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MS340 IMMUNOSUPPRESSIVE AND ANTI-DYSLIPIDEMIC TREATMENT AFTER KIDNEY AND KIDNEY–PANCREAS TRANSPLANTATION
178
Atherosclerosis Supplements 11, no. 2 (2010) 109–222
Memory Stick Presentations
did not influence the activation status of other cell types such as T-helper, cytotoxic T-cells, B cells/plasma cells or neutrophils. Our studies show that, independent of their lipid lowering effect, statins exhibit a dose dependent and highly selective effect on vascular inflammation, an effect that is presumably mediated by an effect on NFkB activity. The changes on chemokine/cytokine level are followed by a reduced activation of selected macrophage subsets but not of other cell types. The selective effect on vessel wall IL-6 expression may explain the reduced CRP levels upon statin therapy.
or migratory and proliferatory activity. EPC displayed pronounced adhesive capacities and did adopt an endothelial phenotype. Conclusion: SMP can be processed to tailored coronary stents that display appropriate radial strength, a pertinent biocompatibility pattern, and potentially beneficial EPC-adhesive capacities. SMP combined with the novel manufacturing technique might represent an interesting coronary stent development strategy potentially reducing ISR or in-stent thrombosis by accelerated reendothelialization.
MS338 ECHOCARDIOGRAPHIC VISUAL VERSUS COMPUTERIZED EVALUATION OF THE DEGREE OF AORTIC VALVE CALCIFICATION IN PATIENTS WITH AORTIC VALVE AND ROOT PATHOLOGY M. Yousry1,2 , M.J. Eriksson1 , A. Rickenlund1 , J. Petrini1 , T. Gustavsson3 , P. Eriksson1 , A. Hamsten1 , A. Franco-Cereceda1 , J. Liska1 , K. Caidahl1 . 1 Karolinska Institutet, Stockholm, Sweden, 2 Suez Canal University, Ismailia, ¨ Egypt, 3 Chalmers School of Technology, Goteborg, Sweden
MS340 IMMUNOSUPPRESSIVE AND ANTI-DYSLIPIDEMIC TREATMENT AFTER KIDNEY AND KIDNEY–PANCREAS TRANSPLANTATION T. Bulum, I. Prkaˇcin, D. Vujani´c, M. Knotek. Department of Nephrology, University Hospital Merkur, Zagreb, Croatia
Aortic valve calcification (AVC) is considered a part of generalized atherosclerosis and has prognostic importance in general population. However, its classification is subjective and requires training. Quantitative measure of valve-echogenicity by computerized grey-scale analysis (GSA) of images from transthoracic (TTE) or transesophageal (TEE) echocardiography might be an objective alternative. Aims: To determine whether GSA improves evaluation of AVC in aortic valve (AV) or aortic-root pathology in comparison to visual evaluation of TTE and TEE real-time images, using intraoperative evaluation as a golden standard. Methods: Two-dimensional short-axis view (2D, SAX) recordings of the AV were obtained by TTE and TEE in 175 patients at surgery for aortic stenosis (n = 110), aortic regurgitation (n = 60) or aortic-root dilatation (n = 5). Visual evaluation was performed in real-time sequences by a 5-degree scale, also applied intraoperatively by the surgeon. The same visual scale was applied on end-diastolic TTE and TEE stop-frames in order to evaluate the importance of real-time images in evaluation. GSA was independently applied at the same end-diastolic stop-frames. Results: Correlations between ultrasonic and intra-operative evaluations of AVC are given in Table 1. Conclusions: Visual evaluation of AVC in ultrasonic real-time sequences was closer related than evaluation in stop-frames to the intraoperative score. In realtime but not in stop-images, TEE was superior to TTE. GSA was not superior to visual assessment of stop-frames, and further development of GSA software also for real-time images might add diagnostic accuracy. Table 1 TTE
Intraoperative evaluation
TEE
GSA
Real-time evaluation
Stop-images evaluation
GSA
Real-time evaluation
Stop-images evaluation
r = 0.61**
r = 0.74**
r = 0.63**
r = 0.49**
r = 0.81**
r = 0.65**
MS339 DEVELOPMENT AND CHARACTERIZATION OF A SHAPE-MEMORY POLYMER-BASED CORONARY STENT WITH ENDOTHELIAL PROGENITOR CELL-ADHESIVE CAPACITY 1 F. Vogt , M. Borinski1 , F. Schreiber2 , C. Flege1 , N. Krott1 , T. Gries2 , C. Weber3 , R. Hoffmann1 , N. Marx1 , R. Blindt1 . 1 Cardiology, Pneumology and Angiology, University Hospital, RWTH Aachen, 2 Institute for Textile Technology, RWTH Aachen University, 3 Institute for Molecular Cardiovascular Research, University Hospital, RWTH Aachen, Aachen, Germany Objective: Shape-memory polymers (SMP) have been advocated for medical applications; endothelial progenitor cell (EPC) recruitment to sites of coronary injury has been shown to accelerate reendothelialization and to reduce ISR. The aim of the present study was to develop processing methods and to characterize mechanical, biocompatibility, and EPC-adhesive properties of a novel coronary polyurethane-based SMP stent. Methods: By a newly developed, three-dimensional braiding machine, polyurethane was melted, shaped to monofilaments, and processed to stents with adjustable properties. Mechanical testings for radial and tensile strength were performed. To assess SMP biocompatibility, during direct and indirect contact of EPC, human umbilical vein endothelial cells, or smooth muscle cells to SMP, viable or necrotic cells and proliferative or migratory activity were determined. EPC attachment and outgrowth were evaluated by a laminar flow chamber assay and by scanning electron microscopy. Results: By adaptation of monofilament and stent diameter, number of monofilaments, monofilament draw ratio, ankle, and heat treatment, tailored production of coronary stents was feasible. By heat treatment at 125ºC, radial strength of SMP stents was increased and comparable to nitinol stents. SMP biocompatibility assessment evidenced no reduction of cellular vitality
Introduction: Hyperlipidemia is a frequent finding among renal transplant recipients. Treatment of dyslipidemias should be part of routine postrenal transplant care. Immunosuppressive agents, particularly corticosteroids, calcineurin inhibitors and rapamycin, have dose-related effects on serum lipid levels. We investigated the frequency of anti-dyslipidemic drugs in relation to immunosuppressive agents. Patients and Methods: 163 patients [median age 44, range 18−70 years, 98M/65F, 98 with kidney transplant (KT) and 64 with kidney and pancreas transplant (SKPT)] have been evaluated for taking of immunosuppressive agents and treatment of dyslipidemia. Results: Seventy-eight (47%) of transplanted patients take lipid lowering drugs, 71 of them (91%) take fluvastatin, 7 patients (9%) atorvastatin. Fifty-three patients with KT (54%) and 25 patients with SPKT (39%) take antilipemic agents. Corticosteroids take 132 of all patients (80.9%), while in 50% of those lipid lowering drugs were introduced. Cyclosporine take 37.4% of all patients, in 55.7% of those lipid lowering drugs were introduced. Rapamycin take only 6 (0.03%) of all patients, in 3 (50%) of them lipid lowering drugs were introduced. Much better lipid profile was on tacrolimus therapy. Conclusion: The presented results show a high incidence of hyperlipidemia in patients with KT and SPKT, which is in line with results from other published studies. The largest number of transplanted patients was on corticosteroid therapy. The most frequent used anti-dyslipidemic drug was fluvastatin according to the largest experience (ALERT study). It is recommended to replace cyclosporine by tacrolimus, to discontinue sirolimus if dyslipidemia occurs, and continue low-dose prednisone. MS341 EFFECT OF NIACIN WITH ATORVASTATIN ON SECRETORY PHOSPHOLIPASE A2 IN MEN WITH CORONARY HEART DISEASE AND LIPOPROTEIN(a) EXCESS E. Trukhacheva, M. Ezhov, V. Titov, O. Afanasieva, M. Afanasieva, A. Lyakishev, V. Kukharchuk, S. Pokrovsky. Federal State Institution “Russian Cardiology Research − and Production Complex Rosmedtekhnologies”, Moscow, Russia Objective: To evaluate the effect of atorvastatin alone and in combination with niacin on level of secretory phospholipase A2 (sPLA2) in men with coronary heart disease (CHD) and lipoprotein(a) [Lp(a)] excess. Methods: We performed randomised controlled study in 60 men (mean age 54 years) with angiographically documented CHD and Lp(a) 30 mg/dl. Patients received either atorvastatin 10−20 mg/day (Group I, n = 30) or its combination with niacin 2.0 g/day (Group II, n = 30). We have measured the serum levels of total cholesterol (TC), triglycerides (TG), HDL-C, Lp(a), high sensitivity C-reactive protein (hsCRP), sPLA2 at baseline and after 6 months of therapy. Results: Before enter the study, the most of patients took statins: 90% in Group I and 60% in Group II. All baseline characteristics were comparable between groups. In 6 months there was significant decreasing of concentrations of TC (5.0±1.1 to 4.1±0.7 mmol/l, p < 0.05), LDL-C (3.0±1.1 to 2.2±0.5 mmol/l, p < 0.05), and Lp(a) (90±10 to 66±13 mg/dl, p < 0.05) in Group II but not in Group I. We obtained lowering of sPLA2 levels both in Group I (642±306 to 415±150 ng/ml, p < 0.05) and Group II (520±310 to 350±221 ng/ml, p < 0.05) and, importantly, in each patient. Concentrations of hsCRP remained unchanged during the study in both groups. Conclusion: In men with coronary heart disease and Lp(a) excess combination of atorvastatin with niacin significantly lowered levels of secretory phospholipase A2 and Lp(a). MS342 EFFECT OF EVEROLIMUS ON PRE-EXISTING ATHEROSCLEROSIS IN LDLR−/− MICE D. Brendel, F. Beutner, D. Teupser, M. Muller, ¨ R. Baber, F. Jeromin, W. Wilfert, U. Ceglarek, J. Thiery. Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Leipzig, Leipzig, Germany Objective: Inflammatory processes and proliferation play a critical role in atherogenesis. Proliferation signal inhibitors rapamycin and everolimus has been shown to decrease de novo development of atherosclerosis in different mouse models. However, their effect on pre-existing atherosclerosis has not
Atherosclerosis Supplements 11, no. 2 (2010) 109–222
Memory Stick Presentations
did not influence the activation status of other cell types such as T-helper, cytotoxic T-cells, B cells/plasma cells or neutrophils. Our studies show that, independent of their lipid lowering effect, statins exhibit a dose dependent and highly selective effect on vascular inflammation, an effect that is presumably mediated by an effect on NFkB activity. The changes on chemokine/cytokine level are followed by a reduced activation of selected macrophage subsets but not of other cell types. The selective effect on vessel wall IL-6 expression may explain the reduced CRP levels upon statin therapy.
or migratory and proliferatory activity. EPC displayed pronounced adhesive capacities and did adopt an endothelial phenotype. Conclusion: SMP can be processed to tailored coronary stents that display appropriate radial strength, a pertinent biocompatibility pattern, and potentially beneficial EPC-adhesive capacities. SMP combined with the novel manufacturing technique might represent an interesting coronary stent development strategy potentially reducing ISR or in-stent thrombosis by accelerated reendothelialization.
MS338 ECHOCARDIOGRAPHIC VISUAL VERSUS COMPUTERIZED EVALUATION OF THE DEGREE OF AORTIC VALVE CALCIFICATION IN PATIENTS WITH AORTIC VALVE AND ROOT PATHOLOGY M. Yousry1,2 , M.J. Eriksson1 , A. Rickenlund1 , J. Petrini1 , T. Gustavsson3 , P. Eriksson1 , A. Hamsten1 , A. Franco-Cereceda1 , J. Liska1 , K. Caidahl1 . 1 Karolinska Institutet, Stockholm, Sweden, 2 Suez Canal University, Ismailia, ¨ Egypt, 3 Chalmers School of Technology, Goteborg, Sweden
MS340 IMMUNOSUPPRESSIVE AND ANTI-DYSLIPIDEMIC TREATMENT AFTER KIDNEY AND KIDNEY–PANCREAS TRANSPLANTATION T. Bulum, I. Prkaˇcin, D. Vujani´c, M. Knotek. Department of Nephrology, University Hospital Merkur, Zagreb, Croatia
Aortic valve calcification (AVC) is considered a part of generalized atherosclerosis and has prognostic importance in general population. However, its classification is subjective and requires training. Quantitative measure of valve-echogenicity by computerized grey-scale analysis (GSA) of images from transthoracic (TTE) or transesophageal (TEE) echocardiography might be an objective alternative. Aims: To determine whether GSA improves evaluation of AVC in aortic valve (AV) or aortic-root pathology in comparison to visual evaluation of TTE and TEE real-time images, using intraoperative evaluation as a golden standard. Methods: Two-dimensional short-axis view (2D, SAX) recordings of the AV were obtained by TTE and TEE in 175 patients at surgery for aortic stenosis (n = 110), aortic regurgitation (n = 60) or aortic-root dilatation (n = 5). Visual evaluation was performed in real-time sequences by a 5-degree scale, also applied intraoperatively by the surgeon. The same visual scale was applied on end-diastolic TTE and TEE stop-frames in order to evaluate the importance of real-time images in evaluation. GSA was independently applied at the same end-diastolic stop-frames. Results: Correlations between ultrasonic and intra-operative evaluations of AVC are given in Table 1. Conclusions: Visual evaluation of AVC in ultrasonic real-time sequences was closer related than evaluation in stop-frames to the intraoperative score. In realtime but not in stop-images, TEE was superior to TTE. GSA was not superior to visual assessment of stop-frames, and further development of GSA software also for real-time images might add diagnostic accuracy. Table 1 TTE
Intraoperative evaluation
TEE
GSA
Real-time evaluation
Stop-images evaluation
GSA
Real-time evaluation
Stop-images evaluation
r = 0.61**
r = 0.74**
r = 0.63**
r = 0.49**
r = 0.81**
r = 0.65**
MS339 DEVELOPMENT AND CHARACTERIZATION OF A SHAPE-MEMORY POLYMER-BASED CORONARY STENT WITH ENDOTHELIAL PROGENITOR CELL-ADHESIVE CAPACITY 1 F. Vogt , M. Borinski1 , F. Schreiber2 , C. Flege1 , N. Krott1 , T. Gries2 , C. Weber3 , R. Hoffmann1 , N. Marx1 , R. Blindt1 . 1 Cardiology, Pneumology and Angiology, University Hospital, RWTH Aachen, 2 Institute for Textile Technology, RWTH Aachen University, 3 Institute for Molecular Cardiovascular Research, University Hospital, RWTH Aachen, Aachen, Germany Objective: Shape-memory polymers (SMP) have been advocated for medical applications; endothelial progenitor cell (EPC) recruitment to sites of coronary injury has been shown to accelerate reendothelialization and to reduce ISR. The aim of the present study was to develop processing methods and to characterize mechanical, biocompatibility, and EPC-adhesive properties of a novel coronary polyurethane-based SMP stent. Methods: By a newly developed, three-dimensional braiding machine, polyurethane was melted, shaped to monofilaments, and processed to stents with adjustable properties. Mechanical testings for radial and tensile strength were performed. To assess SMP biocompatibility, during direct and indirect contact of EPC, human umbilical vein endothelial cells, or smooth muscle cells to SMP, viable or necrotic cells and proliferative or migratory activity were determined. EPC attachment and outgrowth were evaluated by a laminar flow chamber assay and by scanning electron microscopy. Results: By adaptation of monofilament and stent diameter, number of monofilaments, monofilament draw ratio, ankle, and heat treatment, tailored production of coronary stents was feasible. By heat treatment at 125ºC, radial strength of SMP stents was increased and comparable to nitinol stents. SMP biocompatibility assessment evidenced no reduction of cellular vitality
Introduction: Hyperlipidemia is a frequent finding among renal transplant recipients. Treatment of dyslipidemias should be part of routine postrenal transplant care. Immunosuppressive agents, particularly corticosteroids, calcineurin inhibitors and rapamycin, have dose-related effects on serum lipid levels. We investigated the frequency of anti-dyslipidemic drugs in relation to immunosuppressive agents. Patients and Methods: 163 patients [median age 44, range 18−70 years, 98M/65F, 98 with kidney transplant (KT) and 64 with kidney and pancreas transplant (SKPT)] have been evaluated for taking of immunosuppressive agents and treatment of dyslipidemia. Results: Seventy-eight (47%) of transplanted patients take lipid lowering drugs, 71 of them (91%) take fluvastatin, 7 patients (9%) atorvastatin. Fifty-three patients with KT (54%) and 25 patients with SPKT (39%) take antilipemic agents. Corticosteroids take 132 of all patients (80.9%), while in 50% of those lipid lowering drugs were introduced. Cyclosporine take 37.4% of all patients, in 55.7% of those lipid lowering drugs were introduced. Rapamycin take only 6 (0.03%) of all patients, in 3 (50%) of them lipid lowering drugs were introduced. Much better lipid profile was on tacrolimus therapy. Conclusion: The presented results show a high incidence of hyperlipidemia in patients with KT and SPKT, which is in line with results from other published studies. The largest number of transplanted patients was on corticosteroid therapy. The most frequent used anti-dyslipidemic drug was fluvastatin according to the largest experience (ALERT study). It is recommended to replace cyclosporine by tacrolimus, to discontinue sirolimus if dyslipidemia occurs, and continue low-dose prednisone. MS341 EFFECT OF NIACIN WITH ATORVASTATIN ON SECRETORY PHOSPHOLIPASE A2 IN MEN WITH CORONARY HEART DISEASE AND LIPOPROTEIN(a) EXCESS E. Trukhacheva, M. Ezhov, V. Titov, O. Afanasieva, M. Afanasieva, A. Lyakishev, V. Kukharchuk, S. Pokrovsky. Federal State Institution “Russian Cardiology Research − and Production Complex Rosmedtekhnologies”, Moscow, Russia Objective: To evaluate the effect of atorvastatin alone and in combination with niacin on level of secretory phospholipase A2 (sPLA2) in men with coronary heart disease (CHD) and lipoprotein(a) [Lp(a)] excess. Methods: We performed randomised controlled study in 60 men (mean age 54 years) with angiographically documented CHD and Lp(a) 30 mg/dl. Patients received either atorvastatin 10−20 mg/day (Group I, n = 30) or its combination with niacin 2.0 g/day (Group II, n = 30). We have measured the serum levels of total cholesterol (TC), triglycerides (TG), HDL-C, Lp(a), high sensitivity C-reactive protein (hsCRP), sPLA2 at baseline and after 6 months of therapy. Results: Before enter the study, the most of patients took statins: 90% in Group I and 60% in Group II. All baseline characteristics were comparable between groups. In 6 months there was significant decreasing of concentrations of TC (5.0±1.1 to 4.1±0.7 mmol/l, p < 0.05), LDL-C (3.0±1.1 to 2.2±0.5 mmol/l, p < 0.05), and Lp(a) (90±10 to 66±13 mg/dl, p < 0.05) in Group II but not in Group I. We obtained lowering of sPLA2 levels both in Group I (642±306 to 415±150 ng/ml, p < 0.05) and Group II (520±310 to 350±221 ng/ml, p < 0.05) and, importantly, in each patient. Concentrations of hsCRP remained unchanged during the study in both groups. Conclusion: In men with coronary heart disease and Lp(a) excess combination of atorvastatin with niacin significantly lowered levels of secretory phospholipase A2 and Lp(a). MS342 EFFECT OF EVEROLIMUS ON PRE-EXISTING ATHEROSCLEROSIS IN LDLR−/− MICE D. Brendel, F. Beutner, D. Teupser, M. Muller, ¨ R. Baber, F. Jeromin, W. Wilfert, U. Ceglarek, J. Thiery. Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Leipzig, Leipzig, Germany Objective: Inflammatory processes and proliferation play a critical role in atherogenesis. Proliferation signal inhibitors rapamycin and everolimus has been shown to decrease de novo development of atherosclerosis in different mouse models. However, their effect on pre-existing atherosclerosis has not