The potential of using blood circular RNA as liquid biopsy biomarker for human diseases

Circular RNA (circRNA) is a novel class of single-stranded RNAs with a closed loop structure. The majority of circRNAs are formed by a back-splicing process in pre-mRNA splicing. Their expression is dynamically regulated and shows spatiotemporal patterns among cell types, tissues and developmental stages. CircRNAs have important biological functions in many physiological processes, and their aberrant expression is implicated in many human diseases. Due to their high stability, circRNAs are becoming promising biomarkers in many human diseases, such as cardiovascular diseases, autoimmune diseases and human cancers. In this review, we focus on the translational potential of using human blood circRNAs as liquid biopsy biomarkers for human diseases. We highlight their abundant expression, essential biological functions and significant correlations to human diseases in various components of peripheral blood, including whole blood, blood cells and extracellular vesicles. In addition, we summarize the current knowledge of blood circRNA biomarkers for disease diagnosis or prognosis.

Evaluation of perioperative high-sensitive cardiac troponin i as a predictive biomarker of major adverse cardiovascular events after noncardiac surgery

ABSTRACT Background: Various studies suggest that perioperative concentrations of high-sensitivity troponins are incremental and predictive factors of a major adverse cardiac event (MACE) and all-cause mortality. Objective: The objective of the study was to evaluate the predictive value of high-sensitivity cardiac troponin I (hs-cTnI) in the development of MACE and all-cause mortality, within 30-days and 1-year follow-up after noncardiac surgery. Methods: In this prospective cohort study, we included men ≥ 45 years and women ≥ 55 years with ≥ 2 cardiovascular risk factors and undergoing intermediate or high-risk noncardiac surgery. Demographic and clinical information was collected from clinical charts. We measured baseline hs-cTnI 24 h before surgery, and its post-operative concentration 24 h after surgery. Results: In the entire sample, 8 patients (8.6%) developed MACE at 30-days follow-up (4 deaths), 12 (12.9%) within the 1st year (7 deaths), and 17 (18.2%) after complete post-surgical follow-up (10 deaths). We observed higher baseline and post-operative concentrations in patients who presented MACE (12 pg/ml vs. 3.5 pg/ml; p = 0.001 and 18.3 pg/ml vs. 5.45 pg/ml; p = 0.009, respectively). The hazard ratios (HRs) calculated by Cox regression analysis between the hs-cTnI baseline concentration and the post-operative development of MACE at 30-days and 1-year were 5.70 (95% confidence interval [CI], 1.10-29.40) with hs-cTnI > 6.2 pg/ml and 12.86 (95% CI, 1.42-116.34) with hs-cTnI > 3.3 pg/ml, respectively. The estimated post-operative HR death risk at 1-year was 14.43 (95% CI, 1.37-151.61) with hs-cTnI > 4.5 pg/ml. Conclusions: Pre-operative hs-cTnI was an independent predictive risk factor for MACE at 30-days and 1-year after noncardiac surgery and for all-cause mortality at 1-year after noncardiac surgery.

Proteína C reactiva ultrasensible y riesgo cardiovascular en pacientes con diabetes mellitus tipo 2 / Ultrasensitive reactive C protein and cardiovascular risk in patients with type 2 diabetes mellitus

Objetivo: describir el riesgo cardiovascular de pacientes con diabetes mellitus tipo 2 (DM2), según los valores de proteína C reactiva ultrasensible (PCR-us). Material y métodos: estudio descriptivo transversal, realizado en el Patronato del Diabético de zona 1, Ciudad de Guatemala, en el cual participaron 196 pacientes mayores de 50 años de edad, obteniéndose características sociodemográficas, medidas antropométricas. Además, se tomaron muestras de sangre que fueron procesadas en iCroma ll para determinar los valores de Proteína C reactiva ultrasensible (PCR-us). Resultados: los pacientes que aceptaron formar parte del estudio, tuvieron una media de edad de 62±8.62 DE; 74.4% (146) fueron del sexo femenino; 54% (106) eran católicos y el 82.1% (161), residían en la Ciudad de Guatemala. El estado nutricional fue normal en el 26% (50), el 11% (21) tenía sobrepeso y 63% (125), obesidad. Para índice cintura cadera (ICC) con respecto al sexo femenino, se obtuvo una media de 0.89±0.05 DE y una media 0.97±0.05 DE del sexo masculino. Respecto al riesgo cardiovascular, se obtuvo una media en valores de PCR-us de 2.9±2.8 DE, con 76% (148) de los pacientes en riesgo cardiovascular moderado/alto. Conclusiones: los valores de PCR-us tuvieron una media de 2.9±2.8 DE y 8 de cada 10 pacientes están en riesgo moderado/alto. De los pacientes estudiados, 7 de cada 10 fueron mujeres, con una media para a edad de 62 años. Se encontraron 7 de cada 10 con sobrepeso u obesidad, con una media para índice cintura cadera con respecto al sexo elevado.

Objective: to describe the cardiovascular risk of patients with type 2 diabetes mellitus, according to the values of ultrasensitive C-reactive protein (PCR-us). Material and methods: descriptive cross-sectional study, carried out on 196 patients over 50 years of age, from the Diabetic Board of Trustees in Zone 1, Guatemala. Data on sociodemographic characteristics, anthropometric measurements and blood were obtained. The blood samples were processed in iCroma ll to determine the values of ultrasensitive reactive Protein C (PCR-us). Results: the patients who accepted to be part of the study had a mean age of 62 ± 8.62 SD years; 74.4% (146) were female; 54% (106) were catholic, and 82.1% (161) resided in Guatemala City. Nutritional status was normal in 50 patients (26%), 21, overweight (11%) and 125, obese (63%). For the waisthip index, with respect to the female, an average of 0.89 ± 0.05 SD and for males, an average 0.97 ± 0.05 SD were obtained. Regarding cardiovascular risk, an average in PCR-us values of 2.9 ± 2.8 SD was obtained; 76% (148) of patient were at moderate / high cardiovascular risk.

Biogénesis y mecanismo de acción de los MicroARN como biomarcadores séricos en las enfermedades cardiovasculares / Biogenesis and mechanism of action of MicroRNAs as serum biomarkers in cardiovascular diseases

Las enfermedades cardiovasculares constituyen la principal causa de mortalidad y morbilidad en el mundo actualmente, lo que obliga a la realización de los continuos avances en las estrategias diagnóstico precoz y tratamiento con el fin de mejorar el pronóstico y disminuir la mortalidad. Sin duda esto abre las puertas al campo de la investigación y en los últimos años aparecen los llamados biomarcadores séricos y entre ellos los microARN (miARN) que juegan un papel fundamental tanto en el desarrollo y como en la regulación del sistema cardiovascular. Los microARN tienen un tamaño de 19-25 nucleótidos, son el grupo de ARN de pequeño tamaño que ha atraído mayor atención durante los últimos años. Hasta la fecha, se han identificado aproximadamente unos 2500 miARN en el genoma humano. Los miARN desempeñan un papel en la regulación de diversos procesos biológicos, como la embriogénesis, la proliferación y diferenciación celular, la apoptosis o la tumorogénesis. En el sistema cardiovascular, los miARN controlan el crecimiento y la contractilidad de los cardiomiocitos, el desarrollo y mantenimiento del ritmo cardíaco, la formación de la placa arterioesclerótica, el metabolismo de los lípidos y la angiogénesis. Además están vinculados en la fisiopatología de varias enfermedades cardiovasculares, fundamentalmente la insuficiencia cardiaca, el infarto de miocardio, la enfermedad coronaria, la ateroesclerosis, y las cardiomiopatías de diversas etiologías, de allí que su determinación en la circulación podría ser de utilidad en la práctica clínica como potencial biomarcador diagnóstico y pronóstico de las enfermedades cardiovasculares. Palabras clave: Micro RNA; Enfermedades cardiovasculares; Biomarcadores séricos.

Cardiovascular diseases are the main cause of mortality and morbidity in the world today, which forces the continuous progress in early diagnosis and treatment strategies in order to improve the prognosis and decrease mortality. Undoubtedly this opens the doors to the field of research and in recent years there are the so-called serum biomarkers and among them microRNAs (miRNAs) that play a fundamental role both in the development and in the regulation of the cardiovascular system. The microRNAs are 19 to 25 nucleotides in size, they are the small group of RNA that has attracted the most attention in recent years. To date, approximately 2,500 miRNAs have been identified in the human genome. The miRNAs play a role in the regulation of various biological processes, such as embryogenesis, cell proliferation and differentiation, apoptosis or oncogenesis. In the cardiovascular system, miRNAs control the growth and contractility of cardiomyocytes, the development and maintenance of heart rhythm, the formation of atherosclerotic plaque, lipid metabolism and angiogenesis. They are also linked in the pathophysiology of several cardiovascular diseases, mainly heart failure, myocardial infarction, coronary heart disease, atherosclerosis, and cardiomyopathies of various etiologies, hence their determination in circulation could be useful in clinical practice as a potential biomarker in the diagnosis and prognosis of cardiovascular diseases. Keywords: Micro RNA; Cardiovascular diseases; Serum biomarkers.

Does Cystatin C have a role as metabolic surrogate in peritoneal dialysis beyond its association with residual renal function? / Teria a Cistatina C um papel como substituto metabólico na diálise peritoneal além de sua associação com a função renal residual?

ABSTRACT Introduction: It has been suggested that cystatin C levels are modified by obesity and inflammation. Furthermore, cystatin C has been associated with cardiovascular events and mortality outcomes. Aim: To study the association of cystatin C with the metabolic profile and cardiovascular disease of peritoneal dialysis patients. Methods: Data collected included clinical, laboratorial, and multifrequency bioimpedance assessment of 52 stable peritoneal dialysis patients. Minimal residual renal function was defined as > 2mL/min/1.73m2. Results: Serum cystatin C was not significantly associated with peritoneal or urinary cystatin C excretion. Negative correlation of cystatin C with normalized protein catabolic rate (rho -0.33, p = 0.02) and a trend towards positive correlation with relative body fat (rho 0.27, p = 0.05) were not independent from residual renal function. Cystatin C was not significantly associated with cardiovascular disease (p = 0.28), nor with glycated hemoglobin (p = 0.19) or c-reactive protein (p = 0.56). In the multivariate model, both age and diabetes were the strongest predictors of cardiovascular disease (odds ratio 1.09, p = 0.029 and odds ratio 29.95, p = 0.016, respectively), while relative body fat was negatively associated with cardiovascular disease (p = 0.038); neither cystatin C (p = 0.096) nor minimal residual renal function (p = 0.756) reached a significant association with cardiovascular disease. Conclusions: In this group of peritoneal dialysis patients, cystatin C did not correlate with the metabolic or inflammatory status, nor cardiovascular disease, after adjustment for residual renal function.

RESUMO Introdução: Tem sido sugerido que os níveis de cistatina C são modificados pela obesidade e inflamação. Além disso, a cistatina C tem sido associada a eventos cardiovasculares e desfechos de mortalidade. Objetivo: Estudar a associação da cistatina C com o perfil metabólico e doença cardiovascular de pacientes em diálise peritoneal. Métodos: Os dados coletados incluíram avaliação clínica, laboratorial e de bioimpedância múltipla de 52 pacientes estáveis em diálise peritoneal. A função renal residual mínima foi definida como > 2mL/min/1,73m2. Resultados: A cistatina C sérica não esteve significativamente associada à excreção peritoneal ou urinária. A correlação negativa da cistatina C com a taxa catabólica protéica normalizada (rho -0,33, p = 0,02) e uma tendência de correlação positiva com a gordura corporal relativa (rho 0,27, p = 0,05) não foram independentes da função renal residual. A cistatina C não se associou significativamente à doença cardiovascular (p = 0,28), nem com hemoglobina glicada (p = 0,19) ou proteína C reativa (p = 0,56). No modelo multivariado, idade e diabetes foram os mais fortes preditores de doença cardiovascular (razões de probabilidade 1,09, p = 0,029 e 29,95, p = 0,016, respectivamente) enquanto a gordura corporal relativa se associou negativamente à doença cardiovascular (p = 0,038). A cistatina C não se associou significativamente com doença cardiovascular (p = 0,096), tampouco a função residual mínima (p = 0,756). Conclusão: Neste grupo de pacientes em diálise peritoneal, a cistatina C não se correlacionou com o estado metabólico ou inflamatório, nem com doença cardiovascular, após ajuste para função renal residual.

Evaluation of monocyte to high-density lipoprotein ratio, lymphocytes, monocytes, and platelets in psoriasis,

Abstract Background: Psoriasis is a chronic immune-mediated inflammatory skin disease that is associated with cardiovascular comorbidities. Objectives: The objective of this retrospective study is to assess the C-reactive protein, monocyte-to-high-density-lipoprotein ratio, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and monocyte-to-lymphocyte ratio as inflammatory markers in patients with psoriasis and to search for a relationship between these parameters and psoriasis severity, as defined by the psoriasis area and severity index. Methods: There were 94 patients with psoriasis and 118 healthy controls enrolled in the study. The C-reactive protein, monocyte-to-high-density-lipoprotein ratio, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and monocyte-to-lymphocyte ratio values of two groups were retrospectively evaluated. Results: Statistically significant differences were observed in terms of C-reactive protein, monocyte-to-high-density-lipoprotein ratio, neutrophil-to-lymphocyte ratio and monocyte-to-lymphocyte ratio between the patient and control groups (p = 0.001, p = 0.003, p = 0.038, and p = 0.007, respectively). Positive correlations were found between the psoriasis area and severity index and the values of C-reactive protein, monocyte-to-high-density-lipoprotein ratio, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and monocyte-to-lymphocyte ratio (r: 0.381; p < 0.01, r: 0.203; p < 0.05, r: 0.268; p < 0.01, r: 0.374; p < 0.01, r: 0.294; p < 0.01, respectively). Study limitations: The small sample size and the retrospective design of the study are limitations. Conclusion: Elevated C-reactive protein, monocyte-to-high-density-lipoprotein ratio, neutrophil-to-lymphocyte ratio, and monocyte-to-lymphocyte ratio were significantly associated with psoriasis. A positive correlation between C-reactive protein and monocyte-to-high-density-lipoprotein ratio leads to the suggestion that monocyte-to-high-density-lipoprotein ratio might be a reliable parameter in psoriasis during the follow-up. The relationship between the diasease and inflammatory parameters might provide early detection of cardiovascular morbidities in psoriasis patients.

Inflammatory Biomarkers and Carotid Thickness in HIV Infected Patients under Antiretroviral Therapy, Undetectable HIV-1 Viral Load, and Low Cardiovascular Risk / Biomarcadores Inflamatórios e Espessura Carotídea em Pacientes Infectados pelo HIV em Terapia Antirretroviral, com Carga Viral de HIV-1 Indetectável e Baixo Risco Cardiovascular

Abstract Background: People living with HIV are at increased risk of cardiovascular disease and carotid thickness, due to the inflammation caused by the virus, the antiretroviral therapy, and other risk factors. However, few studies have observed the occurrence of cardiovascular diseases and carotid thickness in HIV-positive population at low cardiovascular risk and with undetectable viral load. Objectives: To evaluate the association between levels of inflammatory markers and carotid thickness in people living with HIV, under antiretroviral therapy and at low cardiovascular risk. Methods: To determine low cardiovascular risk in both groups (HIV infected and non-infected individuals), the Framingham Risk Score was used. Inflammatory markers (IFN-γ, TNF-α, IL-1β, IL-6, sVCAM-1, and sICAM-1) were assessed using flow cytometry. Carotid thickness (mm) was measured using Doppler ultrasound. Level of significance was p < 0.05. Results: In People living with HIV, age and smoking status were associated with carotid thickness alterations. In the non-HIV group, age, higher total cholesterol, and LDL levels were associated with increased carotid thickness. Using the multivariate analysis, a significant association between TNF-α and IL- 1( levels, and a higher chance of atherosclerosis development in HIV group were observed. Conclusions: Both groups have a similar risk for developing cardiovascular disease, therefore our study demonstrates that HIV-positive individuals with undetectable viral load in antiretroviral therapy without protease inhibitors and with low cardiovascular risk do not present differences in carotid thickness in relation to uninfected individuals.

Resumo Fundamento: As pessoas que vivem com HIV têm um risco aumentado de doença cardiovascular e espessamento da carótida, devido à inflamação causada pelo vírus, à terapia antirretroviral e a outros fatores de risco. No entanto, poucos estudos observaram a ocorrência de doenças cardiovasculares e espessamento carotídeo na população soropositiva com baixo risco cardiovascular e carga viral indetectável. Objetivos: Avaliar a associação entre níveis de marcadores inflamatórios e espessura da carótida em pessoas vivendo com HIV, sob terapia antirretroviral e com baixo risco cardiovascular. Métodos: Para determinar o baixo risco cardiovascular em ambos os grupos (indivíduos infectados e não-infectados pelo HIV), foi utilizado o Escore de Risco de Framingham. Os marcadores inflamatórios (IFN-γ, TNF-α, IL-1β, IL-6, sVCAM-1 e sICAM-1) foram avaliados por citometria de fluxo. A espessura da carótida (mm) foi mensurada por meio de ultrassom com Doppler. O nível de significância foi de p < 0,05. Resultados: Em pessoas vivendo com HIV, a idade e o tabagismo foram associados a alterações da espessura da carótida. No grupo não-HIV, idade e níveis mais altos de colesterol total e LDL foram associados ao aumento da espessura da carótida. Utilizando a análise multivariada, observou-se associação significativa entre os níveis de TNF-α e IL-1β e maior chance de desenvolvimento de aterosclerose no grupo com HIV. Conclusão: Ambos os grupos têm risco semelhante de desenvolver doença cardiovascular, portanto, nosso estudo demonstra que indivíduos HIV-positivos com carga viral indetectável em terapia antirretroviral sem inibidores de protease e com baixo risco cardiovascular não apresentam diferenças na espessura da carótida em relação aos indivíduos não-infectados.

Associações entre consumo de produtos lácteos, proteína C-reativa e perfil lipídico em adultos: resultados do ELSA-Brasil / Associations between consumption of dairy products, C-reactive protein, and lipid profile in adults: results of the ELSA-Brasil study / Asociaciones entre consumo de productos lácteos, proteína C-reativa y perfil lipídico en adultos: resultados del ELSA-Brasil

Anormalidades lipídicas e inflamação sistêmica subclínica estão associadas ao processo de aterosclerose, sendo utilizadas como marcadores de risco cardiovascular. Estudos sugerem um possível efeito benéfico dos produtos lácteos na saúde cardiovascular, mas os resultados em marcadores lipídicos e inflamatórios ainda são controversos. O objetivo deste trabalho foi avaliar a associação entre o consumo de produtos lácteos e seus diferentes subgrupos e proteína C-reativa (PCR), LDL-colesterol (LDL-C) e razão triglicerídeo/HDL-colesterol (TG/HDL-C) nos participantes do Estudo Longitudinal de Saúde do Adulto (ELSA-Brasil) (n = 9.372). O consumo de lácteos foi avaliado por meio de questionário de frequência alimentar validado e apresentado em porções/dia. O consumo total de lácteos foi descrito em quatro categorias (≤ 1 porção/dia a > 4 porções/dia). As associações foram estimadas por meio do odds ratios (OR), utilizando-se o grupo de menor consumo (≤ 1 porção/dia) como referência. Os menores valores de OR para TG/HDL-C no modelo multivariado (0,70; IC95%: 0,55-0,90 em homens; e 0,55; IC95%: 0,43-0,70 em mulheres) foram encontrados no grupo com consumo > 4 porções/dia de lácteos totais. Esses resultados foram apoiados pelas associações inversas encontradas entre diferentes subgrupos de lácteos e a razão TG/HDL-C. Não foi encontrada associação entre consumo de produtos lácteos e seus subgrupos e valores de LDL-C e de PCR. Os resultados sugerem um possível efeito benéfico dos lácteos no perfil lipídico, porém são necessárias evidências de estudos longitudinais e de intervenção que elucidem os mecanismos de efeito dos diferentes tipos de lácteos.

Lipid abnormalities and subclinical systemic inflammation are associated with atherosclerosis and are used as markers of cardiovascular risk. Studies have suggested a possible beneficial effect of dairy products on cardiovascular health, but the results in lipid and inflammatory markers are still controversial. This study aimed to assess the association between consumption of dairy products and their different subgroups and C-reactive protein (CRP), LDL-cholesterol (LDL-C), and triglyceride/HDL-cholesterol ratio (TG/HDL-C) in participants in the Longitudinal Study of Adult Health (ELSA-Brasil) (n = 9,372). Consumption of dairy products was assessed via a validated food frequency questionnaire and expressed as servings/day. Total consumption of dairy products was described in four categories (≤ 1 serving/day to > 4 servings/day). The associations were estimated via odds ratios (OR), using the group with the lowest consumption (≤ 1 serving/day) as the reference. The lowest ORs for TG/HDL-C in the multivariate model (0.70; 95%CI: 0.55-0.90 in men; and 0.55; 95%CI: 0.43-0.70 in women) were found in the group that consumed > 4 servings day of dairy products. These results were supported by the inverse associations between different subgroups of dairy products and the TG/HDL-C ratio. No association was found between consumption of dairy products and their subgroups and LDL-C and CRP. The results suggest a possible beneficial effect of dairy products on lipid profile, but longitudinal and intervention studies are needed to elucidate the effect mechanisms of different types of dairy products.

Las anormalidades lipídicas e inflamación sistémica subclínica están asociadas con el proceso de arteriosclerosis, siendo utilizadas como marcadores de riesgo cardiovascular. Los estudios sugieren un posible efecto benéfico de los productos lácteos en la salud cardiovascular, pero los resultados en marcadores lipídicos e inflamatorios todavía son controvertidos. El objetivo de este estudio fue evaluar la asociación entre el consumo de productos lácteos y sus diferentes subgrupos y proteína C-reativa (PCR), LDL-colesterol (LDL-C) y razón triglicéridos/HDL-colesterol (TG/HDL-C) en los participantes del Estudio Longitudinal de Salud del Adulto (ELSA-Brasil) (n = 9.372). El consumo de lácteos fue evaluado mediante un cuestionario de frecuencia alimentaria validado, y presentado en porciones/día. El consumo total de lácteos se describió en cuatro categorías (≤ 1 porción/día a > 4 porciones/día). Las asociaciones fueron estimadas mediante odds ratios (OR), utilizando el grupo de menor consumo (≤ 1 porción/día) como referencia. Los menores valores de OR para TG/HDL-C en el modelo multivariado (0,70; IC95%: 0,55-0,90 en hombres; y 0,55; IC95%: 0,43-0,70 en mujeres) se encontraron en el grupo con consumo > 4 porciones/día de lácteos totales. Estos resultados se apoyaron en las asociaciones inversas encontradas entre diferentes subgrupos de lácteos y la razón TG/HDL-C. No se encontró asociación entre consumo de productos lácteos y sus subgrupos y valores de LDL-C y de PCR. Los resultados sugieren un posible efecto benéfico de los lácteos en el perfil lipídico, pese a que se necesitan evidencias de estudios longitudinales y de intervención que eluciden los mecanismos de efecto de los diferentes tipos de lácteos.

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.

Niveles de colesterol no HDL en la población chilena y su asociación con enfermedad cardiovascular y diabetes mellitus: estudio de corte transversal en Encuesta Nacional de Salud 2009-2010 / Non-HDL cholesterol levels in Chilean population and their association with diabetes mellitus and cardiovascular disease

Background Despite aggressive treatment aimed at lowering LDL cholesterol (LDL-C) levels with statins, there is a high residual prevalence of cardiovascular diseases, which may depend on plasma cholesterol transported in other atherogenic lipoproteins. Aims To describe non-HDL cholesterol (non-HDL-C) levels in the Chilean population and their association with diabetes mellitus and cardiovascular disease. To evaluate compliance with non-HDL-C therapeutic goals -according to individual cardiovascular risk- at different levels of triglycerides, in comparison with LDL-C goal achievement. Material and Methods: We analyzed data from 2,792 Chilean subjects aged ≥ 15 years who were included in the 2009-2010 National Health Survey and had valid data for blood lipids, diabetes, and cardiovascular disease. Results Forty five percent of subjects had high non-HDL-C levels. The proportion of diabetic and non-diabetic subjects with high non-HDL-C levels was 81 and 42%, respectively (p < 0.01). A significant discordance was observed in the achievement of therapeutic objectives when LDL-C or non-HDL-C levels were considered, particularly in presence of triglycerides ≥ 150 mg/dl. Namely, 8% of the population showed elevated levels of high non-HDL-C despite adequate LDL-C levels. Conclusions Evaluation and management of elevated non-HDL-C in patients with adequate levels of LDL-C seems worthwhile considering the discordance observed between these blood cholesterol fractions. This strategy may be effective to reduce the residual cardiovascular risk in the Chilean population.

Cardiovascular risk assessment using the lipid accumulation product index among primary healthcare users: a cross-sectional study

ABSTRACT BACKGROUND: The lipid accumulation product (LAP) index is an abdominal adiposity marker. OBJECTIVE: The aim of this study was to describe the cardiovascular risk of primary healthcare users through the LAP index and correlate it with anthropometric and biochemical indicators. DESIGN AND SETTING: Cross-sectional study in primary care units in a city in northeastern Brazil. METHODS: The subjects responded to a structured questionnaire that contained questions about their sociodemographic condition, and then underwent an anthropometric nutritional assessment. The LAP index values were expressed as three degrees of cardiovascular risk intensity: high risk (above the 75th percentile), moderate risk (between the 25th and 75th percentiles) and low risk (below the 25th percentile). RESULTS: The median LAP index was 52.5 cm.mmol/l (range: 28.2-86.6), and there was no statistically significant difference between the sexes: 57.7 cm.mmol/l (24.5-91.1) and 49.5 cm.mmol/l (29.8-85.2) for females and males, respectively (P = 0.576). Among all the subjects, 67.2% were overweight and there was a statistically significant difference in mean LAP index between those who were and those who were not overweight. Statistically significant differences in anthropometric and biochemical markers for cardiovascular risk were observed among individuals who had higher LAP index values. There were significant correlations between the LAP index and all of the biochemical variables. CONCLUSIONS: These significant correlations between the LAP index and the traditional biochemical risk markers may be useful within conventional clinical practice, for cardiovascular risk screening in primary healthcare.

Cardiometabolic risk factors associated with active commuting to school / Fatores de risco cardiometabólicos associados ao deslocamento ativo à escola

ABSTRACT Objective: To verify if there is an association between cardiometabolic risk factors and active daily commuting to school among children and adolescents. Methods: A total of 1,743 schoolchildren aged 7 to 17 years old were evaluated in the city of Santa Cruz do Sul (RS). The way of commuting to school was investigated with a questionnaire, and the cardiometabolic risk factors analyzed were body mass index (BMI), waist circumference (WC), systolic (SBP) and diastolic (DBP) blood pressure, blood glucose, triglycerides, total cholesterol (TC) and fractions, LDL and HDL. Results: The prevalence of active commuting among schoolchildren was 48.0% (95%CI 45.7-50.4), and it was associated, in the crude analysis, with blood glucose and LDL cholesterol levels. Passive schoolchildren had a 1.1 higher prevalence ratio of high glucose and LDL cholesterol levels. However, when sociodemographic variables were included in the model, these associations were not maintained. Conclusions: The prevalence of active commuting in the sample studied is low and it was shown to have a crude association with glucose and LDL cholesterol levels in students. However, sociodemographic factors seem to influence these associations.

RESUMO Objetivo: Verificar se existe associação entre fatores de risco cardiometabólicos e deslocamento ativo à escola em crianças e adolescentes. Métodos: Foram avaliados 1.743 escolares, de sete a 17 anos, do município de Santa Cruz do Sul (RS). A forma de deslocamento até a escola foi investigada por meio de questionário e os fatores de risco cardiometabólicos analisados foram: o índice de massa corpórea (IMC), a circunferência da cintura (CC), a pressão arterial sistólica (PAS) e a diastólica (PAD), glicose, triglicerídeos, colesterol total (CT), LDL e HDL. Resultados: A prevalência de deslocamento ativo entre os escolares foi de 48,0% (IC95% 45,7-50,4) e associou-se, na análise bruta, com os níveis de glicose e colesterol LDL. Escolares que se deslocavam de forma passiva apresentaram uma razão de prevalência (RP) 1,1 vez maior de glicose e colesterol LDL elevados. No entanto, ao serem incluídas variáveis sociodemográficas no modelo, essas associações não se mantiveram. Conclusões: Conclui-se que a prevalência de deslocamento ativo na amostra estudada é baixa e que o deslocamento ativo à escola apresentou associação bruta com os níveis sanguíneos de glicose e de colesterol LDL dos escolares, sendo que se deslocar de forma ativa parece auxiliar na redução desses níveis. Porém, fatores sociodemográficos parecem exercer influência sobre estas associações.

Reduction of relative handgrip strength and cardiometabolic risk in individuals with HIV/AIDS

Abstract INTRODUCTION: Low handgrip strength (HS) is associated with cardiometabolic alterations that have affected people with HIV/AIDS. METHODS: This was a cross-sectional study performed in adults receiving antiretroviral treatment. HS was evaluated using a dynamometer and divided by body weight to obtain the relative strength. The association between relative HS and overweight, increased waist circumference (WC), high body fat percentage, glycemia, and lipid ratios were assessed using logistic regression. RESULTS: Low relative HS was identified in 35% of participants and associated with increased WC (odds ratio = 9.7; 95% confidence interval = 2.8-33.0). CONCLUSIONS: The prevalence of low HS was high and associated with increased WC.

Association of alanine aminotransferase concentration with cardiometabolic risk factors in children and adolescents: the CASPIAN-V cross-sectional study

ABSTRACT BACKGROUND: It has been suggested that the levels of some liver enzymes, and especially alanine aminotransferase (ALT), might be correlatable with cardiometabolic risk factors. We investigated the relationship between ALT concentration and cardiometabolic risk factors among children and adolescents. DESIGN AND SETTING: This nationwide study in Iran was conducted within the framework of the fifth survey of a national surveillance program known as the Childhood and Adolescence Surveillance and PreventIon of Adult Non-communicable disease study (CASPIAN-V). METHODS: The participants comprised 4200 students aged 7-18 years, who were recruited through multi-stage random cluster sampling in 30 provinces in Iran. Physical examinations and laboratory tests were conducted in accordance with standard protocols. RESULTS: Overall, 3843 students (participation rate: 91.5%) completed the survey. Mean ALT levels were significantly higher in individuals with dyslipidemia, in terms of elevated total cholesterol (TC) or LDL-cholesterol or triglycerides (TG), excess weight and dyslipidemia. Some cardiometabolic risk factors were associated with higher levels of ALT, with the following odds ratio (OR) and 95% confidence interval (CI):metabolic syndrome (OR: 1.013; 95% CI: 1.001-1.025); elevated TC (OR: 1.060; 95% CI: 1.039-1.081), elevated LDL (OR: 1.031; 95% CI: 1.016-1.046), elevated TG (OR: 1.056; 95% CI: 1.040-1.072) and dyslipidemia (OR: 1.051; 95% CI: 1.034-1.068). CONCLUSION: This large population-based study revealed that some cardiometabolic risk factors were significantly associated with ALT levels. These findings suggest that an association with fatty liver is an underlying mechanism for development of cardiometabolic risk factors.

Association Between Increased Levels of Cystatin C and the Development of Cardiovascular Events or Mortality: A Systematic Review and Meta-Analysis / Associação entre Níveis Elevados de Cistatina C e o Desenvolvimento de Eventos Cardiovasculares ou Mortalidade: Uma Revisão Sistemática e Meta-Análise

Abstract Background: Cystatin C seems promising for evaluating the risk of cardiovascular events and mortality. Objective: To evaluate the association between high levels of cystatin C and the development of cardiovascular events or mortality. Methods: The articles were selected in the Medline/PubMed, Web of Science, and Scielo databases. The eligibility criteria were prospective cohort observational trials that assessed the association of high serum levels of cystatin C with the development of cardiovascular events or mortality in individuals with normal renal function. Only studies that evaluated the mortality outcome compared the fourth with the first quartile of cystatin C and performed multivariate Cox's proportional hazard regression analysis were included in the meta-analysis. A p value < 0,05 was considered significant. Results: Among the 647 articles found, 12 were included in the systematic review and two in the meta-analysis. The risk of development of adverse outcomes was assessed by eight studies using the hazard ratio. Among them, six studies found an increased risk of cardiovascular events or mortality. The multivariate regression analysis was performed by six studies, and the risk of developing adverse outcomes remained significant after the analysis in four of these studies. The result of the meta-analysis [HR = 2.28 (1.70-3.05), p < 0.001] indicated that there is a significant association between high levels of cystatin C and the risk of mortality in individuals with normal renal function. Conclusion: There is a significant association between high levels of cystatin C and the development of cardiovascular events or mortality in individuals with normal renal function.

Resumo Fundamento: A cistatina C tem-se mostrado promissora para avaliação do risco de eventos cardiovasculares e mortalidade. Objetivo: Avaliar a associação entre níveis elevados de cistatina C e o desenvolvimento de eventos cardiovasculares ou mortalidade. Métodos: A seleção dos artigos foi realizada por meio das bases de dados Medline/PubMed, Web of Science e Scielo. Os critérios de elegibilidade foram estudos observacionais de coorte prospectivos que avaliaram a associação entre níveis séricos elevados de cistatina C e o desenvolvimento de eventos cardiovasculares ou mortalidade em indivíduos com função renal normal. Apenas os estudos que avaliaram o desfecho mortalidade, que compararam o quarto com o primeiro quartil de cistatina C e que realizaram análise de regressão multivariada de riscos proporcionais de Cox foram incluídos na meta-análise. Foi considerado significativo o valor p < 0,05. Resultados: Dentre os 647 artigos encontrados, 12 foram incluídos na revisão sistemática e dois na meta-análise. O risco de desenvolvimento dos desfechos adversos foi avaliado por oito estudos por meio do cálculo do hazard ratio. Dentre estes, seis estudos encontraram um maior risco de eventos cardiovasculares ou mortalidade. A análise de regressão multivariada foi realizada por seis destes estudos, e o risco de desenvolvimento dos desfechos adversos permaneceu significativo após realização desta análise em quatro destes estudos. O resultado da meta-análise [HR = 2,28 (1,70-3,05), p < 0,001] indicou que há uma associação significativa entre níveis elevados de cistatina C e o risco de mortalidade nos indivíduos com função renal normal. Conclusão: Há uma associação significativa entre níveis elevados de cistatina C e o desenvolvimento de eventos cardiovasculares ou mortalidade em indivíduos com função renal normal.

Lipid disorders among Black Africans non-users of lipid-lowering medication

ABSTRACT Objective: Angola is a sub-Saharan African country where the population has scarce access to lipidlowering medication. We sought to determine the frequency of lipid disorders among Angolan nonusers of lipid-lowering medication. Material and methods: A cross-sectional descriptive study was carried out in a sample of 604 workers from the public sector. Blood pressure and anthropometric data were measured along with biochemical parameters including total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C). LDL-C to HDL-C ratio (LDL-C/HDL-C) was obtained from LDL-C and HDL-C levels. Results: High frequencies of elevated blood pressure (44.8%), metabolic syndrome (20.2%), increased TC (39.2%) and increased LDL-C (19.3%) were found. Low HDL-C was more frequent in women (62.4% vs. 36.1%, p < 0.001). Isolated hypercholesterolemia was more frequent in men (9.6% vs. 2.5%, p < 0.001). Among men TC, TG, LDL-C and LDL-C/HDL-C ratio were higher and HDL-C was lower in obese than in low-weight and normal-weight participants. Among women TC, TG, LDL-C and LDL-C/HDL-C ratio were higher in obese than in normal-weight participants. Significant linear trend of increasing TC and LDL-C levels as age increased was detected for both genders (p for trend < 0.05). Conclusion: The results of our study showed a high frequency of lipid disorders in Angolan non-users of lipid-lowering medication.

Platelets volume indexes and cardiovascular risk factors

SUMMARY Obesity, diabetes and hypertension are risk factors for cardiovascular diseases (CVD) because they promote a state of hypercoagulability. It is known that platelets play an important role in the development of atherosclerosis. Recent studies have evaluated platelet volume indexes (PVIs) in individuals with risk factors for CVD to better understand the platelet mechanisms involved in their development. The IVPs indirectly estimate platelet function and are easily obtained from automated hematology analyzers, which provide platelet counts, mean platelet volume (MPV), platelet distribution width (PDW) and the platelet-large cell ratio (P-LCR). The present study aims to review literature studies that investigated the association between PVIs and obesity, diabetes, and arterial hypertension, in order to evaluate its use as a potential subclinical marker of CVD. Studies have shown promising results for MPV, an index that allows for early detection of platelet activation and may be useful in identifying patients before the onset of CVD development so that preventive strategies can be implemented. The PDW, although evaluated by a smaller number of studies, also showed promising results. However, there is still a long way to go in order for the MPV and PDW to be used in clinical practice, since there is still a need for more epidemiological evidence, establishing reference values, and standardizing the way results are presented.

RESUMO A obesidade, o diabetes e a hipertensão arterial são fatores de risco para as doenças cardiovasculares (DCV) por promoverem um estado de hipercoagulabilidade. É sabido que as plaquetas desempenham um importante papel no desenvolvimento da aterosclerose. Diante disso, estudos recentes têm avaliado os índices de volumes plaquetários (IVPs) em indivíduos com fatores de risco para DCV, para melhor se entenderem os mecanismos plaquetários envolvidos no seu desenvolvimento. Os IVPs estimam indiretamente a função plaquetária e são facilmente obtidos a partir de analisadores hematológicos automáticos, que fornecem contagens de plaquetas, volume médio de plaquetas (VPM), largura de distribuição de plaquetas (PDW) e a proporção de plaquetas grandes (P-LCR). O presente trabalho tem por objetivo revisar na literatura estudos que investigaram a associação entre os IVPs e obesidade, diabetes e hipertensão arterial, a fim de avaliar o seu uso como potencial marcador subclínico das DCV. Estudos demonstraram resultados promissores quanto ao VPM, um índice que permite uma detecção precoce da ativação de plaquetas e que pode ser útil na identificação de pacientes antes do início do desenvolvimento de DCV, de tal forma que estratégias preventivas possam ser implantadas. O PDW, embora tenha sido avaliado por um número menor de estudos, também demonstrou resultados promissores. Entretanto, ainda existe um longo caminho a se percorrer para que o VPM e o PDW sejam utilizados na prática clínica, pois ainda são necessárias mais evidências epidemiológicas, o estabelecimento de valores de referência e a padronização da forma de expressar os resultados.

Cardiovascular Risk in Xavante Indigenous Population / Risco Cardiovascular na População Indígena Xavante

Abstract Background: The prevalence of cardiovascular risk factors is little known in Brazilian indigenous populations. In the last two decades, important changes have occurred in the lifestyle and epidemiological profile of the Xavante people. Objective: to assess the prevalence of cardiovascular risk factors in Xavante adults in São Marcos and Sangradouro/Volta Grande reserves, in the state of Mato Grosso, Brazil. Methods: Cross-sectional study carried out with 925 Xavante people aged ≥ 20 years between 2008 and 2012. The following indicators were assessed: triglycerides (TG), total, LDL and HDL-cholesterol, Castelli index I and II, TG/HDL-cholesterol ratio, apo B / Apo A1 ratio, Framingham risk score, C-reactive protein, body mass index (BMI), waist circumference (WC), hypertriglyceridemic waist (HW), glycemia and blood pressure. Kolmogorov-Smirnov, Student's t test and Chi-square test (χ2) were used for statistical analysis, and significance level was set at 5%. Results: High prevalence of elevated cardiovascular risk was observed in men and women according to HDL-cholesterol (66.2% and 86.2%, respectively), TG (53.2% and 51.5%), TG/HDL-cholesterol ratio (60.0% and 49.1%), C-reactive protein (44.1% and 48.1%), BMI (81.3% and 81.7%), WC (59.1% and 96.2%), HW (38.0% and 50,6%) and glycemia (46.8% and 70.2%). Individuals aged 40 to 59 years had the highest cardiovascular risk. Conclusions: The Xavante have a high cardiovascular risk according to several indicators evaluated. The present analysis of cardiovascular risk factors provides support for the development of preventive measures and early treatment, in attempt to minimize the impact of cardiovascular diseases on this population.

Resumo Fundamento: A prevalência de fatores de risco cardiovascular ainda é pouco estudada em populações indígenas brasileiras. Nas duas últimas décadas, observaram- se importantes mudanças no estilo de vida e no perfil epidemiológico dos Xavante. Objetivo: Avaliar a prevalência de fatores de risco cardiovascular na população adulta Xavante das Reservas Indígenas de São Marcos e Sangradouro/Volta Grande - MT. Métodos: Estudo transversal realizado com 925 indígenas Xavante com 20 ou mais anos de idade, no período de 2008 a 2012. Foram considerados os indicadores: níveis séricos de triglicérides (TG), colesterol (total, LDL e HDL), Índices de Castelli I (CT/HDL-c) e II (LDL-c/HDL-c), razão TG/HDL-C, relação Apo B/Apo A1, escore de Framingham, proteína C reativa (PCR), Índice de Massa Corporal (IMC), circunferência da cintura (CC), cintura hipertrigliceridêmica (CH), glicemia e pressão arterial. Foram utilizados os testes Kolmogorov-Smirnov, t de Student e Qui quadrado (χ2), sendo considerado um nível de significância de 5%. Resultados: Verificaram-se altas prevalências de risco cardiovascular elevado, em homens e mulheres, respectivamente, segundo os indicadores HDL-colesterol (66,2% e 86,2%), TG (53,2% e 51,5%), razão TG/HDL-c (60,0% e 49,1%), PCR (44,1% e 48,1%), IMC (81,3% e 81,7%), CC (59,1% e 96,2%), CH (38,0% e 50,6%) e glicemia (46,8% e 70,2%). Os indivíduos de 40 a 59 anos foram os que apresentaram maior risco cardiovascular. Conclusões: Os Xavante apresentam elevado risco cardiovascular segundo vários indicadores avaliados. Este inquérito fornece subsídios para ações de prevenção e tratamento precoce, a fim de minimizar os potenciais danos causados por doenças cardiovasculares entre os Xavante.

Evaluation of inflammatory biomarkers, carotid intima-media thickness and cardiovascular risk in HIV-1 treatment-naive patients

Abstract INTRODUCTION Mortality among HIV patients is 3-15 times higher than that among the general population. Currently, most deaths are due to non-infectious diseases. Chronic inflammation and adverse events due to antiretroviral therapy play crucial roles in increasing cardiovascular risk (CVR). METHODS: This cross-sectional study aimed to evaluate carotid intima-media thickness (CIMT) and inflammatory biomarkers (D-dimer, ADAMTS13, GDF-15, sICAM-1, MPO, myoglobin, NGAL, SAA, sVCAM-1, and p-selectin) among naïve patients. RESULTS: Sixty-seven participants were included: median age, 32 years; males, 82.1%; non-white, 61.1%; higher education level, 62.7%; and exposed to HIV through sexual relationship (men who have sex with men), 68.7%. The median viral load and LTCD4+ value were 42,033 copies/mL and 426 cells/mm³. The prevalence of arterial hypertension was 16.4%; those of diabetes mellitus and dyslipidemia were 3% and 70.1%, respectively. The CIMT was 494.08 (± 96.84mm). The mean vascular age was 33.2 ± 18.9 years, one year longer than the chronological age, without statistical significance. CONCLUSIONS The majority of participants had a low CVR (94%). After reclassification, considering the CIMT percentiles, 13 (19.4%) patients had medium/ high CVR, while 54 (80.6%) patients had low CVR. The difference between the proportions of CVR when considering the CIMT and its corresponding percentile was statistically relevant. Body mass index was the only predictor of higher CVR (p = 0.03). No biomarker was found to predict CVR. People living with HIV have a high prevalence of dyslipidemia before ARV therapy.