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P51 HOMOCYSTEINE AS A CARDIOVASCULAR RISK MARKER IN POLYCYSTIC OVARY SYNDROME
78th EAS Congress
Atherosclerosis Supplements 11, no. 2 (2010) 17–108
and markers of inflammation, adipocytokines, markers of oxidative stress and endothelial dysfunction. Results: When compared with controls, the subgroup of obese men had significantly higher values of oxLDL/beta2GPI, oxLDL and AOPP (all p < 0.01), however in regression analysis only oxLDL/beta2GPI correlated with the immunokine- IL-8 and endothelial dysfunction marker-PAI-I (both p < 0.01). Multiple regression analysis revealed that the correlation of oxLDL/beta2GPI with PAI-I remained significant independently of triglycerides, BMI and WHR. Conclusion: In early-stage of insulin resistance, plasma concentration of the oxLDL/beta2GPI complex reflects both inflammation and endothelial dysfunction. Increased oxLDL/beta2GPI may thus serve as a marker of atherosclerosis initiation on the endothelium level. Supported by MSM0021620814. P49 AN ERYTHROPOIETIN RECEPTOR (EPOR) IN HUMAN ADIPOSE TISSUE (AT) 1 1 K. Moller ¨ 1 , E. Piella2 , P. Algenstaedt2 , D.E. Muller-Wiefel ¨ . Pediatric Nephrology, Children’s Hospital of the University of Hamburg, 2 Endocrinology, Medical Clinic of the Universitiy of Hamburg, Hamburg, Germany
AT is an endocrine organ − secreting inflammatoric and antiinflammatoric adipocytokines playing an important role in the development of atherosclerosis. However, few is known about the regulation of the expression of adipocyte derived products. The observation that renal patients under therapy with an erythropoietin stimulation factor (ESF) have higher serum-adiponectine concentrations than those without therapy leads to the hypothesis that there might be a tissue specific EPOR in AT. We investigated the expression of an EPOR in human AT under the influence of ESF. AT of patients was harvested during an elective surgery. Probes were incubated with ESF vs simple culture medium. The m-RNA of the adipocytes was isolated, a relative quantification by real-time PCR and the sequencing of all three domains of the EPOR was performed. The EPOR and the phosphorylation of Stat5 and Jak2 on protein level were examined by Western blot technique. The expression of an EPOR on RNA and protein level could be demonstrated in AT. After stimulation with ESF there was an increase of mRNA-expression of the EPOR and an increase of the expression of phosphorylated Jak2 and Stat5. Data show for the first time an expression of an EPOR in human AT and its regulation by ESF. Therefore a direct influence of ESF on the regulation of the expression of adipocytokines in human AT can be assumed. The EPOR could be an important factor in the regulation of the endocrine functions of AT and might play a protective role in the development of atherosclerosis. P50 VARIANT IN KIF6 PREDICTS CORONARY EVENTS AND EVENT REDUCTION FROM STATIN THERAPY: CARE, WOSCOPS, PROSPER AND PROVE IT-TIMI 22 STUDIES O. Iakoubova. Cardiovascular Diseases, Celera, Alameda, CA, USA Aims: To identify and validate genetic variants associated with risk for coronary events and differential response to statin therapy, we investigate the association between a 719Arg variant of kinesin family member 6 (encoded by the gene KIF6) and coronary events in placebo groups of CARE and WOSCOPS and response to statin therapy in the CARE, WOSCOPS, PROSPER and PROVE IT-TIMI 22 trials. Results: In placebo-treated patients, carriers of the KIF6 719Arg allele (59% of population) had a hazard ratio of 1.50 (95% CI 1.05–2.15) in CARE, an odds ratio of 1.55 (95% CI 1.14–2.09) in WOSCOPS, and a hazard ratio of 1.28 (95% CI 0.98–1.69) in PROSPER patients with prior vascular disease. Among 719Arg carriers, the absolute risk reduction from pravastatin therapy was 4.9% (95% CI 1.8−8.0) in CARE, 5.5% (95% CI 3.5−7.5) in WOSCOPS, and 6.3% (95% CI 2.5–10.0%) in PROSPER patients with prior vascular disease. In contrast, no significant risk reduction was observed among noncarriers in any of these studies. In PROVE IT-TIMI 22, benefit from high-dose, compared with standard-dose, statin therapy was significantly greater in carriers (p = 0.018 for interaction between 719Arg carrier status and treatment) with an absolute risk reduction of 10.0% (95% CI 4.9–15.0%) in carriers versus 0.8% in noncarriers. In conclusion, we have idenified a KIF6 719Arg variant that predicts risk of coronary events and event reduction during pravastatin therapy. In addition, carriers also received significantly greater benefit (event reduction) from highdose statin therapy than noncarriers received. P51 HOMOCYSTEINE AS A CARDIOVASCULAR RISK MARKER IN POLYCYSTIC OVARY SYNDROME A. Atanasova1 , G. Dimitrov1 , S. Biljali2 . 1 University Clinic for Gynecology and Obstetric, 2 Institute for Clinical Chemistry, Skopje, FYR Macedonia Polycystic ovary syndrome (PCOS) is a condition characterized by oligomenorhea and androgen excess, affects 6−10% of the women in reproductive period. Although the pathogenesis is still uncertain, many studies suggest that PCOS may increase risk for several conditions
27
including insulin resistance, type 2 diabetes, dyslipidemia, hypertension, cardiovascular risk. Woman with PCOS would be expected to be at significantly increased risk for atherosclerotic disease. Hyperhomocysteinemia has been shown as independent predictor of cardiovascular mortality in patients with atherosclerosis. The aim of our study was to determinate levels of homocysteine in woman with polycystic ovary syndrome compared with healthy woman. Thirty two patients (age, 23.5±5.5) with PCOS and twenty five (age, 25.5±4.3) healthy woman were involved in the study. Blood samples were collected in early follicular phase. Total homocysteine was measured using fluorescent immunoassay. Statistically significant differences in serum concentration of homocysteine were observed between groups. Mean homocysteine level we found as (10.2±2.9 vs. 7.0±1.5) in PCOS and normal group respectively (p < 0.05). For Macedonian population we found statistically significant increased homocysteine levels in woman with PCOS. Although the mean homocysteine levels are within normal limits, there are significant higher mean homocysteine concentrations between these two groups. Because increased concentrations of tHcy has been shown as an independent risk factor for cardiovascular alterations, it is essential that in this group of woman are taken measures for early prevention. P52 INFLUENCE OF ARTERIAL STIFFNESS, BODY CONSISTENCY AND SECONDHAND SMOKE EXPOSURE ON CHRONIC VALVE DISEASE AND MYOCARDIAL INFARCTION A. Domonkos Tarnoki1 , D.L. Tarnoki1 , Z. Garami2 , G. Veress3 . 1 Department of Radiology and Oncotherapy, Semmelweis University, Budapest, Hungary, 2 Methodist Hospital DeBakey Heart and Vascular Center, Houston, TX, USA, 3 State Hospital of Cardiology, Balatonfured, Hungary Objective: Pulse Wave Velocity (PWVao) and Augmentation Index (AIxbra) are associated with the structural changes of arteriosclerosis but never investigated between the two subject groups. Aim: To determine the arterial stiffness, body consistency and secondhand smoke (SHS) exposure among patients suffering from chronic valve disease (CVD) and myocardial infarction (MI). Methods: 138 patients were examined (97 MI and 41 CVD) by TensioMed Arteriograph, OMRON BF500 body consistency monitor (via bioimpendance analysis) and a detailed questionnaire. Results: Higher Aixbra was found in MI group (0.85±25.5 vs. −2.9±31%). PWVao was higher in CVD group (12±3.2 vs. 11.2±2.5 m/s). PWVao and Aixbra worsen by aging in both groups. MI group had higher peripherial blood pressure (138/77 vs. 132/74 Hgmm), SBPao (137.7±22.5 vs. 130.3±19.3 Hgmm), MAP (97.6±11.6 vs. 93.19±9.2 Hgmm), decreased DRA (39.64±11.2 vs. 43.87±15.8) and DAI (46.4±9.7 vs. 52±7%), respectively. Higher BMI (29.19±4.6 vs. 27.54±3.7 kg/m2 ), body fat% (32.49±10.8 vs. 30.68±10.2%), visceral fat (12.3±4.3 vs. 10.41±3.9), smoking rate (52.6 vs. 46.3%) and duration (26.6 vs. 22.3 years), significant higher home, workplace and other SHS exposure (1.27 vs 0.45, 1.47 vs 1.03, 0.45 vs 0.27 hours/day) were present in MI group. Conclusions: Increased and abnormal arterial stiffnesses were found in both groups indicating presence of atherosclerosis. Adverse body consistency (higher body fat% and visceral fat) and higher SHS exposure indicate an increased risk of MI. P53 CARDIOPROTECTIVE EFFECT OF RED WINE A. Novakovic1 , L. Gojkovic Bukarica2 , D. Nezic3 , M. Peric3 , V. Kanjuh4 . 1 Dept. of Pharmacology, Faculty of Pharmacy, 2 Dept. of Pharmacology, School of Medicine, 3 Institute of Cardiovascular Diseases “Dedinje”, 4 Academy of Sciences and Arts, Belgrade, Serbia The lower incidence of coronary artery disease in the Soutern French and other Mediterranean populations, despite a diet rich in saturated fat and high smoking habits (the so-called French paradox), has been atributed to the prolonged and moderate red wine consumption by these population. It is considered that resveratrol, as a polyphenol, is presented in red wine in significant amounts, and partly responsible for cardiovascular benefits associated with wine consumption. The mechanism of cardiovascular benefits probably includes vasorelaxation, antioxidant and anti-platelet effects of resveratrol. The mechanisms by which resveratrol causes vasodilatation are uncertain. Aim: The aim of this study was to investigate the mechanism (s) of resveratrol-induced vasorelaxation in human internal mammary artery (HIMA) with endothelium and without endothelium. Methods: HIMA were precontracted with phenylephrine (10 mM). Results: Resveratrol induced a concentration-dependent relaxation of the rings with endothelium and without endothelium. Highly selective blocker of ATPsensitive K+ channels, glibenclamide as well as nonselective blockers of Casensitive K+ channels, tetraethylammonium did not block resveratrol-induced relaxation of HIMA rings. Charybdotoxin, a blocker of calcium-sensitive K+ channels did not affect the resveratrol-induced relaxation. 4-Aminopyridine, non selective blocker of voltage-gated K+ (KV ) channels, and margatoxin that inhibits KV 1 channels abolished relaxation of HIMA rings induced by resveratrol.
Atherosclerosis Supplements 11, no. 2 (2010) 17–108
and markers of inflammation, adipocytokines, markers of oxidative stress and endothelial dysfunction. Results: When compared with controls, the subgroup of obese men had significantly higher values of oxLDL/beta2GPI, oxLDL and AOPP (all p < 0.01), however in regression analysis only oxLDL/beta2GPI correlated with the immunokine- IL-8 and endothelial dysfunction marker-PAI-I (both p < 0.01). Multiple regression analysis revealed that the correlation of oxLDL/beta2GPI with PAI-I remained significant independently of triglycerides, BMI and WHR. Conclusion: In early-stage of insulin resistance, plasma concentration of the oxLDL/beta2GPI complex reflects both inflammation and endothelial dysfunction. Increased oxLDL/beta2GPI may thus serve as a marker of atherosclerosis initiation on the endothelium level. Supported by MSM0021620814. P49 AN ERYTHROPOIETIN RECEPTOR (EPOR) IN HUMAN ADIPOSE TISSUE (AT) 1 1 K. Moller ¨ 1 , E. Piella2 , P. Algenstaedt2 , D.E. Muller-Wiefel ¨ . Pediatric Nephrology, Children’s Hospital of the University of Hamburg, 2 Endocrinology, Medical Clinic of the Universitiy of Hamburg, Hamburg, Germany
AT is an endocrine organ − secreting inflammatoric and antiinflammatoric adipocytokines playing an important role in the development of atherosclerosis. However, few is known about the regulation of the expression of adipocyte derived products. The observation that renal patients under therapy with an erythropoietin stimulation factor (ESF) have higher serum-adiponectine concentrations than those without therapy leads to the hypothesis that there might be a tissue specific EPOR in AT. We investigated the expression of an EPOR in human AT under the influence of ESF. AT of patients was harvested during an elective surgery. Probes were incubated with ESF vs simple culture medium. The m-RNA of the adipocytes was isolated, a relative quantification by real-time PCR and the sequencing of all three domains of the EPOR was performed. The EPOR and the phosphorylation of Stat5 and Jak2 on protein level were examined by Western blot technique. The expression of an EPOR on RNA and protein level could be demonstrated in AT. After stimulation with ESF there was an increase of mRNA-expression of the EPOR and an increase of the expression of phosphorylated Jak2 and Stat5. Data show for the first time an expression of an EPOR in human AT and its regulation by ESF. Therefore a direct influence of ESF on the regulation of the expression of adipocytokines in human AT can be assumed. The EPOR could be an important factor in the regulation of the endocrine functions of AT and might play a protective role in the development of atherosclerosis. P50 VARIANT IN KIF6 PREDICTS CORONARY EVENTS AND EVENT REDUCTION FROM STATIN THERAPY: CARE, WOSCOPS, PROSPER AND PROVE IT-TIMI 22 STUDIES O. Iakoubova. Cardiovascular Diseases, Celera, Alameda, CA, USA Aims: To identify and validate genetic variants associated with risk for coronary events and differential response to statin therapy, we investigate the association between a 719Arg variant of kinesin family member 6 (encoded by the gene KIF6) and coronary events in placebo groups of CARE and WOSCOPS and response to statin therapy in the CARE, WOSCOPS, PROSPER and PROVE IT-TIMI 22 trials. Results: In placebo-treated patients, carriers of the KIF6 719Arg allele (59% of population) had a hazard ratio of 1.50 (95% CI 1.05–2.15) in CARE, an odds ratio of 1.55 (95% CI 1.14–2.09) in WOSCOPS, and a hazard ratio of 1.28 (95% CI 0.98–1.69) in PROSPER patients with prior vascular disease. Among 719Arg carriers, the absolute risk reduction from pravastatin therapy was 4.9% (95% CI 1.8−8.0) in CARE, 5.5% (95% CI 3.5−7.5) in WOSCOPS, and 6.3% (95% CI 2.5–10.0%) in PROSPER patients with prior vascular disease. In contrast, no significant risk reduction was observed among noncarriers in any of these studies. In PROVE IT-TIMI 22, benefit from high-dose, compared with standard-dose, statin therapy was significantly greater in carriers (p = 0.018 for interaction between 719Arg carrier status and treatment) with an absolute risk reduction of 10.0% (95% CI 4.9–15.0%) in carriers versus 0.8% in noncarriers. In conclusion, we have idenified a KIF6 719Arg variant that predicts risk of coronary events and event reduction during pravastatin therapy. In addition, carriers also received significantly greater benefit (event reduction) from highdose statin therapy than noncarriers received. P51 HOMOCYSTEINE AS A CARDIOVASCULAR RISK MARKER IN POLYCYSTIC OVARY SYNDROME A. Atanasova1 , G. Dimitrov1 , S. Biljali2 . 1 University Clinic for Gynecology and Obstetric, 2 Institute for Clinical Chemistry, Skopje, FYR Macedonia Polycystic ovary syndrome (PCOS) is a condition characterized by oligomenorhea and androgen excess, affects 6−10% of the women in reproductive period. Although the pathogenesis is still uncertain, many studies suggest that PCOS may increase risk for several conditions
27
including insulin resistance, type 2 diabetes, dyslipidemia, hypertension, cardiovascular risk. Woman with PCOS would be expected to be at significantly increased risk for atherosclerotic disease. Hyperhomocysteinemia has been shown as independent predictor of cardiovascular mortality in patients with atherosclerosis. The aim of our study was to determinate levels of homocysteine in woman with polycystic ovary syndrome compared with healthy woman. Thirty two patients (age, 23.5±5.5) with PCOS and twenty five (age, 25.5±4.3) healthy woman were involved in the study. Blood samples were collected in early follicular phase. Total homocysteine was measured using fluorescent immunoassay. Statistically significant differences in serum concentration of homocysteine were observed between groups. Mean homocysteine level we found as (10.2±2.9 vs. 7.0±1.5) in PCOS and normal group respectively (p < 0.05). For Macedonian population we found statistically significant increased homocysteine levels in woman with PCOS. Although the mean homocysteine levels are within normal limits, there are significant higher mean homocysteine concentrations between these two groups. Because increased concentrations of tHcy has been shown as an independent risk factor for cardiovascular alterations, it is essential that in this group of woman are taken measures for early prevention. P52 INFLUENCE OF ARTERIAL STIFFNESS, BODY CONSISTENCY AND SECONDHAND SMOKE EXPOSURE ON CHRONIC VALVE DISEASE AND MYOCARDIAL INFARCTION A. Domonkos Tarnoki1 , D.L. Tarnoki1 , Z. Garami2 , G. Veress3 . 1 Department of Radiology and Oncotherapy, Semmelweis University, Budapest, Hungary, 2 Methodist Hospital DeBakey Heart and Vascular Center, Houston, TX, USA, 3 State Hospital of Cardiology, Balatonfured, Hungary Objective: Pulse Wave Velocity (PWVao) and Augmentation Index (AIxbra) are associated with the structural changes of arteriosclerosis but never investigated between the two subject groups. Aim: To determine the arterial stiffness, body consistency and secondhand smoke (SHS) exposure among patients suffering from chronic valve disease (CVD) and myocardial infarction (MI). Methods: 138 patients were examined (97 MI and 41 CVD) by TensioMed Arteriograph, OMRON BF500 body consistency monitor (via bioimpendance analysis) and a detailed questionnaire. Results: Higher Aixbra was found in MI group (0.85±25.5 vs. −2.9±31%). PWVao was higher in CVD group (12±3.2 vs. 11.2±2.5 m/s). PWVao and Aixbra worsen by aging in both groups. MI group had higher peripherial blood pressure (138/77 vs. 132/74 Hgmm), SBPao (137.7±22.5 vs. 130.3±19.3 Hgmm), MAP (97.6±11.6 vs. 93.19±9.2 Hgmm), decreased DRA (39.64±11.2 vs. 43.87±15.8) and DAI (46.4±9.7 vs. 52±7%), respectively. Higher BMI (29.19±4.6 vs. 27.54±3.7 kg/m2 ), body fat% (32.49±10.8 vs. 30.68±10.2%), visceral fat (12.3±4.3 vs. 10.41±3.9), smoking rate (52.6 vs. 46.3%) and duration (26.6 vs. 22.3 years), significant higher home, workplace and other SHS exposure (1.27 vs 0.45, 1.47 vs 1.03, 0.45 vs 0.27 hours/day) were present in MI group. Conclusions: Increased and abnormal arterial stiffnesses were found in both groups indicating presence of atherosclerosis. Adverse body consistency (higher body fat% and visceral fat) and higher SHS exposure indicate an increased risk of MI. P53 CARDIOPROTECTIVE EFFECT OF RED WINE A. Novakovic1 , L. Gojkovic Bukarica2 , D. Nezic3 , M. Peric3 , V. Kanjuh4 . 1 Dept. of Pharmacology, Faculty of Pharmacy, 2 Dept. of Pharmacology, School of Medicine, 3 Institute of Cardiovascular Diseases “Dedinje”, 4 Academy of Sciences and Arts, Belgrade, Serbia The lower incidence of coronary artery disease in the Soutern French and other Mediterranean populations, despite a diet rich in saturated fat and high smoking habits (the so-called French paradox), has been atributed to the prolonged and moderate red wine consumption by these population. It is considered that resveratrol, as a polyphenol, is presented in red wine in significant amounts, and partly responsible for cardiovascular benefits associated with wine consumption. The mechanism of cardiovascular benefits probably includes vasorelaxation, antioxidant and anti-platelet effects of resveratrol. The mechanisms by which resveratrol causes vasodilatation are uncertain. Aim: The aim of this study was to investigate the mechanism (s) of resveratrol-induced vasorelaxation in human internal mammary artery (HIMA) with endothelium and without endothelium. Methods: HIMA were precontracted with phenylephrine (10 mM). Results: Resveratrol induced a concentration-dependent relaxation of the rings with endothelium and without endothelium. Highly selective blocker of ATPsensitive K+ channels, glibenclamide as well as nonselective blockers of Casensitive K+ channels, tetraethylammonium did not block resveratrol-induced relaxation of HIMA rings. Charybdotoxin, a blocker of calcium-sensitive K+ channels did not affect the resveratrol-induced relaxation. 4-Aminopyridine, non selective blocker of voltage-gated K+ (KV ) channels, and margatoxin that inhibits KV 1 channels abolished relaxation of HIMA rings induced by resveratrol.