Comparison of two experimental models of pulmonary hypertension

Objective: To compare two models of pulmonary hypertension (monocrotaline and monocrotaline+pneumonectomy) regarding hemodynamic severity, structure of pulmonary arteries, inflammatory markers (IL-1 and PDGF), and 45-day survival. Methods: We used 80 Sprague-Dawley rats in two study protocols: structural analysis; and survival analysis. The rats were divided into four groups: control; monocrotaline (M), pneumonectomy (P), and monocrotaline+pneumonectomy (M+P). In the structural analysis protocol, 40 rats (10/group) were catheterized for the determination of hemodynamic variables, followed by euthanasia for the removal of heart and lung tissue. The right ventricle (RV) was dissected from the interventricular septum (IS), and the ratio between RV weight and the weight of the left ventricle (LV) plus IS (RV/LV+IS) was taken as the index of RV hypertrophy. In lung tissues, we performed histological analyses, as well as using ELISA to determine IL-1 and PDGF levels. In the survival protocol, 40 animals (10/group) were followed for 45 days. Results: The M and M+P rats developed pulmonary hypertension, whereas the control and P rats did not. The RV/LV+IS ratio was significantly higher in M+P rats than in M rats, as well as being significantly higher in M and M+P rats than in control and P rats. There were no significant differences between the M and M+P rats regarding the area of the medial layer of the pulmonary arteries; IL-1 and PDGF levels; or survival. Conclusions: On the basis of our results, we cannot conclude that the monocrotaline+pneumonectomy model is superior to the monocrotaline model.

Prevalência de hipertensão arterial em Adventistas do Sétimo Dia da capital e do interior paulista

FUNDAMENTO: Sabe-se que hábitos de vida inadequados favorecem a hipertensão, e os adventistas preconizam hábitos saudáveis. OBJETIVO: Avaliar a prevalência da hipertensão nos adventistas do sétimo dia na capital e no interior paulistas. MÉTODOS: Foram estudados 264 adventistas (41,17 ± 15,27 anos, 59,8% mulheres, com alto nível de religiosidade avaliada pela escala Duke-DUREL). A medida da pressão arterial foi realizada com aparelho automático validado. Nível de significância adotado foi p < 0,05. Resultados: A prevalência total de hipertensão foi 22,7%, (27,4% no interior e 15% na capital). Os adventistas da capital diferiram dos do interior (p < 0,05), respectivamente, quanto: escolaridade superior (62% vs 36,6%); ter vínculo empregatício (44%) vs autônomos (40,9%); renda familiar (8,39 ± 6,20 vs 4,59 ± 4,75 salários mínimos) e renda individual (4,54 ± 5,34 vs 6,35 ± 48 salários mínimos); casal responsável pela renda familiar (35% vs 39,6%); vegetarianismo (11% vs 3%); pressão arterial (115,38 ± 16,52/68,74 ± 8,94 vs 123,66 ± 19,62/74,88 ± 11,85 mmHg); etnia branca (65% vs 81,1%); casados (53% vs 68,9%); menor apoio social no domínio material (15,7 ± 5,41 vs 16,9 ± 4,32) e lembrar da última vez que mediu a pressão arterial (65% vs 48,8%). A análise multivariada associou hipertensão com: 1) vegetarianismo (OR 0,051, IC95% 0,004-0,681), 2) escolaridade (OR 5,317, IC95% 1,674-16,893), 3) lembrar quando mediu a pressão (OR 2,725, IC95% 1,275-5,821), 4) aposentado (OR 8,846, IC95% 1,406-55,668), 5) responsável pela renda familiar (OR 0,422, IC95% 0,189-0,942). CONCLUSÃO: A prevalência de hipertensão dos adventistas foi menor se comparada com estudos nacionais, sendo menor na capital em relação ao interior possivelmente por melhores condições socioeconômicas e hábitos de vida.

Ausência de estreita associação entre qualidade de vida e capacidade de exercício na hipertensão arterial pulmonar

FUNDAMENTO: Na hipertensão arterial pulmonar (HAP) a qualidade de vida relacionada saúde (QVRS) tem sido investigada em curtos períodos de tempo (semanas), mas pouco se sabe sobre a perspectiva do paciente no médio e longo prazo. OBJETIVO: Analisar o estado de pacientes em terapias específicas de HAP durante um ano de observação, em termos de QVRS, e investigar se possíveis associações entre a capacidade de exercício (CE) e a QVRS persistem no médio prazo. MÉTODOS: Trinta e quatro pacientes em terapias para a HAP (bosentan e/ou sildenafil) foram selecionados (idade de 14 a 58 anos, mediana de 35,5 anos, classe funcional II ou III), e avaliados no momento basal, e 3, 6, 9 e 12 meses depois, usando o teste de caminhada de 6 minutos e questionário SF-36 de QVRS. RESULTADOS: A distância percorrida nos seis minutos não mudou durante o acompanhamento (387 - 432 metros, valores da mediana, p=0.2775), o mesmo para a classe funcional e saturação periférica de oxigênio. Os escores SF-36 também se mantiveram estáveis, com a saúde física sempre pior que a saúde mental. Das 40 possíveis associações entre a CE e QVRS, apenas 12 foram significativas (30%, p<0,05). A previsão de uma QVRS severamente deprimida com base em uma distância percorrida de 235 metros foi específica em >90%, mas sensível em <43%. CONCLUSÃO: Os pacientes com HAP que se mantêm estáveis em termos da CE também parecem fazê-lo em termos de QVRS. Contudo, CE e QVRS não têm ligação consistente com o tempo, e devem ser analisadas como diferentes perspectivas no paciente individual.

Componentes da síndrome metabólica na hipertensão arterial

Este estudo teve como objetivo identificar e comparar a prevalência da síndrome metabólica entre hipertensos e normotensos. Os aspectos adotados para a definição de síndrome metabólica foram os definidos pelo National Cholesterol Education Program/Adults Treatment Painel (NCEP-ATP III). Os dados referentes aos perfis clínicos e bioquímicos foram processados no programa SPSS para cálculo de frequências absolutas e porcentagens. Utilizou-se o teste t de Student para comparações das médias, sendo as diferenças consideradas estatisticamente significantes para p<0,05. A amostra foi composta por 93 participantes normotensos e 168 hipertensos. Identificou-se a presença de síndrome metabólica em 60,7% dos hipertensos e 18,3% dos normotensos. Os portadores de hipertensão arterial apresentam diferença significante nos valores de pressão arterial (p<0,001), circunferência abdominal (p<0,001), glicemia (p<0,05) e triglicérides plasmáticos (p<0,05). A frequência dos riscos cardiometabólicos associados à síndrome metabólica é maior na presença de doença hipertensiva.

Monogenic forms of hypertension

Arterial hypertension in childhood is less frequent as compared to adulthood but is more likely to be secondary to an underlying disorder. After ruling out more obvious causes, some patients still present with strongly suspected secondary hypertension of yet unknown etiology. A number of these children have hypertension due to single gene mutations inherited in an autosomal dominant or recessive fashion. The finding of abnormal potassium levels (low or high) in the presence of suppressed renin secretion, and metabolic alkalosis or acidosis should prompt consideration of these familial diseases. However, mild hypertension and the absence of electrolyte abnormalities do not exclude hereditary conditions. In monogenic hypertensive disorders, three distinct mechanisms leading to the common final pathway of increased sodium reabsorption, volume expansion, and low plasma renin activity are documented. The first mechanism relates to gain-of-function mutations with a subsequent hyperactivity of renal sodium and chloride reabsorption leading to plasma volume expansion (e.g., Liddle's syndrome, Gordon's syndrome). The second mechanism involves deficiencies of enzymes that regulate adrenal steroid hormone synthesis and deactivation (e.g., subtypes of congenital adrenal hyperplasia, apparent mineralocorticoid excess (AME)). The third mechanism is characterized by excessive aldosterone synthesis that escapes normal regulatory mechanisms and leading to volume-dependent hypertension in the presence of suppressed renin release (glucocorticoid remediable aldosteronism). Hormonal studies coupled with genetic testing can help in the early diagnosis of these disorders.

Position paper on the management of patients with obstructive sleep apnea and hypertension: joint recommendations by the European Society of Hypertension, by the European Respiratory Society and by the members of European COST (COoperation in Scientific and Technological research) ACTION B26 on obstructive sleep apnea

This article is aimed at addressing the current state of the art in epidemiology, pathophysiology, diagnostic procedures and treatment options for appropriate management of obstructive sleep apnea (OSA) in cardiovascular (particularly hypertensive) patients, as well as for the management of cardiovascular diseases (particularly arterial hypertension) in OSA patients. The present document is the result of the work done by a panel of experts participating in the European Union COST (COoperation in Scientific and Technological research) ACTION B26 on OSA, with the endorsement of the European Respiratory Society (ERS) and the European Society of Hypertension (ESH). These recommendations are particularly aimed at reminding cardiovascular experts to consider the occurrence of sleep-related breathing disorders in patients with high blood pressure. They are at the same time aimed at reminding respiration experts to consider the occurrence of hypertension in patients with respiratory problems at night.

Recommendations for the management of patients with obstructive sleep apnoea and hypertension

This article is aimed at addressing the current state-of-the-art in epidemiology, pathophysiology, diagnostic procedures and treatment options for appropriate management of obstructive sleep apnoea (OSA) in cardiovascular (in particular hypertensive) patients, as well as for the management of cardiovascular diseases (in particular arterial hypertension) in OSA patients. The present document is the result of work performed by a panel of experts participating in the European Union COST (Cooperation in Scientific and Technological research) Action B26 on OSA, with the endorsement of the European Respiratory Society and the European Society of Hypertension. In particular, these recommendations are aimed at reminding cardiovascular experts to consider the occurrence of sleep-related breathing disorders in patients with high blood pressure. They are also aimed at reminding respiration experts to consider the occurrence of hypertension in patients with respiratory problems at night.

Candesartan cilexetil in children with hypertension or proteinuria: preliminary data

The angiotensin II receptor blockers irbesartan and losartan effectively reduce blood pressure and proteinuria in childhood. We were impressed by the neutral taste and the small size of the candesartan cilexetil tablets. This angiotensin II receptor blocker was used during 4 months in 17 pediatric patients (aged 0.5-16, median 4.5 years) with chronic arterial hypertension (n=6), overt proteinuria (n=2), or both (n=9). The initial candesartan dose of 0.23 (0.16-0.28) mg/kg body weight once daily (median and interquartile ranged) was doubled in ten patients [final dose 0.35 (0.22-0.47) mg/kg body weight]. No adverse clinical experiences were noted on candesartan. Candesartan increased plasma potassium by 0.3 (0.0-0.8) mmol/l (P<0.01). In children with arterial hypertension, blood pressure decreased by 9 (3-13)/9 (3-18) mmHg (P<0.01); in those with overt proteinuria the urinary albumin/creatinine ratio decreased by 279 (33-652) mg/mmol (P<0.05). In conclusion, in children candesartan reduces blood pressure and proteinuria with an excellent short-term tolerability profile.

[Treatment of hypertension in type 2 diabetes mellitus--2002 update]

Arterial hypertension and diabetes are potent independent risk factors for cardiovascular, cerebral, renal and peripheral (atherosclerotic) vascular disease. The prevalence of hypertension in diabetic individuals is approximately twice that in the non-diabetic population. Diabetic individuals with hypertension have a greater risk of macrovascular and microvascular disease than normotensive diabetic individuals. Hypertension is a major contributor to morbidity and mortality in diabetes, and should be recognized and treated early. Type 2 diabetes and hypertension share certain risk factors such as overweight, visceral obesity, and possibly insulin resistance. Life-style modifications (weight reduction, exercise, limitation of daily alcohol intake, stop smoking) are the foundation of hypertension and diabetes management as the definitive treatment or adjunctive to pharmacological therapy. Additional pharmacological therapy should be initiated when life-style modifications are unsuccessful or hypertension is too severe at the time of diagnosis. All classes of antihypertensive drugs are effective in controlling blood pressure in diabetic patients. For single-agent therapy, ACE-inhibitors, angiotensin receptor blocker, beta-blockers, and diuretics can be recommended. Because of concerns about the lower effectiveness of calcium channel blockers in decreasing coronary events and heart failure and in reducing progression of renal disease in diabetes, it is recommended to use these agents as second-line drugs for patients who cannot tolerate the other preferred classes or who require additional agents to achieve the target blood pressure. The choice depends on the patients specific treatment indications since each of these drugs have potential advantages and disadvantages. In patients with microalbuminuria or clinical nephropathy, both ACE-inhibitors and angiotensin receptor blockers are considered first line therapy for the prevention of and progression of nephropathy. Since treatment is usually life-long, cost effectiveness should be included in treatment evaluation.

Ambulatory arterial stiffness index is increased in hypertensive childhood disease

Arterial hypertension in adults is often associated with an increased arterial stiffness, which correlates with the ambulatory arterial stiffness index (AASI) as derived from ambulatory blood pressure (BP) measurements. The purpose of this study was to demonstrate whether children with diagnosed hypertension have an increased AASI as in hypertensive adults. AASI was calculated from 185 ambulatory BP measurements of 114 hypertensive and 71 normotensive, healthy children. Hypertensive children had higher AASI values compared with their normotensive healthy counterparts (0.370 +/- 0.120 versus 0.204 +/- 0.199, p < 0.0001). Children with longer duration of hypertension or a history of primary or secondary aortic coarctation displayed even more elevated AASI values. A receiver operator curve derived cut-off of AASI set at 0.301 distinguished (p < 0.0001) hypertensive from normotensive children with an odds ratio of 8.2, a sensitivity of 81%, and a specificity of 65%. Moreover, AASI correlated with pulse and systolic BP. In conclusion, AASI is elevated in hypertensive children and correlates with the duration and the origin of hypertension in childhood.

Epidemiology of pulmonary hypertension: new data from the Swiss registry

BACKGROUND: since 1999 data from pulmonary hypertension (PH) patients from all PH centres in Switzerland were prospectively collected. We analyse the epidemiological aspects of these data. METHODS: PH was defined as a mean pulmonary artery pressure of >25 mm Hg at rest or >30 mm Hg during exercise. Patients with pulmonary arterial hypertension (PAH), PH associated with lung diseases, PH due to chronic thrombotic and/or embolic disease (CTEPH), or PH due to miscellaneous disorders were registered. Data from adult patients included between January 1999 and December 2004 were analysed. RESULTS: 250 patients were registered (age 58 +/- 16 years, 104 (41%) males). 152 patients (61%) had PAH, 73 (29%) had CTEPH and 18 (7%) had PH associated with lung disease. Patients <50 years (32%) were more likely to have PAH than patients >50 years (76% vs. 53%, p <0.005). Twenty-four patients (10%) were lost to followup, 58 patients (26%) died and 150 (66%) survived without transplantation or thrombendarterectomy. Survivors differed from patients who died in the baseline six-minute walking distance (400 m [300-459] vs. 273 m [174-415]), the functional impairment (NYHA class III/IV 86% vs. 98%), mixed venous saturation (63% [57-68] vs. 56% [50-61]) and right atrial pressure (7 mm Hg [4-11] vs. 11 mm Hg [4-18]). DISCUSSION: PH is a disease affecting adults of all ages. The management of these patients in specialised centres guarantees a high quality of care. Analysis of the registry data could be an instrument for quality control and might help identify weak points in assessment and treatment of these patients.

Pulmonary hypertension in Switzerland: treatment and clinical course

BACKGROUND: The prognosis of pulmonary hypertension (PH), especially idiopathic pulmonary arterial hypertension (IPAH), has improved during the recent years. The Swiss Registry for PH represents the collaboration of the various centres in Switzerland dealing with PH and serves as an important tool in quality control. The objective of the study was to describe the treatment and clinical course of this orphan disease in Switzerland. METHODS: We analyzed data from 222 of 252 adult patients, who were included in the registry between January 1999 and December 2004 and suffered from either PAH, PH associated with lung diseases or chronic thromboembolic PH (CTEPH) with respect to the following data: NYHA class, six-minute walking distance (6-MWD), haemodynamics, treatments and survival. RESULTS: If compared with the calculated expected figures the one, two and three year mean survivals in IPAH increased from 67% to 89%, from 55% to 78% and from 46% to 73%, respectively. Most patients (90%) were on oral or inhaled therapy and only 10 patients necessitated lung transplantation. Even though pulmonary endarterectomy (PEA) was performed in only 7 patients during this time, the survival in our CTEPH cohort improved compared with literature data and seems to approach outcomes usually seen after PEA. The 6-MWD increased maximally by 52 m and 59 m in IPAH and CTEPH, respectively, but in the long term returned to or below baseline values, despite the increasing use of multiple specific drugs (overall in 51% of IPAH and 29% of CTEPH). CONCLUSION: Our national registry data indicate that the overall survival of IPAH and presumably CTEPH seems to have improved in Switzerland. Although the 6-MWD improved transiently, it decreased in the long term despite specific and increasingly combined drug treatment. Our findings herewith underscore the progressive nature of the diseases and the need for further intense research in the field.

Association of arterial blood pressure and vasopressor load with septic shock mortality: a post hoc analysis of a multicenter trial

INTRODUCTION: It is unclear to which level mean arterial blood pressure (MAP) should be increased during septic shock in order to improve outcome. In this study we investigated the association between MAP values of 70 mmHg or higher, vasopressor load, 28-day mortality and disease-related events in septic shock. METHODS: This is a post hoc analysis of data of the control group of a multicenter trial and includes 290 septic shock patients in whom a mean MAP > or = 70 mmHg could be maintained during shock. Demographic and clinical data, MAP, vasopressor requirements during the shock period, disease-related events and 28-day mortality were documented. Logistic regression models adjusted for the geographic region of the study center, age, presence of chronic arterial hypertension, simplified acute physiology score (SAPS) II and the mean vasopressor load during the shock period was calculated to investigate the association between MAP or MAP quartiles > or = 70 mmHg and mortality or the frequency and occurrence of disease-related events. RESULTS: There was no association between MAP or MAP quartiles and mortality or the occurrence of disease-related events. These associations were not influenced by age or pre-existent arterial hypertension (all P > 0.05). The mean vasopressor load was associated with mortality (relative risk (RR), 1.83; confidence interval (CI) 95%, 1.4-2.38; P < 0.001), the number of disease-related events (P < 0.001) and the occurrence of acute circulatory failure (RR, 1.64; CI 95%, 1.28-2.11; P < 0.001), metabolic acidosis (RR, 1.79; CI 95%, 1.38-2.32; P < 0.001), renal failure (RR, 1.49; CI 95%, 1.17-1.89; P = 0.001) and thrombocytopenia (RR, 1.33; CI 95%, 1.06-1.68; P = 0.01). CONCLUSIONS: MAP levels of 70 mmHg or higher do not appear to be associated with improved survival in septic shock. Elevating MAP >70 mmHg by augmenting vasopressor dosages may increase mortality. Future trials are needed to identify the lowest acceptable MAP level to ensure tissue perfusion and avoid unnecessary high catecholamine infusions.

Determinants of renal tissue oxygenation as measured with BOLD-MRI in chronic kidney disease and hypertension in humans.

Experimentally renal tissue hypoxia appears to play an important role in the pathogenesis of chronic kidney disease (CKD) and arterial hypertension (AHT). In this study we measured renal tissue oxygenation and its determinants in humans using blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI) under standardized hydration conditions. Four coronal slices were selected, and a multi gradient echo sequence was used to acquire T2* weighted images. The mean cortical and medullary R2* values ( = 1/T2*) were calculated before and after administration of IV furosemide, a low R2* indicating a high tissue oxygenation. We studied 195 subjects (95 CKD, 58 treated AHT, and 42 healthy controls). Mean cortical R2 and medullary R2* were not significantly different between the groups at baseline. In stimulated conditions (furosemide injection), the decrease in R2* was significantly blunted in patients with CKD and AHT. In multivariate linear regression analyses, neither cortical nor medullary R2* were associated with eGFR or blood pressure, but cortical R2* correlated positively with male gender, blood glucose and uric acid levels. In conclusion, our data show that kidney oxygenation is tightly regulated in CKD and hypertensive patients at rest. However, the metabolic response to acute changes in sodium transport is altered in CKD and in AHT, despite preserved renal function in the latter group. This suggests the presence of early renal metabolic alterations in hypertension. The correlations between cortical R2* values, male gender, glycemia and uric acid levels suggest that these factors interfere with the regulation of renal tissue oxygenation.

Masked hypertension and cardiac remodeling in middle-aged endurance athletes

OBJECTIVES: Extensive endurance training and arterial hypertension are established risk factors for atrial fibrillation. We aimed to assess the proportion of masked hypertension in endurance athletes and the impact on cardiac remodeling, mechanics, and supraventricular tachycardias (SVT). METHODS: Male participants of a 10-mile race were recruited and included if office blood pressure was normal (<140/90 mmHg). Athletes were stratified into a masked hypertension and normotension group by ambulatory blood pressure. Primary endpoint was diastolic function, expressed as peak early diastolic mitral annulus velocity (E'). Left ventricular global strain, left ventricular mass/volume ratio, left atrial volume index, signal-averaged P-wave duration (SAPWD), and SVT during 24-h Holter monitoring were recorded. RESULTS: From 108 runners recruited, 87 were included in the final analysis. Thirty-three (38%) had masked hypertension. The mean age was 42 +/- 8 years. Groups did not differ with respect to age, body composition, cumulative training hours, and 10-mile race time. Athletes with masked hypertension had a lower E' and a higher left ventricular mass/volume ratio. Left ventricular global strain, left atrial volume index, SAPWD, and SVT showed no significant differences between the groups. In multiple linear regression analysis, masked hypertension was independently associated with E' (beta = -0.270, P = 0.004) and left ventricular mass/volume ratio (beta = 0.206, P = 0.049). Cumulative training hours was the only independent predictor for left atrial volume index (beta = 0.474, P < 0.001) and SAPWD (beta = 0.481, P < 0.001). CONCLUSION: In our study, a relevant proportion of middle-aged athletes had masked hypertension, associated with a lower diastolic function and a higher left ventricular mass/volume ratio, but unrelated to left ventricular systolic function, atrial remodeling, or SVT.