Ausência de estreita associação entre qualidade de vida e capacidade de exercício na hipertensão arterial pulmonar / Lack of tight association between quality of life and exercise capacity in pulmonary arterial hypertension

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.

BACKGROUND: In pulmonary arterial hypertension (PAH) health-related quality of life (HRQOL) has been investigated over the short-term (weeks) but little is known about patient's perspective over the medium and long term. OBJECTIVE: To analyze how patients on specific PAH therapies do over one year of observation in terms of HRQOL, and to investigate if possible associations between the exercise capacity (EC) and HRQOL persist over the medium term. METHODS: Thirty-four patients on PAH therapies (bosentan and/or sildenafil) were enrolled (age 14 to 58 years, median 35.5 years, functional class II or III), and evaluated at baseline, and 3, 6, 9 and 12 months subsequently using the six-minute walk test and the SF-36 HRQOL questionnaire. RESULTS: The six minute walked distance did not change over the follow-up (387-432 meters, median values, p=0.2775), the same for the functional class and peripheral oxygen saturation. The SF-36 scores also remained stable, with physical health always worse than mental health. Of 40 possible associations between EC and HRQOL, only 12 were significant (30%, p<0.05). Prediction of severely depressed HRQOL based on a walked distance of <235 meters was >90% specific but <43% sensitive. CONCLUSION: Patients with PAH who remain stable in terms of EC also seem to do so in terms of HRQOL. However, EC and HRQOL are not consistently tied over time, and should be analyzed as different perspectives in the individual patient.

Lack of tight association between quality of life and exercise capacity in pulmonary arterial hypertension.

BACKGROUND: In pulmonary arterial hypertension (PAH) health-related quality of life (HRQOL) has been investigated over the short-term (weeks) but little is known about patient's perspective over the medium and long term. OBJECTIVE: To analyze how patients on specific PAH therapies do over one year of observation in terms of HRQOL, and to investigate if possible associations between the exercise capacity (EC) and HRQOL persist over the medium term. METHODS: Thirty-four patients on PAH therapies (bosentan and/or sildenafil) were enrolled (age 14 to 58 years, median 35.5 years, functional class II or III), and evaluated at baseline, and 3, 6, 9 and 12 months subsequently using the six-minute walk test and the SF-36 HRQOL questionnaire. RESULTS: The six minute walked distance did not change over the follow-up (387-432 meters, median values, p=0.2775), the same for the functional class and peripheral oxygen saturation. The SF-36 scores also remained stable, with physical health always worse than mental health. Of 40 possible associations between EC and HRQOL, only 12 were significant (30%, p<0.05). Prediction of severely depressed HRQOL based on a walked distance of <235 meters was >90% specific but <43% sensitive. CONCLUSION: Patients with PAH who remain stable in terms of EC also seem to do so in terms of HRQOL. However, EC and HRQOL are not consistently tied over time, and should be analyzed as different perspectives in the individual patient.

Estudo de marcadores de disfunção endotelial e de inflamação em portadores de hipertensão arterial pulmonar: implicações terapêuticas e prognósticas / Markers of endothelial dysfunction and inflammatory mediators in pulmonary arterial hypertension: therapeutic and prognostic implications

A disfunção microvascular, envolvendo células endoteliais, plaquetas e leucócitos, está presente na hipertensão arterial pulmonar (HAP), associando-se a risco aumentado de trombose e menor sobrevida. Estudos sobre disfunção microvascular são escassos em outras formas da doença que não a idiopática. Os objetivos do estudo foram: caracterizar a disfunção microvascular em diferentes formas de HAP através da dosagem de marcadores bioquímicos, avaliando possíveis correlações com índices de gravidade; investigar os efeitos da administração de rosuvastatina em níveis circulantes de marcadores de disfunção microvascular nesses pacientes; e investigar possível associação entre o nível plasmático dos marcadores e prognóstico. Foram incluídos sessenta pacientes: 14 com HAP idiopática ou hereditária, e 46 com HAP associada a cardiopatia congênita (HAPCCg) sem hipoxemia (N=18) ou com hipoxemia (N=28), com idades entre 13 e 60 anos. Foram dosados os níveis plasmáticos circulantes do antígeno do fator de von Willebrand (vWF:Ag), ativador tecidual do plasminogênio (t-PA); inibidor do ativador do plasminogênio (PAI-1), fator de necrose tumoral (TNF-), proteína C reativa (PCR), selectina-P; interleucina-6 (IL-6); e interleucina-10 (IL -10), na condição basal e após 30, 60 e 180 dias de tratamento, por método imunoenzimático. Após randomização, administrouse placebo (N=30) ou dose única oral diária (10mg) de rosuvastatina (N=30), por seis meses. Dados demográficos e funcionais como idade, distância caminhada em seis minutos, saturação periférica de oxigênio em repouso e após esforço, bem como hematócrito, também foram registrados. Pacientes com HAPCCg foram acompanhados por um período de 0,7 a 4,0 anos (mediana de 3,6 anos). Na condição basal, excetuando-se TNF- e PCR, todas as proteínas apresentaram-se significantemente elevadas em relação aos controles (p<0,001), havendo correlação com índices de gravidade clínica. No estudo com rosuvastatina, houve redução significante nos...

Microvascular dysfunction, involving endothelial cells, platelets and leukocytes, is present in pulmonary arterial hypertension (PAH), and is associated to higher risk to thrombotic complications and mortality. Most data about microvascular dysfunction in PAH do not include other forms of the disease beyond idiopathic PAH. The present study was planned to measure plasma levels microvascular dysfunction markers in two different forms of PAH, and investigate possible correlations with indices of severity of the disease; to investigate the effects of chronic rosuvastatin administration versus placebo on the circulating levels of these markers; and to investigate possible associations between levels of these parameters and prognosis. Sixty patients (aged 13 to 60 years) were included, 14 with idiopathic or hereditary PAH, and 46 with congenital heart disease-associated PAH (CHDPAH), in the absence (N=18) or presence (N=28) of hypoxemia. Plasma levels of von Willebrand factor antigen (vWF:Ag), tissue-plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), tumor necrosis factor alpha (TNF-), reactive C protein (RCP), P-selectin, interleukin-6 (IL- 6), and interleukin-10 (IL-10) were measured before treatment and 30, 90, and 180 days on treatment using high-sensitivity enzyme-linked immunosorbent assay kits. Patients were randomly assigned to placebo (N=30) or a single oral dose of rosuvastatin (N=30), 10mg/day, for six months. Demographic and functional data such as age, six-minute walk distance, peripheral oxygen saturation at rest and at the end of the six-minute walk, as well as the hematocrit, were recorded. Patients with CHDPAH were followed-up for 0.7 to 4.0 years (median 3.6 years). At baseline, levels of all proteins (except TNF- and RCP) were significantly increased in patients versus controls (p<0,001), and correlated significantly with indices of severity of the disease. P-selectin level was lower in the rosuvastatin group compar...