Conclusions: In the same number of people treated, the number of CVD events avoided for the overall risk approach is always larger than that of the blood pressure approach. The additional benefits of overall risk approach compared with the blood pressure approach decreases as the percentage of people from the total population is increased. If the current practice and hypertension guidelines in China are shifted to the overall risk approach, many more CVD events could be avoided with the same resources used. / Methods: The sample used in the analyses includes a subsample of 38,673 persons from the 2002 China National Nutrition and Health Survey, who were 30-74 years old, without previous CVD, and had data on all major CVD risk factors. CVD risks of the patients selected by each approach are predicted using suitable risk prediction equation. The RRR of anti-hypertensive drug treatment derived from meta-analyses of RCTs. The difference in the absolute effectiveness between the two approaches is used to quantify how many more CVD events can be prevented in 1000 people treated by the ORA as compared to the BPA. / Objective: To estimate and compare the number of major cardiovascular events that could be avoided by shifting the blood pressure approach to the overall risk approach if the same percentage of people in a large, representative Chinese population is treated with anti-hypertensive drugs. / Results: When 2.5%, 5.5%, 10.1%, 15.5%, 20.7%, 25.7% or 33.0% of the 38,673 subjects were treated by anti-hypertensive drugs by using the two approaches respectively, 22 (95%CI: 17∼28), 13 (11∼16), 9 (8∼10), 7 (6∼8), 6 (5∼7), 5 (4∼6), or 4 (3∼4) more CVD events could be avoided in every 1000 people treated if the blood pressure approach is shifted to the overall risk approach, which is in general a 15% to 25% increase in CVD events prevented. / Qin, Ying. / Adviser: Jin Ling Tang. / Source: Dissertation Abstracts International, Volume: 73-02, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 116-121). / 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, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Objetivo: A hipertensão arterial constitui o principal fator de risco modificável para as doenças cardiovasculares e a maioria dos hipertensos necessitará de medicamento para controlar a pressão. Este estudo analisa a prevalência da hipertensão arterial referida e a utilização de anti-hipertensivos por adultos do município de São Paulo de acordo com variáveis socioeconômicas e demográficas. Métodos: Análise de dados do Inquérito de Saúde no Município de São Paulo – ISA Capital, estudo transversal, de base populacional conduzido em 2003 que possui 1668 adultos com 20 anos ou mais. Para investigar a distribuição das principais classes de anti-hipertensivos, utilização de genérico, forma de obtenção e custeio utilizou-se de um recordatório de três dias. Resultados: A prevalência de hipertensão referida foi de 16,9%, sendo maior nos indivíduos com idade mais avançada, menor escolaridade e sem ocupação. Entre os que referiam hipertensão, a prevalência do consumo de anti-hipertensivo nos três dias que antecederam a entrevista foi de 73,1%. Dos indivíduos que consumiram anti-hipertensivos 38,3% obtiveram o medicamento através do SUS e 35,3% utilizaram genéricos. As principais classes consumidas em monoterapia foram: inibidores da enzima conversora de angiotensina – IECA (41,9%) e diuréticos (24,6%). As principais associações foram: IECA + diurético (36,0%) e diurético + betabloqueador (22,3%). Conclusões: A hipertensão arterial referida se distribui de maneira desigual entre diferentes subgrupos da população. No acesso a medicamento anti-hipertensivo o SUS consegue promover equidade no fornecimento dessas drogas para a população mais desfavorecida. As classes consumidas não estão totalmente de acordo com as diretrizes de hipertensão. / Objective: Hypertension is the major modifiable risk factor for cardiovascular diseases and most of hypertensive patients will require medication for the control of blood pressure. This study analyses the prevalence of self-reported hypertension and the utilization of antihypertensive agents by adults in São Paulo City, Brazil, according to socioeconomic and demographic variables. Methods: Analysis of data from the Health Survey of São Paulo City – ISA Capital, a cross-sectional, population-based survey conducted in 2003 with 1668 adults aged 20 years or over. To investigate the distribution of the main antihypertensive drug classes, utilization of generic drugs and information about how the drugs were obtained, individuals who self-reported hypertension were asked about any drug use for high blood pressure in the previous three days. Results: The prevalence of self-reported hypertension was 16.9%. Advanced age, lower education and not having a job were independently associated with hypertension. The consumption of antihypertensive drugs was 73.1%. Among those who took antihypertensive drugs 38.3% and 35.3%, respectively, obtained the medication from the Brazilian Public Health System (SUS) and used generics. Angiotensin-converting enzyme inhibitors (ACEi) (41.9%) and diuretics (24.6%) were the most used drugs utilized as monotherapy and the most used combinations were ACEi + diuretics (36.0%) and diuretics + beta-blockers (22.3%). Conclusions: The distribution of self-reported hypertension is not equal among different subgroups of the population. The equity in the delivery of antihypertensive drugs is an important component of treatment and control of hypertension and the SUS could perform it to the less advantaged people. The classes consumed do not agree fully with the hypertension guidelines.

Objetivo: A hipertensão arterial constitui o principal fator de risco modificável para as doenças cardiovasculares e a maioria dos hipertensos necessitará de medicamento para controlar a pressão. Este estudo analisa a prevalência da hipertensão arterial referida e a utilização de anti-hipertensivos por adultos do município de São Paulo de acordo com variáveis socioeconômicas e demográficas. Métodos: Análise de dados do Inquérito de Saúde no Município de São Paulo – ISA Capital, estudo transversal, de base populacional conduzido em 2003 que possui 1668 adultos com 20 anos ou mais. Para investigar a distribuição das principais classes de anti-hipertensivos, utilização de genérico, forma de obtenção e custeio utilizou-se de um recordatório de três dias. Resultados: A prevalência de hipertensão referida foi de 16,9%, sendo maior nos indivíduos com idade mais avançada, menor escolaridade e sem ocupação. Entre os que referiam hipertensão, a prevalência do consumo de anti-hipertensivo nos três dias que antecederam a entrevista foi de 73,1%. Dos indivíduos que consumiram anti-hipertensivos 38,3% obtiveram o medicamento através do SUS e 35,3% utilizaram genéricos. As principais classes consumidas em monoterapia foram: inibidores da enzima conversora de angiotensina – IECA (41,9%) e diuréticos (24,6%). As principais associações foram: IECA + diurético (36,0%) e diurético + betabloqueador (22,3%). Conclusões: A hipertensão arterial referida se distribui de maneira desigual entre diferentes subgrupos da população. No acesso a medicamento anti-hipertensivo o SUS consegue promover equidade no fornecimento dessas drogas para a população mais desfavorecida. As classes consumidas não estão totalmente de acordo com as diretrizes de hipertensão. / Objective: Hypertension is the major modifiable risk factor for cardiovascular diseases and most of hypertensive patients will require medication for the control of blood pressure. This study analyses the prevalence of self-reported hypertension and the utilization of antihypertensive agents by adults in São Paulo City, Brazil, according to socioeconomic and demographic variables. Methods: Analysis of data from the Health Survey of São Paulo City – ISA Capital, a cross-sectional, population-based survey conducted in 2003 with 1668 adults aged 20 years or over. To investigate the distribution of the main antihypertensive drug classes, utilization of generic drugs and information about how the drugs were obtained, individuals who self-reported hypertension were asked about any drug use for high blood pressure in the previous three days. Results: The prevalence of self-reported hypertension was 16.9%. Advanced age, lower education and not having a job were independently associated with hypertension. The consumption of antihypertensive drugs was 73.1%. Among those who took antihypertensive drugs 38.3% and 35.3%, respectively, obtained the medication from the Brazilian Public Health System (SUS) and used generics. Angiotensin-converting enzyme inhibitors (ACEi) (41.9%) and diuretics (24.6%) were the most used drugs utilized as monotherapy and the most used combinations were ACEi + diuretics (36.0%) and diuretics + beta-blockers (22.3%). Conclusions: The distribution of self-reported hypertension is not equal among different subgroups of the population. The equity in the delivery of antihypertensive drugs is an important component of treatment and control of hypertension and the SUS could perform it to the less advantaged people. The classes consumed do not agree fully with the hypertension guidelines.

INTRODUÇÃO: A hipertensão é um importante problema de saúde pública e os estudos de Custo-Efetividade (C/E) do tratamento antihipertensivo são raros no Brasil. OBJETIVO: Realizar análise farmacoeconômica retrospectiva do tipo C/E do tratamento medicamentoso em hipertensos. MATERIAL E MÉTODOS: Foi analisado o custo (C) dos medicamentos anti-hipertensivos, do número de visitas médicas não programadas e do tratamento dos efeitos adversos e a efetividade (E) medida pela redução média da pressão arterial em mm Hg ao término de estudo sobre eficácia do tratamento Tradicional iniciado com hidroclorotiazida e atenolol comparado ao tratamento Atual iniciado com losartan e anlodipino, administrados aleatoriamente durante 12 meses a hipertensos sem outras doenças concomitantes pertencentes ao estágios 1 e 2 (grupo HT1-2 = 140 menor ou igual PAS < 180 e 90 menor ou igual PAD < 110 mm Hg) e ao estágio 3 (grupo HT3 = PAS > 180 e PAD > 110 mm Hg). RESULTADOS: A razão C/E (R$/mm Hg) no grupo HT1-2 (n = 231) para PAS/PAD dos tratamentos Atual e Tradicional foi de 112,52 ± 395,28 / 181,26 ± 358,91 e 43,05 ± 50,73 / 80,51 ± 108,31 (p < 0,05) ao passo que no grupo HT3 (n = 132) foi de 115,12 ± 254,87 / 108,14 ± 82,56 e 218,59 ± 891,93 / 173,97 ± 447,23 (p > 0,05). CONCLUSÃO: O tratamento Tradicional foi custo-efetivo em relação ao Atual nos hipertensos estágios 1 e 2. Por outro lado, nos hipertensos estágio 3 não houve diferença na razão C/E entre os tratamentos. Estes resultados foram confirmados quando foi utilizado o menor preço de aquisição dos medicamentos e quando foram considerados somente os pacientes que atingiram o controle da pressão arterial ao final do estudo. / INTRODUCTION: Hypertension is an important public health problem and Cost-Effectiveness (C/E) studies of antihypertensive drug treatment are uncommon in Brazil. OBJECTIVE: To perform a cost-effectiveness (C/E) ratio retrospective pharmacoeconomic analysis of drug treatment in hypertensive patients. MATERIAL AND METHODS: Antihypertensive medication cost (C) was analysed, along with the number of non-scheduled medical visits, treatment of adverse effects, and effectiveness (E) based on the average reduction of arterial blood pressure measured in mm Hg at the end of the study comparing the efficacy of a Traditional Treatment with hydrochlorothiazide and atenolol versus Current Treatment using losartan and amlodipine, administered at random for 12 months to hypertensive patients with no other simultaneous diseases and presenting disease stage 1 and 2 (HT1-2 Group = 140 < or = SBP < 180 and < or = 90 DBP < 110mmHg) and stage 3 (HT3 Group = SBP maior or = 180 and DBP > or = 110mmHg). RESULTS: The C/E ratio (R$/mmHg) in the HT1-2 Group (n=231), based on SBP/DBP, for Current and Traditional Treatments was 112.52 ± 395.28 / 181.26 ± 358.91 and 43.05 ± 50.73 / 80.51 ± 18.31 (p < 0.05), while in the HT3 Group (n=132), 115.12 ± 254.87 / 108.14 ± 82.56 and 218.59 ± 891.93 / 173.97 ± 447.23 (p>0.05). CONCLUSION: Traditional treatment was more cost-effective compared to the Current therapy in hypertensive patients with disease stages 1 and 2. On the other hand, in hypertensive patients with disease stage 3 there was no difference in C/E ratio between the treatment regimens. These results were confirmed by using the lowest purchase price of medication and by considering only patients that reached control of their blood pressures at the end of the study.

Introdução: Pacientes hipertensos resistentes (HR) são indivíduos com pressão arterial não controlada - apesar do tratamento com um diurético e dois anti-hipertensivos com mecanismos de ação diferentes em doses adequadas. Há duas áreas de interesse nesse contexto: a ancestralidade genética que, a princípio, poderia impactar em controles pressóricos, e a farmacometabolômica que, conceitualmente, é um conjunto de mudanças em concentrações de metabólitos - um novo campo que pode esclarecer mecanismos de variações de respostas farmacológicas. Assim, nossos principais objetivos foram: associar mensurações séricas de fármacos anti-hipertensivos e seus metabólitos às respostas farmacoterapêuticas em pacientes hipertensos e analisar a ancestralidade genética em pacientes hipertensos a fim de verificar uma possível associação com as respostas farmacoterapêuticas e a hipertensão resistente. Métodos: Foram utilizadas amostras de 1.597 pacientes, sendo 187 HR. A preparação e a análise da amostra foram realizadas usando uma coluna com nanotubos de carbono de acesso restrito (RACNTs) em um sistema de cromatografia líquida acoplada a espectrômetro de massa (UPLC-MS/MS), em modo column switching. A ancestralidade genética foi realizada usando um painel de 192 marcadores polimórficos; três referências foram usadas (europeia, ameríndia e africana). A raça foi determinada pela autodeclaração, segundo IBGE (branco, pardo, negro e outros). Resultados: O método foi totalmente validado de acordo com as diretrizes da Food and Drug Administration (FDA). O tempo de execução total para cada análise foi de 12,0 min - incluindo a preparação da amostra. Não foram encontradas diferenças significativas nas concentrações de cada analito de acordo com pacientes responsivos e não responsivos, possivelmente, por causa do número de amostra ainda baixo (n total de 171 amostras). As médias das mensurações no grupo dos respondedores foram: clonidina 1,308microg/L; amlodipina 44,044microg/L; enalapril 67,706microg/L; enalaprilato 44,144microg/L; losartana 202,622microg/L; ácido carboxílico de losartana 65,99microg/L, glicuronídeo N-2 de losartana 43,4microg/L e espironolactona 85,87microg/L. Para o grupo dos não respondedores, obtivemos: clonidina 1,4microg/L; amlodipina 78,89microg/L; enalapril 87,821microg/L; enalaprilato 78,878microg/L; losartana 148,026microg/L, ácido carboxílico de losartana 83,535microg/L, glicuronídeo N-2 de losartana 122,452microg/L e espironolactona 79,72microg/L. A raça autodeclarada foi associada aos componentes da ancestralidade genética desses pacientes (p<0,001). A ancestralidade genética, disponível para 1.503 pacientes, teve média geral de 0,53, para europeia; 0,11, para ameríndia; e 0,35, para africana. Não foram encontradas diferenças estatísticas nas médias de ancestralidade de acordo com os grupos respondedor ou HR. Conclusões: O método analítico foi validado e a ancestralidade genética foi realizada, ambos não associados à farmacoterapêutica e à hipertensão resistente / Background: Resistant hypertensive (RH) patients are individuals with uncontrolled blood pressure - despite treatment with one diuretic and two antihypertensives with different mechanisms of action in adequate doses. There are two areas of interest in this context: genetic ancestry that could initially impact on blood pressure controls, and pharmacometabolomics, which conceptually is a set of changes in metabolite concentrations - a new field that can clarify mechanisms of pharmacological response variation. Thus, our main objectives were: to associate serum measurements of antihypertensive drugs and their metabolites to the pharmacotherapeutic responses in hypertensive patients and to analyze genetic ancestry in hypertensive patients in order to verify a possible association with pharmacotherapeutic responses and resistant hypertension. Methods: Samples of 1,597 patients were used, being 187 RH. Sample preparation and analysis were performed using a column with restricted access carbon nanotubes (RACNTs) in a liquid chromatography coupled to mass spectrometer (UPLC-MS/MS) in column switching mode. Genetic ancestry was performed using a panel of 192 polymorphic markers; three references were used (European, Amerindian and African). The race was determined by self-declaration, according to IBGE (white, brown, black and others). Results: The method has been fully validated according to the guidelines of the Food and Drug Administration (FDA). The total run time for each analysis was 12.0 min including sample preparation. No significant differences were found in the concentrations of each analyte according to responsive and nonresponsive patients, possibly because of the still low number of samples (total n of 171 samples). The means of the measurements in the responders group were: clonidine 1.308microg/L; amlodipine 44.044microg/L; enalapril 67.706microg/L; enalaprilat 44.144microg/L; losartan 202.622microg/L; losartan carboxylic acid 65.99microg/L, N-2 glucuronide of losartan 43,4microg/L and spironolactone 85.87microg/L. For the group of non-responders, we obtained: clonidine 1.4 microg/L; amlodipine 78.89microg/L; enalapril 87.821microg/L; enalaprilat 78.878microg/L; losartana 148.026microg/L, losartan carboxylic acid 83.535microg/L, N-2 glucanide of losartan 122.452microg/L and spironolactone 79.72microg/L. Self-reported race was associated with the components of the genetic ancestry of these patients (p<0.001). Genetic ancestry, available for 1,503 patients, had an overall mean of 0.53 for European; 0.11 for Amerindian; and 0.35 for African. No statistical differences were found in the means of ancestry according to responder or RH groups. Conclusion: The analytical method was validated and genetic ancestry was performed, both unrelated to pharmacotherapeutic and resistant hypertension

(1) Were among the antihypertensive drugs with the lowest likelihood of discontinuation implying a potentially superior tolerability profile (2) Had similar odds of short and long term rates of add-on pharmacotherapy implying a similar efficacy with other drug classes (3) Were associated with statistically similar all cause and CVS mortality (4) Had similar odds of presenting with impaired fasting glucose in the short-term. (5) Had higher odds of presenting with hypercholesterolemia in the short-term but the absolute increase in cholesterol was minimal (in the magnitude of 0.14 mmol/1). > (6) Had similar odds of presenting with hyponatremia and hypokalemia in the short-term. / Due to the large sample size these studies are likely to be representative and are new findings among ethnic Chinese patients presenting with uncomplicated hypertension. These results point towards thiazide diuretics as a favorable first-line antihypertensive agent in the management of uncomplicated hypertension in Hong Kong primary practice, in addition to favorable public health considerations including affordability. These studies are in support of guidelines from international authorities recommending thaizide diuretics as the best choice of first-line antihypertensive agent, and suggest that such international guidelines may be generalizable to patients of Chinese race. (Abstract shortened by UMI.) / In these studies we have characterized the major antihypertensive drug classes in terms of their prescription patterns, efficacy, tolerability and association with adverse clinical as well as biochemical outcomes. The completeness of CDARS and e-CMS of the Hospital Authority allows retrieval and comparison of these clinical outcomes of the commonly used antihypertensive agents. The present studies showed that prescription of CCB and BB were high compared with international trends and that of thiazide particularly low and showed a declining trend. Yet when compared with other drug classes, thiazide diuretics: / Wong Chi Sang. / Adviser: Stewart William Mercer. / Source: Dissertation Abstracts International, Volume: 70-09, Section: B, page: . / Thesis submitted in: September, 2008. / Thesis (M.D.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 223-260). / 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, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / School code: 1307.

After adjusted for the effect of baseline MCE risk and reduction in SBP, the multivariate meta-regression showed baseline SBP was not significantly related to the RD for all the relevant outcomes examined (p>0.22) except MCE (p=0.0226). However, the baseline MCE risk remained significantly related to the RD for all the outcomes (p&lt;0.01) except CHD (p=0.1011). The reduction in SBP remained significantly related to the RD for deaths due to CVD, MCE, CHF and stroke (p&lt;0.01) but not to the RD for all-cause death (p=0.3788) and CHD (p=0.8755). / Conclusions. This study showed that baseline CVD risk and reduction in blood pressure were strongly and consistently related to the absolute effect of treatment and surprisingly the baseline blood pressure was not. The findings lend direct support to the overall risk approach to primary prevention and suggest that contrary to conventional wisdom and current practice, the overall CVD risk rather than blood pressure alone should be used to identify and treat people to prevent major CVD events through anti-hypertensive drugs. These findings suggest that anti-hypertensive drugs should be given to those who have a high future CVD risk rather than high blood pressure alone so as to achieve better cost-effectiveness of anti-hypertensive drugs for primary prevention. / Data extraction and analyses: Two reviewers independently abstracted data on baseline variables, variables that determine methodological quality, and outcomes. The following main outcomes were assessed: all-cause deaths, deaths due to cardiovascular disease, death due to causes other than CVD, major cardiovascular events (MCE), congestive heart failure (CHF), stroke, and coronary heart disease (CHD). / Key words. hypertension, antihypertensive drugs, cardiovascular disease, meta-analysis, systematic review, randomized controlled trial, primary prevention, baseline risk, evidence based medicine / Meta-analysis was used to obtain the overall odds ratio (OR) and risk difference (RD). Forest plots, bubble plots and funnel plots were used to show the results visually or to check biases. Meta-regression was used to identify factors that may independently determine the effect of antihypertensive drugs. The control CVD risk, initial mean blood pressure and reduction in blood pressure were examined. / Method. Identification of studies: The databases searched included ACP Journal Club, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, Cumulative Index to Nursing & Allied Health Literature, Chinese Medical Current Contents to identify relevant studies between 1966 and 2005. We also examined references from relevant trials, reviews and meta-analyses. For trials to be included in this review, they have to have the following characteristics: (1) essential hypertension in patients of any age, sex and race; (2) treatment intervention is antihypertensive drugs; (3) control intervention is a placebo or no treatment; (4) endpoint outcomes are all-cause death and major cardiovascular events; and (5) randomized controlled trials. / Objective. Although the overall risk approach to cardiovascular disease (CVD) primary prevention has been widely adopted, direct evidence that supports this policy is however weak and in some aspects lacking. Importantly, there is no direct evidence to show, between blood pressure and CVD risk, which is a better predictor of the absolute benefit from anti-hypertensive drugs. The evidence that the absolute benefit increases as the future CVD risk increases does not necessarily mean that treating high risk people will be more cost-effective than treating hypertensive people as blood pressure may also be positively related to treatment benefit. The high risk approach would be preferable only when we can show with strong evidence that blood pressure is not related to the absolute benefit of treatment or the CVD risk is much more strongly related to the benefit than blood pressure. We thus conducted this systematic review to examine the evidence from randomized controlled trials to directly show how blood pressure and CVD risk are related to the absolute benefit from anti-hypertensive drugs and compare the capability of the two factors in predicting the benefit. The stronger predictor should be a better indicator for identifying those who should be treated with anti-hypertensive drugs. / Results. Twenty-two eligible randomized controlled trials with a total of 55,448 participants were identified from 1967 to 2004. The average follow-up was 45.6 months ranging from 13 to 84 months. The combined RD and OR for all-cause deaths, deaths due to CVD, MCE, CHF, Stroke and CHD were all statistically significant, showing a consistent and considerable reduction in the risk of these outcomes due to the treatment of anti-hypertensive drugs (p&lt;0.01). / Jiang, Yu. / "September 2007." / Adviser: Jin Ling Tang. / Source: Dissertation Abstracts International, Volume: 69-08, Section: B, page: 4657. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (p. 107-115). / 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, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract in English and Chinese. / School code: 1307.

Introdução: Pacientes hipertensos resistentes (HR) são indivíduos com pressão arterial não controlada - apesar do tratamento com um diurético e dois anti-hipertensivos com mecanismos de ação diferentes em doses adequadas. Há duas áreas de interesse nesse contexto: a ancestralidade genética que, a princípio, poderia impactar em controles pressóricos, e a farmacometabolômica que, conceitualmente, é um conjunto de mudanças em concentrações de metabólitos - um novo campo que pode esclarecer mecanismos de variações de respostas farmacológicas. Assim, nossos principais objetivos foram: associar mensurações séricas de fármacos anti-hipertensivos e seus metabólitos às respostas farmacoterapêuticas em pacientes hipertensos e analisar a ancestralidade genética em pacientes hipertensos a fim de verificar uma possível associação com as respostas farmacoterapêuticas e a hipertensão resistente. Métodos: Foram utilizadas amostras de 1.597 pacientes, sendo 187 HR. A preparação e a análise da amostra foram realizadas usando uma coluna com nanotubos de carbono de acesso restrito (RACNTs) em um sistema de cromatografia líquida acoplada a espectrômetro de massa (UPLC-MS/MS), em modo column switching. A ancestralidade genética foi realizada usando um painel de 192 marcadores polimórficos; três referências foram usadas (europeia, ameríndia e africana). A raça foi determinada pela autodeclaração, segundo IBGE (branco, pardo, negro e outros). Resultados: O método foi totalmente validado de acordo com as diretrizes da Food and Drug Administration (FDA). O tempo de execução total para cada análise foi de 12,0 min - incluindo a preparação da amostra. Não foram encontradas diferenças significativas nas concentrações de cada analito de acordo com pacientes responsivos e não responsivos, possivelmente, por causa do número de amostra ainda baixo (n total de 171 amostras). As médias das mensurações no grupo dos respondedores foram: clonidina 1,308microg/L; amlodipina 44,044microg/L; enalapril 67,706microg/L; enalaprilato 44,144microg/L; losartana 202,622microg/L; ácido carboxílico de losartana 65,99microg/L, glicuronídeo N-2 de losartana 43,4microg/L e espironolactona 85,87microg/L. Para o grupo dos não respondedores, obtivemos: clonidina 1,4microg/L; amlodipina 78,89microg/L; enalapril 87,821microg/L; enalaprilato 78,878microg/L; losartana 148,026microg/L, ácido carboxílico de losartana 83,535microg/L, glicuronídeo N-2 de losartana 122,452microg/L e espironolactona 79,72microg/L. A raça autodeclarada foi associada aos componentes da ancestralidade genética desses pacientes (p<0,001). A ancestralidade genética, disponível para 1.503 pacientes, teve média geral de 0,53, para europeia; 0,11, para ameríndia; e 0,35, para africana. Não foram encontradas diferenças estatísticas nas médias de ancestralidade de acordo com os grupos respondedor ou HR. Conclusões: O método analítico foi validado e a ancestralidade genética foi realizada, ambos não associados à farmacoterapêutica e à hipertensão resistente / Background: Resistant hypertensive (RH) patients are individuals with uncontrolled blood pressure - despite treatment with one diuretic and two antihypertensives with different mechanisms of action in adequate doses. There are two areas of interest in this context: genetic ancestry that could initially impact on blood pressure controls, and pharmacometabolomics, which conceptually is a set of changes in metabolite concentrations - a new field that can clarify mechanisms of pharmacological response variation. Thus, our main objectives were: to associate serum measurements of antihypertensive drugs and their metabolites to the pharmacotherapeutic responses in hypertensive patients and to analyze genetic ancestry in hypertensive patients in order to verify a possible association with pharmacotherapeutic responses and resistant hypertension. Methods: Samples of 1,597 patients were used, being 187 RH. Sample preparation and analysis were performed using a column with restricted access carbon nanotubes (RACNTs) in a liquid chromatography coupled to mass spectrometer (UPLC-MS/MS) in column switching mode. Genetic ancestry was performed using a panel of 192 polymorphic markers; three references were used (European, Amerindian and African). The race was determined by self-declaration, according to IBGE (white, brown, black and others). Results: The method has been fully validated according to the guidelines of the Food and Drug Administration (FDA). The total run time for each analysis was 12.0 min including sample preparation. No significant differences were found in the concentrations of each analyte according to responsive and nonresponsive patients, possibly because of the still low number of samples (total n of 171 samples). The means of the measurements in the responders group were: clonidine 1.308microg/L; amlodipine 44.044microg/L; enalapril 67.706microg/L; enalaprilat 44.144microg/L; losartan 202.622microg/L; losartan carboxylic acid 65.99microg/L, N-2 glucuronide of losartan 43,4microg/L and spironolactone 85.87microg/L. For the group of non-responders, we obtained: clonidine 1.4 microg/L; amlodipine 78.89microg/L; enalapril 87.821microg/L; enalaprilat 78.878microg/L; losartana 148.026microg/L, losartan carboxylic acid 83.535microg/L, N-2 glucanide of losartan 122.452microg/L and spironolactone 79.72microg/L. Self-reported race was associated with the components of the genetic ancestry of these patients (p<0.001). Genetic ancestry, available for 1,503 patients, had an overall mean of 0.53 for European; 0.11 for Amerindian; and 0.35 for African. No statistical differences were found in the means of ancestry according to responder or RH groups. Conclusion: The analytical method was validated and genetic ancestry was performed, both unrelated to pharmacotherapeutic and resistant hypertension

Ng, Chun Fai. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 134-150). / Abstracts in English and Chinese. / Abstract --- p.i / Acknowledgements --- p.vii / Table of Contents --- p.ix / Abbreviations --- p.xii / List of Figures --- p.xv / List of Tables --- p.xviii / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- "Introduction to Cardiovascular Disease, Hypertension and Atherosclerosis" --- p.1 / Chapter 1.1.1 --- Cardiovascular Disease --- p.1 / Chapter 1.1.2 --- Hypertension --- p.2 / Chapter 1.1.2.1 --- Background --- p.2 / Chapter 1.1.2.2 --- Causes of Hypertension --- p.3 / Chapter 1.1.2.3 --- Current Western Management and Medication --- p.6 / Chapter 1.1.3 --- Atherosclerosis --- p.9 / Chapter 1.1.3.1 --- Background --- p.9 / Chapter 1.1.3.2 --- Pathogenesis of Atherosclerosis --- p.10 / Chapter 1.1.3.3 --- Current Western Treatment and Medication --- p.12 / Chapter 1.2 --- Selection and Introduction of Current Chinese Medicine Formula --- p.16 / Chapter 1.2.1 --- Cardiac Syndrome in Traditional Chinese Medicine --- p.16 / Chapter 1.2.2 --- Traditional Chinese Medicine as an Complementary or Alternative Medicine --- p.17 / Chapter 1.2.3 --- Selection of TCM Formula from Pharmacopoeia --- p.18 / Chapter 1.2.3.1 --- Compound Formula --- p.18 / Chapter 1.2.4 --- Introduction to Constitutional Herbal Medicine --- p.19 / Chapter 1.2.4.1 --- Danshen (Radix Salviae miltiorrhizae) --- p.19 / Chapter 1.2.4.2 --- Gegen (Radix Puerariae lobatae) --- p.20 / Chapter 1.2.4.3 --- Yanhusuo (Rhizoma Corydalis) --- p.21 / Chapter 1.2.4.4 --- Composition of the Final Formula Used in the Present Study --- p.21 / Chapter 1.2.5 --- Previous work on Danshen-Gegen Formula and its limitations --- p.22 / Chapter 1.3 --- Objectives of the Present Study --- p.25 / Chapter 1.3.1 --- Research Plan --- p.26 / Chapter Chapter 2 --- Experimental Design and General Methodology --- p.27 / Chapter 2.1 --- Source and Authentication of Raw Herbs --- p.27 / Chapter 2.2 --- Materials --- p.29 / Chapter 2.3 --- Ethical Approval --- p.31 / Chapter 2.4. --- General Methods --- p.32 / Chapter 2.4.1 --- Blood Pressure Measurement --- p.32 / Chapter 2.4.2 --- Blood Profile Measurement --- p.33 / Chapter 2.4.3 --- Vascular Reactivity Studies --- p.36 / Chapter 2.5 --- Statistical Analysis --- p.38 / Chapter Chapter 3 --- Anti-hypertensive Studies of Danshen-Gegen Formula on Rat --- p.39 / Chapter 3.1 --- Introduction --- p.39 / Chapter 3.1.1 --- In vivo Anti-Hypertensive Studies --- p.39 / Chapter 3.1.1.1 --- Spontaneously Hypertensive Rat (SHR) --- p.40 / Chapter 3.1.1.2 --- Tail-cuff Blood Pressure Measurement --- p.41 / Chapter 3.1.2 --- Detailed Underlying Mechanistic Studies --- p.42 / Chapter 3.1.2.1 --- Nitric Oxide-mediated Vasodilation --- p.42 / Chapter 3.1.2.2 --- Prostacyclin-mediated Vasodilation --- p.43 / Chapter 3.1.2.3 --- Hyperpolarization-mediated Vasodilation --- p.43 / Chapter 3.1.2.4 --- Endothelium-dependent/-independent Vasodilation --- p.46 / Chapter 3.1.3 --- Long Term Underlying Mechanistic Studies --- p.48 / Chapter 3.2 --- Methods --- p.49 / Chapter 3.2.1 --- In vivo Anti-Hypertensive Studies --- p.49 / Chapter 3.2.2 --- Detailed Underlying Mechanistic Studies --- p.51 / Chapter 3.2.3 --- Long Term Underlying Mechanistic Studies --- p.53 / Chapter 3.2.4 --- Statistical analysis --- p.56 / Chapter 3.3 --- Results --- p.58 / Chapter 3.3.1 --- In vivo Anti-Hypertensive Studies --- p.58 / Chapter 3.3.1.1 --- Preventive Effect in Hypertension --- p.58 / Chapter 3.3.1.2 --- Therapeutic Effect in Hypertension --- p.62 / Chapter 3.3.2 --- Detailed Underlying Mechanistic Studies --- p.66 / Chapter 3.3.2.1 --- DG extract-induced Vasodilation --- p.66 / Chapter 3.3.2.2 --- Endothelium-independent Vasodilation --- p.67 / Chapter 3.3.2.3 --- Nitric Oxide-mediated Vasodilation --- p.68 / Chapter 3.3.2.4 --- Prostacyclin-mediated Vasodilation --- p.69 / Chapter 3.3.2.5 --- Hyperpolarization-mediated Vasodilation --- p.70 / Chapter 3.3.3 --- Long Term Underlying Mechanistic Studies --- p.74 / Chapter 3.4 --- Discussion --- p.79 / Chapter Chapter 4 --- Anti-atherosclerosis Studies of Danshen-Gegen Formula in Rabbits --- p.89 / Chapter 4.1 --- Introduction --- p.89 / Chapter 4.1.1 --- Intima-Media Thickening --- p.89 / Chapter 4.1.2 --- Effect of High Cholesterol Diet in Rabbit --- p.90 / Chapter 4.1.3 --- Thiobarbituric Acid Reactive Substances --- p.91 / Chapter 4.2 --- Methods --- p.93 / Chapter 4.2.1 --- Pilot Study for Establishment of Experimental Protocol --- p.93 / Chapter 4.2.2 --- Effect of DG extract on Intima-media Thickening --- p.97 / Chapter 4.2.3 --- Statistical analysis --- p.99 / Chapter 4.3 --- Result --- p.100 / Chapter 4.3.1 --- Study of the Anti-atherosclerosis Effect of DG extract - First Run --- p.100 / Chapter 4.3.2 --- Study of the Anti-atherosclerosis Effect of DG extract - Second Run --- p.108 / Chapter 4.4 --- Discussion --- p.117 / Chapter Chapter 5 --- General Discussion and Conclusion --- p.122 / Chapter 5.1 --- Significance of the Study --- p.122 / Chapter 5.2 --- Limitations and Future work --- p.127 / Chapter 5.3 --- Clinical Implication of the Use of the DG Preparations for Patients with CVD --- p.132 / References --- p.134

Diss. (sammanfattning) Uppsala : Univ., 2004. / Härtill 4 uppsatser.