Left ventricular hypertrophy (LVH), the detection of which is recommended for routine risk prediction by all guidelines, is more prevalent in groups of African ancestry. This is in-part attributed to higher prevalence rates of obesity. The ability to detect LVH using electrocardiographic (ECG) criteria may be modified in groups of African ancestry. The impact of co-existent obesity on the ability to detect ECG-LVH in this ethnic group has not been determined. Moreover, whether estimated glomerular filtration rate (eGFR) or serum C-reactive protein (CRP concentrations are independently associated with LV mass index (LVMI) and can therefore be used to complement ECG criteria for LVH detection is uncertain. ECG voltage criteria for the detection of echocardiographic LVH were evaluated in 661 participants from a community sample of African ancestry (43% obese). Body mass index (BMI) was inversely associated with Sokolow-Lyon (SL) voltages (partial r=-0.27, p<0.0001) and no BMI-Cornell voltage relations were noted (p=0.21). BMI was associated with voltage criteria that incorporate only limb lead recordings (r=0.17-0.23), but these relationships were weaker than BMI-LVMI relations (r=0.36, p<0.01-p<0.0001 for comparisons of r values). All ECG criteria were as strongly related to blood pressure (BP) as LVMI. Sokolow-Lyon voltage-LVMI relations were noted only after adjustments for BMI (p<0.02) and SL voltages showed no performance for LVH detection. Cornell voltages showed significant performance in the non-obese (area under the receiver operating curve [AUC]=0.67±0.04, p<0.0005), but not the obese (AUC=0.56±0.04, p=0.08). ECG criteria which employ limb-lead recordings only (e.g. RaVL) showed better performance in non-obese than obese (AUC=0.75±0.04 and 0.59±0.04 respectively, p<0.005 for comparison) and markedly reduced specificity for LVH detection in obese (76%) than non-obese (92%, p<0.0001) despite similar sensitivities (32 vs 29%). Thus, in groups of African ancestry, obesity contributes toward a poor validity and performance of all voltage criteria for the detection of LVH. None of the current criteria are recommended for use in obesity in groups of African descent. Alternative approaches are required for LVH detection in these groups.In 621 randomly selected participants from the community sample [332 were normotensive (NT)], eGFR was associated with LVMI and LVM in excess of that predicted from stroke work (inappropriate LVM, LVMinappr) in all participants (LVMI: partial r=-0.18, p<0.0001; LVMinappr: partial r=-0.17, p<0.0001) and NT (LVMI: partial r=-0.23,p<0.0001; LVMinappr: partial r=-0.22, p<0.0001) separate from hypertensives. When replacing clinic BP with either aortic systolic BP (applanation tonometry and SphygmoCor software), 24-hour BP, aortic pulse wave velocity (PWV) (applanation tonometry and SphygmoCor software), stroke work (for LVMI), LV end diastolic diameter (LVEDD), or circumferential wall stress in the regression models, eGFR retained strong associations with LVMI (p=0.01 to <0.0001) and LVMinappr (p<0.005 to <0.0001). Thus, strong relationships between eGFR and LVM occur at a community level irrespective of the presence of hypertension and independent of 24-hour and aortic BP, PWV, LVEDD,stroke work and wall stress. The independent relationships between eGFR and LVMI, support the notion that eGFR may be evaluated for LVH detection. In 361 randomly selected participants from a community with a high prevalence of CRP concentrations considered to be high-risk (54.0%), but without cardiovascular or renal disease, serum CRP concentrations were correlated with both LVMI and LVMinappr (p<0.0001). With adjustments for a number of potential confounders including age, systolic BP, waist circumference (or BMI), and glucose control (glycated haemoglobin), the relationships between serum CRP concentrations and both LVMI and LVMinappr (partial r=0.11, p<0.05 for both) persisted. The independent relationship between CRP and LVMI or LVMinappr translated into a higher multivariate-adjusted LVMI and LVMinappr values in the highest as compared to the lowest quartile of CRP (LVMI; highest quartile CRP=48.8±10.7, lowest quartile CRP=45.0±11, p<0.05; LVMinappr; highest quartile CRP=137±24, lowest quartile CRP=127±24, p<0.05). The independent relationships between CRP and LVMI, support the notion that CRP may also be evaluated for LVH detection. In 358 participants from a randomly selected community sample with a high prevalence of obesity (41%), a combination of CRP concentrations and eGFR above or below the median for the sample respectively showed significant performance (AUC=0.61±0.03, p<0.0005), but a low specificity for LVH detection (77%). When eGFR and CRP concentrations were employed to complement RaVL, although the overall performance did not improve (AUC=0.71±0.03, p<0.0005, RaVL alone: AUC=0.70±0.03), the specificity increased (93%) whilst sensitivity (25%) was in-line with previously reported sensitivities for LVH detection using ECG criteria in alternative population samples. Without changing overall performance, eGFR together with RaVL increased the specificity to 88% and CRP concentrations when considered together with RaVL increased the specificity to 87%. Thus, in a community sample where the specificity and performance of ECG criteria for LVH detection are poor, the use of eGFR and/or CRP concentrations to complement ECG criteria increase the specificity without altering the overall performance. In conclusion, the present thesis provides evidence to indicate that current ECG criteria for the detection of LVH are invalid in obese individuals of African ancestry, but that clinical markers of renal dysfunction and systemic inflammation, which are associated with LVMI independent of haemodynamic factors and co-morbidities may be employed to complement ECG criteria to improve the specificity for LVH detection.

Diss. (sammanfattning) Uppsala : Univ., 2001. / Härtill 5 uppsatser.

Left ventricular hypertrophy (LVH) is more frequently associated with LV dilatation and systolic chamber dysfunction in males than in females. The mechanisms of this effect are uncertain. As excessive adrenergic stimulation may be responsible for LV dilatation and systolic chamber dysfunction in hypertension, in my dissertation I aimed to assess whether gender determines the adverse effects on LV chamber remodeling following 6 months of daily β-adrenergic receptor (AR) stimulation (isoproterenol [ISO] at 0.04 mg.kg-1day-1) in spontaneously hypertensive rats (SHR). LV dilatation was assessed in vivo from LV end diastolic diameter (EDD) (echocardiography) and ex vivo from the volume intercept at 0 mm Hg pressure (V0) of the LV diastolic pressure-volume relationship (isolated, perfused heart technique). LV systolic function was determined in vivo from LV endocardial fractional shortening (FSend) and ex vivo from the slope (LV end systolic elastance [LV Ees]) of the LV end systolic pressure-volume relationship (isolated, perfused heart technique). As compared to saline-treated male SHR (n=13), male SHR receiving ISO for 6 months (n=13) developed an increased LV EDD (Male Saline: 6.56±0.20 mm; Male ISO: 7.78±0.29 mm; p<0.05) and LV V0 (Male Saline: 0.22±0.01 ml; Male ISO: 0.31±0.02 ml; p<0.05). In contrast, ISO administration failed to modify LV EDD (Female Saline, n=13: 6.06±0.15 mm; Female ISO, n=12: 6.33±0.15 mm) or LV V0 (Female Saline: 0.17±0.01ml; Female ISO: 0.17±0.01 ml) in female SHR. In addition, there was a gender-ISO interactive effect on LV Ees (p<0.05; Male Saline: 2268±336 mmHg.ml-1; Male ISO: 1623±164 mmHg.ml-1; Female Saline: 1910±219 mmHg.ml-1; Female ISO: 2302±230 mmHg.ml-1). In conclusion, as compared to female SHR, male SHR are more susceptible to the adverse effects of chronic β-AR activation on LV cavity dimensions and systolic chamber function. These results suggest that the higher prevalence of LV dilatation and systolic chamber dysfunction in males than in females with LVH may be attributed to an increased susceptibility to the adverse effects of adrenergic stimulation.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2002. / Härtill 6 uppsatser.

Thesis (M.Sc.)--Memorial University of Newfoundland, Faculty of Medicine, 2001. / Typescript. Bibliography: leaves 95-112.

Orientadores: Dora Maria Grassi-Kassisse, Regina Celia Spadari-Bratfisch / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-08T18:16:30Z (GMT). No. of bitstreams: 1 Miotto_AlexandreMarcucci_D.pdf: 1787456 bytes, checksum: dd0dd1fd4def2c09dbdbcec80f8f9888 (MD5) Previous issue date: 2006 / Resumo: Diversas doenças como dislipidemia, hiperinsulinemia associada a diabetes tipo 2, hipertensão, aterosclerose e outras doenças cardiovasculares são decorrentes do estilo de vida moderno, principalmente aquele verificado nos ricos países ocidentais. Estas desordens, antes prevalentes nas pessoas mais idosas, estão se tornando atualmente epidêmicas e afetando pessoas de todas as idades. A dieta desbalanceada é, certamente, um dos maiores contribuidores para estas anormalidades. Neste estudo nós alimentamos ratos com uma dieta hiperlípidica por 6 semanas para indução de um estado de hiperlipidemia, com elevação das concentrações plasmáticas de colesterol total, do LDL-colesterol e dos triglicerídeos, além de apresentar também significativo aumento do índice aterogênico. Os resultados mostraram também um desenvolvimento paralelo de hiperinsulinemia (0,75±0,02 vs 1,30 vs 0,12 ng/mL; N vs H) com níveis glicêmicos elevados nos ratos alimentados com dieta hiperlipídica e após jejum overnight (72,6±3 vs 84,1±1,5 mg/dL; N vs H), além de suave hipertensão e hipertrofia ventricular cardíaca. Nós concluímos que estas alterações metabólicas e cardiovasculares foram iniciadas pela dieta hiperlipídica administrada aos ratos, que esta condição se estabeleceu de forma relativamente rápida e que se encontra ainda em estágio inicial, podendo caracterizar o início da Síndrome Plurimetabólica, também conhecida como Síndrome X / Abstract: Several diseases, such as dyslipidemia, hyperinsulinemia and type 2 diabetes mellitus, hypertension, atherosclerosis, cardiovascular diseases, seem to be decurrent of the modern life style, mainly verified in the rich occidental countries. These disorders incidence, before prevalent in the elderly are more and more frequent and became nowepidemic by affecting people of all ages. The disbalanced diet is a greater contributor for these abnormalities. In this study we fed rats with a high fat-cholesterol diet for six weeks to induce a hyperlipidaemia, which showed enhanced levels of total cholesterol, LDLcholesterol and triglycerides, beyond presentate also a significative increase in the atherogenic index. The results showed also a parallel development of hyperinsulinemia (0.75±0.02 vs 1.30 vs 0.12 ng/mL; N vs H) with glicemic levels elevated in rats fed with hyperlipidemic diet and after overnight fast (72.6±3 vs 84.1±1.5 mg/dL; N vs H), beyond mild hypertension and ventricular cardiac hypertrophy after diet administration. We conclude that there was hazardous metabolic and cardiovascular alterations and all of them were triggered by the high fat-cholesterol diet administered to the rats in a very short time, which may characterize the beggining of Plurimetabolic Syndrome or Syndrome X / Doutorado / Fisiologia / Mestre em Biologia Funcional e Molecular

Orientador: Wilson Nadruz Junior / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-07T22:16:04Z (GMT). No. of bitstreams: 1 Sales_MariaLilian_M.pdf: 699325 bytes, checksum: c06952a4445a0175323db1f2dd969bed (MD5) Previous issue date: 2006 / Resumo: A subunidade p22phox é um componente essencial do complexo enzimático NADPH oxidase, o qual é considerado a principal fonte de produtos do stress oxidativo no sistema cardiovascular. O alelo -930G da p22phox tem sido associado com maior stress oxidativo mediado pela NADPH oxidase e hipertensão arterial. Nós recentemente demonstramos que a hipertrofia do ventrículo esquerdo é acompanhada de aumento na expressão miocárdica de p22phox em ratos submetidos à coarctação da aorta, sugerindo que esta proteína pode estar envolvida em lesões de órgão-alvo induzidas por hipertensão, mais especificamente na hipertrofia cardíaca. Foi pesquisada a prevalência deste polimorfismo em 160 indivíduos acompanhados no Ambulatório de Hipertensão Arterial Sistêmica da UNICAMP, e realizada a correlação desta variante com a massa e geometria ventricular esquerda, lesão renal e perfil metabólico destes pacientes. Não foram encontradas correlações significativas entre este polimorfismo e lesão renal ou estrutural em ventrículo esquerdo. Porém, nos indivíduos com genótipo GG foram encontrados níveis séricos de Triglicérides e de LDL colesterol significativamente mais baixos / Abstract: The p22phox subunit is an essential component of the NAD(P)H oxidase enzymatic complex, which is considered the major source of oxidative stress products in the cardiovascular system. The -930G allele of p22-phox has been associated with higher promoter activity, increased NAD(P)H oxidase-mediated oxidative stress and hypertension. NADPH oxidases have been proved important in the pathogenesis of renal damage in models of hypertension. We recently reported that left ventricular hypertrophy is accompanied by increased myocardial p22-phox expression in aortic-banded rats, suggesting that this protein might be involved in hypertensive cardiac hypertrophy. Thus, the aim of the present report was to investigate the role of p22phox -930A/G polymorphism on cardiac hypertrophy, renal damage and metabolic profile in hypertensive patients. We research the -930A/G polimorfism prevalence in 160 hypertensive subjects from Ambulatory Hypertension Unit - UNICAMP. The follow-up was between 2005 and 2006. The variant -930A/G has not relationship with alterations in ventricular structure and with renal damage markers. However, in GG subjects was associated with lower seric levels of Triglycerides and LDL-cholesterol This finding suggest a association between this variant GG genotype with a best metabolic profile in hypertensives / Mestrado / Clinica Medica / Mestre em Clinica Medica

A hipertrofia ventricular esquerda (HVE) é importante fator de risco cardiovascular. O objetivo deste estudo retrospectivo foi verificar a associação de critérios eletrocardiográficos de HVE com as características anatômicas e histológicas do coração, em 51 pacientes submetidos à necropsia. Procedeu-se à medição do diâmetro transverso dos cardiomiócitos e da porcentagem de fibrose do ventrículo esquerdo e direito. Entre os pacientes que apresentavam HVE anatômica, o critério de Romhilt foi positivo em 92,3%, sendo superior aos demais critérios avaliados, com especificidade de 89,5% e sensibilidade de 68,8%, Foi o único que se associou a características anatômicas e histológicas do coração / The left ventricular hypertrophy (LVH) is an important cardiovascular risk factor. The purpose of the present retrospective paper is to examine the association of LVH electrocardiographic criteria with both anatomical and histological characteristics of the heart on 51 patients submitted to the necropsy. The study carried out the measurement of the transverse diameter of cardiomyocytes, as well as the percentage of fibrosis at both left and right ventriculi. Among those patients who presented anatomic LVH, the Romhilt criterium resulted positive in 92.3% of the cases, thus surpassing the other criteria evaluated, with specificity and sensibility up to 89.5% and 68.8% respectively. This was the only criterium associated to both anatomic and histological characteristics of the heart

Made available in DSpace on 2015-03-03T11:52:35Z (GMT). No. of bitstreams: 0 Previous issue date: 2014-07-04Bitstream added on 2015-03-03T12:06:24Z : No. of bitstreams: 1 000808155.pdf: 1450590 bytes, checksum: dd023c166c21f3c5d8b15fbf9b3b87be (MD5) / Fundação para o Desenvolvimento da UNESP (FUNDUNESP) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Vários estudos apontam o elevado risco cardiovascular de pacientes com doença renal crônica (DRC). A DRC tem uma intrínseca relação com hipertensão arterial e cardiomiopatia, sendo essa última caracterizada principalmente por hipertrofia ventricular esquerda (HVE) e fibrose do miocárdio, importantes preditores de mortalidade cardiovascular nos pacientes com DRC. A redução da HVE é associada a aumento da expectativa de vida desses pacientes. A espironolactona é um esteróide sintético, que atua como antagonista da aldosterona, e que, historicamente, não tem sido usada em pacientes com DRC, por causa do risco de hipercalemia. Contudo, a espironolactona e seu metabólito ativo, canrenona, foram capazes de antagonizar a ligação da ouabaína à bomba Na+/K+-ATPase. A ouabaína endógena age como ligante dessa enzima, e contribui para HVE, aumento da resistência periférica total e consequente aumento da pressão arterial. A espironolactona e a canrenona, em pesquisas anteriores, foram capazes de reduzir a HVE em pacientes com DRC em tratamento conservador, o que torna a espironolactona uma ferramenta potencial para o tratamento de pacientes com DRC, em hemodiálise, que apresentam HVE. Os objetivos do presente estudo foram avaliar a eficácia da espironolactona em reduzir a HVE de pacientes com DRC em tratamento hemodialítico, quando associada à terapia anti-hipertensiva convencional, além de verificar a segurança de seu uso, quanto ao surgimento de hipercalemia e sua tolerabilidade quanto à ocorrência de reações adversas, realizando monitoramento farmacoterapêutico e garantindo o uso seguro desse medicamento. Foi realizado estudo de intervenção, unicêntrico, randomizado, duplo-cego, placebo-controlado, composto por dois grupos: um que recebeu 12,5 mg ou 25 mg de espironolactona, associada à terapia anti-hipertensiva convencional (8 pacientes) e outro que recebeu placebo de espironolactona 12,5 mg ou 25 mg associado à ... / Several studies demonstrated the high cardiovascular risk of Chronic Kidney Disease (CKD) patients. The CKD has an intrinsic relationship with hypertension and cardiomyopathy, the latter being mainly characterized by left ventricular hypertrophy (LVH) and myocardial fibrosis, an important predictor of cardiovascular mortality in CKD patients. The reversal of LVH is associated with an increase in life expectancy in these patients. Spironolactone is a synthetic steroid that acts as an antagonist of aldosterone and that historically has not been used in patients with CKD, because of the risk of hyperkalemia. However, spironolactone and its active metabolite, canrenone, are capable of antagonizing the binding of ouabain to its receptor on Na+/K+-ATPase pump. Endogenous ouabain acts as a binder in the Na+/K+-ATPase, and contributes to the left ventricular hypertrophy, elevation of the total peripheral resistance and consequent increase in vascular blood pressure. Spironolactone and canrenone, in previous research, were able to reduce LVH in non-dialysis CKD patients, which make spironolactone a potential tool for the treatment of dialysis CKD patients with LVH. The aim of this study is to verify the effectiveness of spironolactone, when associated with conventional antihypertensive therapy, in reducing LVH in hemodialysis CKD patients. In addition, to verify the safety of its use regarding of hyperkalemia, and, its tolerability as the occurrence of adverse reactions, with pharmacotherapeutic monitoring for the safe use of this drug. Interventional, single-center, randomized, double-blind, placebo-controlled study was conducted, composed of two groups: one that received 12.5 mg or 25 mg of spironolactone associated with conventional antihypertensive therapy (8 patients) and another that receive placebo spironolactone 12.5 mg or 25 mg associated (9 patients) with conventional antihypertensive therapy. Clinical and laboratory ...

Orientador: Luis Cuadrado Martin / Coorientador: Pasqual Barretti / Banca: Fernando Antonio de Almeida / Banca: José Francisco Kerr Saraiva / Banca: Paulo Angelo Lorandi / Banca: Roberto Jorge da Silva Franco / Resumo: Vários estudos apontam o elevado risco cardiovascular de pacientes com doença renal crônica (DRC). A DRC tem uma intrínseca relação com hipertensão arterial e cardiomiopatia, sendo essa última caracterizada principalmente por hipertrofia ventricular esquerda (HVE) e fibrose do miocárdio, importantes preditores de mortalidade cardiovascular nos pacientes com DRC. A redução da HVE é associada a aumento da expectativa de vida desses pacientes. A espironolactona é um esteróide sintético, que atua como antagonista da aldosterona, e que, historicamente, não tem sido usada em pacientes com DRC, por causa do risco de hipercalemia. Contudo, a espironolactona e seu metabólito ativo, canrenona, foram capazes de antagonizar a ligação da ouabaína à bomba Na+/K+-ATPase. A ouabaína endógena age como ligante dessa enzima, e contribui para HVE, aumento da resistência periférica total e consequente aumento da pressão arterial. A espironolactona e a canrenona, em pesquisas anteriores, foram capazes de reduzir a HVE em pacientes com DRC em tratamento conservador, o que torna a espironolactona uma ferramenta potencial para o tratamento de pacientes com DRC, em hemodiálise, que apresentam HVE. Os objetivos do presente estudo foram avaliar a eficácia da espironolactona em reduzir a HVE de pacientes com DRC em tratamento hemodialítico, quando associada à terapia anti-hipertensiva convencional, além de verificar a segurança de seu uso, quanto ao surgimento de hipercalemia e sua tolerabilidade quanto à ocorrência de reações adversas, realizando monitoramento farmacoterapêutico e garantindo o uso seguro desse medicamento. Foi realizado estudo de intervenção, unicêntrico, randomizado, duplo-cego, placebo-controlado, composto por dois grupos: um que recebeu 12,5 mg ou 25 mg de espironolactona, associada à terapia anti-hipertensiva convencional (8 pacientes) e outro que recebeu placebo de espironolactona 12,5 mg ou 25 mg associado à ... / Abstract: Several studies demonstrated the high cardiovascular risk of Chronic Kidney Disease (CKD) patients. The CKD has an intrinsic relationship with hypertension and cardiomyopathy, the latter being mainly characterized by left ventricular hypertrophy (LVH) and myocardial fibrosis, an important predictor of cardiovascular mortality in CKD patients. The reversal of LVH is associated with an increase in life expectancy in these patients. Spironolactone is a synthetic steroid that acts as an antagonist of aldosterone and that historically has not been used in patients with CKD, because of the risk of hyperkalemia. However, spironolactone and its active metabolite, canrenone, are capable of antagonizing the binding of ouabain to its receptor on Na+/K+-ATPase pump. Endogenous ouabain acts as a binder in the Na+/K+-ATPase, and contributes to the left ventricular hypertrophy, elevation of the total peripheral resistance and consequent increase in vascular blood pressure. Spironolactone and canrenone, in previous research, were able to reduce LVH in non-dialysis CKD patients, which make spironolactone a potential tool for the treatment of dialysis CKD patients with LVH. The aim of this study is to verify the effectiveness of spironolactone, when associated with conventional antihypertensive therapy, in reducing LVH in hemodialysis CKD patients. In addition, to verify the safety of its use regarding of hyperkalemia, and, its tolerability as the occurrence of adverse reactions, with pharmacotherapeutic monitoring for the safe use of this drug. Interventional, single-center, randomized, double-blind, placebo-controlled study was conducted, composed of two groups: one that received 12.5 mg or 25 mg of spironolactone associated with conventional antihypertensive therapy (8 patients) and another that receive placebo spironolactone 12.5 mg or 25 mg associated (9 patients) with conventional antihypertensive therapy. Clinical and laboratory ... / Doutor