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Influence of gender and age on chylomicron metabolism
Vinagre
Methods: After dietary stabilization, 6-to-lo-week washout, and a >4-week atorvastatin 10 &day run-in period, 362 patients with LDL-C33.37 mmol/L (mean LDL-C 5.11 mmol/L) and TG G3.99 mmol/L were randomized to ezetimibe 10 mg/d or additional double-blind atorvastatin (10 mg/d) for 4 weeks. The atorvastatin dose was doubled if LDL-C was >2.59 mmol/L after 4 and/or 9 weeks of treatment to a maximum 80 mg/day with atorvastatin alone and 40 mg/day with coadministration. The primary endpoint was the proportion of patients achieving target LDL-C G2.59 mmol/L at Week 14. Results: Addition of ezetimibe to atorvastatin 10 mg/day followed by response-based titration of atorvastatin significantly increased the proportion of patients reaching target LDL-C (31/181, 17%) versus atorvastatin uptitration (S/181, 4%; p
I760 ABDOMINAL
CHYLOMICRON SUBJFCTS
OBESITY IS CORRELATED WITH LIPOLYSIS IN NORMOLIPIDEMIC
C. Vinagre, R.D. Santos, E. Ficker, A. Morikawa, R. Maranhao. Institute, Incor Uniuersify ofSk Pa& Medical School, Brazil
Heart
Background:
The accumulation of fat in the abdominal region has been associated with the metabolic syndrome. Abdominal obesity is related with endogenous hypertriglyceridemia and this may affect chylomicron (CM) metabolism. Chylomicron-like emulsions (CLE) have been used to evaluate CM metabolism in human subjects with the advantage of bypassing absorptive mechanisms. Objective: Evaluate if abdominal obesity correlates with the plasma kinetics of CLE in normolipidemic, non-obese subjects. Methods: 48 normolipidemic men, body mass index (BMI) 25&3 kg/m2, age 58&18 years, total cholesterol 200&42 mg/dL, LDL-C 134&38 mg/dL, triglycerides 113&46 mg/dL and HDL-C 46&l 1 mg/dL were evaluated. One hundred microliters of a CLE were injected into the venous circulation after a 12 hour fasting. Blood samples were collected during 60 minutes. The plasma radioisotope decay curves were determined and the fractional catabolic rates (FCR l/min) of 3H-TO and 14C-CE that represent respectively CM lipolysis and CM and remnant removal from plasma were calculated by compartmental analysis. Abdominal fat was evaluated by the waist measurement (in cm). Results: The FCR of 3H-TO was inversely correlated with the waist measurement (~-0.4, p=O.O27). There was no correlation between the FCR of 3H-TGH and 14C-CE with age, BMI or plasma lipids. Conclusion: Abdominal fat accumulation is related with CM lipolysis even when plasma lipids and BMI are normal. I761 REMOVAL
FROM RICH EMULSION PATIENTS
THE PLASMA OF A CHOLESTEROLIN HEART TRANSPLANTATION
C.G. Puk’, C.C.G. Vinagre’, E. Bocchi’, F. Bacal’, R. Barbosa’, J.A. Ramires’, R.C. Maranhao’. 'Uniuersify ofSk Pa&, ‘Heart Institute (I&or), Uniuersify ofSk Pa&, Brazil Background:
Development of coronary graft disease is currently the first cause of late heart transplantation (HT) failure. HT patients frequently show hypercholeterolemia and we recently showed that they also have alterations in chylomicron metabolism. Those post-HT changes may be important in coronary graft disease development. To clarify whether hypercholesterolemia is due to decrease LDL removal from the plasma we studied the plasma kinetics of a cholesterol-rich emulsion that binds to LDL receptors in 13 HT and 13 healthy normolipidemic subjects paired for sex, age and BMI. Methods: The emulsion labeled with 14-C-cholesteryl oleate was injected 1.V. and blood samples were collected over 24 hs for determination of the decay curves of radioactivity and calculation of fractional clearance rates (FCR). Results: Total (254&45 vs 184&29 mg/dl), LDL (165&36 vs 118&22) and HDL cholesterol (53&S vs 41&8),and triglycerides (179&86 vs 115&36 mg/dl) were greater in HT than in controls (piO.05). FCR in both groups was similar (HT: 0.0558&0.0257; Controls: 0.0452&0.0257).
231
Conclusion: High LDL levels in HT is not due to defficiency in the mechanisms of LDL removal from the plasma, as tested by the cholesterolrich emulsion.
I762 INFLUENCE
METABOLISM
OF EXERCISE TRAINING ON LDL AND LDL OXlDATIVE PROCESS
C.G.C. Vinarre’,‘, E. Ficker’,‘, C.E. Negrao’, A.T. Morikawa’, M.J. Alves' , M.U. Rondon’, R.C. Maranhao’ ‘Heart Institute, Uniuersify ofSk Pa&: 2Uniuersify ofSanta Amaro, Sk Pa&, Brazil
The oxidation of LDL is known to be involved in atherosclerosis. Paradoxically, exercise training and in this case, cycling, which represents a severe form of oxidative stress, presents beneficial effects against atherosclerosis by reducing the risk of cardiovascular diseases. This study evaluated the effects of exercise on LDL metabolism and on the LDL oxidative process. Twenty four cyclists with a 34 times/week average training load for a minimum of 3 years, and 20 sedentary controls were studied. All underwent a maximal cardiopulmonary exercise test on a stationary bicycle to measure peak oxygen uptake (V02peak). An artificial emulsion, similar to LDL labeled with “C-cholesteryl oleate (CO) was injected intravenously in the participants, and blood samples collected at 5 min, 8 and 24 h after the injection, to determine the plasma decay curve and fractional clearance rate (FCR) of the artificial emulsion, by compartmental analysis. The plasma levels of oxidized LDL were determined in blood samples collected before the emulsion injection, by enzyme-linked-immunoassay (ELISA). Results: See the Table. Plasma LDL levels were not altered with exercise, but artifitial LDL plasma kinetic was accelerated as indicated by the higher “C-CO-FCR in cyclists. This indicates that LDL turnover is faster with exercise. In spite of the greater oxidative stress produced by exercise, the cyclists had lower plasma levels of oxidized LDL, perhaps because of their higher LDL turnover rate. In conclusion, exercise can accelerate the plasma kinetic of LDL and lower the plasma levels of oxidized LDL, whichin turn, may protect against atherosclerosis.
Vqpeak
(mlIkg/min)
Clmlesterol
cyclists
sede,hries
5656
34s
<0.001
171%29
180%39
0.4
total (mg/dl)
P
IDL
105524
120%30
0.1
HDL
50511*
41s
0.03
0.0261~0.023
<0.0001
16.053
<0.001
I4C-CO-FIX Oxidized
763
I
ILK
(I/mh)
0.138~0.152
(mU/l)
*
9.0&z*
INFLUENCE OF GENDER METABOLISM
AND AGE
ON CHYLOMICRON
C.G.C. Vinagre, A.T. Morikawa, L.1.V Brandizzi, E. Ficker, R.C. MaranhZo. Heart Institute, Uniuersify ofSk Pa&, Brazil
The atherosclerotic risk is higher with aging. The chylomicron metabolism is related to atherosclerosis. The objective of the present study was to evaluate the plasma kinetic of chylomicron in three different age groups, and in male and female groups. After a overnight fast, an artificial emulsion that mimics chylomicron, labeled with radioactive triglyceride (3H-TG) and cholesteryl oleate (14C-CO) was injected intravenously in 79 normolipidemic subjects. Blood samples were collected in pre-established intervals, during 60 minutes to determine the plasma decay curves and the fractional clearance rate (FCR, in l/min)) of the labels. Results: Male
(,1=50)
Fem&
(,1=29)
P
%TG-FCK
0.031~0.02
0.035%0.024
0.8
14C-CO-FCK
0.012~0.012
0.016~0.015
0.2
Ages
<30 ys (11=15)
40-55
>60 ys (n=33)
%TG-FCK
0.032~0.018
0.034~0.014
0.032~0.022
14C-CO-FCK
0.022~0.013
0.016+/0.014
0.011~0.011*
*P=O.O4, compared
ys (11=19)
to <30 ys group,
The chylomicron metabolism is not related to sex gender. The plasma removal of chylomicrons is reduced with aging as indicated by lower “C-CO-FCR in subjects over 60 ys old. This may contribute with the atherosclerotic process with aging.
73rd EAS Congress
Methods: After dietary stabilization, 6-to-lo-week washout, and a >4-week atorvastatin 10 &day run-in period, 362 patients with LDL-C33.37 mmol/L (mean LDL-C 5.11 mmol/L) and TG G3.99 mmol/L were randomized to ezetimibe 10 mg/d or additional double-blind atorvastatin (10 mg/d) for 4 weeks. The atorvastatin dose was doubled if LDL-C was >2.59 mmol/L after 4 and/or 9 weeks of treatment to a maximum 80 mg/day with atorvastatin alone and 40 mg/day with coadministration. The primary endpoint was the proportion of patients achieving target LDL-C G2.59 mmol/L at Week 14. Results: Addition of ezetimibe to atorvastatin 10 mg/day followed by response-based titration of atorvastatin significantly increased the proportion of patients reaching target LDL-C (31/181, 17%) versus atorvastatin uptitration (S/181, 4%; p
I760 ABDOMINAL
CHYLOMICRON SUBJFCTS
OBESITY IS CORRELATED WITH LIPOLYSIS IN NORMOLIPIDEMIC
C. Vinagre, R.D. Santos, E. Ficker, A. Morikawa, R. Maranhao. Institute, Incor Uniuersify ofSk Pa& Medical School, Brazil
Heart
Background:
The accumulation of fat in the abdominal region has been associated with the metabolic syndrome. Abdominal obesity is related with endogenous hypertriglyceridemia and this may affect chylomicron (CM) metabolism. Chylomicron-like emulsions (CLE) have been used to evaluate CM metabolism in human subjects with the advantage of bypassing absorptive mechanisms. Objective: Evaluate if abdominal obesity correlates with the plasma kinetics of CLE in normolipidemic, non-obese subjects. Methods: 48 normolipidemic men, body mass index (BMI) 25&3 kg/m2, age 58&18 years, total cholesterol 200&42 mg/dL, LDL-C 134&38 mg/dL, triglycerides 113&46 mg/dL and HDL-C 46&l 1 mg/dL were evaluated. One hundred microliters of a CLE were injected into the venous circulation after a 12 hour fasting. Blood samples were collected during 60 minutes. The plasma radioisotope decay curves were determined and the fractional catabolic rates (FCR l/min) of 3H-TO and 14C-CE that represent respectively CM lipolysis and CM and remnant removal from plasma were calculated by compartmental analysis. Abdominal fat was evaluated by the waist measurement (in cm). Results: The FCR of 3H-TO was inversely correlated with the waist measurement (~-0.4, p=O.O27). There was no correlation between the FCR of 3H-TGH and 14C-CE with age, BMI or plasma lipids. Conclusion: Abdominal fat accumulation is related with CM lipolysis even when plasma lipids and BMI are normal. I761 REMOVAL
FROM RICH EMULSION PATIENTS
THE PLASMA OF A CHOLESTEROLIN HEART TRANSPLANTATION
C.G. Puk’, C.C.G. Vinagre’, E. Bocchi’, F. Bacal’, R. Barbosa’, J.A. Ramires’, R.C. Maranhao’. 'Uniuersify ofSk Pa&, ‘Heart Institute (I&or), Uniuersify ofSk Pa&, Brazil Background:
Development of coronary graft disease is currently the first cause of late heart transplantation (HT) failure. HT patients frequently show hypercholeterolemia and we recently showed that they also have alterations in chylomicron metabolism. Those post-HT changes may be important in coronary graft disease development. To clarify whether hypercholesterolemia is due to decrease LDL removal from the plasma we studied the plasma kinetics of a cholesterol-rich emulsion that binds to LDL receptors in 13 HT and 13 healthy normolipidemic subjects paired for sex, age and BMI. Methods: The emulsion labeled with 14-C-cholesteryl oleate was injected 1.V. and blood samples were collected over 24 hs for determination of the decay curves of radioactivity and calculation of fractional clearance rates (FCR). Results: Total (254&45 vs 184&29 mg/dl), LDL (165&36 vs 118&22) and HDL cholesterol (53&S vs 41&8),and triglycerides (179&86 vs 115&36 mg/dl) were greater in HT than in controls (piO.05). FCR in both groups was similar (HT: 0.0558&0.0257; Controls: 0.0452&0.0257).
231
Conclusion: High LDL levels in HT is not due to defficiency in the mechanisms of LDL removal from the plasma, as tested by the cholesterolrich emulsion.
I762 INFLUENCE
METABOLISM
OF EXERCISE TRAINING ON LDL AND LDL OXlDATIVE PROCESS
C.G.C. Vinarre’,‘, E. Ficker’,‘, C.E. Negrao’, A.T. Morikawa’, M.J. Alves' , M.U. Rondon’, R.C. Maranhao’ ‘Heart Institute, Uniuersify ofSk Pa&: 2Uniuersify ofSanta Amaro, Sk Pa&, Brazil
The oxidation of LDL is known to be involved in atherosclerosis. Paradoxically, exercise training and in this case, cycling, which represents a severe form of oxidative stress, presents beneficial effects against atherosclerosis by reducing the risk of cardiovascular diseases. This study evaluated the effects of exercise on LDL metabolism and on the LDL oxidative process. Twenty four cyclists with a 34 times/week average training load for a minimum of 3 years, and 20 sedentary controls were studied. All underwent a maximal cardiopulmonary exercise test on a stationary bicycle to measure peak oxygen uptake (V02peak). An artificial emulsion, similar to LDL labeled with “C-cholesteryl oleate (CO) was injected intravenously in the participants, and blood samples collected at 5 min, 8 and 24 h after the injection, to determine the plasma decay curve and fractional clearance rate (FCR) of the artificial emulsion, by compartmental analysis. The plasma levels of oxidized LDL were determined in blood samples collected before the emulsion injection, by enzyme-linked-immunoassay (ELISA). Results: See the Table. Plasma LDL levels were not altered with exercise, but artifitial LDL plasma kinetic was accelerated as indicated by the higher “C-CO-FCR in cyclists. This indicates that LDL turnover is faster with exercise. In spite of the greater oxidative stress produced by exercise, the cyclists had lower plasma levels of oxidized LDL, perhaps because of their higher LDL turnover rate. In conclusion, exercise can accelerate the plasma kinetic of LDL and lower the plasma levels of oxidized LDL, whichin turn, may protect against atherosclerosis.
Vqpeak
(mlIkg/min)
Clmlesterol
cyclists
sede,hries
5656
34s
<0.001
171%29
180%39
0.4
total (mg/dl)
P
IDL
105524
120%30
0.1
HDL
50511*
41s
0.03
0.0261~0.023
<0.0001
16.053
<0.001
I4C-CO-FIX Oxidized
763
I
ILK
(I/mh)
0.138~0.152
(mU/l)
*
9.0&z*
INFLUENCE OF GENDER METABOLISM
AND AGE
ON CHYLOMICRON
C.G.C. Vinagre, A.T. Morikawa, L.1.V Brandizzi, E. Ficker, R.C. MaranhZo. Heart Institute, Uniuersify ofSk Pa&, Brazil
The atherosclerotic risk is higher with aging. The chylomicron metabolism is related to atherosclerosis. The objective of the present study was to evaluate the plasma kinetic of chylomicron in three different age groups, and in male and female groups. After a overnight fast, an artificial emulsion that mimics chylomicron, labeled with radioactive triglyceride (3H-TG) and cholesteryl oleate (14C-CO) was injected intravenously in 79 normolipidemic subjects. Blood samples were collected in pre-established intervals, during 60 minutes to determine the plasma decay curves and the fractional clearance rate (FCR, in l/min)) of the labels. Results: Male
(,1=50)
Fem&
(,1=29)
P
%TG-FCK
0.031~0.02
0.035%0.024
0.8
14C-CO-FCK
0.012~0.012
0.016~0.015
0.2
Ages
<30 ys (11=15)
40-55
>60 ys (n=33)
%TG-FCK
0.032~0.018
0.034~0.014
0.032~0.022
14C-CO-FCK
0.022~0.013
0.016+/0.014
0.011~0.011*
*P=O.O4, compared
ys (11=19)
to <30 ys group,
The chylomicron metabolism is not related to sex gender. The plasma removal of chylomicrons is reduced with aging as indicated by lower “C-CO-FCR in subjects over 60 ys old. This may contribute with the atherosclerotic process with aging.
73rd EAS Congress