Medicine and Health Sciences Commons^™

Examining The Simultaneous Influence Of Individual And Neighborhood Determinants On Cardiovascular Health: A Multilevel Study In Canadian Adults, Sarah Singh

Electronic Thesis and Dissertation Repository

Introduction: Previous studies have found that the cardiovascular health of individuals may be influenced not only by their personal characteristics, but also independently by their social relationships and the neighborhoods in which they reside. Still, it is unclear how these determinants act together to influence cardiovascular health and whether these determinants account for differences in cardiovascular health among Canadian adults.

Objective: The main objectives were: 1) to examine the status of cardiovascular health in Canadian adults and, 2) to describe how individual and neighborhood determinants can: a) act together to influence cardiovascular health and, b) account for differences …

Assessing The Structure-Function Relationships Of The Apolipoprotein(A) Kringle Iv Sub-Type 10 Domain, Matthew J. Borrelli

Electronic Thesis and Dissertation Repository

Elevated plasma lipoprotein(a) (Lp(a)) is the most prevalent heritable risk factor in the development of cardiovascular disease. The apolipoprotein(a) (apo(a)) component of Lp(a) is strongly implicated in the pathogenicity of Lp(a). It is hypothesized that the inflammatory potential of Lp(a)/apo(a) is mediated by the lysine binding ability of the apo(a) kringle IV10 (KIV10) domain, along with its covalently bound oxidized phospholipid (oxPL). Using targeted mutagenesis, two novel null alleles for the LPA gene that generate non-secretable apo(a) species have been identified, resulting from amino acid substitutions in the KIV10 domain. A potential mechanism by which KIV10 oxPL modification is enriched …

Mapping The Impact And Plasticity Of Cortical-Cardiovascular Interactions In Vascular Disease Using Structural And Functional Mri, Udunna C. Anazodo

Electronic Thesis and Dissertation Repository

There is growing interest in the role of vascular disease in accelerating age-related decline in cerebrovascular structural and functional integrity. Since an increased number of older adults are surviving chronic diseases, of which cardiovascular disease (CVD) is prevalent, there is an urgent need to understand relationships between cardiovascular dysfunction and brain health. It is unclear if CVD puts the brains of older adults, already experiencing natural brain aging, at greater risk for degeneration. In this thesis, the role of CVD in accelerating brain aging is explored. Because physical activity is known to provide neuroprotective benefits to brains of older adults, …

Genetic Approaches To Studying Complex Human Disease, Joseph B. Dube

Electronic Thesis and Dissertation Repository

Common, complex diseases such as cardiovascular disease (CVD) represent an intricate interaction between environmental and genetic factors and now account for the leading causes of mortality in western society. By investigating the genetic component of complex disease etiology, we have gained a better understanding of the biological pathways underlying complex disease and the heterogeneity of complex disease risk. However, the development of high throughput genomic technologies and large well-phenotyped multi-ethnic cohorts has opened the door towards more in-depth and trans-disciplinary approaches to studying the genetics of complex disease pathogenesis. Accordingly, we sought to investigate select complex traits and diseases using …

Shift Work And Cardiovascular Events: Systematic Review And Meta-Analysis, Manav V. Vyas

Electronic Thesis and Dissertation Repository

The prevalence of shift work is increasing in the general population. There is conflicting epidemiologic evidence on the association between shift work and cardiovascular disease. We performed a systematic review and meta-analysis of observational studies that measured shift work-cardiovascular disease associations. We screened 12,350 articles and identified 35 eligible studies. The pooled risk ratios (RR) for myocardial infarction, all coronary events and ischemic stroke were 1.23 (95% confidence interval [CI] 1.15 to 1.31, I² = 0), 1.24 (95% CI 1.10 to 1.39, I² = 85%) and 1.05 (95% CI 1.01 to 1.09, I² = 0), respectively. The …

Elucidating The Genetic Determinants Of The Archetypal Complex Disease Hypertriglyceridemia, Christopher T. Johansen

Electronic Thesis and Dissertation Repository

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in Canada. Among non-traditional risk factors, plasma triglyceride (TG) concentration is re-emerging as a significant risk factor. Patients with hypertriglyceridemia (HTG) – an archetypal complex phenotype defined by fasting plasma TG concentration >95^th percentile – thus have significantly increased CVD risk, compounded by associated co-morbidities such as obesity, metabolic syndrome and type 2 diabetes. However, the molecular pathways contributing to HTG susceptibility are incompletely defined. A better understanding of the genetic determinants that underlie the phenotypic spectrum of plasma TG and HTG susceptibility is necessary to identify novel …