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.

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.

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.