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M.570 Serum apolipoproteins as acute phase reactants in patients with infection
132
Miscellaneous
Liberapaulas
85 women) suffering fram acute myacardial infarctian (either STAMI ar NSTAMI) in 1999-2000. At the discharge 175 af 200 patients received ACE-inhibitor (87%), 121 (60%) beta-blacker, 180 (90%) antiplatelet and 102 (51%) statin therapy. At the time af the cantral perfallned 6 month later 85% af the patients were an ACE-inhibitar, 88% an beta-blacker, 77% an asph'in and 47% an statin therapy. Having found these data the authors investigated patients suffering fl'am acute caranary syndrome with elevated trapanin-T levels in the year 2002. The use af beta-receptar blocker in therapy elevated ta 85%, antiplatelet drug and statin administratian rised ta 95% and 57%. Although these results are camparable with the published Hungarian and internatianal ones, the regular cantral and further imprave af secandary prevention treatment is essential.
M•.569•
ALTERATIONS OF SERUM PARAOXONASE 1 (PON1) AND SERUM AND HDL-ASSOCIATED PLATELETACTIVATING-FACTOR ACETYLHYDROLASE (PAF-AH) ACTIVITIES DURING HAEMODIALYSIS
E. Liberapaulas, E. Papavasiliau, A. Tselepis, K. Siamapaulas, M. Elisaf.
Department of lnternal Medicine and Department of Biochemistry, School of Chemistry, University of loannina, loannina, Greece Objective: Alteratians af serum PON1, total serum and HDL-assaciated PAF-AH activities have been implicated in the pathagenesis af atherasclerasis in uremic patients. Hawever, there are na studies cancerning passible changes in the activities af these enzymes during a hemadialysis (HD) session. Methods: 76 patients an regular HD wele studied. 35 patients were receiving canventianal HD with cellulose membranes and 40 well-matched individuals were an high-flux HD with biacampatible membranes. Serum lipids and enzyme activities were measured befare (pre-HD) and after the end af an HD session (past-HD). The past-HD values were calvected far haemacancen~atian. Results: Patients an high-flux HD had significantly lawer levels af pre-HD serum PON1 (54.9 4- 41.7 vs 74.5 4- 51.4 IU/L, p<0.01) compared ta those an canventianal HD. Hawever, na differences in serum and HDL-assaciated PAF-AH activities were noticed between the twa graups. The levels af serum lipids were nat significantly altered during the HD session in either group, nar did the serum PON1 and the total serum PAF-AH activity. Hawever, a significant increase in the HDL-assaciated PAF-AH activity, which is considered ta cantribute ta the antiaxidant praperties af HDL, was abserved in both conventional and high-flux HD groups: by 31% (fl'am 1.10 -4- 0.33 ta 1.44 -4- 0.44 nmal/ml/min, p=0.04) and by 45.7% (fi'am 1.16 -4- 0.28 ta 1.69 -4- 0.44 nmal/ml/min, p=0.0009), respectively (p<0.05 far camparisan between the twa graups). Conclusion: Antiatheragenic HDL-assaciated PAF-AH activity increases during HD and this increase is more pranaunced in patients receiving highflux HD.
~70~
SERUM APOLIPOPROTEINS AS ACUTE PHASE REACTANTS IN PATIENTS WITH INFECTION
E. Liberapaulas, F. Apastalau, K. Seferiadis, A. Tselepis, M. Elisaf.
Department of lnternal Medicine, Department of Biochemistry, School of Medicine, Department of Biochemistry, School of Chemistry, University of loannina, loannina, Greece Objective: There are limited data an the effect af the acute inflammatary lespanse an the serum levels af apalipapratein (Apa) E and lipapratein (a) [Lp(a)]. Methods: Serum lipid parameters were meastu'ed in patients with acute infection an admission and six months after theh" discharge. Results: 40 patients (20 M-20 F, mean age 44.6 yrs) were studied. 21 patients had bacterial infections, 14 patients vh'al infections and 5 patients had parasitic infections. During the follow-up, significant increases in the levels af tatal cholesterol (by 69.8%, fi'am 104.8 4- 30.9 ta 178.05 4- 42.06 mg/dl, p<0.00001), HDL chalesteral (by 74.8%, fi'am 19.9 4- 10.7 ta 34.8 4- 10.1 mg/dl, p<0.00001), LDL cholesterol (by 119.5%, fi'am 54.2 4- 27.3 ta 119.0 4- 36.9 mg/dl, p<0.00001), ApaAI (by 83%, fi'am 61.2 4- 28.0 ta 112.0 4- 30.3 mg/dl, p<0.00001), and ApaB (by 16.7%, fi'am 76.2 4- 32.7 ta 88.6 4- 28.6 mg/dl, p=0.05) were abserved. The levels af triglycerides were nat changed significantly dtu'ing the same periad. Finally, ApaE levels were significantly reduced by 52.3% (fi'am 6.96 4- 3.91 ta 4.57 4- 1.65 mg/dl, p--0.001), whereas levels af Lp(a) were significantly increased by 142% [fi'am 1.9 (0.8-18.0) ta 4.6 (0.8-52.0) mg/dl, p<0.01].
Conclusion: Our data point aut that Lp(a) may be a negative acute phase reactant in patients with infection. Furthermare, we studied the effect af the acute inflammatary response an the serum ApaE levels far the first time, and we suggest that ApaE is a positive acute phase pratein in such patients.
•]
EVALUATION OF THE LONG-TERM SAFETY AND TOLERABILITY PROFILE OF EZETIMIBE PLUS ATORVASTATIN COADMINISTRATION THERAPY IN PATIENTS WITH PRIMARY HYPERCHOLESTEROLEMIA
L. Lipka, C. Ballantyne, P. Sager, J. SU'any, J. Alizadeh, R. Smesh, E. Velu'i. Schering-Plough Research Institute, Kenilworth, Baylor College
of Medicine, Houston, USA Purpose: Evaluate lang-terrn safety and talerability af ezetimibe (EZE) plus atarvastatin (ATV) caadministratian therapy campated ta ATV manatherapy in patients with primary hyperchalesteralemia fallawed far 1 year. Methods: Upon campletian af a randamized, double-blind, placeba (Pba)-cantralled, 12-week study, camparing: EZE 10 rag; ATV 10, 20, 40, ar 80 rag; EZE + ATV 10, 20, 40, ar 80 rag; ar Pba, 246 patients enralled in a 12-manth extensian study, with reassignment ta double-blind EZE 10 mg ar matching Pba (4:1 ratia) caadministered daily with open-label ATV 10 rag. At intervals af _>6 weeks, patients nat at NCEP ATPII LDL-C goal were titrated ta the next higher ATV dose (maximum af 80 rag/d). Safety evaluatians included adverse event (AE) reparts and labaratary test results. Results: The fi'equency af AE and discantinuatians due ta ~eatmentrelated AE were similar between the ~eatment graups. There were na clinically significant elevatians in hepatic transaminases ar creatine phasphakinase, and na cases af myapathy ar rhabdamyalysis in either graup. After 6 weeks, EZE+ATV 10 mg praduced greater reductians in LDL-C (53% vs. 37%) and TG (28% vs. 12%), and similar increases in HDL-C (4.6% vs. 4.5%) campared ta ATV 10 rag. These effects were maintained aver 1 year. Campared ta ATV manatherapy, fewer EZE+ATV patients requfl'ed upward titratian af ATV ta achieve LDL-C gaals (22% vs. 9%, respectively). Adverse Events (AE) Safety Endpoints Treatment-emergentAE Treatment-related AE* Discontinued due to Weatment-relatedAE ALT or AST > 3 x ULN (consecutive) CPK > i0x ULN
Incidence of Adverse Events % (n) ATV (N=45) EZE+ATV(N=20I) 67% (30) 27% (12) 7% (3) 0 0
71% (142) 22% (45) 7% (13) 0 0
*Considered possibly,probably, or definffelytreatment-related by the investigator. Conclusions: CaadminisU'atian af EZE+ATV far 12 months was well talerated and mole efficacious than ATV manatherapy.
~ 2 ]
INVASIVE MEASUREMENTS OF PULSE WAVE VELOCITY CORRELATE WITH THE DEGREE OF E C H O C A R D I O G R A P H I C AORTIC VALVE CALCIFICATION AND ITS SEVERITY IN AGED PATIENTS WITH DEGENERATIVE AORTIC VALVE STENOSIS
P. Liu, W. Tsai, C. Lin, C. Hsu, J. Chen. Naitional Cheng-Kung University
Hospital, Tainan, Taiwan Objective: Ta assess the assaciatian between invasive pulse wave velocity (PWV) and the echacardiagraphic severity, calcificatian score af degenerative aartic stenasis (AS) Patients and Methods: We enralled 30 patients (16 males, age 61.3 -48.2 years) with diagnasis af degenerative AS and additianal 30 age-and-sex matched can~al graup patients. Invasive PWV methads with pigtail catheter and dauble channel recarding were perfarrned in both graups. We scared the severity af calcificatian at the aartic valve during echacardiagraphy. The assaciatian between the U'ans-valvular pressure gradient, the severity af valvular calcificatian and the value af PWV were analyzed. Serum levels af maU'ix metallaprateinase (MMP)-9, MMP-3, and TIMP-1 were measured by ELISA kits. Results: With higher mean aartic valve pressure gradient (56.0 vs. 9.5 mmHg), we found that the calcified aartic valve scoring was higher in the degenerative AS graup (3.3-4-1.2 vs. 2.1-4-0.9, p<0.001). During invasive
74th EAS Congress, 17-20 April 2004, Seville, Spain
Miscellaneous
Liberapaulas
85 women) suffering fram acute myacardial infarctian (either STAMI ar NSTAMI) in 1999-2000. At the discharge 175 af 200 patients received ACE-inhibitor (87%), 121 (60%) beta-blacker, 180 (90%) antiplatelet and 102 (51%) statin therapy. At the time af the cantral perfallned 6 month later 85% af the patients were an ACE-inhibitar, 88% an beta-blacker, 77% an asph'in and 47% an statin therapy. Having found these data the authors investigated patients suffering fl'am acute caranary syndrome with elevated trapanin-T levels in the year 2002. The use af beta-receptar blocker in therapy elevated ta 85%, antiplatelet drug and statin administratian rised ta 95% and 57%. Although these results are camparable with the published Hungarian and internatianal ones, the regular cantral and further imprave af secandary prevention treatment is essential.
M•.569•
ALTERATIONS OF SERUM PARAOXONASE 1 (PON1) AND SERUM AND HDL-ASSOCIATED PLATELETACTIVATING-FACTOR ACETYLHYDROLASE (PAF-AH) ACTIVITIES DURING HAEMODIALYSIS
E. Liberapaulas, E. Papavasiliau, A. Tselepis, K. Siamapaulas, M. Elisaf.
Department of lnternal Medicine and Department of Biochemistry, School of Chemistry, University of loannina, loannina, Greece Objective: Alteratians af serum PON1, total serum and HDL-assaciated PAF-AH activities have been implicated in the pathagenesis af atherasclerasis in uremic patients. Hawever, there are na studies cancerning passible changes in the activities af these enzymes during a hemadialysis (HD) session. Methods: 76 patients an regular HD wele studied. 35 patients were receiving canventianal HD with cellulose membranes and 40 well-matched individuals were an high-flux HD with biacampatible membranes. Serum lipids and enzyme activities were measured befare (pre-HD) and after the end af an HD session (past-HD). The past-HD values were calvected far haemacancen~atian. Results: Patients an high-flux HD had significantly lawer levels af pre-HD serum PON1 (54.9 4- 41.7 vs 74.5 4- 51.4 IU/L, p<0.01) compared ta those an canventianal HD. Hawever, na differences in serum and HDL-assaciated PAF-AH activities were noticed between the twa graups. The levels af serum lipids were nat significantly altered during the HD session in either group, nar did the serum PON1 and the total serum PAF-AH activity. Hawever, a significant increase in the HDL-assaciated PAF-AH activity, which is considered ta cantribute ta the antiaxidant praperties af HDL, was abserved in both conventional and high-flux HD groups: by 31% (fl'am 1.10 -4- 0.33 ta 1.44 -4- 0.44 nmal/ml/min, p=0.04) and by 45.7% (fi'am 1.16 -4- 0.28 ta 1.69 -4- 0.44 nmal/ml/min, p=0.0009), respectively (p<0.05 far camparisan between the twa graups). Conclusion: Antiatheragenic HDL-assaciated PAF-AH activity increases during HD and this increase is more pranaunced in patients receiving highflux HD.
~70~
SERUM APOLIPOPROTEINS AS ACUTE PHASE REACTANTS IN PATIENTS WITH INFECTION
E. Liberapaulas, F. Apastalau, K. Seferiadis, A. Tselepis, M. Elisaf.
Department of lnternal Medicine, Department of Biochemistry, School of Medicine, Department of Biochemistry, School of Chemistry, University of loannina, loannina, Greece Objective: There are limited data an the effect af the acute inflammatary lespanse an the serum levels af apalipapratein (Apa) E and lipapratein (a) [Lp(a)]. Methods: Serum lipid parameters were meastu'ed in patients with acute infection an admission and six months after theh" discharge. Results: 40 patients (20 M-20 F, mean age 44.6 yrs) were studied. 21 patients had bacterial infections, 14 patients vh'al infections and 5 patients had parasitic infections. During the follow-up, significant increases in the levels af tatal cholesterol (by 69.8%, fi'am 104.8 4- 30.9 ta 178.05 4- 42.06 mg/dl, p<0.00001), HDL chalesteral (by 74.8%, fi'am 19.9 4- 10.7 ta 34.8 4- 10.1 mg/dl, p<0.00001), LDL cholesterol (by 119.5%, fi'am 54.2 4- 27.3 ta 119.0 4- 36.9 mg/dl, p<0.00001), ApaAI (by 83%, fi'am 61.2 4- 28.0 ta 112.0 4- 30.3 mg/dl, p<0.00001), and ApaB (by 16.7%, fi'am 76.2 4- 32.7 ta 88.6 4- 28.6 mg/dl, p=0.05) were abserved. The levels af triglycerides were nat changed significantly dtu'ing the same periad. Finally, ApaE levels were significantly reduced by 52.3% (fi'am 6.96 4- 3.91 ta 4.57 4- 1.65 mg/dl, p--0.001), whereas levels af Lp(a) were significantly increased by 142% [fi'am 1.9 (0.8-18.0) ta 4.6 (0.8-52.0) mg/dl, p<0.01].
Conclusion: Our data point aut that Lp(a) may be a negative acute phase reactant in patients with infection. Furthermare, we studied the effect af the acute inflammatary response an the serum ApaE levels far the first time, and we suggest that ApaE is a positive acute phase pratein in such patients.
•]
EVALUATION OF THE LONG-TERM SAFETY AND TOLERABILITY PROFILE OF EZETIMIBE PLUS ATORVASTATIN COADMINISTRATION THERAPY IN PATIENTS WITH PRIMARY HYPERCHOLESTEROLEMIA
L. Lipka, C. Ballantyne, P. Sager, J. SU'any, J. Alizadeh, R. Smesh, E. Velu'i. Schering-Plough Research Institute, Kenilworth, Baylor College
of Medicine, Houston, USA Purpose: Evaluate lang-terrn safety and talerability af ezetimibe (EZE) plus atarvastatin (ATV) caadministratian therapy campated ta ATV manatherapy in patients with primary hyperchalesteralemia fallawed far 1 year. Methods: Upon campletian af a randamized, double-blind, placeba (Pba)-cantralled, 12-week study, camparing: EZE 10 rag; ATV 10, 20, 40, ar 80 rag; EZE + ATV 10, 20, 40, ar 80 rag; ar Pba, 246 patients enralled in a 12-manth extensian study, with reassignment ta double-blind EZE 10 mg ar matching Pba (4:1 ratia) caadministered daily with open-label ATV 10 rag. At intervals af _>6 weeks, patients nat at NCEP ATPII LDL-C goal were titrated ta the next higher ATV dose (maximum af 80 rag/d). Safety evaluatians included adverse event (AE) reparts and labaratary test results. Results: The fi'equency af AE and discantinuatians due ta ~eatmentrelated AE were similar between the ~eatment graups. There were na clinically significant elevatians in hepatic transaminases ar creatine phasphakinase, and na cases af myapathy ar rhabdamyalysis in either graup. After 6 weeks, EZE+ATV 10 mg praduced greater reductians in LDL-C (53% vs. 37%) and TG (28% vs. 12%), and similar increases in HDL-C (4.6% vs. 4.5%) campared ta ATV 10 rag. These effects were maintained aver 1 year. Campared ta ATV manatherapy, fewer EZE+ATV patients requfl'ed upward titratian af ATV ta achieve LDL-C gaals (22% vs. 9%, respectively). Adverse Events (AE) Safety Endpoints Treatment-emergentAE Treatment-related AE* Discontinued due to Weatment-relatedAE ALT or AST > 3 x ULN (consecutive) CPK > i0x ULN
Incidence of Adverse Events % (n) ATV (N=45) EZE+ATV(N=20I) 67% (30) 27% (12) 7% (3) 0 0
71% (142) 22% (45) 7% (13) 0 0
*Considered possibly,probably, or definffelytreatment-related by the investigator. Conclusions: CaadminisU'atian af EZE+ATV far 12 months was well talerated and mole efficacious than ATV manatherapy.
~ 2 ]
INVASIVE MEASUREMENTS OF PULSE WAVE VELOCITY CORRELATE WITH THE DEGREE OF E C H O C A R D I O G R A P H I C AORTIC VALVE CALCIFICATION AND ITS SEVERITY IN AGED PATIENTS WITH DEGENERATIVE AORTIC VALVE STENOSIS
P. Liu, W. Tsai, C. Lin, C. Hsu, J. Chen. Naitional Cheng-Kung University
Hospital, Tainan, Taiwan Objective: Ta assess the assaciatian between invasive pulse wave velocity (PWV) and the echacardiagraphic severity, calcificatian score af degenerative aartic stenasis (AS) Patients and Methods: We enralled 30 patients (16 males, age 61.3 -48.2 years) with diagnasis af degenerative AS and additianal 30 age-and-sex matched can~al graup patients. Invasive PWV methads with pigtail catheter and dauble channel recarding were perfarrned in both graups. We scared the severity af calcificatian at the aartic valve during echacardiagraphy. The assaciatian between the U'ans-valvular pressure gradient, the severity af valvular calcificatian and the value af PWV were analyzed. Serum levels af maU'ix metallaprateinase (MMP)-9, MMP-3, and TIMP-1 were measured by ELISA kits. Results: With higher mean aartic valve pressure gradient (56.0 vs. 9.5 mmHg), we found that the calcified aartic valve scoring was higher in the degenerative AS graup (3.3-4-1.2 vs. 2.1-4-0.9, p<0.001). During invasive
74th EAS Congress, 17-20 April 2004, Seville, Spain