Thesis (doctoral) - Universität, Rostock, 2005. / Includes bibliographical references (p. [187]-214).

Treament with oral anticoagulation is highly effective in reducing the burden of thromboembolic complications in several clinical conditions. The number of patients receiving oral anticoagulation is growing steadily. InSwedenabout 1.5 percent of the population receives treatment. Although the treatment is highly effective in preventing thromboembolic complications, it is also associated with a substantial increase in the risk of bleeding. In clinical practice every physician has to balance the potential benefit of treatment against the risk of bleeding complications in the individual patient. To aid in this decision making, risk scores addressing the likelihood of thromboembolic events, as well as the risk of bleeding complications, have been developed. These scores are imperfect and, to some degree limited by the fact that the risk factors predictive of thromboembolic events are also often associated with bleeding complications. The addition of biomarkers has the potential to increase the predictive ability of risk scores and further enhance the net benefit of oral anticoagulant treatment in the individual patient. In this thesis several potential biomarkers for thromoboembolic and haemorrhagic complications of anticoagulant therapy have been investigated in a longitudinal cohort study of 719 patients with a median follow-up time of 4.2 years. Thrombomodulin is a key component in the generation of activated protein C and hence, a coagulation inhibitor. Conversely, it is also a key component in the inhibition of fibrinolysis by activation of trombin-activated fibrinolysis inhibitor. In warfarin-treated patients we demonstrate that thrombomodulin predicts an increased risk of bleeding complications, but not cardiovascular events. Thus, thrombomodulin has potential as a biomarker specifically for bleeding complications. Von Willebrand factor plays a central and intricate role in the aggregation of platelets and low levels of VWF have been associated with bleeding as a manifestation of von Willebrand’s disease. In our study we noted that high levels of von Willebrand factor predict an increased risk of cardiovascular as well as all-cause mortality, possibly as an expression of endothelial dysfunction. We also noted that high levels of WVF seem to be associated with serious bleeding complications. Decreased renal function is usually measured by an increase in the levels of creatinine and cystatin C, or a decrease in the calculated glomerular filtration rate. A decrease in kidney function is regarded as a marker of an increased risk of bleeding complications. We investigated all the mentioned markers of kidney function and no association with bleeding complications became apparent. However, a clear association between a decrease in kidney function and mortality was noted. Our findings indicate that the emphasis on impaired kidney function as a risk marker needs to be shifted from bleeding complications toward thromboembolic events. Fibrinolysis is important in containing coagulation and several constituents of the fibrinolytic pathway have been shown to predict cardiovascular events and mortality. We found that fibrinolytic factors seem to predict cardiovascular events in patients with oral anticoagulation and that D-dimer also predicts bleeding complications. In conclusion, we have found several biomarkers which exhibit different predictive abilities in patients with oral anticoagulation. It is likely that biomarkers, either alone, in combination, or as ancillary components of risk scores, can contribute to improved risk stratification in patients with oral anticoagulation.

Background: Diabetes is one of the leading causes of death and disability among chronic diseases in the United States. Type 2 diabetes, which accounts for 90-95% of all diabetes cases, is a preventable form of disease which can be controlled through diet and physical activity. But residents of places such as ‘food deserts’, with no access to fresh food, often bear the burden of chronic diseases such as diabetes. There have been very few studies which have particularly looked at the association between food environment and diabetes prevalence in such deprived areas. Objective: The study investigated the association between living in food desert and developing diabetes or dying from the disease. It considered factors such as access to grocery stores and supermarkets, convenience stores, food joints and owning a personal vehicle that might affect diabetes related morbidity and mortality. It has also looked at factors such as income and race which might influence the association. Methodology: The study emphasizes on the lack of access to food, in low income and deprived neighborhoods and its impact on diabetes mortality and morbidity at the micro level of census tracts in Fulton County, Georgia. Diabetes related data was obtained from OASIS and Fulton County Department of Health and Wellness for the years 1994-2010 for 204 census tracts of Fulton County. Data for food desert distribution was extracted from the ‘Food desert Locator’ tool of the United States Department of Agriculture (USDA). Data on food stores was obtained through ReferenceUSA. Demographic information was acquired from American Fact Finder of the US Census Bureau. SPSS version 21 was used to calculate Pearson’s correlation to find the association between food environment and diabetes as well as to see whether there is an association between income and vehicle ownership with diabetes occurrence. ArcGIS 10.1 was used to represent data as maps showing the geographical distribution of various factors across the County and their association with the occurrence of diabetes. Results: Low income African American dominated census tracts which have been designated as food deserts have a higher occurrence of morbidity and mortality from diabetes. The correlation between number of supermarkets and grocery stores, convenience stores and full service restaurants has no statistically significant relation with diabetes. Similarly, there is no statistically significant relation between car ownership and diabetes. But the relationship between income and diabetes has a statistical significance. Conclusion: This study did not find any significant statistical association between diabetes and living in food desert. But from the GIS maps it can be observed that the number of food markets (supermarkets and grocery stores) is much less in the low income tracts than elsewhere and these are also the tracts which have higher occurrence of diabetes. Similarly, the numbers of convenience stores, which usually do not have a healthy collection of food, are more in the low income neighborhoods. The weak association between the factors studied might be because other factors such as education and access to healthcare have not been considered for this study. More research in this field is required to get a better picture of the diabetes health status in food desert areas.

Background: Recently, some US cohorts have shown a moderate association between red and processed meat consumption and mortality supporting the results of previous studies among vegetarians. The aim of this study was to examine the association of red meat, processed meat, and poultry consumption with the risk of early death in the European Prospective Investigation into Cancer and Nutrition (EPIC). Methods: Included in the analysis were 448,568 men and women without prevalent cancer, stroke, or myocardial infarction, and with complete information on diet, smoking, physical activity and body mass index, who were between 35 and 69 years old at baseline. Cox proportional hazards regression was used to examine the association of meat consumption with all-cause and cause-specific mortality. Results: As of June 2009, 26,344 deaths were observed. After multivariate adjustment, a high consumption of red meat was related to higher all-cause mortality (hazard ratio (HR) = 1.14, 95% confidence interval (CI) 1.01 to 1.28, 160+ versus 10 to 19.9 g/day), and the association was stronger for processed meat (HR = 1.44, 95% CI 1.24 to 1.66, 160+ versus 10 to 19.9 g/day). After correction for measurement error, higher all-cause mortality remained significant only for processed meat (HR = 1.18, 95% CI 1.11 to 1.25, per 50 g/d). We estimated that 3.3% (95% CI 1.5% to 5.0%) of deaths could be prevented if all participants had a processed meat consumption of less than 20 g/day. Significant associations with processed meat intake were observed for cardiovascular diseases, cancer, and 'other causes of death'. The consumption of poultry was not related to all-cause mortality. Conclusions: The results of our analysis support a moderate positive association between processed meat consumption and mortality, in particular due to cardiovascular diseases, but also to cancer.

Disturbances in mineral metabolism contribute to vascular calcification and mortality risk in chronic kidney disease (CKD). Serum levels of fibroblast growth factor (FGF)23, a bone derived, phosphaturic peptide, are associated with cardiovascular mortality in CKD. Membrane bound klotho(KL) is an obligate co receptor for FGF23 signaling in the kidney. To study aspects of FGF23 in mild to moderate impairment of renal function we have analyzed FGF23, estimated glomerular filtration rate (eGFR), parathyroid hormone(PTH), 1,25 (OH)2 vitamin D (1,25D), calcium and phosphate in one patient with a FGF23 producing tumor, before and after tumor removal (study 1), in 72 CKD patients with varying degree of renal dysfunction (study 2), in 9 healthy kidney donors, before and after nephrectomy (study 3). We also analyzed FGF23 (study 4), and performed genotyping of 27 single nucleotide polymorphisms (SNP) of the KL gene (study 5) in 2838 elderly Swedish men (MrOs study) and examined the association with mortality. FGF23 normalizes in 30-45 minutes after removal of a FGF23 producing tumor (study 1). 1,25D increases in hours and remains elevated months, even when the other parameters have normalized. FGF23 increase early in CKD, initially slowly, in correlation with PTH, but exponentially when hyperphosphatemia ensues (study 2). After unilateral nephrectomy (study 3) mineral homeostasis remain stable, initially due to a rise in PTH and later to an increase in FGF23. FGF23 levels are not correlated with mortality in elderly men after adjustment for eGFR, but with mortality due to cardiovascular disease, even in persons with normal eGFR (study 4). Polymorphism of the KL gene do not correlate with increased mortality risk in elderly men (study 5), but there is a modulating effect on FGF23 levels. FGF23 is of importance in maintaining phosphate homeostasis as renal function declines. It is co regulated with PTH until advanced renal dysfunction, and adjust the 1,25D to the actual GFR. FGF23 is associated with cardiovascular mortality. Further studies are needed to determine the mechanism, and if reduction of FGF23 by reducing phosphate intake may be beneficial even in persons with mild to moderate renal function.

There is a well-established connection between adult mortality and the conditions an individual is exposed to while in utero. There is a wealth of research that connects conditions such as asthma and allergies, mortality due to heart disease and diagnoses of schizophrenia to conditions during an individual?s early life and even their time in utero. The aim of this dissertation is to see if this same connection can be made to infant mortality, and further will there be any connection in contemporary cohorts? I use the Linked Birth/Infant Death dataset available from the Centers for Disease Control (CDC) for the years 2000 to 2004. This dissertation specifically uses the dependent variable "cause specific infant death" with various measures of the time the infant was born or was in utero. I undertake three multinomial logistic regression models with the dependent variable "cause specific infant death." I then proceed to a multilevel multinomial logistic regression model using state-level climate measures at the second level. I conclude with the construction of maps displaying the spatial relationship between infant mortality and climate. The first analysis uses the independent variable of interest "month of birth," the second analysis uses the independent variable of interest "months of first trimester," and the last level-one analysis uses the independent variable of interest "months of third trimester." After running all three models, I determined that the most effective independent variable of interest is "month of birth," which I use in a multilevel logistic regression model. The multilevel model uses the month of birth variable at level-one and incorporates state level measures of climate at the second level. I find that the humidity index and the temperature index are negatively associated with the month of birth variable and cause specific infant death variables, meaning that the higher these indices, the more the benefit to an infant's chances of survival. The wind index is consistently positive, meaning that the interaction of wind with cause specific infant death and month of birth is detrimental to an infant's survival. The last methods chapter shows the spatial relationship between infant mortality and climate. In this chapter I find that infant mortality in the United States is concentrated in the Southern U.S., which is also where there is a concentration of high temperature states. The connections between wind and humidity with the infant mortality rate are less consistent.

Thesis (M.A.) in Mathematics--University of Maine, 2004. / Includes vita. Includes bibliographical references (leaf 51).

Thesis (Ph. D.)--University of Hong Kong, 2010. / Includes bibliographical references (p. [301]-321). Also available in print.

Heterogeneity within the Hispanic population in the United States (US) has important implications for health. Despite the empirical work examining heterogeneity in Hispanic health and mortality by nativity, generational status, and country of origin, relatively little research has been devoted to understanding if and how racial identification impacts Hispanic health outcomes. Racial differences in health and mortality are well documented throughout the literature, particularly for non-Hispanic blacks and non-Hispanic whites. Meanwhile, current socio-demographic and health literature commonly compares US non-Hispanic racial groups with people who claim Hispanic ethnicity, the latter of whom are comprised of multiple racial groups. Thus, this dissertation examines the racial heterogeneity of the Hispanic population and the implications of race for physical health among Hispanics. Using the National Health Interview Survey and the National Centers for Health Statistics Linked Birth/Infant Death Cohort Files, the key findings of this dissertation are (1) racial identity is associated with socioeconomic status among Hispanics, (2) infants born to Hispanic black mothers displayed statistically significant higher odds of being born with low birth weight when compared to infants born to Hispanic white mothers, (3) there is evidence of weathering in the infant health of Hispanics, as measured using birth weight, (4) black-white disparities in the risk of infant mortality exist within the Hispanic population, (5) both Hispanic blacks and those of other races have greater odds of functional limitations than Hispanic whites and for Hispanic blacks; moreover, this disadvantage increases with age, (6) I show no race differences in the odds of hypertension or poorly self-assessed health status. In short, the results of this dissertation suggest that the social experience for Hispanic blacks and whites is different and that this difference affects health outcomes. It is imperative that future research and health policy recognize the racial heterogeneity of this population, in both empirical analyses and policy decisions regarding social influences on physical health. / text

The inverse association between individuals' own education and adverse health outcomes is well established, but the influence of other people's education -- particularly those with close social ties or who are family members -- and adult health outcomes is not. The material and non-material resources available to individuals via their own education likely are shared within a marriage to become resources at the household or family-level. Research on spousal education and adult health outcomes is sparse -- especially in the United States. Therefore, this dissertation examines how husbands and wives' education combine within marriage to influence each other's self-rated health and annual risk of death in the United States. The analyses utilize two nationally representative data sources: the National Health Interview Survey (NHIS) and the National Health Interview Survey Linked Mortality File (NHIS-LMF). Chapter Two establishes an inverse association between spousal education and poor/fair self-rated health among married adults in the United States. The results also showed that spousal education attenuated the association between one's own education and fair/poor self-rated health more for married women than married men and age-specific analyses revealed that these differences were largest among married persons ages 45-64. Chapter Three reveals that individuals' own education and their spouse's education each share an inverse association with the annual risk of death among married adults. Although this association generally does not vary by gender, spousal education apparently is a more important determinant of all-cause mortality risk among married non-Hispanic whites in comparison to married non-Hispanic blacks. Age-specific analyses also suggest that the influence of own and spousal education on adult mortality risk weakened with increasing age. Chapter Four assesses life expectancy differentials between men and women in different marital status groups at different points in the educational distribution. The results imply that spousal education substantially contributes to life expectancy disparities between married and unmarried persons. The results also imply that focusing only on the relationship between married persons' own education and life expectancy masks substantial heterogeneity within educational groups attributable to spousal education. Overall, the findings strongly suggest that education is a shared or household health resource among husbands and wives. / text