Project Summary/Abstract
Coronary heart disease (CHD) remains among the leading causes of deaths in the U.S. While a sedentary
lifestyle, unhealthful diets, smoking behaviors, and genetic predispositions are established risk factors of CHD,
emerging evidence suggests that environmental pollutants, such as per- and polyfluoroalkyl substances
(PFAS), may also contribute to the CHD etiology. Potential connections between PFAS exposures and
dyslipidemia have been extensively examined in epidemiological studies, although significant heterogeneity
among studies was observed. More recent evidence suggests that PFAS may particularly interfere with the
metabolism of pro-atherogenic lipoprotein subspecies that carry apolipoprotein CIII and other apolipoproteins,
which are significantly associated with CHD risk in multiple prospective studies. This new evidence points to a
new pathway through which PFAS may influence CHD risk. Data are still sparse regarding the inter-
relationships among PFAS, lipoprotein subspecies, and incident CHD risk in the U.S. population who are
ubiquitously exposed to PFAS. The proposed research aims to address these important knowledge gaps by
conducting cross-sectional and longitudinal investigations to substantiate the associations of PFAS with
lipoprotein subspecies and CHD risk in four well-characterized U.S. cohort studies consisting of ethnically-
diverse participants: the Health Professionals Follow-up Study, Nurses’ Health Study (NHS), NHSII, and
Hispanic Community Health Study / Study of Latinos (SOL). The rich, existing resources and data allow the
investigators to cost-effectively examine these study aims: 1) to examine various PFAS in relation to lipoprotein
subspecies in blood samples repeatedly collected during the past three decades; 2) to evaluate longitudinally
the changes of PFAS in relation to the contemporaneous changes of lipoprotein subspecies in repeat blood
samples collected ~10 years apart in the NHS/NHSII and SOL cohorts; and 3) to investigate prospective
associations between PFAS and CHD risk and to explore the role of the lipoprotein subspecies in these
associations of interest. Besides filling the knowledge gaps, the innovation of the proposed research also lies
in the coverage of some newly emerged PFAS that can only be meaningfully measured in blood samples
collected recently, the examination of longitudinal relationships between PFAS and lipoprotein subspecies, and
the inclusion of Hispanic participants from the SOL cohort. A highly experienced investigator team consisting of
environmental and cardiovascular disease epidemiologists, lipoprotein and PFAS research experts, and
biostatisticians has been assembled to achieve the study goals in a timely fashion with great qualities. Data
from this proposed research will shed light on the role of PFAS exposures in modulating lipoprotein subspecies
and CHD risk in U.S. populations. Such evidence may also aid in policy-making processes for making more
evidence-based regulations toward the production and use of PFAS in the U.S.
Public Health Relevance Statement
Project Narrative/Relevance
Per- and polyfluoroalkyl substances (PFAS) may predispose human beings to an elevated risk of developing
coronary heart disease (CHD) through modulating blood lipoprotein subspecies that are particularly relevant to
CHD etiology, although epidemiological studies that examine inter-relationships among PFAS, blood
lipoprotein subspecies, and CHD risk are limited. The proposed research aims to narrow significant knowledge
gaps by evaluating prospective associations of PFAS exposures with lipoprotein subspecies and CHD
incidence in well-characterized cohort studies of free-living individuals. Data from this research will shed light
on potential effects of PFAS on cardiovascular health and may inform policy-making processes for regulating
the production and use of PFAS in the U.S.
NIH Spending Category
No NIH Spending Category available.
Project Terms
AddressApolipoprotein EApolipoproteinsBloodBlood specimenCardiovascular DiseasesCause of DeathChemicalsCohort StudiesCollectionCoronary heart diseaseDataDeteriorationDietDyslipidemiasEnvironmental PollutantsEpidemiologistEthnic OriginEtiologyExposure toFollow-Up StudiesGenetic Predisposition to DiseaseGoalsHealth ProfessionalHeterogeneityHigh Density LipoproteinsHispanicHispanic Community Health Study/Study of LatinosHispanic PopulationsHumanIncidenceIndividualInvestigationKnowledgeLDL Cholesterol LipoproteinsLinkLipidsLipoproteinsMeasuresMediatingMeta-AnalysisMetabolismMinorityNurses' Health StudyOverweightParticipantPathway interactionsPilot ProjectsPolicy MakingPoly-fluoroalkyl substancesPopulationProcessProductionProspective StudiesRaceRegulationResearchResearch DesignResearch PersonnelResourcesRiskRisk FactorsRoleSmoking BehaviorTimeanthropogenesisapolipoprotein C-IIIblood lipidblood lipoproteincardiometabolismcardiovascular healthcase controlcigarette smokingcohortcostdietaryepidemiology studyethnic diversityevidence baseexcessive weight gainexperienceheart disease riskhigh riskimprovedinnovationinterestlipoprotein cholesterolmodifiable risknovelparticleperfluorooctane sulfonateperfluorooctanoic acidpreventprospectivesedentary lifestylestudy population
National Institute of Environmental Health Sciences
CFDA Code
113
DUNS Number
030811269
UEI
QN6MS4VN7BD1
Project Start Date
16-April-2024
Project End Date
31-January-2029
Budget Start Date
16-April-2024
Budget End Date
31-January-2025
Project Funding Information for 2024
Total Funding
$765,745
Direct Costs
$537,576
Indirect Costs
$228,169
Year
Funding IC
FY Total Cost by IC
2024
National Institute of Environmental Health Sciences
$765,745
Year
Funding IC
FY Total Cost by IC
Sub Projects
No Sub Projects information available for 1R01ES036206-01
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