Diss. (sammanfattning) Stockholm : Karolinska institutet, 2010.

Stroke is a devastating, neurological dysfunction due to brain blood supply disturbance. It is responsible for increasingly high rate of mortality and disability worldwide. This thesis comprises two original studies involving 868 patients at risk of ischemic stroke and/or hemorrhagic stroke. The first study investigated aspirin’s effect among patients with intracranial hemorrhage. Unlike Caucasians which hemorrhagic strokes account for 10-15% of all strokes; in Chinese, intracranial hemorrhages strike up to 35%. After such, anti-platelet agent like aspirin is often avoided for fear of recurrent intracranial hemorrhages, despite compelling indications. However, clinical data is limited. In this single-centered observational study, we included 440 consecutive Chinese patients with a first spontaneous intracranial hemorrhage surviving the first month performed during 1996-2010. 56 patients (12.7%) of these 440 patients were prescribed aspirin after intracranial hemorrhage (312 patient-aspirin years). After a mean follow-up of 62.2 ± 1.8 months, 47 patients had recurrent intracranial hemorrhage(10.7%, 20.6 per 1,000 patient years). Patients prescribed aspirin did not have higher risk of recurrent intracranial hemorrhage compared with those without (22.7 per 1,000 patient-aspirin years vs. 22.4 per 1,000 patient years, p=0.70). Multivariate analysis identified age > 60 years and hypertension as independent predictors for recurrent intracranial hemorrhage. In a subgroup analysis: the incidence of combined vascular events including recurrent intracranial hemorrhage, ischemic stroke, and acute coronary syndrome was statistically lower in patients prescribed aspirin than without (52.4 per 1,000 patient-aspirin years, vs. 112.8 per 1,000 patient-years, p=0.04). Implications of the results: despite having a substantial risk for recurrent intracranial hemorrhage, post-intracranial hemorrhage ones are at risk for thrombotic vascular events and management goal should thus focus on ameliorating overall cardiovascular risk instead of preventing recurrent intracranial hemorrhage. Hence, thrombo-prophylaxis should still be considered. The second study investigated the relation between premature atrial complexes and new-onset atrial fibrillation together with other cardiovascular events. Premature atrial complexes though taken as benign phenomenon, are common in patients with underlying conditions such as coronary heart disease, chronic rheumatic heart disease. While prompt management of atrial fibrillation may prevent ischemic stroke, atrial fibrillation is often unfound until ischemic stroke occurs. In this study, 428 patients without atrial fibrillation but complained of palpitations, dizziness or syncope were recruited. 107 patients with >100 premature atrial complexes/day were defined to have frequent premature atrial complexes. After a mean follow-up of 6.1 ±1.3 years, 31 patients (29%) with frequent premature atrial complexes developed atrial fibrillation compared with 29 patients (9%) with premature atrial complexes?100/day (p<0.01). Cox regression analysis revealed: frequent premature atrial complexes, age>75 years and coronary artery disease were independent predictors. In secondary endpoint (ischemic stroke, congestive heart failure, and death), patients with frequent premature atrial complexes were more at risk than those without (34.5% vs. 19.3%) (Hazard ratio: 1.95, 95% confidence interval: 1.37-3.50, p=0.001). Cox regression analysis showed: age> 75 years, coronary artery disease and frequent premature atrial complexes were independent predictors. These permit early identification of high risks patients of new atrial fibrillation and other events, thus promoting appropriate preventive treatment. / published_or_final_version / Medicine / Master / Master of Philosophy

The purpose of this dissertation was to examine factors associated with cardiovascular disease (CVD) risk among emerging adults in college aged 18-25 years. CVD risks that develop during this period often persist into adulthood making it an ideal time to target CVD prevention. The specific aims of this dissertation were to 1) explore perceptions of cardiovascular risk among emerging adult men in college; 2) compare differences in unhealthy behaviors and obesity between emerging adults in college living in rural, Appalachian Kentucky and urban Fayette County, Kentucky; and 3) compare measures of general and abdominal obesity in predicting blood pressure among emerging adults in college. Specific Aim One was addressed by a qualitative study of perceptions of cardiovascular risk in 10 emerging adult males in college. Specific Aims Two and Three were addressed by a study of emerging adult college students living in rural, Appalachian and urban Fayette County, Kentucky. We hypothesized that students in rural, Appalachian Kentucky would engage in more unhealthy behaviors and be obese due to living in an austere environment with barriers to healthy behaviors. Although obesity and hypertension are known to be related, researchers have not determined whether body fat distribution, general vs. abdominal, is predictive of blood pressure in emerging adults. Knowing which body fat distribution is the strongest predictor of blood pressure may help in evaluating cardiovascular risk in emerging adults. Emerging adult men emphasized difficulty engaging in CVD health behaviors while attending college and choose to ignore long-term CVD risk. Overcoming college-specific and developmental barriers to engaging in healthy behaviors is critical to reducing cardiovascular risk in this population. Students living in rural, Appalachian Kentucky had more CVD risk behaviors and more were obese compared to those in urban Fayette County, Kentucky. Reducing CVD risk behaviors and obesity among students in rural Appalachian Kentucky may help decrease the high burden of CVD in this region. Findings suggest that waist circumference was the best predictor of systolic blood pressure among emerging adults in college.

published_or_final_version / abstract / Medical Sciences / Master / Master of Medical Sciences

The prevalence of obesity in both the developed and developing world have increased, which leads to diverse health outcomes and is placing a heavy burden on the economy. Abdominal obesity proved to be one of the main features in predicting metabolic and cardiovascular disease (CVD) risk and may be the link that unifies the metabolic syndrome (MS) through pro-inflammatory pathways. While the pathogenesis of the MS and each of its components are complex and not well understood, abdominal obesity remains the mechanism that relates to increased lipolysis causing the liver to increase blood glucose and very low lipoprotein output. This in turns leads to raised blood glucose, triglycerides, low-density lipoprotein cholesterol (LDL-C), blood pressure and inflammatory markers (C-reactive protein, interleukin-6 and tumor necrosis factor-a) and decreased high-density lipoprotein cholesterol (HDL-C). Prevention of the metabolic syndrome and treatment of its main characteristics are now considered of utmost importance in order to combat the increased CVD risk and all-cause mortality. Decreasing sedentary behaviour through regular physical activity is a key element in successful treatment of obesity through an increase in energy expenditure, but the ability to decrease low-grade systemic inflammation may be an even greater outcome. Aims The aims of this study was firstly, to determine by means of a literature review, how obesity could be related to a state of chronic systemic inflammation (increased CRP and IL-6). Secondly to determine whether physical activity could serve as a suitable method to decrease inflammation associated with obesity and related disorders. Thirdly to determine if abdominal obesity is a predictor of the metabolic syndrome and CVD and finally, to determine if measures of obesity can predict risk for the metabolic syndrome and CVD risk. Methods For this review study, a computer-assisted literature search were utilized to identify research published between 1990 and 2005. the following databases were utilized for the search: NEXUS, Science Direct, PubMed and Medline. Keywords related to obesity (abdominal obesity, overweight), metabolic syndrome (insulin resistance syndrome, dysmetabolic syndrome, syndrome X), cardiovascular disease (coronary heart disease, coronary artery disease), cardiovascular risk factors (hypertension, dyslipidemia, diabetes mellitus, physical activity), inflammatory markers (CRP, IL-6, chronic low-grade inflammation) and physical activity (fitness, exercise and training) were included as part of the search, including the references identified by previous reviewers (not identified as part of the computerized literature search). Results and conclusions Several research studies concluded that obesity could be an inflammatory disorder due to low-grade systemic inflammation. Adipose tissue is known to be a sectretory organ producing cytokines, acute phase reactants and other circulating factors. The synthesis of adipose tissue TNF-a could induce the production of IL-6, CRP and other acute phase reactants. CRP is a acute phase reactant, synthesized primarily in hepatocytes and secreted by the liver in response to a variety of inflammatory cytokines of which IL-6 and TNF-a are mainly involved. CRP increases rapidly in response to trauma, inflammation and infection. Thus, enhanced levels of CRP can be used as a marker of inflammation. Several studies of large population cohorts provide evidence for an inverse, independent dose-response relation between plasma CRP concentration and level of physical activity in both men and women. Trends for decreased IL-6, TNF-a and CRP concentrations were linear with increasing amounts of reported exercise in most of the research studies, physical activity proved effective in lowering measures of adiposity (BMI, WHR, WC and percentage body fat) and obesity related inflammatory markers (CRP & IL-6). Thereby indicating a potential anti-inflammatory effect. In the studies reviewed in this article abdominal obesity is identified as a predictor and independent risk factor for CVD in both men and women. High levels of deep abdominal fat have also been correlated with components of the metabolic syndrome, glucose intolerance, hyperinsulinemia, hypertension, diabetes, increases in plasma triglyceride levels and a decrease in HDL-C levels (dyslipidemia) in many of the studies. Prospective epidemiological studies have revealed that abdominal obesity (determined by WC and WHR) conveys an independent prediction of CVD risk and is more relevant compared to general obesity (determined by BMI). Abdominal fat has been linked to metabolic risk factors like high systolic blood pressure, atherogenic dyslipidemia, with increased serum TG and decreased HDL-C, and glucose intolerance. Although magnetic resonance imaging (MRI) and computerized tomography (CT) have been used successfully in many studies to measure adipose compartments of the abdomen (subcutaneous and visceral fat), anthropometrical measures like WHR and WC have been proven to be an effective measure in predicting the metabolic syndrome. WC has also been included in the metabolic syndrome definitions of the WHO, ATP Ill and new IDF. / The prevalence of obesity in both the developed and developing world have increased, which leads to diverse health outcomes and is placing a heavy burden on the economy. Abdominal obesity proved to be one of the main features in predicting metabolic and cardiovascular disease (CVD) risk and may be the link that unifies the metabolic syndrome (MS) through pro-inflammatory pathways. While the pathogenesis of the MS and each of its components are complex and not well understood, abdominal obesity remains the mechanism that relates to increased lipolysis causing the liver to increase blood glucose and very low lipoprotein output. This in turns leads to raised blood glucose, triglycerides, low-density lipoprotein cholesterol (LDL-C), blood pressure and inflammatory markers (C-reactive protein, interleukin-6 and tumor necrosis factor-a) and decreased high-density lipoprotein cholesterol (HDL-C). Prevention of the metabolic syndrome and treatment of its main characteristics are now considered of utmost importance in order to combat the increased CVD risk and all-cause mortality. Decreasing sedentary behaviour through regular physical activity is a key element in successful treatment of obesity through an increase in energy expenditure, but the ability to decrease low-grade systemic inflammation may be an even greater outcome. Aims The aims of this study was firstly, to determine by means of a literature review, how obesity could be related to a state of chronic systemic inflammation (increased CRP and IL-6). Secondly to determine whether physical activity could serve as a suitable method to decrease inflammation associated with obesity and related disorders. Thirdly to determine if abdominal obesity is a predictor of the metabolic syndrome and CVD and finally, to determine if measures of obesity can predict risk for the metabolic syndrome and CVD risk. Methods For this review study, a computer-assisted literature search were utilized to identify research published between 1990 and 2005. the following databases were utilized for the search: NEXUS, Science Direct, PubMed and Medline. Keywords related to obesity (abdominal obesity, overweight), metabolic syndrome (insulin resistance syndrome, dysmetabolic syndrome, syndrome X), cardiovascular disease (coronary heart disease, coronary artery disease), cardiovascular risk factors (hypertension, dyslipidemia, diabetes mellitus, physical activity), inflammatory markers (CRP, IL-6, chronic low-grade inflammation) and physical activity (fitness, exercise and training) were included as part of the search, including the references identified by previous reviewers (not identified as part of the computerized literature search). Results and conclusions Several research studies concluded that obesity could be an inflammatory disorder due to low-grade systemic inflammation. Adipose tissue is known to be a sectretory organ producing cytokines, acute phase reactants and other circulating factors. The synthesis of adipose tissue TNF-a could induce the production of IL-6, CRP and other acute phase reactants. CRP is a acute phase reactant, synthesized primarily in hepatocytes and secreted by the liver in response to a variety of inflammatory cytokines of which IL-6 and TNF-a are mainly involved. CRP increases rapidly in response to trauma, inflammation and infection. Thus, enhanced levels of CRP can be used as a marker of inflammation. Several studies of large population cohorts provide evidence for an inverse, independent dose-response relation between plasma CRP concentration and level of physical activity in both men and women. Trends for decreased IL-6, TNF-a and CRP concentrations were linear with increasing amounts of reported exercise in most of the research studies, physical activity proved effective in lowering measures of adiposity (BMI, WHR, WC and percentage body fat) and obesity related inflammatory markers (CRP & IL-6). Thereby indicating a potential anti-inflammatory effect. In the studies reviewed in this article abdominal obesity is identified as a predictor and independent risk factor for CVD in both men and women. High levels of deep abdominal fat have also been correlated with components of the metabolic syndrome, glucose intolerance, hyperinsulinemia, hypertension, diabetes, increases in plasma triglyceride levels and a decrease in HDL-C levels (dyslipidemia) in many of the studies. Prospective epidemiological studies have revealed that abdominal obesity (determined by WC and WHR) conveys an independent prediction of CVD risk and is more relevant compared to general obesity (determined by BMI). Abdominal fat has been linked to metabolic risk factors like high systolic blood pressure, atherogenic dyslipidemia, with increased serum TG and decreased HDL-C, and glucose intolerance. Although magnetic resonance imaging (MRI) and computerized tomography (CT) have been used successfully in many studies to measure adipose compartments of the abdomen (subcutaneous and visceral fat), anthropometrical measures like WHR and WC have been proven to be an effective measure in predicting the metabolic syndrome. WC has also been included in the metabolic syndrome definitions of the WHO, ATP Ill and new IDF. / Thesis (M.A. (Human Movement Science))--North-West University, Potchefstroom Campus, 2006.

The global burden of heart disease increases every year. It has been estimated that by the year 2020, coronary artery disease (CAD) will be the number one cause of death worldwide. Indian populations throughout the world have the highest prevalence of CAD and early onset of the disease compared to other ethnic groups. Glutathione S-transferases (GSTs) detoxify environmental agents which influence the onset and progression of disease. Dysfunctional detoxification enzymes are responsible for prolonged exposure to reactive molecules and can contribute to endothelial damage, an underlying factor in CAD. Uncoupling proteins (UCPs) 2 and 3 play an important role in the regulation of oxidative stress which contributes to chronic inflammation. Coronary artery disease is a chronic inflammatory disorder characterized by elevated levels of C-reactive protein (CRP) and pro-inflammatory cytokines such as interleukin 6 (IL-6). Polymorphisms of these genes have been linked to CAD and other chronic diseases. Statins, metabolised in the liver, are the most commonly used drug to control atherosclerosis progression in CAD patients. The pleiotropic effects of statins have been attributed to both favourable and adverse outcomes in CAD patients particularly related to myopathy and hepatotoxicity. All patients (n=102) recruited into this study were South African Indian males. A corresponding age-, gender- and ethnicity-matched control group (n=100) was also recruited. The frequency of the GSTM1 +/0, GSTP1 A105/G105, IL6 -174G/C and CRP -390C/A/T genotypes was assessed by polymerase chain reaction (PCR) and PCR restriction fragment length polymorphism (PCR-RFLP). For the in vitro study, the biological effect of atorvastatin on HepG2 cells was assessed. The metabolic activity, cytotoxicity, oxidative stress and nitric oxide production was assessed by the ATP, lactate dehydrogenase (LDH), thiobarbituric acid reactive substance (TBARS) and Griess assays, respectively. The profile of 84 microRNA (miRNA) species was evaluated using the miRNA Pathway Finder PCR SuperArray. The predicted targets of up-regulated miRNAs were determined using the online software, Targetscan. The mRNA levels of guanidinoacetoacetate (GAMT), arginine glycine aminotransferase (AGAT) and spermine oxidase (SMO) were determined using quantitative PCR. Western blotting was used to determine GAMT and phosphorylated p53 levels in treated cells. The GSTM1 0/0 and GSTP1 A105/A105 genotypes occurred at higher frequencies in CAD patients compared with the control group (36% vs. 18% and 65% vs. 48%, respectively). A significant association with CAD was observed in GSTM1 0/0 (odds ratio (OR)=2.593; 95% confidence interval (CI) 1.353 - 4.971; p=0.0043) and GSTP1 A105/A105 OR=0.6011; 95% CI 0.3803 - 0.9503; p=0.0377). We found a significant association between smoking and CAD; the presence of either of the respective genotypes together with smoking increased the CAD risk (GSTP1 A105 relative risk (RR)=1.382; 95% CI 0.958 - 1.994; p=0.0987 and GSTM1 null RR=1.725; 95% CI 1.044 - 2.851; p=0.0221). The UCP2 -866G/A and UCP3 -55C/C genotypes occurred at highest frequency in CAD patients (59% vs. 52% and 66% vs. controls: 63% respectively) and did not influence the risk of CAD. Homozygous UCP3 -55T/T genotype was associated with highest fasting glucose (11.87±3.7mmol/L vs. C/C:6.11±0.27mmol/L and C/T:6.48±0.57mmol/L, p=0.0025), HbA1c (10.05±2.57% vs. C/C:6.44±0.21% and C/T:6.76±0.35%, p=0.0006) and triglycerides (6.47±1.7mmol/Lvs. C/C:2.33±0.17mmol/L and C/T:2.06±0.25mmol/L, p<0.0001) in CAD patients. A significant association between the G allele of the IL6 -174 polymorphism and non-diabetic CAD patients was found (p=0.0431 odds ratio: 1.307, 95% CI: 1.047-1.632). A significant association with the C allele of the -390 CRP triallelic variants and CAD (p=0.021 odds ratio: 1.75, 95% CI: 1.109-2.778) was also found using a contingency of the C allele vs. the minor A and T allele frequencies. The strength of the association of the C allele with non- diabetic CAD subjects was much higher (p=0.0048 odds ratio: 2.634, 95% CI: 1.350-5.138). Circulating median levels of IL-6 (0.9 (0.90, 0.91) pg/ml and 0.9 (0.87, 0.92) pg/ml) and CRP (5.65 (1.9, 8.2) mg/l and 2.90 (1.93, 8.35) mg/l) were similar between CAD patients and controls, respectively. A similar finding was observed between controls and non-diabetic CAD subjects. Levels of IL-6 and CRP in CAD subjects were not significantly influenced by polymorphic variants of IL-6 and CRP. In the control group, the level of IL-6 was significantly influenced by the IL6 -174 G allele (p=0.0002) and the CRP -390 C allele (p=0.0416), where subjects with the homozygous GG (0.9 (0.9, 1,78) pg/ml) and CC (0.9 (0.9, 0.95) pg/ml) genotype had higher levels than the C allele carriers (0.9 (0.64, 0.91) pg/ml) or A and T carriers (0.9 (0.69, 0.91) pg/ml) combined. The lowest measure of proliferation/metabolism in HepG2 cells was observed at 20μM atorvastatin, with 82±9.8% viability. The level of cytotoxicity was increased in statin treated cells from 0.95±0.02 units to 1.11±0.03 units (p=0.001) and malondialdehyde levels was reduced from 0.133±0.003 units to 0.126±0.005 units (p=0.009) whilst nitrite levels were elevated (0.0312±0.003 units vs. control: 0.027±0.001 units, p=0.044). MicroRNAs most significantly upregulated by atorvastatin included miR-302a-3p (3.05-fold), miR-302c-3p (3.61-fold), miR-124-3p (3.90-fold) and miR-222-3p (4.4-fold); miR-19a-3p, miR-101-3p and let-7g were downregulated (3.63-fold, 2.92-fold, 2.81-fold, respectively). A list of miRNA targets identified included those with a role in metabolism and inflammation. The miR-124a specifically targets the mRNA of GAMT and SMO. / Thesis (M.Med.)-University of KwaZulu-Natal, Durban, 2012.

The emphasis of the study was to determine the degree of correlation between the Conicity Index and known risk factors for heart disease. Conicity Index was shown in one study to be a useful screening tool in assessing the relationship between body composition and risk for heart disease. This study was designed to provide nutrition education and teach lifestyle modification to fourteen Veteran's Affairs patients. Change in specific risk factors including Waist-to-Hip Ratio, Body Mass Index, serum lipid levels and dietary intakes were correlated with change in Conicity Index over the six month study. Results from the present study did not suggest that the Conicity Index would serve as an effective screening tool for the present population. Mean body weight, body mass index, hip circumference, cholesterol and triglyceride levels, total caloric and fat intake all decreased significantly as a result of the program. Through nutrition education, behavior modification and group support, the risk for heart disease was successfully modified in this population. / Department of Family and Consumer Sciences

Hospitals have been directed by the Centers for Disease Control and Prevention and the Occupational Safety and Health Administration to educate health care workers about bloodborne pathogens. The purpose of this descriptive study is to assess the knowledge and concerns of health care workers regarding bloodborne pathogens and describe the application of universal precautions in practice.Orem's Theory of Self-Care was used for the framework because nurses are self-care agents, responsible for personal well-being, as well as patient's well-being. The instrument "Bloodborne Pathogens and Universal Precautions Test" was used to collect the data (Jones & Ryan, 1992). A convenience sample of twelve hospitals within the state of Indiana with four hundred-fifty licensed nursing personnel responded to the questionnaire.Findings revealed a mean score of 84.5 on the knowledge scale. Perception of availability of supplies and equipment ranged from consistently available (68.5% to 98.7%) to never available (0.0% to 0.9%). Perception of application of universal precautions ranged from consistently applied (32.4% to 84.0%) to never applied (0.0% to 9.5%). Content analysis of concerns related by health care workers included fear of contagion and accidental injury.Conclusions indicated knowledge of transmission and availability of supplies do not ensure compliance with universal precautions. Increased knowledge levels will decrease, but not eliminate, fear of contagion.Universal precaution training alone does not adequately prepare health care workers for HIV/AIDS patients. On-going educational endeavors are needed, including affective concerns. / School of Nursing

This study examined percent fat, fat distribution, and resting cortisol concentrations between personality types for coronary artery disease (CAD) risk. Males (n= 29, 43 ± 8.8 years) selected through the Jenkins Activity Survey, scoring >_ 75th percentile (Type A=15) or S 30th percentile (Type B=14), had the following measures: percent fat, lipid profile, and waist-to-hip ratio. Each hour, heart rate, blood pressure (SBP, DBP), and cortisol were measured. A prediction model determined risk of CAD. Type A had a tendency to have higher DBP, but was only significant at one time point (F= 3.390, p= .022). Type B showed significantly higher total (t= -2.688, p= .012) and LDL cholesterol (t= -3.612, p= .001). Although we did not show many significant differences between groups, within groups, many significant correlations were detected among the variables measured. Further studies will justify the associations between percent fat, fat distribution, and cortisol across personality types. / School of Physical Education

Access to abstract permanently restricted to Ball State community only / Access to thesis permanently restricted to Ball State community only / School of Physical Education, Sport, and Exercise Science