- Email: [email protected]
W16-P-022 Study of the effect of atorvastatin on markers for prethrombotic state in patients with unstable angina and dyslipidaemia
Workshops W16 Treatment of atherosclerosis risk
106
and TC were 24.42% (p<0.01), 25.33 (p<0.01), and 2028 (p<0.01), respectively. Mean increasing in HDL-C was 8.33% (p>0.01). Mean reduction in homocysteine was 21.10% (p<0.01). In the control group, mean percent reductions for TC, LDL-C, and TC were 26.89% (p<0.01), 29.01 (p<0.01), and 18.17 (p<0.01), respectively. Mean increasing in HDL-C was 6.70% (p>0.01). Mean reduction in homocysteine was 8.74% (p>0.01). Conclusions: Low dose atorvastatin reduces TC, LDL-C, and TG significatively and has no significant effect on HDL-C although such levels tends to increase slightly. In our patients, in the absence of concomitant treatment with vitamin B 12 or folic acid, atorvastatin also reduced homocysteine concentrations in hyperhomocysteinemic patients but there were no significant changes in homocysteine concentrations in patients with normal levels of homocysteine. If low dose of statins can diminish hyperlipidemia-associated hyperhomocysteinemia, the need of supplementation with vitamin B 12 and folic acid could be avoided.
I w l 6-P-0221 STUDY O F THE EFFECT OF ATORVASTATIN ON M A R K E R S F O R P R E T H R O M B O T I C STATE IN PATIENTS W I T H UNSTABLE ANGINA AND DYSLIPIDAEMIA I
N. Doncheva 1, Z. Kuneva 2, D. Zeldeeva 3 , L. Parvanova4 . 2Department of
Clinical Lipidology, Medical Institute-Ministry of Interior, Sofia, Bulgaria; 2 University Hospital "Alexandrovska", Sofia, Bulgaria; 3Emergency Medical Institute "Pirogov", Sofia, Bulgaria; 4National Research Veterinary Medicine Institute, Sofia, Bulgaria Objective: The aim of the study was to investigate the effect of Atorvastatin in patients with UA and primary dyslipidaemia. Methods: Forty patients were divided into 2 groups. Group one were treated by 20 mg Atorvastatin for 10 months; second group were left on dietary DLP correction. Initially and on the 5th, 8 th, and 10th months were measured lipids, lipid indices, FG+LDL-C/HDL-C, apolipoproteins, Lp(a), ASAT, ALAT, CPK, Prothrombin fragment 1+2 (Fl+2), ThrombinAntithrombin III complex (TAT), fibrin monomer (FM), FG and MPV. Results: In group one on the 5th month: TC, LDL-C, TG, indices and TAT decreased, but HDL-C was elevated significantly; LDL-C reached target value. On the 8 th month A p t AI was increased, while A p t B decreased significantly. MPV, FG, Lp(a), FM, Fl+2 and enzymes were not shifted significantly till the 10th month. In group two LDL-C was reduced, while MPV was elevated. In patients with clinical aggravation Lp(a), MPV, TAT, FM and Fl+2 were elevated on the 5th and 10th months. No fatal coronary events emerged in group one, but there were two in 2 nd group, in patients with high values of Lp(a), TAT, Fl+2. Conclusions: UA was accompanied by moderately expressed DLP and haemostasis disturbances predisposing to thrombotic events. Atorvastatin effect on lipids and haemostasis was most apparent on the 5 th month. Evaluation of Lp(a), TAT and Fl+2 in UA patients may contribute to early estimation of thrombotic risk.
W16-P-0231 LIPID L O W E R I N G THERAPY EFFECT ON POSTPRANDIAL LIPID PROFILE IN PATIENTS W I T H H E A R T I S C H E M I C DISEASE AND M E T A B O L I C DYSFUNCTION E.F. Dorodneva, I.V. Medvedeva, Y.G. Usacheva, U.B. Gorbunova. Tyumen
Department of the South-Ural Center of Russian Academy of Medical Science, Tyumen, Russia Purpose: To anaiyze the influence of lipid lowering therapy by atorvastatin ("Liprimar") on changes in postprandial profile of plasma lipids and level of general cholesterol and its fractions in thrombocyte membrane. Methods: 30 males with heart ischemic disease, II-III functional class, average age of 46.2 5= 2.7 year were examined. All patients suffered accompanying metabolic disorders such as abdominal obesity (body mass index >27 kg/m 2, waist circumference > 102 cm), arterial hypertension 1-2 degrees and dyslipidemia. Exclusion criteria were as following: clinical manifestation of the carbohydrate metabolism dysfunctions, complications of arterial hypertension, severe concomitant somatic diseases, elderly age. All patients underwent food load test by animal fat (50 g of butter) with estimation of postprandial metabolism before and after the therapy of atorvastatin. Remits: The results of the study showed significant changes in postprandial lipid metabolism and thrombocyte membranes in patients with heart ischemic disease and metabolic dysfunctions. Among statistically signifi-
cant changes am: increased level of cholesterol, triglycerides of the plasma, LDL-cholesterol (p=0.032), decreased level of HDL-cholesterol (p=0.048), accompanied by increasing level of general cholesterol (p=0.007) and its ethers (p=0.018) in thrombocyte membrane during 6 hour postprandial period after food load, LDL-cholesterol test by animal fat (the butter, 50 g). After 30 days of atorvastatin therapy (10 nag daily) no significant increasing of lipid fraction was registered in postprandial period that was accompanied by increasing of level of general cholesterol in thrombocyte membranes and significant increasing its etherificated fractions (p=0.038). Conclusions: Atorvastatin therapy not only normalizes postprandial response of blood plasma lipids, but also promotes the reduction of general cholesterol level in thrombocyte membranes along with increasing level of its etherification, which also motivates prescription of lipid lowering therapy in complex treatment of patients with described pathology.
I W16-P-024 I E F F E C T OF L O N G - T E R M DIET AND N-3 FATTY ACID INTERVENTION ON A S Y M M E T R I C D I M E T H Y L A R G I N I N E (ADMA) I
H.M.A. Eid 1, H. Amesen 2, E.M. Hjerkinn I , T. Lyberg 1, I. Ellingsen 1, I. Seljeflot 1 . ] Center for Clinical Research, Ulleval University Hospita~
Oslo, Norway; 2Department of Cardiology, UUeval University Hospital, Oslo, Norway Objectives: Impaired vasedilation which is related to atherosclerosis, has been suggested to be caused by inhibition of nitric oxide generation by asymmetric dimethylarginine (ADMA) and/or alteration in the L-arginine to ADMA ratio. We wanted to explore whether n-3 polyunsaturated fatty acid (PUFA) supplementation and/or diet intervention beneficially influence endothelial function assessed as plasma ADMA levels and the L-arginine/ADMA ratio. Methods: A male population (n=563, age 704-6 yrs) with long-standing hyperlipidemia, was included, randomly allocated to receive n-3 PUFA placebo capsules and no dietary advice; dietary advice; n-3 PUFA capsules (2.4 g/d); or dietary advice combined with n-3 PUFA capsules, and followed for 3 years. Fasting blood samples were drawn at baseline and the end of the study. Results: No influence of either regimens on ADMA levels were obtained. However, n-3 PUFA supplementation was accompanied by an increase in L-arginine levels, different from the decrease observed in the placebo group (p<0.05). This was even more pronounced in individuals with low body mass index (<26 kg/m 2) (p=0.01), in which also the Larginine/ADMA ratio was reduced on placebo compared to those receiving n-3 PUFA (n=0.04). Conclusion: In this rather large long-term intervention study, ADMA levels were not influenced by dietary counseling, n-3 PUFA seems, however, to counteract the time-related reduction in L-arginine seen on placebo, which might be discussed as an improvement of endothelial dysfunction.
I W16-P-025 I CHANGES OF PLASMA ATHEROSCLEROSIS I
RISK
FACTORS' LEVELS CAUSED BY ESTROGEN REPLACEMENT THERAPY
T. Fait, M. Vrablik, M. Kostirova. General Faculty Hospital and 1st
Faculty of Medicine Charles University, Prague, Czech republic Objectives: Conclusions from observation studies demonstrated a positive effect of hormone replacement therapy (HRT) in menopause in both primary and secondary prevention of ischaemic heart disease. But all randomised trials failed to prove this positive effect. Only the EPAT trial indicate possible positive effects of some HRT regimens. We describe metabolic changes, which could explain these discrepancies. Material and methods: 40 hysterectomisod women more then 6 weeks after a surgically induced menopause or after an interruption of HRT were divided in two groups. All women have suffered from an acute climacteric syndrome. Two ERT regimens (2 mg estradiol pills, 50 ug/day transdermal patches) were administered randomly in twelve weeks crossover study design. Hormone levels, blood count, liver enzymes, lipid profile, coagulation markers, hsCRP, PAI-1 and TPHI were measured at baseline, after three and six months therapy. Results: Estradiol pills had significantly better impact on plasma lipids and lipoproteins than transdermal patches. Effects on other variables am being analysed. Conclusions: We know from daily experience and literature that not only individualisation but also timing and way of administration of sexual
75th EAS Congress, 23-26 April 2005, Prague, Czech Republic
106
and TC were 24.42% (p<0.01), 25.33 (p<0.01), and 2028 (p<0.01), respectively. Mean increasing in HDL-C was 8.33% (p>0.01). Mean reduction in homocysteine was 21.10% (p<0.01). In the control group, mean percent reductions for TC, LDL-C, and TC were 26.89% (p<0.01), 29.01 (p<0.01), and 18.17 (p<0.01), respectively. Mean increasing in HDL-C was 6.70% (p>0.01). Mean reduction in homocysteine was 8.74% (p>0.01). Conclusions: Low dose atorvastatin reduces TC, LDL-C, and TG significatively and has no significant effect on HDL-C although such levels tends to increase slightly. In our patients, in the absence of concomitant treatment with vitamin B 12 or folic acid, atorvastatin also reduced homocysteine concentrations in hyperhomocysteinemic patients but there were no significant changes in homocysteine concentrations in patients with normal levels of homocysteine. If low dose of statins can diminish hyperlipidemia-associated hyperhomocysteinemia, the need of supplementation with vitamin B 12 and folic acid could be avoided.
I w l 6-P-0221 STUDY O F THE EFFECT OF ATORVASTATIN ON M A R K E R S F O R P R E T H R O M B O T I C STATE IN PATIENTS W I T H UNSTABLE ANGINA AND DYSLIPIDAEMIA I
N. Doncheva 1, Z. Kuneva 2, D. Zeldeeva 3 , L. Parvanova4 . 2Department of
Clinical Lipidology, Medical Institute-Ministry of Interior, Sofia, Bulgaria; 2 University Hospital "Alexandrovska", Sofia, Bulgaria; 3Emergency Medical Institute "Pirogov", Sofia, Bulgaria; 4National Research Veterinary Medicine Institute, Sofia, Bulgaria Objective: The aim of the study was to investigate the effect of Atorvastatin in patients with UA and primary dyslipidaemia. Methods: Forty patients were divided into 2 groups. Group one were treated by 20 mg Atorvastatin for 10 months; second group were left on dietary DLP correction. Initially and on the 5th, 8 th, and 10th months were measured lipids, lipid indices, FG+LDL-C/HDL-C, apolipoproteins, Lp(a), ASAT, ALAT, CPK, Prothrombin fragment 1+2 (Fl+2), ThrombinAntithrombin III complex (TAT), fibrin monomer (FM), FG and MPV. Results: In group one on the 5th month: TC, LDL-C, TG, indices and TAT decreased, but HDL-C was elevated significantly; LDL-C reached target value. On the 8 th month A p t AI was increased, while A p t B decreased significantly. MPV, FG, Lp(a), FM, Fl+2 and enzymes were not shifted significantly till the 10th month. In group two LDL-C was reduced, while MPV was elevated. In patients with clinical aggravation Lp(a), MPV, TAT, FM and Fl+2 were elevated on the 5th and 10th months. No fatal coronary events emerged in group one, but there were two in 2 nd group, in patients with high values of Lp(a), TAT, Fl+2. Conclusions: UA was accompanied by moderately expressed DLP and haemostasis disturbances predisposing to thrombotic events. Atorvastatin effect on lipids and haemostasis was most apparent on the 5 th month. Evaluation of Lp(a), TAT and Fl+2 in UA patients may contribute to early estimation of thrombotic risk.
W16-P-0231 LIPID L O W E R I N G THERAPY EFFECT ON POSTPRANDIAL LIPID PROFILE IN PATIENTS W I T H H E A R T I S C H E M I C DISEASE AND M E T A B O L I C DYSFUNCTION E.F. Dorodneva, I.V. Medvedeva, Y.G. Usacheva, U.B. Gorbunova. Tyumen
Department of the South-Ural Center of Russian Academy of Medical Science, Tyumen, Russia Purpose: To anaiyze the influence of lipid lowering therapy by atorvastatin ("Liprimar") on changes in postprandial profile of plasma lipids and level of general cholesterol and its fractions in thrombocyte membrane. Methods: 30 males with heart ischemic disease, II-III functional class, average age of 46.2 5= 2.7 year were examined. All patients suffered accompanying metabolic disorders such as abdominal obesity (body mass index >27 kg/m 2, waist circumference > 102 cm), arterial hypertension 1-2 degrees and dyslipidemia. Exclusion criteria were as following: clinical manifestation of the carbohydrate metabolism dysfunctions, complications of arterial hypertension, severe concomitant somatic diseases, elderly age. All patients underwent food load test by animal fat (50 g of butter) with estimation of postprandial metabolism before and after the therapy of atorvastatin. Remits: The results of the study showed significant changes in postprandial lipid metabolism and thrombocyte membranes in patients with heart ischemic disease and metabolic dysfunctions. Among statistically signifi-
cant changes am: increased level of cholesterol, triglycerides of the plasma, LDL-cholesterol (p=0.032), decreased level of HDL-cholesterol (p=0.048), accompanied by increasing level of general cholesterol (p=0.007) and its ethers (p=0.018) in thrombocyte membrane during 6 hour postprandial period after food load, LDL-cholesterol test by animal fat (the butter, 50 g). After 30 days of atorvastatin therapy (10 nag daily) no significant increasing of lipid fraction was registered in postprandial period that was accompanied by increasing of level of general cholesterol in thrombocyte membranes and significant increasing its etherificated fractions (p=0.038). Conclusions: Atorvastatin therapy not only normalizes postprandial response of blood plasma lipids, but also promotes the reduction of general cholesterol level in thrombocyte membranes along with increasing level of its etherification, which also motivates prescription of lipid lowering therapy in complex treatment of patients with described pathology.
I W16-P-024 I E F F E C T OF L O N G - T E R M DIET AND N-3 FATTY ACID INTERVENTION ON A S Y M M E T R I C D I M E T H Y L A R G I N I N E (ADMA) I
H.M.A. Eid 1, H. Amesen 2, E.M. Hjerkinn I , T. Lyberg 1, I. Ellingsen 1, I. Seljeflot 1 . ] Center for Clinical Research, Ulleval University Hospita~
Oslo, Norway; 2Department of Cardiology, UUeval University Hospital, Oslo, Norway Objectives: Impaired vasedilation which is related to atherosclerosis, has been suggested to be caused by inhibition of nitric oxide generation by asymmetric dimethylarginine (ADMA) and/or alteration in the L-arginine to ADMA ratio. We wanted to explore whether n-3 polyunsaturated fatty acid (PUFA) supplementation and/or diet intervention beneficially influence endothelial function assessed as plasma ADMA levels and the L-arginine/ADMA ratio. Methods: A male population (n=563, age 704-6 yrs) with long-standing hyperlipidemia, was included, randomly allocated to receive n-3 PUFA placebo capsules and no dietary advice; dietary advice; n-3 PUFA capsules (2.4 g/d); or dietary advice combined with n-3 PUFA capsules, and followed for 3 years. Fasting blood samples were drawn at baseline and the end of the study. Results: No influence of either regimens on ADMA levels were obtained. However, n-3 PUFA supplementation was accompanied by an increase in L-arginine levels, different from the decrease observed in the placebo group (p<0.05). This was even more pronounced in individuals with low body mass index (<26 kg/m 2) (p=0.01), in which also the Larginine/ADMA ratio was reduced on placebo compared to those receiving n-3 PUFA (n=0.04). Conclusion: In this rather large long-term intervention study, ADMA levels were not influenced by dietary counseling, n-3 PUFA seems, however, to counteract the time-related reduction in L-arginine seen on placebo, which might be discussed as an improvement of endothelial dysfunction.
I W16-P-025 I CHANGES OF PLASMA ATHEROSCLEROSIS I
RISK
FACTORS' LEVELS CAUSED BY ESTROGEN REPLACEMENT THERAPY
T. Fait, M. Vrablik, M. Kostirova. General Faculty Hospital and 1st
Faculty of Medicine Charles University, Prague, Czech republic Objectives: Conclusions from observation studies demonstrated a positive effect of hormone replacement therapy (HRT) in menopause in both primary and secondary prevention of ischaemic heart disease. But all randomised trials failed to prove this positive effect. Only the EPAT trial indicate possible positive effects of some HRT regimens. We describe metabolic changes, which could explain these discrepancies. Material and methods: 40 hysterectomisod women more then 6 weeks after a surgically induced menopause or after an interruption of HRT were divided in two groups. All women have suffered from an acute climacteric syndrome. Two ERT regimens (2 mg estradiol pills, 50 ug/day transdermal patches) were administered randomly in twelve weeks crossover study design. Hormone levels, blood count, liver enzymes, lipid profile, coagulation markers, hsCRP, PAI-1 and TPHI were measured at baseline, after three and six months therapy. Results: Estradiol pills had significantly better impact on plasma lipids and lipoproteins than transdermal patches. Effects on other variables am being analysed. Conclusions: We know from daily experience and literature that not only individualisation but also timing and way of administration of sexual
75th EAS Congress, 23-26 April 2005, Prague, Czech Republic