Cardiovascular risk and obesity.

BACKGROUND: This is an overview of the mechanisms of obesity and its relation to cardiovascular risks, describing the available treatment options to manage this condition. MAIN BODY: The pathogenesis of obesity includes the balance between calories consumed and energy expenditure followed by the maintenance of body weight. Diet, physical activity, environmental, behavioral and physiological factors are part of the complex process of weight loss, since there are several hormones and peptides involved in regulation of appetite, eating behavior and energy expenditure. The cardiovascular complications associated to obesity are also driven by processes involving hormones and peptides and which include inflammation, insulin resistance, endothelial dysfunction, coronary calcification, activation of coagulation, renin angiotensin or the sympathetic nervous systems. Pharmacological treatments are often needed to insure weight loss and weight maintenance as adjuncts to diet and physical activity in people with obesity and overweight patients. CONCLUSION: To accomplish satisfactory goals, patients and physicians seek for weight loss, weight maintenance and improvement of the risk factors associated to this condition, especially cardiovascular risk.

Nutritional status and food intake of children with cow's milk allergy.

INTRODUCTION AND OBJECTIVES: Cow's milk allergy (CMA) is common, especially in children. The treatment is based on the exclusion of milk and dairy products and guidance regarding the exclusion diet. This study aimed to compare the anthropometric measurements and food intake of children with CMA with those of healthy controls, and to evaluate the serum concentrations of Vitamin A and 25(OH)D in children with CMA. METHODS: This is a cross-sectional study with 27 children in the CMA group and 30 in the control group. z-Scores of body mass index and height, skinfolds, food intake and serum concentrations of retinol, beta-carotene, lycopene, 25(OH)D, parathyroid hormone and high sensitivity C-reactive protein were evaluated. RESULTS: Mean age was four years (±1.9). The CMA group evidenced a lower height compared to those from the control group (p=0.0043). The CMA group showed a lower intake of calcium (p=0.0033) and lipids (p=0.0123). Low serum concentrations of retinol, beta-carotene, lycopene, 25(OH)D were found in 25.9%, 59.3%, 48.1% and 70.3% of the CMA group, respectively. CONCLUSIONS: Children with CMA consume smaller amounts of calcium and lipids and have shorter height compared to healthy controls. Insufficient levels of vitamins A and D were frequent in the CMA group, emphasizing the need for nutritional guidance and monitoring.

Effects of simvastatin/ezetimibe on microparticles, endothelial progenitor cells and platelet aggregation in subjects with coronary heart disease under antiplatelet therapy

It is not known whether the addition of ezetimibe to statins adds cardiovascular protection beyond the expected changes in lipid levels. Subjects with coronary heart disease were treated with four consecutive 1-week courses of therapy (T) and evaluations. The courses were: T1, 100 mg aspirin alone; T2, 100 mg aspirin and 40 mg simvastatin/10 mg ezetimibe; T3, 40 mg simvastatin/10 mg ezetimibe, and 75 mg clopidogrel (300 mg initial loading dose); T4, 75 mg clopidogrel alone. Platelet aggregation was examined in whole blood. Endothelial microparticles (CD51), platelet microparticles (CD42/CD31), and endothelial progenitor cells (CD34/CD133; CDKDR/CD133, or CD34/KDR) were quantified by flow cytometry. Endothelial function was examined by flow-mediated dilation. Comparisons between therapies revealed differences in lipids (T2 and T3<T1 and T4 for total cholesterol, LDL-C, and triglycerides; P<0.002 for all), as well as for endothelial function (T2>T1 and T4, P=0.001). Decreased platelet aggregation was observed after aspirin (arachidonic acid, T1<T3 and T4, P=0.034) and clopidogrel (adenosine, T3 and T4<T1 and T2, P<0.0001) therapy. Simvastatin/ezetimibe diphosphate did not change platelet aggregation, the amount of circulating endothelial and platelet microparticles, or endothelial progenitor cells. Cardiovascular protection following therapy with simvastatin/ezetimibe seems restricted to lipid changes and improvement of endothelial function not affecting the release of microparticles, mobilization of endothelial progenitor cells or decreased platelet aggregation.

Effects of simvastatin/ezetimibe on microparticles, endothelial progenitor cells and platelet aggregation in subjects with coronary heart disease under antiplatelet therapy.

It is not known whether the addition of ezetimibe to statins adds cardiovascular protection beyond the expected changes in lipid levels. Subjects with coronary heart disease were treated with four consecutive 1-week courses of therapy (T) and evaluations. The courses were: T1, 100 mg aspirin alone; T2, 100 mg aspirin and 40 mg simvastatin/10 mg ezetimibe; T3, 40 mg simvastatin/10 mg ezetimibe, and 75 mg clopidogrel (300 mg initial loading dose); T4, 75 mg clopidogrel alone. Platelet aggregation was examined in whole blood. Endothelial microparticles (CD51), platelet microparticles (CD42/CD31), and endothelial progenitor cells (CD34/CD133; CDKDR/CD133, or CD34/KDR) were quantified by flow cytometry. Endothelial function was examined by flow-mediated dilation. Comparisons between therapies revealed differences in lipids (T2 and T3T1 and T4, P=0.001). Decreased platelet aggregation was observed after aspirin (arachidonic acid, T1

Differences in synthesis and absorption of cholesterol of two effective lipid-lowering therapies

Effective statin therapy is associated with a marked reduction of cardiovascular events. However, the explanation for full benefits obtained for LDL cholesterol targets by combined lipid-lowering therapy is controversial. Our study compared the effects of two equally effective lipid-lowering strategies on markers of cholesterol synthesis and absorption. A prospective, open label, randomized, parallel design study, with blinded endpoints, included 116 subjects. We compared the effects of a 12-week treatment with 40 mg rosuvastatin or the combination of 40 mg simvastatin/10 mg ezetimibe on markers of cholesterol absorption (campesterol and β-sitosterol), synthesis (desmosterol), and their ratios to cholesterol. Both therapies similarly decreased total and LDL cholesterol, triglycerides and apolipoprotein B, and increased apolipoprotein A1 (P < 0.05 vs baseline for all). Simvastatin/ezetimibe increased plasma desmosterol (P = 0.012 vs baseline), and decreased campesterol and β-sitosterol (P < 0.0001 vs baseline for both), with higher desmosterol (P = 0.007) and lower campesterol and β-sitosterol compared to rosuvastatin, (P < 0.0001, for both). In addition, rosuvastatin increased the ratios of these markers to cholesterol (P < 0.002 vs baseline for all), whereas simvastatin/ezetimibe significantly decreased the campesterol/cholesterol ratio (P = 0.008 vs baseline) and tripled the desmosterol/cholesterol ratio (P < 0.0001 vs baseline). The campesterol/cholesterol and β-sitosterol/cholesterol ratios were lower, whereas the desmosterol/cholesterol ratio was higher in patients receiving simvastatin/ezetimibe (P < 0.0001 vs rosuvastatin, for all). Pronounced differences in markers of cholesterol absorption and synthesis were observed between two equally effective lipid-lowering strategies.

Differences in synthesis and absorption of cholesterol of two effective lipid-lowering therapies.

Effective statin therapy is associated with a marked reduction of cardiovascular events. However, the explanation for full benefits obtained for LDL cholesterol targets by combined lipid-lowering therapy is controversial. Our study compared the effects of two equally effective lipid-lowering strategies on markers of cholesterol synthesis and absorption. A prospective, open label, randomized, parallel design study, with blinded endpoints, included 116 subjects. We compared the effects of a 12-week treatment with 40 mg rosuvastatin or the combination of 40 mg simvastatin/10 mg ezetimibe on markers of cholesterol absorption (campesterol and ß-sitosterol), synthesis (desmosterol), and their ratios to cholesterol. Both therapies similarly decreased total and LDL cholesterol, triglycerides and apolipoprotein B, and increased apolipoprotein A1 (P < 0.05 vs baseline for all). Simvastatin/ezetimibe increased plasma desmosterol (P = 0.012 vs baseline), and decreased campesterol and ß-sitosterol (P < 0.0001 vs baseline for both), with higher desmosterol (P = 0.007) and lower campesterol and ß-sitosterol compared to rosuvastatin, (P < 0.0001, for both). In addition, rosuvastatin increased the ratios of these markers to cholesterol (P < 0.002 vs baseline for all), whereas simvastatin/ezetimibe significantly decreased the campesterol/cholesterol ratio (P = 0.008 vs baseline) and tripled the desmosterol/cholesterol ratio (P < 0.0001 vs baseline). The campesterol/cholesterol and ß-sitosterol/cholesterol ratios were lower, whereas the desmosterol/cholesterol ratio was higher in patients receiving simvastatin/ezetimibe (P < 0.0001 vs rosuvastatin, for all). Pronounced differences in markers of cholesterol absorption and synthesis were observed between two equally effective lipid-lowering strategies.

Highly sensitive C-reactive protein and male gender are independently related to the severity of coronary disease in patients with metabolic syndrome and an acute coronary event.

Patients with metabolic syndrome are at high-risk for development of atherosclerosis and cardiovascular events. The objective of this study was to examine the major determinants of coronary disease severity, including those coronary risk factors associated with metabolic syndrome, during the early period after an acute coronary episode. We tested the hypothesis that inflammatory markers, especially highly sensitive C-reactive protein (hsCRP), are related to coronary atherosclerosis, in addition to traditional coronary risk factors. Subjects of both genders aged 30 to 75 years (N = 116) were prospectively included if they had suffered a recent acute coronary syndrome (acute myocardial infarction or unstable angina pectoris requiring hospitalization) and if they had metabolic syndrome diagnosed according to the National Cholesterol Education Program/Adult Treatment Panel III. Patients were submitted to a coronary angiography and the burden of atherosclerosis was estimated by the Gensini score. The severity of coronary disease was correlated (Spearman's or Pearson's coefficient) with gender (r = 0.291, P = 0.008), age (r = 0.218, P = 0.048), hsCRP (r = 0.256, P = 0.020), ApoB/ApoA ratio (r = 0.233, P = 0.041), and carotid intima-media thickness (r = 0.236, P = 0.041). After multiple linear regression, only male gender (P = 0.046) and hsCRP (P = 0.012) remained independently associated with the Gensini score. In this high-risk population, male gender and high levels of hsCRP, two variables that can be easily obtained, were associated with more extensive coronary disease, identifying patients with the highest potential of developing new coronary events.

Highly sensitive C-reactive protein and male gender are independently related to the severity of coronary disease in patients with metabolic syndrome and an acute coronary event

Patients with metabolic syndrome are at high-risk for development of atherosclerosis and cardiovascular events. The objective of this study was to examine the major determinants of coronary disease severity, including those coronary risk factors associated with metabolic syndrome, during the early period after an acute coronary episode. We tested the hypothesis that inflammatory markers, especially highly sensitive C-reactive protein (hsCRP), are related to coronary atherosclerosis, in addition to traditional coronary risk factors. Subjects of both genders aged 30 to 75 years (N = 116) were prospectively included if they had suffered a recent acute coronary syndrome (acute myocardial infarction or unstable angina pectoris requiring hospitalization) and if they had metabolic syndrome diagnosed according to the National Cholesterol Education Program/Adult Treatment Panel III. Patients were submitted to a coronary angiography and the burden of atherosclerosis was estimated by the Gensini score. The severity of coronary disease was correlated (Spearman’s or Pearson’s coefficient) with gender (r = 0.291, P = 0.008), age (r = 0.218, P = 0.048), hsCRP (r = 0.256, P = 0.020), ApoB/ApoA ratio (r = 0.233, P = 0.041), and carotid intima-media thickness (r = 0.236, P = 0.041). After multiple linear regression, only male gender (P = 0.046) and hsCRP (P = 0.012) remained independently associated with the Gensini score. In this high-risk population, male gender and high levels of hsCRP, two variables that can be easily obtained, were associated with more extensive coronary disease, identifying patients with the highest potential of developing new coronary events.

Radiographic assessment of Gardner's syndrome.

The detection of osteomas in the maxillofacial region may be the initial clinical finding in Gardner's syndrome (GS). The most common location of osteomas is in the skull, but the lesion can also occur in the jaws. We present a case of a 47 year old male patient with GS who was referred for radiological evaluation. Extraoral examination revealed an epidermoid cyst and the patient had a history of intestinal polyps. A panoramic radiograph demonstrated numerous osteomas and diffuse sclerosis of the mandible, and compound odontomas with impacted teeth. CT scan allowed the localization and extension of the osteomas, and showed other sites in the maxillofacial region as well. CT images also revealed a different behaviour of osteoma, invading the mandibular canal.

Achieving 2003 European lipid goals with rosuvastatin and comparator statins in 6743 patients in real-life clinical practice: DISCOVERY meta-analysis.

BACKGROUND: There is an increasing body of evidence to support the benefits of reducing low-density lipoprotein cholesterol (LDL-C) levels and this has been reflected in a lowering of LDL-C goals recommended by international guidelines. Therefore, there is a growing need for effective lipid-modifying therapies to optimise the achievement of these more stringent LDL-C goals. OBJECTIVE: A meta-analysis of data pooled from five studies participating in the DISCOVERY (DIrect Statin COmparison of LDL-C Values: an Evaluation of Rosuvastatin therapY) Programme was performed to compare the effect of rosuvastatin treatment with other statins in real-life clinical practice. RESULTS: These studies included 6743 patients with hypercholesterolaemia from different ethnicities, countries and cultural environments. The meta-analysis showed that significantly more patients receiving rosuvastatin 10 mg achieved the 2003 European LDL-C goals compared with those who received atorvastatin 10 mg or simvastatin 20 mg (p < 0.001 for both comparisons). A significantly greater proportion of patients receiving rosuvastatin 10 mg also achieved the 2003 European total cholesterol goal compared with those on atorvastatin 10 mg (p < 0.001). CONCLUSIONS: The meta-analysis showed that rosuvastatin was more effective than comparator statins at lowering LDL-C levels and enabling patients to achieve lipid goals at recommended start doses. In addition, all statins studied were well tolerated and confirmed that rosuvastatin had a similar safety profile to other statins.

Relationship between gene polymorphisms and prevalence of myocardial infarction among diabetic and non-diabetic subjects.

This study was aimed to examine cholesteryl ester transfer protein (CETP), apolipoprotein AI and CIII gene polymorphisms, and to verify whether these genetic determinants are associated with the prevalence of myocardial infarction (MI) or type 2 diabetes. The TaqIB restriction fragment length polymorphism (RFLP) in intron I of the CETP gene, the MspI in the third intron of the APOAI gene, and also SstI in the 3' untranslated region of the APOCIII gene were determined using standard methods. The prevalence of these polymorphisms was compared between diabetic (n = 119), and non-diabetic (n = 100) middle-aged individuals of both sexes. We found a higher prevalence of the B2B2 genotype of the CETP gene among diabetics than that observed in non-diabetics (P < 0.05), and a lower prevalence of this genotype among patients with previous MI (P < 0.02). The MspI polymorphisms of the APOAI gene showed that M1++ genotype was found mainly in diabetic patients (P < 0.04). Conversely, the SstI polymorphism of APOCIII gene was not significantly associated with either MI or diabetes. Therefore, among these genetic polymorphisms, TaqIB of CETP and MspI of apolipoprotein AI appeared to help significantly to identify diabetic individuals. In particular, the former may have an additional role in the primary prevention of coronary disease.

Hydrochlorothiazide abolishes the anti-atherosclerotic effect of quinapril.

1. Antihypertensive treatment has been demonstrated to result in persistent reductions in morbidity and mortality due to stroke. However, the coronary risk attributable to hypertension has been only partially reversed. We hypothesized that diuretics could have unfavourable effects on atherosclerosis. 2. New Zealand rabbits were fed a 0.5% cholesterol-enriched diet for 12 weeks, followed by a 0.1% cholesterol diet for another 12 weeks. During the last 12 week period, 40 animals were randomly assigned to one of four groups: (i) group I was the control group; (ii) group II received hydrochlorothiazide (10 mg/day); (iii) group III received quinapril (30 mg/day); and (iv) group IV was treated with hydrochlorothiazide (10 mg/day) plus quinapril (30 mg/day). 3. The treatments did not affect either the lipid profile or serum electrolytes and oxidative stress. However, endothelium-dependent vasorelaxation in isolated aortic rings was significantly improved with quinapril (group III) treatment (P < 0.001 vs other groups). In addition, therapy with quinapril promoted a significant reduction in atherosclerosis (intima area, intima/media ratio and perimeter of vessel with plaque; P < 0.05 vs other groups), as well as in cholesterol content of the aorta (P < 0.05 vs groups II and IV). 4. In conclusion, hydrochlorothiazide did not modify atherosclerosis and, when added to quinapril treatment, impaired the anti-atherosclerotic effect seen with quinapril alone.

Influência da técnica de coleta sobre a taxa de recuperaçäo de embriöes eqüinos / Effect of embryo collection technique on embryo recovery rate in mares

Foram realizadas 114 coletas de embriöes em éguas mestiças das raças Bretä e Campolina, distribuídas ao acaso em dois tratamentos: T1 - fluxo interrompido, método tradicional que utiliza filtro de embriäo (n=56) e T2 - fluxo direto, sem interrupçäo do fluxo e sem utilizaçäo do filtro (n=58). O meio utilizado nas lavagens foi o Ringer lactato. Näo houve diferenças entre tratamentos em relaçäo à taxa de recuperaçäo de embriöes (58,9 e 44,8 por cento), à qualidade dos embriöes (3,56 e 3,53), à taxa de recuperaçäo do meio de coleta (98,1 por cento e 98,1 por cento) e à taxa de gestaçäo (52,9 e 81,8 por cento), respectivamente, para T1 e T2. Observaram-se diferenças entre tratamentos quanto ao tempo de duraçäo da coleta (10,3 e 7,4 minutos) e ao intervalo de tempo da coleta à inovulaçäo (39,5 e 65,7 minutos)

Chronic endothelial dysfunction after oversized coronary balloon angioplasty in pigs: a 12-week follow-up of coronary vasoreactivity in vivo and in vitro.

Previous studies have reported the development of vasoconstriction immediately after invasive coronary interventions. Other studies in animals have demonstrated that using oversized balloon angioplasty, vasospasm can be suppressed, even in the presence of endothelial denudation due to important structural alteration in vascular smooth muscle. The regenerated endothelium also appears to be impaired chronically by selective attenuation of in vitro endothelial dependent relaxation related to pertussis toxin-sensitive G proteins. The purpose of this investigation was to verify in vivo and in vitro vasoreactivity to bradykinin (BK) and serotonin (5-hydroxytryptamine; 5-HT) (endothelial dependent agonists) as well as to nitroglycerin (NTG) (exogenous nitric oxide donor) at different times after oversized balloon angioplasty intervention ranging from 1 h to 12 weeks, in normal porcine coronary arteries. BK-induced vasodilatation in vivo was impaired acutely, but it was restored after 4 weeks. Serotonin caused vasoconstriction in vivo that was significantly augmented after 12 weeks. Conversely, endothelium-dependent vasodilatation in vitro to BK and 5-HT remained attenuated during the whole period of follow-up. Finally, relaxation elicited by NTG was reduced in the in vivo experiment until the first week after the procedure. Histological analysis showed severe arterial injury, and complete recovery of endothelial coverage after 4 weeks. In conclusion, this experiment supports evidence for the occurrence of the acute attenuation of vasoresponsiveness and chronic endothelial dysfunction following overstretching coronary balloon angioplasty. Abnormal remodeling associated with the severity of injury may contribute to chronic endothelial dysfunction. Differences found between in vivo and in vitro studies also suggest that multiple endogenous influences present in the former can attenuate the greater endothelial dysfunction demonstrated by endothelial assessment in vitro.

Fontes lipídicas dietéticas associadas ou näo à gonadotrofina coriônica humana (hCG) na funçäo reprodutiva e no metabolismo de lípides de novilhas / Dietary lipid sources associated or not to hCG on the reproductive function and lipid metabolism of heifers

Vinte e quatro novilhas foram utilizadas para avaliar o efeito de diferentes fontes dietéticas lipídicas associadas ou näo ao hCG sobre os níveis de progesterona e de metabólitos lipídicos e sobre a funçäo luteal cíclica de novilhas. O delineamento experimental foi de blocos ao acaso, em um esquema fatorial de 2 x 3, (com e sem injeçäo de hCG e três dietas isoprotéicas). A concentraçäo sérica de progesterona do sexto ao 12§ dia pós-estro foi maior nas novilhas alimentadas com dietas hiperlipídicas em relaçäo à da dieta-controle. As dietas hiperlipídicas interferiram no perfil metabólico lipídico, especialmente do sexto ao nono dia após o início do estro. Observou-se interaçentre aplicaçäo de hCG e dietas hiperlipídicas. Os metabólitos lipídicos que melhor indicaram alteraçöes metabólicas foram o colesterol total e as lipoproteínas de alta densidade (HDL). Houve correlaçäo positiva entre colesterol total, HDL e concentraçäo de progesterona na fase luteal do ciclo estral. Colesterol total e HDL interferem na funçäo luteal de novilhas, provavelmente como precursores na síntese esteroidogênica do ovário

Amamentaçäo controlada no desempenho reprodutivo de vacas de corte / Limited nursing effects on reproductive performance of beef cows

Utilizaram-se 144 vacas gestantes (Charolês x Zebu) com a finalidade de se estudar a alimentaçäo controlada dos bezerros sobre o desempenho reprodutivo de vacas de corte. As vacas foram aleatoriamente distribuídas em um delineamento experimental completamente casualizado com três tratamentos. T1 - Vacas com bezerros, amamentaçäo livre (controle); T2 - vacas com amamentaçäo controlada uma vez ao dia e T3 - vacas com amamentaçäo livre, interrompida por 72 horas a cada 21 dias. No final do período da estaçäo de monta (15 de setembro a 15 de dezembro), os bezerros voltaram para junto das vacas, sem interrupçöes de mamadas até à desmama. Graus de sangue, ano e suas interaçöes com o tratamento näo interferiram nas características estudadas. Näo houve diferenças quanto à variaçäo de peso da vaca durante o período experimental. A condiçäo corporal foi afetada pelo efeito do tratamento. A melhor condiçäo corporal foi para as vacas que tiveram amamentaçäo controlada uma vez ao dia, seguida pela condiçäo das vacas com separaçäo dos bezerros por 72 horas a cada 21 dias. A maior taxa de fertilidade foi para as vacas do T2, 66,7 por cento, seguida de T3, 45,6 por cento e finalmente T1, 37,5 por cento. As taxas de natalidade foram de 56,2 por cento em T2, 35,4 por cento em T3 e 25,0 por cento em T1. A eficiência média de produçäo das vacas no ano subseqüente (kg de bezerros desmamados por vacas em serviço) foi maior para as vacas do T2, 3907kg, e menor para as vacas do T3 e do T1, com 2577kg e 1864kg, respectivamente