Angiopoietin-2 confers Atheroprotection in apoE-/- mice by inhibiting LDL oxidation via nitric oxide

Atherosclerosis is promoted by a combination of hypercholesterolemia and vascular inflammation. The function of Angiopoietin (Ang)-2, a key regulator of angiogenesis, in the maintenance of large vessels is unknown. A single systemic administration of Ang-2 adenovirus (AdAng-2) to apoE-/- mice fed a Western diet significantly reduced atherosclerotic lesion size 8 40%) and oxidized LDL and macrophage content of the plaques. These beneficial effects were abolished by the inhibition of nitric oxide synthase (NOS). In endothelial cells, endothelial NOS activation per se inhibited LDL oxidation and Ang-2 stimulated NO release in a Tie2-dependent manner to decrease LDL oxidation. These findings demonstrate a novel atheroprotective role for Ang-2 when endothelial cell function is compromised and suggest that growth factors, which stimulate NO release without inducing inflammation, could offer atheroprotection.

LDL-Lipids from patients with hypercholesterolaemia and Alzheimer's disease are inflammatory to microvascular endothelial cells:mitigation by statin intervention

Elevated LDL concentration in mid-life increases the risk of developing Alzheimer's disease (AD) in later life. Increased oxidative modification (oxLDL) and nitration is observed during dementia and hypercholesterolemia. We investigated the hypothesis that statin intervention in mid-life mitigates the inflammatory effects of oxLDL on the microvasculature. Human microvascular endothelial cells (HMVEC) were maintained on transwells to mimic the microvasculature and exposed to patient and control LDL. Blood was obtained from statin-naïve, normo- and hyperlipidaemic subjects, AD with vascular dementia (AD-plus) and AD subjects (n=10/group) at baseline. Only hyperlipidaemic subjects with normal cognitive function received 40mg simvastatin intervention/day for three months. Blood was re-analysed from normo- and hyper-lipidaemic subjects after three months. LDL isolated from statin-naïve hyperlipidaemic, AD and AD-plus subjects was more oxidised (agarose gel electrophoretic mobility, protein carbonyl content and 8-isoprostane F2α) compared to control subjects. Statin intervention decreased protein carbonyls (2.5±0.4 Vs 3.95±0.2nmol/mg; P<0.001) and 8-isoprostane F2α (30.4±4.0 pg/ml Vs 43.5±8.42 pg/ml; P<0.05). HMVEC treatment with LDL-lipids from hyperlipidaemic, AD and AD-plus subjects impaired endothelial tight junction expression and decreased total glutathione levels (AD; 18.61±1.3, AD-plus; 16.5±0.7nmol/mg protein) compared to untreated cells (23.8±1.2 vs nmol/mg protein). Basolateral IL-6 secretion was increased by LDL-lipids from hyperlipidaemic (78.4±1.9 pg/ml), AD (63.2±5.9 pg/ml) and AD-plus (80.8±0.9 pg/ml) groups compared to healthy subject lipids (18.6±3.6 pg/ml). LDL-Lipids isolated after statin intervention did not affect endothelial function. In summary, LDL-lipids from hypercholesterolaemic, AD and AD-plus patients are inflammatory to HMVEC. In vivo intervention with statins reduces the damaging effects of LDL-lipids on HMVEC.

Oxidised LDL lipids, statins and a blood-brain barrier

Elevated cholesterol in mid-life has been associated with increased risk of dementia in later life. We have previously shown that low density lipoprotein (LDL) is more oxidised in the plasma of dementia patients although total cholesterol levels remained unchanged. Increased systemic oxidative modification (oxLDL) and nitration is also observed during hypercholesterolemia. We have investigated the hypothesis that disruption of blood brain barrier (BBB) function by oxLDL and their lipids may increase risk of neurodegeneration in later life and that statin intervention can mitigate the effects of hyperlipidaemia in mid-life. LDL isolated from statin-naïve hypercholesterolaemic subjects had higher mobility by agarose gel electrophoresis (Rf;0.53±0.06) and 8-isoprostane F2α concentration (43.5±8.42pg/ml) compared to control subjects (Rf; 0.46±0.05 and 24.2±5.37pg/ml respectively; p<0.05). Compared to HMVEC treatment with the LDL-lipids (5μM) from normolipidaemic subjects, LDL-lipids from hypercholesterolaemic subjects increased barrier permeability (103.4±12.5 Ωcm2 v 66.7±7.3 Ωcm2,P<0.01) and decreased cellular glutathione levels (18.5nmol/mg v 12.3nmol/mg) compared to untreated cells (26.2±3.6nmol/mg). LDL-lipids isolated from normolipidaemic subjects shows reduced risk to damage a BBB model compared with LDL-lipids from hypercholesterolaemic subjects. Moreover, a three month statin-intervention reduced the propensity for LDL-lipids from subjects with hyperlipidaemia to damage HMVEC. Post-statin treatment the cytotoxic and pro-inflammatory effects of LDL lipids disappeared. These data support the hypothesis that in vivo intervention with statins modifies LDL lipid oxidation, exerting a protective effect against in microvascular damage independent of cholesterol concentration.

Dietary Quality and Comorbidities of Adults at Medical Risk for Diabetes

Background and aims: The current study evaluates following a special diet with diet quality and comorbidities (hypertension, hypercholesterolemia, and obesity) in four racial/ethnic groups diagnosed with prediabetes or “at risk for diabetes”. Methods and results: This is a cross-sectional analysis of data from the National Health and Nutrition Examination Surveys (NHANES), 2007- 2008 and 2009-2010. Sample weights were used to achieve a representative sample. Data were available for N = 2666 adults, aged ≥20 years (508 Mexican American, 294, Other Hispanic, 616 Black non-Hispanic, and 1248 White non-Hispanic) who were medically diagnosed with either prediabetes or “at risk for diabetes”. Those reporting following a special diet had greater odds of meeting saturated fat guidelines (

The relationship between dietary magnesium intake, stroke and its major risk factors, blood pressure and cholesterol, in the EPIC-Norfolk cohort

Copyright © 2015. Published by Elsevier Ireland Ltd.

The relationship between dietary magnesium intake, stroke and its major risk factors, blood pressure and cholesterol, in the EPIC-Norfolk cohort

Copyright © 2015. Published by Elsevier Ireland Ltd.

The relationship between dietary magnesium intake, stroke and its major risk factors, blood pressure and cholesterol, in the EPIC-Norfolk cohort

Copyright © 2015. Published by Elsevier Ireland Ltd.

Irregularidade do ciclo menstrual no Menacme como marcador para fatores de risco cardiovasculares na pós-menopausa

A associação entre fatores de risco cardiovascular (FRCV) na pósmenopausa e o antecedente de irregularidade menstrual no menacme foi avaliado em estudo caso-controle envolvendo 414 mulheres na pósmenopausa com idade de 60,4 ± 5,5 anos e IMC de 25,3 ± 4,7 kg/m2. As variáveis consideradas foram: caracterização do ciclo menstrual entre 20 e 35 anos (independente) e relato atual sobre ocorrência de hipertensão arterial, dislipidemia, diabetes mellitus e doença arterial coronariana (dependentes). Utilizou-se o teste qui-quadrado e modelos de regressão logística, ajustados para outras variáveis implicadas no risco para doenças CV, com nível de significância 5%. Observou-se que mulheres que relataram irregularidade menstrual prévia estiveram associadas com risco aumentado para ocorrência de algum FRCV [odds ratio ajustado (OR)= 2,14; IC-95%= 1,02–4,48], quando comparadas àquelas com ciclos regulares. Análise estratificada demonstrou as seguintes associações significativas com o antecedente de irregularidade menstrual: hipertensão arterial (OR= 2,4; 95% IC= 1,39–5,41), hipercolesterolemia (OR= 2,32; 95% IC= 1,17–4,59), hipertrigliceridemia (OR= 2,09; 95% IC= 1,10–4,33) e angioplastia coronariana (OR= 6,82; 95% IC= 1,44–32,18). Os dados sugerem que o antecedente de irregularidade menstrual, indicativo da ocorrência da síndrome dos ovários policísticos na idade reprodutiva, pode estar relacionado com aumento do risco para doenças CV na pós-menopausa __________________________________________________ABSTRACT Menstrual Cycle Irregularity as a Marker of Cardiovascular Risk Factors at Postmenopausal Years.To evaluate the association between cardiovascular risk factors (CVRF)during postmenopausal years and previous menstrual irregularity during reproductive years, we performed a case-control study in 414 postmenopausal women (mean age 60.4 ± 5.5 years; BMI 25.3 ± 4.7 kg/m2). The variables assessed were: menstrual cycle characteristics at age 20–35y (independent) and records of arterial hypertension, dyslipidemia, diabetes mellitus, and coronary heart disease (dependent). Statistical analysis used the chi-square test and logistic regression, adjusting for potential confounders for cardiovascular risk, with significance set at 5%. Women reporting previous menstrual irregularity were associated with increased risk for some CVRF [adjusted odds ratio (OR) 2.14; CI-95%= 1.02–4.48], when compared with those reporting regular menstrual cycles. Stratified analysis demonstrated significant associations of previous menstrual irregularity with: arterial hypertension [OR= 2.74; CI-95%= 1.39–5.41), hypercholesterolemia (OR= 2.32; CI-95%= 1.17–4.59), hypertriglyceridemia (OR= 2.09; CI-95%=1.10–4.33), and coronary angioplasty (OR= 6.82; CI-95%= 1.44–32.18). These data suggest that a prior history of menstrual irregularity, as indicative of polycystic ovary syndrome, may be related to increased risk for CVD during postmenopausal years

Irregularidade do ciclo menstrual no Menacme como marcador para fatores de risco cardiovasculares na pós-menopausa

A associação entre fatores de risco cardiovascular (FRCV) na pósmenopausa e o antecedente de irregularidade menstrual no menacme foi avaliado em estudo caso-controle envolvendo 414 mulheres na pósmenopausa com idade de 60,4 ± 5,5 anos e IMC de 25,3 ± 4,7 kg/m2. As variáveis consideradas foram: caracterização do ciclo menstrual entre 20 e 35 anos (independente) e relato atual sobre ocorrência de hipertensão arterial, dislipidemia, diabetes mellitus e doença arterial coronariana (dependentes). Utilizou-se o teste qui-quadrado e modelos de regressão logística, ajustados para outras variáveis implicadas no risco para doenças CV, com nível de significância 5%. Observou-se que mulheres que relataram irregularidade menstrual prévia estiveram associadas com risco aumentado para ocorrência de algum FRCV [odds ratio ajustado (OR)= 2,14; IC-95%= 1,02–4,48], quando comparadas àquelas com ciclos regulares. Análise estratificada demonstrou as seguintes associações significativas com o antecedente de irregularidade menstrual: hipertensão arterial (OR= 2,4; 95% IC= 1,39–5,41), hipercolesterolemia (OR= 2,32; 95% IC= 1,17–4,59), hipertrigliceridemia (OR= 2,09; 95% IC= 1,10–4,33) e angioplastia coronariana (OR= 6,82; 95% IC= 1,44–32,18). Os dados sugerem que o antecedente de irregularidade menstrual, indicativo da ocorrência da síndrome dos ovários policísticos na idade reprodutiva, pode estar relacionado com aumento do risco para doenças CV na pós-menopausa __________________________________________________ABSTRACT Menstrual Cycle Irregularity as a Marker of Cardiovascular Risk Factors at Postmenopausal Years.To evaluate the association between cardiovascular risk factors (CVRF)during postmenopausal years and previous menstrual irregularity during reproductive years, we performed a case-control study in 414 postmenopausal women (mean age 60.4 ± 5.5 years; BMI 25.3 ± 4.7 kg/m2). The variables assessed were: menstrual cycle characteristics at age 20–35y (independent) and records of arterial hypertension, dyslipidemia, diabetes mellitus, and coronary heart disease (dependent). Statistical analysis used the chi-square test and logistic regression, adjusting for potential confounders for cardiovascular risk, with significance set at 5%. Women reporting previous menstrual irregularity were associated with increased risk for some CVRF [adjusted odds ratio (OR) 2.14; CI-95%= 1.02–4.48], when compared with those reporting regular menstrual cycles. Stratified analysis demonstrated significant associations of previous menstrual irregularity with: arterial hypertension [OR= 2.74; CI-95%= 1.39–5.41), hypercholesterolemia (OR= 2.32; CI-95%= 1.17–4.59), hypertriglyceridemia (OR= 2.09; CI-95%=1.10–4.33), and coronary angioplasty (OR= 6.82; CI-95%= 1.44–32.18). These data suggest that a prior history of menstrual irregularity, as indicative of polycystic ovary syndrome, may be related to increased risk for CVD during postmenopausal years

Risco metabólico em crianças de 7 a 12 anos

Introdução – A frequência de dislipidemia em crianças e adolescentes tem vindo a aumentar rapidamente nos últimos anos, estando o seu aparecimento associado a fatores genéticos e ambientais. Este indicador, associado a outras doenças como a obesidade, constituem a síndrome metabólica e são considerados fatores de risco para doença cardiovascular e diabetes, que quando presentes na infância podem conduzir precocemente ao aparecimento destas doenças. Objetivos – Avaliar o perfil de indicadores de saúde de crianças no início de um Programa de Educação Contínua; Verificar os efeitos do Programa de Educação Contínua aplicado durante 36 meses (ginástica funcional, brincadeiras de rua e das aulas de natação), sobre os resultados dos exames iniciais de colesterol, triglicerídeos e do IMC. Métodos - Estudo quantitativo, exploratório e descritivo de corte transversal, realizado entre 2012 e 2015 numa amostra não probabilística por conveniência de 165 crianças, 70,0% da população-alvo. As crianças tinham entre 7 a 12 anos de idade, 40,59% entre 11 e 12 anos e 54% eram do sexo feminino. Eram beneficiárias de um plano de saúde que integrava um programa de intervenção (educação contínua e atividade física), designado Crescendo com Saúde e foram selecionadas através de critérios, como: dislipidemia (colesterol total e/ou triglicerídeos elevados), sobrepeso e/ou obesidade, e história familiar de HAS e DM. Os dados clínicos foram obtidos na consulta de enfermagem, utilizando-se a recolha de sangue para dosemanento do perfil lipídico no início do programa e a cada 6 meses e avaliação do IMC na fase inicial do programa e semanalmente. Para classificação do estado nutricional foram utilizados os pontos de corte da OMS (2007). Resultados – no início do programa 69% das crianças apresentavam hipercolesterolémia, 32% aumento do colesterol, 45% tinham excesso de peso (sobrepeso e obesidade) e 12% risco de sobrepeso. Após o programa de intervenção, das 53% crianças que participaram de forma regular, 29% apresentaram redução do colesterol, 16% dos triglicerídeos e o excesso de peso reduziu em 9%, aumentando contudo o risco de sobrepeso para 22%. Das que participaram de forma irregular, apenas 3% reduziram o perfil lipídico e 1% o estado nutricional. Conclusões – O programa de intervenção permitiu uma redução dos fatores de risco de doença metabólica e permitiu melhorar os hábitos das crianças estudadas e suas famílias. Estes resultados comprovam a eficácia a curto e médio prazo dos programas de intervenção na comunidade, e realçam o papel das intervenções preventivas de educação contínua e de atividade física regular, para o processo de redução dos indicadores de risco metabólico desde a infância. Palavra-chave: Crianças; Perfil lipídico; Obesidade; Programa de intervenção .

Common dyslipidemias, high lipoprotein(a) concentrations and endothelial function in the children of the STRIP study families

Extreme lipid values predisposing on illnesses are dyslipidemias. Dyslipidemias evolve in early childhood, but their significance or persistency is not well known. Common dyslipidemias may aggregate in the same families. This thesis is a part of the longitudinal randomized Special Turku coronary Risk factor Intervention Project STRIP, in which 1054 families with six months old children were randomized to a control or to an intervention group. The family lipid data from the first 11 years was used. Fasting samples at the age of five years defined the lipid phenotypes. The dyslipidemias coexisting in the parent and the child were studied. At the age of 11 years 402 children participated artery ultrasound studies. The significance of the childhood dyslipidemias and lipoprotein(a) concentration on endothelial function was evaluated with the flow mediated arterial dilatation test. Frequently elevated non-HDL cholesterol concentration from one to seven-year-old children associated to similar parental dyslipidemia that improved the predictive value of the childhood sample. The familial combinations were hypercholesterolemia (2.3%), hypertriglyceridemia (2.0%), familial combined hyperlipidemia (1.8%), and isolated low HDL-cholesterol concentration (1.4%). Combined hyperlipidemia in a parent predicted most frequently the child’s hyperlipidemia. High lipoprotein(a) concentration aggregated in some families and associated to childhood attenuated brachial artery dilatation. Hypercholesterolemia and high lipoprotein(a) concentration at five years of age predicted attenuated dilatation. This study demonstrated that parental dyslipidemias and high lipoprotein(a) concentration help to find early childhood dyslipidemias. The association of hypercholesterolemia and lipoprotein(a) concentration with endothelial function emphasizes the importance of the early recognition of the dyslipidemias.

Possible inhibition of hydroxy methyl glutaryl CoA reductase activity by nicotinic acid and ergosterol: as targeting for hypocholesterolemic action.

Objective: Coronary artery diseases including atherosclerosis is considered as commonest problem worldwide. Ergosterols are the main components of vegetable oils and nuts. The objective of this study was to evaluate the potential hypoplipidemic and hypocholesterolemic effects of ergosterol in combination with niacin in rats fed high fat diet (HFD). Methods: Eighty male albino rats were included in this study divided into two main groups: Group I: Normal rats fed standard diet treated with either niacin (8.5 mg /kg b.w) or ergosterol (100 mg/kg b.w) or both. Group II; rats fed HFD treated with either niacin (8.5 mg /kg b.w) or ergosterol (100 mg/kg b.w) or both The feeding and treatment lasted for 8 weeks. Results: A significant elevation in the levels of total cholesterol, triacylglycerol, VLDL-c, LDL-c and atherogenic factor (p<0.001) in rats fed on HFD compared with normal control while HDL-c was significantly reduced in HFD rats compared with control group. Supplementation of diet with niacin or ergosterol or combined exerts improvement in the studied parameters by lowering triacylglycerol, total cholesterol, LDL-c and atherogenic factor and elevate HDL-c near to the value of control. Niacin combined with ergosterol were effective in the reduction of hydroxy methyl glutaryl-CoA reducatase (HMGCoA) compared with control (p<0.001). The combined effect was more potent than individual alone. Conclusion: Utilization of niacin and ergosterol may prevent the hypercholesterolemia and incidence of coronary heart diseases. These functional foods act as nutriceutical as dyslipidemics.

Calcium Intake, Major Dietary Sources and Bone Health Indicators in Iranian Primary School Children

Background: Adequate calcium intake may have a crucial role with regards to prevention of many chronic diseases, including hypertension, hypercholesterolemia, different types of cancer, obesity and osteoporosis. In children, sufficient calcium intake is especially important to support the accelerated growth spurt during the preteen and teenage years and to increase bone mineral mass to lay the foundation for older age. Objectives: This study aimed to assess daily calcium intake in school-age children to ensure whether they fulfill the FGP dairy serving recommendations, the recommended levels of daily calcium intake and to assess the relationship between dietary calcium intake and major bone health indicators. Patients and Methods: A total of 501 Iranian school-age children were randomly selected. Calcium intake was assessed using a semi-quantitative food frequency questionnaire. Bone health indicators were also assessed. Results: Dairy products contributed to 69.3% of the total calcium intake of the children. Daily adequate intake of calcium was achieved by 17.8% of children. Only 29.8% met the Food guide pyramid recommendations for dairy intake. Dietary calcium intake was not significantly correlated with serum calcium and other selected biochemical indicators of bone health. Conclusions: The need for planning appropriate nutrition strategies for overcoming inadequate calcium intake in school age children in the city of Tehran is inevitable.

Frequency of metabolic syndrome in women treated at the Menopause Clinic of the “Dr. José Eleuterio González” University Hospital of the UANL in Northeastern Mexico

Objectives: To determine the frequency of metabolic syndrome (MS) in patients with menopause, and to compare the incidence of MS between surgical and natural menopause. Methods: This was an observational, longitudinal, descriptive, retrospective, unblinded study of cases seen at the Menopause Clinic of the University Hospital “Dr. José eleuterio González” of the Universidad Autónoma de Nuevo León from March 2009 to December 2011. The frequency of MS was determined based on Adult Treatment Panel III (ATPIII) classiication. Results: at the end of the study, 391 patients were evaluated. The mean age was 50.1 years. We found a frequency of MS of 38.1%, the risk factor most often found was low HDL cholesterol (62.5%), followed by obesity (46.5%), hypercholesterolemia (42.3%), hyperglycemia (11.5%), and hypertension (7.7%). The incidence of natural and surgical menopause was 37.6% vs. 39.2% respectively; however, the result was not statistically signiicant (p = 0.093). Conclusions: Patients with menopause are at increased risk of developing MS. it is important to detect MS early in this of patients, when they have one risk factor to avoid complications which may trigger the syndrome. We recommend screening for MS during perimenopause, in order to detect and try to delay it in a timely manner and recommend primary prevention (diet and exercise), or secondary prevention in cases with one or more risk factors.

Frequency of metabolic syndrome in women treated at the Menopause Clinic of the “Dr. José Eleuterio González” University Hospital of the UANL in Northeastern Mexico

Objectives: To determine the frequency of metabolic syndrome (MS) in patients with menopause, and to compare the incidence of MS between surgical and natural menopause. Methods: This was an observational, longitudinal, descriptive, retrospective, unblinded study of cases seen at the Menopause Clinic of the University Hospital “Dr. José eleuterio González” of the Universidad Autónoma de Nuevo León from March 2009 to December 2011. The frequency of MS was determined based on Adult Treatment Panel III (ATPIII) classiication. Results: at the end of the study, 391 patients were evaluated. The mean age was 50.1 years. We found a frequency of MS of 38.1%, the risk factor most often found was low HDL-cholesterol (62.5%), followed by obesity (46.5%), hypercholesterolemia (42.3%), hyperglycemia (11.5%), and hypertension (7.7%). The incidence of natural and surgical menopause was 37.6% vs. 39.2% respectively; however, the result was not statistically signiicant (p = 0.093). Conclusions: Patients with menopause are at increased risk of developing MS. it is important to detect MS early in this of patients, when they have one risk factor to avoid complications which may trigger the syndrome. We recommend screening for MS during perimenopause, in order to detect and try to delay it in a timely manner and recommend primary prevention (diet and exercise), or secondary prevention in cases with one or more risk factors.