OBJETIVOS: Comparar as respostas do Teste de Esforço Cardiopulmonar (TECP) em imersão, numa esteira subaquáticas, com as de solo; investigar e entender o desempenho cardiorrespiratório de coronariopatas (DAC) durante esforço em imersão comparando-os aos do grupo de indivíduos saudáveis. Entender os procedimentos, materiais e equipamentos necessários na realização do teste em imersão e na coleta de dados reprodutíveis e confiáveis. MÉTODOS: O estudo contou com 40 indivíduos, sendo: 20 pacientes com diagnóstico médico de DAC, 63,7 ± 8,89 anos de idade e classificação I e II segundo New York Heart Association (NYHA) e 20 sujeitos saudáveis, 64,7 ± 7,09 anos; realizaram dois testes ergoespirométricos em uma instalação equipada com esteira no solo, piscina aquecida, esteira subaquática, analisador de gases e Eletrocardiograma (ECG). Foi calculado o Poder Estatístico do teste para ANOVA com erro beta de 0.861. Por ser um exame normatizado tecnicamente e reconhecidamente seguro, o primeiro teste foi realizado em esteira no solo de 3 a 7 dias deste, o segundo teste foi realizado em esteira subaquática com imersão ao nível do manúbrio, em uma piscina com temperatura controlada entre 33 e 34°C. Os dados foram coletados em 5 momentos expressivos: 1- Repouso; 2- Limiar Anaeróbio; 3- Ponto de Compensação Respiratória; 4- Esforço Máximo e 5- Recuperação. RESULTADOS: A análise de variância deste estudo revelou haver efeito principal para DAC nas variáveis: FC, VO2 e VCO2; (p > 0.01) em relação ao ambiente. O teste em imersão apresentou significância nas variáveis FC, VO2, VCO2 e VO2/FC (p > 0.01). As interações com estágio caracterizam o comportamento dos sujeitos ao longo do experimento e neste contexto, as variáveis PEB, FC, VO2, VCO2 e VO2/FC (p > 0.01) mostraram interações significantes entre estágio e ambiente. Em adição, há interação significante entre etiologia e estágio para as variáveis FC, VO2 e VCO2 (p > 0.01). DAC e saudáveis possuem comportamentos diferentes no decorrer dos estágios do experimento em relação a estas variáveis. Alterações eletrocardiográficas compatíveis com isquemia miocárdica ou arritmia não foram observadas e a Pressão Arterial Sistólica e Diastólica (PAS/D) não se alterou significativamente. Os indivíduos deste estudo tiveram percepção de esforço na Escala de Borg menor na água em todos os estágios do que em terra (p > 0.01). CONCLUSÃO: Os achados deste estudo mostram que os procedimentos operacionais, materiais e equipamentos utilizados no TECP em piscina produziram dados reprodutíveis, confiáveis e que atenderam as determinações estabelecidas no \"Clinician´s Guide to Cardioplulmonary Exercice Testing in Adults\". O esforço foi bem tolerado por todos os participantes, sem ocorrência de evento adverso. As diferenças estatísticas observadas nos testes na água contra os de solo nos levam a entender que o exercício em imersão pode ser realizado por pacientes com DAC e que os efeitos fisiológicos da imersão não causam qualquer risco para este grupo. Conclui-se também que por ser reprodutível e confiável, o teste em imersão pode ser adotado para prognosticar capacidades individuais de pacientes coronariopatas ao exercício dinâmico em piscina / OBJECTIVES: To compare responses to a Cardiopulmonary Exercise Test (CPX) conducted in water, (on a underwater treadmill), with the responses to the same tests conducted on land, (on a land treadmill); to investigate and assess the cardiorespiratory performance of coronary artery disease (CAD) patients while immersed in warm water when compared to the performance of healthy individuals; to assess the procedures, feasibility, resources and equipment required for conducting a CPX in individuals in water so as to collect reliable and replicable data. METHODS: The sample was comprised by 40 subjects, 20 of whom diagnosed with coronary artery disease (CAD) and aged 63.7 ± 8.89, functional class I and II (in compliance with the New York Heart Association [NYHA]), and 20 healthy subjects aged 64.7 ± 7.09. Two CPX tests were conducted in a facility equipped with a land treadmill, a warm pool, an underwater treadmill, a gas analyzer and an electrocardiogram (ECG) device. The statistical significances were calculated through a ANOVA test with (1 - beta) power of 0.861. As CPX is technically regulated and acknowledged as safe the first test was conducted on a land treadmill and the second test was conducted 3-7 days later on an underwater treadmill. Subjects were submerged in a temperature-controlled pool (33-34oC) with water at manubrium level. Data were collected at 5 relevant test stages or cardiorespiratory levels: 1- Rest; 2- Anaerobic Threshold (AT); 3- Respiratory Compensation Point (RCP); 4- Maximum Effort (ME); and 5- Recovery (R). FINDINGS: ANOVA analysis showed a major significance for CAD subjects regarding variables HB, VO2 and VCO2 (p < 0.01) in relation to the environment. The test performed with submerged patients showed some significance for variables HB, VO2, VCO2 and VO2/HB (p < 0.01). The stages for data collected featured the subjects performance throughout this experiment, and within the given context, variables RPE, HB, VO2, VCO2 and VO2/HB (p < 0.01) showed significant interactions between test stage and environment. Additionally, there was a significant interaction between the etiology and the test stage for variables HB, VO2 and VCO2 (p < 0.01). CAD patients and healthy subjects showed different performances throughout the test stages in relation to the referred variables. Electrocardiographic (ECG) changes that are compatible with myocardial ischemia or arrhythmia were not observed. Systolic and diastolic blood pressure (SDBP) did not show significant changes. The subjects of this study showed lower rates of Borg\'s perceived exertion scale in the water than at every one of the test stages on land (p < 0.01). CONCLUSION: This study show that the procedures, resources and equipment used during CPX conducted in a warm pool demonstrated to be feasible and yielded replicable and reliable data, which complied with the provisions of the \"Clinician´s Guide to Cardiopulmonary Exercise Testing in Adults\". The effort exerted was well tolerated by all the participants without any adverse events. Statistical differences observed in water versus on land allow us to conclude that patients with CAD are able to carry out physical activities in water and that the physiological effects of immersion do not present any risk for such patients. We may also conclude that given its replicability and reliability, CPX conducted in water may be used to diagnose and to estimate the exertion capability of CAD patients to perform dynamic exercise in a warm pool

Chan Fat-Yiu. / Thesis (M.Sc.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references (leaves 85-93). / Abstracts in English and Chinese. / ACKNOWLEDGEMENTS --- p.4 / SUMMARY --- p.5 / ABBREVIATIONS --- p.9 / LIST OF TABLES --- p.11 / LIST OF FIGURES --- p.13 / Chapter CHAPTER I --- INTRODUCTION --- p.14 / Chapter 1.1 --- The Historical Aspects of C-Reaction Protein --- p.15 / Chapter 1.2 --- Biochemistry of CRP --- p.16 / Chapter 1.3 --- Physiology of CRP --- p.18 / Chapter 1.4 --- Current Clinical Applications of Serum CRP Assay --- p.19 / Chapter 1.5 --- Recent Findings of CRP --- p.21 / Chapter 1.5.1 --- Pathophysiology of atherosclerosis --- p.22 / Chapter 1.5.2 --- A nother atherogenic risk factor: hs- CRP --- p.26 / Chapter 1.5.3 --- Can hs-CRP replace other risk factors? --- p.30 / Chapter 1.5.4 --- Altering hs-CRP result in medication --- p.32 / Chapter 1.6 --- Methods of Measurement of CRP Concentration --- p.33 / Chapter 1.7 --- Analytical Considerations in the Measurement of hs-CRP --- p.34 / Chapter CHAPTER II --- OBJECTIVES AND SIGNIFICANCE --- p.36 / Chapter 2.1 --- Objectives --- p.37 / Chapter 2.2 --- Issues and Problems --- p.37 / Chapter 2.3 --- Significance and Value of this Study --- p.38 / Chapter CHAPTER III --- MA TERIALS AND METHODS I Setting up the serum hs-CRP assay on the Hitachi 911 Analyzer --- p.39 / Chapter 3.1 --- Materials --- p.40 / Chapter 3.1.1 --- Reagents from Roche Diagnostics --- p.40 / Chapter 3.1.2 --- Reagents for the Beckman Coulter Array ® Analyzer --- p.40 / Chapter 3.1.3 --- In-house reagents --- p.41 / Chapter 3.2. --- Apparatus and Equipment --- p.41 / Chapter 3.2.1 --- Hitachi 911 Analyzer --- p.41 / Chapter 3.2.2 --- Beckman Coulter Array ® 360 Analyzer --- p.42 / Chapter 3.3 --- The Tina-quant a C-Reactive Protein (Latex) Ultrasensitive Assay --- p.42 / Chapter 3.3.1 --- Priniciple of the Dual-Radius Enhanced Latex (DuREL´ёØ) technology --- p.42 / Chapter 3.3.2 --- Assessment of Analytical Performance --- p.45 / Chapter CHAPTER IV --- MA TERIALS AND METHODS II Serum hs-CRP in Chinese chronic-renal-failure patients with atherosclerotic vascular disease or cardiac valve calcification --- p.48 / Chapter 4.1 --- Patient Recruitment --- p.49 / Chapter 4.2. --- Blood Specimens --- p.49 / Chapter 4.3 --- Assay Methods --- p.50 / Chapter 4.3.1 --- hs-CRP --- p.50 / Chapter 4.3.2 --- TC --- p.50 / Chapter 4.3.3 --- TG --- p.51 / Chapter 4.3.4 --- HDL-C --- p.51 / Chapter 4.3.5 --- LDL-C --- p.52 / Chapter 4.3.6 --- Apo A-1 --- p.52 / Chapter 4.3.7 --- Apo B --- p.53 / Chapter 4.3.8 --- Lp(a) --- p.53 / Chapter 4.4 --- Ultrasound measurement of carotid artery inter-media thickness --- p.53 / Chapter 4.5 --- Statistical analysis --- p.54 / Chapter CHAPTER V --- RESUTLSI Setting up the serum hs-CRP assay on the Hitachi 911 Analyzer --- p.55 / Chapter 5.1 --- Imprecision --- p.56 / Chapter 5.2 --- Linearity --- p.56 / Chapter 5.3 --- Recovery --- p.56 / Chapter 5.4 --- Detection Limit --- p.57 / Chapter 5.5 --- Carry-over --- p.57 / Chapter CHAPTER VI --- RESULTS II Serum hs-CRP in Chinese chronic-renal-failure patients with atherosclerotic vascular disease or cardiac valve calcification --- p.63 / Chapter 6.1 --- Patient Recruitment --- p.64 / Chapter 6.2 --- Chinese chronic-renal-failure patients with AVD --- p.64 / Chapter 6.3 --- Chinese chronic-renal-failure patients with CVC --- p.65 / Chapter CHAPTER VII --- DISCUSSION I Performance of the serum hs-CRP assay on the Hitachi 911 Analyzer --- p.75 / Chapter 7.1 --- "Imprecision, Detection Limit, Linearity, and Recovery of hs-CRP Assay" --- p.76 / Chapter 7.1.1 --- Imprecision --- p.76 / Chapter 7.1.2 --- Detection Limit --- p.76 / Chapter 7.1.3 --- Linearity --- p.76 / Chapter 7.1.4 --- Recovery --- p.77 / Chapter 7.2 --- Overall Performance --- p.77 / Chapter CHAPTER VIII --- DISCUSSION II Serum hs-CRP in Chinese chronic-renal-failure patients with atherosclerotic vascular disease or cardiac valve calcification --- p.79 / Chapter 8.1 --- CAPD Patients --- p.80 / Chapter 8.2 --- Serum hs-CRP Concentration of AVD and CVC Patients --- p.81 / Chapter 8.3 --- Other risk factors in AVD and CVC Patients --- p.82 / Chapter 8.4 --- Conclusion --- p.83 / REFERENCES --- p.85

Made available in DSpace on 2016-01-26T12:51:55Z (GMT). No. of bitstreams: 1 renataaccarini_dissert.pdf: 311540 bytes, checksum: 6e73d654b99ae5ef0d517cb9c91c09bb (MD5) Previous issue date: 2006-10-16 / Ainda permanecem controvérsias quanto à ligação causal e mecanismos fisiopatológicos que expliquem a associação entre Doença Periodontal e Doenças Cardiovasculares. Objetivo: Detectar a existência de associação entre doença periodontal ativa (DP) e ocorrência de Síndromes Coronárias Agudas (SCA). Casuística e Método: Foram avaliados 361 pacientes (57,3% do sexo masculino), com idades variando de 27 a 89 (média&#61617;DP=60,5&#61617;12,2 anos) internados na Unidade de Tratamento Intensivo de um Hospital de Ensino com quadro clínico e complementar de SCA. Todos foram submetidos a exame periodontal completo, no próprio ambiente da UTI sendo que 325 (90,0%) realizaram cinecoronariografia para confirmação diagnóstica e/ou programação de conduta terapêutica. O exame periodontal consistiu na avaliação de todos os dentes presentes na cavidade oral e dos seguintes parâmetros: profundidade clínica de sondagem, nível de inserção clinica, índice de placa e índice gengival. Resultados: Dos 325 pacientes, 91 (28,0%) apresentavam artérias coronárias isentas de obstrução ou com obstruções discretas (<= 50% de perda de diâmetro), havendo obstruções importantes nos 72,0% restantes. O teste exato de Fisher mostrou valor de P de 0,0245 e ODDS Ratio de 2,571 (IC 95% 1,192 a 5,547), ou seja, documentou-se cerca de 2,5 vezes mais possibilidade de presença de DP ativa no grupo com SCA e coronariopatia obstrutiva significante. Conclusão: Constatou-se associação significante entre presença de doença periodontal ativa e doença coronária obstrutiva de grau importante em pacientes com Síndrome Coronária Aguda, reforçando a importância da prevenção e tratamento adequado da doença periodontal, que deve ser considerada como fator de risco potencial na etiologia e na instabilização da placa aterosclerótica. Abstract Positive association between periodontal disease and coronary diseases is unclear concerning physiopathologic mechanisms and causal relationship. The aim of this study was to assess the association between active periodontal disease active and obstructive coronary artery disease in patients with acute coronary syndromes. Method: 361 (57.3% males; mean age 60.5+12.2) patients referred for diagnostic coronary vessel disease were assessed for periodontal disease and also submitted to coronary angiography with diagnostic and prognostic purposes. Each patient underwent a full-mouth periodontal examination which included gingival bleeding, plaque index, periodontal pocket depths, attachment levels and missing teeth. For statistical analysis was used the Exact Fisher test and was accepted an Alfa error of 5%. Results: 28% patients haven t significant coronary vessel obstructions (<50% diameter obstruction) and 72.0% had significant obstructive disease (>50% diameter obstruction). The Exact Fisher Test showed p-value of 0.0245 and ODDS Ratio of 2.571 (95%CI from 1.192 to 5.547). So there was a 2.5 fold increase in the chance for active periodontal disease in patients with significant obstructive coronary artery disease. Conclusion: Our study indicates a positive and significant association between periodontal disease and obstructive coronary disease among patients with acute coronary syndromes becoming periodontal disease as a potential risk factor in etiology and outcome of atherosclerotic plaque. Results of this and other investigations should be taken into account in the future researches in order to validate this association. / Ainda permanecem controvérsias quanto à ligação causal e mecanismos fisiopatológicos que expliquem a associação entre Doença Periodontal e Doenças Cardiovasculares. Objetivo: Detectar a existência de associação entre doença periodontal ativa (DP) e ocorrência de Síndromes Coronárias Agudas (SCA). Casuística e Método: Foram avaliados 361 pacientes (57,3% do sexo masculino), com idades variando de 27 a 89 (média DP=60,5 12,2 anos) internados na Unidade de Tratamento Intensivo de um Hospital de Ensino com quadro clínico e complementar de SCA. Todos foram submetidos a exame periodontal completo, no próprio ambiente da UTI sendo que 325 (90,0%) realizaram cinecoronariografia para confirmação diagnóstica e/ou programação de conduta terapêutica. O exame periodontal consistiu na avaliação de todos os dentes presentes na cavidade oral e dos seguintes parâmetros: profundidade clínica de sondagem, nível de inserção clinica, índice de placa e índice gengival. Resultados: Dos 325 pacientes, 91 (28,0%) apresentavam artérias coronárias isentas de obstrução ou com obstruções discretas (<= 50% de perda de diâmetro), havendo obstruções importantes nos 72,0% restantes. O teste exato de Fisher mostrou valor de P de 0,0245 e ODDS Ratio de 2,571 (IC 95% 1,192 a 5,547), ou seja, documentou-se cerca de 2,5 vezes mais possibilidade de presença de DP ativa no grupo com SCA e coronariopatia obstrutiva significante. Conclusão: Constatou-se associação significante entre presença de doença periodontal ativa e doença coronária obstrutiva de grau importante em pacientes com Síndrome Coronária Aguda, reforçando a importância da prevenção e tratamento adequado da doença periodontal, que deve ser considerada como fator de risco potencial na etiologia e na instabilização da placa aterosclerótica.

Diversos estudos mostram a associação entre doenças respiratórias e doença arterial coronariana (DAC). Além de fatores de risco semelhantes, como tabagismo e sedentarismo, ambos estão associadas à idade avançada e inflamação sistêmica. O uso de tomografia computadorizada coronariana (TCC) com múltiplos detectores é método diagnóstico de doença coronariana, descrevendo a anatomia e a gravidade da obstrução. Uma das formas de se estimar o risco de eventos cardiovasculares é o escore de cálcio coronariano (ECC) obtido neste exame. Muitos pacientes são encaminhados para realizar a TCC para investigar DAC ou classificar o risco de eventos cardíacos futuros. Devido à associação entre os fatores de risco da doença respiratória e DAC, é provável que muitos desses pacientes tenham redução da função pulmonar associada. O objetivo deste estudo foi estabelecer a prevalência de alterações espirométricas na população em investigação cardiopatia por TCC e o impacto da alteração funcional no uso de recursos de saúde. Pacientes encaminhados para a realização de TCC realizaram espirometria. Esses foram, então, divididos de acordo com o padrão espirométrico em grupo função pulmonar normal e alterada (FPN e FPA). O FPA foi subdividido em padrão obstrutivo e restritivo (PO e PR). Os indivíduos foram seguidos por 1 ano quanto a internações hospitalares, procura a pronto-socorro e óbitos. Completaram o protocolo 205 pacientes. A prevalência de alteração espirométrica foi de 28,3% (11,2% no grupo PO e 17,2% no grupo PR). Apenas 8% da população do estudo tinha diagnóstico prévio de doença respiratória. Os preditores de alteração espirométrica foram tabagismo, idade e presença de lesão obstrutiva detectada na TCC. O grupo FPA apresentou aumento significativo no ECC (36 vs 1) e maior proporção de lesões obstrutivas coronarianas (57,2% VS 25,4%), principalmente à custa do grupo PR. Pacientes do grupo FPA tiveram maior procura à PS (20,7% vs 9,5%) e mortalidade (6,9% vs 0%) que o grupo FPN. Concluímos que existe alta prevalência de alterações espirométricas em pacientes encaminhados para a realização de TCC. Tanto a DPOC quanto doenças restritivas pulmonares são subdiagnosticadas nessa população. E a presença de alteração espirométrica está associada à maior morbidade cardiovascular e têm implicações prognósticas. Estes achados sugerem que durante a investigação de DAC a avaliação concomitante da função pulmonar é de grande relevância / Several studies have shown the association between respiratory disease and coronary artery disease (CAD). In addition to similar risk factors such as smoking and physical inactivity, both are associated with systemic inflammation and advanced age. Coronary computed tomography (CCT) with multiple detectors is diagnostic method for coronary heart disease, describing anatomy and vessel obstruction severity. One way to estimate risk of cardiovascular events is the coronary calcium score (CCS) from this examination. Many patients are referred to CCT in order to investigate CAD or classify the risk for future cardiac events. Because of the association between risk factors for respiratory disease and CAD, it is likely that many of these patients may have reduced lung function. The study objective was to establish the prevalence of spirometric changes in population investigating heart disease by CCT and the impact of functional changes in use of health care resources. Patients referred for CCT performed spirometry. They were then divided according to spirometry results in normal and abnormal lung function group (NLF and ALF). The ALF was subdivided into obstructive and restrictive pattern (OP and RP). Subjects were followed for 1 year regarding hospital admissions, emergency room visits and deaths. 205 patients completed the protocol. Spirometric change prevalence was 28.3% (11.2% in OP group and 17.2% in the RP group). Only 8% of the study population had a previous diagnosis of respiratory disease. Spirometric changes predictors were smoking, age and obstructive lesion detected in CCT. The ALF group showed significant increase in ECC (36 VS 1) and higher proportion of coronary obstructive lesions (57.2% vs 25.4%), mainly at the expense of the RP group. Patients in ALF group had greater demand for emergency visits (20.7% vs 9.5%) and mortality (6.9% vs 0%) that the NLF group. We conclude that there is a high prevalence of spirometric changes in patients referred for CCT. Both COPD and restrictive lung diseases are underdiagnosed in this population. And the presence of spirometric change is associated with increased cardiovascular morbidity and has prognostic implications. These findings suggest that during DAC assessment, concomitant evaluation of lung function is of great importance

Coronary heart diseases (CHD) remain the most prevalent cause of premature death. Ischemic hearts often result from coronary vasculature occlusion. Significant efforts have been made for the treatment of CHD, including medications and surgical procedures. Currently there are still no effective drugs or therapeutics available for the treatment of the disease. Growing new coronary vessels to naturally bypass narrowed/occluded arteries or forming sufficient collaterals to the ischemic region would lead to substantially improved blood perfusion and correction of ischemia. However, this aim remains a theoretical ideal due to the negligible ability to grow new coronary vessels even with current advances in therapeutic angiogenesis. In the present study, we have isolated and identified an active fraction of Geum japonicum (AFGJ) showing significant activity in induction of efficient coronary angiogenesis and heart function improvement. / In addition, proteomics methods were applied to investigate the protein alterations in CHD ischemic hearts and HUVECs. Two dimensional polyacrylamide gel electrophoresis (2-D PAGE) of the heart tissues of CHD rats showed 16 differentially expressed spots compared with sham and vehicle hearts, of which 8 were identified. Furthermore, 11 identified proteins of HUVECs treated with AFGJ or Angio-G at different time points were also observed by 2-D PAGE. The majority of identified proteins was found to be involved in the process of energy metabolisms. / In conclusion, these results have demonstrated therapeutic properties of AFGJ to induce early reconstitution of damaged coronary vasculature through both angiogensis and vasculogenesis. AFGJ treatments may provide a novel therapeutic modality for effective treatment of ischemic heart diseases. / The therapeutic effect of AFGJ on CHD through reconstitution of partially occluded coronary vessels in CHD animal models was demonstrated with underlying signaling mechanisms identified. Briefly, AFGJ could promote the proliferation of human umbilical vein endothelial cells (HUVECs) in vitro and the growth of new blood vessels or coronary collaterals in CHD models after 2-week treatment. The number of newly formed coronary vessels in treated hearts was more than that of vehicle treated hearts, as indicated by both MicroCT and histology analysis. Echocardiography studies demonstrated significant improvement of heart functions 2 weeks after treatment with AFGJ. Furthermore, ECG measurements showed that the altered ST segment in AFGJ treated CHD models almost had full recovery to a normal level while rats in the vehicle group consistently suffered from heart ischemia. Moreover, the results of MicroCT reconstruction directly demonstrated the reconstitution of the damaged coronary vessels with newly formed functional coronary collaterals, as illustrated by more blood vessels density (AFGJ vs vehicle [%]: 4.5+/-0.5 vs 2+/-0.35) and more branching points (AFGJ vs vehicle: 0.94+/-0.07 vs 0.65+/-0.10). These data suggest that AFGJ treatment significantly corrects the ischemia of the affected regions of the heart. / We also explored possible mechanisms underlying the effect of AFGJ. Firstly, AFGJ could induce mesenchymal stem cell (MSC) differentiation into vascular endothelial cells and the differentiated MSCs were involved in the tube formation. Secondly, Angio-G, the component derived from AFGJ, was able to stimulate significant proliferation of HUVECs in a dose dependent manner. Thirdly, in our tube-like capillary formation test of HUVECs in vitro, the length of formed tubes was greatly amplified with increasing concentration of Angio-G. Furthermore, the total length of Angio-G induced tubes was significantly reduced with increasing concentrations of AG490, an inhibitor of JAK/STAT pathways indicating possible involvement of the JAK/STAT signaling pathway. / Chen, Hao. / "December 2009." / Source: Dissertation Abstracts International, Volume: 72-01, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 136-145). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Chung, Jennifer Siu Toye. / "June 2008." / Thesis (M.Phil.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 145-157). / Abstracts in English and Chinese, some text in appendix also in Chinese. / Abstract of Thesis in English --- p.i / Abstract of Thesis in Chinese --- p.iii / Acknowledgments --- p.v / List of Tables --- p.xi / List of Figures --- p.xiii / List of Abbreviations --- p.xiv / List of Publications and Presentations related to Thesis --- p.xvi / Contributions related to Thesis --- p.xvii / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Introduction of the Thesis --- p.1 / Chapter 1.2 --- Review on Coronary Heart Disease --- p.3 / Chapter 1.2.1 --- Definition of Coronary Heart Disease --- p.3 / Chapter 1.2.2 --- Risk factors for the development of Coronary Heart Disease --- p.3 / Chapter 1.2.3 --- Worldwide Figures for Coronary Heart Disease --- p.9 / Chapter 1.2.4 --- Coronary Heart Disease in Asia Pacific --- p.10 / Chapter 1.2.5 --- Coronary Heart Disease in Hong Kong --- p.11 / Chapter 1.3 --- Dyslipidaemia --- p.14 / Chapter 1.3.1 --- Lipid Transport and Lipoprotein Metabolism --- p.14 / Chapter 1.3.2 --- Definition and Classification of Dyslipidaemia --- p.16 / Chapter 1.3.3 --- Coronary Heart Disease and Dyslipidaemia --- p.17 / Chapter 1.3.4 --- Lifestyle Modifications for the Management of Dyslipidaemia --- p.19 / Chapter 1.3.4.1 --- Dietary Measures --- p.20 / Chapter 1.3.4.2 --- Cigarette Smoking --- p.23 / Chapter 1.3.4.3 --- Physical Activity --- p.24 / Chapter 1.3.4.4 --- Weight Control --- p.25 / Chapter 1.3.5 --- Lipid-lowering Drug Therapy for Dyslipidaemia --- p.29 / Chapter 1.3.5.1 --- Statins --- p.31 / Chapter 1.3.5.2 --- Bile Acid Sequestrants --- p.35 / Chapter 1.3.5.3 --- Fibrates --- p.36 / Chapter 1.3.5.4 --- Ezetimibe --- p.37 / Chapter 1.3.5.5 --- Nicotinic Acid Group --- p.38 / Chapter 1.4 --- International Guidelines for Dyslipidaemic Management --- p.39 / Chapter 1.4.1 --- National Service Framework for Coronary Heart Disease (UK) --- p.39 / Chapter 1.4.1.1 --- National Service Framework Lipid-lowering Goals --- p.40 / Chapter 1.4.1.2 --- The Joint British Societies' Guidelines --- p.41 / Chapter 1.4.1.3 --- Achievement of the NSF Lipid Profile Targets --- p.42 / Chapter 1.4.2 --- National Cholesterol Education Program (United States) --- p.43 / Chapter 1.4.2.1 --- The Third Report of the National Cholesterol Education Program --- p.43 / Chapter 1.4.2.2 --- Review of Clinical Trials --- p.43 / Chapter 1.4.2.3 --- Low-Density Lipoprotein Cholesterol Goal Targets --- p.46 / Chapter 1.4.2.4 --- Compliance with the NCEP ATP III Guidelines --- p.48 / Chapter 1.4.3 --- Dyslipidaemic Guidelines for Study --- p.51 / Chapter 1.5 --- Clinical Pharmacy Services --- p.52 / Chapter 1.5.1 --- The Healthcare System in Hong Kong --- p.52 / Chapter 1.5.2 --- Clinical Pharmacy Services in Hong Kong --- p.54 / Chapter 1.5.3 --- Examples of successful Clinical Pharmacy Services --- p.55 / Chapter 1.5.3.1 --- Hypertension Clinic --- p.55 / Chapter 1.5.3.2 --- Diabetes Mellitus Clinic --- p.56 / Chapter 1.5.3.3 --- Smoking Cessation Clinic --- p.57 / Chapter 1.5.3.4 --- Anticoagulation Clinic --- p.57 / Chapter 1.5.3.5 --- Haematology-oncology Clinic --- p.57 / Chapter 1.5.4 --- Pharmacist-managed Lipid Clinics --- p.58 / Chapter 1.6 --- Objective & General Aims of the Study --- p.60 / Chapter 1.6.1 --- Objectives --- p.60 / Chapter 1.6.2 --- Study Hypothesis --- p.60 / Chapter 1.6.3 --- General Aims of the Study --- p.60 / Chapter Chapter 2 --- Methodology of Study --- p.62 / Chapter 2.1 --- Background Setting --- p.62 / Chapter 2.2 --- Subject Selection and Recruitment --- p.62 / Chapter 2.3 --- Intervention and Control Groups --- p.63 / Chapter 2.4 --- Validation of Survey --- p.67 / Chapter 2.5 --- Data Collection --- p.67 / Chapter 2.6 --- Outcome Measures --- p.68 / Chapter 2.6.1 --- Lipid value changes --- p.68 / Chapter 2.6.2 --- Compliance rate with medications --- p.68 / Chapter 2.6.3 --- Patient satisfaction survey assessment --- p.69 / Chapter 2.6.4 --- Time spent and Cost of clinical pharmacist --- p.69 / Chapter 2.7 --- Statistical Analysis --- p.70 / Chapter 2.7.1 --- Sample Size Calculation --- p.70 / Chapter 2.7.2 --- Methods of Statistical Analysis --- p.71 / Chapter Chapter 3 --- Results of Study --- p.72 / Chapter 3.1 --- Recruitment Details --- p.72 / Chapter 3.2 --- Demographic Characteristics of Patients --- p.73 / Chapter 3.3 --- Drug Therapy of Patients during Study Period --- p.75 / Chapter 3.4 --- LDL-C Lowering Potency of Statin Doses Prescribed --- p.80 / Chapter 3.5 --- Coronary Heart Disease Risk Category of Patients --- p.84 / Chapter 3.6 --- Lipid Profile Changes --- p.85 / Chapter 3.7 --- NCEP ATP III LDL-C Goal Attainment --- p.87 / Chapter 3.8 --- Relationship between Patient Characteristics and LDL-C Goal Attainment --- p.91 / Chapter 3.9 --- Compliance with Medications --- p.94 / Chapter 3.10 --- Pharmacist Intervention --- p.98 / Chapter 3.10.1 --- Range of Pharmacist Intervention --- p.98 / Chapter 3.10.2 --- Time spent by Pharmacist --- p.100 / Chapter 3.10.2.1 --- Time spent on Documentation --- p.100 / Chapter 3.10.2.2 --- Time spent on Direct Communication with Patients --- p.101 / Chapter 3.10.3 --- Cost of Clinical Pharmacy Service at the Lipid Clinic --- p.102 / Chapter 3.10.3.1 --- Cost of Pharmacist Involvement --- p.102 / Chapter 3.10.3.2 --- Potential Healthcare Cost Saving --- p.103 / Chapter 3.11 --- Clinical Pharmacy Service Satisfaction Survey --- p.105 / Chapter 3.11.1 --- Validation of Survey --- p.105 / Chapter 3.11.2 --- Questionnaire Survey for Intervention and Control Groups --- p.107 / Chapter 3.11.3 --- Physician Questionnaire Survey on Clinical Pharmacy Service --- p.110 / Chapter Chapter 4 --- Discussion --- p.111 / Chapter 4.1 --- Clinical Outcomes of Study --- p.111 / Chapter 4.1.1 --- Changes in Lipid Parameters --- p.111 / Chapter 4.1.2 --- Reduction in CHD risk --- p.113 / Chapter 4.1.3 --- Attainment in NCEP ATP III LDL-C goals --- p.114 / Chapter 4.1.4 --- Predictors for LDL-C Goal Attainment --- p.117 / Chapter 4.2 --- Drug-related Problems --- p.119 / Chapter 4.2.1 --- Statin Dosing and LDL-C Lowering Potency --- p.119 / Chapter 4.2.2 --- Adherence to Drug Therapy --- p.121 / Chapter 4.2.3 --- Polypharmacy --- p.126 / Chapter 4.2.4 --- Adverse Drug Events and Drug Interactions --- p.129 / Chapter 4.2.5 --- Patient Busy Lifestyle --- p.131 / Chapter 4.3 --- Role of Clinical Pharmacist --- p.133 / Chapter 4.3.1 --- Role of Pharmacist --- p.133 / Chapter 4.3.2 --- Multidisciplinary Team --- p.135 / Chapter 4.3.3 --- Healthcare Cost Saving --- p.137 / Chapter 4.4 --- Limitations of Study --- p.139 / Chapter 4.5 --- Further Study --- p.142 / Chapter Chapter 5 --- Conclusion --- p.144 / Chapter 5.1 --- Conclusion of Study --- p.144 / Bibliography --- p.145 / Appendices --- p.158 / Appendix I Data collection form --- p.158 / Appendix II Information sheet on study protocol to patient --- p.160 / Appendix III Patient consent form for study --- p.164 / Appendix IV Framingham risk scoring system for male --- p.165 / Appendix V Framingham risk scoring system for female --- p.166 / Appendix VI Patient educational leaflet --- p.167 / Appendix VII Physician-pharmacist communication sheet --- p.169 / Appendix VIII Telephone checklist --- p.170 / Appendix IX Questionnaire survey provided to Intervention Group --- p.172 / Appendix X Questionnaire survey provided to Control Group --- p.174 / Appendix XI Questionnaire survey provided to Physicians --- p.176

Introdução: A doença arterial coronariana (DAC) constitui uma das principais causas de mortalidade mundial à despeito dos avanços no seu tratamento. Neste sentido, importantes comorbidades podem contribuir para este cenário desfavorável. Um dos fatores de pior prognóstico nos pacientes com DAC é a presença da doença renal crônica (DRC). Entre os potenciais novos candidatos para este prognóstico desfavorável, podemos citar os distúrbios do sono. Diversos estudos sugerem que a apneia obstrutiva do sono (AOS) e a curta duração do sono (CDS) isoladamente estão associados com piores desfechos cardiovasculares, incluindo uma maior incidência de DAC. No entanto, não está claro se a interação da AOS com a CDS está associada com pior função renal e com maior taxa de DRC em pacientes com DAC bem como maior taxa combinada de eventos cardiovasculares e não cardiovasculares. Métodos: Foram recrutados pacientes consecutivos com DAC estabelecida (pacientes com indicação clínica para a intervenção coronária percutânea, ICP) eletiva. Após a realização da ICP com implante de stent com sucesso (estenose residual < 20% e fluxo TIMI 2- 3), todos os pacientes foram submetidos à monitorização do sono com a poligrafia portátil (Embletta Gold®) por uma noite (ainda durante a internação hospitalar) e à actigrafia de pulso (Actiwatch 2, Respironics®) durante sete dias (após o retorno do paciente às atividades habituais). Definimos a AOS por um índice de apneia-hipopneia (IAH) >=15 eventos/hora e a CDS por <6 horas por noite de sono. Nós estratificamos a associação da AOS, da CDS e a interação de ambas baseada na taxa de filtração glomerular (TFG) e a presença de DRC com exame de creatinina coletado pré-ICP. Estimamos a TFG usando a equação do Chronic Kidney Disease: Epidemiology Consortium (CKD-EPI) de forma contínua e categorizada em dois níveis: TFG < 60mL/min/1.73 m2 (diminuição moderada a grave) e TFG > 60mL/min/1.73 m2 (normal ou levemente diminuído). Após o exame do sono, o seguimento clínico foi realizado por meio de ligações telefônicas e checagem dos prontuários com 1 mês, 6 meses e depois anualmente procurando avaliar a ocorrência de eventos cardiovasculares fatais e não fatais de forma sistematizada. Resultados: Foram estudados 262 pacientes (64,1% sexo masculino, idade média: 63±10 anos e índice de massa corpórea [IMC] 27,8±4,4 Kg/m2). A frequência da AOS e CDS foi de 58,4% e 25,6%, respectivamente. Pacientes com AOS apresentaram pior TFG em relação aos pacientes sem AOS (62±26 vs. 74±20 mL/min/1,73m2, p < 0,001) e consequentemente maior taxa de DRC (42,1 vs. 26,6%, p=0,009). Em contraste, a TFG foi similar nos pacientes com e sem CDS (65±29 vs. 68±23 mL/min/1,73m2, p=0,38) e uma frequência não significante de DRC (44.8 vs. 32.5%, p=0.07). Na análise multivariada, AOS, mas não a CDS, foi independentemente associada com a TFG: beta= -10,57 (-16,46 - - 4,68), p < 0,001) e com a DRC (OR=1,95; 95% IC=1,12-3.38, p=0,01). As interações da AOS e da CDS com a TFG e a presença da DRC não foram significantes. Os resultados permaneceram similares após avaliarmos a AOS (pelo IAH) e a duração do sono de forma continua ou ao classificarmos a CDS como < 5 horas. Em uma análise exploratória, após seguimento mediano foi de 25 meses, ocorreram 43 eventos cardiovasculares (15 infartos agudos do miocárdio; 1 revascularização do miocárdio; 6 acidentes vasculares cerebrais; 7 óbitos cardiovasculares e 14 reestenoses de stent). Considerando os eventos combinados, não encontramos até o momento diferenças significantes entre os grupos com AOS e CDS quando comparados aos respectivos grupos sem estes distúrbios. Conclusão: Em pacientes com DAC, a AOS, mas não a CDS, foi independentemente associada com pior TFG e DRC, marcadores de pior prognóstico nestes pacientes / Introduction: Coronary artery disease (CAD) is one of the main causes of worldwide mortality despite advances in the medical treatment. In this sense, important comorbidities can contribute to this unfavorable scenario. One of the factors associated with poor prognosis in patients with CAD is the presence of chronic kidney disease (CKD). Sleep disorders are potential new candidates contributing to poor prognosis in CAD as well. Although not consistent, several studies suggested that obstructive sleep apnea (OSA) or short sleep duration (SSD) are associated with a higher prevalence of CAD and poor cardiovascular outcomes, including higher CAD incidence. However, it is unclear whether the interaction of OSA with SSD is associated with lower renal function and higher frequency of CKD in patients with established CAD, as well as with increased rate of cardiovascular and non-cardiovascular events. Methods: Consecutive patients with established CAD (those with clinical indication for elective percutaneous coronary intervention, PCI) were recruited. After a successful PCI procedure (residual stenosis < 20% and TIMI 2-3 flow), all patients underwent sleep monitoring with portable polygraphy (Embletta Gold®) for one night (during hospital stay) and wrist actigraphy (Actiwatch 2, Respironics®) for seven days (after patient return to usual activities). We defined OSA by an apnea-hypopnea index (AHI) >= 15 events / hour and SSD for < 6 hours per night of sleep. We stratified the association of OSA, SSD and their interaction based on the eGFR and the presence of CKD with the creatinine collected pre PCI procedure. We estimated eGFR using the Chronic Kidney Disease: Epidemiology Consortium (CKD-EPI) equations and categorized into two levels: eGFR < 60mL / min / 1.73 m2 (moderate to severe decrease) and eGFR > 60mL / min / 1.73 m2 (normal or mildly decreased). After the sleep study, clinical follow-up was performed through phone calls and medical records revisions at 1 month, 6 months, and then annually, searching for the occurrence of fatal and non-fatal cardiovascular events in a systematized way. Results: A total of 262 patients (64.1% males, mean age: 63±10 years and body mass index [BMI] 27.8±4.4 kg/m2) were studied. The frequencies of OSA and SSD were 58.4% and 25.6%, respectively. Patients with OSA had lower eGFR compared to patients without OSA (62±26 vs. 74±20 mL/min/1.73m2, p < 0.001) and consequently a higher rate of CKD (42.1 vs. 26.6%, p=0.009). In contrast, eGFR was similar in patients with and without SSD (65±29 vs. 68±23 mL/min/1.73 m2, p=0.38) and a no significance frequency of CKD (44.8 vs. 32.5%, p=0.07). In the multivariate analysis, AOS, but not SSD, was independently associated with eGFR (-10.57 (-16.46 - -4.68), p < 0.001) and with CKD (OR = 1.95, 95% CI=1.12-3.38, p=0.01). The interactions of OSA and SSD with eGFR and the presence of CKD were not significant. These results remained unchanged after evaluating AHI and sleep duration as continuous variables or setting SSD as < 5 hours. In an exploratory analysis, after a median follow up of 25 months, forty-three cardiovascular events (15 episodes of acute myocardial infarction, 1 coronary artery bypass graft, 6 strokes, 7 deaths and 14 stent restenosis). Considering the combined events, we did not find significant differences between OSA and SSD groups and their counterparts so far. Conclusion: In patients with CAD, OSA, but not SSD was independently associated with lower GFR and CKD, markers of poor prognosis in these patients

Background: The ageing process not only increases the risk of coronary artery disease (CAD) but also complicates its diagnosis and treatment. It is therefore important to understand the newer concepts of cardiovascular ageing physiology as well as methods of predicting the outcomes of therapeutic options available for the elderly with severe CAD. Studies of atrioventricular (AV) ring or plane motion have attracted considerable interest in the last few years as a means of assessing ventricular and atrial function. As the displacement of AV rings towards the ventricular apex is a direct reflection of longitudinal fibre contraction, its measurement by echocardiography provides additional information regarding global and regional systolic and diastolic function. Left ventricular (LV) long axis amplitude of motion, referred to as mitral valve annular (MA) motion, is reduced in CAD and to some extent in the elderly as part of the normal ageing process. Objectives &amp; Methods: The aim of the present study was two-fold. First, to investigate the relationship between the timing of MA motion and transmitral and pulmonary venous flow in healthy subjects, and to define the physiological significance of that relationship including its potential diagnostic utility. Second, to investigate the relationship between the clinical outcome and the behaviour of long axis function in patients with severe ischaemic LV dysfunction (SLVD) after percutaneous coronary angioplasty (PTCA). Transmitral early (E) and late (A) filling, and pulmonary venous flow reversal (Ar) were studied by Doppler echocardiography, while at the left lateral AV ring, the MA motion in early (Em) and late (Am) diastole were recorded by Doppler tissue imaging (DTI) and M-mode echocardiography. Results: Healthy subjects – In early diastole the onsets of LV filling (E) and relaxation (Em) were simultaneous, and peak Em preceded peak E by 26 msec in all age groups, constituting a time interval referred to as early diastolic temporal discordance (EDTD). Similarly, the onsets of Am, A and Ar were simultaneous at onset and began approximately 84 msec after the electrocardiographic P wave. Peak Am preceded peak A by 23 msec in the young and by 13 msec in the elderly, a time interval referred to as late diastolic temporal discordance (LDTD). Peak Ar, on the other hand, coincided with peak Am in all age groups. With increasing age and sequential prolongation of isovolumic relaxation time, the peaks of Am, Ar and A converged. This point of convergence is described as atrial mechanical alignment (AMA). Patients – MA total amplitude of motion, rates of shortening and lengthening were all reduced in patients with SLVD. At mid-term, 3-6 months after PTCA, there was improvement in all these variables. A pre-procedure long axis cut off value of ≥5 mm was associated with favourable symptomatic outcome. Overall angiographic success was 95.2%, and event-free survival was 78.4% at one month and declined steadily to 62.3% at one year with 2.5% mortality. Conclusions: EDTD, which reflects ventricular restoring forces (suction) is age independent while the narrowing of LDTD leading to AMA provides a novel method to identify healthy subjects at increased dependency on left atrial contraction for late diastolic filling. Peak atrial contraction (Am) coincides with peak Ar, thus the timing of regional atrial contraction by DTI can be used to estimate corresponding measurements of Ar, which is often difficult to image by transthoracic echocardiography. In patients with SLVD long axis total amplitude of at least 5 mm at the left MA suggests a significant potential for segmental function recovery after PTCA. Keywords: Echocardiography, Doppler tissue imaging, ageing, coronary disease, left ventricular dysfunction, atrial contraction, electromechanical function, coronary angioplasty.

The main expansion of the discovery of genetic variants associated with complex diseases has occurred during the last decade. This expansion has been accompanied, and in some sense motivated, by the desire to use this information to improve the predictive capacity of many diseases with an unidentified familial component, including coronary heart disease (CHD), with the aim of translating this genetic knowledge into clinical practice. This doctoral thesis is structured in two lines of investigation that address distinct aspects of this issue, first to evaluate the possible role of genetic variation in a candidate gene in modulating CHD risk, and second to evaluate whether genetic information can be used to improve risk assessment tools used in clinical practice. In the first research line (described in Part I), we investigate the contribution of genetic variation in one of the most widely-studied genes in cardiovascular genetics, ESR1, which encodes the Oestrogen receptor α protein. We provide a solid meta-analysis of evidence regarding the most widely-studied variant in this gene and we further explore the role of a broad range of common and uncommon variants in this gene in CHD risk. Using these approaches, we find no evidence of association between the genetic variants studied and CHD risk. However, although we can confidently accept that common genetic polymorphisms are not associated with cardiovascular disease, we cannot discard the possibility that other types of variation in this gene (for instance epigenetic variation) could modify susceptibility to cardiovascular disease, or that other elements of this pathway are associated with an increased risk of CHD. In this research I have provided a reliable answer to this long running unanswered question in cardiovascular genetics, allowing research to re-focus on other elements of this system or other pathways. In the second line, we explored the possible utility of genetic information obtained from genome-wide association studies (GWAS) in prediction of 10-year risk of CHD events by adding this information to cardiovascular risk functions. We have followed the recommendations proposed by the American Heart Association for evaluating the utility of novel biomarkers in clinical practice, and have demonstrated that although the magnitudes of the effects of these genetic variants on CHD risk are modest, there is a tendency towards improvement in the capacity of the risk functions to predict future CHD events. The translation of genetic information into clinical practice was one of the main motivations for the investment in genome-wide association studies, and my research represents one of the first efforts to explore this possibility. / L’expansió principal pel que fa al descobriment de variants genètiques associades amb malalties complexes s’ha dut a terme durant la última dècada. Aquesta expansió ha estat acompanyada, i d’alguna forma motivada, pel desig d’usar aquesta informació per millorar la capacitat de predicció d’aquelles malalties on hi és present un cert component familiar però en les que no es coneixien les variants que conferien un major risc de patir la malaltia, entre elles la cardiopatia isquèmica (CI). La present tesis doctoral està estructurada en dues línies d’investigació que avaluen el possible rol d’un gen candidat en la susceptibilitat de la CI i també avalua la millora en la capacitat de predicció d’un esdeveniment coronari de les eines usades habitualment en la pràctica clínica mitjançant la inclusió d’informació genètica. Més concretament, la primera línea d’investigació es centra en la contribució de la variació genètica en un dels gens més estudiats en relació amb CI: el gen que codifica pel receptor d’estrogens alfa (ESR1). En aquesta línea hem proveït un sòlid meta-anàlisis entre la variant més àmpliament estudiada d’aquest gen i risc coronari i també hem explorat el paper de la majoria de les variants comunes descrites en aquest gen i risc de CI. Mitjançant cap dels anàlisis hem trobat evidència d’associació entre les variants genètiques en aquest gen i el risc de CI. No obstant això, i encara que podem acceptar que les variants genètiques comunes d’aquest gen no estan associades amb esdeveniments coronaris, no podem descartar que altres tipus de variació en aquest gen (com per exemple variació epigenètica) pugui estar modificant la susceptibilitat a patir un esdeveniment coronari, ni tampoc que altres elements de la mateixa cadena de senyalització estiguin associats amb la malaltia. En la segona línea d’investigació, hem explorat el possible paper de les variants genètiques, obtingudes mitjançant estudis d’associació global del genoma (GWAS), en la millora de la capacitat de predicció a 10 anys dels esdeveniments coronaris, mitjançant la seva addició en les funcions de risc cardiovascular clàssiques. Hem seguit les recomanacions proposades per la American Heart Association per l’avaluació en la pràctica clínica de nous biomarcadors, i hem demostrat que, tot i que la magnitud de l’associació d’aquestes variants és modesta, hi ha una tendència cap a la millora de la capacitat de predicció de les funcions de risc.

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 4 uppsatser.