Project Summary
Cardiovascular disease (CVD) accounts for the largest proportion of mortality and morbidity worldwide. While a
strong body of evidence supports a role for long-term air pollution exposure in CVD among adults, relatively
little is known about how air pollution exposures may affect the development of subclinical atherogenesis in
younger populations. Early markers of these pathogenic processes, including carotid artery intima-media
thickness (CIMT), arterial stiffening (CAS), and arterial wall composition as measured by echogenicity, may
provide insight into different facets of the beginnings of disease. The lack of longitudinal studies with repeated
characterization of measures of subclinical atherosclerosis in younger populations is a major gap in the field
and it is unclear whether early life exposures to air pollutants may impact the progression of carotid
atherosclerosis from childhood into adulthood. We hypothesize that ambient and traffic-related air pollutant
exposures may influence the development of adverse subclinical cardiovascular phenotypes, indicated by
carotid atherosclerosis progression, as children grow into early adulthood. We will test this hypothesis within
the Southern California Children's Health Study (CHS), one of the largest and most comprehensive
investigations of the long-term effects of air pollution on children's health. Carotid artery ultrasounds were
performed on a subset of CHS children at age 10, providing an early measure of subclinical atherosclerosis. As
these participants now approach early adulthood (~21-23 years), we are uniquely poised to address the
question of whether lifetime air pollution exposures are associated with changes in atherosclerosis markers
from childhood into early adulthood. Using childhood carotid artery ultrasound images as a baseline measure,
we propose to leverage ongoing follow-up of CHS participants to obtain a repeat assessment of subclinical
atherosclerosis measures (CIMT and CAS), and calculate carotid echogenicity (GSM), a novel metric of arterial
wall composition, from baseline and follow-up ultrasound images. We will evaluate the effects of residential
ambient and traffic-related air pollutants on changes in these measures of subclinical atherosclerosis over
time, as well as attained level of atherosclerosis in early adulthood. We will also evaluate the relation between
air pollution exposure and biomarkers of cardiometabolic dysfunction (glucose, lipids, HbA1c), to begin to
investigate potential mechanisms underlying early atherosclerosis. This novel study will fill a critical gap in our
knowledge of subclinical atherosclerosis in children over time and investigate the impact of lifetime air pollution
exposure on early phases of disease progression.
