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M.601 Management of dyslipidemia in childhood obesity
Miscellaneous
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GENETIC AND ENVIRONMENTAL FACTORS AFFECTING THE RESPONSE TO STATIN THERAPY IN PATIENTS WITH FAMILIAL HYPERCHOLESTEROLEMIA
G. Miltiadous, S. Xenophontos, E. Bafl-aktari, V. Tsimixodimos, M. Kalogfl'ou, M. Cariolou, M. Elisaf. Department oflnternal Medicine,
Biochemistry Laboratory, Medical School, University of loannina, loannina, Greece; and Molecular Genetics Unit B-DNA Identification Laboratory, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus We studied the effects of genetic [LDL receptor (LDLR) gene mutations, apolipoprotein (apo) E and apo AIV 347 gene polymorphisms and cholesteryl ester transfer protein (CETP) Taq IB polymorphism] and environmental factors (age, sex, smoking habit) on the lipid response to statin therapy in patients with moleculax'ly defined familial hypercholesterolemia (FH). In all cases blood samples were obtained after a 14-hour overnight fast for the genetic analysis and the determination of lipid paa'ameters. Atorvastatin 20mg/day was prescribed in 32 patients with heterozygous FH and the lipid profile was re-examined after 12 weeks of therapy. Also, atorvastatin 80mg/day was prescribed in 7 moleculax'ly defined homozygous FH patients. Our data point out that only the type of the LDLR gene mutation affects the response of heterozygous FH patients to statin therapy. In detail, heterozygotes sharing a type V mutation of the LDLR (G1775A) showed a higher percentage decrement in LDL-C after atorvastatin administration compaa'ed with patients shaa'ing type II mutations (G1646A and C858A) (49-4-9 vs 34+9%, p=0.001 by analysis of covafiance taking into account the baseline value as a covafiate). In addition, when atorvastatin (80mg/day) was administered in homozygous patients for the G1775A mutation a pronounced decrease in LDL-C by 35% was observed. We conclude that the type of the LDLR gene mutation affects the lipid response to statin therapy in FH patients. Also, therapy with statins (especially with the most potent drugs of this class) should be considered in homozygous FH patients shaa'ing a type V mutation of the LDLR gene.
•9•
GLYCAEMIC CONTROL AND ENDOGENOUS INSULIN RELATE TO ENDOTHELIAL FUNCTION IN DIABETIC PATIENTS WITH UNSTABLE ANGINA
N.V. Dubyanskaya, R.D. Kurbanov, R.K. Trigulova, G.K. Kiyakbaev, S.I. Ismailov. Institute of Endocrinology, Center of Cardiology, Tashkent,
Uzbekistan Diabetes predicts a worse outcome after an episode of unstable angina. This may reflect an impafl-ment vasodilator response to both endotheliumdependent (ED) and endothelium- independent (EID) vasodilators. Aim of the study was to evaluate the association between paa'ameters of caa'bohydrate metabolism and changes of endothelial function in patients with unstable angina (UA) and type 2 diabetes. Materials and Methods: We examined 69 male patients with UA. 35 of these patients have diabetes (ga'oup 1), 34 patients were non-diabetic (group 2). Duration of overt CHD, mean age, mean BMI, systolic and diastolic blood pressure, levels of LDL-cholesterol were the same in two ga'oups. Diabetic patients never have taken insulintherapy. Endothelial function test with reactive hyperemia and nitroglycerin were pel£ormed in all patients. Fasting and postprandial levels of plasma glucose and flee insulin, HbAlc levels were estimated in diabetic patients. Results: Vasodilatation by response to reactive hyperemia (2,74-4-1,51 versus 4,79-4-2,17 Dd%) and nitroglycerin (10,48-4-1,91 versus 17,29-4-2,98 Dd%) was significantly blunted in ga'oup 1 patients compaa'ed with group 2 patients. In addition, significant cola'elation was found between dega'ee of ED vasodilatation and both HbAlc levels (r= - 0,676; p<0,05) and fasting and postprandial plasma insulin levels (r=0,777; p<0,05; r=0,579; p<0,05). Conclusion: Diabetic patients with UA have more deep disorders of endothelial function compaa'ed with non-diabetic UA patients. Better glycaemic control and preserved insulin secretion were associated with higher dega'ee ED vasodilatation.
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ez
139
CONJUGATED LINOLEIC ACID (CLA) DOES NOT IMPROVE LDL PHENOTYPE IN MODERATELY OVERWEIGHT SUBJECTS WITH LDL PHENOTYPE B
E. Naumann, Y. Carpentier, A. Saebo, T. Lassel, I. Dupont, R. Mensink, J. S b dio. Maastricht University, Department of Human Biology,
Maastricht, The Netherlands; Universit Libre de Bruxelles, L. Deloyers Laboratory for Experimental Surgery, Brussels, Belgium; Natural Lipids Ltd. AS., Hovdebygda, Norway; Danone-Vitapole Palaiseau; INRA, Unit de Nutrition Lipidique, Paris, France Objective: To test the hypothesis, emerging fi'om our pilot study, that especially cis-9, trans-11 (c9, t11) CLA decreases plasma small dense LDL in moderately overweight subjects (BMI 25-32.5 kg/m 2) with phenotype B (_>35% LDL cholesterol in LDL >= 1.040 g/mL). Methods: After a run-in period of one week 48 men and 39 women consumed daily for 13 weeks a drinkable dafl'y product enriched with 3 g of a high-oleic acid sunflower oil (control product; n=34), with 3 g c9, t l l CLA (n=34), or with 3 g tl0, c12 CLA (n=19). LDL was isolated fi'om fasting plasma by ultracentrifugation to determine LDL phenotype. Differences between treatments in responses, defined as the change between values obtained at the end of the intervention and run-in periods, wele analyzed by the Kruskal- Wallis test or ANOVA. Results: Compared with control, both c9, t l l CLA and tl0, c12 CLA decleased small dense LDL cholesterol non-significantly by 1.9%. c9, t l l CLA changed serum LDL cholesterol non-significantly by -0.02 -4- 0.52 mmol/L and tl0, c12 CLA by 0.17 -4- 0.62 mmol/L. No significant changes in HDL cholesterol and triacylglycerol were observed. Condusion: In humans c9, tll CLA o1"tl0, c12 CLA does not favorably affect serum lipoproteins. Support: European Commission, Fifth (EC) fi'amework programme QLK1-1999-00076.
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MANAGEMENT OF DYSLIPIDEMIA IN C H I L D H O O D OBESITY
M. Nikolovska, M. Damjanska. Health Center, Skopje, Macedonia Several studies have shown that childhood obesity has been connected to dyslipidemia, which is recognized as a significant risk for atherosclerotic disease. The rationale for management of dyslipidemia in childhood is strong: to limit the development of atherosclerosis, to establish lifelong lifestyle habits, and to prevent the acquisition of additional risk factors. The aim of the study is to present the management of dyslipidemia in our pediatric primaay health caa'e. Data synthesis: our study included 45 children with BMI_>95th percentile selected fi'om the local schoolchildren who were following regulax" continuing health caa'e (aged 8-18 yeaa's) and who had no family histoly of CHD. Children at high risk for obesity-related caa'diovasculaa" disease received family-based individualized treatment. After causes od secondaa'y dyslipidemia had been ruled out o1"treated, dietaa'y therapy was the primax'y intervention. Exercises were also included. The diets prescribed were those used in adults; energy intake levels were selected to support growth and development, and to reach or maintain desfl'able body weight. There was no pediatric patient 10 yeaa's of age o1" older with LDL-cholesterol, which is the major determinant of atherosclerotic process beginning in childhood that had remained very high despite vigorous lifestyle intervention. That's why phaa-macotherapy was not considered Conclusion: in order to reduce the risk of cax'diovasculax" disease it is very important for the practitioner to undertake effective treatment of dyslipidemia in childhood.
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WALNUT DIET IMPROVES ENDOTHELIAL FUNCTION IN HYPERCHOLESTEROLEMIC SUBJECTS: A RANDOMIZED CROSSOVER TRIAL
I. N ez, R. Gilabert, A. P rez-Heras, M. Sen'a, E. Casals, R. Deulofeu, E. Ros. Centre de Diagn stic per l'Imatge, Lipid Clinic (Endocrinology &
Nutrition Service) and Centre de Diagn stic Biol gic, Hospital CI nic, Barcelona, Spain Epidemiological studies suggest that nut intake decreases coronary artery disease (CAD) risk. Nuts have a cholesterol-lowering effect that partly explains this benefit. Endothelial dysfunction is associated with CAD and its risk factors, and is reversed by antioxidants and marine n-3 fatty acids. Walnuts are a rich source of both antioxidants and a-linolenic acid (ALA), a plant n-3 fatty acid. Subjects and Methods: To test the hypothesis that walnut intake will
74th EAS Congress, 17-20 April 2004, Seville, Spain
•9•
GENETIC AND ENVIRONMENTAL FACTORS AFFECTING THE RESPONSE TO STATIN THERAPY IN PATIENTS WITH FAMILIAL HYPERCHOLESTEROLEMIA
G. Miltiadous, S. Xenophontos, E. Bafl-aktari, V. Tsimixodimos, M. Kalogfl'ou, M. Cariolou, M. Elisaf. Department oflnternal Medicine,
Biochemistry Laboratory, Medical School, University of loannina, loannina, Greece; and Molecular Genetics Unit B-DNA Identification Laboratory, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus We studied the effects of genetic [LDL receptor (LDLR) gene mutations, apolipoprotein (apo) E and apo AIV 347 gene polymorphisms and cholesteryl ester transfer protein (CETP) Taq IB polymorphism] and environmental factors (age, sex, smoking habit) on the lipid response to statin therapy in patients with moleculax'ly defined familial hypercholesterolemia (FH). In all cases blood samples were obtained after a 14-hour overnight fast for the genetic analysis and the determination of lipid paa'ameters. Atorvastatin 20mg/day was prescribed in 32 patients with heterozygous FH and the lipid profile was re-examined after 12 weeks of therapy. Also, atorvastatin 80mg/day was prescribed in 7 moleculax'ly defined homozygous FH patients. Our data point out that only the type of the LDLR gene mutation affects the response of heterozygous FH patients to statin therapy. In detail, heterozygotes sharing a type V mutation of the LDLR (G1775A) showed a higher percentage decrement in LDL-C after atorvastatin administration compaa'ed with patients shaa'ing type II mutations (G1646A and C858A) (49-4-9 vs 34+9%, p=0.001 by analysis of covafiance taking into account the baseline value as a covafiate). In addition, when atorvastatin (80mg/day) was administered in homozygous patients for the G1775A mutation a pronounced decrease in LDL-C by 35% was observed. We conclude that the type of the LDLR gene mutation affects the lipid response to statin therapy in FH patients. Also, therapy with statins (especially with the most potent drugs of this class) should be considered in homozygous FH patients shaa'ing a type V mutation of the LDLR gene.
•9•
GLYCAEMIC CONTROL AND ENDOGENOUS INSULIN RELATE TO ENDOTHELIAL FUNCTION IN DIABETIC PATIENTS WITH UNSTABLE ANGINA
N.V. Dubyanskaya, R.D. Kurbanov, R.K. Trigulova, G.K. Kiyakbaev, S.I. Ismailov. Institute of Endocrinology, Center of Cardiology, Tashkent,
Uzbekistan Diabetes predicts a worse outcome after an episode of unstable angina. This may reflect an impafl-ment vasodilator response to both endotheliumdependent (ED) and endothelium- independent (EID) vasodilators. Aim of the study was to evaluate the association between paa'ameters of caa'bohydrate metabolism and changes of endothelial function in patients with unstable angina (UA) and type 2 diabetes. Materials and Methods: We examined 69 male patients with UA. 35 of these patients have diabetes (ga'oup 1), 34 patients were non-diabetic (group 2). Duration of overt CHD, mean age, mean BMI, systolic and diastolic blood pressure, levels of LDL-cholesterol were the same in two ga'oups. Diabetic patients never have taken insulintherapy. Endothelial function test with reactive hyperemia and nitroglycerin were pel£ormed in all patients. Fasting and postprandial levels of plasma glucose and flee insulin, HbAlc levels were estimated in diabetic patients. Results: Vasodilatation by response to reactive hyperemia (2,74-4-1,51 versus 4,79-4-2,17 Dd%) and nitroglycerin (10,48-4-1,91 versus 17,29-4-2,98 Dd%) was significantly blunted in ga'oup 1 patients compaa'ed with group 2 patients. In addition, significant cola'elation was found between dega'ee of ED vasodilatation and both HbAlc levels (r= - 0,676; p<0,05) and fasting and postprandial plasma insulin levels (r=0,777; p<0,05; r=0,579; p<0,05). Conclusion: Diabetic patients with UA have more deep disorders of endothelial function compaa'ed with non-diabetic UA patients. Better glycaemic control and preserved insulin secretion were associated with higher dega'ee ED vasodilatation.
•0•
N
ez
139
CONJUGATED LINOLEIC ACID (CLA) DOES NOT IMPROVE LDL PHENOTYPE IN MODERATELY OVERWEIGHT SUBJECTS WITH LDL PHENOTYPE B
E. Naumann, Y. Carpentier, A. Saebo, T. Lassel, I. Dupont, R. Mensink, J. S b dio. Maastricht University, Department of Human Biology,
Maastricht, The Netherlands; Universit Libre de Bruxelles, L. Deloyers Laboratory for Experimental Surgery, Brussels, Belgium; Natural Lipids Ltd. AS., Hovdebygda, Norway; Danone-Vitapole Palaiseau; INRA, Unit de Nutrition Lipidique, Paris, France Objective: To test the hypothesis, emerging fi'om our pilot study, that especially cis-9, trans-11 (c9, t11) CLA decreases plasma small dense LDL in moderately overweight subjects (BMI 25-32.5 kg/m 2) with phenotype B (_>35% LDL cholesterol in LDL >= 1.040 g/mL). Methods: After a run-in period of one week 48 men and 39 women consumed daily for 13 weeks a drinkable dafl'y product enriched with 3 g of a high-oleic acid sunflower oil (control product; n=34), with 3 g c9, t l l CLA (n=34), or with 3 g tl0, c12 CLA (n=19). LDL was isolated fi'om fasting plasma by ultracentrifugation to determine LDL phenotype. Differences between treatments in responses, defined as the change between values obtained at the end of the intervention and run-in periods, wele analyzed by the Kruskal- Wallis test or ANOVA. Results: Compared with control, both c9, t l l CLA and tl0, c12 CLA decleased small dense LDL cholesterol non-significantly by 1.9%. c9, t l l CLA changed serum LDL cholesterol non-significantly by -0.02 -4- 0.52 mmol/L and tl0, c12 CLA by 0.17 -4- 0.62 mmol/L. No significant changes in HDL cholesterol and triacylglycerol were observed. Condusion: In humans c9, tll CLA o1"tl0, c12 CLA does not favorably affect serum lipoproteins. Support: European Commission, Fifth (EC) fi'amework programme QLK1-1999-00076.
•0•
MANAGEMENT OF DYSLIPIDEMIA IN C H I L D H O O D OBESITY
M. Nikolovska, M. Damjanska. Health Center, Skopje, Macedonia Several studies have shown that childhood obesity has been connected to dyslipidemia, which is recognized as a significant risk for atherosclerotic disease. The rationale for management of dyslipidemia in childhood is strong: to limit the development of atherosclerosis, to establish lifelong lifestyle habits, and to prevent the acquisition of additional risk factors. The aim of the study is to present the management of dyslipidemia in our pediatric primaay health caa'e. Data synthesis: our study included 45 children with BMI_>95th percentile selected fi'om the local schoolchildren who were following regulax" continuing health caa'e (aged 8-18 yeaa's) and who had no family histoly of CHD. Children at high risk for obesity-related caa'diovasculaa" disease received family-based individualized treatment. After causes od secondaa'y dyslipidemia had been ruled out o1"treated, dietaa'y therapy was the primax'y intervention. Exercises were also included. The diets prescribed were those used in adults; energy intake levels were selected to support growth and development, and to reach or maintain desfl'able body weight. There was no pediatric patient 10 yeaa's of age o1" older with LDL-cholesterol, which is the major determinant of atherosclerotic process beginning in childhood that had remained very high despite vigorous lifestyle intervention. That's why phaa-macotherapy was not considered Conclusion: in order to reduce the risk of cax'diovasculax" disease it is very important for the practitioner to undertake effective treatment of dyslipidemia in childhood.
•
0
•
A
WALNUT DIET IMPROVES ENDOTHELIAL FUNCTION IN HYPERCHOLESTEROLEMIC SUBJECTS: A RANDOMIZED CROSSOVER TRIAL
I. N ez, R. Gilabert, A. P rez-Heras, M. Sen'a, E. Casals, R. Deulofeu, E. Ros. Centre de Diagn stic per l'Imatge, Lipid Clinic (Endocrinology &
Nutrition Service) and Centre de Diagn stic Biol gic, Hospital CI nic, Barcelona, Spain Epidemiological studies suggest that nut intake decreases coronary artery disease (CAD) risk. Nuts have a cholesterol-lowering effect that partly explains this benefit. Endothelial dysfunction is associated with CAD and its risk factors, and is reversed by antioxidants and marine n-3 fatty acids. Walnuts are a rich source of both antioxidants and a-linolenic acid (ALA), a plant n-3 fatty acid. Subjects and Methods: To test the hypothesis that walnut intake will
74th EAS Congress, 17-20 April 2004, Seville, Spain