ABSTRACT
Cardiovascular disease (CVD) is the leading cause of death in women in the US and globally. Menopausal
transition poses remarkably elevated risk of CVD making postmenopausal women a population of special
attention. There is an increasing concern about the exposure to environmental chemicals, particularly persistent
organic pollutants (POPs), that disrupt human endocrine milieu and adversely affect cardiovascular health. The
bioaccumulation of POPs over lifetime induces significant long-term health impact, especially among older
population. However, the long-term effect of POPs on subclinical atherosclerosis progression, an early
pathological feature of CVD, has not been studied well in postmenopausal women. In addition, the effect of POPs
on atherosclerosis progression has not been evaluated in the US population. To our knowledge, no longitudinal
study has been conducted to investigate the effects of POP mixtures and atherosclerosis progression. The only
longitudinal study reporting an adverse effect of a specific class of POPs, per- and polyfluoroalkyl substances
(PFASs), on increased carotid intima-media thickness (IMT, ultrasound) over 10 years was from a Swedish
senior cohort. To fill the gaps in our understanding, we will investigate the long-term associations of plasma
POPs concentrations and atherosclerosis progression in postmenopausal women in a unique cohort; Early vs
Late Intervention Trial with Estradiol (ELITE) with 5-year longitudinal measurements of subclinical carotid
atherosclerosis including gold-standard ultrasound measures (IMT, echogenicity, and stiffness) and frozen
plasma samples to analyze absolute concentrations of 60 POPs from four main classes (polychlorinated
biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), organochlorinated pesticides (OCPs), and
(PFASs). ELITE is a randomized clinical trial including 596 early (<6years since menopause) and late (≥10years
since menopause) postmenopausal women comparing rates of atherosclerosis progression over 5 years
between women randomized to hormone therapy (HT) and placebo. Beyond the goal of investigating the effect
of POP mixtures on atherosclerosis progression, we will investigate the impact of POP mixtures on risk factors
of atherosclerosis including metabolic (lipids, glucose, HbA1c, and insulin resistance) and inflammatory
biomarkers. Important covariates including the design factors (HT and placebo, early and late-postmenopausal
groups), obesity, smoking, diet, and physical activity will be adjusted for in the analysis. To assess the
generalizability of the adverse effect of POP exposure across various subgroups of postmenopausal women, we
will evaluate POPs’ associations with atherosclerosis progression in subgroups of women randomized to HT and
placebo, as well as early and late postmenopausal groups. This study will provide important evidence on long-
term effect of POP mixtures on atherosclerosis progression and related metabolic and inflammatory
pathophysiology among postmenopausal women who are at high risk of CVD. Findings from this study will help
identify key individual and subgroups of POPs as targets for regulations, remediations, and CVD prevention.