Alterações da rigidez arterial em doentes com síndrome de apneia obstrutiva do sono, sonolentos e não sonolentos

RESUMO: Introdução: A intervenção no tratamento da Síndrome de Apneia Obstrutiva do Sono (SAOS) pretende ser, cada vez mais, abrangente, uma vez que é conhecida a estreita ligação entre a SAOS e doença cardiovascular. Por este motivo, vai muito para além do componente cognitivo que normalmente conduz ao diagnóstico. Existem extensos trabalhos de investigação sobre a epidemiologia da SAOS e relações de causalidade entre as duas entidades (SAOS e doença cardiovascular). Idealmente, a identificação de um biomarcador que pudesse, em fase precoce, detetar os indivíduos em que existe maior repercussão da doença sobre o aparelho cardiovascular, permitiria um grande avanço na terapêutica da SAOS. A SAOS associa-se a aumento da rigidez arterial, avaliada através da medição de um marcador não invasivo: a velocidade de onda de pulso. A velocidade de onda de pulso carotídeo-femoral (VOP-cf) é um marcador de lesão de órgão alvo no estudo da hipertensão arterial, com valor preditivo de mortalidade cardiovascular. Após a terapêutica com CPAP (continuous positive airways pressure) verifica-se melhoria da rigidez arterial. Contudo, em doentes com SAOS e sem o quadro clínico característico de sonolência diurna excessiva, não é conhecido se existe esse mesmo efeito relativamente ao endotélio vascular. Objetivos: Este projeto de investigação teve como objetivo geral, o explorar diferenças na evolução da rigidez arterial em doentes com SAOS, sonolentos e não sonolentos, submetidos a tratamento com CPAP. Métodos: Trata-se de um estudo prospetivo, tendo sido estudados doentes consecutivos, com idade inferior a 65 anos, enviados a consulta de Sono do HSM por roncopatia ou queixas sugestivas de SAOS. Os doentes foram recrutados na condição de apresentarem SAOS de grau moderado a grave (Índice de apneia/hipopneia - IAH>15/h). Foram excluídos os doentes em que existia patologia cardíaca para além de hipertensão arterial, doença vascular periférica ou outras doenças crónicas graves. Todos os doentes foram avaliados em consulta de Sono, preenchendo a Escala de Sonolência de Epworth. Foram realizadas uma avaliação analítica basal, avaliação antropométrica, registo de pressão arterial nas 24 horas (MAPA) e avaliação da velocidade de onda de pulso carotídeo femoral (VOP-cf). Os participantes foram classificados em dois grupos principais: doentes sonolentos (Epworth>10) e doentes não sonolentos (Epworth ≤ 10). Foram considerados hipertensos quando apresentaram valores de MAPA alterados ou faziam medicação anti-hipertensora. Quando tinham glicemias elevadas em jejum foi solicitada prova de tolerância oral à glucose, e excluídos se eram diabéticos. A dislipidemia e a síndrome metabólica foram diagnosticadas de acordo com as recomendações recentes internacionais. Ao fim de 4 meses de terapêutica com CPAP foi repetida a avaliação inicial. Para efeitos deste estudo foram considerados apenas doentes aderentes a ventiloterapia. Resultados: foram incluídos 34 doentes, com idade média 55.2 (7.9) anos. Destes, 13 (38.2%) eram sonolentos, 79.4% apresentaram hipertensão arterial, 61.8 % síndrome metabólica e 82.4% dislipidemia. Em 61,2% dos doentes a hipertensão era desconhecida ou não estava controlada. Os doentes sonolentos apresentaram uma SAOS mais grave do que os não sonolentos, sendo IAH 44.8 (19.0) vs 29.7 (15.7), p=0.018. Não se verificaram diferenças nos restantes parâmetros avaliados – antropométricos, analíticos e vasculares, mas a análise univariável permitiu identificar que a VOP-cf se associou à sonolência diurna(p=0.004)., à pressão arterial sistólica nas 24h(p=<0.001), à pressão de pulso(p=<0.001), à pressão arterial sistólica diurna(p=<0.001), à pressão arterial sistólica noturna (p=0.002), e à síndrome metabólica (p=0.025). Após 4 meses de terapêutica com CPAP verificou-se uma redução de VOP-cf (p=0.086), mas houve diferenças significativas entre doentes sonolentos e não sonolentos, com redução significativa apenas nos doentes sonolentos (p=0.012). Na análise multivariável, a sonolência diurna, a idade, a pressão de pulso e o tempo (CPAP) foram variáveis associadas com a VOP-cf. Verificou-se ainda uma interação entre a sonolência e o tempo (CPAP), de tal forma que, ajustados para os restantes fatores, se verificou uma redução mais significativa de cf-VOP nos doentes sonolentos, após tratamento com CPAP. No grupo de doentes não sonolentos, valores basais de pressão de pulso mais elevados e valores de LDL-colesterol mais baixos foram preditivos de uma maior redução de VOP-cf após CPAP. Conclusões: Na presente investigação avaliou-se o risco cardiovascular de doentes com SAOS, antes e após tratamento com CPAP, no meio clínico e utilizando instrumentos quantitativos estandardizados. Numa coorte de doentes do sexo masculino, com SAOS moderada a grave, e sem comorbilidades significativas, os doentes sonolentos apresentaram uma melhoria da rigidez arterial após 4 meses de terapêutica com CPAP superior à dos doentes não sonolentos, de forma independente da idade e da pressão de pulso. A avaliação da rigidez arterial na SAOS, através da VOP-cf pode ser um método eficaz para monitorizar a progressão da doença e a eficácia do tratamento, em doentes cumpridores de CPAP e com sonolência diurna. Para além da sonolência diurna, encontrou-se ainda associação entre parâmetros de risco cardiovascular e uma maior redução da VOP-cf após CPAP, enquanto que os parâmetros de estudo de sono, indicadores da gravidade da SAOS, foram pouco influentes.ABSTRACT: Introduction: The management in the treatment of obstructive sleep apnea (OSA) intends to be increasingly comprehensive because of the close link between OSA and cardiovascular disease, and it goes well beyond the cognitive component that usually leads to diagnosis. There are extensive publications that investigate the epidemiology of OSAS, and causal relationships between the two entities (OSAS and cardiovascular disease). Ideally, the identification of a biomarker which could, at an early stage, determine which individuals with OSAS are most affected by the cardiovascular system, would allow a great advance in the treatment of OSA. OSA is associated with increased arterial stiffness, evaluated by carotid-femoral pulse wave velocity, which is a marker of asymptomatic organ damage in the evaluation of hypertensive patients, predictive of cardiovascular mortality. There is an improvement after continuous positive airway treatment (CPAP) but, in the absence of daytime sleepiness, it is not known whether the same effect occurs in vascular endothelium. This study aim to assess differences in changes in arterial stiffness of two groups of patients, defined as having daytime sleepiness or not, after continuous positive airway pressure (CPAP) treatment. Methods: this is a prospective study that studied a selected cohort of consecutive male patients, under 65 years old, with moderate to severe OSA and without great number of comorbidities. All patients were referred to Sleep Consultation by snoring or other complaints suggestive of OSA. Patients were excluded if they had established cardiovascular disease beyond hypertension, diabetes or other chronic diseases, evaluated by chronic use of medication. Metabolic syndrome or dyslipidaemia were allowed. Daytime sleepiness was evaluated by Epworth Sleepiness Scale (ESS) and its was defined by ESS > 10. The diagnosis was confirmed by home respiratory poligraphy. An ambulatory blood pressure (BP) monitoring and carotid-femoral pulse wave velocity (cf-PWV) measurements were performed, before and after four months under CPAP. Compliant patients, sleepy and non-sleepy, were compared using linear mixed effects regression models. A further stratified analysis was performed with non-sleepy patients. Results: 34 patients were recruited, with mean age 55.2 (7.9) years, 38.2% were sleepy, 79.4% with hypertension, 61.8% with metabolic syndrome and 82.4% with dyslipidaemia. In 61.2% of patients, hypertension was uncontrolled or was unknown. Sleepy patients presented a more severe OSAS than non-sleepy, with AHI 44.8 (19.0) vs 29.7 (15.7), p = 0.018. There were no differences in the other parameters evaluated - anthropometric, analytical and vascular - but the univariate analysis allowed to identify that cf-PWV was associated with daytime somnolence (p=0.004), systolic blood pressure in 24h (p<0.001), systolic diurnal blood pressure (p<0.001), nocturnal systolic blood pressure (p= 0.002), and metabolic syndrome (p= 0.025).There was a cf-PWV reduction after CPAP treatment (p=0.086), but the effects of treatment differed significantly between groups, with no changes in non-sleepy patients, while in sleepy patients a significant decrease was observed (p = 0.012). On multivariable regression, a significant interaction between time (CPAP) and sleepiness was found. Evaluating non-sleepy patients group under CPAP therapy, results showed that both higher pulse pressure and lower LDL-cholesterol levels at baseline were associated to higher cf-PWV changes. Conclusions: In a cohort of male patients with moderate to severe OSA, we found that patients with daytime sleepiness had a more severe OSA and presented a greater arterial stiffness improvement after CPAP therapy, independently from age and BP. Besides sleepiness, cf-PWV reduction after CPAP therapy was mainly associated to cardiovascular risk factors, and less to sleep study parameters

Use of CPAP to reduce arterial stiffness in moderate-to-severe obstructive sleep apnoea, without excessive daytime sleepiness (STIFFSLEEP): an observational cohort study protocol

Introduction: Sleepiness is a cardinal symptom in obstructive sleep apnoea (OSA) but most patients have unspecific symptoms. Arterial stiffness, evaluated by pulse wave velocity (PWV), is related to atherosclerosis and cardiovascular (CV) risk. Arterial stiffness was reported to be higher in patients with OSA, improving after treatment with continuous positive airway pressure (CPAP). This study aims to assess whether the same effect occurs in patients with OSA and without sleepiness. Methods and analysis: This observational study assesses the CV effect of CPAP therapy on a cohort of patients with moderate-to-severe OSA; the effect on the subcohorts of sleepy and non-sleepy patients will be compared. A systematic and consecutive sample of patients advised CPAP therapy will be recruited from a single outpatient sleep clinic (Centro Hospitalar de Lisboa Central-CHLC, Portugal). Eligible patients are male, younger than 65 years, with confirmed moderate-to-severe OSA and apnoea-hypopnea index (AHI) above 15/hour. Other sleep disorders, diabetes or any CV disease other than hypertension are exclusion criteria. Clinical evaluation at baseline includes Epworth Sleepiness Scale (ESS), and sleepiness is defined as ESS above 10. OSA will be confirmed by polygraphic study (cardiorespiratory, level 3). Participants are advised to undertake an assessment of carotid-femoral PWV (cf-PWV) and 24 hours evaluation of ambulatory blood pressure monitoring (ABPM), at baseline and after 4 months of CPAP therapy. Compliance and effectiveness of CPAP will be assessed. The main outcome is the variation of cf-PWV over time. Ethics and dissemination: This protocol was approved by the Ethics Committees of CHLC (reference number 84/2012) and NOVA Medical School (number36/2014/CEFCM), Lisbon. Informed, written consent will be obtained. Its results will be presented at conferences and published in peer-reviewed journals.publishersversionpublishe

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The role of sleepiness on arterial stiffness improvement after CPAP therapy in males with obstructive sleep apnea: a prospective cohort study

Abstract Background Obstructive sleep apnea (OSA) is associated with increased cardiovascular risk. This study aim to assess differences in changes in arterial stiffness of two groups of patients, defined as having daytime sleepiness or not, after continuous positive airway pressure (CPAP) treatment. Methods A selected cohort of consecutive male patients, under 65 years old, with moderate to severe OSA and without great number of comorbidities was studied. The diagnosis was confirmed by home respiratory poligraphy. Sleepiness was considered with an Epworth Sleepiness Scale (ESS) > 10. An ambulatory blood pressure (BP) monitoring and carotid-femoral pulse wave velocity (cf-PWV) measurements were performed, before and after four months under CPAP. Compliant patients, sleepy and non-sleepy, were compared using linear mixed effects regression models. A further stratified analysis was performed with non-sleepy patients. Results Thirty-four patients were recruited, with mean age 55.2 (7.9) years, 38.2% were sleepy, 79.4% with hypertension, 61.8% with metabolic syndrome and 82.4% with dyslipidaemia. In univariable analysis, cf-PWV was strongly related to systolic BP parameters and age, but also to antihypertensive drugs (p = 0.030), metabolic syndrome (p = 0.025) and daytime sleepiness (p = 0.004). Sleepy patients had a more severe OSA, with AHI 44.8 (19.0) vs 29.7 (15.7) events/h (p = 0.018), but sleep study parameters were not associated with cf-PWV values. On multivariable regression, a significant interaction between time (CPAP) and sleepiness (p = 0.033) was found. There was a weak evidence of a cf-PWV reduction after CPAP treatment (p = 0.086), but the effects of treatment differed significantly between groups, with no changes in non-sleepy patients, while in sleepy patients a significant decrease was observed (p = 0.012). Evaluating non-sleepy patients group under CPAP therapy, results showed that both higher pulse pressure (p = 0.001) and lower LDL-cholesterol levels (p = 0.015) at baseline were associated to higher cf-PWV changes. Conclusions Patients with daytime sleepiness had a more severe OSA and presented a greater arterial stiffness improvement after CPAP therapy, independently from age and BP. Besides sleepiness, cf-PWV reduction after CPAP therapy was mainly associated to CV risk factors, and less to sleep study parameters. Trial registration Clinicaltrials.gov NCT02273089 23.10.2014 retrospectively registered