Per- and polyfluoroalkyl substances, apolipoproteins, and risk of coronary heart disease

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.