Family history (FH) is a risk factor for many diseases. Disease guidelines often include family history as important in assessing chronic disease risks, but the empirical evidence base to inform the routine use of family history in primary care in practice appears largely lacking. An environmental scan of how family history is represented in prevention guidelines for five conditions showed that, while family history is often included in guidelines, there is variation in the definition used, recommendation given and evidence cited. A dataset on cardiovascular health in women was analyzed to examine whether family history offers useful discrimination value above standard risk factors. Regression results showed that family history is an independent risk predictor for coronary heart disease which improves discrimination beyond classical clinical factors. However, the absolute amount of discriminatory ability alone or with other factors is moderate at best, raising issues regarding clinical utility.

Heart failure accounts for more deaths in the United States than any other pathology. Unfortunately, repairing the heart after pathological injury has become an overwhelming task for physicians and researchers to overcome. Fortunately, cellular cardiomyoplasty has emerged as a promising solution for sufferers of heart failure. Such a therapy is limited in efficacy due to poor engraftment efficiencies, however. To address this issue, we have developed a tissue engineered vehicle for cell delivery. Use of a "cardiac patch" resulted in localized and efficient delivery of human mesenchymal stem cells (hMSC) to infarcted myocardium. Application of a cardiac patch also attenuated adverse remodeling. Additionally, the culture of stem/progenitor cells within three dimensional collagen constructs led to modulations in cell function, which did not promote enhanced angiogenesis in vitro or in vivo. Despite enhanced neovessel formation, hMSC patches were more beneficial at augmenting myocardial repair compared to directly injected hMSC. Lastly, although hMSC represent an effective cell source option for enhancing cardiac repair they require additional purification and expansion steps which inherently delay the turnover before treatment. Therefore, suitable cell alternative are being sought. Human embryonic stem cell derived mesenchymal (B4) cells display several phenotypic similarities to hMSC. B4 progenitor cells responded similarly to hMSC in 3D culture. In addition B4 progenitor cell patch application to infarcted myocardium resulted in similar indices of repair compared to hMSC. Thus, a tissue engineering approach represents an effective cell delivery strategy and induces modulations in cell function which may demonstrate pathological significance.

Thesis (Ph. D.)--University of Missouri-Columbia, 2001. / Typescript. Vita. Includes bibliographical references (leaves 157-169). Also available on the Internet.

Thesis (Ph. D.)--University of Missouri-Columbia, 2001. / Typescript. Vita. Includes bibliographical references (leaves 157-169). Also available on the Internet.

Thesis (M. Phil.)--Hong Kong University of Science and Technology, 2003. / Includes bibliographical references (leaves 99-121). Also available in electronic version. Access restricted to campus users.

The purpose of this thesis was to assess the prevalence and management of established cardiovascular (CV) risk factors and the prevalence and influence of self-reported markers (number of teeth and frequency of gum bleeding) of periodontal disease (PD), a less explored CV risk factor, in patients with stable chronic coronary heart disease (CHD). We studied patients from the global STabilization of Atherosclerotic plaque By Initiation of darapLadIb TherapY (STABILITY) trial (n=15,828), in which patients with stable chronic CHD were randomized to either darapladib or placebo. Our studies were performed using descriptive statistics and multivariable linear, logistic and Cox regression models. The use of secondary preventive medications was generally high across the whole study population. Despite this, CV risk factors were highly prevalent, including obesity, hypertension and hypercholesterolemia. Achievement of guideline-recommended treatment targets was lacking and little improvement was seen throughout the study duration. Approximately 40% of patients reported having <15 remaining teeth and 25% reported gum bleeding. More tooth loss was associated with a greater CV risk factor burden after adjustment, while the associations for gum bleeding were less evident. After multivariable adjustment for CV risk factors and socioeconomic status, more tooth loss was associated with an increased risk of major adverse CV events (a composite of CV death, myocardial infarction and stroke), CV mortality, all-cause mortality and fatal or non-fatal stroke. We found associations between a higher degree of tooth loss and elevated levels of several prognostic biomarkers known to reflect various pathophysiological mechanisms involved in CV morbidity and mortality. Most biomarkers had little attenuating effect on the relationship between tooth loss and outcomes in a multivariable model. In conclusion, we found an inadequate CV risk factor control despite a high use of evidence-based pharmacological therapies, likely to explain some of the excess risk in CHD patients. Further, we demonstrated a high prevalence of PD markers, tooth loss in particular, that were associated with a wide range of established CV risk factors, prognostic biomarkers and outcomes. Collectively, these findings indicate that tooth loss may be a significant risk factor among patients with stable chronic CHD.

published_or_final_version / Medicine / Master / Master of Research in Medicine

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

published_or_final_version / abstract / Medicine / Master / Master of Philosophy

published_or_final_version / Community Medicine / Doctoral / Doctor of Philosophy