Effect of clinical treatments for metabolic syndrome on albuminuria: a systematic review protocol

Introduction:Metabolic syndrome (MetS) predicts cardiovascular disease, and patients with this condition and type 2 diabetes have increased albuminuria, significantly impacting cardiovascular mortality and kidney disease progression. A considerable number of interventions to control MetS exist and are considered efficient, including the use of medication and changes in lifestyle. However, which approaches are effective in controlling albuminuria remains unclear. This systematic review protocol aims to map in the available literature whether lifestyle, medication, and surgical intervention for MetS have an impact on reducing albuminuria in adult patients. Methods: The Joanna Briggs Institute methodology for systematic reviews will be followed. Cochrane Database of Systematic Reviews, Scopus, Embase, and MEDLINE/PubMed databases will be used. For the Gray Literature, the DART-Europe E-theses Portal. There will be no language restriction. Studies written after 2009 will be included due to the consensus and definition of metabolic syndrome. This review will include studies considering pharmacological and non-pharmacological treatments for controlling albuminuria in patients with MetS. Studies where MetS is described in children and adolescents, animals, pregnant women, and patients with type 1 diabetes will be excluded. First, the selection will be based on reading the title and summary of the texts retrieved in the search strategy, followed by reading the relevant texts in full by two reviewers. After the selection of the studies, the extraction of the data, analysis, and synthesis will be conducted according to the JBI methodology

Association of C-reactive Protein with Cardiovascular Outcomes: A Mendelian Randomization Study in the Japanese Population / 生物医学与环境科学（英文）

OBJECTIVE@#Traditional epidemiological studies have shown that C-reactive protein (CRP) is associated with the risk of cardiovascular diseases (CVDs). However, whether this association is causal remains unclear. Therefore, Mendelian randomization (MR) was used to explore the causal relationship of CRP with cardiovascular outcomes including ischemic stroke, atrial fibrillation, arrhythmia and congestive heart failure.@*METHODS@#We performed two-sample MR by using summary-level data obtained from Japanese Encyclopedia of Genetic association by Riken (JENGER), and we selected four single-nucleotide polymorphisms associated with CRP level as instrumental variables. MR estimates were calculated with the inverse-variance weighted (IVW), penalized weighted median and weighted median. MR-Egger regression was used to explore pleiotropy.@*RESULTS@#No significant causal association of genetically determined CRP level with ischemic stroke, atrial fibrillation or arrhythmia was found with all four MR methods (all Ps > 0.05). The IVW method indicated suggestive evidence of a causal association between CRP and congestive heart failure ( OR: 1.337, 95% CI: 1.005-1.780, P = 0.046), whereas the other three methods did not. No clear pleiotropy or heterogeneity were observed.@*CONCLUSIONS@#Suggestive evidence was found only in analysis of congestive heart failure; therefore, further studies are necessary. Furthermore, no causal association was found between CRP and the other three cardiovascular outcomes.

Visceral adiposity indicators and cardiovascular risk in hemodialytic patients

ABSTRACT Objective: Cardiovascular diseases represent the main cause of death in chronic kidney disease (CKD). We aimed to evaluate the prevalence and association of the hypertriglyceridemia-waist phenotype (HWP) and visceral adiposity index (VAI) with cardiometabolic risk factors (CR) in patients with CKD on hemodialysis (HD). Materials and methods: The study is based on a cross-sectional design with 265 HD patients in two cities in northeastern Brazil. The VAI was calculated considering the variables body mass index (BMI), waist circumference (WC), triglycerides (TG) and high density lipoprotein cholesterol (HDL-c). HWP was defined as the concomitant elevation of WC and TG. The Poisson Regression Model with robust variance estimation was adjusted considering a hierarchical approach for explanatory variables. Prevalence ratios (PR) were also estimated. The level of significance adopted was 5%. Results: In our study HWP and VAI prevalence's were 29.82% and 58.49%, respectively. In the final model, there was an association between VAI and female gender (PR = 1.46; p < 0.0001) and high body fat (% BF) (PR = 1.33; p < 0.0019). HWP was associated with females (PR = 1.80; p = 0.002), alcohol consumption (PR = 1.58; p = 0.033), obesity (PR = 1.89; p = 0.0001), high %BF (PR = 1.76; p = 0.012) and reduced HDL-c (PR = 1.48; p = 0.035). Conclusion: The HWP stood out as the association with more CR factors, representing a promising method for tracking cardiometabolic risk in HD patients, mainly female.

Análise de dislipidemia em pacientes com insuficiência renal crônica sob tratamento por hemodiálise pelo sistema único de saúde: estudo longitudinal / Analysis of dyslipidemia in patients with chronic kidney failure under hemodialysis treatment by the brazilian health system: a longitudinal study

Introdução: A atual transição demográfica e epidemiológica no Brasil, refletida no envelhecimento populacional, apresenta maior prevalência de doenças crônicas não transmissíveis (DCNT) como as doenças cardiovasculares (DC), neoplasias, distúrbios metabólicos, doenças respiratórias crônicas e insuficiência renal crônica. Essas podem ser decorrentes de fatores risco modificáveis como dislipidemia, hipertensão arterial, diabetes, tabagismo, anemia, sedentarismo, estresse, obesidade e alcoolismo. A insuficiência renal no estágio crônico ocorre devido à perda lenta, progressiva e irreversível da função renal e tem as doenças cardiovasculares como principal causa de morbimortalidade ocasionada por ateromas decorrentes de dislipidemias. Objetivos: Embasados na dislipidemia como fator de risco modificável para as doenças cardiovasculares e na suscetibilidade do desenvolvimento da mesma por pacientes renais crônicos, o objetivo deste estudo foi analisar se o tratamento por hemodiálise com acompanhamento médico é eficiente para minimizar ou evitar a dislipidemia nesses pacientes. Metodologia: Trata-se de um estudo descritivo longitudinal realizado por meio da análise de dados laboratoriais dos exames relacionados ao perfil lipídico: Colesterol Total, HDL, LDL e Triglicérides de novembro de 2018 a junho de 2019. Resultados: Foram acompanhados e analisados 20 pacientes, sendo 50% idosos com idade entre 60 e 69 anos e com doença de base prévia como hipertensão arterial (45%), hipertensão associada à diabetes (25,0%) e diabetes isolada (10,0%). Para análise da presença de dislipidemia, os exames laboratoriais que mais apresentaram alterações foram o HDL com resultado abaixo do desejado (<40,0mg/dl) e o triglicérides com resultados considerados acima da normalidade (> 150,0 mg/dl ) com risco para DC. Do total de pacientes, apenas 1 (5,0%) do sexo feminino apresentou todos os resultados do perfil lipídico alterados durante todo o estudo mesmo fazendo uso do medicamento estatina, enquanto a maioria (95%) dos pacientes obteve resultados desejáveis. Ao analisar conjuntamente todos os resultados do perfil lipídico, observou-se que apenas um paciente do sexo masculino apresentou alteração em todo período de estudo com Triglicerídeos e HDL indesejáveis. No sexo feminino, destaca-se a paciente número 14 que apresentou alterações em todos os exames durante todo o período de análise, com Colesterol Total, Triglicerídeos e LDL-colesterol com valores indesejáveis acima da normalidade e HDL-colesterol indesejável com valor abaixo do desejável. O exame que mais apresentou alteração com resultados indesejáveis foi o de Triglicerídeos em 11 (55,0%) pacientes, principalmente no sexo feminino, com subsequente LDL acima da normalidade e HDL reduzidos, sendo considerado importante fator de risco cardiovascular pela formação de ateromas. Conclusão: Para os pacientes com IRC, é de extrema importância o acompanhamento médico e o tratamento por hemodiálise realizado em sua maioria pelo SUS no Brasil, demonstrado neste estudo como método eficaz para controle e prevenção das dislipidemias minimizando o risco para as doenças cardiovasculares na população vulnerável.

Introduction: The current demographic and epidemiological transition in Brazil, reflected in the aging population, has a higher prevalence of chronic non-communicable diseases (NCDs) such as cardiovascular diseases (CD), neoplasms, metabolic disorders, chronic respiratory diseases, and chronic renal failure (CRF). These diseases may be due to mod-ifiable risk factors, such as dyslipidemia, high blood pressure, diabetes, smoking, anemia, physical inactivity, stress, obesity, and alcoholism. Chronic renal failure occurs due to the slow, progressive, and irreversible loss of renal function, and cardiovascular diseases are the main cause of morbidity and mortality caused by atheroma resulting from dyslipidemia. Objectives: Based on dyslipidemia as a modifiable risk factor for cardiovascular diseases and on the susceptibility of its development by chronic renal patients, the objective of this study was to analyze whether the hemodialysis treatment and the medical monitoring is efficient to minimize or avoid dyslipidemia in these patients. Methodology: This is a longi-tudinal descriptive study carried out through an analysis of laboratory data of tests related to the lipid profile: Total Cholesterol, HDL, LDL, and Triglycerides from November 2018 to June 2019. Results: Twenty patients were followed up and had their data analyzed, 50% were aged between 60 and 69 years old and had a previous underlying disease, such as arterial hypertension (45%), hypertension associated with diabetes (25.0%), and isolated diabetes (10.0%). The analysis of the presence of dyslipidemia showed the laboratory tests that had the most changes were HDL with a result under the desirable (<40.0mg / dl) and triglycerides with results considered above normal (> 150.0 mg / dl) with risk for DC. Only 1 female subject (5.0%) presented all the results of the lipid profile altered throughout the study, even using the statin drug, while the majority (95%) of the patients had desirable results. The analysis of all the results of the lipid profile showed that only one male subject presented changes in the entire study period with undesirable triglycerides and HDL, while in the female sex, patient number 14 presented changes in all tests throughout the anal-ysis period, with Total Cholesterol, Triglycerides, and LDL-cholesterol with undesirable values above normal and undesirable HDL-cholesterol with values under the desirable. The triglycerides test showed the most alteration with undesirable results in 11 (55.0%) subjects, mainly female, with subsequent LDL above normal and reduced HDL, considered an important cardiovascular risk factor due to the formation of atheromas. Conclusion: For patients with CRF, medical follow-up and the hemodialysis treatment performed by the Brazilian Health System is extremely important. This study demonstrated it is as an effective method for the control and prevention of dyslipidemias, minimizing the risk for cardiovascular diseases in this vulnerable population.

El corazón en los tiempos del COVID-19 / The heart in the times of COVID-19

SarsCov2 infection produces a clinical syndrome known as COVID-19, which presents mainly respiratory manifestations and various conditions are associated with a higher rate of complications of this pathology, with acute cardiovascular syndrome by COVID-19 being a relatively common complication. In this article we will review the most frequent manifestations, the prognosis, the diagnostic and therapeutic approach of these.

High levels of chemerin associated with variants in the NOS3 and APOB genes in rural populations of Ouro Preto, Minas Gerais, Brazil

Chemerin is an adipokine that has been associated with components of metabolic syndrome. It has been described to affect adipocyte metabolism and inflammatory responses in adipose tissue, as well as the systemic metabolism of lipids and glucose. Few epidemiological studies have evaluated classical and genetics cardiovascular risk factors (CVRFs) in the mixed adult rural population in Brazil. Therefore, the present study explored possible associations between CVRFs and chemerin. This cross-sectional study included 508 adults from the rural localities of Lavras Novas, Chapada, and Santo Antônio do Salto in Ouro Preto, Minas Gerais, Southeast Brazil. Demographic, behavioral, clinical, biochemical, anthropometric variables, and 12 single nucleotide polymorphisms (SNPs) linked with metabolic syndrome phenotypes were evaluated for associations with chemerin level. There was a significant association of high triglyceride levels [odds ratio (OR)=1.91, 95%CI: 1.23−2.98], insulin resistance (OR=1.82, 95%CI: 1.03−3.22), age (OR=1.64, 95%CI: 1.08−2.49), and sex (OR=1.99, 95%CI: 1.35−2.95) with high levels of chemerin. High chemerin levels were significantly associated with the genetic polymorphisms rs693 in the APOB gene (OR=1.50, 95%CI: 1.03−2.19) and rs1799983 in the NOS3 gene (OR=1.46, 95%CI: 1.01−2.12) for the AA and GT+TT genotypes, respectively. In the concomitant presence of genotypes AA of rs693 and GT+TT of rs1799983, the chance of presenting high levels of chemerin showed a 2.21-fold increase (95%CI: 1.25−3.88) compared to the reference genotype. The development of classical CVRFs in this population may be influenced by chemerin and by two risk genotypes characteristic of variants in well-studied genes for hypertension and dyslipidemia.

Sex-Related Effects of Prenatal Stress on Region-Specific Expression of Monoamine Oxidase A and β Adrenergic Receptors in Rat Hearts / Efeitos Sexo-Específicos de Estresse Pré-Natal na Expressão Região-Específica de Monoamina Oxidase A e Receptores Adrenérgicos Β no Coração de Ratos

Abstract Background: Prenatal stress may increase risk of developing cardiovascular disorders in adulthood. The cardiotoxic effects of catecholamines are mediated via prolonged adrenergic receptor stimulation and increased oxidative stress upon their degradation by monoamine oxidase A (MAO-A). Objectives: We investigated long-term effects of prenatal stress on β (1, 2, 3) adrenergic receptors and MAO-A gene expression in the hearts of adult rat offspring. Methods: Pregnant rats were exposed to unpredictable mild stress during the third week of gestation. RNA was isolated from left ventricular apex and base of adult offspring. Quantitative PCR was used to measure gene expression in collected ventricular tissue samples. The level of significance was set to p < 0.05. Results: β3 adrenergic receptor mRNA was undetectable in rat left ventricle. β1 adrenergic receptor was the predominantly expressed subtype at the apical and basal left ventricular myocardium in the control females. Male offspring from unstressed mothers displayed higher apical cardiac β1 than β2 adrenergic receptor mRNA levels. However, β1 and β2 adrenergic receptor mRNAs were similarly expressed at the ventricular basal myocardium in males. Unlike males, prenatally stressed females exhibited decreased β1 adrenergic receptor mRNA expression at the apical myocardium. Prenatal stress did not affect cardiac MAO-A gene expression. Conclusions: Collectively, our results show that prenatal stress may have exerted region- and sex-specific β1 and β2 adrenergic receptor expression patterns within the left ventricle.

Resumo Fundamento: Estresse pré-natal pode aumentar os riscos de desenvolver doenças cardiovasculares na idade adulta. Os efeitos cardiotóxicos de catecolaminas são mediados pela estimulação prolongada dos receptores adrenérgicos e pelo aumento do estresse oxidativo após sua degradação pela monoamina oxidase A (MAO-A). Objetivos: Investigamos os efeitos a longo prazo de estresse pré-natal nos receptores β (1, 2, 3) adrenérgicos e na expressão do gene MAO-A nos corações da prole adulta de ratos. Método: Ratas prenhes foram expostas a estresse crônico moderado imprevisível durante a terceira semana de gestação. O RNA foi isolado do ápice e da base do ventrículo esquerdo da prole adulta. Utilizou-se PCR quantitativa em tempo real para medir a expressão gênica nas amostras de tecido ventricular coletadas. O nível de significância foi estabelecido em p < 0,05. Resultados: Foi indetectável o mRNA do receptor adrenérgico β3 no ventrículo esquerdo dos ratos. O receptor adrenérgico β1 foi o subtipo mais expresso no miocárdio ventricular esquerdo apical e basal nas fêmeas controle. A prole masculina das mães não estressadas apresentou níveis cardíacos apicais de mRNA do receptor adrenérgico β1 mais altos do que os de β2. Porém, mRNAs dos receptores adrenérgicos β1 e β2 foram expressos de forma semelhante no miocárdio basal ventricular na prole masculina em geral. Ao contrário da prole masculina, a prole feminina exposta ao estresse pré-natal exibiu uma expressão diminuída do mRNA do receptor adrenérgico β1 no miocárdio apical. O estresse pré-natal não afetou a expressão gênica de MAO-A cardíaca. Conclusões: Coletivamente, nossos resultados mostram que estresse pré-natal pode ter exercido padrões de expressão região- e sexo-específica dos receptores adrenérgicos β1 e β2 no ventrículo esquerdo.

Inhibition of the sodium-glucose co-transporter 2 in the elderly: clinical and mechanistic insights into safety and efficacy

SUMMARY The prevalence of type 2 diabetes mellitus (T2DM) in the elderly grew sharply over the last decade. Reduced insulin sensitivity and secretory capacity, weight gain, sarcopenia, and elevated adiposity are all common metabolic and body changes in the aging population that favor an increased risk of hypoglycemia, frailty syndrome, falls, and cognitive dysfunction. First line antidiabetic therapy is frequently not safe in older individuals because of its high risk of hypoglycemia and prevalent co-morbid diseases, such as chronic kidney disease, osteoporosis, cardiovascular disease, and obesity. Sodium-glucose cotransporter 2 inhibitor (SGLT2i) is a new class of antidiabetic therapy that inhibits glucose and sodium reabsorption on renal proximal convoluted tubule. Its effect is well demonstrated in various clinical scenarios in the younger population. This review and metanalysis describe particularities of the SGLT2i on the elderly, with mechanistic insights of the potential benefit and remaining challenges about the use of these drugs in this important age group. Further, we will present a meta-analysis of the main effects of SGLT2i reported in post-hoc studies in which the median age of the subgroups analyzed was over 60 years. Despite the absence of specific clinical trials for this population, our findings suggest that SGLT2i therapy on older individuals is effective to lower glucose and maintain its effect on systolic blood pressure and body weight.

RESUMO A prevalência da diabetes mellitus tipo 2 em idosos cresceu muito na última década. A redução na sensibilidade à insulina e na capacidade secretora, ganho de peso, sarcopenia e adiposidade elevada são todas alterações metabólicas e corporais comuns entre a população idosa. Essas mudanças críticas favorecem o aumento no risco de hipoglicemia, síndrome de fragilidade, quedas e disfunções cognitivas. A primeira linha de tratamento contra a diabete muitas vezes não é segura para indivíduos mais velhos devido ao alto risco de hipoglicemia e a prevalência de comorbidades patogênicas, como doença renal crônica, osteoporose, doença cardiovascular e obesidade. Os inibidores do cotransportador sódio-glicose 2 (SGLT2) são uma nova classe de tratamento contra a diabete que inibe reabsorção de glicose e sódio na parte convoluta do túbulo proximal. Seu efeito é claramente demonstrado em diversos cenários clínicos em populações mais jovens. Esta revisão e meta-análise descreve as particularidades dos SGLT2 na população idosa, abordando os mecanismos dos potenciais benefícios e desafios ainda presentes do uso destes medicamentos nesse grupo etário tão importante. Além disso, apresentaremos uma meta-análise dos principais efeitos dos SGLT2 encontrados em estudos post-hoc nos quais a idade média dos subgrupos analisados foi acima de 60 anos. Apesar da ausência de ensaios clínicos que incluem essa população, os dados encontrados sugerem que o tratamento com SGLT2 em idosos é eficaz para diminuir os níveis de glicose e tem efeitos na pressão arterial sistólica e no peso corporal.

Metabolic and hormonal assessment of adolescent and young adult women with prior premature adrenarche

OBJECTIVE: Follow-up studies of girls with premature adrenarche have reported the development of polycystic ovary syndrome, insulin resistance, and dyslipidemia and a propensity to cardiovascular disease. The aim of this study was to analyze the presence of these conditions in patients previously treated at the Universidade Federal do Triângulo Mineiro. METHODS: A total of 130 medical records reported premature adrenarche. One hundred and twenty-two patients were invited to participate, of whom 54 accepted; 34 patients were selected, as they had reached their final height. Anthropometric, blood glucose, insulin, and lipid and hormonal profile (LH, FSH, estradiol, 17α-OH-progesterone, androstenedione, dehydroepiandrosterone sulfate, testosterone) data were obtained, the HOMA-IR index was calculated, and pelvic ultrasonography was performed. To characterize polycystic ovary syndrome and metabolic syndrome, the Rotterdam and International Diabetes Federation criteria, respectively, were used. Data were analyzed according to measures of dispersion, frequency and correlations of interest. RESULTS: The age of the participants ranged from 15.2 to 28.2 years/months; 23.5% of the patients were overweight, 11.8% were obese, 29.4% had a large waist circumference, and 8.8% were hypertensive. None of the patients had altered glucose levels, and insulin levels and HOMA-IR were elevated in 29.4% and 38.2% of the participants, respectively; 14.7% of the patients exhibited acanthosis nigricans. The lipid profiles of the participants were variable, and one patient (2.9%) had metabolic syndrome. Polycystic ovary syndrome was found in 41.2% of patients. CONCLUSION: The percentage of patients with polycystic ovary syndrome who also had overweight, obesity and insulin resistance corroborates the literature data about the need for follow-up aiming at interventions, especially for conditions associated with cardiometabolic risk.

Role of miRNAs on the Pathophysiology of Cardiovascular Diseases / Papel dos miRNAs na Fisiopatologia das Doenças Cardiovasculares

Abstract MiRNA (or microRNA) is a subclass of non-coding RNAs that is responsible for post-transcriptional gene regulation. It has approximately 22 nucleotides and regulates gene expression in plants and animals at the post-transcriptional level, by the cleavage of a target mRNA or by suppression of its translation. Although many of the processes and mechanisms have not yet been fully elucidated, there is a strong association between miRNA expression and several diseases. It is known that miRNAs are expressed in the cardiovascular system, but their role in cardiovascular diseases (CVDs) has not been clearly established. In this non-systematic review of the literature, we first present the definition of miRNAs and their action at the cellular level. Afterward, we discuss the role of miRNAs as circulating biomarkers of CVDs, and then their role in cardiac remodeling and atherosclerosis. Despite the complexity and challenges, it is crucial to identify deregulated miRNAs in CVDs, as it allows a better understanding of underlying cellular and molecular mechanisms and helps in the development of more accurate diagnostic and prognostic circulating biomarkers, and new therapeutic strategies for different stages of CVDs.

Resumo O miRNA (ou microRNA) constitui uma subclasse de RNAs não codificantes responsáveis pela regulação gênica pós-transcricional. Ele possui aproximadamente 22 nucleotídeos e regula a expressão gênica em plantas e animais ao nível pós-transcricional, pela clivagem de um mRNA alvo ou da repressão de sua tradução. Embora muitos processos e mecanismos ainda não estejam completamente elucidados, existe uma forte associação entre a expressão de miRNAs e diversas doenças que acometem o organismo. Os miRNAs são expressos no sistema cardiovascular, contudo o seu papel no desenvolvimento das doenças cardiovasculares (DCVs) ainda não está totalmente elucidado. Diante disso, realizou-se uma revisão não sistemática da literatura a fim de se discutir a relação entre os miRNAs e as DCVs. Nesta revisão, primeiramente é discutido o que são os miRNAs e a sua ação a nível celular. Após, é discutido o papel dos miRNAs como biomarcadores circulantes de DCVs e então o seu papel no remodelamento cardíaco e na aterosclerose. Apesar da complexidade e dos desafios, a identificação dos miRNAs desregulados nas DCVs é crucial, uma vez que possibilita uma melhor compressão dos mecanismos celulares e moleculares envolvidos, assim como auxilia o desenvolvimento de marcadores circulantes de diagnóstico e prognóstico mais acurados e de novas estratégias terapêuticas para os diferentes estágios da DCV.

Impact of self-reported fasting duration on lipid profile variability, cardiovascular risk stratification and metabolic syndrome diagnosis

ABSTRACT Objective We sought to investigate the impact of self-reported fasting duration times on the lipid profile results and its impact on the cardiovascular risk stratification and metabolic syndrome diagnosis. Subjects and methods We analyzed data from all consecutive individuals evaluated in a comprehensive health examination at the Hospital Israelita Albert Einstein from January to December 2015. We divided these patients in three groups, according to the fasting duration recalled (< 8h, 8-12h and > 12h). We calculated the global cardiovascular risk and diagnosed metabolic syndrome according to the current criteria and estimated their change according to fasting duration. Results A total of 12,196 (42.3 ± 9.2 years-old, 30.2% females) patients were evaluated. The distribution of cardiovascular risk was not different among groups defined by fasting duration in both men and women (p = 0.547 for women and p = 0.329 for men). Similarly, the prevalence of metabolic syndrome was not influenced by the fasting duration (p = 0.431 for women and p = 0.166 for men). Conclusion Self-reported fasting duration had no significant impact on the lipid profile results, including triglyceride levels. Consequently, no changes on the cardiovascular risk stratification using the Framingham risk score nor changes on the prevalence of metabolic syndrome were noted.

Visceral adiposity index and triglyceride/high-density lipoprotein cholesterol ratio in hypogonadism

ABSTRACT Background Cardiometabolic risk is high in patients with hypogonadism. Visceral adiposity index (VAI) and triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio are the practical markers of atherosclerosis and insulin resistance and independent predictors of cardiaovascular risk. To date, no study has evaluated VAI levels and TG/HDL-C ratio in hypogonadism. Subjects and methods A total of 112 patients with congenital hypogonadotrophic hypogonadism (CHH) (mean age, 21.7 ± 2.06 years) and 124 healthy subjects (mean age, 21.5 ± 1.27 years) were enrolled. The demographic parameters, VAI, TG/HDL-C ratio, asymmetric dimethylarginine (ADMA), high-sensitivity C-reactive protein (hs-CRP), and homeostatic model assessment of insulin resistance (HOMA-IR) levels were measured for all participants. Results The patients had higher total cholesterol (p = 0.04), waist circumference, triglycerides, insulin, and HOMA-IR levels (p = 0.001 for all) than the healthy subjects. VAI and ADMA and TG/HDL-C levels were also higher in patients than in healthy subjects (p < 0.001 for all). VAI was weakly correlated with ADMA (r = 0.27, p = 0.015), HOMA-IR (r = 0.22, p = 0.006), hs-CRP (r = 0.19, p = 0.04), and total testosterone (r = −0.21, p = 0.009) levels, whereas TG/HDL-C ratio was weakly correlated weakly with ADMA (r = 0.30, p = 0.003), HOMA-IR (r = 0.22, p = 0.006), and total testosterone (r = −0.16, p = 0.03) levels. Neither VAI nor TG/HDL-C ratio determined ADMA, HOMA-IR, and hs-CRP levels. Conclusions The results of this study demonstrate that patients with hypogonadism have elevated VAI and TG/HDL-C ratio. These values are significantly correlated with the surrogate markers of endothelial dysfunction, inflammation, and insulin resistance. However, the predictive roles of VAI and TG/HDL-C ratio are not significant. Prospective follow-up studies are warranted to clarify the role of VAI and TG/HDL-C ratio in predicting cardiometabolic risk in patients with hypogonadism.

Salivary cortisol and alpha-amylase: subclinical indicators of stress as cardiometabolic risk

Currently, the potential for cardiovascular (CV) stress-induced risk is primarily based on the theoretical (obvious) side effects of stress on the CV system. Salivary cortisol and α-amylase, produced respectively by the hypothalamus-pituitary-adrenal (HPA) axis and the sympathetic-adrenomedullary (SAM) system during stress response, are still not included in the routine evaluation of CV risk and require additional and definitive validation. Therefore, this article overviews studies published between 2010 and 2015, in which salivary cortisol and α-amylase were measured as stress biomarkers to examine their associations with CV/CMR (cardiometabolic risk) clinical and subclinical indicators. A comprehensive search of PubMed, Web of Science and Scopus electronic databases was performed, and 54 key articles related to the use of salivary cortisol and α-amylase as subclinical indicators of stress and CV/CMR factors, including studies that emphasized methodological biases that could influence the accuracy of study outcomes, were ultimately identified. Overall, the biological impact of stress measured by salivary cortisol and α-amylase was associated with CV/CMR factors. Results supported the use of salivary cortisol and α-amylase as potential diagnostic tools for detecting stress-induced cardiac diseases and especially to describe the mechanisms by which stress potentially contributes to the pathogenesis and outcomes of CV diseases.

Altos niveles de adiposidad se asocian a un deterioro en la salud metabólica en adultos chilenos / Higher adiposity levels are associated with detrimental metabolic health in Chilean adults

RESUMEN Antecedentes: El exceso de grasa corporal es uno de los principales factores de riesgo de enfermedades cardiometabólicas. Objetivo: Investigar las asociaciones entre indicadores de adiposidad y metabólicos en población adulta chilena. Métodos: Estudio observacional de corte transversal en 475 adultos, a quienes se evaluó el índice de masa corporal (IMC), perímetro cintura (PC) y porcentaje de masa grasa (%MG). Se midió presión arterial, glicemia, insulina, HOMA-IR, colesterol total, triglicéridos, colesterol HDL y LDL, alanina-amino transpeptidasa, gama-glutamil transpeptidasa, leptina y proteína C-reactiva ultra sensible (PCRus). La asociación entre indicadores de adiposidad y marcadores metabólicos fue determinada mediante regresión lineal múltiple. Resultados: Los tertiles superiores de IMC, PC y %MG se asociaron significativamente (p< 0,05) con niveles bajos de colesterol HDL y altos de insulina, HOMAIR, triglicéridos, colesterol total, colesterol LDL, ALT, GGT, PCRus y leptina; esto para ambos sexos. Se observó además que los valores de presión arterial sistólica y presión arterial diastólica, fueron significativamente mayores en mujeres en relación a un mayor IMC. Conclusión: A medida que aumentó el nivel de adiposidad, se deterioran los marcadores de salud cardiovascular y metabólica, independientemente del indicador de adiposidad empleado.

ABSTRACT Background: Adiposity is positively associated with metabolic and inflammatory markers, which increase the risk of developing metabolic disease related to obesity. Aim: To investigate the association between adiposity markers and metabolic health in Chilean adults. Methods: We conducted a cross-sectional study with 475 participants. Body mass index (BMI), waist circumference (WC) and body fat (using 4 skinfold) were measured. The outcomes of interest were blood pressure, fasting glucose, insulin, HOMA-IR, total cholesterol, triglycerides (TG), HDL and LDL cholesterol,γ-glutamyltransferase (GGT), alanine aminotransferase (ALT), leptin and high sensitive C-reactive protein (hsCRP). The association between adiposity and metabolic outcomes were investigated using multiple linear regression analysis. Results: Individuals in the highest tertile for BMI, WC and body fat had a lower concentration of HDL-cholesterol and higher concentration of insulin, HOMA-IR, TG, LDL and total cholesterol, GGT, ALT, leptin and hsCRP. Blood pressure was higher with increasing BMI in females only. There was no significant association between fasting glucose and any of the adiposity markers. Conclusion: Higher adiposity levels were associated with a detrimental metabolic health. The effect of higher BMI, WC and body fat were similar across metabolic markers.

Ser físicamente activo modifica los efectos nocivos del sedentarismo sobre marcadores de obesidad y cardiometabólicos en adultos / Being physically active modifies the detrimental effect of sedentary behavior on obesity and cardiometabolic markers in adults

Background: Sedentary behavior is a major risk factor for cardiovascular disease and mortality. Aim: To investigate whether the associations between sedentary behavior and cardiometabolic markers differs across physical activity levels. Materials and Methods: Cross sectional study of 314 participants aged 18 to 65 years. Body mass index (BMI) and waist circumference were measured, and body fat was derived from the sum of four skinfolds. Physical activity was measured objectively using accelerometers (Actigraph GT1M, USA®). A fasting blood sample was obtained to measure glucose, insulin, HOMA-IR, lipid profile and high sensitive C reactive protein (hsCRP). Those participants with an activity level > 600 MET.min-1.week-1 were classified as physically active. Results: Thirty four percent of participants were physically inactive and spent an average of 8.7 h.day-1 in sedentary pursuits. Physically inactive individuals had poorer cardiometabolic health than their physically active counterparts. Per one hour decrease in overall sedentary behavior, there was a significant improvement in glucose (-8.46 and -4.68 mg.dl-1), insulin (-2.12 and -1.77 pmol.l-1), HOMA-IR (-0.81 and -0.56) BMI (-0.93 and -0.62 kg.m-2) and waist circumference (-2.32 and -1.65 cm) in physically active and inactive participants, respectively. Conclusions: Being physically active may modify the detrimental effects of sedentary behavior on cardiometabolic and obesity-related traits.

Biomarcadores de função endotelial em doenças cardiovasculares: hipertensão / Biomarkers of endothelial function in cardiovascular diseases: hypertension

Resumo A incidência de hipertensão arterial sistêmica está aumentando mundialmente. Sua prevenção baseia-se na identificação dos hipertensos. Atualmente, biomarcadores são utilizados com fins de diagnosticar, estratificar e prognosticar doenças. Neste estudo, objetivou-se revisar artigos dos últimos cinco anos relacionados a biomarcadores nas doenças cardiovasculares. Pesquisaram-se dados de PubMed, SciELO, Science Direct e MEDLINE, mediante as palavras-chave: hipertensão arterial, biomarcadores cardiovasculares, óxido nítrico, função endotelial e dimetilarginina assimétrica. Os estudos levantados mostram que as doenças cardiovasculares possuem uma etiologia complexa. Neste artigo, evidenciaram-se interações entre o óxido nítrico e a dimetilarginina assimétrica na regulação, no metabolismo e na determinação dos níveis intracelulares, e reviram-se outros biomarcadores relacionados à hipertensão. Alguns estudos indicam os biomarcadores como uma ferramenta útil na predição de eventos cardíacos, e outros reportam que eles contribuem pouco para a avaliação. A seleção e combinação desses pode ser uma alternativa para validar o uso dos biomarcadores devido à pouca especificidade existente para diagnosticar a hipertensão.

Abstract The incidence of systemic arterial hypertension is increasing worldwide. The foundation of prevention is identification of people with hypertension. Nowadays, biomarkers are used to diagnose and stratify diseases and estimates prognosis. The objective of this study was to review articles published over the last 5 years on the subject of biomarkers of cardiovascular diseases. The PubMed, SciELO, Science Direct and MEDLINE databases were searched using the keywords: arterial hypertension, cardiovascular biomarkers, nitric oxide, endothelial function and asymmetric dimethylarginine. The studies reviewed show that cardiovascular diseases have complex etiologies. This article describes evidence demonstrating interactions between nitric oxide and asymmetric dimethylarginine that are involved in regulation, in metabolism, and in determination of intracellular levels, and also discusses other biomarkers related to hypertension. Some studies indicate that biomarkers are useful tools for prediction of cardiac events, whereas others state that they have little to contribute to assessments. Careful selection of tests and combinations of tests may be the key to validating use of biomarkers, in view of their low specificity for diagnosing hypertension.

Alterações Cardiometabólicas em Ratos Wistar Alimentados com Dieta Hiperlipídica e Hipercolesterolêmica por Seis Semanas / Cardiometabolic Alterations in Wistar Rats on a Six-Week Hyperlipidic, Hypercholesterolemic Diet

Fundamento: Alta ingestão de lipídeos e colesterol compõe a dieta da sociedade moderna e está envolvida com o desenvolvimento de doenças cardiometabólicas. Entretanto, há lacunas na literatura quanto à existência de modelos de dislipidemias em ratos Wistar. Objetivos: Analisar o perfil cardiometabólico de ratos Wistar alimentados com dieta hiperlipídica e hipercolesterolêmica por seis semanas. Métodos: Ratos Wistar jovens foram alimentados com dieta hiperlipídica e hipercolesterolêmica por seis semanas para induzir a hiperlipidemia. Os ratos foram submetidos à cateterização da artéria carótida para determinar a pressão arterial. Após jejum, amostras de sangue foram coletadas por meio do cateter, e as concentrações de colesterol total, colesterol HDL, triglicerídeos e glicose foram determinadas. Amostras do tecido cardíaco foram removidas para análise histológica, a fim de se verificar a hipertrofia ventricular. Resultados: A ingestão da dieta por seis semanas foi eficaz em induzir alterações cardiometabólicas. O perfil dislipidêmico apresentado pelos ratos Wistar foi acompanhado de hiperinsulinemia, hipertensão moderada e hipertrofia ventricular do coração. Não houve alterações na glicemia. Conclusões: A administração de dieta hiperlipídica e hipercolesterolêmica em ratos Wistar jovens por seis semanas induziram alterações cardiometabólicas tornando-se um modelo eficaz para distúrbios dessa natureza

Background: The diet of modern society is composed by large intakes of lipids and cholesterol, involved in the development of cardiometabolic diseases. However, there are gaps in the literature regarding the existence of dyslipidemia models in Wistar rats. Objectives: To analyze the cardiometabolic profile of Wistar rats on a six-week hyperlipidic, hypercholesterolemic diet. Methods: Young Wistar rats were kept on a hyperlipidic, hypercholesterolemic diet for six weeks to induce hyperlipidemia. The rats underwent catheterization of the carotid artery to determine blood pressure. After fasting, blood samples were drawn through the catheter, and concentrations of total cholesterol, HDL cholesterol, triglycerides and glucose were determined. Cardiac tissue samples were taken for a histological analysis to check for ventricular hypertrophy. Results: The six-week diet was effective in inducing cardiometabolic alterations. The dyslipidemic profile presented by the Wistar rats was accompanied by hyperinsulinemia, moderate hypertension and cardiac ventricular hypertrophy. There were no alterations in glycemia. Conclusion: The six-week hyperlipidic, hypercholesterolemic diet in young Wistar rats induced cardiometabolic alterations, becoming an effective model for disorders of this nature

Ingestão de ácidos graxos monoinsaturados e metabolismo lipídico / Monounsaturated fatty acid intake and lipid metabolism

Esta revisão teve como objetivo apresentar e discutir os achados mais recentes do efeito dos ácidos graxos monoinsaturados (AGMI) sobre marcadores plasmáticos do metabolismo lipídico em estudos pós-prandiais e de intervenção clínica nutricional. Realizou-se busca em diferentes bases de dados entre 2010 e 2014, usando os seguintes termos de indexação: MUFA, Lipemia, Lipid Metabolism, Triglycerides e Postprandial. O consumo de refeição com alto conteúdo de AGMI tem demonstrado efeito benéfico na resposta lipidêmica pós-prandial, mas se essa resposta pode ser alterada em indivíduos com excesso de peso e/ou outras doenças crônicas após consumo de AGMI, ainda não está totalmente elucidado. De modo geral, após a intervenção com AGMI, os fatores de risco cardiovascular diminuíram, além de haver melhora no perfil lipídico. Em conclusão, os estudos recentes têm demonstrado um efeito benéfico do consumo de AGMI em curto e longo prazos, mediante aumento/manutenção das concentrações de HDL colesterol e diminuição do LDL colesterol.

The objective of this review is to present and discuss the most recent findings related to the effects of monounsaturated fatty acids (MUFA) on plasma markers of lipid metabolism observed in postprandial studies and clinical nutritional intervention studies. Searches were conducted on several different databases for publications from 2010 to 2014 using the following keywords: MUFA, Lipemia, Lipid Metabolism, Triglycerides and Postprandial. High-MUFA meal has presented beneficial effect on postprandial lipidemia response, but it is not yet completely clear whether this response to MUFA intake may be different in people with excess weight and/or other chronic diseases. In general, cardiovascular risk factors were reduced and lipid profiles improved after interventions with MUFA. In conclusion, recent studies have demonstrated that consuming MUFA has beneficial effects at short and long time by increasing/maintaining HDL-cholesterol concentrations and reducing levels of LDL cholesterol.

Autofagia en el sistema cardiovascular: pasado, presente y futuro / Cardiovascular autophagy: past, present and future

La enfermedad cardiovascular se mantiene como la principal causa de morbimortalidad a nivel mundial a pesar de los avances científicos y tecnológicos recientes, por esto existe la necesidad de búsqueda de nuevas dianas terapéuticas. La autofagia es un mecanismo de degradación de proteínas y organelos disfuncionales que ocurre en vacuolas especializadas de doble membrana denominadas autofagosomas y que requiere la participación de los lisosomas. Este proceso permite el auto abastecimiento celular de energía a través del reciclaje de diversos substratos energéticos. Se activa en respuesta a diversas formas de estrés, principalmente debido a la ausencia de nutrientes y su presencia ha sido caracterizada en todos los tipos celulares que componen el sistema cardiovascular. Existe una ventana de actividad de autofagia óptima la que se relaciona con la mantención de la homeostasis cardiovascular y su desregulación participa en la patogénesis de diversas patologías cardiovasculares. En este artículo se revisa el curso temporal que llevó el descubrimiento de la autofagia, la contribución al área del Dr. Ohsumi, reciente Premio Nobel de Medicina, los principales conceptos, mecanismos celulares y moleculares de la formación del auto-fagosoma, nodos de regulación y sintetizamos su participación en la homeostasis del corazón y en la patogénesis de las enfermedades cardiovasculares y sus perspectivas futuras.

Cardiovascular disease continues to be the leading cause of morbi-mortality worldwide despite the recent scientific and technological advances. Therefore, more research is needed to discover novel therapeutic targets. Autophagy mediates the removal of dysfunctional proteins and organelles. This process takes place in double-membrane vesicles, named autophagosomes, which later fuse with lysosomes. The mechanism allows self-renewal energy repletion through diverse energy substrate recycling. Diverse forms of cellular stress, mainly nutrient deprivation, activate this process. Autophagy has been widely characterized within the cells of the cardiovascular system. There is a window of optimal autophagy activity implicated in maintaining cardiovascular homeostasis and its dysregulation participates in the pathogenesis of different cardiovascular diseases. In this article, we review the time course of auto-phagy discovery, the Nobel Prize winner Dr. Ohsumi contribution, main concepts, mechanisms involved in autophagosome formation and its regulatory no-des. Additionally, we summarized the role of auto-phagy in cardiovascular homeostasis and pathogenesis and future perspectives.