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3P-0785 Comparison of lipid profile and blood sugar between peripheral venous, peripheral arterial and coronary artery blood samples
234 3P-0784
Wednesday October 1, 2003: Poster Session Lipid and lipoprotein metabolism Evaluation of apolipoprotein A-I kinetics in rabbits in vivo using endogenous and exogenous radioiodination methods
B. Zhang, E. Shimoji, K. Saku. Fukuoka University, Japan Objectives: The in vivo kinetics of apolipoprotein (apo) A-I radioiodinated by the iodine monochloride (ICl) method of McFarlane as modified by Bilheimer and co-workers and by using the IODO Beads Iodination Reagent were evaluated in rabbits. The effects of different radiolabeling procedures in the ICl method, i.e., apo A-I radiolabeled as a part of intact HDL (in situ labelling) and apo A-I radiolabeled separately (exogenous labelling), and the effects of the in vitro incubation conditions on the in vivo kinetics of apo A-I were also investigated. Methods: HDL or apo A-I was radioiodinatioed and injected into rabbits. The fractional catabolic rate (FCR) was derived from the radioactivity decay curve. Results: Both human apo A-I and rabbit HDL radioiodinated by the IODO Beads Iodination Reagent were cleared faster from plasma of rabbits than those radiolabeled by the ICl method. However, the different radiolabeling procedures in the ICl method were not associated with a significant difference in the in vivo kinetics of apo A-I if apo A-I was prepared by the guanidine HCl method and used fresh. 125 I-apo A-I subjected to delipidation and lyophilization was cleared only slightly faster from the plasma of rabbits than fresh 125 I-apo A-I. We also found that apo A-I separated by the guanidine HCl method and used fresh was cleared faster from the plasma of rabbits when it was injected as free apo A-I without adding serum albumin or after in vitro incubation with rabbit HDL than when injected after reassociation with rabbit plasma. Conclusion: The ICl method is a more appropriate radioiodination method for studying the in vivo kinetics of HDL than the IODO Beads Iodination Reagent and that the in vitro incubation conditions before injection, are important factors that affect the in vivo kinetics of apo A-I. 3P-0785
Comparison of lipid profile and blood sugar between peripheral venous, peripheral arterial and coronary artery blood samples
M. Dehghani, H. Saneei. Isfahan Medical School, Isfahan, Iran Background: Atherosclerotic coronary artery disease (CAD) is the most common cause of death in developed & developing countries. Atherosclerosis has focality nature and involves the arterial bed selectively. Dyslipidemia &diabetes mellitus (DM) are the major risk factors for atherosclerosis, so we suggest that difference in concentration of these risk factors at different part of circulation may be play a role in atherosclerosis focality, and then we measured lipid profile & fasting blood sugar in different part of circulation and compared them. Method & Material: In this study 50 individuals that because of different reasons scheduled for coronary angiography, selected randomly and blood sample was taken from brachial vein, femoral artery &left main coronary artery simultaneously and examined for lipid profile (TC, LDL, HDL, TG) & blood sugar after at least 8 hour fasting. Then results of laboratory data were analyzed statistically by SPSS-software with methods such as one-way ANOVA and PEARSON correlation test. Results: In this research mean value of lipid profile & blood sugar was greater in arterial than venous bed insignificantly but not meaningful statistically (P-value >0.05) and had significant correlation (r=0.972, P-value <0.001). In this study, also, based on sex, BMI, presences or absence of DM &CAD, analysis was done separately, but differences were not significant (P-value >0.05). Conclusion: Lipid profile & blood sugar were greater in arterial than venous bed but was insignificant and probably has not role in atherosclerosis focality. 3P-0786
Rosuvastatin: Kinetics of apoB-containing lipoproteins in moderate hypercholesterolemia
M. Caslake 1 , D. Bedford 1 , G. Stewart 1 , M. Palmer 2 , F. McTaggart 2 , N. Joss 1 , C.J. Packard 1 . 1 University of Glasgow, Scotland; 2 AstraZeneca Pharmaceuticals Ltd, United Kingdom In a double-blind placebo-controlled crossover study we examined the effects of rosuvastatin (40 mg/d) for 8 weeks on the apoB-containing lipoproteins: VLDL1 (Sf 60-400), VLDL2 (Sf 20-60), IDL (Sf 12-20) and LDL (Sf 0-12). 12 Subjects (10 M, 2 F, mean age 52.8y) undertook two 2 week studies using deuterated leucine to follow apoB kinetics in each of the lipoprotein fractions.
On placebo mean triglyceride (TG) was 1.7 ± 0.58, LDLC 4.5 ± 0.5 and HDLC 1.3 ± 0.4 mmol/L. The kinetic parameters were calculated using multi-compartmental modelling and comparisons were made between the rosuvastatin and placebo phases. Rosuvastatin reduced mean LDLC by 58%, P<0.001 and median TG by 27%, P<0.005. Treatment did not significantly induce any changes in the direct production of any of the lipoprotein fractions or in VLDL1 apoB pool size. There were significant reductions in mean apoB pool sizes of VLDL2 (-35%), IDL (-62%) and LDL (-53%) all P<0.001. This was principally due to an increase in fractional catabolic rate of VLDL2, (8.2 ± 3.1 to 10.9 ± 4.4 pools/d, P=0.06), more efficient transfer of IDL to LDL (1.2 ± 0.5 to 3.1 ± 1.1 pools/d, P<0.001) and a doubling of the fractional catabolic rate of LDL (0.34 ± 0.11 to 0.66 ± 0.13 pools/d, P<0.001). Compositional analysis revealed perturbations in the lipid content of the particles such that they became depleted in cholesterol ester and enriched with TG These results indicate that in moderate hypercholesterolaemia the principal effect of rosuvastatin is to stimulate the removal of the smaller highly atherogenic, cholesterol-rich apoB-containing lipoproteins, presumably by receptors in the liver. 3P-0787
Relationship between hyperinsulinemia and particle size of remnant-like lipoprotein particles in patients with impaired glucose tolerance
M. Ai 1 , A. Tanaka 2 , F. Numano 1 , F. Numano 1 , K. Shimokado 1 . 1 Tokyo Medical and Dental University, Tokyo; 2 Kanto-gakuin University, Japan We have been doing clinical research on the relationship between insulin resistance and remnant like particles (RLPs). We reported fasting plasma RLPs concentrations are increased in patients with type 2 diabetes or impaired glucose tolerance (IGT). The relationship between plasma insulin and RLPcholesterol (RC) concentration is very close, especially in IGT patients. We also reported that postprandial hyperlipidemia is severer in hyperinsulinemic patients with type 2 diabetes than normoinsulinemic by measurement of postfat-load plasma RLP concentrations, showing the degree of hyperinsulinemia may contribute more to increase in RLPs than hyperglycemia. To explore further the association between insulin resistance and RLP, we studied particle size of RLPs (RLPsize) in IGT patients. Previous study showed that there is a significant correlation between RLPsize and RLP-triglyceride (RTG) to RC ratio (RTG/RC) when RLPsize distribution is predominantly or mostly in VLDL fraction. We examined plasma RLP obtained from IGT individuals, and found that their RLPsize is predominantly VLDL. We used the sum of the plasma insulin concentrations before and 30, 60, 90, 120, and 180 min after a 75-g oral glucose load (IRI) as a marker of insulin resistance in 78 subjects with IGT. IRI was determined on 2 occasions, before and 16 weeks after initiation of a diet and exercise program. There were inverse correlation between IRI and RTG/RC both at baseline (r= -0.29, p= 0.02) and after lifestyle intervention (r= -0.33, p= 0.01). The changes in IRI following intervention was also associated with differences in RTG/RC ratio (r= -0.535, p<0.001). These results demonstrate that hyperinsulinemic individuals have not only higher plasma RC level but also smaller and more cholesterol-rich RLPs, indicating they may be in more atherogenic condition. 3P-0788
Severe chylomicronemia: Clinical epidemiology and recommendations for treatment
H.U. Kloer, A. Hauenschild. Third Medical Department, Justus-Liebig University Giessen, Germany Chylomicronemia (Chy) is an acute clinical condition characterized by significant morbidity and, sometimes, even mortality (fatal acute pancreatitis). At least in Western countries Chy is much more common than generally believed. In a collaborative German study we have identified 326 such patients (245 males, 81 females, TG up to 15000 mg/dl, TC up to 1550mg/dl). Most patients were normal weight (85%), non-alcoholic (90%). The presence of diabetes (31%) was linked to the severity of Chy as well as the presence of recurrent pancreatitis (20%). Contrary to the opinion voiced in the literature, 25% of the patients had clinically manifest atherosclerotic vascular disease (MI, Angina, CHD by angiography, PVD). Because Chy represents a clinical emergency, immediate and effective treatment has to be installed. Lipid-Apheresis utilizing a cascade filtration system (e.g. MONET, Fresenius, Germany) has to be repeatedly performed until Plasma TG is below 500 mg/dl. Simultaneously, and for a few days subsequently, a formula diet (“Giessener Trunk”) consisting of MCT and Omega-3 fatty acids in combination has to be given until TG
XIIIth International Symposium on Atherosclerosis, September 28–October 2, 2003, Kyoto, Japan
Wednesday October 1, 2003: Poster Session Lipid and lipoprotein metabolism Evaluation of apolipoprotein A-I kinetics in rabbits in vivo using endogenous and exogenous radioiodination methods
B. Zhang, E. Shimoji, K. Saku. Fukuoka University, Japan Objectives: The in vivo kinetics of apolipoprotein (apo) A-I radioiodinated by the iodine monochloride (ICl) method of McFarlane as modified by Bilheimer and co-workers and by using the IODO Beads Iodination Reagent were evaluated in rabbits. The effects of different radiolabeling procedures in the ICl method, i.e., apo A-I radiolabeled as a part of intact HDL (in situ labelling) and apo A-I radiolabeled separately (exogenous labelling), and the effects of the in vitro incubation conditions on the in vivo kinetics of apo A-I were also investigated. Methods: HDL or apo A-I was radioiodinatioed and injected into rabbits. The fractional catabolic rate (FCR) was derived from the radioactivity decay curve. Results: Both human apo A-I and rabbit HDL radioiodinated by the IODO Beads Iodination Reagent were cleared faster from plasma of rabbits than those radiolabeled by the ICl method. However, the different radiolabeling procedures in the ICl method were not associated with a significant difference in the in vivo kinetics of apo A-I if apo A-I was prepared by the guanidine HCl method and used fresh. 125 I-apo A-I subjected to delipidation and lyophilization was cleared only slightly faster from the plasma of rabbits than fresh 125 I-apo A-I. We also found that apo A-I separated by the guanidine HCl method and used fresh was cleared faster from the plasma of rabbits when it was injected as free apo A-I without adding serum albumin or after in vitro incubation with rabbit HDL than when injected after reassociation with rabbit plasma. Conclusion: The ICl method is a more appropriate radioiodination method for studying the in vivo kinetics of HDL than the IODO Beads Iodination Reagent and that the in vitro incubation conditions before injection, are important factors that affect the in vivo kinetics of apo A-I. 3P-0785
Comparison of lipid profile and blood sugar between peripheral venous, peripheral arterial and coronary artery blood samples
M. Dehghani, H. Saneei. Isfahan Medical School, Isfahan, Iran Background: Atherosclerotic coronary artery disease (CAD) is the most common cause of death in developed & developing countries. Atherosclerosis has focality nature and involves the arterial bed selectively. Dyslipidemia &diabetes mellitus (DM) are the major risk factors for atherosclerosis, so we suggest that difference in concentration of these risk factors at different part of circulation may be play a role in atherosclerosis focality, and then we measured lipid profile & fasting blood sugar in different part of circulation and compared them. Method & Material: In this study 50 individuals that because of different reasons scheduled for coronary angiography, selected randomly and blood sample was taken from brachial vein, femoral artery &left main coronary artery simultaneously and examined for lipid profile (TC, LDL, HDL, TG) & blood sugar after at least 8 hour fasting. Then results of laboratory data were analyzed statistically by SPSS-software with methods such as one-way ANOVA and PEARSON correlation test. Results: In this research mean value of lipid profile & blood sugar was greater in arterial than venous bed insignificantly but not meaningful statistically (P-value >0.05) and had significant correlation (r=0.972, P-value <0.001). In this study, also, based on sex, BMI, presences or absence of DM &CAD, analysis was done separately, but differences were not significant (P-value >0.05). Conclusion: Lipid profile & blood sugar were greater in arterial than venous bed but was insignificant and probably has not role in atherosclerosis focality. 3P-0786
Rosuvastatin: Kinetics of apoB-containing lipoproteins in moderate hypercholesterolemia
M. Caslake 1 , D. Bedford 1 , G. Stewart 1 , M. Palmer 2 , F. McTaggart 2 , N. Joss 1 , C.J. Packard 1 . 1 University of Glasgow, Scotland; 2 AstraZeneca Pharmaceuticals Ltd, United Kingdom In a double-blind placebo-controlled crossover study we examined the effects of rosuvastatin (40 mg/d) for 8 weeks on the apoB-containing lipoproteins: VLDL1 (Sf 60-400), VLDL2 (Sf 20-60), IDL (Sf 12-20) and LDL (Sf 0-12). 12 Subjects (10 M, 2 F, mean age 52.8y) undertook two 2 week studies using deuterated leucine to follow apoB kinetics in each of the lipoprotein fractions.
On placebo mean triglyceride (TG) was 1.7 ± 0.58, LDLC 4.5 ± 0.5 and HDLC 1.3 ± 0.4 mmol/L. The kinetic parameters were calculated using multi-compartmental modelling and comparisons were made between the rosuvastatin and placebo phases. Rosuvastatin reduced mean LDLC by 58%, P<0.001 and median TG by 27%, P<0.005. Treatment did not significantly induce any changes in the direct production of any of the lipoprotein fractions or in VLDL1 apoB pool size. There were significant reductions in mean apoB pool sizes of VLDL2 (-35%), IDL (-62%) and LDL (-53%) all P<0.001. This was principally due to an increase in fractional catabolic rate of VLDL2, (8.2 ± 3.1 to 10.9 ± 4.4 pools/d, P=0.06), more efficient transfer of IDL to LDL (1.2 ± 0.5 to 3.1 ± 1.1 pools/d, P<0.001) and a doubling of the fractional catabolic rate of LDL (0.34 ± 0.11 to 0.66 ± 0.13 pools/d, P<0.001). Compositional analysis revealed perturbations in the lipid content of the particles such that they became depleted in cholesterol ester and enriched with TG These results indicate that in moderate hypercholesterolaemia the principal effect of rosuvastatin is to stimulate the removal of the smaller highly atherogenic, cholesterol-rich apoB-containing lipoproteins, presumably by receptors in the liver. 3P-0787
Relationship between hyperinsulinemia and particle size of remnant-like lipoprotein particles in patients with impaired glucose tolerance
M. Ai 1 , A. Tanaka 2 , F. Numano 1 , F. Numano 1 , K. Shimokado 1 . 1 Tokyo Medical and Dental University, Tokyo; 2 Kanto-gakuin University, Japan We have been doing clinical research on the relationship between insulin resistance and remnant like particles (RLPs). We reported fasting plasma RLPs concentrations are increased in patients with type 2 diabetes or impaired glucose tolerance (IGT). The relationship between plasma insulin and RLPcholesterol (RC) concentration is very close, especially in IGT patients. We also reported that postprandial hyperlipidemia is severer in hyperinsulinemic patients with type 2 diabetes than normoinsulinemic by measurement of postfat-load plasma RLP concentrations, showing the degree of hyperinsulinemia may contribute more to increase in RLPs than hyperglycemia. To explore further the association between insulin resistance and RLP, we studied particle size of RLPs (RLPsize) in IGT patients. Previous study showed that there is a significant correlation between RLPsize and RLP-triglyceride (RTG) to RC ratio (RTG/RC) when RLPsize distribution is predominantly or mostly in VLDL fraction. We examined plasma RLP obtained from IGT individuals, and found that their RLPsize is predominantly VLDL. We used the sum of the plasma insulin concentrations before and 30, 60, 90, 120, and 180 min after a 75-g oral glucose load (IRI) as a marker of insulin resistance in 78 subjects with IGT. IRI was determined on 2 occasions, before and 16 weeks after initiation of a diet and exercise program. There were inverse correlation between IRI and RTG/RC both at baseline (r= -0.29, p= 0.02) and after lifestyle intervention (r= -0.33, p= 0.01). The changes in IRI following intervention was also associated with differences in RTG/RC ratio (r= -0.535, p<0.001). These results demonstrate that hyperinsulinemic individuals have not only higher plasma RC level but also smaller and more cholesterol-rich RLPs, indicating they may be in more atherogenic condition. 3P-0788
Severe chylomicronemia: Clinical epidemiology and recommendations for treatment
H.U. Kloer, A. Hauenschild. Third Medical Department, Justus-Liebig University Giessen, Germany Chylomicronemia (Chy) is an acute clinical condition characterized by significant morbidity and, sometimes, even mortality (fatal acute pancreatitis). At least in Western countries Chy is much more common than generally believed. In a collaborative German study we have identified 326 such patients (245 males, 81 females, TG up to 15000 mg/dl, TC up to 1550mg/dl). Most patients were normal weight (85%), non-alcoholic (90%). The presence of diabetes (31%) was linked to the severity of Chy as well as the presence of recurrent pancreatitis (20%). Contrary to the opinion voiced in the literature, 25% of the patients had clinically manifest atherosclerotic vascular disease (MI, Angina, CHD by angiography, PVD). Because Chy represents a clinical emergency, immediate and effective treatment has to be installed. Lipid-Apheresis utilizing a cascade filtration system (e.g. MONET, Fresenius, Germany) has to be repeatedly performed until Plasma TG is below 500 mg/dl. Simultaneously, and for a few days subsequently, a formula diet (“Giessener Trunk”) consisting of MCT and Omega-3 fatty acids in combination has to be given until TG
XIIIth International Symposium on Atherosclerosis, September 28–October 2, 2003, Kyoto, Japan