Clinical Studies

The LCBR research portfolio includes molecular and genetic Epidemiology family-based genetic research, clinical trials and basic studies using murine models of disease. Listed below are some of the many studies that we are involved with.

Status: Active
 Thrombosis Genetics in African Americans
Primary Investigator: Russell Tracy
Purpose: The primary objectives of this project is to measure several emerging thrombosis and inflammation plasma biomarkers that are likely to reflect and/or account for increased thrombogenicity and therefore may contribute to higher rates of CVD in African Americans, and to assess the association of thrombosis biomarkers and biomarker-associated genetic variants with more complex subclinical and clinical CVD endpoints available in JHS and other African American cohorts, including REGARDS.
Status: Active
 Thrombosis and Bleeding Risk Assessment in Medical Patients
Primary Investigator: Neil Zakai
Purpose: The proposed study would develop and validate robust models to assess hospital-acquired bleeding and VTE risk, and determine the period of increased risk for bleeding and VTE after discharge from the hospital.   
Status: Active
The Fragile Families Cardiovascular Health Follow Up Study
Primary Investigator: Russell Tracy
Purpose: This proposal aims to understand the role of early life adversity in the evolution of cardiovascular health and cardiovascular disease, and potential epigenetic mediation
Status: Active
 Role of Femoral Atherosclerosis in Functional Status, CVD Events and Mortality
Primary Investigator: Margaret Doyle
Purpose: This study examines the association of measures of femoral artery atherosclerosis and stiffness with functional status measures/claudications/ischemia, cardiovascular disease events and mortality using a Venous Incidence cohort.
Status: Active  
 Cardiovascular Health Effects of the Great Recession
Primary Investigator: Peter Durda
Purpose: The “Great Recession” of 2008-2009/10 represents a “natural experiment”, offering enhanced opportunities to assess causal links between socioeconomic status and health. This study will investigate the impact of the Great Recession on the health trajectories of Americans using information on biological indicators of health risks, extent of sub-clinical atherosclerotic disease, and key health behaviors collected in the Multi-Ethnic Study of Atherosclerosis (MESA).
Status: Active
Identification of the Role of HDL Function in Human Cardiovascular Disease through Proteomics and Genetics
Primary Investigator: Neil Zakai
Purpose: The aim of this proposal is to assess the genetic and structural association between HDL and cardiovascular disease and stroke using a nested case-cohort study of Reasons for Geographic And Racial Differences in Stroke (REGARDS).
Status: Active
 VCID and Stroke in a Biracial National Cohort
Primary Investigator: Mary Cushman
Purpose: This study extends follow-up for incident stroke and cognitive decline in a national cohort of 30,000 black and white community dwelling participants.  This proposal will identify mechanisms of racial and geographic disparities in dementia, and identify pathways and biomarkers for the development of hypertension and diabetes.
More Information: http://www.regardsstudy.org/
Status: Active
 Risk Underlying Rural Areas Longitudinal Cohort (RURAL) Study
Primary Investigator: Russell Tracy
Purpose: This proposal will characterize a multilevel exposome (measures of cumulative chronic adverse exposures: macrosocial factors, group-level characteristics, individual exposures and behaviors), and relate it to the HLBS continuum (RF, subclinical and clinical disease) to understand differences in risk and resilience in RURAL.
Status: Active

Impact of Early Antiretroviral Therapy on Kidney Disease Outcomes

Primary Investigator: Russ Tracy
Purpose: This study plans to to determine the long-term impact of immediate versus deferred antiretroviral therapy on clinically relevant markers of chronic kidney disease in HIV-positive persons with high CD4 followed for up to 5 years.
Status: Active
 Jackson Heart Study - Specimen Repository
Primary Investigator: Russell Tracy
Purpose: The major goal of this project is to maintain storage of approximately 95,000 previously collected JHS specimen vials, and to insure the availability of the stored biospeciments for assays.
Status: Active
 Epidemiology of Venous Thrombosis and Pulmonary Embolism
Primary Investigator: Mary Cushman
Purpose: A renewal of the Longitudinal Investigation of Thromboembolism Etiology (LITE), this study of venous thromboembolism (VTE) in the Atherosclerosis Risk in Communities (ARIC) Study and Cardiovascular Health Study (CHS) cohorts, comprises 21,680 participants followed for two decades.  LITE's overal objective is to idenify risk factors for deep venous thromboembolism (DVT) and pulmonary embolism (PE), in order to better understand the etiologyand possible prevention of VTE.

Status: Active
 Collaborative Cohort of Cohorts for COVID-19 Research (C4R)
Primary Investigator: Russell Tracy
Purpose: This study aims to interact with C4R committees to develop an in-home dried blood spot and/or saliva collection program and facilitate interactions with REGARDS leadership to facilitate approval of all protocols as well as review and harmonize COVID-19 questionnaires with other cohorts for use in REGARDS interviews.
Status: Active

Role of peripheral immune cells in cognitive aging: the Farmingham Offspring Study

Primary Investigator: Margaret Doyle
Purpose:  This study aims to profile circulating immune cell phenotypes in a community based sample of men and women across a wide age range and identify cross-sectional correlates of the immune cell phenotypes including age, sex, and cytomegalovirus (CMV) status
Status: Active
Vermont Center for Cardiovascular and Brain Health: Centers of Biomedical Research Excellence (COBRE)
Primary Investigator: Mary Cushman
Purpose: The purpose of this proposal is to create a center to conduct research to reduce death and disability from the #1 and #5 causes of death in the US, coronary heart disease and stroke
Status: Active
 Subclinical Vascular Contributions to Alzheimer’s Disease: MESA
Primary Investigator: Nels Olson
Purpose: The purpose of this proposal is to investigate molecular and mechanical pathways linking vascular disease to Alzheimer’s Disease pathology
Status: Active
The National Longitudinal Study of Adolescent Health Wave VI  
Primary Investigator: Mary Cushman
Purpose:  This study aims to coordinate and conduct collection of biological samples in ~7500 participants of the National Longitudinal Study of Adolescent Health Wave VI exam and measure metabolic, renal, hepatic, inflammation, and infectious disease biomarkers previously assayed at Wave V.
Status: Active  

 Microglial, Inflammatory and Omics Markers of Cerebral Small Vessel Disease in CHARGE Consortium

Primary Investigator: Russell Tracy
Purpose: This project aims to measure markers of microglial inflammation and astroglial injury in persons across 5 CHARGE cohorts and relate this to data on brain MRI, white matter hyper-intensities, lacunar brain infarcts and cerebral microbleeds, and assess the utility of these measures as biomarkers of cognitive impairment and as biomarkers of future stroke and dementia risk.
Status: Active  
 Molecular Transducers of Physical Activity Consortium Coordinator Center
Primary Investigator: Russell Tracy
Purpose: The goal of this proposal is to provide support for the organization, administration, planning, standardization, documentation, monitoring and reporting activities relating to the Molecular Transducers of Physical Activity Consortium (MoTrPAC).
Satus: Active  

ACTIV-IV Anticoagulation Trial Scientific Organization

Primary Investigator: Russ Tracy
Purpose:  The purpose of this proposal is to perform randomized controlled clinical trials (RCTs) on anticoagulation in the setting of COVID-19, including the nature of the intervention, dosage, frequency, etc. for pre-hospital, hospitalized and post-hospital COVID-19 patients
Status: Active  
 Contemporary Venous Thrombolism Treatment
Primary Investigator: Neil Zakai
Purpose: This grant uses data from two large U.S. commercial claims databases to see whether real-life outcomes differ between traditional treatment of VTE and novel treatments and if bleeding and recurrent thrombosis differ.

Completed

Status: Completed
Etiology of Geographic and Racial Differences in Stroke Mortality (REGARDS)
Primary Investigator: Mary Cushman
Purpose: Analytes related to stroke risk in a 30,000-person national observational study are measured to assess reasons for geographic and racial differences in stroke risk. All participant evaluations will take place in participants' homes.
More Information: http://www.regardsstudy.org/
Status: Completed
 National Longitudinal Study of Adolescent Health – Wave V
Primary Investigator: Mary Cushman
Purpose: We will assemble and store a biorepository related to the Wave V examination of the National Longitudinal Study of Adolescent Health and measure biomarkers of health status in order to facilitate studies of early life precursors of chronic disease 
Status: Completed
 Targeting Hypercoagulation to Reduce Inflammation in Treated HIV Disease
Primary Investigator: Russell Tracy
Purpose: The goal of this proposal is to investigate the role of hypercoagulation in the pathogenesis of long-term non-AIDS defining complications among contemporary patients with treated HIV diseas
Status: Completed
 Enabling Reduction of Low-grade Inflammation in Seniors
Primary Investigator: Russell Tracy
Purpose: This study tests anti-inflammatory interventions for improving walking speed or preventing its decline to determine if reduction of inflammatory markers improves mobility in older persons.
Status: Completed
 Genomics and Pharmacodynamics of Statin-Related Rhabdomyolysis
Primary Investigator: Russell Tracy
Purpose: The purpose of this proposal is to follow up on potential functional variants (PFVs) which have been identified as the rate-limited step in translating genomic data into viable diagnostic, therapeutic, and ultimately modifiable targets.
Status: Completed
Exceptional Survival Trajectories to Function
Primary Investigator: Mary Cushman
Purpose: This study will determine the likelihood of maintaining function, identify the trajectories that distinguish those destined to do well, and define the importance, independence and interactions of physiologic predictors of functional aging in CHS participants over 80 years of age.
Status: Completed
Immune Function and the Risk of Cardiovascular Disease among HIV+ and Uninfected Veterans
Primary Investigator: Russell Tracy
Purpose: This proposal aims to study whether the activation, number, and proportion of innate and adaptive immune cell subsets, the depletion of anti-atherosclerotic adaptive immune cell subsets, and immunosenescence will all be associated with CVD events and contribute to the excess risk of CVD among HIV+ people.
Status: Completed
Impact of Disordered Mineral Metabolism on Stroke and Cognitive Impairment
Primary Investigator: Nancy Jenny
Purpose: An ancillary study utilizing the REGARDS (Reasons for Geographic and Racial Difference in Stroke) cohort, the goals of this study are to measure a variety of biomarkers of mineral metabolism and to determine their associations with stroke and cognitive impairment in U.S. whites and blacks.
Status: Completed
Ginko Evaluation of Memory Study
Primary Investigator: Russell Tracy
Purpose: The goal of this project is to enroll and follow 2000 participants in randomized trial of 240 mg of gingko biloba as compared to placebo in men and women, median age of 80.
Status: Completed
Multi Ethnic Study of Atherosclerosis (MESA)
Primary Investigator: Russell Tracy
Purpose: The major goal of this project is to provide laboratory-support for non-standard tests in areas such as hemostasis, lipoprotein metabolism, inflammation, genetic markers in a multi center, longitudinal epidemiological study of the incidence and progression of subclinical CVD.
More Information: http://www.mesa-nhlbi.org/
Status: Completed
Cardiovascular Health Study
Primary Investigator: Russell Tracy
Purpose: The major goal of this project is to determine cardiovascular disease risk factors in a longitudinal study of the elderly. The Vermont component is to perform all blood tests on the cohort (n=5000). Ongoing from 1988 thru 2015
Status: Completed
Regional and Racial Differences in Hemostasis and Risk of Stroke and Heart Disease
Primary Investigator: Neil Zakai
Purpose: An investigation into the regional and racial difference in stroke incidence as mediated by differences in coagulation proteins.
Status: Completed
Immune Activation and Immunosenescence Biomarkers and Cardiovascular Disease Risk
Primary Investigator: Nels Olson
Purpose: The primary goal of this research is to prospectively evaluate immune cell subpopulations and biomarkers of immune activation as emerging risk factors for future cardiovascular events.
Status: Completed
 Vitamin D to Prevent Type 2 Diabetes (D2d)
Primary Investigator: Michael Lewis
Purpose: This is a Multicenter, randomized (1:1), double-masked, placebo-controlled, primary prevention parallel-group clinical trial with 2 arms (oral daily vitamin D vs. placebo) in participants at high risk for diabetes (with pre-diabetes) who will be followed for an average of 3 years after randomization for incident diabetes. The aim is to assess whether, in participants with pre-diabetes, oral daily vitamin D3 supplementation reduces the rate of progression from pre-diabetes to clinical diabetes.
Status: Completed
Phenotypes of Aging and Senescence
Primary Investigator: Russell Tracy
Purpose: The primary objective of this project is to develop a panel of circulating protein and miRNA markers specific to cell senescence, and to validate their associations with the risk of aging-related diseases, healthy survival, and exceptional longevity.


Status: Completed

 Transition for Risk Factors to Heart Failure: Prevalence, Pathogenesis, and Phenomics

Primary Investigator: Margaret Doyle
Purpose: This project aims to determine the prevalence of early heart failure; elucidate the pathogenesis of early heart failure and to delineate the key antecedent risk factor combinations associated with the transition from Stage B to Stage C heart failure among 3,500 older adults attending the year-15 examination of MESA.
Status: Completed
 Comprehensive Evaluation of Aging-Related Clinical Outcomes and Geroproteins
Primary Investigator: Russell Tracy
Purpose: The primary objectives of this project is to determine whether higher levels of specific proteins are associated with specific clinical outcomes and whether associations between these proteins and physiologic measures vary across the lifespan.
Status: Completed
 Transitions to Family Caregiving and the Impact on Caregivers' Health
Primary Investigator: Mary Cushman
Purpose: The general aim of this project is to examine the health effects of family caregiving across a range of self-report, health care utilization and biomarkers of disease and disease risk.
Status: Completed
Tissue Sodium, Inflammation and Blood Pressure in MESA
Primary Investigator: Margaret Doyle
Purpose: This project examines the association of tissue Na+ with blood pressure and circulating cellular markers of inflammation in MESA participants.
Status: Completed
 CHS Biorepository Support Services
Primary Investigator: Russell Tracy
Purpose: To maintain storage of the CHS biorepository and to insure the availability of the stored biospecimens for assays.
 
Status: Completed
 Impact of Early Antiretroviral Therapy on Kidney Disease Outcomes
PrimaryInvestigator: Russell Tracy
Purpose: This proposal aims to determine the long-term impact of immediate versus deferred antiretroviral therapy on clinically relevant markers of chronic kidney disease in HIV-positive persons with high CD4 followed for up to 5 years.
 

Research Spotlight

REGARDS Executive Steering Committee

The RURAL Cohort Study aims to address critical gaps in our knowledge of heart and lung disorders in rural counties in the southeastern US. With our mobile research vehicle, we will travel to rural counties to research their health. We hope that our research findings will promote the health of rural communities.