Repositório RCAAP

Abstract Phytosterols are bioactive compounds found in foods of plant origin, which can be divided into plant sterols and plant stanols. Clinical studies consistently indicate that the intake of phytosterols (2 g/day) is associated with a significant reduction (8-10%) in levels of low-density lipoprotein cholesterol (LDL-cholesterol). Thus, several guidelines recommend the intake of 2 g/day of plant sterols and/or stanols in order to reduce LDL-cholesterol levels. As the typical western diet contains only about 300 mg/day of phytosterols, foods enriched with phytosterols are usually used to achieve the recommended intake. Although phytosterols decrease LDL-cholesterol levels, there is no evidence that they reduce the risk of cardiovascular diseases; on the contrary, some studies suggest an increased risk of atherosclerosis with increasing serum levels of phytosterols. This review aims to address the evidence available in the literature on the relationship between phytosterols and risk of cardiovascular disease.

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Abstract Background: Endomyocardial fibrosis (EMF) is a rare disease, characterized by diastolic dysfunction which leads to reduced peak oxygen consumption (VO2). Cardiopulmonary exercise testing (CPET) has been proved to be a fundamental tool to identify central and peripheral alterations. However, most studies prioritize peak VO2 as the main variable, leaving aside other important CPET variables that can specify the severity of the disease and guide the clinical treatment. Objective: The aim of this study was to evaluate central and peripheral limitations in symptomatic patients with EMF by different CPET variables. Methods: Twenty-six EMF patients (functional class III, NYHA) were compared with 15 healthy subjects (HS). Functional capacity was evaluated using CPET and diastolic and systolic functions were evaluated by echocardiography. Results: Age and gender were similar between EMF patients and HS. Left ventricular ejection fraction was normal in EMF patients, but decreased compared to HS. Peak heart rate, peak workload, peak VO2, peak oxygen (O2) pulse and peak pulmonary ventilation (VE) were decreased in EMF compared to HS. Also, EMF patients showed increased Δ heart rate /Δ oxygen uptake and Δ oxygen uptake /Δ work rate compared to HS. Conclusion: Determination of the aerobic capacity by noninvasive respiratory gas exchange during incremental exercise provides additional information about the exercise tolerance in patients with EMF. The analysis of different CPET variables is necessary to help us understand more about the central and peripheral alterations cause by both diastolic dysfunction and restrictive pattern.

Abstract Background: Diabetes mellitus is a severe chronic disease leading to systemic complications, including cardiovascular dysfunction. Previous cell therapy studies have obtained promising results with the use bone marrow mesenchymal stromal cells derived from healthy animals (MSCc) in diabetes animal models. However, the ability of MSC derived from diabetic rats to improve functional cardiac parameters is still unknown. Objectives: To investigate whether bone-marrow-derived MSC from diabetic rats (MSCd) would contribute to recover metabolic and cardiac electrical properties in other diabetic rats. Methods: Diabetes was induced in Wistar rats with streptozotocin. MSCs were characterized by flow cytometry, morphological analysis, and immunohistochemistry. Cardiac electrical function was analyzed using recordings of ventricular action potential. Differences between variables were considered significant when p < 0.05. Results: In vitro properties of MSCc and MSCd were evaluated. Both cell types presented similar morphology, growth kinetics, and mesenchymal profile, and could differentiate into adipogenic and osteogenic lineages. However, in an assay for fibroblast colony-forming units (CFU-F), MSCd formed more colonies than MSCc when cultured in expansion medium with or without hydrocortisone (1 µM). In order to compare the therapeutic potential of the cells, the animals were divided into four experimental groups: nondiabetic (CTRL), diabetic (DM), diabetic treated with MSCc (DM + MSCc), and diabetic treated with MSCd (DM + MSCd). The treated groups received a single injection of MSC 4 weeks after the development of diabetes. MSCc and MSCd controlled hyperglycemia and body weight loss and improved cardiac electrical remodeling in diabetic rats. Conclusions: MSCd and MSCc have similar in vitro properties and therapeutic potential in a rat model of diabetes induced with streptozotocin.

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Resumo Fundamentação: desde o primeiro posicionamento da Sociedade Brasileira de Diabetes (SBD) sobre diabetes e prevenção cardiovascular, em 2014,1 importantes estudos têm sido publicados na área de prevenção cardiovascular e tratamento do diabetes,2 os quais contribuíram para a evolução na prevenção primária e secundária nos pacientes com diabetes. Ferramentas de estratificação de risco mais precisas, novos fármacos hipolipemiantes e novos antidiabéticos com efeitos cardiovasculares e redução da mortalidade, são parte desta nova abordagem para os pacientes com diabetes. O reconhecimento de que o diabetes é uma doença heterogênea foi fundamental, sendo claramente demonstrado que nem todos os pacientes diabéticos pertencem a categorias de risco alto ou muito alto. Um porcentual elevado é composto por pacientes jovens, sem os fatores de risco clássicos, os quais podem ser classificados adequadamente em categorias de risco intermediário ou mesmo em baixo risco cardiovascular. O presente posicionamento revisa as melhores evidências atualmente disponíveis e propõe uma abordagem prática, baseada em risco, para o tratamento de pacientes com diabetes. Estruturação: perante este desafio e reconhecendo a natureza multifacetada da doença, a SBD uniu-se à Sociedade Brasileira de Cardiologia (SBC) e à Sociedade Brasileira de Endocrinologia e Metabolismo (SBEM), e formou um painel de especialistas, constituído por 28 cardiologistas e endocrinologistas, para revisar as melhores evidências disponíveis e elaborar uma diretriz contendo recomendações práticas para a estratificação de risco e prevenção da Doença Cardiovascular (DVC) no Diabetes Melito (DM). As principais inovações incluem: (1) considerações do impacto de novos hipolipemiantes e das novas medicações antidiabéticas no risco cardiovascular; (2) uma abordagem prática, baseada em fator de risco, para orientar o uso das estatinas, incluindo novas definições das metas da Lipoproteína de Baixa Densidade-colesterol (LDL-colesterol) e colesterol não Lipoproteína de Alta Densidade HDL; (3) uma abordagem baseada em evidências, para avaliar a isquemia miocárdica silenciosa (IMS) e a aterosclerose subclínica em pacientes com diabetes; (4) as abordagens mais atuais para o tratamento da hipertensão; e (5) recomendação de atualizações para o uso de terapia antiplaquetária. Esperamos que esta diretriz auxilie os médicos no cuidado dedicado aos pacientes com diabetes. Métodos: inicialmente, os membros do painel foram divididos em sete subcomitês para definirem os tópicos principais que necessitavam de uma posição atualizada das sociedades. Os membros do painel pesquisaram e buscaram no PubMed estudos clínicos randomizados e metanálises de estudos clínicos e estudos observacionais de boa qualidade, publicados entre 1997 e 2017, usando termos MeSH: [diabetes], [diabetes tipo 2], [doença cardiovascular], [estratificação de risco cardiovascular] [doença arterial coronária], [rastreamento], [isquemia silenciosa], [estatinas], [hipertensão], [ácido acetilsalicílico]. Estudos observacionais de baixa qualidade, metanálises com alta heterogeneidade e estudos transversais não foram incluídos, embora talvez tenham impactado no Nível de Evidência indicado. A opinião de especialistas foi usada quando os resultados das buscas não eram satisfatórios para um item específico. É importante salientar que este posicionamento não teve a intenção de incluir uma revisão sistemática rigorosa. Um manuscrito preliminar, destacando recomendações de graus e níveis de evidência (Quadro 1), foi esboçado. Este passo levou a várias discussões entre os membros dos subcomitês, que revisaram os achados e fizeram novas sugestões. O manuscrito foi, então, revisto pelo autor líder, encarregado da padronização do texto e da inclusão de pequenas alterações, sendo submetido à apreciação mais detalhada pelos membros dos comitês, buscando uma posição de consenso. Depois desta fase, o manuscrito foi enviado para a banca editorial e edição final, sendo encaminhado para publicação. Quadro 1 Graus de recomendações e níveis de evidências adotados nesta revisão Grau de recomendação Classe I A evidência é conclusiva ou, se não, existe consenso de que o procedimento ou tratamento é seguro e eficaz Classe II Há evidências contraditórias ou opiniões divergentes sobre segurança, eficácia, ou utilidade do tratamento ou procedimento Classe IIa As opiniões são favoráveis ao tratamento ou procedimento. A maioria dos especialistas aprova Classe IIb A eficácia é bem menos estabelecida, e as opiniões são divergentes Classe III Há evidências ou consenso de que o tratamento ou procedimento não é útil, eficaz, ou pode ser prejudicial Níveis de Evidência A Múltiplos estudos clínicos randomizados concordantes e bem elaborados ou metanálises robustas de estudos clínicos randomizados B Dados de metanálises menos robustas, um único estudo clínico randomizado ou estudos observacionais C Opinião dos especialistas

Abstract Background: Bioresorbable vascular scaffolds (BVS) were developed to improve the long-term results of percutaneous coronary intervention, restoring vasomotion. Objectives: To report very late follow-up of everolimus-eluting Absorb BVS (Abbott Vascular, Santa Clara, USA) in our center. Methods: Observational retrospective study, in a single Brazilian center, from August 2011 to October 2013, including 49 patients submitted to Absorb BVS implantation. Safety and efficacy outcomes were analyzed in the in-hospital and very late follow-up phases (> 2 years). Results: All 49 patients underwent a minimum follow-up of 2.5 years and a maximum of 4.6 years. Mean age was 56.8 ± 7.6 years, 71.4% of the patients were men, and 26.5% were diabetic. Regarding clinical presentation, the majority (94%) had stable angina or silent ischemia. Device success was achieved in 100% of cases with 96% overall procedure success rate. Major adverse cardiovascular events rate was 4% at 30 days, 8.2% at 1 year, and 12.2% at 2 years, and there were no more events until 4.6 years. There were 2 cases of thrombosis (1 subacute and 1 late). Conclusions: In this preliminary analysis, Absorb BVS showed to be a safe and effective device in the very late follow-up. Establishing the efficacy and safety profiles of these devices in more complex scenarios is necessary.

Abstract Background: Depressive symptoms are independently associated with an increased risk of cardiovascular disease (CVD) among individuals with non-diagnosed CVD. The mechanisms underlying this association, however, remain unclear. Inflammation has been indicated as a possible mechanistic link between depression and CVD. Objectives: This study evaluated the association between persistent depressive symptoms and the onset of low-grade inflammation. Methods: From a database of 1,508 young (mean age: 41 years) individuals with no CVD diagnosis who underwent at least two routine health evaluations, 134 had persistent depressive symptoms (Beck Depression Inventory - BDI ≥ 10, BDI+) and 1,374 had negative symptoms at both time points (BDI-). All participants had been submitted to repeated clinical and laboratory evaluations at a regular follow-up with an average of 26 months from baseline. Low-grade inflammation was defined as plasma high-sensitivity C-Reactive Protein (CRP) concentrations > 3 mg/L. The outcome was the incidence of low-grade inflammation evaluated by the time of the second clinical evaluation. Results: The incidence of low-grade inflammation was more frequently observed in the BDI+ group compared to the BDI- group (20.9% vs. 11.4%; p = 0.001). After adjusting for sex, age, waist circumference, body mass index, levels of physical activity, smoking, and prevalence of metabolic syndrome, persistent depressive symptoms remained an independent predictor of low-grade inflammation onset (OR = 1.76; 95% CI: 1.03-3.02; p = 0.04). Conclusions: Persistent depressive symptoms were independently associated with low-grade inflammation onset among healthy individuals.

Abstract Background: The diterpene Sclareol has antimicrobial action, cytotoxic and cytostatic effects and anti-tumor activities. However, researches on the cardiovascular system are scarce. Objective: This study was designed to investigate the mechanisms involved in the Sclareol cardiovascular effect in normotensive and hypertensive rats. Methods: The arterial hypertension was promoted using 2-kidneys 1-clip model in rats. The effect of sclareol on blood pressure was performed by using three dose (10, 20 and 40 mg/kg). Cumulative dose-response curves for Sclareol were determined for endothelium-intact and endothelium-denuded aortic rings in presence or absence of L-NAME and ODQ. The NOx levels were measure in the plasma sample. Results: The Sclareol administration in vivo caused a significant reduction in blood pressure in both groups. In vitro the sclareol promoted relaxation in aorta, with endothelium, pre-contracted to Phe. The inhibitors of the nitric oxide synthase and soluble guanylate cyclase were as efficient as the removal of endothelium, in inhibiting the Sclareol-induced relaxation. Otherwise, it was no change of NOx. Also, for unknown reasons, the Sclareol is not selective for hypertensive animals. Conclusion: The diterpene Sclareol showed in vivo hypotensive and in-vitro vasodilator effects; The chemiluminescence plasmatic NO analysis showed no significant difference between groups and The Sclareol exhibit better effect on normotensive than hypertensive animals to reduce blood pressure. It is concluded that the diterpenes metabolites would be a promising source prototype for the development of new agents in the cardiovascular therapy.

Abstract Background: The endothelium is a monolayer of cells that extends on the vascular inner surface, responsible for the modulation of vascular tone. By means of the release of nitric oxide (NO), the endothelium has an important protective function against cardiovascular diseases. Objective: Verify if cis- [Ru(bpy)2(NO2)(NO)](PF6)2 (BPY) improves endothelial function and the sensibility of conductance (aorta) and resistance (coronary) to vascular relaxation induced by BPY. Methods: Normotensive (2K) and hypertensive (2K-1C) Wistar rats were used. For vascular reactivity study, thoracic aortas were isolated, rings with intact endothelium were incubated with: BPY(0.01 to10 µM) and concentration effect curves to acetylcholine were performed. In addition, cumulative concentration curves were performed to BPY (1.0 nM to 0.1 µM) in aortic and coronary rings, with intact and denuded endothelium. Results: In aorta from 2K-1C animals, the treatment with BPY 0.1µM increased the potency of acetylcholine-induced relaxation and it was able to revert the endothelial dysfunction. The presence of the endothelium did not modify the effect of BPY in inducing the relaxation in aortas from 2K and 2K-1C rats. In coronary, the endothelium potentiated the vasodilator effect of BPY in vessels from 2K and 2K-1C rats. Conclusion: Our results suggest that 0.1 µM of BPY is able to normalize the relaxation endothelium dependent in hypertensive rats, and the compound BPY induces relaxation in aortic from normotensive and hypertensive rats with the same potency. The endothelium potentiate the relaxation effect induced by BPY in coronary from normotensive and hypertensive rats, with lower effect on coronary from hypertensive rats.

Abstract Cardiovascular diseases (CVD) account annually for almost one third of all deaths worldwide. Among the CVD, systemic arterial hypertension (SAH) is related to more than half of those outcomes. Type 2 diabetes mellitus is an independent risk factor for SAH because it causes functional and structural damage to the arterial wall, leading to stiffness. Several studies have related oxidative stress, production of free radicals, and neuroendocrine and genetic changes to the physiopathogenesis of vascular aging. Indirect ways to analyze that aging process have been widely studied, pulse wave velocity (PWV) being considered gold standard to assess arterial stiffness, because there is large epidemiological evidence of its predictive value for cardiovascular events, and it requires little technical knowledge to be performed. A pulse wave is generated during each cardiac contraction and travels along the arterial bed until finding peripheral resistance or any bifurcation point, determining the appearance of a reflected wave. In young individuals, arteries tend to be more elastic, therefore, the reflected wave occurs later in the cardiac cycle, reaching the heart during diastole. In older individuals, however, the reflected wave occurs earlier, reaching the heart during systole. Because PWV is an important biomarker of vascular damage, highly valuable in determining the patient’s global cardiovascular risk, we chose to review the articles on vascular aging in the context of cardiovascular risk factors and the tools available to the early identification of that damage.

Abstract Background: Mitral valve regurgitation (MR), present in up to 74% of the patients with severe aortic stenosis (AS), can be a negative prognostic factor when moderate or severe. The outcome of MR after percutaneous transcatheter aortic valve implantation (TAVI) and predictors associated with that outcome have not been well established in the literature. Objective: To assess the outcome of primary MR in patients submitted to TAVI and to identify associated factors. Methods: Observational study of patients with symptomatic severe AS submitted to TAVI from January 2009 to April 2015 at two specialized centers. Echocardiographic outcome was assessed with data collected before and 1 year after TAVI. Results: Of the 91 patients with MR submitted to TAVI and followed up for at least 12 months, 67 (73.6%) had minimum/mild MR before the procedure and 24 (26.4%) had moderate/severe MR. Of those with minimum/mild MR, 62 (92.5%) had no change in the MR grade (p < 0.001), while 5 (7.5%) showed worsening. Of those with moderate/severe MR, 8 (33.3%) maintained the same grade and 16 (66.7%) improved it (p = 0.076). Patients with moderate/severe MR who improved MR grade had lower EuroSCORE II (p = 0.023) and STS morbidity (p = 0.027) scores, as compared to those who maintained the MR grade. Conclusion: MR grades change after TAVI. This study suggests a trend towards improvement in moderate/severe MR after TAVI, which was associated with lower preoperative risk scores.

Abstract Background: The oxidative biomarkers play an important role in the genesis of cardiometabolic risk-related processes. Objective: To investigate the total antioxidant capacity of plasma and its association with cardiometabolic risk in non-obese and clinically healthy young adults. Methods: University students of the state of Sergipe, Brazil, aged between 18 and 25 years, were recruited for this study from May of 2013 and October of 2014. Anthropometric, clinical and biochemical parameters were measured and analyzed using protocols which were previously standardized and described in the literature. The measurement of plasma total antioxidant capacity was based on the ability that all the antioxidants present in the sample (plasma) have to inhibit the oxidation of the oxidizable substrate ABTS (2,2`- Azino-di-[3-ethylbenzthiazoline sulphonate]) to ABTS•+ by metmyoglobin. Results: Approximately 25% of the sample presented more than one component of cardiometabolic risk. Low HDL-cholesterol was the most prevalent component. Compared to absence of components, the subjects with at least one component presented greater body weight and waist circumference, higher levels of diastolic blood pressure and fasting glucose, greater total cholesterol/HDL-c ratio, and lower levels of HDL-c (p < 0.05). Fasting glycemia was the only parameter which was associated with total antioxidant capacity (R2 = 0.10; β = 0.17; p = 0.001). Conclusions: The plasma total antioxidant capacity was not able to predict the cardiometabolic risk components due possibly to the establishment of compensatory mechanisms that become activated in physiological conditions.

Abstract Background: A family history of hypertension is associated with vascular and autonomic abnormalities, as well as an impaired neurohemodynamic response to exercise. Objective: To test the hypothesis that normotensive individuals with a family history of hypertension present an impaired peripheral vascular resistance response to exercise. Methods: The study included 37 normotensive volunteers of both sexes who were sedentary, eutrophic, and nonsmokers, comprising 23 with (FH+; 24 ± 3 years) and 14 without (FH-; 27 ± 5 years) a family history of hypertension. Blood pressure, heart rate (DIXTAL®), forearm blood flow (Hokanson®), and peripheral vascular resistance were simultaneously measured for 3 minutes during rest and, subsequently, for 3 minutes during an isometric exercise at 30% of maximal voluntary contraction (Jamar®). Results: At rest, the FH+ and FH- groups present similar mean blood pressure (83 ± 7 versus 83 ± 5 mmHg, p = 0.96), heart rate (69 ± 8 bpm versus 66 ± 7 bpm, p = 0.18), forearm blood flow (3 ± 1 mL/min/100 mL versus 2.7 ± 1 mL/min/100 mL, p = 0.16), and peripheral vascular resistance (30 ± 9 units versus 34±9 units, p = 0.21), respectively. Both groups showed a significant and similar increase in mean blood pressure (∆ = 15 ± 7 mmHg versus 14 ± 7 mmHg, p = 0.86), heart rate (∆ = 12 ± 8 bpm versus 13 ± 7 bpm, p = 0.86), and forearm blood flow (∆ = 0.8 ± 1.2 mL/min/100 mL versus 1.4 ± 1.1 mL/min/100 mL, p = 0.25), respectively, during exercise. However, individuals in the FH+ group showed no reduction in peripheral vascular resistance during exercise, which was observed in the FH- group (∆ = -0.4 ± 8.6 units versus -7.2 ± 6.3 units, p = 0.03). Conclusion: Normotensive individuals with a family history of hypertension present an impaired peripheral vascular resistance response to exercise.

ABSTRACT Objective: There are no values defined as standard in the literature for the parameters of assessment of cervical sagittal balance in patients with idiopathic scoliosis. This study describes the sagittal cervical parameters in patients with idiopathic scoliosis. Methods: Study carried out in a tertiary public hospital in patients with adolescent idiopathic scoliosis, through the evaluation of panoramic radiographs in lateral view. The Cobb method was used to evaluate cervical lordosis from C2 to C7, distance from the center of gravity (COG) of the skull to C7, measurement of T1 slope, thoracic inlet angle (TIA), neck tilt, and plumb line from C7 to S1 (SVA C7-S1). A statistical analysis was performed, to demonstrate the relationship between the alignment of the thoracic spine in the sagittal plane and the cervical sagittal balance of patients with scoliosis. Results: Thirty-four patients were female (69.4%) and 15 male (30.6%). The mean values for COG-C7 were 0.71 mm (median 0.8 mm/standard deviation [SD]= 0.51 mm). For Cobb C2-C7, the mean was -11.7° (median -10°/SD= 20.4°). The mean slope of T1 was 23.5° (median 25°/SD= 9.5°). The mean cervical version was 58.8° (median 60°/DP= 15.4°). The mean TIA was 81.8° (median 85°/SD= 16.7°). The mean plumb line C7-S1 was -0.28 (-0.3/SD= 1.0). Conclusion: The analysis of the results showed that the mean values for the cervical lordosis are lower than the values described as normal in the literature, suggesting a loss of sagittal cervical balance in these patients.

ABSTRACT Objective: To define histological scores for intervertebral disc degeneration that would enable the definition of morphological characteristics of disease, besides improving knowledge of the lumbar degenerative disc disease by means of immunohistochemical markers. Methods: Hematoxylin and Eosin, Alcian/PAS, Masson Trichrome and Safranin O/FCF staining was used on the intervertebral disc degeneration sections of patients with lumbar degenerative disc disease. The protein markers defined in immunohistochemistry were cell proliferation (Ki-67) and apoptosis (p53). Results: The study data enabled the determination of Safranin O/FCF stain as the most effective one for evaluating parameters such as area, diameter, and number of chondrocyte clusters. The importance of using stains in association, such as Safranin O/FCF, Masson Trichrome, Alcian/PAS and Hematoxylin and Eosin, was also determined, as they are complementary for the histopathological verification of intervertebral disc degeneration. By expressing proteins using the immunohistochemistry technique, it was possible to consider two stages of disc degeneration: cell proliferation with chondrocyte cluster formation, and induction of apoptosis. Conclusion: This study enabled the histological and immunohistochemical characterization to be determined for lumbar degenerative disc disease, and its degrees of evolution, by determining new disc degeneration scores.

ABSTRACT Objective: To evaluate the results of an interdisciplinary program administered to patients with failed back surgery syndrome, aiming at functional improvement, modulation of pain, reduction of anxiety symptoms and depression, and improvement of quality of life. Method: This is a non-randomized prospective study with a sample of patients with failed back surgery pain syndrome diagnosed with persistent or recurrent pain after surgery to the lumbar spine (laminectomy and arthrodesis) referred to liaison in the Pain Clinic (n= 26). The instruments used were Brief Pain Inventory, Roland-Morris Questionnaire and Beck Anxiety and Depression Inventories. The generic WHOQOL-bref13 questionnaire was used to evaluate the quality of life and the fear of moving was assessed by the Tampa Scale for Kinesiophobia. Results: There was a predominance of females, the mean age was 42.3 ± 5.8 years, 43% were married and average schooling was 7 ± 4.5 years. The mean time of pain reported was 8 ± 6.8 months in addition to high levels of anxiety, depression and kinesiophobia. After the intervention, there was a significant improvement in the perception of quality of life and of all parameters evaluated (p<0.05), with functional gains as well as decreased pain threshold. Conclusion: The interdisciplinary intervention in patients with failed back surgery syndrome provides better functional performance, decreases the intensity of pain, anxiety and depression symptoms, and improves quality of life. The inclusion of this intervention associated with drug therapy may the patient develop an active and independent lifestyle.