Use of novel biomarkers (Homocysteine, vitamin B6, B9 and B12) on the assessing the progression of cardiovascular disease

A large number of evidences correlate elevated levels of homocysteine (Hcys) with a higher cardiovascular diseases (CVDs) risk, especially, atherosclerosis. Similarly, abnormal low levels of the vitamins B6, B9 and B12 are associated to an instability in the methionine cycle with an over production of Hcys. Thus, biomedical sciences are looking forward for a cheaper, faster, precise and accurate analytical methodology to quantify these compounds in a suitable format for the clinical environment. Therefore the objective of this study was the development of a simple, inexpensive and appropriate methodology to use at the clinical level. To achieve this goal, a procedure integrating a digitally controlled (eVol®) microextraction by packed sorbent (MEPS) and an ultra performance liquid chromatography (UPLC) coupled to a photodiode array detector (PDA) was developed to identify and quantify Hcys vitamins B6, B9 and B12. Although different conditions were assayed, we were not able to combine Hcys with the vitamins in the same analytical procedure, and so we proceeded to the optimization of two methods differing only in the composition of the gradient of the mobile phase and the injected volume. It was found that MEPS did not bring any benefit to the quantification of the Hcys in the plasma. Therefore, we developed and validate an alternative method that uses the direct injection of treated plasma (reduced and precipitated). This same method was evaluated in terms of selectivity, linearity, limit of detection (LOD), limit of quantification (LOQ), matrix effect and precision (intra-and inter-day) and applied to the determination of Hcys in a group composed by patients presenting augmented CVD risk. Good results in terms of selectivity and linearity (R2> 0.9968) were obtained, being the values of LOD and LOQ 0.007 and 0.21 mol / L, respectively. The intra-day precision (1.23-3.32%), inter-day precision (5.43-6.99%) and the recovery rate (82.5 to 93.1%) of this method were satisfactory. The matrix effect (>120%) was, however, higher than we were waiting for. Using this methodology it was possible to determine the amount of Hcys in real plasma samples from individuals presenting augmented CVD risk. Regarding the methodology developed for vitamins, despite the optimization of the extraction technique and the chromatographic conditions, it was found that the levels usually present in plasma are far below the sensitivity we obtained. Therefore, further optimizations of the methodology developed are needed. As conclusion, part of the objectives of this study was achieved with the development of a quick, simple and cheaper method for the quantification of Hcys.

Síndrome metabólica e risco cardiovascular na pós- menopausa: avaliação por diferentes critérios diagnósticos e influência de fatores sócio-econômicos

The metabolic syndrome (MetS) involves a group of risk factors and is associated with a significantly higher risk of developing cardiovascular diseases (CVD) and type 2 diabetes. Recent studies have shown the importance of preventing CVD through early diagnosis and treatment of patients with MetS. The objective of our study was to determine the prevalence of MetS by different diagnostic criteria in postmenopausal women and analyze the influence of socioeconomic factors on cardiovascular risk in this sample of the population. A cross-sectional study involving 127 postmenopausal women (45 to 64 years) from Natal and Mossoró, Brazil. The study was approved by the Research Ethics Committee of the Federal University of Rio Grande do Norte. The experimental protocol consisted of applying structured interview, clinical examination and implementation of dosages blood. The diagnosis of MetS was based on NCEP-ATP III (National Cholesterol Education Program-Adult Treatment Panel III) and IDF (International Diabetes Federation) criteria. The research was accomplished with the participation of an interdisciplinary team in their several phases. The result of the sample studied had mean age of 53.9 ± 4.6 years and per capita income of 54.5 dollars. The prevalence of MetS, according to NCEP-ATP III and IDF criteria, was 52.8% and 61.4$, respectively. The agreement rate between NCEP-ATP III and IDF criteria was 81.9%, with a kappa value of 0.63 (CI 95%, 0.49-0.76), indicating good agreement between the two definitions. The most prevalent cardiovascular risk factor was HDL < 50 mg/dl, observed in 96.1% of the women analyzed, followed by increased waist circumference (≥ 80 cm) in 78.0%, elevated blood pressure in 51.2%, triglycerides ≥ 150 mg/dl in 40.9% and glycemia ≥ 100 mg/dl in 37.0% of the women. The occurrence of MetS was significantly associated with schooling and body mass index (BMI). High blood pressure was significantly associated with low family income, low schooling and weight gain. There was no significant association between the intensity of climacteric symptomatology and the occurrence of MetS. The conclusions of the research were that MetS and its individual components show a high prevalence in postmenopausal Brazilian women, and significant associations with weight gain and low socioeconomic indicators. The data point to the need for an interdisciplinary approach at the basic health care level, directed toward the early identification of risk factors and the promotion of cardiovascular health of climacteric women.

Doença cardiovascular em mulheres com histórico de pré-eclâmpsia e seguimento no sistema único de saúde

The aim of the present study was to analyze cardiovascular risk of women with a history of preeclampsia, as well as its follow-upin the National Health System.This is a cross-sectional quantitative research conducted at the Januário Cicco Maternity School. The study population was composed of 573 women selected from a databank belonging to the Women s Health Research Group of the Gynecology Department at Universidade Federal do Rio Grande do Norte, with a history of preeclampsia, and normotensives who gave birth at this institution five years before. The final sample consisted of 147 women, 64 in the group with a history of PE and 83 normotensives. Data were collected on a questionnaire containing the following: sociodemographic aspects, anthropometric measures, life habits, personal and family history of pregnancy-induced hypertension, family history of cardiovascular diseases and frequency of measuring current blood pressure levels. In relation to the association between cardiovascular risk and altered blood pressure (≥130x85 mmHg), the likelihood of exhibiting the latter condition was significantly higher in women with a history of preeclampsia (CI 95% 4.12-38.92), the overweight and obese (CI 95% 1.70-20.75), and in those with a family historyof CVD and personal history of PIH (CI 95% 0.78-47.07 and CI 95% 3.20-25.39) respectively. Likewise, the probability of having altered blood pressure was higher in women with fasting glycemia ≥100mg/dL (CI 95% 2.09-24.73), as well as in those with triglycerides ≥150mg/dl (CI 95% 1.72-9.66). After fitting the logistic model, diagnosis previous preeclampsia and altered triglycerides remained as explanatory variables.The women with a history of preeclampsia five years before exhibited altered blood pressure levels, clinical and laboratory manifestations suggestive of elevated risk for cardiovascular disease, as well as family and personal history of hypertension. There is no differential treatment or adequate outpatient follow-up for this population in basic health care units

Antitumoral, mutagenic and (anti)estrogenic activities of tingenone and pristimerin

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Effect of gender on training-induced vascular remodeling in SHR

There is accumulating evidence that physical inactivity, associated with the modern sedentary lifestyle, is a major determinant of hypertension. It represents the most important modifiable risk factor for cardiovascular diseases, which are the leading cause of morbidity and mortality for both men and women. In addition to involving sympathetic overactivity that alters hemodynamic parameters, hypertension is accompanied by several abnormalities in the skeletal muscle circulation including vessel rarefaction and increased arteriole wall-to-lumen ratio, which contribute to increased total peripheral resistance. Low-intensity aerobic training is a promising tool for the prevention, treatment and control of high blood pressure, but its efficacy may differ between men and women and between male and female animals. This review focuses on peripheral training-induced adaptations that contribute to a blood pressure-lowering effect, with special attention to differential responses in male and female spontaneously hypertensive rats (SHR). Heart, diaphragm and skeletal muscle arterioles (but not kidney arterioles) undergo eutrophic outward remodeling in trained male SHR, which contributed to a reduction of peripheral resistance and to a pressure fall. In contrast, trained female SHR showed no change in arteriole wall-to-lumen ratio and no pressure fall. on the other hand, training-induced adaptive changes in capillaries and venules (increased density) were similar in male and female SHR, supporting a similar hyperemic response to exercise.

Relação entre a doença periodontal e doença cardiovascular: há uma preocupação por parte dos que fazem clínica médica e odontológica na cidade de Natal?

The relationship between periodontal and cardiovascular diseases is a reality in the current days. The knowledge about the role of periodontal disease as a risk factor to cardiovascular disease from dentistry and physicians is very important to try to eliminate this risk factor. The aim of this work was to investigate, using a questionary, if physicians and dentistry are aware about this relationship and if they think that it is important. These forms were distributed in 4 groups: cardiologists (n=90), physicians from other specialist (POS) (n=110), periodontists (n=35) and dentistry from other specialist (DOE) (n=85). We had a loss off 32,4% of the total sample due to a lack of response of some professionals. Our results showed that all cardiologists, all dentists and 68,2% of POE said that they had gotten information about the relationship between periodontal and cardiovascular disease, and just 6 POS don t believe that this relationship can occur. When questioned if, even when a periodontal disease is diagnosed, there is a habit to treat or orient the patient for treatment, 29,5% of cardiologists answered no, 25,5% of POE also answered that they did not orient and only 1 DOE answered that he did not treat nor orient. All periodontists said that treat their patients when periodontal disease was identify. The physicians seem not to find important the relationship that exist between periodontal and cardiovascular diseases and the dentistry have shown a good knowledge about this subject. Maybe, if physicians and dentistry work together, the incidence of cardiovascular disease decreases

Perfil de mortalidade de idosos no Rio Grande do Norte: estudo comparativo entre duas faixas etárias e fatores relacionados

Measures of mortality represent one of the most important indicators of health conditions. For comprising the larger rate of deaths, the study of mortality in the elderly population is regarded as essential to understand the health situation. In this sense, the present study aims to analyze the mortality profile of the population from 60 to 69 (young elders) and older than 80 years old (oldest old) in the Rio Grande do Norte state (Brazil) in the period 2001 to 2011, and to identify the association with contextual factors and variables about the quality of the Mortality Information System (SIM). For this purpose, Mortality Proportional (MP) was calculated for the state and Specific Mortality Rate by Age (CMId) , according to chapters of ICD- 10, to the municipalities of Rio Grande do Norte , through data from the Mortality Information System (SIM) and the Brazilian Institute of Geography and Statistics (IGBE). In order to identify groups of municipalities with similar mortality profiles, Nonhierarchical Clustering K-means method was applied and the Factor Analysis by the Principal Components Analysis was resort to reduce contextual variables. The spatial distribution of these groups and the factors were visualized using the Spatial Analysis Areas technique. During the period investigated, 21,813 younger elders deaths were recorded , with a predominance of deaths from circulatory diseases (32.75%) and neoplasms (22.9 %) . Among the oldest old, 50,637 deaths were observed, which 35.26% occurred because of cardiovascular diseases and 17.27% of ill-defined causes. Clustering Analysis produced three clusters to the two age groups and Factor Analysis reduced the contextual variables into three factors, also the sum of the factor scores was considered. Among the younger elders, the groups are called misinformation profile, development profile and development paradox, which showed a statistically significant association with education and poverty and extreme poverty factors, factorial sum and the variable related to underreporting of deaths. Misinformation profile remained in the oldest old group, accompanied by the epidemiological transition profile and the epidemiological paradox, that were statistically associated with the development and health factor, as well as with the variables that indicate the SIM quality: proportion of blank fields about the schooling and underreporting. It proposed that the mortality profiles of the younger elders and oldest old differ on the importance of the basic causes and that are influenced by different contextual aspects , observing that 60 to 69 years group is more affected by such aspects. Health inequalities can be reduced by measures aimed to improve levels of education and poverty, especially in younger elders, and by optimizing the use of health services, which is more associated to the oldest old health situation. Furthermore, it is important to improve the quality of information for the two age groups

Frequência de fatores de risco cardiovascular em voluntários participantes de evento de educação em saúde

INTRODUCTION. Cardiovascular diseases (CVD) are the main cause of death in Brazil.OBJECTIVE. To evaluate the frequency of CVD risk factors In a population attending a health education community event.METHODS. Retrospective study that included 428 completed forms with clinical and demographic information of volunteers attending a public event, in May, 2006. Data were expressed by means and standard deviation or proportions and compared by Student's t test or Chi-square test. Associations between Arterial Hypertension (AH), Diabetes Mellitus (DM) and clinical variables were analyzed by multinomial logistic regression. Significance level was p<0.05.RESULTS. Mean age was 57 +/- 14years, and women represented 58% of the total population. The main cardiovascular risk factors were AH (39.5%), DM (15.4%) and dyslipidemia (25.89%). The frequency of unawareness about these risk factors was respectively 8.4%, 17.5% and 33.1%.. Family history of CVD was reported by 41% while only 67% reported having any information about DM or dyslipidemia. Among obese individuals (IMC >= 30 Kg/m2, 27.3% of the population), systolic blood pressure (133 +/- 16mmHg), diastolic blood pressure (84 +/- 11.5mmHg) and casual glycemia (124 +/- 52.5mg/dl) were higher when compared to non-obese (p<0.05). There was a significant association between obesity and dyslipidemia (p=0.04). Age and IMC were independently associated with AH and DM.CONCLUSION. The high frequency of modifiable cardiovascular risk factors in this population suggests the need for educational programs to promote primary prevention, mainly for the elderly and overweight. [Rev Assoc Med Bras 2009; 55(5): 606-10]

Immunovirological parameters and cytokines in HIV infection

Enquanto modernas terapias antirretrovirais (TARV) têm resultado em menores índices de morbidade e mortalidade e na melhora visível dos parâmetros clínicos e laboratoriais em infectados pelo HIV, sabe-se que seu uso em longo prazo contribui com aparecimento dos vários eventos não associados à aids como doenças cardiovasculares, cânceres e osteoporose, comorbidades as quais têm sido propostas como algumas das mais importantes que privam a maioria dos infectados pelo vírus a apresentarem prognóstico ainda melhor. Isso ocorre porque, mesmo com diminuição da inflamação e ativação imune após intervenção medicamentosa ao paciente, tais parâmetros continuam maiores que os apresentados por indivíduos saudáveis e o desequilíbrio dos perfis de citocinas também persiste. Por isso, avaliações de outros biomarcadores na prática clínica são necessárias para complementar os exames já realizados rotineiramente e permitir o monitoramento mais eficaz dos portadores do HIV. Esta revisão tem o intuito de investigar o papel das citocinas como potenciais marcadores, relacionando estudos sobre o comportamento de várias delas em diversas fases da infecção por HIV, na presença ou não de TARV.

Motivos do abandono do seguimento médico no cuidado a portadores de hipertensão arterial: a perspectiva do sujeito

A hipertensão arterial é um expressivo problema de saúde pública enquanto fator de risco para as doenças cardiovasculares e principal grupo de causas de mortalidade no Brasil. A baixa adesão e o abandono do tratamento estão entre os principais obstáculos às estratégias individuais de controle. Estudam-se os motivos do abandono do seguimento médico em uma coorte de pacientes em tratamento de hipertensão arterial, em serviço de atenção primária à saúde, acompanhados por um período de quatro anos. Foram realizadas entrevistas semiestruturadas com cinquenta pessoas com hipertensão que abandonaram o seguimento médico. As respostas foram analisadas mediante a técnica de análise temática de conteúdo. Os motivos relatados para o abandono do seguimento mostraram predomínio de razões ligadas ao próprio serviço de saúde - sua organização, estrutura e a relação médico-paciente - e, ainda, tratamento em outro serviço de saúde. Razões de natureza psicossocial, como a ausência de sintomas, a melhora e/ou a normalização da pressão arterial e o consumo de álcool também contribuíram para o abandono do cuidado. Estudar os motivos do abandono na perspectiva do próprio sujeito permitiu verificar a riqueza e diversidade de problemas envolvidos no cuidado requerido.

Early physical activity promotes lower prevalence of chronic diseases in adulthood

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Sudden cardiac death athletes: a systematic review

Previous events evidence that sudden cardiac death (SCD) in athletes is still a reality and it keeps challenging cardiologists. Considering the importance of SCD in athletes and the requisite for an update of this matter, we endeavored to describe SCD in athletes. The Medline (via PubMed) and SciELO databases were searched using the subject keywords sudden death, athletes and mortality. The incidence of SCD is expected at one case for each 200,000 young athletes per year. Overall it is resulted of complex dealings of factors such as arrhythmogenic substrate, regulator and triggers factors. In great part of deaths caused by heart disease in athletes younger than 35 years old investigations evidence cardiac congenital abnormalities. Athletes above 35 years old possibly die due to impairments of coronary heart disease, frequently caused by atherosclerosis. Myocardial ischemia and myocardial infarction are responsible for the most cases of SCD above this age (80%). Pre-participatory athletes' evaluation helps to recognize situations that may put the athlete's life in risk including cardiovascular diseases. In summary, cardiologic examinations of athletes' pre-competition routine is an important way to minimize the risk of SCD. © 2010 Ferreira et al; licensee BioMed Central Ltd.

Effect of exercise training on the cardiovascular and biochemical parameters in women with eNOS gene polymorphism

Context: Presence of endothelial nitric oxide synthase (eNOS) gene polymorphism has been associated with cardiovascular disease (CVD) whereas exercise training (EX) promotes beneficial effects on CVD which is related to increased nitric oxide levels (NO). Objective: To evaluate if women with eNOS gene polymorphism at position-G894T would be less responsive to EX than those who did not carry T allele. Methods: Women were trained 3 days/week, 40 minutes session during 6 months. Cardio-biochemical parameters and genetic analysis were performed in a double-blind fashion. Results: Plasma NOx - levels were similar in both groups at baseline (GG genotype: 18.44±3.28 μM) and (GT + TT genotype: 17.19±2.43 μM) and after EX (GG: 29.20±4.33 and GT+TT: 27.38±3.12 μM). A decrease in blood pressure was also observed in both groups. Discussion and conclusion: The presence of eNOS polymorphism does not affect the beneficial effects of EX in women. © 2011 Informa UK, Ltd.

Pathological and behavioral risk factors for higher serum c-reactive protein concentrations in free-living adults - A Brazilian community-based study

Low-grade chronic systemic inflammation is often associated with chronic non-communicable diseases, and its most frequently used marker, the C-reactive protein (CRP), has become an identifier of such diseases as well as an independent predictor for cardiovascular disorders and mortality. CRP is produced in response to pro-inflammatory signaling and to individual and behavioral factors, leading to pathological states. The aim of this study was to rank the predicting factors of high CRP concentrations in free-living adults from a community-based sample. We evaluated 522 adults (40-84 years old; 381 women) for anthropometric characteristics, dietary intake, clinical and physical tests, and blood analysis. Subjects were assigned to groups, according to CRP concentrations, as normal CRP (G1;<3.0 mg/L; n = 269), high CRP (G2; 3.0-6.0 mg/L; n = 139), and very high CRP (G3; >6.0 mg/dL; n = 116). Statistical comparison between groups used one-way ANOVA or Kruskal-Wallis tests, and prediction of altered values in increasing CRP was evaluated by proportional hazard models (odds ratio). CRP distribution was influenced by gender, body mass index, body and abdominal fatness, blood leukocytes, and neutrophil counts. The higher CRP group was discriminated by the above variables in addition to lower VO2max, serum metabolic syndrome components (triglycerides, glucose, and HDL cholesterol), higher insulin, homeostasis assessment of insulin resistance, uric acid, gamma-GT, and homocysteine. After adjustments, only fatness, blood leukocytes, and hyperglycemia remained as independent predictors for increased serum CRP concentrations. Intervention procedures to treat low-grade chronic inflammation in overweight women would mainly focus on restoring muscle mass and functions in addition to an antioxidant-rich diet. © 2012 Springer Science+Business Media, LLC.

Tissue-engineered blood vessel substitute by reconstruction of endothelium using mesenchymal stem cells induced by platelet growth factors

Background: Cardiovascular diseases remain leaders as the major causes of mortality in Western society. Restoration of the circulation through construction of bypass surgical treatment is regarded as the gold standard treatment of peripheral vascular diseases, and grafts are necessary for this purpose. The great saphenous vein is often not available and synthetic grafts have their limitations. Therefore, new techniques to produce alternative grafts have been developed and, in this sense, tissue engineering is a promising alternative to provide biocompatible grafts. This study objective was to reconstruct the endothelium layer of decellularized vein scaffolds, using mesenchymal stem cells (MSCs) and growth factors obtained from platelets. Methods: Fifteen nonpregnant female adult rabbits were used for all experiments. Adipose tissue and vena cava were obtained and subjected to MSCs isolation and tissue decellularization, respectively. MSCs were subjected to differentiation using endothelial inductor growth factor (EIGF) obtained from human platelet lysates. Immunofluorescence, histological and immunohistochemical analyses were employed for the final characterization of the obtained blood vessel substitute. Results: The scaffolds were successfully decellularized with sodium dodecyl sulfate. MSCs actively adhered at the scaffolds, and through stimulation with EIGF were differentiated into functional endothelial cells, secreting significantly higher quantities of von Willebrand factor (0.85 μg/mL; P < .05) than cells cultivated under the same conditions, without EIGF (0.085 μg/mL). Cells with evident morphologic characteristics of endothelium were seen at the lumen of the scaffolds. These cells also stained positive for fascin protein, which is highly expressed by differentiated endothelial cells. Conclusions: Taken together, the use of decellularized bioscaffold and subcutaneous MSCs seems to be a potential approach to obtain bioengineered blood vessels, in the presence of EIGF supplementation. © 2013 Society for Vascular Surgery.