Prevalence and association of mycoplasma infection in the development of coronary artery disease / Prevalência e associação de infecção por micoplasma no desenvolvimento de doença arterial coronariana

Coronary heart disease (CHD) has been associated with significant morbidity and mortality worldwide. Although remain controversial, several studies have demonstrated the association of M. pneumoniae infections with atherosclerosis. We evaluated the possible association of mycoplasma infections in patients diagnosed with atherosclerosis by ELISA and PCR methods. Atherosclerotic tissue samples and blood samples were collected for the detection of mycoplasma antibodies (IgA) by ELISA from the 97 patients with coronary artery disease (CAD). M. pneumoniae specific IgA, IgG and IgM were measured by using the Anti-M. pneumoniae IgA/IgG/IgM ELISA. Detection of M. pneumoniae targeting the P1 adhesion gene was performed by PCR Acute infection of M. pneumoniae was diagnosed in 43.3% (42) of patients by PCR. The M. pneumoniae specific antibodies were detected in 36.1% (35) of patients. Twenty-five (25.8%) cases had IgG antibodies, 15 (15.5%) cases had IgM antibodies, 3 (3.1%) cases had IgA antibodies, 10 (10.3%) cases had both IgM + IgG antibodies and 1 (1%) case of each had IgM + IgA and IgG + IgA antibodies. None of the cases was positive for all three antibodies. A Pearson correlation coefficient analysis revealed an excellent correlation between the PCR and the serological results (r=0.921, p70 years of age. Our study reported an unusually higher prevalence of M. pneumoniae by serological tests (36.1%) and PCR (43.3%). Although the hypothesis of the association of M. pneumoniae and CAD is yet to be proven, the unusually high prevalence of M. pneumoniae in CAD patients indicates an association, if not, in the development of atherosclerosis.

A doença coronariana (DCC) tem sido associada a significativa morbidade e mortalidade em todo o mundo. Embora ainda sejam controversos, vários estudos têm demonstrado a associação de infecções por M. pneumoniae com aterosclerose. Avaliamos a possível associação de infecções por micoplasma em pacientes com diagnóstico de aterosclerose pelos métodos ELISA e PCR. Amostras de tecido aterosclerótico e amostras de sangue foram coletadas para a detecção de anticorpos contra micoplasma (IgA) por ELISA de 97 pacientes com doença arterial coronariana (DAC). IgA, IgG e IgM específicos para M. pneumoniae foram medidos usando o Anti-M. pneumoniae IgA / IgG / IgM ELISA. A detecção de M. pneumoniae visando o gene de adesão P1 foi realizada por PCR. A infecção aguda por M. pneumoniae foi diagnosticada em 43,3% (42) dos pacientes pela PCR. Os anticorpos específicos para M. pneumoniae foram detectados em 36,1% (35) dos pacientes. Vinte e cinco (25,8%) casos tinham anticorpos IgG, 15 (15,5%) casos tinham anticorpos IgM, 3 (3,1%) casos tinham anticorpos IgA, 10 (10,3%) casos tinham anticorpos IgM + IgG e 1 (1%) caso de cada um tinha anticorpos IgM + IgA e IgG + IgA. Nenhum dos casos foi positivo para os três anticorpos. A análise do coeficiente de correlação de Pearson revelou uma excelente correlação entre o PCR e os resultados sorológicos (r = 0,921, p 70 anos de idade. Nosso estudo relatou uma prevalência incomumente maior de M. pneumoniae por testes sorológicos (36,1%) e PCR (43,3%). Embora a hipótese da associação de M. pneumoniae e DAC ainda não tenha sido comprovada, a prevalência incomumente alta de M. pneumoniae em pacientes com DAC indica uma associação, se não, no desenvolvimento de aterosclerose.

Prevalencia de hipotiroidismo subclínico y biomarcadores de riesgo cardiovascular en pacientes del Hospital General de Riobamba / Prevalence of subclinical hypothyroidism and biomarkers of cardiovascular risk in patients of the General Hospital of Riobamba

El Hipotiroidismo subclínico (HSC) es definido bioquímicamente por una elevación en la concentración sérica de la hormona TSH con niveles normales de T4 libre. El objetivo de este estudio fue determinar la prevalencia de HSC en los pacientes que asistieron a la consulta de medicina interna del Hospital General IESS de Riobamba. Así como, analizar la correlación entre los parámetros hormonales y ciertos marcadores bioquímicos asociados con el incremento de riesgo cardiovascular. Se realizó una investigación de tipo descriptiva, observacional, con un diseño no experimental de corte transversal, que abarcó el periodo comprendido desde enero de 2019 hasta septiembre de 2021. 245 pacientes fueron diagnosticados con HSC, lo cual representó el 10.58 % del universo poblacional estudiado, 61.2% eran del sexo femenino, mientras que el 38.8% del sexo masculino. El mayor número de casos (59.61 %) se observó en el grupo etario mayor de 65 años, distribuidos de la siguiente manera: (22.86% hombres y 36.75% mujeres), también se encontró que el HSC está asociado con un perfil lipídico aterogénico, caracterizado por un incremento en la concentración de colesterol total y LDL los cuales se correlacionaron positivamente con las concentraciones de TSH.

Subclinical hypothyroidism (SH) is biochemically defined by an elevation in the serum concentration of TSH hormone with normal levels of free T4. The aim of this study was to determine the prevalence of SH in patients attending the internal medicine clinic of the General Hospital IESS of Riobamba. Also, to analyze the correlation between hormonal parameters and certain biochemical markers associated with increased cardiovascular risk. A descriptive, observational, non-experimental cross-sectional design was performed, covering the period from January 2019 to September 2021. 245 patients were diagnosed with SH, which represented 10.58 % of the population universe studied, 61.2% were female, while 38.8% were male. The highest number of cases (59.61 %) was observed in the age group over 65 years, distributed as follows: (22.86% men and 36.75% women), it was also found that SH is associated with an atherogenic lipid profile, characterized by an increase in the concentration of total cholesterol and LDL which correlated positively with TSH concentrations.

Relación de la actividad física medida objetivamente con dislipidemias y factores de riesgo cardiovascular en escolares de la Región de La Araucanía / Relationship of objectively measured physical activity with dyslipidemias and cardiovascular risk factors in schoolchildren from Región de La Araucanía cases

INTRODUCCIÓN: Las dislipidemias favorecen la formación precoz de placas ateroscleróticas, aumentando el riesgo de enfermedades cardiovasculares (ECVs). La Actividad Física (AF) es un factor protector de ECVs, por lo que el objetivo de este trabajo fue evaluar la asociación entre AF medida objetivamente y dislipidemias en población pediátrica. METODOLOGÍA: La AF fue evaluada en 159 niños (9-13 años) de la Región de La Araucanía a través de acelerometría (ActiGraph GT3X+). Por este medio se estimó el porcentaje de AF moderada a vigorosa (AFMV) y el de conducta sedentaria (CS). Sujetos con ≥60 min de AFMV se consideraron físicamente activos según recomendación de la Organización Mundial de la Salud (OMS). Individuos con %CS>75° percentil fueron considerados sedentarios. El perfil lipídico fue determinado usando métodos convencionales. Fueron calculados índices de aterogenicidad TG/cHDL e índice de aterogenicidad del plasma (IAP). RESULTADOS: 37,1% presentó dislipidemia, 8% hipercolesterolemia, 19,5% hipertrigliceridemia, 6,3% cLDL elevado y 25,2% cHDL disminuido. Solo un 9,4% fueron considerados físicamente activos de acuerdo a la recomendación de la OMS. En los sujetos físicamente activos no hubo caso de dislipidemias (p= 0,032) y tampoco bajos niveles de cHDL (p= 0,013). El %AFMV estaba reducido en sujetos con cHDL bajo y se correlacionó positivamente con HDL-c (r= 0,157, p=0,048). Además, el %AFMV se correlacionó con menores valores de TG/cHDL (r= -0,193, p=0,015) e IAP (r= -0,214, p=0,006). Si bien el comportamiento sedentario no estuvo asociado con riesgo de dislipidemias, el %CS se correlacionó positivamente con niveles de glucosa (r= 0,159, p=0,044) y HOMA-IR (r= 0,178, p=0,037) y negativamente con Quicki (r= -0,160, p=0,044). CONCLUSIONES: Los hallazgos sugieren que la AF se correlaciona a menor frecuencia de dislipidemias y la práctica de AFMV aumentaría los valores de HDL-c y reduciría los índices aterogénicos, por lo que promoverla puede significar disminuir el riesgo de ECVs en nuestra población. Además, la CS se relaciona con un aumento en valores de glucosa e índices de resistencia insulínica en escolares de la Región de La Araucanía.

Dyslipidemias cause early formation of atherosclerotic plaque, increasing the risk of cardiovascular diseases (CVD). Physical Activity (PA) is a protective factor against CVDs. The aim of this study is to evaluate the association between objectively measured PA with dyslipidemias in a pediatric population. METHOD: The PA was evaluated in 159 children (9-13 years old) from Región de La Araucanía using accelerometry (ActiGraph GT3X +). The percentage of moderate to vigorous PA (MVPA) and sedentary behavior (SB) were estimated. Subjects with ≥60 min of MVPA were considered physically active according to the recommendation of the World Health Organization (WHO). Individuals with %SB >75th percentile were sedentary. The lipid profile was determined using conventional methods. TG/HDL-C ratio and atherogenic index of plasma (AIP) were calculated. RESULTS: 37.1% presented dyslipidemia, 8% hypercholesterolemia, 19.5% hypertriglyceridemia, 6.3% elevated LDL-C and 25.2% decreased HDL-C. Only 9.4% were physically active according to the WHO recommendation. In physically active subjects where no cases of dyslipidemias (p =0.032) and no low HDL-C (p = 0.013). The %MVPA was reduced in subjects with low HDL-C and positively correlated with HDL-c (r = 0.157, p = 0.048). In addition, %MVPA was correlated with lower TG / HDL-C values (r = -0.193, p = 0.015) and AIP (r = -0.214, p = 0.006). SB was not associated with risk of dyslipidemia, % SB was positively correlated with glucose levels (r = 0.159, p = 0.044) and HOMA-IR (r = 0.178, p = 0.037) and negatively with Quicki (r = -0.160, p = 0.044). CONCLUSIONS: Our results suggested that PA is it correlates to a lower frequency of dyslipidemia and the practice of MVPA would increase HDL-c values and reduce atherogenic index, promoting it may been reducing the risk of CVDs in our population. In addition, the SB is related to an increase in glucose values and insulin resistance index in schoolchildren in Región de La Araucanía.

The APOB rs693 polymorphism impacts the lipid profile of Brazilian older adults

The apolipoprotein B (APOB) gene contains several polymorphic sites described as risk modifiers for cardiovascular events. The objective of this study was to verify the association of the classic APOB Xba I polymorphism (rs693) with atherosclerotic risk factors in a segment of the Brazilian elderly population considering their usual dietary intake. Clinical and biochemical characteristics as well as total caloric and fat intake data were determined from 644 elderly individuals. Polymorphism analysis was performed by conventional polymerase chain reaction followed by enzyme restriction. Statistical analyses compared measures and proportions according to different APOB genotypic combinations. Statistically significant association was found between Xba I polymorphism and serum LDL, total cholesterol, and total lipid levels, with important elevations among T homozygotes compared to the other genotypes. There was homogeneity in all other parameters analyzed (including intake pattern), with a tendency for reduced levels of circulating apolipoprotein B among TT individuals. Our results pointed out that genetic variation in APOB affected the lipemic profile of elderly individuals in a context not biased by diet, generating a pattern suggestive of secretory disorder of lipoprotein particles, with possible implication in atherosclerotic risk.

Increased levels of plasma IL-1b and BDNF can predict resistant depression patients

SUMMARY BACKGROUND: There is no strong evidence on the link between inflammatory profile and pattern of drug treatment response in depressive patients that could result in Coronary Artery Disease occurrence. OBJECTIVE: This study aimed to compare the subclinical atherosclerosis markers, inflammatory profile, and BDNF production in Resistant Depression (RD) or Bipolar Affective Disorder (BAD) patients under conventional treatment. METHODS: The population evaluated was comprised of 34 RD, 43 BAD, and 41 controls. Subclinical atherosclerosis markers were evaluated using ultrasonography, tomography, and exercise stress test. Plasma concentrations of TNFα, IL-1β, IL-6, and BDNF were measured using Luminex100™. The usCRP concentration was measured using turbidimetric immunoassay. IL1B, IL6, and TNFA expression were determined using TaqMan®. For the statistical analysis, the significance level was established at p<0.05. RESULTS: Concerning subclinical atherosclerosis markers, only O2 consumption was reduced in the BAD group (p = 0.001). Although no differences were found in gene expression, BDNF and IL-1β plasma concentration was increased in the RD group (p = 0.002 and p = 0.005, respectively) even with an antidepressant treatment, which suggests that these drugs have no effect in IL-1β secretion and that the inflammasome may play a role in therapy response. CONCLUSION: Taken together, both BDNF and IL-1β plasma concentrations could be used to the early identification of RD patients.

RESUMO FUNDAMENTAÇÃO: Não há fortes evidências sobre a associação entre o perfil inflamatório e o padrão de resposta ao tratamento medicamentoso em pacientes depressivos que podem resultar em ocorrência de doença coronariana. OBJETIVO: O objetivo deste estudo foi comparar os marcadores de aterosclerose subclínica, o perfil inflamatório e a produção de BDNF em pacientes com Depressão Resistente (DR) ou Transtorno Afetivo Bipolar (BAD) sob tratamento convencional. MÉTODOS: A população avaliada incluiu 34 RD, 43 BAD e 41 controles. Os marcadores de aterosclerose subclínica foram avaliados por ultrassonografia, tomografia e teste de esforço. As concentrações plasmáticas de TNFα, IL-1β, IL-6 e BDNF foram medidas utilizando Luminex100TM. A concentração de usCRP foi medida por imunoensaio turbidimétrico. A expressão de IL1B, IL6 e TNFA foi determinada usando TaqMan®. Para as análises estatísticas, foi estabelecido o nível de significância de p < 0,05. RESULTADOS: Quanto aos marcadores de aterosclerose subclínica, apenas o consumo de O2 foi reduzido no grupo BAD (p = 0,001). Embora não tenham sido encontradas diferenças na expressão gênica, a concentração plasmática de BDNF e IL-1β foi aumentada no grupo RD (p = 0,002 e p = 0,005, respectivamente) mesmo sob tratamento antidepressivo, o que sugere que esses medicamentos não têm efeito na secreção de IL-1β e que o inflamassomo pode desempenhar um papel na resposta terapêutica. CONCLUSÃO: Juntas, as concentrações BDNF e IL-1β poderiam ser usadas para a identificação precoce de pacientes com DR.

Serum irisin and apelin levels and markers of atherosclerosis in patients with subclinical hypothyroidism

ABSTRACT Objective: In this study, we aimed to evaluate serum irisin and apelin levels in patients with subclinical hypothyroidism (SCH) when they were subclinical hypothyroid and become euthyroid after levothyroxine therapy and association of these adipokines with markers of atherosclerosis such as serum homocysteine levels and carotid intima-media thickness (IMT). Subjects and methods: The study included 160 patients with newly diagnosed subclinical hypothyroidism due to Hashimoto's thyroiditis and 86 euthyroid healty subjects. Serum glucose and lipid profile, insulin, HOMA, TSH, free T3, free T4, anti-thyroperoxidase and anti-thyroglobulin antibodies, homocysteine, apelin and irisin levels were measured in all study subjects. Thyroid and carotid ultrasound examinations were performed. The subclinical hypothyroid group was reevaluated after 12-weeks of levothyroxine therapy when they became euthyroid. Results: Clinical characteristics of the patient and control group were similar. Glucose, insulin and HOMA levels, lipid parameters and free T3 were similar between the two groups.. Serum homocystein was higher and apelin was lower in patients with SCH, but irisin levels were similar between the two groups. While thyroid volume was lower, carotid IMT was significantly greater in patients with SCH (pCarotidIMT:0,01). After 12-weeks of levothyroxine therapy, all the studied parameters remained unchanged except, serum freeT4, TSH, homocystein and apelin. While homocystein decreased (p: 0,001), apelin increased significantly (p = 0,049). In multivariate analysis, low apelin levels significantly contributed to carotid IMT (p = 0,041). Conclusions: Apelin-APJ system may play a role in vascular and cardiac dysfunction in patients with SCH and treatment of this condition may improve the risk of cardiovascular disease.

Assessment of the Relationship between Monocyte to High-Density Lipoprotein Ratio and Myocardial Bridge / Avaliação da Relação entre a Razão de Monócitos para Lipoproteínas de Alta Densidade e a Ponte Miocárdica

Abstract Background: Assessing the monocyte to high-density lipoprotein ratio (MHR) is a new tool for predicting inflamation, which plays a major role in atherosclerosis. Myocardial bridge (MB) is thought to be a benign condition with development of atherosclerosis, particularly at the proximal segment of the brigde. Objective: To evaluate the relationhip between MHR and the presence of MB. Methods: We consecutively scanned patients referred for coronary angiography between January 2013- December 2016, and a total of 160 patients who had a MB and normal coronary artery were enrolled in the study. The patients' angiographic, demographic and clinic characteristics of the patients were reviewed from medical records. Monocytes and HDL-cholesterols were measured via complete blood count. MHR was calculated as the ratio of the absolute monocyte count to the HDL-cholesterol value. MHR values were divided into three tertiles as follows: lower (8.25 ± 1.61), moderate (13.11 ± 1.46), and higher (21.21 ± 4.30) tertile. A p-value of < 0.05 was considered significant. Results: MHR was significantly higher in the MB group compared to the control group with normal coronary arteries. We found the frequency of MB (p = 0.002) to increase as the MHR tertiles rose. The Monocyte-HDL ratio with a cut-point of 13.35 had 59% sensitivity and 65.0% specificity (ROC area under curve: 0.687, 95% CI: 0.606-0.769, p < 0.001) in accurately predicting a MB diagnosis. In the multivariate analysis, MHR (p = 0.013) was found to be a significant independent predictor of the presence of MB, after adjusting for other risk factors. Conclusion: The present study revealed a significant correlation between MHR and MB.

Resumo Fundamento: A avaliação da razão de monócitos para lipoproteínas de alta densidade (MHR, sigla em inglês) é uma nova ferramenta para se prever o processo inflamatório, o qual desempenha um papel importante na aterosclerose. A ponte miocárdica (PM) é considerada uma condição benigna com desenvolvimento de arteriosclerose, particularmente no segmento proximal da ponte. Objetivo: Avaliar a relação entre a MHR e a presença de PM. Métodos: Examinamos concecutivamente pacientes encaminhados para angiografia coronariana entre janeiro de 2013 e dezembro de 2016, e um total de 160 pacientes, uma parcela dos quais com PM, e outra com artérias coronárias normais, foram incluídos no estudo. As características angiográficas, demográficas e clínicas dos pacientes foram revisadas a partir de registros médicos. Monócitos e colesteróis HDL foram medidos através de hemograma completo. A MHR foi calculada como a razão entre a contagem absoluta de monócitos e o valor do colesterol HDL. Os valores de MHR foram divididos em três tercis, da seguinte forma: tercil inferior (8,25 ± 1,61); tercil moderado (13,11 ± 1,46); e tercil superior (21,21 ± 4,30). Considerou-se significativo um valor de p < 0,05. Resultados: A MHR foi significativamente maior no grupo com PM, em comparação com grupo controle com artérias coronárias normais. Verificamos que a prevalência de PM (p=0,002) aumentou à medida que se elevavam os tercis de MHR. A razão monócitos-colesterol HDL com ponto de corte de 13,35 apresentou sensibilidade de 59% e especificidade de 65,0% (área ROC sob a curva: 0,687, IC95%: 0,606-0,769, p < 0,001) na predição acurada do diagnóstico de PM. Na análise multivariada, a MHR (p = 0,013) mostrou-se um preditor independente significativo da presença de PM, após ajustes para outros fatores de risco. Conclusão: O presente estudo revelou uma correlação significativa entre MHR e PM.

Consumption of animal-based and processed food associated with cardiovascular risk factors and subclinical atherosclerosis biomarkers in men

SUMMARY OBJECTIVE To evaluate the frequency of food consumption in apparently healthy men and their association with cardiovascular risk factors and biomarkers of subclinical atherosclerosis. METHODS In this observational study, 88 men had their food standard obtained through the food frequency questionnaire (FFQ). Associations of dietary patterns with cardiovascular risk factors, such as anthropometric data, laboratory and clinical evaluations, carotid-femoral arterial stiffness (IMT) and pulse wave velocity were evaluated. RESULTS The highest values were observed, for most of the risk factors evaluated, with the highest frequency of weekly consumption of dairy products, meats, sweets, fats, cold meats, sodas, milk and white chocolate; and lower frequency of weekly consumption of fruits, cereals, vegetables, legumes, oilseeds, and soy. There was no significant difference for coffee and dark chocolate CONCLUSIONS A diet with high consumption of animal products has a higher correlation with cardiovascular risk factors; the opposite is true for the consumption of plant-based food, associated with the profile of more favorable biomarkers for cardiovascular health and better biochemical and structural parameters.

RESUMO OBJETIVO Avaliar a frequência do consumo alimentar de indivíduos homens aparentemente saudáveis e a associação desta com fatores de risco cardiovascular e biomarcadores de aterosclerose subclínica. MÉTODOS Neste estudo observacional, 88 homens tiveram o padrão alimentar obtido por meio do questionário de frequência alimentar (QFA). Foram avaliadas as associações dos padrões alimentares com os fatores de risco cardiovascular, como dados antropométricos, avaliações laboratoriais e clínica, rigidez arterial determinada pela carótida-femoral (IMT) e velocidade da onda de pulso (VOP). RESULTADOS O padrão observado para a maioria dos fatores de risco avaliados foi de valores mais altos, segundo maior frequência de consumo semanal de lácteos, carnes, doces, gorduras/frituras, embutidos, refrigerantes, chocolates ao leite e branco; e de menor frequência de consumo semanal de frutas, cereais, legumes, verduras, leguminosas, oleaginosas e soja. Não houve diferença significativa para café e chocolate amargo. CONCLUSÕES Uma dieta com alto consumo de produtos animais apresenta maior correlação com fatores de risco cardiovascular, sendo o oposto para o consumo de alimentos de origem vegetal, associado ao perfil de biomarcadores de saúde cardiovascular mais favorável e melhores parâmetros bioquímicos e estruturais.

Alta prevalencia de dislipidemias y riesgo aterogénico en una población infanto-juvenil / High prevalence of dyslipidemia and high atherogenic index of plasma in children and adolescents

Background: Dyslipidemias in childhood increase the risk of cardiovascular events in adult life. Aim: To evaluate the prevalence of dyslipidemia and risk of atherogenicity based in the atherogenic index of plasma (AIP) in a sample of school children and adolescents. Material and Methods: Cross-sectional study of 208 children aged 10.4 ± 1.0 years (107 women). Demographic data were obtained, and a clinical evaluation was conducted, including pubertal development according to Tanner and anthropometric parameters. A fasting blood sample was obtained to measure total cholesterol (CT), HDL cholesterol (cHDL) and triglycerides (TG), glucose and insulin. LDL cholesterol (cLDL), Non-HDL cholesterol and the indices CT/cHDL, cLDL/cHDL and AIP (log[TG/cHDL]) were calculated. Risk categories according to AIP for the pediatric population were also determined (low: AIP < 0.11, intermediate: AIP 0.11-0.21, high: AIP > 0.21). Results: Thirty eight percent of participants had dyslipidemia, without differences by gender and pubertal development. The frequency of dyslipidemia was significantly higher in children with obesity (54%, p < 0.01) and a waist circumference over percentile 90 (61%; p < 0.01). The later conditions had also higher CT/cHDL, cLDL/cHDL and AIP. According to AIP, 54% of children had a high atherogenicity risk along with alterations in anthropometric parameters and insulin resistance. All anthropometric and insulin resistance parameters were significantly correlated with the AIP. Conclusions: There is a high prevalence of dyslipidemia in the studied population, which is associated with an increased cardiometabolic risk. The indices of atherogenicity and particularly AIP are correlated with nutritional status, abdominal obesity and parameters of insulin resistance.

Is Lipid Accumulation Product Associated with an Atherogenic Lipoprotein Profile in Brazilian Subjects? / O Produto de Acumulação Lipídica está Associado a um Perfil Aterogênico de Lipoproteínas em Indivíduos Brasileiros?

Abstract Background: Lipid accumulation product (LAP), a simple and low-cost tool, is a novel biomarker of central lipid accumulation and represents a potential surrogate marker for atherogenic lipoprotein profile. However, its association with lipoprotein subfractions has not been described in the literature. Objective: To determine whether LAP index could be used as a marker of low- and high-density lipoprotein (LDL and HDL) size in Brazilian individuals. Methods: This cross-sectional study included patients (n = 351) of both sexes and age between 30-74 years. Clinical and sociodemographic data and family history of diseases were evaluated. Lipoprotein size, and levels of total cholesterol (TC), lipoproteins, apolipoprotein AI and B (APO AI/APO B), glucose, insulin, insulin resistance index (HOMA-IR) and non-esterified fatty acids (NEFA) were assessed in blood samples. LAP was calculated by the formulas [(waist circumference[cm]-58) × (triglycerides[mmol/L]) for women and (waist circumference [cm]-65) × (triglycerides [mmol/L]) for men]. The association between LAP and metabolic parameters were tested by linear trend (general linear model, GLM test) before and after multiple adjustments for potential confounders (sex, age, smoking, statin, fibrate, and hypoglycemic drugs) at significant level p < 0.05. Results: LAP was positively associated with TC, APO B, NEFA, glucose, insulin and HOMA-IR values, and negatively associated with HDL-C. Higher central lipid accumulation was corelated with higher percentage of intermediate HDL and of small LDL and HDL and less amount of large HDL. LDL size was also reduced in greater LAP index values. The negative impact of LAP was maintained after adjustment for multiple variables. Conclusion: LAP was robustly associated with atherogenic profile of lipoprotein subfractions, independently of multiple confounders.

Resumo Fundamento: O produto de acumulação lipídica (LAP), um instrumento simples e de baixo custo, é um novo biomarcador de acúmulo de gordura central e representa um marcador substituto potencial para o perfil aterogênico de lipoproteínas. No entanto, sua associação com subfrações de lipoproteínas ainda não foi descrita na literatura. Objetivo: Determinar se o LAP pode ser usado como um marcador de tamanho da lipoproteína de baixa densidade (LDL) e de alta densidade (HDL) em indivíduos brasileiros. Métodos: Este estudo transversal incluiu 351 pacientes de ambos os sexos e idade entre 30 e 74 anos. Dados clínicos e sociodemográficos e história familiar de doenças foram avaliados. O tamanho das lipoproteínas, e níveis de colesterol total (CT), lipoproteínas, apolipoproteína AI e B (APO AI/APO B), glicose, ácidos graxos não esterificados (AGNEs) e insulina, e índice de resistência insulínica (HOMA-IR) foram avaliados em amostras de sangue. O LAP foi calculado utilizando-se as fórmulas (circunferência da cintura (cm]-58) × (triglicerídeos[mmol/L]) para mulheres e (circunferência da cintura[cm]-65) × (triglicerídeos [mmol/L]) para homens. Associações entre LAP e parâmetros metabólicos foram testadas por tendência linear (modelo linear generalizado, GLM) antes e após ajustes por fatores de confusão (sexo, idade, tabagismo, uso de estatinas, fibratos e hipoglicemiantes) ao nível de significância de p < 0,05). Resultados: LAP apresentou uma associação positiva com CT, APO B, AGNEs, glicose, insulina, HOMA-IR, e uma associação negativa com HDL-C. Maior acúmulo de gordura central correlacionou-se com maior porcentagem de HDL intermediária e de partículas pequenas de LDL e HDL, e menor porcentagem de HDL grande. O tamanho da LDL também era reduzido em valores de LAP mais elevados. O impacto negativo do LAP foi mantido após ajuste para múltiplas variáveis. Conclusão: o LAP esteve fortemente associado com o perfil aterogênico de subfrações de lipoproteínas, independetemente dos fatores de confusão.

Allantoin as an independent marker associated with carotid intima-media thickness in subclinical atherosclerosis

Allantoin is the main product of uric acid oxidation and was found to be augmented in atherosclerotic plaque in human autopsy and in animal models of atherosclerosis. Uric acid is abundant in human plasma and is prone to oxidation in inflammatory conditions such as atherosclerosis. In this study, we found a significant increase in plasma uric acid (P=0.002) and allantoin (P=0.025) in participants of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) that presented common carotid intima-media thickness (c-IMT) within the 75th percentile (c-IMT≥P75). Multiple linear regression showed an association of c-IMT with uric acid (β=0.0004, P=0.014) and allantoin (β=0.018, P=0.008). This association was independent of age, the traditional risk factor LDL/HDL ratio, and non-traditional risk factors: pulse pressure, neck circumference, and the inflammatory marker myeloperoxidase. The independent and strong association of allantoin with c-IMT shows that it might be a useful marker, along with other traditional risk factors, to evaluate an early stage of atherosclerosis.

Increased ROS production and DNA damage in monocytes are biomarkers of aging and atherosclerosis

BACKGROUND: New evidence demonstrates that aging and dyslipidemia are closely associated with oxidative stress, DNA damage and apoptosis in some cells and extravascular tissues. However, in monocytes, which are naturally involved in progression and/or resolution of plaque in atherosclerosis, this concurrence has not yet been fully investigated. In this study, we evaluated the influence of aging and hypercholesterolemia on serum pro-inflammatory cytokines, oxidative stress, DNA damage and apoptosis in monocytes from apolipoprotein E-deficient (apoE-/-) mice compared with age-matched wild-type C57BL/6 (WT) mice. Experiments were performed in young (2-months) and in old (18-months) male wild-type (WT) and apoE-/- mice. RESULTS: Besides the expected differences in serum lipid profile and plaque formation, we observed that atherosclerotic mice exhibited a significant increase in monocytosis and in serum levels of pro-inflammatory cytokines compared to WT mice. Moreover, it was observed that the overproduction of ROS, led to an increased DNA fragmentation and, consequently, apoptosis in monocytes from normocholesterolemic old mice, which was aggravated in age-matched atherosclerotic mice. CONCLUSIONS: In this study, we demonstrate that a pro-inflammatory systemic status is associated with an impairment of functionality of monocytes during aging and that these parameters are fundamental extra-arterial contributors to the aggravation of atherosclerosis. The present data open new avenues for the development of future strategies with the purpose of treating atherosclerosis.

Circulation levels of acute phase proteins pentraxin 3 and serum amyloid A in atherosclerosis have correlations with periodontal inflamed surface area

Abstract Objectives One of the plausible mechanisms in the relationship between periodontitis and coronary artery disease (CAD) is the systemic inflammatory burden comprised of circulating cytokines/mediators related to periodontitis. This study aims to test the hypothesis that periodontal inflamed surface area (PISA) is correlated with higher circulating levels of acute phase reactants (APR) and pro-inflammatory cytokines/mediators and lower anti-inflammatory cytokines/mediators in CAD patients. Material and Methods Patients aged from 30 to 75 years who underwent coronary angiography with CAD suspicion were included. Clinical periodontal parameters (probing depth - PD, clinical attachment loss, and bleeding on probing - BOP) were previously recorded and participants were divided into four groups after coronary angiography: Group 1: CAD (+) with periodontitis (n=20); Group 2: CAD (+) without periodontitis (n=20); Group 3: CAD (-) with periodontitis (n=21); Group 4: CAD (-) without periodontitis (n = 16). Serum interleukin (IL) −1, −6, −10, tumor necrosis factor (TNF)-α, serum amyloid A (SAA), pentraxin (PTX) 3, and high-sensitivity C-reactive protein (hs-CRP) levels were measured with ELISA. Results Groups 1 and 3 showed periodontal parameter values higher than Groups 2 and 4 (p<0.0125). None of the investigated serum parameters were statistically significantly different between the study groups (p>0.0125). In CAD (-) groups (Groups 3 and 4), PISA has shown positive correlations with PTX3 and SAA (p<0.05). Age was found to predict CAD significantly according to the results of the multivariate regression analysis (Odds Ratio: 1.17; 95% Confidence Interval: 1.08-1.27; p<0.001). Conclusions Although age was found to predict CAD significantly, the positive correlations between PISA and APR in CAD (-) groups deserve further attention, which might depend on the higher PISA values of periodontitis patients. In further studies conducted in a larger population, the stratification of age groups would provide us more accurate results.

Correlation between serum 25-hydroxyvitamin D levels and carotid intima-media thickness in a Brazilian population descended from African slaves

Hypovitaminosis D has been identified as a possible new cardiovascular risk factor. However, the results of studies correlating serum vitamin D levels with markers of subclinical atherosclerosis have been conflicting. The aim of this study was to correlate serum levels of 25-hydroxyvitamin D [25(OH)D] with carotid intima-media thickness (C-IMT) and conventional cardiovascular risk factors in Afro-descendants. A cross-sectional analysis was performed on a sample of 382 individuals from a cohort of descendants of African slaves, inhabitants of "Quilombola" communities, with a mean age of 57.79 ±15.3 years, 54.5% of whom were women. Socio-demographic and clinical data were collected and biochemical tests were performed, including serum levels of 25(OH)D by electrochemiluminescence and urinary albumin excretion, evaluated by the albumin/creatinine ratio (ACR) in a spot urine sample. All participants underwent high-resolution ultrasonography for C-IMT measurement. Hypovitaminosis D was defined as serum 25(OH)D levels <30 ng/mL. The mean serum 25(OH)D levels were 50.4±13.5 ng/mL, with a low prevalence of hypovitaminosis D (4.86%). By simple linear correlation, a significant inverse association between 25(OH)D levels and C-IMT (r=-0.174, P=0.001) was observed. However, after multiple linear regression analysis, the significance of the association between serum levels of 25(OH)D and C-IMT measurement was lost (β=-0.039, P=0.318) and only male gender, age, smoking, systolic blood pressure, glucose and low density lipoprotein (LDL)-cholesterol remained significantly associated with C-IMT. Levels of 25(OH)D were independently and positively associated with HDL-cholesterol and inversely associated with age and ACR. In conclusion, no independent association between 25(OH)D levels and C-IMT was observed in this population. On the other hand, there was an inverse association with albuminuria, a marker of endothelial lesion.

Evaluación del lipidograma y ciertos factores de riesgo de ateroesclerosis en niños cuyos padres tuvieron arteriopatía coronaria de inicio temprano / Assessment of lipid profile and some risk factors of atherosclerosis in children whose parents had early onset coronary artery disease

Antecedentes/Objetivo. El objetivo de nuestro estudio fue analizar el lipidograma y ciertos factores de riesgo de ateroesclerosis, tales como las lipoproteínas de baja densidad oxidadas (ox-LDL, por su sigla en inglés) y las lipoproteínas de baja densidad pequeñas y densas (sdLDL, por su sigla en inglés) en los hijos de pacientes con cardiopatía coronaria (CC) prematura. Población y métodos. Hijos de padres con CC de inicio temprano emparejados con pares de su misma edad y mismo sexo. Se analizaron las concentraciones de lípidos, apolipoproteínas (ApoA, B, E), ox-LDL, sdLDL y lipoproteína (a) [Lp(a)] en los niños de estudio y de referencia. Los datos se evaluaron con el programa SPSS, junto con la prueba t de Student y la prueba U de Mann-Whitney. Resultados. Los niños del grupo de estudio (n: 43) tenían niveles más elevados de LDL, Lp(a) y ox-LDL y cocientes mayores de CT/HDL, ApoB/ApoA, LDL/HDL y ox-LDL/HDL (p < 0,05) que los del grupo de referencia. Conclusión. Con base en estos hallazgos, se sugiere que la dislipidemia y las concentraciones elevadas de LDL, Lp(a) y ox-LDL son frecuentes en los hijos de pacientes con CC de inicio temprano y representan gran parte de la predisposición familiar a tener CC

Background/Aim: The objective of our study was to analyze the lipid profile and some risk factors of atherosclerosis such as oxidized-low density lipoprotein (ox-LDL), small dense LDL (sd LDL) in the offspring of patients with premature coronary heart disease (CHD). Population and Methods: Children whose parents had early onset CHD were matched with age and sex pairs. Study and controls were analyzed for lipid levels, apolipoproteins (Apo- A,B,E), ox-LDL, sd LDL and lipoprotein (a) [Lp(a)]. The data were evaluated with SPSS using "Student tand Mann-Whitney U" tests. Results: Thestudy group children (n: 43) had higher LDL, Lp(a) and ox-LDL levels, ratios of TC/HDL, Apo-B/A, LDL/HDL and ox-LDL/HDL (p<0.05) than control group. Conclusion: These findings suggest that dyslipidemia and increased LDL, Lp(a) and ox-LDL levels are common in the offspring of patients with early onset CHD and account largely for their familial predisposition for CHD.

Circulating early biomarkers of atherogenesis in participants of the Longitudinal Study of Adult Health (ELSA-Brasil) without diabetes or cardiovascular disease

ABSTRACT Objective Our aim was to describe the distribution of selected biomarkers according to age and sex, adjusted for HOMA-IR and adiposity, in a subset of middle-aged individuals of Brazilian Longitudinal Study of Adult Health-ELSA without diabetes mellitus or CVD. Subjects and methods This cross-sectional study was conducted in 998 participants of the ELSA-Brasil without diabetes and/or cardiovascular disease. In addition to the traditional risk factors, several biomarkers concentrations were compared according to sex, age groups (35-44; 45-54 yrs) and HOMA-IR tertiles. Linear regression was used to examine independent associations of sex and age with selected novel biomarkers, adjusted for body adiposity and HOMA-IR. Results Fifty-five percent were women. Men had higher mean values of body mass index, waist circumference, blood pressure, plasma glucose, HOMA-IR, worse lipid profile and higher E-selectin and lower leptin concentrations than women; while women had higher levels of HDL-cholesterol and leptin than men. Mean values of waist circumference, systolic BP, plasma glucose and apolipoprotein B (Apo B) increased with age in both sexes. Leptin and E-selectin concentrations increased across HOMA-IR tertiles. Independent associations of Apo B with age were found only in male sex, while of leptin with body mass index and HOMA-IR, and of E-selectin with HOMA-IR in both sexes. Conclusions In conclusion, our data indicate age, sex, adiposity and, consequently, insulin resistance, influence circulating levels of Apo B, leptin and E-selectin, suggesting that those aspects should be taken into consideration when assessing these parameters for research or clinical purposes in individuals at relatively low cardiometabolic risk.

Early Markers of Atherosclerotic Disease in Individuals with Excess Weight and Dyslipidemia / Marcadores Precoces de Doença Aterosclerótica em Indivíduos com Excesso de Peso e Dislipidemia

Abstract Background: Excessive weight is a cardiovascular risk factor since it generates a chronic inflammatory process that aggravates the endothelial function. Objective: To evaluate the endothelial function in individuals with excess weight and mild dyslipidemia using brachial artery flow-mediated dilation (BAFMD), and the association of endothelial function with anthropometric and biochemical variables. Methods: Cross-sectional study that included 74 individuals and evaluated anthropometric variables (body mass index [BMI], waist-hip ratio [WHR], waist circumference [AC], and percentage of body fat [PBF]), biochemical (blood glucose, insulinemia, ultrasensitive C-reactive protein, fibrinogen, total cholesterol, HDL-cholesterol, triglycerides, and LDL-cholesterol) and endothelial function (BAFMD, evaluated by ultrasound). The statistical analysis was performed with SPSS, version 16.0. To study the association between the variables, we used chi-square, Student's t and Mann-Whitney tests, and Pearson's correlation. Logistic regression analyzed the independent influence of the factors. Values of p < 0.05 were considered significant. Results: The participants had a mean age of 50.8 years, and 57% were female. BMI, WC, WHR, and PBF showed no significant association with BAFMD. The male gender (p = 0.02) and higher serum levels of fibrinogen (p = 0.02) were significantly and independently associated with a BAFMD below 8%. Conclusions: In individuals with excess weight and mild untreated dyslipidemia, male gender and higher levels of fibrinogen were independently associated with worse BAFMD.

Resumo Fundamento: O excesso de peso é um fator de risco cardiovascular, pois gera um processo inflamatório crônico que agrava a função endotelial. Objetivo: Avaliar a função endotelial de indivíduos com excesso de peso e dislipidemia leve através da dilatação da artéria braquial mediada pelo fluxo (DABMF) e sua associação com variáveis antropométricas e bioquímicas. Métodos: Estudo transversal com inclusão de 74 indivíduos e avaliação de variáveis antropométricas (índice de massa corporal [IMC], razão cintura-quadril [RCQ], circunferência abdominal [CA] e percentual de gordura corporal [PGC]), bioquímicas (glicemia, insulinemia, proteína C reativa ultrassensível, fibrinogênio, colesterol total, HDL-colesterol, triglicerídeos e LDL-colesterol) e função endotelial (DABMF, avaliada por ultrassonografia). A análise estatística foi realizada pelo programa SPSS, versão 16.0. Para estudar a associação entre as variáveis, foram utilizados os testes do qui-quadrado, t de Student, Mann-Whitney e correlação de Pearson. Regressão logística analisou a influência independente dos fatores. Valores de p < 0,05 foram considerados significativos. Resultados: Os participantes tinham uma média de idade de 50,8 anos e 57% eram do gênero feminino. O IMC, a CA, a RCQ e o PGC não mostraram associação significativa com a DABMF. O gênero masculino (p = 0,02) e níveis séricos mais elevados de fibrinogênio (p = 0,02) estiveram significativamente e independentemente associados a uma DABMF inferior a 8%. Conclusões: Em indivíduos com excesso de peso e dislipidemia leve não tratada, o gênero masculino e níveis mais elevados de fibrinogênio foram associados de forma independente com uma pior DABMF.

Galpha12 Protects Vascular Endothelial Cells from Serum Withdrawal-Induced Apoptosis through Regulation of miR-155

PURPOSE: Apoptosis of vascular endothelial cells is a type of endothelial damage that is associated with the pathogenesis of cardiovascular diseases such as atherosclerosis. Heterotrimeric GTP-binding proteins (G proteins), including the alpha 12 subunit of G protein (Galpha12), have been found to modulate cellular proliferation, differentiation, and apoptosis of numerous cell types. However, the role of Galpha12 in the regulation of apoptosis of vascular cells has not been elucidated. We investigated the role of Galpha12 in serum withdrawal-induced apoptosis of human umbilical vein endothelial cells (HUVECs) and its underlying mechanisms. MATERIALS AND METHODS: HUVECs were transfected with Galpha12 small-interfering RNA (siRNA) to knockdown the endogenous Galpha12 expression and were serum-deprived for 6 h to induce apoptosis. The apoptosis of HUVECs were assessed by Western blotting and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The expressions of microRNAs were analyzed by quantitative real-time PCR. RESULTS: Knockdown of Galpha12 with siRNA augmented the serum withdrawal-induced apoptosis of HUVECs and markedly repressed the expression of microRNA-155 (miR-155). Serum withdrawal-induced apoptosis of HUVECs was inhibited by the overexpression of miR-155 and increased significantly due to the inhibition of miR-155. Notably, the elevation of miR-155 expression prevented increased apoptosis of Galpha12-deficient HUVECs. CONCLUSION: From these results, we conclude that Galpha12 protects HUVECs from serum withdrawal-induced apoptosis by retaining miR-155 expression. This suggests that Galpha12 might play a protective role in vascular endothelial cells by regulating the expression of microRNAs.