Cardiac Perfusion, Structure, and Function across the Primary Aldosteronism Spectrum
原发性醛固酮增多症谱系的心脏灌注、结构和功能
基本信息
- 批准号:10609914
- 负责人:
- 金额:$ 19.28万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-04-15 至 2027-03-31
- 项目状态:未结题
- 来源:
- 关键词:Adrenal GlandsAdultAdvisory CommitteesAldosteroneAmmoniaAtherosclerosis Risk in CommunitiesAwardBiologicalBiologyBiostatistical MethodsBlood PressureBlood VesselsBlood capillariesCardiacCardiac MyocytesCardiovascular DiseasesCardiovascular systemCharacteristicsChronicChronic Kidney FailureClinicalClinical ResearchClinical TrialsCoronary ArteriosclerosisCross-Sectional StudiesDataDedicationsDevelopmentDevelopment PlansDiabetes MellitusDisease OutcomeEEF2 geneEFRACEchocardiographyEndotheliumEpidemicEpidemiologic MethodsEpidemiologyEssential HypertensionExclusionExtracellular MatrixFibrosisFunctional ImagingFunctional disorderFundingGeneral PopulationGoalsHeartHeart DiseasesHeart failureHeterogeneityHigh PrevalenceHormonalHospitalizationHyperaldosteronismHypertensionImaging DeviceImaging TechniquesIndustryInflammationInterventionInvestigationIschemiaKidneyLeft Ventricular RemodelingMeasuresMediatingMedicineMentorsMicrovascular DysfunctionMineralocorticoid ReceptorMyocardialMyocardial perfusionNational Heart, Lung, and Blood InstituteObesityOutcomeOxidative StressParticipantPathogenesisPathogenicityPathologicPathway interactionsPatientsPerfusionPharmaceutical PreparationsPhenotypePhysiciansPositron-Emission TomographyPrecision therapeuticsPrevalencePreventionProductionReceptor ActivationRegistriesReninResearchRiskRisk FactorsRoleScientistSeveritiesSiteSmooth MuscleSmooth Muscle MyocytesSpironolactoneStructureSymptomsSyndromeTechniquesUnited States National Institutes of HealthVascular DiseasesVascular EndotheliumVascular blood supplyVentricular DysfunctionVentricular RemodelingWorkantagonistatherosclerosis riskcardiovascular disorder riskcardiovascular effectscardiovascular imagingcardiovascular risk factorcareercareer developmentclinical epidemiologyclinical translationcohortcomorbiditydesignendothelial dysfunctionepidemiology studyeplerenoneheart imagingimaging biomarkerimprovedimproved outcomeinsightlongitudinal analysismodifiable riskmortalitynovelpatient populationpatient responsepatient subsetspreservationprognosticskillstargeted treatmenttranslational scientisttreatment response
项目摘要
PROJECT SUMMARY/ABSTRACT
Heart failure with preserved ejection fraction (HFpEF) is a growing epidemic associated with multiple
comorbidities, including hypertension. In part because of its heterogeneity, clinical trials in HFpEF have been
largely disappointing to date, though the NHLBI-funded TOPCAT trial of spironolactone, a mineralocorticoid
receptor (MR) antagonist, had promising results. This has prompted several ongoing NIH and industry trials of
MR antagonists in HFpEF. However, the mechanisms through which MR antagonists may treat HFpEF remain
poorly understood. The MR is expressed in cardiomyocytes and vascular endothelial and smooth muscle cells.
Activation of the MR at these sites causes inflammation, oxidative stress, endothelial dysfunction, and fibrosis
– all pathways implicated in HFpEF. Primary aldosteronism (PA) is a cause of both hypertension and
disproportionate cardiovascular risk that is treated with MR antagonists, which target the underlying
pathophysiology: renin-independent production of aldosterone that chronically activates the MR. Though
considered rare, PA has recently been identified in up to 15-20% of apparently “essential” hypertension, with a
continuum of severity ranging from subclinical to overt, paralleling blood pressure and responsiveness to MR
antagonists: termed ‘subclinical PA.’ These data suggest an expanded role for MR antagonists as precision
therapy in the appropriate patients. Given its prevalence in hypertension, subclinical PA may be an
unrecognized mechanism of HFpEF pathogenesis and identify a patient subgroup best treated with MR
antagonists. The current proposal aims to evaluate the relationship between subclinical PA and HFpEF risk
and to probe the mechanism of risk using physiologic imaging techniques. Specific Aim 1 is to evaluate both
the cross-sectional relationship with cardiac structure and function and the longitudinal relationship between
subclinical PA and incident HFpEF in the NHLBI Atherosclerosis Risk in Communities (ARIC) cohort. Specific
Aim 2 leverages the mentors’ established Adrenal and Cardiac PET registries to investigate the relationship
between PA and myocardial flow reserve, a marker of vascular dysfunction and cardiovascular risk, by
evaluating the effect of an MR antagonist. This research will be accomplished within a comprehensive career
development plan designed to provide Dr. Brown with the skills to become an independent physician-scientist.
Her long-term career goal is be an independent, R01-funded physician-scientist focused on understanding the
underlying biological and hormonal mechanisms of heart failure risk, using physiologic imaging tools to identify
and characterize subclinical phenotypes that can be leveraged to enrich for responsive patient populations in
clinical trials, and ultimately to identify targets for heart failure prevention. An outstanding mentoring team and
advisory committee of established scientists in the fields of aldosterone and vascular biology, HFpEF, state-of-
the-art cardiovascular imaging, cardiovascular clinical trials, and epidemiological and biostatistical methods will
guide the candidate’s transition to scientific independence over the course of the award period.
项目总结/文摘
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Jenifer Michelle Brown其他文献
Jenifer Michelle Brown的其他文献
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{{ truncateString('Jenifer Michelle Brown', 18)}}的其他基金
Cardiac Perfusion, Structure, and Function across the Primary Aldosteronism Spectrum
原发性醛固酮增多症谱系的心脏灌注、结构和功能
- 批准号:
10448000 - 财政年份:2022
- 资助金额:
$ 19.28万 - 项目类别:
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