The effect of continuous positive airway pressure on blood pressure in patients with obstructive sleep apnea and uncontrolled hypertension - Study design and challenges during the COVID-19 pandemic

OBJECTIVES: To describe the MORPHEOS (Morbidity in patients with uncontrolled HTN and OSA) trial, and describe the challenges imposed by the COVID-19 pandemic. METHODS: MORPHEOS is a multicenter (n=6) randomized controlled trial designed to evaluate the blood pressure (BP) lowering effects of treatment with continuous positive airway pressure (CPAP) or placebo (nasal strips) for 6 months in adult patients with uncontrolled hypertension (HTN) and moderate-to-severe obstructive sleep apnea (OSA). Patients using at least one antihypertensive medication were included. Uncontrolled HTN was confirmed by at least one abnormal parameter in the 24-hour ABPM and ≥80% medication adherence evaluated by pill counting after the run-in period. OSA was defined by an apnea-hypopnea index ≥15 events/hours. The co-primary endpoints are brachial BP (office and ambulatory BP monitoring, ABPM) and central BP. Secondary outcomes include hypertension-mediated organ damage (HMOD) to heart, aorta, eye, and kidney. We pre-specified several sub-studies from this investigation. Visits occur once a week in the first month and once a month thereafter. The programmed sample size was 176 patients but the pandemic prevented this final target. A post-hoc power analysis will be calculated from the final sample. ClinicalTrials.gov: NCT02270658. RESULTS: The first 100 patients are predominantly males (n=69), age: 52±10 years, body mass index: 32.7±3.9 kg/m2 with frequent co-morbidities. CONCLUSIONS: The MORPHEOS trial has a unique study design including a run-in period; pill counting, and detailed analysis of hypertension-mediated organ damage in patients with uncontrolled HTN that will allow clarification of the impact of OSA treatment with CPAP.

Identificação da demanda da populaçãoidosa assistida em hospital de ensino / Identification of population demand Elderly assisted in teaching hospital

Objetivo - Partindo da premissa que o envelhecimento da população brasileira acarreta aumento da demanda nos hospitais,este estudo objetivou analisar indicadores que retratem a demanda de idosos atendidos em instituição hospitalar. Método: Estudoquantitativo, transversal, retrospectivo e analítico desenvolvido em um hospital de ensino do município de São Paulo. Resultados: Onúmero total de atendimentos foi 268.757, sendo que esses foram prestados a 67.608 idosos no período de janeiro de 2004 a agosto de2014. A média de idade é de 71,6 anos. A especialidade de clínica médica foi a mais procurada. Os diagnósticos mais frequentes foramdor da região lombar baixa, infecções de trato urinário e hipertensão essencial. A maioria das altas foi para residência com permanênciahospitalar entre menos de uma hora a 91 dias. Conclusão: Esses resultados induzem a refletir sobre a necessidade de implementar novosmodelos assistências que vão além de suprir os aspectos biomédicos.

Factors associated with statin-related adverse muscular events in adult dyslipidemic outpatients

ABSTRACT Statins are the most prescribed lowering-cholesterol drugs. They are well tolerated, however, some patients present muscular adverse symptoms. Clinical and laboratory data from 120 dyslipidemic patients prescribed with statins were obtained from January to December/2013 at a University Hospital in Sao Paulo city, Brazil, to study factors associated with statin-related adverse muscular events (AME). Pharmacotherapy and statin-related AME data (serum CK elevation and any degree of myopathy, myalgia, myositis or rhabdomyolysis) of the dyslipidemic patients were recorded. The study was approved by local Ethics Committees. Simvastatin (70%) and atorvastatin (25%) were the most prescribed statins. AME related to statin treatment were found in 17% of the patients. Mean age and use of simvastatin were lower in AME group than non-AME group (p<0.05). Simvastatin users were less likely to develop AME than atorvastatin users (OR=0.21; 95%CI=0.07-0.57; p<0.01). The use of P-glycoprotein (ABCB1) efflux pump inhibitors was associated with high risk for AME (OR=5.26; 95%CI=1.55-17.79; p<0.01). Serum liver enzymes were increased up to three-fold in 2.5% of the statin-treated patients. The results are suggestive that the type of statin prescribed and the concomitant use of ABCB1 inhibitors increase the susceptibility to adverse muscular events during statin therapy in dyslipidemic outpatients

Exposure to potentially inappropriate medications in Brazilian elderly outpatients with metabolic diseases

ABSTRACT Management of pharmacotherapy in elderly with metabolic diseases is challenging and potentially inappropriate medications (PIMs) are risk factors for drug interactions and adverse events. The exposure to PIMs in elderly outpatients with metabolic diseases and its relationship with polypharmacy and other variables was investigated. PIMs prescribed to 207 elderly patients (aged 60 to 96 years) with metabolic diseases who attended a University Hospital of Sao Paulo city, Brazil, from April/2010 to January/2011, were evaluated. PIMs were detected using both 2003 Beers and 2008 STOPP criteria. The association between PIMs and age, gender and polypharmacy was also examined. 2008 STOPP criteria detected more PIMs (44.4 %) than 2003 Beers criteria (16.0%, p<0.001). Beers detected mainly PIMs antihypertensive (clonidine, 20.0%; doxazosin, 10.0%) and antidepressant (fluoxetine, 15.0%; amitriptyline, 10.0%) PIMs. Medicines used for cardiovascular (aspirin, 53.7%) and endocrine system (glibenclamide, 21.3%) were PIMs more frequently detected by 2008 STOPP. Unlike age and gender, polypharmacy increased the risk of PIMs by both 2003 Beers (OR: 4.0, CI95%: 1.2-13.8, p<0.031) and 2008 STOPP (OR: 6.8, CI95%: 3.0-15.3, p<0.001). Beers and STOPP criteria are important tools to evaluate the exposure to PIMs, which is strongly associated with polypharmacy in elderly outpatients with metabolic diseases.

Leptin receptor gene polymorphisms are associated with adiposity and metabolic alterations in Brazilian individuals / Polimorfismos no gene do receptor de leptina são associados com adiposidade e alterações metabólicas em indivíduos brasileiros

OBJECTIVE: The aim of the study was to investigate whether adiposity and metabolic markers, such as leptin, glucose, and lipids, are influenced by leptin (LEP) and leptin receptor (LEPR) gene polymorphisms in a sample of our population. SUBJECTS AND METHODS: A group of 326 individuals of Caucasian-European descent, aged 30 to 80 years, 87 men and 239 women, 148 obese and 178 non-obese, was randomly selected at two clinical hospitals in the city of Sao Paulo, Brazil. All individuals declared their ethnic group as white during the initial interview. Anthropometric measurements, body mass index (BMI), and fat mass were evaluated. Blood samples were drawn for DNA extraction and measurements of leptin, soluble leptin receptor, glucose, and lipids. LEP -2548G>A and LEPR Lys109Arg (c.326A>G), Gln233Arg (c.668A>G) and Lys656Asn (c.1968G>C) polymorphisms were detected by PCR-RFLP. RESULTS: Increased leptin and serum lipids, and LEPR Arg223Arg (GG genotype) were associated with higher risk for obesity (p < 0.05), while reduced risk was found in LEPR Arg109Arg (GG genotype) carriers (OR: 0.38, 95%CI: 0.19-0.77, p = 0.007). Multiple linear regression analysis showed a relationship between LEPR 223Arg, increased waist circumference, and leptinemia (p < 0.05), while LEPR 109Arg was associated with high total cholesterol and triglycerides (p < 0.05). LEPR haplotype 3 (AGG: 109Lys/233Arg/656Lys) carriers have increased risk for obesity (OR: 2.56, 95% CI: 1.19-5.49, p = 0.017). Moreover, this haplotype was associated with increased BMI, waist circumference, and leptinemia (p < 0.05). CONCLUSIONS: LEPR polymorphisms are associated with obesity, hyperleptinemia, and atherogenic lipid profile, suggesting their potential role for leptin resistance and cardiovascular risk. Moreover, LEPR haplotype 3 confers susceptibility to adiposity and hyperleptinemia in our population.

OBJETIVO: O estudo teve por objetivo investigar a influência de polimorfismos nos genes da leptina (LEP) e do receptor de leptina (LEPR) na adiposidade e em marcadores metabólicos, como leptina, glicose e lipí­deos, em uma amostra de nossa população. SUJEITOS E MÉTODOS: Um grupo de 326 indivíduos com idade de 30 a 80 anos, 87 homens e 239 mulheres, 148 obesos e 178 não obesos, e de etnia branca foi selecionado aleatoriamente em dois hospitais clínicos da cidade de São Paulo, Brasil. Medidas antropométricas, índice de massa corporal (IMC) e gordura corporal foram avaliados. Amostras de sangue foram obtidas para extração de DNA e determinações de leptina, receptor de leptina solúvel, glicose e lipídeos. Os polimorfismos LEP -2548G>A e LEPR Lys109Arg (c.326A>G), Gln233Arg (c.668A>G) e Lys656Asn (c.1968G>C) foram detectados por PCR-RFLP. RESULTADOS: Leptina e lipídeos séricos aumentados e LEPR Arg223Arg (genótipo GG) foram associados com maior risco de obesidade (p < 0,05), enquanto foi encontrado risco reduzido de obesidade, em portadores de LEPR Arg109Arg (genótipo GG) (OR: 0,38, 95%CI: 0,19-0,77, p = 0,007). A análise de regressão linear múltipla mostrou relação entre o alelo LEPR 223Arg e circunferência abdominal e leptinemia aumentadas (p < 0,05), enquanto o alelo LEPR 109Arg foi associado com aumento de colesterol total e triglicerídeos (p < 0,05). Os portadores do haplotipo 3 do LEPR (AGG: 109Lys/233Arg/656Lys) tiveram maior risco aumentado para obesidade (OR: 2.56, 95% CI: 1.19-5.49, p = 0,017). Além disso, esse haplótipo foi associado com IMC, circunferência abdominal e leptinemia aumentados (p < 0,05). CONCLUSÕES: Polimorfismos de LEPR são associados com obesidade, hiperleptinemia e perfil lipídico aterogênico sugerindo seu papel potencial para a resistência à leptina e risco cardiovascular.

Terapia antirretroviral altamente eficaz para infecção pelo vírus da imunodeficiência humana aumenta a rigidez aórtica / Potent antiretroviral therapy for human immunodeficiency virus infection increases aortic stiffness

FUNDAMENTO: Sabe-se que a terapia antirretroviral altamente potente para Aids reconhecida aumenta o risco cardiovascular, mas os efeitos dos agentes antirretrovirais de acordo com o gênero ainda são desconhecidos. OBJETIVO: O presente estudo avaliou o impacto do tratamento para o vírus da imunodeficiência humana (HIV) na rigidez aórtica de acordo com o gênero. MÉTODOS: Foram recrutados 28 pacientes com Aids submetidos à terapia antirretroviral altamente potente (HAART), 28 pacientes infectados pelo HIV virgens de tratamento, 44 pacientes com diabetes tipo 2, e 30 controles. A rigidez aórtica foi determinada pela medição da Velocidade da Onda de Pulso (VOP), utilizando um equipamento automático validado e não invasivo. RESULTADOS: Os resultados médios brutos da VOP (e intervalo de confiança de 95%) para participantes nos grupos terapia antirretroviral potente, HIV virgem de tratamento, diabéticos, e controles foram 9,77 m/s (9,17-10,36), 9,00 m/s (8,37-9,63), 9,90 m/s (9,32-10,49) e 9,28 m/s (8,61-9,95), respectivamente, para os homens (p de tendência = 0,14) e 9,61 m/s (8,56-10,66), 8,45 m/s (7,51-9,39), 9,83 (9,21-10,44) e 7,79 m/s (6,99-8,58), respectivamente, para as mulheres (p valor de tendência < 0,001). Análises post-hoc revelaram uma diferença significativa entre os valores médios de VOP no grupo com HAART e controles em mulheres (p < 0,01). Ajustes para as demais covariáveis potenciais, incluindo pressão arterial sistólica e diabetes, não alteraram esses resultados. Os achados indicam que o impacto do tratamento com HAART na rigidez aórtica foi amplificado nas mulheres com hipertensão, dislipidemia e síndrome metabólica. CONCLUSÃO: Agentes antirretrovirais potentes utilizados no tratamento da infecção pelo HIV aumentam a rigidez da aorta, especialmente em mulheres com maior risco cardiovascular.

BACKGROUND: Highly active antiretroviral therapy for AIDS is known to increase cardiovascular risk, but the effects of potent antiretroviral agents according to gender are unknown. OBJECTIVE: The present study evaluated the impact of HIV infection treatment on aortic stiffness according to gender. METHODS: From university-affiliated hospitals, we recruited 28 AIDS patients undergoing highly active antiretroviral treatment (HAART), 28 treatment-naïve HIV-infected patients, 44 patients with type 2 diabetes, and 30 controls. Aortic stiffness was determined by measuring pulse wave velocity (PWV) using a validated and non-invasive automatic device. RESULTS: The crude mean PWV values and 95% confidence intervals (95% CI) for HAART, diabetics, and controls were 9.77 m/s (95% CI 9.17-10.36), , 9.00 m/s (95% CI 8.37-9.63), 9.90 m/s (95% CI 9.32-10.49), and 9.28 m/s (95% CI 8.61-9.95), respectively, for men (P-value for trend = 0.14), and 9.61 m/s (95% CI 8.56-10.66), 8.45 m/s (95% CI 7.51-9.39), 9.83 (95% CI 9.21-10.44), and 7.79 m/s (95% CI 6.99-8.58), respectively, for women (P-value for trend <0.001). Post-hoc analysis revealed a significant difference between the mean PWV values in the HAART group and controls in women (P-value <0.01). After adjusting for other potential covariates, including systolic blood pressure and diabetes, these results did not change. The findings indicate that the impact of HAART treatment on aortic stiffness was amplified in women with hypertension, dyslipidemia, and metabolic syndrome. CONCLUSION: Potent anti-retroviral agents used in the treatment of HIV infection increases aortic stiffness, mainly among women with higher cardiovascular risk.

Pharmaceutic guidance to hypertensive patients at USP University Hospital: effect on adherence to treatment

This study was carried out in the outpatient unit of the Teaching Hospital of the University of São Paulo (USP), and studied the impact of an educational program aimed at improving hypertensive patients' compliance to treatment. Seventy five (75) hypertensive patients of both sexes took part in the study which had no age or race discrimination. Participants presented no other concomitant pathology, except obesity, diabetes and dyslipidemia. Forty one patients were allocated to an experimental group (EG). Experimental patients attended lectures on the use of medication and artery hypertension (AH) and received personal pharmaceutical guidance for nine months. The control group (CG) comprised 34 patients who did not attend lectures or receive pharmaceutical advice in this period. The results were assessed by means of serum levels of cholesterol and fractions of tryacylglicerol (TG), urine sodium and potassium, arterial pressure (AP), body mass index (BMI), waist-hip ratio (WHR), and also based on responses to a questionnaire focusing on AH and treatment. Patients who received the guidance showed a greater decrease in AP, TG and WHR, besides an increase of potassium excretion through urine. The experimental group also scored higher on the questionnaires compared to the CG. It was concluded that the educational process, applied under the conditions of the present study, improves clients' clinical response to antihypertensive treatment and should be included in therapeutic strategies of health care services dealing with hypertensive patients.

Este trabalho, realizado no ambulatório do Hospital Universitário da USP, estudou a repercussão de um programa educacional visando melhorar a adesão do paciente hipertenso ao tratamento. Participaram do trabalho 75 pacientes de ambos os sexos, sem discriminação de idade ou raça, sem outras patologias concomitantes, exceto obesidade, diabetes e dislipidemia. Quarenta e um pacientes assistiram palestras sobre uso de medicamentos e hipertensão arterial (HA), receberam orientação farmacêutica individualizada durante nove meses e foram denominados grupo experimental (GE); o grupo controle (GC), composto por 34 pacientes não assistiu palestras nem recebeu orientação farmacêutica, neste período. Os resultados foram avaliados por meio de níveis séricos de colesterol e frações, triacil-gliceróis (TG), sódio e potássio urinários, pressão arterial (PA), índice de massa corpórea (IMC), relação cintura/quadril (RCQ), além de respostas a questionário enfocando HA e tratamento. Verificou-se que os pacientes orientados apresentaram maior decréscimo da PA, TG e da RCQ, além de aumento da excreção urinária de potássio e do percentual de acertos em questionários, em relação ao GC. Concluiu-se que o processo educativo, utilizado nas condições deste estudo, melhora a resposta clínica do paciente ao tratamento anti-hipertensivo e deve fazer parte das estratégias terapêuticas de serviços de atendimento a pacientes hipertensos.

Framingham Heart Study e a teoria do contínuo de Pickering: duas contribuições da epidemiologia para a associaçäo entre pressäo arterial e doença cardiovascular / The Framingham Heart Study and Pickering' theory of continuum: two contributions to epidemiology to hypertension management

As doenças cardiovasculares säo a causa principal de morte na maioria dos países ocidentais desde o final da Segunda Guerra Mundial. Em 1948, iniciou-se o Framingham Heart Study, com o objetivo de identificar as causas dessas doenças. Vários fatores de risco para as doenças cardiovasculares surgiram depois das primeiras análises da coorte de Framingham, tais como pressäo arterial elevada, diabetes, colesterol elevado, obesidade e sedentarismo. Além dos dados empíricos de Framingham, a relaçäo entre hipertensäo e doença cardiovascular ficou bem instituída por George Pickering ao estabelecer a teoria do contínuo. A pressäo arterial deve ser considerada um contínuo de risco, em vez de uma relaçäo linear, ou seja, quanto maior a pressäo arterial, maior será o risco. No entanto, na prática clínica, toma-se necessário dividir os indivíduos em normotensos e hipertensos. Como conseqüência da teoria de Pickering, Geoffrey Rose postulou uma nova teoria para prevençäo de doenças crônicas, unificando a abordagem coletiva e individual das medidas preventivas em cardiologia

Glomerulopatias: classificacao e etiopatogenia / Glomerulopathies: classification and ethiopathogenesis

As desordens glomerulares de grande importancia no contexto clinico atual, continuam sendo topico de constantes debates e reclassificacoes. Os autores fazem uma revisao das glomerulopatias, enfatizando a sua classificacao por sindromes clinicas, bem como fatores de importancia prognostica, etiopatogenica e terapeutica