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YI-847 MULTIVARIATE REDUCTION OF PROGNOSTIC CARDIOVASCULAR RISK
YI Young investigators in diabetes, with potential improvements also possible in established atherosclerosis. YI-847
MULTIVARIATE REDUCTION OF PROGNOSTIC CARDIOVASCULAR RISK
V.V. Pryanishnikov 1 , I.A. Sobenin 1,2 . 1 Institute of General Pathology and Pathophysiology, Moscow, Russia; 2 Institute for Atherosclerosis Research, Moscow, Russia Background: Polyetiological nature of atherosclerosis allows suggesting that complex reduction of several risk factors is valid way to the prevention of cardiovascular diseases. Aim and Methods: Double-blinded placebo-controlled study was performed in 51 CHD patients and 79 intermediate- and high-risk patients for evaluation of the changes in prognostic risk calculated by algorithms from Framingham and PROCAM Studies. 12-months treatment with garlic-based drug Allicor was used for risk reduction. Results: In CHD patients, the treatment resulted in the significant decrease of 10-year prognostic risk of AMI (fatal and non-fatal) and sudden death by 1.5-fold in men (p<0.05). The main reason for such reduction was the decrease in LDL cholesterol by 32.9±6.6 mg/dl. In women these changes did not reach statistical significance. In patients at elevated risk, Allicor treatment lowered 10-years prognostic risk of CHD development by 13.2% from the baseline level in men (p<0.05), and by 7.1% in women (p<0.05). Prognostic risk of AMI and sudden death was lowered by 26.1% from the baseline level in men (p<0.05), but not in women. The effects were mainly due to the decrease in LDL cholesterol by 23.5±6.5 mg/dl in men, and the rise in HDL cholesterol by 2.7±1.5 mg/dl in women. Conclusions: The obtained results demonstrate the effectiveness of garlic powder tablets in the reduction of the overall multivariate cardiovascular risk in targeted patients. Being the remedy of natural origin, Allicor is safe with the respect to adverse effects and allows perpetual administration, which is quite necessary for the prevention of atherosclerotic diseases. YI-848
SIMVASTATIN MAY HALT THE PROGRESSION OF ATHEROSCLEROSIS IN END-STAGE RENAL DISEASE PATIENTS
We aimed to evaluate the effects of simvastatin 10 mg/day on left ventricular hypertrophy (LVH) and endothelial vascular function in end-stage renal disease (ESRD) patients on haemodialysis (HD). 76 patients with ESRD on HD (45M, 31 F; mean age 42,2±3,6 years, mean time on HD 4,1±1,5 years) were enrolled. 33 (43,42%)patients with total cholesterol (TC) ≥5,2 mmol/l or LDL-C ≥ 3,5 mmol/l received simvastatin 10 mg/day (study group), while 43 (56,57%)- without lipid damage (control group) received no statin treatment for 24 weeks. The lipid profile was measured in the blood. On echocardiography and doppler we determined the left ventricular mass index (LVMI)and the flow-mediated dilation (FMD) in the brachial artery during reactive hyperemia. 25 (75,75%) patients achieved the LDL-C goal ≤ 2,6 mmol/L and 30(91%)-the TC goal ≤4,5 mmol/L. Mean TC, LDL-C, TG and VLDL-C decreased by 22,3%, 43,2%,36,2% and 28,3% respectively, while mean HDL-C increased by 17,5%. All patients had LVH at baseline. At week 24 in the study group LVMI decreased by 2,89%, since it was evidently increased in the control group by 5,17%.FMD was impaired in 61(80,26%) patients.Decreased FMD was correlated with the LVMI(r = -0,48, p < 0,01). After treatment the FMD had been improved by 78,3% and normalized in 22 (66,6%)patients, while it impaired in the control group. Simvastatin may provide beneficial effects for the reduction of cardiovascular risk factors, morbidity and mortality in this population.
expression in the lungs and heart of wild-type (C57BL/6) and genetically modified (eNOS knockout) mice and the role of transcription factor NF-κB and AP-1 in the TF gene expression. Expression of P-selectin and PSGL-1 mRNA was significantly decreased in the lungs and heart of wild-type mice treated by simvastatin (1 mg/kg) when compared to control mice, while its levels in eNOS knockout mice were unchanged. Our data show that tissue factor mRNA levels were also decreased in the lungs and heart of wild-type mice treated by simvastatin when compared to control mice, while its levels in eNOS knockout mice were unchanged. Expression of eNOS gene was induced in the lungs and heart of simvastatin-treated wild-type mice. We examined the possible molecular mechanisms of the regulation of tissue factor gene expression in the lung by simvastatin. TF sequence-specific complex binding to AP-1 and NF-κB domains was decreased in the lungs of simvastatin-treated mice. These results suggest that simvastatin decreases P-selectin, PSGL-1 and tissue factor mRNA expression in the lungs and heart via induction of eNOS gene expression and that regulatory elements AP-1 and NF-κB may be involved in the regulation of tissue factor gene expression by simvastatin and that the suppression of P-selectin and tissue factor is important in its antithrombotic action. In conclusion, simvastatin decreases expression of P-selectin, PSGL-1 and tissue factor mRNA by induction of eNOS. YI-850
DOSE-DEPENDENT IMPROVEMENT IN HIGH-DENSITY LIPOPROTEIN METABOLISM WITH ROSUVASTATIN IN THE METABOLIC SYNDROME
E.M.M. Ooi 1 , G.F. Watts 1 , P.J. Nestel 2 , D. Sviridov 2 , A. Hoang 2 , P.H.R. Barrett 1 . 1 School of Medicine and Pharmacology, University of Western Australia, Perth, Australia; 2 Baker Heart Research Institute, Melbourne, Victoria, Australia Background: Low plasma concentration of HDL cholesterol is a risk factor for cardiovascular disease (CVD) and a feature of the metabolic syndrome. Rosuvastatin has been shown to increase HDL cholesterol concentration, but the mechanisms remain unclear. Methods: Twelve dyslipidemic men with the metabolic syndrome were studied in a randomized, double-blind, three-way, crossover trial of fiveweek therapeutic periods with placebo (P), 10mg/day rosuvastatin (R10) or 40mg/day rosuvastatin (R40), with two-week placebo washout between each period. Results: There was a significant dose-dependent increase in HDL cholesterol (R10 +4.4% R40 +9.7%, p=0.011), HDL particle size (R10 +3.1%, R40 +8.2%, p=0.019) and LpAI concentration (R10 +7% R40 +17%, p=0.030). The increase in LpAI concentration was associated with a significant dose-dependent reduction in triglyceride concentration (R10 -23% R40 -42%, p<0.001) and LpAI fractional catabolic rate (FCR) (P 0.50[0.03], R10 0.42[0.03], R40 0.38[0.03], pools/day, p=0.004) with no change to LpAI production rate (PR). There was a significant dosedependent reduction in LpAI:AII FCR (P 0.30[0.01], R10 0.27[0.02], R40 0.24[0.02], pools/day, p<0.001) with concomitant reduction in LpAI:AII PR (P 11.49[0.72], R10 10.89[0.96], R40 8.98[0.70], mg/kg/day, p<0.01), and hence no change in LpAI:AII concentration. Conclusions: Rosuvastatin dose-dependently increase plasma HDL cholesterol and LpAI concentrations in the metabolic syndrome. This could relate to reduction in plasma triglycerides with remodeling of HDL particles and reduction in LpAI fractional catabolism. The findings explain the mechanisms for the HDL raising effect of rosuvastatin in the metabolic syndrome with implications for reduction in CVD. YI-851
DOSE-DEPENDENT EFFECT OF ROSUVASTATIN ON APOLIPOPROTEIN B-100 KINETICS IN THE METABOLIC SYNDROME
E.M.M. Ooi 1 , P.H.R. Barrett 1 , D.C. Chan 1 , P.J. Nestel 2 , G.F. Watts 1 . School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia; 2 Baker Heart Research Institute, Melbourne, Victoria, Australia 1
YI-849
SIMVASTATIN DECREASES P-SELECTIN AND TISSUE FACTOR MESSENGER RNA EXPRESSION IN MOUSE LUNGS AND HEART: POSSIBLE ROLE IN ITS ANTITHROMBOTIC ACTION
D.O. Minchenko, I.L. Opentanova, O.I. Iljina, O.H. Minchenko. Department of Molecular Biology, Palladin Institute of Biochemistry, Kiev, Ukraine We studied the effect of simvastatin on P-selectin, PSGL-1 and TF mRNA
Aim: The aim of our study was to investigate the dose-dependent effect of rosuvastatin on apolipoprotein (apo) B-100 kinetics in the metabolic syndrome. Methods: Twelve dyslipidemic men with the metabolic syndrome were studied in a randomized, double-blind, three-way, crossover trial of five-week treatment periods with placebo or rosuvastatin (10mg/day or 40mg/day) with two-week placebo wash-outs between treatments.
76th Congress of the European Atherosclerosis Society, June 10–13, 2007, Helsinki, Finland
YOUNG INVESTIGATORS
W.J. Haykal, O.V. Kuryata. Dpt. of Chronic Haemodialysis, Regional Hospital Named After I.I. Mechnikov, Dnepropetrovsk, Ukraine
225
MULTIVARIATE REDUCTION OF PROGNOSTIC CARDIOVASCULAR RISK
V.V. Pryanishnikov 1 , I.A. Sobenin 1,2 . 1 Institute of General Pathology and Pathophysiology, Moscow, Russia; 2 Institute for Atherosclerosis Research, Moscow, Russia Background: Polyetiological nature of atherosclerosis allows suggesting that complex reduction of several risk factors is valid way to the prevention of cardiovascular diseases. Aim and Methods: Double-blinded placebo-controlled study was performed in 51 CHD patients and 79 intermediate- and high-risk patients for evaluation of the changes in prognostic risk calculated by algorithms from Framingham and PROCAM Studies. 12-months treatment with garlic-based drug Allicor was used for risk reduction. Results: In CHD patients, the treatment resulted in the significant decrease of 10-year prognostic risk of AMI (fatal and non-fatal) and sudden death by 1.5-fold in men (p<0.05). The main reason for such reduction was the decrease in LDL cholesterol by 32.9±6.6 mg/dl. In women these changes did not reach statistical significance. In patients at elevated risk, Allicor treatment lowered 10-years prognostic risk of CHD development by 13.2% from the baseline level in men (p<0.05), and by 7.1% in women (p<0.05). Prognostic risk of AMI and sudden death was lowered by 26.1% from the baseline level in men (p<0.05), but not in women. The effects were mainly due to the decrease in LDL cholesterol by 23.5±6.5 mg/dl in men, and the rise in HDL cholesterol by 2.7±1.5 mg/dl in women. Conclusions: The obtained results demonstrate the effectiveness of garlic powder tablets in the reduction of the overall multivariate cardiovascular risk in targeted patients. Being the remedy of natural origin, Allicor is safe with the respect to adverse effects and allows perpetual administration, which is quite necessary for the prevention of atherosclerotic diseases. YI-848
SIMVASTATIN MAY HALT THE PROGRESSION OF ATHEROSCLEROSIS IN END-STAGE RENAL DISEASE PATIENTS
We aimed to evaluate the effects of simvastatin 10 mg/day on left ventricular hypertrophy (LVH) and endothelial vascular function in end-stage renal disease (ESRD) patients on haemodialysis (HD). 76 patients with ESRD on HD (45M, 31 F; mean age 42,2±3,6 years, mean time on HD 4,1±1,5 years) were enrolled. 33 (43,42%)patients with total cholesterol (TC) ≥5,2 mmol/l or LDL-C ≥ 3,5 mmol/l received simvastatin 10 mg/day (study group), while 43 (56,57%)- without lipid damage (control group) received no statin treatment for 24 weeks. The lipid profile was measured in the blood. On echocardiography and doppler we determined the left ventricular mass index (LVMI)and the flow-mediated dilation (FMD) in the brachial artery during reactive hyperemia. 25 (75,75%) patients achieved the LDL-C goal ≤ 2,6 mmol/L and 30(91%)-the TC goal ≤4,5 mmol/L. Mean TC, LDL-C, TG and VLDL-C decreased by 22,3%, 43,2%,36,2% and 28,3% respectively, while mean HDL-C increased by 17,5%. All patients had LVH at baseline. At week 24 in the study group LVMI decreased by 2,89%, since it was evidently increased in the control group by 5,17%.FMD was impaired in 61(80,26%) patients.Decreased FMD was correlated with the LVMI(r = -0,48, p < 0,01). After treatment the FMD had been improved by 78,3% and normalized in 22 (66,6%)patients, while it impaired in the control group. Simvastatin may provide beneficial effects for the reduction of cardiovascular risk factors, morbidity and mortality in this population.
expression in the lungs and heart of wild-type (C57BL/6) and genetically modified (eNOS knockout) mice and the role of transcription factor NF-κB and AP-1 in the TF gene expression. Expression of P-selectin and PSGL-1 mRNA was significantly decreased in the lungs and heart of wild-type mice treated by simvastatin (1 mg/kg) when compared to control mice, while its levels in eNOS knockout mice were unchanged. Our data show that tissue factor mRNA levels were also decreased in the lungs and heart of wild-type mice treated by simvastatin when compared to control mice, while its levels in eNOS knockout mice were unchanged. Expression of eNOS gene was induced in the lungs and heart of simvastatin-treated wild-type mice. We examined the possible molecular mechanisms of the regulation of tissue factor gene expression in the lung by simvastatin. TF sequence-specific complex binding to AP-1 and NF-κB domains was decreased in the lungs of simvastatin-treated mice. These results suggest that simvastatin decreases P-selectin, PSGL-1 and tissue factor mRNA expression in the lungs and heart via induction of eNOS gene expression and that regulatory elements AP-1 and NF-κB may be involved in the regulation of tissue factor gene expression by simvastatin and that the suppression of P-selectin and tissue factor is important in its antithrombotic action. In conclusion, simvastatin decreases expression of P-selectin, PSGL-1 and tissue factor mRNA by induction of eNOS. YI-850
DOSE-DEPENDENT IMPROVEMENT IN HIGH-DENSITY LIPOPROTEIN METABOLISM WITH ROSUVASTATIN IN THE METABOLIC SYNDROME
E.M.M. Ooi 1 , G.F. Watts 1 , P.J. Nestel 2 , D. Sviridov 2 , A. Hoang 2 , P.H.R. Barrett 1 . 1 School of Medicine and Pharmacology, University of Western Australia, Perth, Australia; 2 Baker Heart Research Institute, Melbourne, Victoria, Australia Background: Low plasma concentration of HDL cholesterol is a risk factor for cardiovascular disease (CVD) and a feature of the metabolic syndrome. Rosuvastatin has been shown to increase HDL cholesterol concentration, but the mechanisms remain unclear. Methods: Twelve dyslipidemic men with the metabolic syndrome were studied in a randomized, double-blind, three-way, crossover trial of fiveweek therapeutic periods with placebo (P), 10mg/day rosuvastatin (R10) or 40mg/day rosuvastatin (R40), with two-week placebo washout between each period. Results: There was a significant dose-dependent increase in HDL cholesterol (R10 +4.4% R40 +9.7%, p=0.011), HDL particle size (R10 +3.1%, R40 +8.2%, p=0.019) and LpAI concentration (R10 +7% R40 +17%, p=0.030). The increase in LpAI concentration was associated with a significant dose-dependent reduction in triglyceride concentration (R10 -23% R40 -42%, p<0.001) and LpAI fractional catabolic rate (FCR) (P 0.50[0.03], R10 0.42[0.03], R40 0.38[0.03], pools/day, p=0.004) with no change to LpAI production rate (PR). There was a significant dosedependent reduction in LpAI:AII FCR (P 0.30[0.01], R10 0.27[0.02], R40 0.24[0.02], pools/day, p<0.001) with concomitant reduction in LpAI:AII PR (P 11.49[0.72], R10 10.89[0.96], R40 8.98[0.70], mg/kg/day, p<0.01), and hence no change in LpAI:AII concentration. Conclusions: Rosuvastatin dose-dependently increase plasma HDL cholesterol and LpAI concentrations in the metabolic syndrome. This could relate to reduction in plasma triglycerides with remodeling of HDL particles and reduction in LpAI fractional catabolism. The findings explain the mechanisms for the HDL raising effect of rosuvastatin in the metabolic syndrome with implications for reduction in CVD. YI-851
DOSE-DEPENDENT EFFECT OF ROSUVASTATIN ON APOLIPOPROTEIN B-100 KINETICS IN THE METABOLIC SYNDROME
E.M.M. Ooi 1 , P.H.R. Barrett 1 , D.C. Chan 1 , P.J. Nestel 2 , G.F. Watts 1 . School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia; 2 Baker Heart Research Institute, Melbourne, Victoria, Australia 1
YI-849
SIMVASTATIN DECREASES P-SELECTIN AND TISSUE FACTOR MESSENGER RNA EXPRESSION IN MOUSE LUNGS AND HEART: POSSIBLE ROLE IN ITS ANTITHROMBOTIC ACTION
D.O. Minchenko, I.L. Opentanova, O.I. Iljina, O.H. Minchenko. Department of Molecular Biology, Palladin Institute of Biochemistry, Kiev, Ukraine We studied the effect of simvastatin on P-selectin, PSGL-1 and TF mRNA
Aim: The aim of our study was to investigate the dose-dependent effect of rosuvastatin on apolipoprotein (apo) B-100 kinetics in the metabolic syndrome. Methods: Twelve dyslipidemic men with the metabolic syndrome were studied in a randomized, double-blind, three-way, crossover trial of five-week treatment periods with placebo or rosuvastatin (10mg/day or 40mg/day) with two-week placebo wash-outs between treatments.
76th Congress of the European Atherosclerosis Society, June 10–13, 2007, Helsinki, Finland
YOUNG INVESTIGATORS
W.J. Haykal, O.V. Kuryata. Dpt. of Chronic Haemodialysis, Regional Hospital Named After I.I. Mechnikov, Dnepropetrovsk, Ukraine
225