. Variants in ABCG8 and ABO have been associated with circulating plant sterol levels and CVD, thereby suggesting atherogenic effects of plant sterols or of cholesterol uptake. Methods The cholestanol-to-cholesterol ratio (CR) was used as an estimate of cholesterol absorpt…

medicine.medical_specialtySingle-nucleotide polymorphism030204 cardiovascular system & hematologyHigh cholesterolIntestinal absorption03 medical and health scienceschemistry.chemical_compound0302 clinical medicineEzetimibeInternal medicineABO blood group systemmedicineRisk factor030304 developmental biology2. Zero hunger0303 health sciencesCholesterolbusiness.industrymedicine.diseaseEndocrinologychemistryIntestinal cholesterol absorptionlipids (amino acids peptides and proteins)businessCardiology and Cardiovascular Medicinemedicine.drugJournal of the American College of Cardiology
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