A Single Controlled Exposure to Secondhand Smoke May Not Alter Thrombogenesis or Trigger Platelet Activation.

INTRODUCTION: Chronic secondhand smoke (SHS) exposure increases cardiovascular events, particularly acute thrombotic events. There are little human data on acute SHS exposure. The aim of this study was to determine whether a single controlled exposure of humans to SHS increased thrombogenesis. METHODS: After 6-8 hours fast, subjects (n = 50) were exposed to constant dose SHS (particulate level of 500 µg/m(3)) for 120 minutes in a temperature-regulated and ventilated, simulated bar environment. Blood was drawn before and immediately after SHS exposure for thromboelastography (TEG) and flow cytometry. Maximum clot strength (MA) was measured using TEG and platelet leukocyte aggregates (LPA) were measured as an index of platelet activation. Anti-CD 14 antibodies were used as leukocyte markers and anti-CD 41 antibodies as platelet markers for cytometry. Data were analyzed using students' t test for paired samples. RESULTS: There was no effect of acute exposure to SHS on platelet activation or thrombogenesis. Also, intra group (smokers [n = 19] and nonsmokers [n = 31]) comparisons of LPA and TEG parameters did not show changes with SHS exposure. CONCLUSIONS: While there are abundant data showing enhanced thrombogenesis and platelet activation following repeated exposure to SHS, our study suggests that a single exposure does not appear to significantly alter thrombin kinetics nor result in platelet activation. The effects of SHS on thrombogenesis might be nonlinear.

National alert campaign about increased cholesterol: determination of cholesterol levels in 81,262 Brazilians.

OBJECTIVE: To determine the levels of total cholesterol in a significant sample of the Brazilian population. METHODS: Blood cholesterol was determined in 81.262 individuals > 18 years old (51% male, 44.7 +/- 15.7 years), using Accutrend equipment, in the cities São Paulo, Campinas, Campos do Jordão, São José dos Campos, Santos, Santo André , Ribeirão Preto, Porto Alegre, Rio de Janeiro, Belo Horizonte, Curitiba, Brasília, Salvador and documented in the presence of other risk factors (RF) for coronary artery disease (CAD) (systemic hypertension, CAD in the family, smoking, and diabetes). Participants were classified according to sex, age, and the presence or absence of RF, respectively, as 0 RF, 1 RF and > 2 RF. The percentage of individuals with cholesterol > 200 mg/dL and > 240 mg/dL was evaluated. RESULTS: The prevalence of individuals with 0, 1, and > 2 risk factors was 30% (n = 24,589), 36% (n =29,324), and 34% (n = 27,349) respectively, (P=0.657), and the mean total cholesterol of the population was 199.0 +/- 35.0 mg/dL. Cholesterol levels above 200 and 240 mg/dL were found, respectively, in 40% (n = 32,515) and 13% (10.942) of individuals. The greater the number of risk factors the higher the levels of cholesterol (P<0.0001) and the greater the proportion of individuals with cholesterol > 200 mg/dL (P=0.032). No difference existed in the proportion of individuals with cholesterol > 240 mg/dL (P=0.11). CONCLUSION: A great percentage of individuals with cholesterol levels above those recommended to prevent coronary artery disease was found.

The polymorphism -1131T>C in apolipoprotein A5 gene is associated with dyslipidemia in Brazilian subjects.

BACKGROUND: Polymorphisms in apolipoprotein A5 gene (APOA5) have been associated with higher triglyceride levels in many populations. The aim of the study was to determine the allelic and genotypic distribution of the APOA5 -1131T>C polymorphism and to identify the association of the genetic variant and the risk for dyslipidemia. METHODS: We genotyped 109 dyslipidemic subjects and 107 controls. The total cholesterol, triglycerides and HDL-c were determined enzymatically. Comparison of means among groups was calculated by ANOVA. Significant differences among groups were evaluated by Student-Newman-Keuls test. RESULTS: The minor allele C was more frequent in dyslipidemic subjects than controls (p=0.019) and confers an increased individual risk for dyslipidemia (OR=1.726, CI 95%=1.095-2.721). The genotype analysis by gender showed that this allele was more frequent in dyslipidemic males (p=0.037; OR=2.050, CI 95%=1.042-4.023). When participants were analyzed according to genotypes TT and TC/CC, C-carriers presented higher cholesterol and triglycerides levels than TT homozygous (p=0.046 and 0.049, respectively). CONCLUSIONS: The allele C confers higher total cholesterol and triglycerides levels in dyslipidemic adults. The APOA5 -1131T>C polymorphism is associated with dyslipidemia in male subjects.

Association of lipoprotein lipase D9N polymorphism with myocardial infarction in type 2 diabetes: the genetics, outcomes, and lipids in type 2 diabetes (GOLD) study.

The association of polymorphisms affecting lipid metabolism with the risk of myocardial infarction (MI) in type 2 diabetes mellitus was investigated. The Genetics, Outcomes and Lipids in type 2 Diabetes (GOLD) Study is a prospective, multicenter study, conducted on 990 patients presenting diabetes and MI (n=386), or diabetes without previous manifestation of stroke, peripheral or coronary arterial disease (n=604), recruited from 27 institutions in Brazil. APO A1 (A/G -75 and C/T +83) and APO C3 (C/G 3'UTR) non-coding sequences, CETP (Taq 1B), LPL (D9N), APO E (epsilon2, epsilon3, epsilon4,), PON-1 (Q192R), and two LCAT variants Arg(147)-->Trp and Tyr(171)-->Stop were tested by PCR-RFLP. There was a higher prevalence of LPL DN genotype (19% vs.12%, p=0.03) and a higher frequency of the N allele (11% vs. 7%) among subjects with MI when compared to controls, with an odds ratio of MI for carriers of 9N allele of 2.46 (95% CI=1.79-3.39, p<0.0001). This association was present in men and women, in non-smokers and in hypertensive patients. A logistic regression model including gender, duration of diabetes, systolic blood pressure, HDL-C, left ventricle hypertrophy and D9N polymorphism showed that the latter still remained significantly associated with MI (OR=1.50, 95% CI=1.02-2.25, p=0.049). These findings suggest that D9N polymorphism can be a useful risk marker for myocardial infarction and that further potential candidate genes should be screened for exploratory analysis and for future therapeutic intervention in diabetes.

Homocysteine and methylenetetrahydrofolate reductase in subjects undergoing coronary angiography.

OBJECTIVE: To determine plasma homocysteine levels and the incidence of methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism in a group of subjects who underwent coronary angiography, in an attempt to establish a correlation between these parameters and the severity of coronary artery disease (CAD), as well as investigate the correlation between hyperhomocysteinemia and the presence of polymorphism. METHODS: Twenty subjects with no coronary atheromatosis (controls), fourteen subjects with mild/moderate atheromatosis, and twenty-nine subjects with severe atheromatosis were evaluated. RESULTS: Significant differences were observed in mean homocysteine levels between the control and the severe atheromatosis groups (p < 0.001). No significant differences were observed among the other groups. The severe atheromatosis group showed rates of 62.0% and 6.9% for the C677T MTHFR gene polymorphism, in heterozygous and homozygous subjects, respectively. However, there was no correlation between the presence of mutation and hyperhomocysteinemia. A positive correlation of 41.91% (p < 0.001) was found between hyperhomocysteinemia and CAD. CONCLUSION: The most important finding of this study was the association between hyperhomocysteinemia and coronary stenosis > 70%; yet, whether elevated plasma homocysteine worsens atherosclerosis or is a consequence remains to be established.

Increased serum levels of lipoprotein(a) correlated with the severity of coronary artery disease in patients submitted to angiography.

OBJECTIVE: To determine serum levels of lipoprotein(a) and lipid profile of a group of individuals submitted to coronary angiography, with the aim of establishing the possible correlation between these parameters and the severity of coronary artery disease. METHODS: Serum levels of total cholesterol, HDLC, LDLC, triglycerides, lipoprotein(a), apolipoproteins A-I and B were measured in blood samples of 17 subjects with absence of atheromatosis in the coronary arteries (control), 12 subjects presenting mild/moderate atheromatosis and 28 subjects presenting severe atheromatosis. RESULTS: No significant statistical differences were found between the means of the three groups for the parameters assessed, except for lipoprotein(a) serum levels which presented significant differences between the means of the control, mild/moderate atheromatosis and severe atheromatosis groups (p<0.001). CONCLUSION: The means obtained in the three groups for Lp(a) indicate a progressive increase in the serum levels of this parameter according to the severity of coronary atheromatosis. These findings suggest the need of additional studies in order to obtain enough evidence to support the introduction of routine assessment of Lp(a) levels in clinical laboratories in the monitoring of patients at risk for coronary artery disease (CAD).

Homocistéina e metilenotetrahidrofolato redutase em indivíduos submetidos à angiografia coronariana / Homocysteine and methylenetetrahydrofolate reductase in subjects undergoing coronary angiography

OBJETIVO: Determinar os níveis plasmáticos de homocisteína e a incidência do polimorfismo C677T no gene da enzima metilenotetrahidrofolato redutase (MTHFR) em um grupo de indivíduos submetidos a angiografia coronariana, buscando estabelecer a possível correlação entre esses parâmetros e a gravidade da doença arterial coronariana (DAC), bem como investigar a correlação entre hiper-homocisteinemia e a presença do polimorfismo. MÉTODOS: Vinte indivíduos com ausência de ateromatose nas coronárias (controles), quatorze indivíduos apresentando ateromatose leve/moderada e vinte e nove indivíduos apresentando ateromatose grave foram avaliados. RESULTADOS: Para o parâmetro homocisteína foram observadas diferenças significativas entre as médias dos grupos controle e ateromatose grave (p < 0,001). Entre os demais grupos não foram observadas diferenças significativas. O grupo ateromatose grave apresentou uma freqüência de 62,0 por cento e 6,9 por cento para o polimorfismo C677T no gene da enzima MTHFR, em heterozigose e homozigose, respectivamente. Entretanto, não foi observada correlação entre a presença da mutação e hiper-homocisteinemia. Foi observada uma correlação positiva da ordem de 41,91 por cento (p < 0,001) entre hiper-homocisteinemia e a presença de DAC. CONCLUSÃO: O achado mais importante deste estudo foi a associação entre hiper-homocisteinemia e a presença de estenose coronariana superior a 70 por cento; entretanto, permanece a dúvida se o aumento da concentração plasmática de homocisteína constitui um fator determinante para o agravamento da lesão aterosclerótica nas coronárias ou se o mesmo é uma conseqüência desta lesão.

OBJECTIVE: To determine plasma homocysteine levels and the incidence of methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism in a group of subjects who underwent coronary angiography, in an attempt to establish a correlation between these parameters and the severity of coronary artery disease (CAD), as well as investigate the correlation between hyperhomocysteinemia and the presence of polymorphism. METHODS: Twenty subjects with no coronary atheromatosis (controls), fourteen subjects with mild/moderate atheromatosis, and twenty-nine subjects with severe atheromatosis were evaluated. RESULTS: Significant differences were observed in mean homocysteine levels between the control and the severe atheromatosis groups (p < 0.001). No significant differences were observed among the other groups. The severe atheromatosis group showed rates of 62.0 percent and 6.9 percent for the C677T MTHFR gene polymorphism, in heterozygous and homozygous subjects, respectively. However, there was no correlation between the presence of mutation and hyperhomocysteinemia. A positive correlation of 41.91 percent (p < 0.001) was found between hyperhomocysteinemia and CAD. CONCLUSION: The most important finding of this study was the association between hyperhomocysteinemia and coronary stenosis > 70 percent; yet, whether elevated plasma homocysteine worsens atherosclerosis or is a consequence remains to be established.

Níveis plasmáticos elevados de lipoproteína(a) correlacionados com a gravidade da doença arterial coronariana em pacientes submetidos à angiografia / Increased serum levels of lipoprotein(a) correlated with the severity of coronary artery disease in patients submitted to angiography / Increased serum levels of lipoprotein(a) correlated with the severity of coronary artery disease in patients submitted to angiography

OBJETIVO: Determinar os níveis plasmáticos de lipoproteína(a) e perfil lipídico de um grupo de indivíduos submetidos à angiografia coronariana, buscando estabelecer a possível correlação entre estes parâmetros e a gravidade da doença coronariana. MÉTODOS: Níveis plasmáticos de colesterol total, HDL C, LDL C, triglicérides, lipoproteína(a), apolipoproteínas A-I e B foram medidos em amostras de sangue de 17 indivíduos com ausência de ateromatose nas coronárias (controles), 12 indivíduos apresentando ateromatose leve/moderada e 28 indivíduos apresentando ateromatose grave. RESULTADOS: Não foram encontradas diferenças estatisticamente significativas entre as médias dos três grupos para os parâmetros avaliados, exceto para os níveis plasmáticos de lipoproteína(a) que apresentaram diferenças significativas entre as médias dos grupos controle, ateromatose leve/moderada e ateromatose grave (p<0,001). CONCLUSÃO: As médias obtidas nos três grupos para Lp(a) sinalizam um aumento progressivo nos níveis plasmáticos deste parâmetro, de acordo com a gravidade da ateromatose coronariana. Estes achados sugerem a necessidade de estudos adicionais, visando obter suficiente evidência para a introdução rotineira da avaliação dos níveis de Lp(a) em laboratórios clínicos, no monitoramento de pacientes apresentando risco para doença arterial coronariana (DAC).

OBJECTIVE: To determine serum levels of lipoprotein(a) and lipid profile of a group of individuals submitted to coronary angiography, with the aim of establishing the possible correlation between these parameters and the severity of coronary artery disease. METHODS: Serum levels of total cholesterol, HDL C, LDL C, triglycerides, lipoprotein(a), apolipoproteins A-I and B were measured in blood samples of 17 subjects with absence of atheromatosis in the coronary arteries (control), 12 subjects presenting mild/moderate atheromatosis and 28 subjects presenting severe atheromatosis. RESULTS: No significant statistical differences were found between the means of the three groups for the parameters assessed, except for lipoprotein(a) serum levels which presented significant differences between the means of the control, mild/moderate atheromatosis and severe atheromatosis groups (p<0.001). CONCLUSION: The means obtained in the three groups for Lp(a) indicate a progressive increase in the serum levels of this parameter according to the severity of coronary atheromatosis. These findings suggest the need of additional studies in order to obtain enough evidence to support the introduction of routine assessment of Lp(a) levels in clinical laboratories in the monitoring of patients at risk for coronary artery disease (CAD).

Fragmento 1+2 da protrombina em indivíduos submetidos à angiografia coronariana / Prothrombin fragment 1+2 in subjects undergoing coronary angiography

A trombina exerce um papel fundamental na conversão do fibrinogênio em fibrina, no processo de coagulação. O fator X ativado transforma a protrombina em trombina e fragmento 1+2 da protrombina (F1+2). Os níveis plasmáticos de F1+2 refletem a geração de trombina e podem ser usados como um marcador de hipercoagulabilidade in vivo, já que a trombina é uma substância instável e facilmente degradada, que não pode ser medida diretamente no plasma. O presente estudo teve como objetivo determinar os níveis plasmáticos do F1+2 de um grupo de indivíduos submetidos à angiografia coronariana, buscando estabelecer a possível correlação entre este parâmetro e a gravidade da doença arterial coronariana (DAC). Os níveis plasmáticos do F1+2 foram determinados em amostras de sangue de 17 indivíduos com ausência de ateromatose nas coronárias (controles), 12 indivíduos apresentando ateromatose leve/moderada e 28 indivíduos apresentando ateromatose grave, utilizando-se o conjunto diagnóstico Enzignost F1+2 (Behring® Diagnostics GmbH, Marburg, Germany). Não foram encontradas diferenças estatisticamente significativas entre as médias dos três grupos para o parâmetro avaliado. Portanto, as médias obtidas nos três grupos para os níveis plasmáticos de F1+2 não sinalizam para a existência de um estado de hipercoagulabilidade na população estudada. Entretanto, 73,7 por cento dos indivíduos faziam uso regular de ácido acetilsalicílico, o que pode ter influenciado nos resultados de F1+2, uma vez que este medicamento promove a inibição da enzima ciclooxigenase, diminuindo a liberação de tromboxane A2 e a agregação plaquetária. Portanto, presume-se que a redução da ativação plaquetária poderia estar contribuindo para uma menor formação de trombina e, conseqüentemente, diminuindo o potencial de hipercoagulabilidade.

Thrombin plays a basic role in the conversion of fibrinogen to fibrin in the coagulation process. Activated factor X transforms the prothrombin into thrombin and breaks up prothrombin fragment 1+2 (F1+2). F1+2 plasma levels reflect the thrombin generation and can be used as in vivo markers of hypercoagulability since the thrombin is an unstable and easily degraded substance that cannot be directly measured in the plasma. The present study aims at determining the F1+2 plasma levels of a group of subjects undergoing coronary angiography, attempting to establish a possible correlation between this parameter and the severity of the coronary artery disease. F1+2 plasma levels were determined in blood samples of 17 subjects with absence of atheromatosis in coronary arteries (controls), 12 subjects presenting mild/moderate atheromatosis and 28 subjects presenting severe atheromatosis, using the Enzignost F1+2 (Behring® Diagnostics GmbH, Marburg, Germany) diagnostic Kit. Significant differences between the averages for the three groups in respect to the evaluated parameters were not found. Therefore, F1+2 plasma level averages for the three groups did not point to a state of hypercoagulability in the studied population. However, 73.7 percent of the individuals were taking acetylsalicylic acid, which may have influenced the F1+2 plasma levels, considering that this medicine promotes the inhibition of the enzyme cyclo-oxygenase, diminishing the release of thromboxane A2 and the platelet aggregation. Therefore, it is presumed that platelet activation reduction could be contributing to a lower formation of thrombin and, consequently, diminishing the hypercoagulability potential.

Avaliação da eficácia e segurança do etofibrato em pacientes dislipidêmicos. Estudo multicêntrico / Evaluation of efficacy and safety of etofibrate in primary hyperlipidemia. A multicenter study

PURPOSE: To evaluate the clinical efficacy of etofibrate in primary hyperlipidemia in patients from clinical centers representative of all main Brazilian cities. METHODS: One thousand, nine hundred and fourty three hyperlipidemic patients were submitted to diet and drug treatment with etofibrate (500 mg/day) for eight weeks. The data b WAS analyzed as to changes in the lipoprotein profile, as well as the side effects. RESULTS: There was an important reduction in total cholesterol (19.88), triglycerides (29.59), LDL-c (14.89) and VLDL-c (14.54) concentration. There was a significant increase in HDL-c (18.14). Adverse effects were observed in 8.5 of the patients, without major clinical relevance, however, in 1.44 the treatment had to be interrupted. CONCLUSION: Administration of etofibrate promoted positive changes in all parameters of the lipid and lipoprotein profile, thus reducing the risk of atherosclerotic disease, without significant side effects in the great majority of sample studied.

Campanha nacional de alerta sobre o colesterol elevado. Determinaçäo do nível de colesterol de 81.262 brasileiros / National alert campaign about increased cholesterol: determination of cholesterol levels in 81.262 Brazilians

OBJECTIVE: To determine the levels of total cholesterol in a significant sample of the Brazilian population. METHODS: Blood cholesterol was determined in 81.262 individuals > 18 years old (51 percent male, 44.7 ± 15.7 years), using Accutrend equipment, in the cities São Paulo, Campinas, Campos do Jordäo, São José dos Campos, Santos, Santo André, Ribeirão Preto, Porto Alegre, Rio de Janeiro, Belo Horizonte, Curitiba, Brasília, Salvador and documented in the presence of other risk factors (RF) for coronary artery disease (CAD) (systemic hypertension, CAD in the family, smoking, and diabetes). Participants were classified according to sex, age, and the presence or absence of RF, respectively, as 0 RF, 1 RF and > 2 RF. The percentage of individuals with cholesterol > 200 mg/dL and > 240 mg/dL was evaluated. RESULTS: The prevalence of individuals with 0, 1, and > 2 risk factors was 30 percent (n = 24,589), 36 percent (n =29,324), and 34 percent (n = 27,349) respectively, (P=0.657), and the mean total cholesterol of the population was 199.0 ± 35.0 mg/dL. Cholesterol levels above 200 and 240 mg/dL were found, respectively, in 40 percent (n = 32,515) and 13 percent (10.942) of individuals. The greater the number of risk factors the higher the levels of cholesterol (P<0.0001) and the greater the proportion of individuals with cholesterol > 200 mg/dL (P=0.032). No difference existed in the proportion of individuals with cholesterol > 240 mg/dL (P=0.11). CONCLUSION: A great percentage of individuals with cholesterol levels above those recommended to prevent coronary artery disease was found

O papel das estratégias de mudanças do estilo de vida para a redução de eventos ateroscleróticos / The role of lifestyle changes strategies for atherosclerotic events reduction

Neste artigo, a autora avalia as estratégias de mudança do estilo de vida para redução do risco de eventos cardiovasculares. Inicialmente, situa a doença ateroscierótíca (DAC) e seus principais eventos infarto do miocárdio e acidente vascular cerebral como as principais causas de morte no mundo ocidental, que aumentam anualmente, sendo considerada a doença ateroscierótica uma doença da vida moderna. Neste sentido, realiza ampla revisão bibliográfica mencionando as diretrizes e metas da Sociedade Brasileira de Cardiologia-Departamento de Aterosolerose. Em seguida, nas estratégias de mudança do estilo de vida, menciona o abandono do tabagismo, os benefícios terapêuticas da atividade física e a importância da dieta, apresentando amplos dados bibliográficos com referência à modificação do perfil lipídico e da função endotelial e suas aplicações clínicas. Na discussão, apresenta resultados favoráveis e outras publicações sobre a associação entre o exercício físico e o risco do desenvolvimento da DAC, comprovando a necessidade da promoção da atividade física como prioridade da saúde pública. Com relação à terapêutica dietética, salienta a importância das fibras (soluvéis e insolúveis) e suas fontes, bem como as recomendações das quantidades nos Estados Unidos da América do Norte. Menciona o mecanismo de ação das fibras e os dados epidemiológicos que relacionam sua ingestão com a diminuição da incidência de coronariopatias, bem como ações da fibra dietática sobre a redução dos níveis de lipídeos (colesterol) e também a importância das fibras na terapêutica das dislipidemias, sendo atualmente reconhecidas como alimentos funcionais.