Person:

Dorans, Kirsten

This dissertation assesses the associations of residential proximity to a major roadway and residential ambient fine particulate matter exposure with artery calcification, a correlate of atherosclerosis, among Framingham Heart Study participants. It also explores using quantile regression to model outcomes with distributions similar to that of artery calcification, which is zero-inflated and right-skewed, an excess of zeros followed by a long tail to the right. Chapter I examines associations of residential distance to a major roadway and residential fine particulate matter (PM2.5) exposure with coronary artery calcium Agatston score (CAC) among Framingham Heart Study participants living in the Northeastern U.S. CAC is a quantitative estimate of total coronary atheroma and a strong risk factor for coronary heart disease. We observed no associations of these exposures with the presence, extent or progression of CAC. Chapter II examines associations of residential distance to a major roadway and residential PM2.5 exposure with thoracic aortic calcium Agatston score (TAC) and abdominal aortic calcium Agatston score (AAC), correlates of systemic atherosclerosis. There were no associations of these exposures with the presence or extent of TAC or AAC or with AAC progression. The direction of some estimates ran counter to expectation. Overall, these exposures were not strongly related to artery calcification among participants living in a region with relatively low levels of and little variation in PM2.5. Chapter III assesses quantile regression performance when modeling outcomes with zero-inflated or right-skewed distributions, such as CAC. Quantile regression has the potential to identify associations of exposures with shifts in parts of the distribution of an outcome that linear regression may miss. When analyzing data in Chapters I and II, we found quantile regression performed poorly when modeling CAC. In an effort to better understand this performance, we examined quantile regression for simulated outcomes that had varying amounts of zero-inflation and skew. Quantile regression performed poorly for some scenarios in which there was zero-inflation, suggesting traditional multivariable quantile regression may not work well for zero-inflated outcomes. When using quantile regression in practice, users should check model performance by assessing shapes of covariate-outcome relationships and looking for unreasonable model predictions.

Background: Short‐term exposure to elevated air pollution has been associated with higher risk of acute cardiovascular diseases, with systemic oxidative stress induced by air pollution hypothesized as an important underlying mechanism. However, few community‐based studies have assessed this association. Methods and Results: Two thousand thirty‐five Framingham Offspring Cohort participants living within 50 km of the Harvard Boston Supersite who were not current smokers were included. We assessed circulating biomarkers of oxidative stress including blood myeloperoxidase at the seventh examination (1998–2001) and urinary creatinine‐indexed 8‐epi‐prostaglandin F2α (8‐epi‐PGF 2α) at the seventh and eighth (2005–2008) examinations. We measured fine particulate matter (PM 2.5), black carbon, sulfate, nitrogen oxides, and ozone at the Supersite and calculated 1‐, 2‐, 3‐, 5‐, and 7‐day moving averages of each pollutant. Measured myeloperoxidase and 8‐epi‐PGF 2α were loge transformed. We used linear regression models and linear mixed‐effects models with random intercepts for myeloperoxidase and indexed 8‐epi‐PGF 2α, respectively. Models were adjusted for demographic variables, individual‐ and area‐level measures of socioeconomic position, clinical and lifestyle factors, weather, and temporal trend. We found positive associations of PM 2.5 and black carbon with myeloperoxidase across multiple moving averages. Additionally, 2‐ to 7‐day moving averages of PM 2.5 and sulfate were consistently positively associated with 8‐epi‐PGF 2α. Stronger positive associations of black carbon and sulfate with myeloperoxidase were observed among participants with diabetes than in those without. Conclusions: Our community‐based investigation supports an association of select markers of ambient air pollution with circulating biomarkers of oxidative stress.

Objectives: Traffic and ambient air pollution exposure are positively associated with cardiovascular disease, potentially through atherosclerosis promotion. Few studies have assessed associations of these exposures with thoracic aortic calcium Agatston score (TAC) or abdominal aortic calcium Agatston score (AAC), systemic atherosclerosis correlates. We assessed whether living close to a major road and residential fine particulate matter (PM2.5) exposure were associated with TAC and AAC in a Northeastern US cohort. Design: Cohort study. Setting: Framingham Offspring and Third Generation participants residing in the Northeastern USA. Participants and outcome measures Among 3506 participants, mean age was 55.8 years; 50% female. TAC was measured from 2002 to 2005 and AAC up to two times (2002–2005; 2008–2011) among participants from the Framingham Offspring or Third Generation cohorts. We first assessed associations with detectable TAC (logistic regression) and AAC (generalised estimating equation regression, logit link). As aortic calcium scores were right skewed, we used linear regression models and mixed-effects models to assess associations with natural log-transformed TAC and AAC, respectively, among participants with detectable aortic calcium. We also assessed associations with AAC progression. Models were adjusted for demographic variables, socioeconomic position indicators and time. Results: There were no consistent associations of major roadway proximity or PM2.5 with the presence or extent of TAC or AAC, or with AAC progression. Some estimates were in the opposite direction than expected. Conclusions: In this cohort from a region with relatively low levels of and variation in PM2.5, there were no strong associations of proximity to a major road or PM2.5 with the presence or extent of aortic calcification, or with AAC progression.