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MS2 EFFECTS OF SIBUTRAMINE PLUS L-CARNITINE COMPARED TO SIBUTRAMINE OR PLACEBO ON INFLAMMATORY PARAMETERS
Atherosclerosis Supplements 11 (2010) 109–222
78th EAS Congress, 20−23 June, 2010, Hamburg, Germany Memory Stick Presentations MS1 REGULAR EXERCISE IMPROVED ENDOTHELIAL DYSFUNCTION IN YOUNG MALE ADULTS WITH METABOLIC SYNDROME G. Fornieles-Gonzalez1 , M.A. Rosety-Rodriguez2 , I. Rosety-Rodriguez2 , F.J. Ordonez ˜ 2 , N. Garcia-Gomez3 , A. Camacho4 , M. Rosety-Rodriguez1 . 1 Internal Medicine, 2 School of Sport Medicine, 3 Pathologic Anatomy, University of Cadiz, Cadiz, 4 Medicine, Hospital Juan Ramon Jimenez, Huelva, Spain
MS3 BLOOD PRESSURE-LOWERING RESPONSE TO AMLODIPINE AS A DETERMINANT OF THE ANTIOXIDATIVE ACTIVITY OF SMALL, DENSE HDL3 IN HYPERTENSIVE SUBJECTS B. Hansel1 , X. Girerd2 , D. Bonnefont-Rousselot2 , R. Bittar2 , S. Chantepie1 , A. Orsoni1 , E. Bruckert2 , M.J. Chapman1 , A. Kontush1 . 1 INSERM Unit 939, 2 AP-HP Pitie-Salpetriere, Paris, France
Background and Aims: It is widely accepted endothelial dysfunction may play an important role during the development of atherosclerotic plaque. Recent studies have reported regular exercise may reduce proinflammatory biomarkers in patients with metabolic syndrome However to date little information is available on the influence of exercise on levels of endothelial adhesion molecules. This study was designed to determine the influence of exercise on soluble vascular cell adhesion molecule (VCAM-1) in young male adults with metabolic syndrome. Method: Sixty adult men with metabolic syndrome according to the criteria reported by the National Cholesterol Education Program Adult Treatment Panel III volunteered for this study. Forty-five were randomly included in experimental group to perform a 12-week aerobic training program, 3 days/week, consisting of warm up (10-min), main part (20−35-min [increasing 5 minutes each 3 weeks]) at a work intensity of 60−75% of peak heart rate (increasing 5% each 3 weeks) and cool-down (10-min). Control group included 15 age, sex and BMI-matched men with metabolic syndrome that will not perform any program. Further our protocol was approved by an institutional ethic committee. Serum soluble VCAM-1 concentration was measured by ELISA, using a commercially available kit (Parameter, R&D Systems) twice: 72-hours before starting the program and after its ending. Results: When compared to baseline soluble VCAM-1 concentration was decreased significantly after our 6-week protocol (456.1±18.4 vs 382.7±20.3 ng/ml; p < 0.05). No changes were reported in controls. Conclusion: A 12-week training program decreased soluble VCAM-1 concentration in young male adults with metabolic syndrome.
Objective: Beneficial effects of calcium channel blockers on cardiovascular disease may in part be related to the reduction of oxidative stress, potentially enhancing antioxidative activity (AOX) of high-density lipoprotein (HDL). We assessed the effect of a one-month treatment by amlodipine on HDL AOX in hypertensive subjects. Methods: 28 hypertensive (obesity=46%; metabolic syndrome=57%) patients received 10 mg Amlodipine daily during 1 month. HDL AOX was assessed as the capacity of the small, dense HDL3c subpopulation to inhibit LDL oxidation. Results: HDL3c AOX did not significantly change in the whole study population; changes in AOX were however positively correlated with changes in SBP (r = 0.37, p = 0.05 for maximal diene concentration; r = 0.34, p = 0.08 for LDL oxidation rate). When population was divided in two subgroups according to the blood pressure response to Amlodipine, good responders having SBP/DBP drop above the median (22/10 mmHg) and poor responders below, HDL3c AOX was significantly improved in good responders vs. poor responders (change in the LDL oxidation rate in the presence of HDL3c, −6.8% (11.2) vs +1.9% (5.2) respectively, p = 0.04; maximal diene concentration, −8.6% (13.0) vs +1.9% (8.2) respectively, p < 0.05). By contrast, changes in plasma concentration of oxidized LDL, a marker of systemic oxidative stress, and in chemical composition of HDL3c did not differ between the subgroups. Conclusions: In hypertensive patients, treatment with Amlodipine resulted in the enhancement of HDL AOX only in subjects with the over-the-median decrease in blood pressure, an effect which appears to be secondary to the hypotensive effect of the drug.
MS2 EFFECTS OF SIBUTRAMINE PLUS L-CARNITINE COMPARED TO SIBUTRAMINE OR PLACEBO ON INFLAMMATORY PARAMETERS G. Derosa1 , I. Ferrari1 , P. Maffioli1 , S. Salvadeo1 , A. Gravina1 , R. Mereu1 , A. D’Angelo1 , I. Palumbo1 , S. Randazzo1 , A. Cicero2 . 1 University of Pavia, Pavia, 2 University of Bologna, Bologna, Italy Aim: To evaluate the effects of one year treatment with sibutramine plus L-carnitine compared to sibutramine or placebo on body weight, lipid profile, insulin resistance, and on inflammatory state in type 2 diabetic patients. Material and Methods: Three hundred and seventy-five diabetics were randomised to take sibutramine 10 mg plus L-carnitine 2 g or sibutramine 10 mg alone or placebo alone. We evaluated at baseline, and after 3, 6, 9, and 12 months these parameters: body weight, homeostasis model assessment insulin resistance index (HOMA-IR), fasting plasma insulin (FPI), lipid profile, adiponectin (ADN), tumor necrosis factor-alfa (TNF-alfa), resistin, and high sensitivity-C reactive protein (Hs-CRP). Results: After 12 months of treatment we observed a better improvement of body weight with sibutramine plus L-carnitine compared to the other treatments. Regarding insulin resistance the best improvement of HOMA-IR, and FPI was obtained with sibutramine plus L-carnitine. An improvement of total cholesterol and triglycerides was observed with sibutramine and with sibutramine plus L-carnitine even if with sibutramine plus L-carnitine there was also an improvement of LDL-C. A similar improvement of resistin, TNF-alfa, and Hs-CRP was obtained with sibutramine and with sibutramine plus L-carnitine, while a better improvement of ADN was recorded with sibutramine plus L-carnitine. Conclusions: Sibutramine and L-carnitine gave a better improvement of lipid profile and of inflammatory parameters compared to placebo even if sibutramine plus L-carnitine had a better effect on HOMA-IR, FPI, LDL-C, ADN and body weight compared to sibutramine alone. 1567-5688/ $ – see front matter © 2010 Elsevier Ireland Ltd. All rights reserved.
MS4 CHRONIC INFLAMMATORY STATE PRESENT IN FAMILIAL HYPERCHOLESTEROLEMIA IS REDUCED AFTER A FAT OVERLOAD RICH IN UNSATURATED FATTY ACIDS S. Martinez-Hervas1,2,3 , C. Ivorra3 , T. Pedro4 , V. Gonzalez-Albert3 , R. Hilario3 , J.F. Ascaso1,2 , R. Carmena1,2 , J.T. Real1,2 , F.J. Chaves3 . 1 Endocrinology and Nutrition, Hospital Clinico Universitario de Valencia, Valencia, 2 Ciber de Diabetes y Enfermedades Metabolicas Asociadas, CIBERDEM, Barcelona, 3 Unidad de Genotipado y Diagnostico Genetico, Fundacion para la Investigacion, Instituto INCLIVA, Hospital Clinico Universitario de Valencia, Valencia, 4 Endocrinology and Nutrition, Hospital Marina Alta, Denia, Spain Introduction: Alterations in inflammation and postprandial lipemia have been involved in the development of atherosclerosis. Familial hypercholesterolemia (FH) is a primary dyslipidemia with high risk of atherosclerosis and coronary disease. However, few data is available about the response of markers of inflammation to a fat overload. Objective: The aim of this study was to examine the effects of a fat load rich in mono and polyunsaturated fatty acids in inflammatory markers along postprandial state in patients with FH and in healthy subjects. Methods: We studied 14 FH patients and 22 normocholesterolemic controls underwent a fat load (Supracal, SHS International). Blood samples were obtained before the fat overload (time 0) and at regular time intervals up to 8 hours (2, 4, 6 and 8 h) after the administration of the liquid load. Glucose, insulin, lipid values, and inflammatory markers, (IL1A, IL4, IL6, IL17, EGF, eotaxin, VEGF, mIp1-a, and MIP1-b), were measured. Results: Although tryglicerides rise after fat overload, a significant decrease in most of the inflammatory markers (IL17, EGF, eotaxin, VEGF, mIp1a, and MIP1-b) was detected. Moreover the decrease was higher in hypercholesterolemic patients than controls. Conclusions: This study reports that a fat load enriched in monounsaturated fatty acids reduces the levels of low grade inflammatory markers related to atherosclerosis in controls and hypercholesterolemic patients, being the
78th EAS Congress, 20−23 June, 2010, Hamburg, Germany Memory Stick Presentations MS1 REGULAR EXERCISE IMPROVED ENDOTHELIAL DYSFUNCTION IN YOUNG MALE ADULTS WITH METABOLIC SYNDROME G. Fornieles-Gonzalez1 , M.A. Rosety-Rodriguez2 , I. Rosety-Rodriguez2 , F.J. Ordonez ˜ 2 , N. Garcia-Gomez3 , A. Camacho4 , M. Rosety-Rodriguez1 . 1 Internal Medicine, 2 School of Sport Medicine, 3 Pathologic Anatomy, University of Cadiz, Cadiz, 4 Medicine, Hospital Juan Ramon Jimenez, Huelva, Spain
MS3 BLOOD PRESSURE-LOWERING RESPONSE TO AMLODIPINE AS A DETERMINANT OF THE ANTIOXIDATIVE ACTIVITY OF SMALL, DENSE HDL3 IN HYPERTENSIVE SUBJECTS B. Hansel1 , X. Girerd2 , D. Bonnefont-Rousselot2 , R. Bittar2 , S. Chantepie1 , A. Orsoni1 , E. Bruckert2 , M.J. Chapman1 , A. Kontush1 . 1 INSERM Unit 939, 2 AP-HP Pitie-Salpetriere, Paris, France
Background and Aims: It is widely accepted endothelial dysfunction may play an important role during the development of atherosclerotic plaque. Recent studies have reported regular exercise may reduce proinflammatory biomarkers in patients with metabolic syndrome However to date little information is available on the influence of exercise on levels of endothelial adhesion molecules. This study was designed to determine the influence of exercise on soluble vascular cell adhesion molecule (VCAM-1) in young male adults with metabolic syndrome. Method: Sixty adult men with metabolic syndrome according to the criteria reported by the National Cholesterol Education Program Adult Treatment Panel III volunteered for this study. Forty-five were randomly included in experimental group to perform a 12-week aerobic training program, 3 days/week, consisting of warm up (10-min), main part (20−35-min [increasing 5 minutes each 3 weeks]) at a work intensity of 60−75% of peak heart rate (increasing 5% each 3 weeks) and cool-down (10-min). Control group included 15 age, sex and BMI-matched men with metabolic syndrome that will not perform any program. Further our protocol was approved by an institutional ethic committee. Serum soluble VCAM-1 concentration was measured by ELISA, using a commercially available kit (Parameter, R&D Systems) twice: 72-hours before starting the program and after its ending. Results: When compared to baseline soluble VCAM-1 concentration was decreased significantly after our 6-week protocol (456.1±18.4 vs 382.7±20.3 ng/ml; p < 0.05). No changes were reported in controls. Conclusion: A 12-week training program decreased soluble VCAM-1 concentration in young male adults with metabolic syndrome.
Objective: Beneficial effects of calcium channel blockers on cardiovascular disease may in part be related to the reduction of oxidative stress, potentially enhancing antioxidative activity (AOX) of high-density lipoprotein (HDL). We assessed the effect of a one-month treatment by amlodipine on HDL AOX in hypertensive subjects. Methods: 28 hypertensive (obesity=46%; metabolic syndrome=57%) patients received 10 mg Amlodipine daily during 1 month. HDL AOX was assessed as the capacity of the small, dense HDL3c subpopulation to inhibit LDL oxidation. Results: HDL3c AOX did not significantly change in the whole study population; changes in AOX were however positively correlated with changes in SBP (r = 0.37, p = 0.05 for maximal diene concentration; r = 0.34, p = 0.08 for LDL oxidation rate). When population was divided in two subgroups according to the blood pressure response to Amlodipine, good responders having SBP/DBP drop above the median (22/10 mmHg) and poor responders below, HDL3c AOX was significantly improved in good responders vs. poor responders (change in the LDL oxidation rate in the presence of HDL3c, −6.8% (11.2) vs +1.9% (5.2) respectively, p = 0.04; maximal diene concentration, −8.6% (13.0) vs +1.9% (8.2) respectively, p < 0.05). By contrast, changes in plasma concentration of oxidized LDL, a marker of systemic oxidative stress, and in chemical composition of HDL3c did not differ between the subgroups. Conclusions: In hypertensive patients, treatment with Amlodipine resulted in the enhancement of HDL AOX only in subjects with the over-the-median decrease in blood pressure, an effect which appears to be secondary to the hypotensive effect of the drug.
MS2 EFFECTS OF SIBUTRAMINE PLUS L-CARNITINE COMPARED TO SIBUTRAMINE OR PLACEBO ON INFLAMMATORY PARAMETERS G. Derosa1 , I. Ferrari1 , P. Maffioli1 , S. Salvadeo1 , A. Gravina1 , R. Mereu1 , A. D’Angelo1 , I. Palumbo1 , S. Randazzo1 , A. Cicero2 . 1 University of Pavia, Pavia, 2 University of Bologna, Bologna, Italy Aim: To evaluate the effects of one year treatment with sibutramine plus L-carnitine compared to sibutramine or placebo on body weight, lipid profile, insulin resistance, and on inflammatory state in type 2 diabetic patients. Material and Methods: Three hundred and seventy-five diabetics were randomised to take sibutramine 10 mg plus L-carnitine 2 g or sibutramine 10 mg alone or placebo alone. We evaluated at baseline, and after 3, 6, 9, and 12 months these parameters: body weight, homeostasis model assessment insulin resistance index (HOMA-IR), fasting plasma insulin (FPI), lipid profile, adiponectin (ADN), tumor necrosis factor-alfa (TNF-alfa), resistin, and high sensitivity-C reactive protein (Hs-CRP). Results: After 12 months of treatment we observed a better improvement of body weight with sibutramine plus L-carnitine compared to the other treatments. Regarding insulin resistance the best improvement of HOMA-IR, and FPI was obtained with sibutramine plus L-carnitine. An improvement of total cholesterol and triglycerides was observed with sibutramine and with sibutramine plus L-carnitine even if with sibutramine plus L-carnitine there was also an improvement of LDL-C. A similar improvement of resistin, TNF-alfa, and Hs-CRP was obtained with sibutramine and with sibutramine plus L-carnitine, while a better improvement of ADN was recorded with sibutramine plus L-carnitine. Conclusions: Sibutramine and L-carnitine gave a better improvement of lipid profile and of inflammatory parameters compared to placebo even if sibutramine plus L-carnitine had a better effect on HOMA-IR, FPI, LDL-C, ADN and body weight compared to sibutramine alone. 1567-5688/ $ – see front matter © 2010 Elsevier Ireland Ltd. All rights reserved.
MS4 CHRONIC INFLAMMATORY STATE PRESENT IN FAMILIAL HYPERCHOLESTEROLEMIA IS REDUCED AFTER A FAT OVERLOAD RICH IN UNSATURATED FATTY ACIDS S. Martinez-Hervas1,2,3 , C. Ivorra3 , T. Pedro4 , V. Gonzalez-Albert3 , R. Hilario3 , J.F. Ascaso1,2 , R. Carmena1,2 , J.T. Real1,2 , F.J. Chaves3 . 1 Endocrinology and Nutrition, Hospital Clinico Universitario de Valencia, Valencia, 2 Ciber de Diabetes y Enfermedades Metabolicas Asociadas, CIBERDEM, Barcelona, 3 Unidad de Genotipado y Diagnostico Genetico, Fundacion para la Investigacion, Instituto INCLIVA, Hospital Clinico Universitario de Valencia, Valencia, 4 Endocrinology and Nutrition, Hospital Marina Alta, Denia, Spain Introduction: Alterations in inflammation and postprandial lipemia have been involved in the development of atherosclerosis. Familial hypercholesterolemia (FH) is a primary dyslipidemia with high risk of atherosclerosis and coronary disease. However, few data is available about the response of markers of inflammation to a fat overload. Objective: The aim of this study was to examine the effects of a fat load rich in mono and polyunsaturated fatty acids in inflammatory markers along postprandial state in patients with FH and in healthy subjects. Methods: We studied 14 FH patients and 22 normocholesterolemic controls underwent a fat load (Supracal, SHS International). Blood samples were obtained before the fat overload (time 0) and at regular time intervals up to 8 hours (2, 4, 6 and 8 h) after the administration of the liquid load. Glucose, insulin, lipid values, and inflammatory markers, (IL1A, IL4, IL6, IL17, EGF, eotaxin, VEGF, mIp1-a, and MIP1-b), were measured. Results: Although tryglicerides rise after fat overload, a significant decrease in most of the inflammatory markers (IL17, EGF, eotaxin, VEGF, mIp1a, and MIP1-b) was detected. Moreover the decrease was higher in hypercholesterolemic patients than controls. Conclusions: This study reports that a fat load enriched in monounsaturated fatty acids reduces the levels of low grade inflammatory markers related to atherosclerosis in controls and hypercholesterolemic patients, being the