Background: Resistant hypertension (RH) is defined as blood pressure (BP) that remains elevated (>140/90mmHg) despite being treated with an antihypertensive regimen of 3 or more medications from different classes, including a long-acting calcium channel blocker, an angiotensin converting enzyme inhibitor or angiotension receptor blocker and a diuretic. The prevalence of RH in South Africa is currently unknown, however, clinical reports suggest that it is not rare. Patients with RH are significantly predisposed to cardiovascular (CV) diseases compared to patients with controlled BP. Consequences of RH include left ventricular hypertrophy, heart failure, ischaemic heart disease, chronic kidney disease leading to end-stage renal disease, stroke, vascular dementia, CV death and peripheral arterial disease. A proportion of patients with RH who never achieve BP control despite maximal medical treatment, represent a potentially novel and distinctive phenotype which is different from RH patients whose BP canbe controlled. Recognising and categorising such patients becomes the initial and crucial step in stratifying phenotypes and defining mechanisms of treatment resistance. Objectives: The aim of this study was to identify patients with resistant uncontrolled hypertension (RUH) and compare phenotypes in these patients to resistant controlled hypertensives (RCH). Methods: We enrolled 50 patients from the Groote Schuur Hospital Hypertension Clinic: a teriary referral hospital for RH. Patients on 4 or more antihypertensive medication including a diuretic, with BP< 140/90mmHg were considered RCH, and those with BP ≥ 140/90 considered RUH. Assessments included clinical examination, electrocardiography, echocardiography, applanation tonometry, serum biomarkers and cardiovascular magnetic resonance (CMR - which included biventricular volumes and function, myocardial strain, tissue characteristics and late gadolinium enhancement - LGE). Results: Thirty were diagnosed with RUH and twenty with RCH. Patients with RUH were more likely to have a longer duration since diagnosis of hypertension (10.5±10.7 vs. 3.6±3.4, p=0.02) and more likely to be on treatment that included an ACE-inhibitor (90% vs. 58%, p=0.01). As expected, patients with RUH had significantly higher systolic BP (155.6±21.6 vs. 137.8±16.5 mmHg, p< 0.001), diastolic BP (88.4±14.5 vs. 77.5±13.6 mmHg, p= 0.03), mean arterial BP (115.4±17.2 vs 101±15.3 mmHg, p= 0.004) and pulse pressure (67.3±14.2 vs. 60.1±12.4 mmHg, p=0.001). Further, RUH patients had significantly lower large artery elasticity (12.5±4 vs 14.7±3.8ml/mmHgx100, p=0.08) and lower small artery elasticity (4.1±2.1 vs. 6.9±3.6ml/mmHgx100, p< 0.001). RUH patients also had a higher systemic vascular resistance (1754±418.4 vs. 1363±371.5dyneXsecXcm-5, p=0.002). On CMR, RUH patients had lower right ventricular (RV) end-systolic and end-diastolic volumes (p=0.02), as well as higher indexed left ventricular mass (LVMI) (61.6±17.6 vs 52.9±13.9 g/m2 , p= 0.06). There were no differences in native T1, extracellular volume quantification and LGE volume fraction between RUH and RCH patients. Conclusions: Patients with RUH have a greater involvement and more severe CV phenotype, that is likely to result in increased CV morbidity and mortality, including greater target end organ damage as a result of vascular adaptations and concentric remodeling.

No description available.

Heart failure contributes to nearly 60,000 deaths per year in the USA and is often caused by hypertension and preceded by the development of left ventricular hypertrophy (LVH). LVH is usually accompanied by intensive interstitial and perivascular fibrosis which may contribute to arrhythmogenic sudden cardiac death. Emerging evidence indicates that LV dysfunction in patients and animal models of cardiac hypertrophy is closely associated with perivascular inflammation. To investigate the role of perivascular inflammation in coronary artery remodeling and cardiac fibrosis during hypertrophic ventricular remodeling, we used a well-established mouse model of pressure-overload-induced LVH: transverse aortic constriction (TAC). Early perivascular inflammation was indicated by accumulation of macrophages and T lymphocytes 24 hours post-TAC and which peaked at day 7. Coronary luminal platelet deposition was observed along with macrophages and lymphocytes at day 3. Also, LV protein levels of VEGF and MCP-1 were significantly increased. Consistent with lymphocyte accumulation, cardiac expression of IL-10 mRNA was elevated. Furthermore, circulating platelet-leukocyte aggregates tended to be higher after TAC, compared to sham controls. Platelets have been shown to modulate perivascular inflammation and may facilitate leukocyte recruitment at sites of inflamed endothelium. Therefore, we investigated the impact of thrombocytopenia in the response to TAC. Immunodepletion of platelets decreased early perivascular accumulation of T lymphocytes and IL-10 mRNA expression, and altered subsequent coronary artery remodeling. The contribution of lymphocytes was examined in Rag1-/- mice, which displayed significantly more intimal hyperplasia and perivascular fibrosis compared to wild-type mice following TAC. Collectively, our studies support a role of early perivascular accumulation of platelets and T lymphocytes in pressure overload-induced inflammation which will contribute to long-term LV remodeling. One potential mechanism for inflammatory cells to modulate their environment and affect surrounding cells is through release of cargo stored in granules. To determine the contribution of granule release from inflammatory cells in the development of LVH, we used Unc13dJinx (Jinx) mice, which contain a single point mutation in Unc13d gene resulting in defects in Munc13-4. Munc13-4 is a limiting factor in vesicular priming and fusion during granule secretion. Therefore, Jinx mice have defects in degranulation of platelets, NK cells, cytotoxic T lymphocytes, neutrophils, mast and other cells. With the use of bone marrow transplantation, Jinx chimeric mice were created to determine whether the ability of hematopoietic cells to secrete granule contents affects the development of LVH. Wild-type mice (WT) that were transplanted with WT bone marrow (WT>WT) and WT mice that received Jinx bone marrow (Jinx>WT) developed LVH and a classic fetal reprogramming response early after TAC (7 days), but at later times (5 weeks), Jinx>WT mice failed to sustain the cardiac hypertrophic response observed in WT>WT mice. No difference in cardiac fibrosis was observed at early or late times. Repetitive injection of WT platelets or platelet releasate restored cardiac hypertrophy in Jinx>WT mice. These results suggest that sustained LVH in the setting of pressure overload depends on factor(s) secreted, likely from platelets. In conclusion, our studies demonstrate that platelets and lymphocytes are involved in early perivascular inflammation post-TAC, which may contribute to later remodeling in the setting of LVH. Factors released from hematopoietic cells, including platelets, in a Munc13-4-dependent manner are required to promote cardiac hypertrophy. These findings focus attention on modulating perivascular inflammation and targeting granule cargo release to prevent the development and consequences of LVH.

Background Coarctation of the aorta (CoA) constitutes 5-8 % of all congenital heart disease (CHD) and is associated with long-term complications such as hypertension (HTN) and left ventricular hypertrophy (LVH). Factors associated with HTN, LVH, and diffuse myocardial fibrosis, are not yet fully explored in this population. Methods Papers I-III: The Swedish national register of congenital heart disease (SWEDCON) was used to identify adult patients with repaired CoA. Paper IV: Data on 2,424 adult patients with CHD was extracted from SWEDCON and compared to controls (n = 4,605) regarding height, weight and body mass index (BMI). Paper V: Adults with CoA (n = 21, age 28.5 (19.1-65.1) years, 33.3 % female) referred for CMR were investigated with T1 mapping to determine left ventricular extracellular volume fraction (ECV). Results Papers I-II: Out of 653 patients, 344 (52.7 %) had HTN. In a multivariable model, age (years) (OR 1.07, CI 1.05-1.10), sex (male) (OR 3.35, CI 1.98-5.68) and BMI (kg/m2) (OR 1.09, CI 1.03-1.16) were associated with having HTN, and so was systolic arm-leg blood pressure (BP) gradient where an association was found at the ranges (10, 20] mmHg (OR 3.58, CI 1.70-7.55) and &gt; 20 mmHg (OR 11.38, CI 4.03-32.11), in comparison to the range [0, 10] mmHg. When investigating 243 patients with diagnosed HTN, 127 (52.3 %) had elevated BP (≥ 140/90 mmHg). Age (years) (OR 1.03, CI 1.01-1.06) was associated with elevated BP, and so was systolic arm-leg BP gradient in the ranges (10, 20] mmHg (OR 4.92, CI 1.76-13.79), and &gt; 20 mmHg (OR 9.93, CI 2.99-33.02), in comparison to the reference interval [0, 10] mmHg. Patients with elevated BP had more classes of anti-hypertensive medication classes prescribed (1.9 vs 1.5, p = 0.003). Paper III: Out of 506 patients, 114 (22.5 %) were found to have LVH. Systolic BP (mmHg) (OR 1.02, CI 1.01-1.04), aortic valve disease, (OR 2.17, CI 1.33–3.53), age (years) (OR 1.03, CI 1.01–1.05), and HTN (OR 3.02, CI 1.81-5.02), were associated with LVH, while sex (female) (OR 0.41, CI 0.24-0.72) was negatively associated with LVH. Paper IV: There was no difference in height, weight, or BMI between patients with CoA (n = 414) and the reference population. Paper V: In the population of 21 patients, an increased left ventricular myocardial ECV was found in 6 cases (28.6 %). Of the patients with increased ECV, 5/6 (83.3 %) were female (p = 0.002). Patients with increased ECV did not otherwise differ from the rest of the study population. iv Conclusions In adults with repaired CoA, HTN and LVH were common, and many patients with HTN had elevated BP despite treatment. The potentially modifiable factors BMI and systolic arm-leg BP gradient were associated with HTN, and the gradient was also associated with elevated BP among patients with diagnosed HTN. The gradient’s significance remained even within what the current guidelines consider acceptable ranges. Potentially modifiable factors associated with LVH were systolic BP and aortic valve disease. We found no general difference in height, weight, or BMI between patients with CoA and the reference population. While LVH was more common among men, increased myocardial ECV was more common among women.

L'hypertrophie ventriculaire gauche (HVG) est un remodelage prédicteur du développement d'une insuffisance cardiaque et de la mortalité cardiovasculaire. L'hypertension artérielle est une cause majeure de l'HVG, puisque 30% des patients hypertendus développent une HVG. Un dépistage biologique précoce de l'HVG post hypertensive permettrait d'optimiser la prise en charge des patients et d'empêcher que l'HVG évolue vers l'insuffisance cardiaque. L'utilisation de biomarqueurs est un outil rapide, efficace et peu couteux pour le diagnostic de nombreuses pathologies. Dans la pratique clinique il n'existe pas de biomarqueurs pour identifier les patients hypertendus avec HVG de ceux sans ce remodelage. Le premier objectif de notre étude a été d'identifier des biomarqueurs plasmatiques de l'HVG post hypertensive. Une analyse métabolomique obtenue par spectroscopie de résonance magnétique nucléaire du proton (H1) a été effectuée sur les échantillons de plasma de 48 patients hypertendus avec HVG, 48 hypertendus sans HVG et 24 témoins. A l'aide d'outils bio-informatiques et d'analyses statistiques adaptées, nous avons mis en évidence la présence d'un ratio des groupements chimiques méthylène/ méthyle (-CH2-/-CH3) des chaines aliphatiques des lipides plasmatiques augmenté chez les patients hypertendus avec HVG (p<0.001). Ce ratio détecte la présence d'une HVG chez les patients hypertendus avec une sensitivité de 52.08% et une spécificité de 85.42%. Nous proposons que le ratio -CH2-/-CH3 des chaines aliphatiques lipidiques présent dans plasma représente un biomarqueur diagnostique de l'HVG dans l'hypertension artérielle. L'incidence de l'HVG est aussi augmentée chez les patients qui souffrent du syndrome métabolique (MetS). Le MetS est défini par la présence d'une obésité abdominale plus deux facteurs parmi la dyslipidémie, l'insulino-résistance et l'hypertension artérielle. Ces facteurs synergisent et sont les responsables de l'instauration d'une HVG et d'une progression vers l'insuffisance cardiaque. Des données publiées montrent que les patients MetS ont un taux réduit de l'insulin-like growth factor binding protein 2 (IGFBP2). L'IGFBP2 a un rôle potentiel dans le diabète et dans le métabolisme, mais il n'existe pas d'étude sur son rôle dans les pathologies cardiaques causées par une dérégulation métabolique. Le premier objectif de notre étude sur l'IGFBP2 a été de mesurer le taux plasmatique d'IGFBP2 et le taux d'expression cardiaque de l'ARN messager d'IGFBP2 dans une cohorte de patients avec et sans MetS. Nous avons montré que le taux plasmatique ainsi que le taux d'ARN messager cardiaque d'IGFBP2 sont diminués chez les patients avec le Mets comparé à des témoins. Puis, nous avons mesuré le tôt cardiaque d'ARN messager de l'IGFBP2 dans un model murin de MetS. Pour générer ce modèle, nous avons nourri des souris C57BL/6J avec du régime gras à 60% pendant 15 semaines. Le taux d'expression cardiaque de l'ARN messager de l'IGFBP2 est réduit chez les souris avec Mets, en accord avec les résultats obtenu chez l'homme. Enfin, nous avons testé si la thérapie génique utilisant un virus adeno-associé qui exprime l'IGFBP2 humaine (AAV9-hIGFBP2) pouvait restaurer un niveau normal d'IGFBP2 et interférer avec l'HVG causé par le MetS chez ces souris. Nos résultats montrent que l'injection de l'AAV9-hIGFBP2 rétabli durablement le niveau cardiaque d'IGFBP2 chez la souris avec MetS et qu'IGFBP2 prévient l'épaississement des parois du ventricule gauche, l'hypertrophie et la dysfonction cardiaque. Nos résultats suggèrent qu'IGFBP2 est une nouvelle cible thérapeutique potentielle de l'HVG. / Left ventricular hypertrophy (LVH) is a strong predictor of future heart failure and cardiovascular mortality. Arterial hypertension is considered as the main causative agent for LVH as 30% of hypertensive patients develop LVH. These patients have an increased risk for cardiovascular complications and heart failure. Early diagnosis of LVH and prompt treatment are crucial to reduce LVH and stop its progression towards heart failure. Biomarkers could represent a rapid, effective and low-cost tool to discriminate hypertensive patients with LVH from those with normal LV size. Therefore, we aimed to identify plasma metabolomics biomarkers by 1H NMR to provide novel diagnostic tools for rapid detection of LVH in populations of hypertensive individuals. We realized a cross-sectional study including 48 hypertensive patients with LVH matched with 48 hypertensive patients with normal LV size, and 24 healthy controls. Two-dimensional targeted M-mode echocardiography was performed to measure left ventricular mass index. Partial least squares discriminant analysis was used for the multivariate analysis of the 1H NMR spectral data. From the 1H NMR analysis, we found that the methylene/methyl (-CH2-/-CH3) ratio of aliphatic chain from plasma lipids was significantly increased (p<0.001) in hypertensive patients with LVH compared to hypertensive patients without LVH and to control. Receiver operating characteristic curve showed that a cutoff value of 2.34 provided a 52.08% sensitivity and 85.42% specificity for discriminating LVH (AUC=0.703, p-value<0.001). We propose the -CH2/-CH3 ratio from plasma aliphatic lipid chains as a biomarker for the diagnosis of LVH in arterial hypertension. LVH incidence is also increased in patients with metabolic syndrome (MetS). MetS is defined by central obesity plus any two medical conditions such as dyslipidemia, insulin resistance, and hypertension. These factors synergize to cause LV dysfunction and HF. Published data have shown that MetS patients have low plasma insulin-like growth factor binding protein 2 (IGFBP2). IGFBP2 was shown to play a role in diabetes and metabolism, but studies investigating its role in cardiac diseases are lacking. We first aimed to investigate plasma IGFBP2 levels and cardiac IGFBP2 mRNA levels in MetS patients. Both plasma levels and heart expression levels of IGFBP2 were decreased in patients with MetS compared to control patients. Further, in a C57BL/6J mouse model of 60% high fat diet-induced MetS, we measured cardiac mRNA IGFBP2 levels. According to the observed data in human, mice with MetS showed a decreased cardiac IGFBP2 mRNA level. Finally, we investigated whether a gene therapy strategy using adeno-associated virus 9 carrying human IGFBP2 coding sequence (AAV9-hIGFBP2) could prevent from MetS associated left ventricular hypertrophy. Our data showed that AAV9-hIGFBP2 injection restored durably cardiac IGFBP2 levels in mouse heart and prevented from left ventricle wall thickening, hypertrophy and dysfunction. These clinical and animal data suggest that IGFBP2 is a potential new cardiac therapeutic target in MetS.

Alterações cardiovasculares e hiperlipidemias são comuns em cães obesos. As apolipoproteínas (Apos) constituem um componente importante do perfil lipídico e, pelo menos em humanos, auxiliam na determinação do risco de aterosclerose, doenças vasculares e cardíacas. Sendo assim, o objetivo deste estudo foi relacionar a ocorrência de alterações cardiovasculares com fatores associados à aterosclerose, verificando também a influência da perda de peso sobre tais fatores e os parâmetros cardíacos e pressóricos. Vinte cadelas castradas, sendo 9 com ECC 4-5 (grupo controle) e 11 com ECC 8-9 (grupo obesidade) participaram desta pesquisa. Em relação ao grupo controle, o grupo obesidade apresentou o aumento da: massa gorda (em Kg e %), contagem de leucócitos, pressão arterial (PA) sistólica, concentração de triglicérides e VLDL, além da maior observação de cistites e de sinais de hipertrofia ventricular. Estes parâmetros se aproximaram da situação controle, após o emagrecimento, exceto pela ocorrência de cistites. Comparando-se os valores médios, os grupos controle e obesidade não diferiram nas avaliações eletrocardiográfica e ecocardiográfica e, tão pouco, nas concentrações de Apo A-I e B. Os resultados indicam que a redução da gordura corporal traz benefícios, devido à diminuição da concentração de colesterol (total, LDL e VLDL) e triglicérides, além da melhora nos parâmetros da avaliação cardiovascular. Além disso, a determinação das Apo A-I e Apo B podem auxiliar na avaliação do perfil lipídico, mas não apresentaram relação com as alterações cardiovasculares observadas nas cadelas obesas. / Cardiovascular alterations and hyperlipidemia are common in obese dogs. In humans, apolipoproteins (Apos) are part of lipid profile and are used to determine the atherosclerosis, vascular and cardiac diseases risks. Therefore, the objective of this study was to relate the cardiovascular changes with atherosclerotic factors, also verifying the weight loss influence on such factors and cardiac and pressure parameters. Twenty neutered dogs female, 9 with ECC 4-5 (control group) and 11 with ECC 8-9 (obesity group) participated of this study. In relation to control group, the obesity group presented the increase of: fat mass (in kg and %), leukocyte counts, systolic blood pressure (BP), triglyceride and VLDL concentrations, as well as the higher number of females with cystitis and ventricular hypertrophy signs. These parameters returned the control situation after weight loss, except the cases of cystitis. Comparing the mean values, the control and obesity groups did not differ in the electrocardiographic and echocardiographic evaluations and in Apo A-I and B concentrations. The results indicate that the reduction of body fat has benefits, due to cholesterol (total, LDL and VLDL) and triglycerides decrease and improvement of cardiovascular evaluation. In addition, Apo A-I and Apo B determination may assist in lipid profile assessing, but were not related to cardiovascular changes observed in obese female dogs.

Introdução: A obesidade bem como um aumento da ativação do sistema renina angiotensina cardíaco estão profundamente envolvidos com o desenvolvimento de doenças cardiovasculares. Por outro lado, o treinamento físico aeróbio, previne o desenvolvimento da obesidade e reduz o sistema renina angiotensina cardíaco em algumas patologias. Dessa forma, nosso objetivo foi de investigar se a obesidade e sua associação com o treinamento físico aeróbio alteram os componentes do sistema renina angiotensina sistêmico e cardíaco em ratos Zucker obesos. Métodos: Os ratos Zucker foram divididos da seguinte forma: grupo magro (GM), grupo obeso (GO), grupo magro treinado (GMTR) e grupo obeso treinado (GOTR). O Protocolo de treinamento aeróbio de natação foi realizado por um período de 10 semanas com 5 sessões semanais de 60 minutos de duração. A freqüência cardíaca, pressão arterial sistólica, hipertrofia e função cardíaca, bem como os alguns dos componentes do sistema renina angiotensina sistêmico e cardíaco foram avaliadas após o período de treinamento físico. Mensuramos também no final do protocolo de treinamento a glicose, triglicérides, colesterol total, bem como suas frações: lipoproteína de baixa densidade e lipoproteína de alta densidade. Resultados: Ambos os grupos obesos apresentaram um aumento significativo do peso corporal em relação aos grupos magros, entretanto, o grupo obeso treinado apresentou um ganho do peso corporal reduzido (-59%) comparado com o grupo obeso sedentário. Essas modificações foram acompanhadas por uma queda de (-12%) na frequência cardíaca de repouso, (-57%) dos triglicérides, (-61%) da lipoproteina de baixa densidade e aumentou a lipoproteina de alta densidade em (+42%) no grupo obeso quando comparado com o grupo obeso sedentário. Além do mais, nossos resultados demonstraram que o treinamento aeróbio reduziu o aumento da massa cardíaca (-13%), da atividade (-27%) e expressão (-63%) da enzima conversora de angiotensina, angiotensina II (-44%), e do receptor de angiotensina II do tipo 2 (-35%) no coração e melhorou a disfunção diastólica na obesidade. Ainda, o treinamento físico aeróbio independente da obesidade aumentou a enzima conversora de angiotensina do tipo 2 cardíaca em ambos os grupos magros. Conclusão: Nossos dados demonstraram que o treinamento físico aeróbio reverteu os prejuízos metabólicos e cardíacos causados pela obesidade / Introduction: Obesity and cardiac renin angiotensin system hyperactivity are profoundly involved in cardiovascular diseases. On the other hand, aerobic exercise training can prevent obesity and reduce cardiac renin angiotensin system components in some models of cardiac pathology. Therefore, our hypotheses was to investigate if obesity and its association with aerobic exercise training alters the systemic and cardiac renin angiotensin system components in an obese Zucker rat strain. Methods: The rats were divided in the follow groups: Lean group (LG); lean group plus aerobic exercise training (LGTR); obese group (OG) and obese group plus aerobic exercise training (OGTR). Aerobic exercise training protocol consisted of 10 weeks swimming sessions of 60 min, 5 days/week. At the end of the protocol training we evaluated heart rate, systolic blood pressure, cardiac hypertrophy and function, local and system component of renin angiotensin system. We also measured systemic glucose, triglycerides and total cholesterol such as their fractions: low density lipoprotein and high density lipoprotein. Results: Both obese groups showed a significant augment in body weight when compared with lean groups, however, the obese trained group had less weight gain (-59%) than obese untrained group. These alterations were accompanied by (-12%) less resting heart rate, (-57%) triglycerides, (-61%) low density lipoprotein and augmented (+42%) high density lipoprotein in the obese group when compared with untrained obese group. Moreover, our results showed that exercise training reduced the increased cardiac mass (-13%), cardiac angiotensin converting enzyme activity (-27%) and expression (-63%), angiotensin II (-44%), and type 2 angiotensin II receptor (-35%), and improve the loss of diastolic function caused by obesity. Furthermore, exercise augmented cardiac ACE2 in both training groups. Conclusion: Our results showed that the aerobic exercise training improved the metabolic and cardiac alterations caused by obesity

Made available in DSpace on 2016-08-19T18:16:04Z (GMT). No. of bitstreams: 1 Dissertacao Gilvan.pdf: 1264814 bytes, checksum: 315e543380c1d084e9507ab66fbf221f (MD5) Previous issue date: 2012-06-18 / Background: A specific acromegaly-related cardiomyopathy has been described in the literature, largely in Caucasians, which is independent of other risk factors, mainly hypertension. Objective: The aim of this study was to assess the cardiac changes in an extensively admixed acromegalic population and also the relevance of the aetiopathogenic factors involved, such as disease activity and hypertension. Methods: In a cross-sectional design, 37 acromegalic patients (20 brown, 14 blacks and 3 whites) and 74 controls matched by age, gender and hypertension were evaluated. Cardiac morphology and function were addressed using echocardiography parameters. Results: The mean age of patients was 46.9 ± 12.8 years, with 67.6% being female and 43.2% hypertensive. The prevalence of left ventricular hypertrophy (LVH) between acromegalics was 56.8% versus 10.8% in the controls (p< 0.001). About 86% of patients with LVH had active disease (p = 0.023). Logistic regression revealed that disease activity presented a stronger association (OR = 5.925; CI = 1.085 32.351; p = 0.040) with LVH than hypertension (OR = 3.237; CI = 0.702 14.924; p = 0.132). Most acromegalics (51.4%) presented with diastolic dysfunction that directly correlated with age and with blood pressure levels and did not correlate with the percentage of upper limit of the normal range of IGF-I (% ULNR-IGF-I). Systolic function was not affected. When black acromegalics were compared to brown ones, no statistically significant differences were observed. Conclusion: In conclusion, chronically hyperactive somatotropic axis remains as an independent and determining factor in the development of LVH, as it is more associated with this condition than hypertension in a largely admixed population with a high prevalence of blacks. / Introdução: Uma miocardiopatia específica da acromegalia vem sendo descrita na literatura, principalmente em caucasianos e que é independente de outros fatores de risco, sobretudo, da Hipertensão Arterial Sistêmica (HAS). Objetivo: avaliar as alterações cardíacas em uma população acromegálica altamente miscigenada, assim como a importância dos fatores etiopatogênicos envolvidos, a saber: atividade da doença e HAS. Metodologia: Em um estudo transversal, 37 pacientes acromegálicos (20 pardos, 14 negros e 3 brancos) e 74 indivíduos do grupo controle pareados por faixa etária, sexo e presença de HAS foram avaliados. A morfologia e a função cardíacas foram avaliadas usando parâmetros ecocardiográficos. Resultados: a média de idade dos pacientes foi de 46.9 ± 12.8 anos, com 67.6% de mulheres e 43.2% de hipertensos. A prevalência de hipertrofia de ventrículo esquerdo (HVE) entre acromegálicos foi de 56.8% versus 10.8% no grupo-controle (p< 0.001). Cerca de 86% dos pacientes com HVE apresentaram doença ativa (p = 0.023). A análise por regressão logística demonstrou que a atividade da doença apresentou uma associação mais forte (OR = 5.925; CI = 1.085 32.351; p = 0.040) com HVE que HAS (OR = 3.237; CI = 0.702 14.924; p = 0.132). A maioria dos acromegálicos (51.4%) apresentou disfunção diastólica que se correlacionou diretamente com a idade e com os níveis de pressão arterial e não demonstrou correlação com a percentagem do limite superior da variação do normal de IGF-I (% LSN-IGF-I). Não houve alteração da função sistólica. Diferenças estatisticamente significantes não foram observadas quando os acromegálicos negros foram comparados aos pardos. Conclusão: A hiperatividade do eixo somatotrófico permanece como um fator determinante e independente para o desenvolvimento de HVE, visto que é mais associado com esta condição que HAS, em uma população de acromegálicos de ampla diversidade étnica e com alta prevalência de negros.

O sistema cardiovascular pode adaptar-se ao treinamento. Pouco se sabe sobre a influência do treinamento sobre a regulação autonômica, estrutura cardíaca e função em crianças e adolescentes atletas. O objetivo deste estudo foi avaliar a estrutura e função do ventrículo esquerdo em nadadores adolescentes. Foram comparados 28 atletas nadadores entre 15 e 17 anos (15 meninos e 13 meninas), que nadavam entre 25 km e 45 km/semana, nos últimos 2 anos, com grupo controle de 28 adolescentes (14 meninos e 14 meninas) com idade, peso e altura similares. Foi realizado ecocardiograma bidimensional e modo-M para avaliação cardiológica. Foram avaliados: diâmetro interno do ventrículo esquerdo durante a sístole (VES), diâmetro interno do ventrículo esquerdo durante a diástole (VED), septo interventricular (S), parede posterior do ventrículo esquerdo (PP), através da ecocardiografia modo-M. A massa do ventrículo esquerdo (MVE), índice de massa do VE, fração de encurtamento (ΔD) e fração de ejeção (FE) foram calculadas. Parâmetros diastólicos incluindo a velocidade do fluxo pela valva mitral e pelas veias pulmonares foram medidos: velocidade de enchimento rápido (pico da onda E), e tardio (pico da onda A), relação E/A, tempo de relaxamento isovolumétrico (TRIV) e tempo de desaceleração (TD), velocidade da onda de fluxo sistólico e diastólico pulmonar. Para comparar os dois grupos foi utilizando Teste t de Student para amostras independentes. Não foram encontradas diferenças antropométricas significativas entre os grupos. Comparado com o controle, nadadores do sexo masculino apresentaram uma diferença significativamente maior nas medidas do diâmetro interno do VED (53,6 ± 4,3 mm, p = 0,009), na espessura do septo interventricular (7,9 ± 1 mm, p = 0,0001) e da espessura da parede posterior do ventrículo esquerdo (7,90 ± 1,3 mm vs. 6,4 ± 0,08 mm, p = 0,001) e aumento da massa do VE (192,7 ± 54,7 g vs. 128,7 ± 28,6 g, p = 0,001). As nadadoras do sexo feminino apresentaram um significante aumento do diâmetro interno do VED (48 ± 3,7 vs. 45 ± 2,4 mm, p = 0,007), mas não houve diferenças nas medidas de S e PP, nem da massa do VE. Os parâmetros de fluxo transmitral foram semelhantes em ambos os grupos, exceto pelo prolongamento do TD nos nadadores (220 ± 47 vs. 181 ± 20 ms, p = 0,008 no sexo masculino, e 227 ± 50 vs. 177 ± 31 ms, p = 0,004 no sexo feminino). Estes achados sugerem que o treinamento de natação por um período prolongado em adolescentes causa aumento do tamanho e da massa do VE, mantendo a função sistólica normal e melhorando a complacência ventricular. A hipertrofia do VE com aumento da complacência ventricular é característico da adaptação fisiológica ao treinamento de endurance. Os parâmetros de fluxo transmitral foram semelhantes em ambos os grupos, exceto pelo prolongamento do TD nos nadadores (220 ± 47 vs. 181 ± 20 ms, p = 0,008 no sexo masculino, e 227 ± 50 vs. 177 ± 31 ms, p = 0,004 no sexo feminino). Estes achados sugerem que o treinamento de natação por um período prolongado em adolescentes causa aumento do tamanho e da massa do VE, mantendo a função sistólica normal e melhorando a complacência ventricular. A hipertrofia do VE com aumento da complacência ventricular é característico da adaptação fisiológica ao treinamento de endurance. / The cardiovascular system can adapt to aerobic training. Little is known about the influence of training on autonomic regulation and cardiac structure and function in children and adolescent athletes. The purpose of the present study was to evaluate left ventricular structure and function in adolescent swimmers. We compared 28 eight swimmers between 15 and 17 years old (15 boys and 13 girls), training between 25 km to 45 km /week for the last three years and 28 non training control subjects (14 boys and 14 girls) similar in age, weight and height of the athletes. Two-dimensional, M-mode and Doppler-echocardiography were performed. Left ventricular internal diameters in diastole (LVIDd) and systole (LVIDs), interventricular septum thickness (IVS), left ventricular posterior wall (LVPW) were measured from M-mode echocardiography. Left ventricular mass (LVM), LVM index, shortening fraction (SF) and ejection fraction (EF) were calculated. Diastolic parameters including mitral valve inflow velocities and pulmonary vein flow were measured: maximal early (peak E wave), and late (peak A wave) mitral velocities, E/A ratio, isovolumic relaxation time (IVRT) and deceleration time (DT), pulmonary systolic (S), diastolic (D) and Ar wave velocities. Comparisons between the two groups were made using the independent samples Student t-test. There were no significant anthropometric differences between the two groups. Compared with controls, male swimmers showed a significantly greater LVIDd (53.6 ± 4.3 mm, p < 0.009), a thicker IVS (7.9 ± 1 mm, p < 0.0001) and LVPW (7.90 ± 1.3 mm vs. 6.4 ± 0.08 mm, p < 0,001), an increased LVM (192.7 ± 54.7 g vs. 128.7 ± 28.6 g, p < 0.001). Female swimmers had a significanty greater LVIDd (48 ± 3.7 vs. 45 ± 2.4 mm, p < 0.007), but no greater IVS or LVPW thickness, neither LVM. SF and EF were similar in both groups. Transmitral inflow parameters were similar in both groups, except for a prolonged TD in the swimmers group (220 ± 47 vs. 181 ± 20 ms, p < 0.008 in males and 227 ± 50 vs. 177 ± 31 ms, p < 0.004 in females). These findings suggest that long-term swimming in adolescents promotes increase in left ventricular size and mass with normal systolic function and improved diastolic compliance. LV hypertrophy with an improved compliance is characteristic of physiological adaptation of endurance training.

O sistema cardiovascular pode adaptar-se ao treinamento. Pouco se sabe sobre a influência do treinamento sobre a regulação autonômica, estrutura cardíaca e função em crianças e adolescentes atletas. O objetivo deste estudo foi avaliar a estrutura e função do ventrículo esquerdo em nadadores adolescentes. Foram comparados 28 atletas nadadores entre 15 e 17 anos (15 meninos e 13 meninas), que nadavam entre 25 km e 45 km/semana, nos últimos 2 anos, com grupo controle de 28 adolescentes (14 meninos e 14 meninas) com idade, peso e altura similares. Foi realizado ecocardiograma bidimensional e modo-M para avaliação cardiológica. Foram avaliados: diâmetro interno do ventrículo esquerdo durante a sístole (VES), diâmetro interno do ventrículo esquerdo durante a diástole (VED), septo interventricular (S), parede posterior do ventrículo esquerdo (PP), através da ecocardiografia modo-M. A massa do ventrículo esquerdo (MVE), índice de massa do VE, fração de encurtamento (ΔD) e fração de ejeção (FE) foram calculadas. Parâmetros diastólicos incluindo a velocidade do fluxo pela valva mitral e pelas veias pulmonares foram medidos: velocidade de enchimento rápido (pico da onda E), e tardio (pico da onda A), relação E/A, tempo de relaxamento isovolumétrico (TRIV) e tempo de desaceleração (TD), velocidade da onda de fluxo sistólico e diastólico pulmonar. Para comparar os dois grupos foi utilizando Teste t de Student para amostras independentes. Não foram encontradas diferenças antropométricas significativas entre os grupos. Comparado com o controle, nadadores do sexo masculino apresentaram uma diferença significativamente maior nas medidas do diâmetro interno do VED (53,6 ± 4,3 mm, p = 0,009), na espessura do septo interventricular (7,9 ± 1 mm, p = 0,0001) e da espessura da parede posterior do ventrículo esquerdo (7,90 ± 1,3 mm vs. 6,4 ± 0,08 mm, p = 0,001) e aumento da massa do VE (192,7 ± 54,7 g vs. 128,7 ± 28,6 g, p = 0,001). As nadadoras do sexo feminino apresentaram um significante aumento do diâmetro interno do VED (48 ± 3,7 vs. 45 ± 2,4 mm, p = 0,007), mas não houve diferenças nas medidas de S e PP, nem da massa do VE. Os parâmetros de fluxo transmitral foram semelhantes em ambos os grupos, exceto pelo prolongamento do TD nos nadadores (220 ± 47 vs. 181 ± 20 ms, p = 0,008 no sexo masculino, e 227 ± 50 vs. 177 ± 31 ms, p = 0,004 no sexo feminino). Estes achados sugerem que o treinamento de natação por um período prolongado em adolescentes causa aumento do tamanho e da massa do VE, mantendo a função sistólica normal e melhorando a complacência ventricular. A hipertrofia do VE com aumento da complacência ventricular é característico da adaptação fisiológica ao treinamento de endurance. Os parâmetros de fluxo transmitral foram semelhantes em ambos os grupos, exceto pelo prolongamento do TD nos nadadores (220 ± 47 vs. 181 ± 20 ms, p = 0,008 no sexo masculino, e 227 ± 50 vs. 177 ± 31 ms, p = 0,004 no sexo feminino). Estes achados sugerem que o treinamento de natação por um período prolongado em adolescentes causa aumento do tamanho e da massa do VE, mantendo a função sistólica normal e melhorando a complacência ventricular. A hipertrofia do VE com aumento da complacência ventricular é característico da adaptação fisiológica ao treinamento de endurance. / The cardiovascular system can adapt to aerobic training. Little is known about the influence of training on autonomic regulation and cardiac structure and function in children and adolescent athletes. The purpose of the present study was to evaluate left ventricular structure and function in adolescent swimmers. We compared 28 eight swimmers between 15 and 17 years old (15 boys and 13 girls), training between 25 km to 45 km /week for the last three years and 28 non training control subjects (14 boys and 14 girls) similar in age, weight and height of the athletes. Two-dimensional, M-mode and Doppler-echocardiography were performed. Left ventricular internal diameters in diastole (LVIDd) and systole (LVIDs), interventricular septum thickness (IVS), left ventricular posterior wall (LVPW) were measured from M-mode echocardiography. Left ventricular mass (LVM), LVM index, shortening fraction (SF) and ejection fraction (EF) were calculated. Diastolic parameters including mitral valve inflow velocities and pulmonary vein flow were measured: maximal early (peak E wave), and late (peak A wave) mitral velocities, E/A ratio, isovolumic relaxation time (IVRT) and deceleration time (DT), pulmonary systolic (S), diastolic (D) and Ar wave velocities. Comparisons between the two groups were made using the independent samples Student t-test. There were no significant anthropometric differences between the two groups. Compared with controls, male swimmers showed a significantly greater LVIDd (53.6 ± 4.3 mm, p < 0.009), a thicker IVS (7.9 ± 1 mm, p < 0.0001) and LVPW (7.90 ± 1.3 mm vs. 6.4 ± 0.08 mm, p < 0,001), an increased LVM (192.7 ± 54.7 g vs. 128.7 ± 28.6 g, p < 0.001). Female swimmers had a significanty greater LVIDd (48 ± 3.7 vs. 45 ± 2.4 mm, p < 0.007), but no greater IVS or LVPW thickness, neither LVM. SF and EF were similar in both groups. Transmitral inflow parameters were similar in both groups, except for a prolonged TD in the swimmers group (220 ± 47 vs. 181 ± 20 ms, p < 0.008 in males and 227 ± 50 vs. 177 ± 31 ms, p < 0.004 in females). These findings suggest that long-term swimming in adolescents promotes increase in left ventricular size and mass with normal systolic function and improved diastolic compliance. LV hypertrophy with an improved compliance is characteristic of physiological adaptation of endurance training.