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UBC Theses and Dissertations

Emerging environmental, molecular, and genetic risk factors in stable coronary artery disease Heslop, Claire Louise

Abstract

Both environmental and inherited risk factors make significant contributions to coronary artery disease, however susceptibility and age of disease onset for individuals with similar risk profiles varies widely. Novel biomarkers may yet be found which could improve detection of high-risk individuals, and highlight new areas of research for treatment discovery. This thesis explores risk factors for coronary artery disease and cardiovascular mortality. The first study investigates one specific environmental variable—neighbourhood socioeconomic status—in a cohort of patients who underwent selective coronary angiography. In patients with coronary artery disease, neighbourhood-level disparities contributed to risk of non-cardiovascular mortality, particularly to deaths from cancer, but did not influence cardiovascular mortality risk. Although disparities in health and access to care may persist, these findings suggest other risk factors should be explored to improve cardiovascular patient risk assessment. Inflammation and oxidative stress contribute to all stages of atherosclerosis, and subsequent chapters focus on contributions of these pathways to cardiovascular risk. Interleukin-6 and C-reactive protein haplotypes were compared to plasma concentrations for prediction of coronary artery disease and cardiovascular mortality. Significant relationships observed between haplotypes, plasma concentrations, angiographic disease, and cardiovascular mortality did not demonstrate causality, which underscores the challenge of distinguishing causal from confounding pathways. Plasma oxidative stress biomarkers were measured to evaluate their utility for risk prediction, compared to conventional cardiovascular risk factors. Elevated plasma myeloperoxidase predicted coronary artery disease and cardiovascular mortality risk, independent of conventional risk factors and disease severity. Polymorphisms in candidate oxidative stress genes were also explored for associations with coronary artery disease, and effects on plasma biomarkers. A compound genotype of five polymorphisms predicted angiographic coronary artery disease and elevations in plasma myeloperoxidase. Following validation, these polymorphisms may be useful markers of lifetime oxidative stress burden and cardiovascular disease risk. Novel cardiovascular risk markers are explored in this thesis, and tested for association with angiographic coronary artery disease, conventional risk factors, and risk of mortality. New questions are raised regarding how disease susceptibility is influenced by environmental and inherited factors, and ideas for future research are discussed.

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Attribution-NonCommercial-NoDerivatives 4.0 International

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