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Carbohydrate-deficient transferrin and homocysteine in patients with mixed hyperlipidemia
Dzhekova-Stojkova
with ischemic heart disease who did not reach LDL-C target levels on conventional treatment. The average triglyceride, total cholesterol, HDLc and LDLc levels before and after treatment in all patients were 170±113 vs. 124±91; 269±74 vs. 132±48; 42±8 vs. 37±7.9 and 196±77 vs. 80±52 (mg/dl), respectively. Comparing the results on DALI to those on plasma exchange in a subgroup of seven patients, we found that while the reduction in triglyceride, total cholesterol and LDLc were similar, the effect on HDLc concentration was different. From an average of 39.7±8.7 and 23±5.7 (mg/dl) before and after plasma exchange to an average of 43.9±8.1 and 38.4±7 (mg/dl) before and after LDL apheresis, respectively. Five patients developed treatment-related adverse events. Of these, three experienced allergic reactions including shortness of breath, urticaria and facial flushing. One had rhabdomyolysis and one myopathy with back pain. All adverse events occurred during the first few treatment sessions. In conclusion, LDL apheresis using the DALI system is highly efficacious for the treatment of hypercholesterolemia. It is associated with a significant number of side effects usually occurring during the first treatment sessions. In those who did not experience adverse effects DALI was well tolerated, and provided a remarkable clinical benefit.
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ACUTE EFFECT OF ETHANOL EXPOSURE ON H D L CHOLESTEROL
Y. N e u m a r k 1 , Y. Friedlander 1 , R. Durst 2, D. Jaffe 1 , E. Butbul2,
E. Leitersdorf2. JBraun School of Public Health, Hebrew University
of Jerusalem; 2Center for Research, Prevention and Treatment of Atherosclerosis, Hadassah University Hospital, Jerusalem, Israel The anti-atherogenic effect of moderate alcohol intake is partially mediated via its effects on HDL-C. Objective: To test the hypothesis that this cardio-protection is absent for episodic drinking and that exposure to a low-dose alcohol infusion induces a short-term reduction in HDL-C. M e t h o d s : 94 healthy male university students underwent an intravenous alcohol clamp - 6% ethanol in Ringers was infused according to a physiologically-based pharmacokinetic model designed to reach a steadystate target of 50±5 mg% at 20 minutes. Blood samples were drawn at baseline and 30 minutes after onset of steady-state. Results: For 93% of subjects HDL-C decreased significantly (4.11±3.0 mg) from a mean baseline of 46.7±9.5 mg to steady-state; HDL-C levels for the seven other subjects remained unchanged or increased <6 mg. To assess the possible effect of plasma-dilution on these changes, 18 randomly selected subjects underwent an alcohol-free clamp under identical experimental conditions. There was no significant difference in basic characteristics and baseline HDL-C between the 18 control subjects and the 76 other subjects, or between the 18 at alcohol-clamp baseline and control-clamp baseline. The slight drop (2.2±2.1 mg) in HDL-C for the 18 saline-only clamps, was significantly less than the 4.04±3.13 mg decrease experienced by the 76 alcohol-subjects, and by the 18 subjects during their alcohol-clamp (4.4±3.1 mg, p<0.05). C o n c l u s i o n s : The widely-supported recommendations of regular lowmoderate alcohol drinking may not be appropriate in light of the episodic nature and low levels of drinking in Israel. Background:
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CORONARY HEART DISEASE MORTALITY DECLINE AND INFECTIOUS DISEASES IN THE CZECH POPULATION
A. Dvorakova, R. Poledne. Centre for Experimental Cardiovascular Research, IKEM, Prague, Czech Republic Coronary heart disease mortality has decreased in the Czech population substantially during the last 15 years. This unusually fast positive change might be used as a model situation to analyze additional positive effects related to CHD mortality. Out of possible reasons 14% decrease of nonHDL cholesterol concentration has been proved between 1989 and 1997. We searched for infectious factors that might have influenced CHD mortality. M e t h o d s : Dynamics of CHD mortality changes was compared to incidence of several infectious diseases and seropositivity for two pathogens. R e s u l t s : Standardized mortality for all ages has dropped for 30% and for age under 70 years for almost 50% between 1987 and 2000. Seropositivity for herpes-zooster virus did not change within last 20 years, while seropositivity for cytomegalovirus increased about 20%. Influenza incidence showed accidental oscilations with no trend. There was a decrease in incidence of hepatitis A and tuberculosis. C o n c l u s i o n s : From comparison of dynamic of CHD mortality and infections we conclude that no time coincidence was observed with exception of
103
incidence of tuberculosis and hepatitis A, but these changes were 20 years apart each other. This work was supported with grant from the Ministry of Education, Youth, and Sports of the Czech Republic LN 00A069. [ 1 - ~ CARBOHYDRATE-DEFICIENT TRANSFERRIN AND HOMOCYSTEINE IN PATIENTS W I T H MIXED HYPERLIPIDEMIA J. Dvorakova, L. Dubska, J. Hyanek, L. Taborsky. Department of Clinical Biochemistry, Hospital Na Homolee, Prague, Czech Republic Lipidologists in their everyday practice perform differential diagnosis of primary or secondary mixed hyperlipidemias/HLP/. An important cause of HLP is an alcohol intake. Anamnestic data can be contradictory. Classical markers (y-glutamyltransferase, GGT) or erythrocyte mean corpuscular volume (MCV) used widely to screen for alcoholism show lower sensitivities. Carbohydrate-deficient transferrin (CDT) is the most specific marker of chronic alcohol abuse so far. 95 patients (47M, 48F) with mixed HLP and 24 healthy control persons (12M, 12F) were enrolled in our study. We determined CDT (TIA, ROCHE, cut-off value 5%), MCV, GGT, lipid parameters, plasma total homocysteine (tHCY, FPIA) and vitamins (serum folate, vitamin B12 and vitamin B6). The group of patients was divided into two groups according to the CDT value (lst group: CDT > 5%, suspect of alcohol intake, 2nd group: CDT ~< 5%). In the 1st group there were significantly higher MCV (M:p<0.016, F:p<0.0001) and GGT activity (M:p<0.0001) than in the 2nd group. The 1st group has significantly higher tHCY compared with the control group (M:p<0.0002, F:p<0.02). Women of the 1st group had significantly higher tHCY compared with the women of the 2nd group (p<0.03), in men the differences did not reach statistical significance. In the 1st group vitamin B12 (M:p<0.048, F:p<0.0007) and vitamin B6 in men (p<0.015) were significantly lower than in the control group. Serum CDT is an important factor in differential diagnosis of mixed hyperlipidemias. Alcohol intake affects the plasma tHCY levels. In a group of alcoholics with mixed hyperlipidemia we noted significantly higher tHCY compared with controls. ~DIET AND METFORMIN IN THE TREATMENT OF THE ABDOMINAL OBESE PATIENTS E Dzgoeva. Russian Endocrinology Research Centre, Moscow, Russia The effects of two therapeutic methods (diet only and diet with metformin) on weight loss and on some biological parameters related to atherosclerosis studied during 12 months in 64 non diabetic patients (48 men and 16 women, age from 18 to 43 years, BMI from 31 to 45, body weight from 82 to 136 kg, waist circumference (WC) more than 88 (females) and 100 (males) cm). All patients started a dietetic treatment: 6 months low caloric diet (20 patients received 1000 mg metformin per day with the diet) and 6 months eucaloric diet. R e s u l t s : Patients treated with the diet only showed considerable anthropometric parameters and total cholesterol decrease after 6 and 12 months of treatment. Both groups had the same LDL cholesterol reduce (13,8; 17,3 and 15,1; 18 percents respectively). Metformin patients showed more considerable decrease of fasting insulinemia and HDL cholesterol increase in comparison with dietetic patients. C o n c l u s i o n : 12-months-diet promotes the atherogenic parameters decrease through the loss of body weight and abdominal visceral fat. Metformin decreases cardiovascular disease risk directly and through the reducing of insulin and insulinresistance in patients with abdominal obesity. Metformin has long lasting effect, which can be supported by the diet. ~
OXIDATIVE STRESS STATUS IN ADULTS W I T H DIABETES MELLITUS
S.A. Dzhekova-Stoikova 1, M.A. Krstevska 1, G.L. Bosilkova 1, Z.G. Stojkova 2. I Department of Medical and Experimental Biochemistry,
2Department of Medical and Experimental Physiology, Medical Faculty, Skopje, Macedonia All healthy mammalian organisms are characterized by an equilibrium between the occurrence of the highly reactive oxygen species and their destruction by antioxidants. Numerous diseases go hand in hand with a disturbance of the homeostasis. The aim of this study is to determine the antioxidant status and blood lipids in adults with non insulin dependent
73rd EAS Congress
with ischemic heart disease who did not reach LDL-C target levels on conventional treatment. The average triglyceride, total cholesterol, HDLc and LDLc levels before and after treatment in all patients were 170±113 vs. 124±91; 269±74 vs. 132±48; 42±8 vs. 37±7.9 and 196±77 vs. 80±52 (mg/dl), respectively. Comparing the results on DALI to those on plasma exchange in a subgroup of seven patients, we found that while the reduction in triglyceride, total cholesterol and LDLc were similar, the effect on HDLc concentration was different. From an average of 39.7±8.7 and 23±5.7 (mg/dl) before and after plasma exchange to an average of 43.9±8.1 and 38.4±7 (mg/dl) before and after LDL apheresis, respectively. Five patients developed treatment-related adverse events. Of these, three experienced allergic reactions including shortness of breath, urticaria and facial flushing. One had rhabdomyolysis and one myopathy with back pain. All adverse events occurred during the first few treatment sessions. In conclusion, LDL apheresis using the DALI system is highly efficacious for the treatment of hypercholesterolemia. It is associated with a significant number of side effects usually occurring during the first treatment sessions. In those who did not experience adverse effects DALI was well tolerated, and provided a remarkable clinical benefit.
F
•
T
H
E
ACUTE EFFECT OF ETHANOL EXPOSURE ON H D L CHOLESTEROL
Y. N e u m a r k 1 , Y. Friedlander 1 , R. Durst 2, D. Jaffe 1 , E. Butbul2,
E. Leitersdorf2. JBraun School of Public Health, Hebrew University
of Jerusalem; 2Center for Research, Prevention and Treatment of Atherosclerosis, Hadassah University Hospital, Jerusalem, Israel The anti-atherogenic effect of moderate alcohol intake is partially mediated via its effects on HDL-C. Objective: To test the hypothesis that this cardio-protection is absent for episodic drinking and that exposure to a low-dose alcohol infusion induces a short-term reduction in HDL-C. M e t h o d s : 94 healthy male university students underwent an intravenous alcohol clamp - 6% ethanol in Ringers was infused according to a physiologically-based pharmacokinetic model designed to reach a steadystate target of 50±5 mg% at 20 minutes. Blood samples were drawn at baseline and 30 minutes after onset of steady-state. Results: For 93% of subjects HDL-C decreased significantly (4.11±3.0 mg) from a mean baseline of 46.7±9.5 mg to steady-state; HDL-C levels for the seven other subjects remained unchanged or increased <6 mg. To assess the possible effect of plasma-dilution on these changes, 18 randomly selected subjects underwent an alcohol-free clamp under identical experimental conditions. There was no significant difference in basic characteristics and baseline HDL-C between the 18 control subjects and the 76 other subjects, or between the 18 at alcohol-clamp baseline and control-clamp baseline. The slight drop (2.2±2.1 mg) in HDL-C for the 18 saline-only clamps, was significantly less than the 4.04±3.13 mg decrease experienced by the 76 alcohol-subjects, and by the 18 subjects during their alcohol-clamp (4.4±3.1 mg, p<0.05). C o n c l u s i o n s : The widely-supported recommendations of regular lowmoderate alcohol drinking may not be appropriate in light of the episodic nature and low levels of drinking in Israel. Background:
•
CORONARY HEART DISEASE MORTALITY DECLINE AND INFECTIOUS DISEASES IN THE CZECH POPULATION
A. Dvorakova, R. Poledne. Centre for Experimental Cardiovascular Research, IKEM, Prague, Czech Republic Coronary heart disease mortality has decreased in the Czech population substantially during the last 15 years. This unusually fast positive change might be used as a model situation to analyze additional positive effects related to CHD mortality. Out of possible reasons 14% decrease of nonHDL cholesterol concentration has been proved between 1989 and 1997. We searched for infectious factors that might have influenced CHD mortality. M e t h o d s : Dynamics of CHD mortality changes was compared to incidence of several infectious diseases and seropositivity for two pathogens. R e s u l t s : Standardized mortality for all ages has dropped for 30% and for age under 70 years for almost 50% between 1987 and 2000. Seropositivity for herpes-zooster virus did not change within last 20 years, while seropositivity for cytomegalovirus increased about 20%. Influenza incidence showed accidental oscilations with no trend. There was a decrease in incidence of hepatitis A and tuberculosis. C o n c l u s i o n s : From comparison of dynamic of CHD mortality and infections we conclude that no time coincidence was observed with exception of
103
incidence of tuberculosis and hepatitis A, but these changes were 20 years apart each other. This work was supported with grant from the Ministry of Education, Youth, and Sports of the Czech Republic LN 00A069. [ 1 - ~ CARBOHYDRATE-DEFICIENT TRANSFERRIN AND HOMOCYSTEINE IN PATIENTS W I T H MIXED HYPERLIPIDEMIA J. Dvorakova, L. Dubska, J. Hyanek, L. Taborsky. Department of Clinical Biochemistry, Hospital Na Homolee, Prague, Czech Republic Lipidologists in their everyday practice perform differential diagnosis of primary or secondary mixed hyperlipidemias/HLP/. An important cause of HLP is an alcohol intake. Anamnestic data can be contradictory. Classical markers (y-glutamyltransferase, GGT) or erythrocyte mean corpuscular volume (MCV) used widely to screen for alcoholism show lower sensitivities. Carbohydrate-deficient transferrin (CDT) is the most specific marker of chronic alcohol abuse so far. 95 patients (47M, 48F) with mixed HLP and 24 healthy control persons (12M, 12F) were enrolled in our study. We determined CDT (TIA, ROCHE, cut-off value 5%), MCV, GGT, lipid parameters, plasma total homocysteine (tHCY, FPIA) and vitamins (serum folate, vitamin B12 and vitamin B6). The group of patients was divided into two groups according to the CDT value (lst group: CDT > 5%, suspect of alcohol intake, 2nd group: CDT ~< 5%). In the 1st group there were significantly higher MCV (M:p<0.016, F:p<0.0001) and GGT activity (M:p<0.0001) than in the 2nd group. The 1st group has significantly higher tHCY compared with the control group (M:p<0.0002, F:p<0.02). Women of the 1st group had significantly higher tHCY compared with the women of the 2nd group (p<0.03), in men the differences did not reach statistical significance. In the 1st group vitamin B12 (M:p<0.048, F:p<0.0007) and vitamin B6 in men (p<0.015) were significantly lower than in the control group. Serum CDT is an important factor in differential diagnosis of mixed hyperlipidemias. Alcohol intake affects the plasma tHCY levels. In a group of alcoholics with mixed hyperlipidemia we noted significantly higher tHCY compared with controls. ~DIET AND METFORMIN IN THE TREATMENT OF THE ABDOMINAL OBESE PATIENTS E Dzgoeva. Russian Endocrinology Research Centre, Moscow, Russia The effects of two therapeutic methods (diet only and diet with metformin) on weight loss and on some biological parameters related to atherosclerosis studied during 12 months in 64 non diabetic patients (48 men and 16 women, age from 18 to 43 years, BMI from 31 to 45, body weight from 82 to 136 kg, waist circumference (WC) more than 88 (females) and 100 (males) cm). All patients started a dietetic treatment: 6 months low caloric diet (20 patients received 1000 mg metformin per day with the diet) and 6 months eucaloric diet. R e s u l t s : Patients treated with the diet only showed considerable anthropometric parameters and total cholesterol decrease after 6 and 12 months of treatment. Both groups had the same LDL cholesterol reduce (13,8; 17,3 and 15,1; 18 percents respectively). Metformin patients showed more considerable decrease of fasting insulinemia and HDL cholesterol increase in comparison with dietetic patients. C o n c l u s i o n : 12-months-diet promotes the atherogenic parameters decrease through the loss of body weight and abdominal visceral fat. Metformin decreases cardiovascular disease risk directly and through the reducing of insulin and insulinresistance in patients with abdominal obesity. Metformin has long lasting effect, which can be supported by the diet. ~
OXIDATIVE STRESS STATUS IN ADULTS W I T H DIABETES MELLITUS
S.A. Dzhekova-Stoikova 1, M.A. Krstevska 1, G.L. Bosilkova 1, Z.G. Stojkova 2. I Department of Medical and Experimental Biochemistry,
2Department of Medical and Experimental Physiology, Medical Faculty, Skopje, Macedonia All healthy mammalian organisms are characterized by an equilibrium between the occurrence of the highly reactive oxygen species and their destruction by antioxidants. Numerous diseases go hand in hand with a disturbance of the homeostasis. The aim of this study is to determine the antioxidant status and blood lipids in adults with non insulin dependent
73rd EAS Congress