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Abstracts / Atherosclerosis 235 (2014) e192–e301
Results: 32.5% of HD patients had WHR 0.6 Mean differences between both groups with BMI, standard body weight (SBW) and fat mass index (FMI) (all, p<0.001), were found. Multivariate analysis adjusted by gender showed significant relation between WHR with body composition parameters (BMI, SBW, FMI; p<0.01) and metabolic risk factors (plasma glucose, serum triglycerides and C-HDL; all, p <0.05). WHR > 0.6 was a predictive marker of metabolic risk when was analyzed by ROC curves. Conclusion: WHR a simple anthropomorphic measure of metabolic risk was a predictive marker of metabolic syndrome and higher CV risk in HD patients. 39 - Microbiota EAS-0570. CHANGING DIETARY CONTENT OF GLUTEN–AND POTENTIALLY THE GUT MICROBIOTA, DID NOT RESULT IN INCREASED ATHEROSCLEROSIS IN THE APOE-/-MOUSE I. Runea, B. Rolinb, J. Lykkesfeldta, B. Chistoffersenc, R.K. Kirkd, A.K. Hansena a
Experimental Animal Models, University of Copenhagen, Frederiksberg C, Denmark; b Translational Pharmacology, Novo Nordisk A/S, Maaloev, Denmark; c Diabetes Pharmacology - PK/PD, Novo Nordisk A/S, Maaloev, Denmark; d Histology and Imaging, Novo Nordisk A/S, Maaloev, Denmark Objectives: The aim of this study was to investigate whether a naturally occurring concentration of gluten is capable of worsening disease progression of atherosclerosis in comparison with a gluten-free diet. Methods: B6.129P2-Apoetm1Unc N11 female mice were kept on a hydrolysed gluten-free diet high in fat and cholesterol (HF) from birth until 16 weeks of age. A group of animals received a calorimetric diet added 1 % gliadin corresponding to 3.5 % gluten (HF+G). Animals were subjected to oral glucose tolerance tests (OGTT) and blood sampling at week 5 and prior to termination at week 16, where aortas where harvested and plaque area determined. Results: Body weight (BW) did not differ between the groups at any time point. At study termination BW was 26.32 0.96 g and 26.18 0.93 g in the HF group and the HF+G group respectively (p¼0.2783). Oral glucose tolerance measured as area under the curve (AUCglucose) was similar between the groups at 5 as well as 16 weeks of age (p¼0.8183 and p¼0.2783 respectively). Differences in insulin levels during the first 30 minutes of an OGTT (DInsulin) at 16 weeks of age did not differ between the groups (37.97 17.65 pM vs. 39.22 10.20 pM; p¼0.6036). Macroscopically measured plaque area (‘en face’) did not show any difference between the groups (21.22 1.35 % vs. 23.47 1.17 %; p¼0.1273) and neither did plaque area measured histologically at the aortic sinus (8.04 1.07 % vs. 7.30 1.30 %; p¼0.7899). Plasma levels of the oxidative stress marker malondialdehyde (MDA) did not differ between the groups at 16 weeks of age (0.617 0.077 nmol/ml vs. 0.473 0.104 nmol/ml; p¼0.5859). Conclusion: A gliadin concentration mimicking the one naturally occurring in rodent chow does not seem to impact development of neither atherosclerosis nor glucose intolerance in the ApoE gene knockout mouse. 40 - Inherited dyslipidemias EAS-1067. SDLDL/LDL RATIO IN FAMILIAL COMBINED HYPERLIPIDAEMIA PATIENTS AND FAMILIAL HYPERCHOLESTEROLEMIA PATIENTS S. Jamala, A.C. Alvesa, A.M. Medeirosa, M. Bourbona a Unidade de I&D Grupo de Investigação Cardiovascular Departamento de Promoção da Saúde e Prevenção de Doenças Não Transmissíveis, Instituto Nacional de Saúde Dr. Ricardo Jorge AND Center for Biodiversity Functional & Integrative Genomics (BioFIG) Faculdade de Ciências Universidade de Lisboa Lisboa Portugal, Lisboa, Portugal
Objectives: Familial Hypercholesterolemia (FH) and Familial Combined Hypercholesterolemia (FCHL) are genetic dyslipidemias with increased
cardiovascular risk. FH patients present only very high levels of LDLc since birth but FCHL patients present a complex phenotype with high LDLc and/ or triglycerides that can change during the life cycle. LDL is composed of heterogeneous particles differing in density, size and chemical composition and FCHL patients are known to have a higher concentration of sdLDL. The aim of this study was to compare the sdLDL/LDL ratio between FH and FCHL patients with and without treatment. Methods: sdLDL were measured in 165 FH and 72 FCHL patients, by enzymatic/colorimetric clearance method (Daytona, Randox Laboratories) and LDL by a direct enzymatic/colorimetric (Cobas INTEGRA, Roche). Statistical analysis was performed using the SPSS version 17.0. Results: In patients without lipid medication significant lower levels of LDL and sdLDL were observed in FCHL (n¼35) compared to FH (n¼46) patients (LDL, 140.839.5 and 229.576.4 mg/dL,p<0.001; sdLDL, 39.820.6 and 57.140.1 mg/dL,p¼0.023). However the ratio sdLDL/LDL is higher in FCHL (0.280.11vs0.230.10) although it does not reach significance difference. Also in FCHL (n¼37) and FH (n¼119) patients on medication it was observed that LDL levels were significantly lower in FCHL vs FH patients (LDL, 122.563.8 vs 186.566.0 mg/dL, p<0.001) but sdLDL, although lower, were not statistical different (sdLDL, 39.924.4 and 43.824.4 mg/ dL, p¼0.39). The ratio sdLDL/LDL is also higher in FCHL vs FH patients (0.340.16 vs 0.230.8), being statistically significantly different (p<0.001). Conclusion: FCHL patients have a higher ratio of sdLDL/LDL than FH patients presenting this way a more atherogenic profile with a higher concentration of cholesterol in sdLDL particles in relation to large and buoyant particles. Under statins the ratio sdLDL/LDL does not improve in any condition, showing even an increase in FCHL patients. 40 - Inherited dyslipidemias EAS-1066. INVERSE CORRELATION BETWEEN HOMOCYSTEINE AND HDL-C A.R. Manaçasa, A.C. Alvesa, Q. Ratob, M. Bourbona a Departamento de Promoção da Saúde e Prevenção de Doenças não Transmissíveis, Instituto Nacional de Saúde Dr. Ricardo Jorge AND Center for Biodiversity Functional & Integrative Genomics (BioFIG) Faculdade de Ciências Universidade de Lisboa Lisboa Portugal, Lisboa, Portugal; b Serviço de Cardiologia, Hospital de São Bernardo Setúbal Portugal, Setúbal, Portugal
Objectives: Homocysteine (Hcy) is a sulfur-containing amino acid formed during the metabolism of methionine and is present in all individuals. However when Hcy is produced in excess it can confer a higher risk of development of cardiovascular diseases. Hyperhomocysteinemia may induce endothelium injury and consequently a myocardial infarction or thrombosis. This work intends to analyze the relationship between the concentration of Hcy and others risk factors as Total Cholesterol, LDL Cholesterol (LDL-C), HDL Cholesterol (HDL-C), small dense LDL (sdLDL), Lipoprotein (a) (Lp (a)) and C Reactive Protein (CRP). Methods: A random sample of 205 individuals from the Central Region of Portugal was selected from the e_COR study. These individuals were not treated for Dyslipidemia or Diabetes. The biochemical parameters, Hcy, Total Cholesterol, LDL-C, HDL-C, sdLDL, Lp (a) and CRP were determined by automatic methods in a Cobas Integra 400 plus analyzer (Roche) and sdLDL in a Daytona Analyzer (Randox). For the statistic analyses it was used a non-parametric correlation (Spearman Correlation). Results: A correlation between the concentration of Hcy and all the others biochemical parameters was observed. The correlations between Hcy and the parameters sdLDL, C-HDL and LDL are classified as moderate. The correlations between Hcy and the parameters Lp (a), Total Cholesterol and CRP are classified as weak. The most significant correlation was observed between Hcy and HDL-C (p Conclusion: We conclude that the concentration of Hcy and HDL-C are highly interconnected. In future studies it would be important to understand the physiological relation between these two biochemical parameters so new drugs that can decrease Hcy and increase HDL-C can be developed to prevent atherosclerosis and thrombosis.
Abstracts / Atherosclerosis 235 (2014) e192–e301
Results: 32.5% of HD patients had WHR 0.6 Mean differences between both groups with BMI, standard body weight (SBW) and fat mass index (FMI) (all, p<0.001), were found. Multivariate analysis adjusted by gender showed significant relation between WHR with body composition parameters (BMI, SBW, FMI; p<0.01) and metabolic risk factors (plasma glucose, serum triglycerides and C-HDL; all, p <0.05). WHR > 0.6 was a predictive marker of metabolic risk when was analyzed by ROC curves. Conclusion: WHR a simple anthropomorphic measure of metabolic risk was a predictive marker of metabolic syndrome and higher CV risk in HD patients. 39 - Microbiota EAS-0570. CHANGING DIETARY CONTENT OF GLUTEN–AND POTENTIALLY THE GUT MICROBIOTA, DID NOT RESULT IN INCREASED ATHEROSCLEROSIS IN THE APOE-/-MOUSE I. Runea, B. Rolinb, J. Lykkesfeldta, B. Chistoffersenc, R.K. Kirkd, A.K. Hansena a
Experimental Animal Models, University of Copenhagen, Frederiksberg C, Denmark; b Translational Pharmacology, Novo Nordisk A/S, Maaloev, Denmark; c Diabetes Pharmacology - PK/PD, Novo Nordisk A/S, Maaloev, Denmark; d Histology and Imaging, Novo Nordisk A/S, Maaloev, Denmark Objectives: The aim of this study was to investigate whether a naturally occurring concentration of gluten is capable of worsening disease progression of atherosclerosis in comparison with a gluten-free diet. Methods: B6.129P2-Apoetm1Unc N11 female mice were kept on a hydrolysed gluten-free diet high in fat and cholesterol (HF) from birth until 16 weeks of age. A group of animals received a calorimetric diet added 1 % gliadin corresponding to 3.5 % gluten (HF+G). Animals were subjected to oral glucose tolerance tests (OGTT) and blood sampling at week 5 and prior to termination at week 16, where aortas where harvested and plaque area determined. Results: Body weight (BW) did not differ between the groups at any time point. At study termination BW was 26.32 0.96 g and 26.18 0.93 g in the HF group and the HF+G group respectively (p¼0.2783). Oral glucose tolerance measured as area under the curve (AUCglucose) was similar between the groups at 5 as well as 16 weeks of age (p¼0.8183 and p¼0.2783 respectively). Differences in insulin levels during the first 30 minutes of an OGTT (DInsulin) at 16 weeks of age did not differ between the groups (37.97 17.65 pM vs. 39.22 10.20 pM; p¼0.6036). Macroscopically measured plaque area (‘en face’) did not show any difference between the groups (21.22 1.35 % vs. 23.47 1.17 %; p¼0.1273) and neither did plaque area measured histologically at the aortic sinus (8.04 1.07 % vs. 7.30 1.30 %; p¼0.7899). Plasma levels of the oxidative stress marker malondialdehyde (MDA) did not differ between the groups at 16 weeks of age (0.617 0.077 nmol/ml vs. 0.473 0.104 nmol/ml; p¼0.5859). Conclusion: A gliadin concentration mimicking the one naturally occurring in rodent chow does not seem to impact development of neither atherosclerosis nor glucose intolerance in the ApoE gene knockout mouse. 40 - Inherited dyslipidemias EAS-1067. SDLDL/LDL RATIO IN FAMILIAL COMBINED HYPERLIPIDAEMIA PATIENTS AND FAMILIAL HYPERCHOLESTEROLEMIA PATIENTS S. Jamala, A.C. Alvesa, A.M. Medeirosa, M. Bourbona a Unidade de I&D Grupo de Investigação Cardiovascular Departamento de Promoção da Saúde e Prevenção de Doenças Não Transmissíveis, Instituto Nacional de Saúde Dr. Ricardo Jorge AND Center for Biodiversity Functional & Integrative Genomics (BioFIG) Faculdade de Ciências Universidade de Lisboa Lisboa Portugal, Lisboa, Portugal
Objectives: Familial Hypercholesterolemia (FH) and Familial Combined Hypercholesterolemia (FCHL) are genetic dyslipidemias with increased
cardiovascular risk. FH patients present only very high levels of LDLc since birth but FCHL patients present a complex phenotype with high LDLc and/ or triglycerides that can change during the life cycle. LDL is composed of heterogeneous particles differing in density, size and chemical composition and FCHL patients are known to have a higher concentration of sdLDL. The aim of this study was to compare the sdLDL/LDL ratio between FH and FCHL patients with and without treatment. Methods: sdLDL were measured in 165 FH and 72 FCHL patients, by enzymatic/colorimetric clearance method (Daytona, Randox Laboratories) and LDL by a direct enzymatic/colorimetric (Cobas INTEGRA, Roche). Statistical analysis was performed using the SPSS version 17.0. Results: In patients without lipid medication significant lower levels of LDL and sdLDL were observed in FCHL (n¼35) compared to FH (n¼46) patients (LDL, 140.839.5 and 229.576.4 mg/dL,p<0.001; sdLDL, 39.820.6 and 57.140.1 mg/dL,p¼0.023). However the ratio sdLDL/LDL is higher in FCHL (0.280.11vs0.230.10) although it does not reach significance difference. Also in FCHL (n¼37) and FH (n¼119) patients on medication it was observed that LDL levels were significantly lower in FCHL vs FH patients (LDL, 122.563.8 vs 186.566.0 mg/dL, p<0.001) but sdLDL, although lower, were not statistical different (sdLDL, 39.924.4 and 43.824.4 mg/ dL, p¼0.39). The ratio sdLDL/LDL is also higher in FCHL vs FH patients (0.340.16 vs 0.230.8), being statistically significantly different (p<0.001). Conclusion: FCHL patients have a higher ratio of sdLDL/LDL than FH patients presenting this way a more atherogenic profile with a higher concentration of cholesterol in sdLDL particles in relation to large and buoyant particles. Under statins the ratio sdLDL/LDL does not improve in any condition, showing even an increase in FCHL patients. 40 - Inherited dyslipidemias EAS-1066. INVERSE CORRELATION BETWEEN HOMOCYSTEINE AND HDL-C A.R. Manaçasa, A.C. Alvesa, Q. Ratob, M. Bourbona a Departamento de Promoção da Saúde e Prevenção de Doenças não Transmissíveis, Instituto Nacional de Saúde Dr. Ricardo Jorge AND Center for Biodiversity Functional & Integrative Genomics (BioFIG) Faculdade de Ciências Universidade de Lisboa Lisboa Portugal, Lisboa, Portugal; b Serviço de Cardiologia, Hospital de São Bernardo Setúbal Portugal, Setúbal, Portugal
Objectives: Homocysteine (Hcy) is a sulfur-containing amino acid formed during the metabolism of methionine and is present in all individuals. However when Hcy is produced in excess it can confer a higher risk of development of cardiovascular diseases. Hyperhomocysteinemia may induce endothelium injury and consequently a myocardial infarction or thrombosis. This work intends to analyze the relationship between the concentration of Hcy and others risk factors as Total Cholesterol, LDL Cholesterol (LDL-C), HDL Cholesterol (HDL-C), small dense LDL (sdLDL), Lipoprotein (a) (Lp (a)) and C Reactive Protein (CRP). Methods: A random sample of 205 individuals from the Central Region of Portugal was selected from the e_COR study. These individuals were not treated for Dyslipidemia or Diabetes. The biochemical parameters, Hcy, Total Cholesterol, LDL-C, HDL-C, sdLDL, Lp (a) and CRP were determined by automatic methods in a Cobas Integra 400 plus analyzer (Roche) and sdLDL in a Daytona Analyzer (Randox). For the statistic analyses it was used a non-parametric correlation (Spearman Correlation). Results: A correlation between the concentration of Hcy and all the others biochemical parameters was observed. The correlations between Hcy and the parameters sdLDL, C-HDL and LDL are classified as moderate. The correlations between Hcy and the parameters Lp (a), Total Cholesterol and CRP are classified as weak. The most significant correlation was observed between Hcy and HDL-C (p Conclusion: We conclude that the concentration of Hcy and HDL-C are highly interconnected. In future studies it would be important to understand the physiological relation between these two biochemical parameters so new drugs that can decrease Hcy and increase HDL-C can be developed to prevent atherosclerosis and thrombosis.