Despite advances, stroke remains the largest cause of disability and fourth leading cause of death in the United States. The relationship between changes in human vasculature (atherosclerosis and arteriosclerosis) prior to clinical incident, and other risk factors for stroke remains unclear. This dissertation represents work towards the identification of imaging biomarkers for vascular change, focusing on ultrasound to characterize persons at risk, including differences among race/ethnic groups. This research contained three distinct projects. The first goal was to determine if changes within ultrasonographic measures of carotid vasculature could be found across race/ethnic groups after adjustment for risk factors. The second was to determine if those same measures were related to changes in cerebral white matter known to be associated with ongoing cerebrovascular disease; we compared ultrasound to an MRI marker of subclinical vascular disease, white matter hyperintensity volume (WMHV). Finally, we sought to investigate a known and well-studied ultrasound marker for atherosclerosis, carotid intima-medial thickness, with those same MRI markers of subclinical vascular disease (WMHV). All studies were conducted within an on-going multiethnic cohort that has been followed since 1990, The Northern Manhattan Study. The population is comprised of persons who self-identify as Hispanic (52%), Black (24%), or White (21%), with less than 3% identified as “race/other.” We found race/ethnic differences in carotid arterial stiffness and diameter; carotid diameter increases with age among Hispanics, but not among blacks or whites. A significant correlation was also found between diastolic diameter and subclinical vascular disease, and this relationship was also increased among Hispanics; neither black race nor white race was associated with corresponding increases in both MRI white matter hyperintensity and diastolic diameter. Finally, using a surrogate marker for atherosclerosis, carotid intima-medial thickness (cIMT), we document for the first time, positive associations between cIMT and WMHV. There are important developments still to be made in the field of vascular risk. Use of inexpensive and non-invasive ultrasound technology to approximate ongoing cerebrovascular disease could lead to better understanding of the effect of known risk factors, and could help stroke risk assessment and treatment modification.

Polycyclic aromatic hydrocarbons (PAHs) are environmental and occupational carcinogens that are produced by the incomplete combustion of organic material, such as from the burning of tobacco, coal, and petroleum products. In addition to causing cancer, exposure to PAHs is hypothesized to contribute to atherosclerosis and to lead to increased incidence rates of cardiovascular disease in populations. Considering the number of deaths attributable to tobacco smoke exposure, ambient air pollution, and occupational hazards, PAHs may be a significant contributor to the prevalence of cardiovascular disease in human populations. However, a clear exposure-response relationship between PAHs and measures of cardiovascular disease has not been demonstrated. While PAH exposure has been shown to be associated with indicators of cardiovascular disease in research animals, this relationship has not been studied comprehensively in human populations. Using data from the continuous National Health and Nutrition Examination Surveys (NHANES) 1999 - 2004 of a representative sample of the entire US civilian population, this study investigated predictors of total body burden of PAHs and associations between urinary metabolites of PAHs and biomarkers of cardiovascular disease in 4,492 study participants aged 20 years and older. Using various analytic approaches, this research project identified tobacco smoke exposure as a significant predictor of urinary levels of low molecular weight PAHs but not as a predictor of urinary levels of high molecular weight PAHs in a large population of individuals without known occupational exposure to PAHs. Worker occupational category was not associated with urinary levels of any PAH metabolites. The results of this study also indicate a possible association between exposure to PAHs and the development of cardiovascular disease in humans. Levels of multiple metabolites of specific PAHs, naphthalene, fluorene, and phenanthrene were significantly associated with increases in total cholesterol, triglycerides, WBC count, and C-reactive protein levels. Additionally, this study examined the utility of factor analysis for data reduction of 23 urinary PAH metabolites to two latent factors representing low and high molecular weight PAHs to streamline investigations of the associations of PAH exposures with various health outcomes. Results of this study suggest mechanisms by which PAH exposure contributes to the burden of cardiovascular disease on human populations and the methods by which human body burden on PAHs can be measured.

In the past two decades studies have indicated that oral health might be associated with the prevalence for cardiovascular disease (CVD), although the biological link still remains unknown. Bacteria and inflammatory mediators causing periodontal disease have also been suggested to influence the progression of atherosclerosis. The aims of this thesis were to study oral inflammation and associations between different oral health parameters and CVD. Inflammatory mediators such as interleukin-1 (IL-1) as well as bone resorption activity (BRA) were significantly higher in gingival crevicular fluid (GCF) from sites with periodontal disease compared to healthy sites. Treatment resulted in a reduction of BRA as well as the levels of IL-1 for most of the diseased pockets. The levels of IL-1 were not correlated to the amount of BRA. Number of teeth (NT) was consistently associated to CVD and was the only oral health parameter that related to all-cause mortality and mortality in CVD in a dose-dependent manner. Subjects with <10 teeth had a 7-fold increase risk for mortality in coronary heart disease compared to those with >25 teeth. Furthermore, NT was also significantly associated to the levels of leukocytes and to the metabolic syndrome, which consists of a combination of cardiovascular risk factors. Other investigated oral health parameters, such as severity of periodontal disease, number of deepened pockets, and bleeding on probing, were not related to CVD in a consistent way. Oral health parameters as well as myocardial infarction (MI) were related to serum antibody levels against Porphyromonas gingivalis (Pg), indicating that Pg might be a link between oral health and MI. In conclusion, treatment reduced the increased levels of IL-1 and BRA in GCF from sites with periodontal disease. Oral health was associated to CVD with number of teeth being the only oral health parameter that consistently was associated to CVD. Serum antibody levels against P. gingivalis were related to myocardial infarction (MI) as well as to oral health parameters, suggesting that this bacteria could be a link between oral health and CVD.

Objectives Patients with type 2 diabetes are at much greater risk of developing cardiovascular diseases (CVD), including coronary heart disease (CHD), compared to non-diabetics. The lowering of glucose, blood pressure, and plasma lipid levels has been shown to reduce CHD risk, and treatment goals for these risk factors are now part of clinical practice guidelines. However, the incidence and outcome of CHD in diabetic patients does not show the same favourable trend as in the general population. Thus, the overall aim of the thesis was to investigate how the treatment goals for CVD risk factors contained in the national guidelines for diabetes care were reflected in clinical practice, and to explore factors that might influence the remaining high incidence of CHD in the type 2 diabetes population. Research designs and results I. The effectiveness of the introduction of treatment goals for dyslipidaemia was evaluated in a retrospective observational population-based cross-sectional study of 971 diabetic patients participating in the Västerbotten Intervention Programme (VIP) 1995–2004. There was a stronger trend of decrease in cholesterol levels among patients with diabetes compared to the non-diabetic population in 2000–2004. Increased use of lipid-lowering agents influenced the trend in diabetic patients, even though only 25.3% received lipid-lowering treatment after the introduction of the new guidelines. II. The experiences of general practitioners relating to treatment practice for type 2 diabetes with specific focus on the prevention of cardiovascular disease were explored in a focus group study. The overall theme was ‘dilemmas’ in GPs’ treatment practice for patients with type 2 diabetes. Five main dilemma categories were identified. First, GPs were hesitant about labelling a person who feels healthy as ill. Second, as regards communicating a diabetes diagnosis and its consequences, GPs were unsure as to whether patients should be frightened or comforted. Third, GPs experienced uncertainty in their role: should they take responsibility for the care or not? Fourth, GPs expressed concern over a conflict between lifestyle changes and drug treatment. Fifth, the GPs described difficulties when attempting to translate science into reality. III. Screening for microvascular and coronary heart disease according to national guidelines was evaluated in a cross-sectional study of 201 screening-detected patients with type 2 diabetes 1.5±0.7 years after diagnosis. A larger proportion of diabetic patients was screened for nephropathy and retinopathy than for CHD. Twenty-three percent of the patients had minor or major ECG abnormalities, but ECG findings seemed to have little or no impact on CHD prevention using lipid-lowering medication and ASA. A clinical history of CHD correlated with a larger proportion of patients receiving secondary prevention. IV. Time trends relating to the achievement of treatment goals and 10-year CHD risk at three years of diabetes duration were studied in 19,382 patients with type 2 diabetes without CHD, who were reported by primary health care sources in the National Diabetes Register in 2003–2008. National treatment goals for glycaemia, blood pressure, total cholesterol, and LDL cholesterol were achieved in 78.4%, 65.5%, 55.6%, and 61.0%, respectively, of the diabetic patients in 2008 following a trend of improved results in 2003–2008. Absolute 10-year risk of CHD increased between year of diagnosis and follow up in a studied subgroup while modifiable risk decreased. Conclusions The introduction of treatment goals for dyslipidemia in Swedish national guidelines in 1999 were reflected in lowered cholesterol levels in people with type 2 diabetes. Since the introduction of the guidelines, an increasing number of diabetic patients are treated in accordance with guidelines. A remaining microvascular focus on the patients together with the revealed dilemmas within the GP’s consultation with diabetic patients might negatively influence the remaining high incidence of CHD in the type 2 diabetes population. Lipid levels, blood pressure and smoking are targets for further improvements. / Kappa

Bakgrund: Hjärt-kärlsjukdom är en av våra vanligaste folksjukdomar iSverige och majoriteten av dessa kan, med hjälp av vården, förebyggasgenom livsstilförändringar. Trots en medvetenhet hos individen om attdennas vanor är ohälsosamma är förändringarna svåra att genomföra. Syfte:Syftet var att undersöka vilka omständigheter som försvårarlivsstilsförändringar hos personer med, eller med ökad risk att utveckla,hjärt-kärlsjukdom. Metod: Studien gjordes som en allmän litteraturstudieför att sammanställa aktuell forskning inom området. Sökningar gjordes idatabaserna cinahl, PubMed och PsycINFO och resulterade i 10 kvalitativaartiklar. Resultat: De fem huvudkategorierna i studien var: bristandeinformation från vårdpersonal, fysiska och praktiska hinder, upplevda kravfrån omgivningen och deltagarna själva, bristande stöd från vårdpersonaloch närstående, konflikt mellan förnuft och känsla. Hindrande faktorer förlivsstilsförändringar visade sig vara information som inte var anpassad efterindividernas levnadsförhållanden och förutsättningar, att individen kändebristande kontroll över den egna hälsan och sjukdomsutvecklingen samt attprioriteringen för livsstilsförändringar minskade när tiden gick ochsymtomen avklingade. Diskussion: Vid arbetet med livsstilsförändringar ärdet viktigt att vårdpersonal utgår från individen och gör denna delaktig iförändringsarbetet. Genom att erbjuda ett långsiktigt stöd där informationkontinuerligt fylls på, förtydligas och upprepas samt att frågor kan besvaraskan förmågan att genomföra livsstilförändringar öka. / Background: Cardiovascular disease is one of the most common nationaldiseases in Sweden and the majority of cases can be prevented by lifestylechanges. Despite the fact that patients frequently demonstrate a high degreeof awareness with regards to the effect that negative lifestyle habits mayhave on their health it is often difficult to implement the required changes.Purpose: The aim was to investigate the circumstances which makelifestyle changes difficult for individuals with cardiovascular disease andthose at risk of developing cardiovascular disease. Method: The study wasconducted with view to gathering and evaluating literature on researchrelating to the subject. Searches were made in the databases Cinahl, PubMedand PsycINFO and resulted in 10 qualitative articles. Result: The five maincategories in this study were: lack of information from health professionals,physical and practical barriers, perceived demands from their socialenvironment as well as demands participants have on themselves, lack ofsupport from health professionals and conflict between reason and emotions.Hindering factors for lifestyle changes proved to be information that was notadjusted to participants’ living conditions and circumstances, thatindividuals felt lack of control over their own health and diseasedevelopment and lower prioritization of lifestyle changes as time went andthe symptoms faded away. Discussion: When supporting lifestyle changes,it is important that health professionals in their treatment closely involve theindividual and that the individual’s personal needs are taken intoconsideration. The chance of successfully implementing preventive lifestylechanges greatly increases if information is updated, clarified, repeated andany questions arising are answered.

Objective: Although associations between testosterone and cardiovascular (CV) morbidity in women have been proposed, no large prospective study has evaluated potential associations between testosterone and mortality in women. The objective was to determine whether baseline testosterone levels in women are associated with future overall or CV morbidity and mortality. Design: Prospective cohort study with a 4.5-year follow-up period. Methods: From a representative sample of German primary care practices, 2914 female patients between 18 and 75 years were analyzed for the main outcome measures: CV risk factors, CV diseases, and all-cause mortality. Results: At baseline, the study population was aged 57.96±14.37 years with a mean body mass index of 26.71±5.17 kg/m2. No predictive value of total testosterone for incident CV risk factors or CV diseases was observed in logistic regressions. Patients with total testosterone levels in the lowest quintile Q1, however, had a higher risk to die of any cause or to develop a CV event within the follow-up period compared to patients in the collapsed quintiles Q2–Q5 in crude and adjusted Cox regression models (all-cause mortality: Q2–Q5 versus Q1: crude hazard ratios (HR) 0.49, 95% confidence interval (CI) 0.33–0.74; adjusted HR 0.62, 95% CI 0.42–0.939; CV events: Q2–Q5 versus Q1: crude HR 0.54, 95% CI 0.38–0.77; adjusted HR 0.68, 95% CI 0.48–0.97). Kaplan–Meier curves revealed similar data. Conclusions: Low baseline testosterone in women is associated with increased all-cause mortality and incident CV events independent of traditional risk factors.

Effective risk communication is essential in the field of health to ensure patients understand the information being presented to them by medical professionals and appreciate the level of risk involved in treatments. Cardiovascular disease, being the leading cause of death worldwide, is relevant to consider when examining risk communication in a health setting. Those afflicted with cardiovascular ailments are both high in number and exposed to information communicating risk. This research aims to identify presentation formats that are more effective communicating risk information to recovering cardiovascular patients at the University of Ottawa Heart Institute. The formats’ effectiveness is measured by gauging the population’s understanding of the material and perception of the information as it relates to risk and motivation. The research draws on Max Weber’s concept of rationality and subsequent scholars who developed social judgment theory, the heuristic-systematic model, expected utility theory, protection motivation theory, and the extended parallel process model. Utilizing an experimental research design, risk information handouts and questionnaires are distributed to, and completed by, a stratified sample of cardiovascular disease patients. Effective presentation formats are examined, and the results identify comparatively effective presentation formats for minimizing and maximizing risk perception. The results also identify presentation formats’ impact on a patient’s level of motivation to avoid / indulge in behaviours that may maximize or minimize risk. The results, synthesized herein, suggest a model (communicative cardiovascular physician-patient model of message preparation-perception), which may contribute to the effectiveness of risk communication between physicians and cardiovascular disease patients.

Elevated Thyroid-Stimulating Hormone (TSH) is associated with an increased risk of cardiovascular disease (CVD). We hypothesized that TSH-stimulated FA release from adipocytes contributes to macrophage inflammation. 3T3-L1 and human subcutaneous differentiated adipocytes were treated with TSH for 4 hours under various conditions and lipolysis assessed via glycerol secretion. Optimal conditions were determined and protein expression of ATGL, HSL and perilipin remained stable. TSH-stimulated 3T3-L1 or human adipocyte-conditioned medium (T-ACM) was placed on murine J774 or human THP-1 macrophages, respectively, and macrophage cytokine mRNA levels (IL-1β, IL-6, MCP-1, and TNFα) were measured by real-time RT-PCR. T-ACM did not change cytokine mRNA expression in J774 macrophages or THP-1 macrophages when compared to ACM. Absence of BSA in the medium may have hindered release of FA from differentiated adipocytes into the medium, BSA may be required to permit adequate FA accumulation in the medium to then evaluate the effect of T-ACM on macrophages. Further investigation is required to determine the effect of FA on J774 and THP-1 inflammatory response.

The expanding field of tissue engineering provides a new approach to regenerative medicine for common ailments such as cardiovascular disease and type-I diabetes. Biomaterials can be administered as a delivery vehicle to introduce therapeutic cells to sites of damaged or diseased tissue. A specific class of biomaterials, termed hydrogels, is suitable for this application as they can provide a biocompatible, biodegradable scaffold that mimics the physical properties of the native soft tissue. Injectable hydrogels are increasingly being developed for biomedical applications due to their ability to be delivered in a minimally invasive manner. One potential use for such materials is in the delivery of therapeutics such as cells or growth factor-releasing particles. In this study, the first aim was to determine the interactive effects between collagen-based hydrogels and additives (cells and microspheres) for cardiac regeneration. The results demonstrated that the addition of either cells or microspheres to a collagen-based hydrogel decreased its gelation time and increased its viscosity. Increased cross-linker concentrations resulted in lower cell viability. However, this cell loss could be minimized by delivering cells with the cross-linker neutralizing agent, glycine. As a potential application of these materials, the second aim of this study was to develop a hydrogel for use as an ectopic islet transplant site. Specifically, collagen-chitosan hydrogels were synthesized and characterized, with and without laminin, and tested for their ability to support angiogenic and islet cell survival and function. Matrices synthesized with lower chitosan content (20:1 collagen:chitosan) displayed greater cell compatibility for both angiogenic cells and for islets and weaker mechanical properties, while matrices with higher chitosan content (10:1 collagen:chitosan) had the opposite effect. Laminin did not affect the physical properties of the matrices, but did improve angiogenic cell and islet survival and function. Overall the proposed collagen-based hydrogels can be tailored to meet the physical property requirements for cardiac and islet tissue engineering applications and demonstrated promising cell support capabilities.

Currently, the labeling of functional food products is highly regulated in Canada. Although certain nutrient content claims and five generic health claims have been allowed, the inability to make additional nutrient content and health claims decreases functional food firms incentives to produce and commercialize new and healthy food products. This, in turn, has consequences for functional food demand, consumer welfare, and health care costs. The primary objective of this thesis is to examine the potential welfare implications of functional food labeling for Canadian society.<p>A benefit cost analysis is conducted to examine a specific case study of omega-3 enriched eggs. The benefit cost analysis evaluates the welfare effects of functional food labeling policy and helps realize the magnitude of potential benefits that could be gained if not for restrictive and complicated labeling regulations. Based on a range of assumptions and using three different scenarios to cover a range of estimates, the health benefits from the reduction in the risk of coronary heart disease due to the current consumption of omega-3 enriched eggs, and the production and labeling-related costs are estimated. By comparing the estimated benefits and costs, the results indicate that the current consumption of omega-3 enriched eggs provides a considerable net economic gain. Therefore, labeling information on health components can contribute to facilitating a healthy lifestyle with reduced medical costs, stimulating agricultural innovation, and increasing economic welfare.<p>Realizing the positive overall impact that the current consumption of omega-3 enriched eggs has on consumers health and economy in Canada, a possible policy that could regulate all eggs to be enriched with omega-3 fatty acids is proposed. This policy could potentially be used to correct not only information asymmetry but also the negative externalities that are created by health and disability insurances. The benefit cost analysis show that the health benefits would be greatly increased while costs would slightly increase due to reduced labeling-related costs. Therefore, the results indicate that the net economic gain is even stronger if the mandatory development of omega-3 enriched eggs were required.