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<p>Background: Genome wide association studies (GWAS) performed in Caucasian populations have identified several single nucleotide polymorphisms (SNPs) associated with coronary artery disease (CAD), although their cumulative impact in other ethnicities is unknown. Using a genetic risk score (GRS), we examined the impact of CAD related SNPs on myocardial infarction (MI) in a multi-ethnic population.</p> <p>Methods: We included 4083 MI cases and 4473 controls from the INTERHEART case: control study, stratified by six ethnic groups: European, South Asian, other Asian, Arab, Latin American, and African. We created a GRS comprised of 25 SNPS, and tested its association with MI in individual ethnicities using logistic regression, and across ethnic groups through meta-analyses. Results were adjusted for age, sex, and modifiable risk factors.</p> <p>Results: The GRS was significantly associated with MI in Europeans (odds ratio [OR] = 1.08, 95% confidence interval [CI] 1.04-1.12 per risk allele), South Asians (OR = 1.09, 95% CI 1.05-1.14), other Asians (OR = 1.09, 95% CI 1.04-1.15), and Arabs (OR = 1.07, 95% CI 1.03-1.12). In Latin Americans and Africans the GRS was not significant. Meta-analysis of ethnic groups demonstrated a 1.06 (95% CI 1.03-1.09) increase in the odds of MI with the GRS per risk allele. Significant heterogeneity was observed, which was reduced by exclusion of Latin Americans (I2=63% to 0%). Above clinical risk factors, the GRS modestly increased population attributable risk (PAR) (0.92 to 0.94), concordance statistic (0.73 to 0.74), net reclassification improvement (0.14), and integrated discriminatory improvement (0.007).</p> <p>Conclusions:<strong> </strong>The GRS was associated with a significant increase in the odds of MI in multiple ethnic groups. Improvements in PAR, discrimination and reclassification were modest above clinical factors.</p> / Master of Science (MSc)

Ascorbate (Asc) is a key antioxidant in preventing cardiovascular dysfunction during diseases exacerbated by altered shear stress. According to the literature endothelial responses to hypotonic shock share some characteristics with those induced by shear stress. Thus to study the physiological responses of endothelium to shear stress, the characterization of the Asc release by pig coronary artery endothelial cells in response to hypotonic shock was performed. The pig coronary artery endothelial cells that had been loaded with ^14C Asc and ^3H deoxyglucose, were exposed to buffers of varying osmolality for different time periods and the release of ^14C Asc and ^3H deoxyglucose was examined. Based on various parameters like relative release of ^14C Asc and ^3H deoxyglucose, their rate of release and protein loss, it was decided to use buffer of .67 percent osmolality for 2 min for these characterization studies. The Asc release was authentic and not a result of membrane damage. The hypotonic shock induced Asc release was not due to endogenously released ATP. The inhibition of ATP induced release by anion channel inhibitors niflumic acid and NPPB was complete but only partial in case of hypotonic shock induced release. The release was not inhibited under nominally Ca^2+ free conditions. Additive release by hypotonic shock and ATP or hypotonic shock and Ca^2+ ionophore A23187 suggests that there are two independent Asc release pathways. Asc release by two different mechanisms may help endothelial cells deal with stressful conditions efficiently and preserve endothelial function. / Thesis / Master of Science (MS)

The physiological and psychosocial benefits of sustained exercise adherence among individuals with coronary artery disease (CAD) have been well-documented (e.g., Blumenthal et al., 1997; Rozanski et al., 1999; Wenger et al., 1995). Despite these known benefits, approximately 80% of patients who enter the maintenance phase of cardiac rehabilitation drop out after one year (Balady et al., 1994; Hedback, Perk, Wodlin, 1993 ). Among this 80%, less than 25% continue to exercise at levels that will maintain or improve cardiorespiratory fitness (Daltroy, 1985; Radtke, 1989). Self-efficacy has been identified as a significant predictor of adherence to exercise beyond the initial 6 months of participation. In addition to self-efficacy, outcome satisfaction has been suggested as a potentially significant predictor of adherence to exercise beyond the initiation phase (i.e., beyond the first 6 months). Unfortunately, most research examining these predictors of adherence has been conducted among asymptomatic populations. Thus, little is known about the predictive utility of self-efficacy and outcome satisfaction in relation to sustained exercise adherence among the CAD population. The purpose of the present study was to examine self-efficacy (Bandura, 1986) and outcome satisfaction (Rothman, 2000) in the prediction of adherence to maintenance cardiac rehabilitation in 101 men (M age= 68.15 ± 8.03) with coronary artery disease (CAD). A series of three hierarchical multiple regression analyses were conducted to predict onsite, offsite and total adherence to the maintenance cardiac rehabilitation exercise prescription. Interestingly, Exercise Beliefs (i.e., days of aerobic exercise per week believed necessary to maintain cardiovascular health), one of the study covariates, emerged as an important predictor of both offsite and total exercise adherence and explained a significant amount of variance in these variables (R2 = .25 [offsite], .23 [total],ps < .01). As predicted, self-regulatory efficacy was a significant predictor and explained a significant amount of variance in onsite exercise adherence (R2 = .17 [scheduling],p < .001). Task self-efficacy was not a significant predictor and did not account for a significant amount of variance in onsite exercise adherence. Also as predicted, task self-efficacy was a significant predictor and explained a significant amount of variance in offsite exercise adherence (R2= .10,p < .05). Self-regulatory efficacy was not a significant predictor and did not account for a significant amount of variance in offsite exercise adherence. In addition, consistent with hypothesis, both task self-efficacy and self-regulatory efficacy were significant predictors of total exercise adherence and explained a significant amount of the variance in this variable (R2 = .12 [task], .07 [scheduling],ps < .05). Contrary to hypothesis, outcome satisfaction did not explain a significant amount of variance in exercise adherence (onsite, offsite, and total) beyond that explained by self-efficacy (task and self-regulatory) alone. Taken together, this research has enhanced our knowledge of the psychosocial predictors of adherence to the maintenance cardiac rehabilitation exercise prescription among men with CAD. These findings also have important implications for health care professionals working in the area of cardiac rehabilitation. Specifically, it is up to health care professionals to ensure that patient beliefs regarding the maintenance cardiac rehabilitation exercise prescription are accurate, and that patients are efficacious in their ability to engage in the elemental physical aspects of exercise and to effectively schedule exercise into their daily lives. / Thesis / Master of Science (MS)

Introduction: Coronary artery bypass grafting surgery is an effective treatment for coronary heart disease for many patients; however, evidence suggests that there are some patients who do not report a good post-operative recovery. Although several studies have begun investigating possible reasons for these observations, little is known about the impact of CABG on quality of life and there still remains a lack of information that can help clinicians identify those people more likely to experience poorer recovery so that interventions can be targeted appropriately. Aims: The overall aim was to investigate barriers to and facilitators of recovery after CABG. Method: Phase 1 was a retrospective qualitative study involving semi-structured interviews with eleven patients who had undergone CABG and with ten health professionals experienced in caring for these patients. Data were analysed using thematic analysis. Phase 2 was a prospective study comprising two components, questionnaire and interview. The questionnaire included measures of quality of life, perceived recovery, demographic and psychosocial variables and was administered prior to surgery and at six and twelve months post-surgery. A sample of ten people who completed questionnaires were interviewed at the same time points and data analysed using framework analysis. Results: Interview data described the patient experience of undergoing CABG and identified components of a good recovery from the patient perspective. Patient and health professional participants identified numerous barriers and facilitators to recovery at three key time points - prior to surgery, during the hospital inpatient stay and post-CABG - and noted the complex inter-relationships between them, thus emphasising the need for a holistic approach to investigating recovery. Questionnaire data described the pattern of psychosocial functioning, quality of life and perceived recovery across the surgical pathway and identified depression and self-efficacy as the main predictors of post-CABG quality of life and perceived recovery. Using interview and questionnaire data a model of recovery is proposed. Conclusions: Findings from this research have identified a complex inter-related network of barriers and facilitators to recovery, suggested the possible mechanisms by which they impact on post-CABG outcome and identified recommendations for clinical practice.

INTRODUCTION: The risk factors for cardiovascular disease (CVD) are associated with coronary atherosclerosis and having multiple risk factors potentiates atherosclerosis. This study examined the prevalence of multiple biological and lifestyle/behavioral risk factors and their association with coronary artery calcium (CAC), a marker for subclinical coronary atherosclerosis. METHODS: This is a cross-sectional study of 1607 community-dwelling asymptomatic individuals from central Appalachia who participated in CAC screening between January 2011 and December 2012. Data on demographics (sex and age) and 7 traditional risk factors for coronary artery disease (CAD) were collected and categorized into 5 groups (0-1, 2, 3, 4, and ≥5). Prevalence of these risk factors and CAC scores (0, 1-99, 100-399, ≥400) were assessed, and the impact of the number of risk factors on CAC scores were delineated using multiple logistic regression. RESULTS: Over 98% of participants had ≥1 risk factor. While obesity, diabetes, hypertension, and family history of CAD significantly increased the odds of having CAC, CAC scores significantly increased with number of risk factors. After adjusting for demographic factors, having 3, 4, and ≥5 risk factors was significantly associated with increased odds of having higher CAC scores when compared to zero CAC score by more than one and half times [OR=1.65, CI (1.20-2.25)], two times [OR=2.32, CI (1.67-3.23)] and three times [OR=3.45, CI (2.42-4.92)], respectively. CONCLUSION: The high prevalence of multiple risk factors in the study population suggests the need for aggressive multiple risk factors interventions for primary prevention of CAD, which could address CVD health disparities.

Aim: To examine the association of cardiovascular disease risk factors with and their cumulative effect on coronary artery calcium in hard-to-reach asymptomatic patients with diabetes. Methods: : A total of 2563 community-dwelling asymptomatic subjects from Central Appalachia participated in coronary artery calcium screening at a heart centre. Binary variable was used to indicate that coronary artery calcium was either present or absent. Independent variables consisted of demographic and modifiable risk factors and medical conditions. Descriptive statistics and multinomial logistic regression analyses were conducted. Results: : In total, 55.8% and 13.7% of study participants had subclinical atherosclerosis (coronary artery calcium ⩾1) and diabetes, respectively. The presence of coronary artery calcium was higher in subjects with diabetes (68.5%) than those without (53.8%). Compared to subjects without diabetes with coronary artery calcium = 0, obesity, hypertension, hypercholesterolaemia and smoking increased the odds of the presence of coronary artery calcium (coronary artery calcium score ⩾1) regardless of diabetes status; however, with larger odds ratios in subjects with diabetes. Compared to subjects without diabetes with coronary artery calcium score = 0, having 3, 4 and ⩾5 risk factors increased the odds of presence of coronary artery calcium in subjects with diabetes by 14.06 (confidence interval = 3.26–62.69), 32.30 (confidence interval = 7.41–140.82) and 47.12 (confidence interval = 10.35–214.66) times, respectively. Conclusion: : There is a need for awareness about subclinical atherosclerosis in patients with diabetes and more research about coronary artery calcium in subpopulations of patients.

Η ασβέστωση των στεφανιαίων αρτηριών αποτελεί αξιόπιστο δείκτη της στεφανιαίας αθηρωμάτωσης. Η ψηφιακή ακτινοσκόπηση/ακτινογράφηση είναι μία ακριβής μη αιματηρή μέθοδος ανάδειξης της στεφανιαίας ασβέστωσης, εύκολα διαθέσιμη, χαμηλού κόστους, γρήγορη και με χαμηλή δόση ακτινοβολίας. Μέχρι τώρα δεν έχει ερευνηθεί πολύπλευρα η αξία της για την ανίχνευση της ασβέστωσης των στεφανιαίων αρτηριών. / Coronary artery calcification is a reliable indicator of coronary artery atherosclerosis. Digital subtraction cinefluoroscopy is an accurate, noninvasive, rapid, widely available method for coronary calcium detection, with low average skin penetration dose. Until now, digital cinefluoroscopy value for coronary calcium detection has not been fully elucidated.