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779 THE PROGNOSTIC SIGNIFICANCE OF THE FREQUENCY AND THE MORPHOLOGY OF PREMATURE VENTRICULAR CONTRACTIONS DURING AMBULATORY HOLTER MONITORING
79th EAS Congress
Atherosclerosis Supplements 12, no. 1 (2011) 13–184
777 A PACLITAXEL DERIVATIVE (PACLITAXEL OLEATE) ASSOCIATED WITH A CHOLESTEROL-RICH NANOEMULSION DECREASES THE TRANSPLANT HEART VASCULAR DISEASE IN RABBIT GRAFT MODEL 1 R. Maranhao ˜ 1,2 , D.D. Louren¸co-Filho1 , C.A. Mendez-Contreras ´ , E.R. Tavares1 , F.R. Freitas1 , N.A. Stolf1 . 1 Heart Institute, Medical School Hospital, University ˜ Paulo, 2 Faculty of Pharmaceutical Science, University of Sao ˜ Paulo, of Sao ˜ Paulo, Brazil Sao Introduction: Previously, cholesterol-rich nanoemulsions (LDE) resembling low-density lipoprotein (LDL) were shown to concentrate in atherosclerotic lesions of rabbits. Lesions were pronouncedly reduced by treatment with paclitaxel-oleate associated to LDE. Objecitve: This study aimed to verify whether LDE-paclitaxel-oleate could concentrate in grafted hearts of rabbits and to ameliorate coronary allograft vasculopathy following the transplantation procedure. Methods: Twenty-one New Zealand rabbits fed 0.5% cholesterol underwent heterotopic heart transplantation at cervical position. All rabbits were treated with cyclosporine A (10 mg/kg/day, os). Eleven rabbits were treated with LDEpaclitaxel-oleate (4 mg/kg body weight paclitaxel/week, I.V.) and 10 control rabbits with saline, for 6 weeks. Four control animals were injected LDE labeled with [14 C]-cholesteryl oleate-ether to determine tissue uptakes. Results: Radioactive LDE uptake by grafts hearts was four fold that of native hearts. Treatment with LDE-paclitaxel-oleate reduced 50% the degree of stenosis in grafted hearts. Arterial lumen area in grafts hearts of LDE-paclitaxeloleate treated group was three-fold larger than in controls and macrophage infiltration was reduced seven-fold. LDE-paclitaxel-oleate also reduced the width of the arterial intima layer and inhibited destruction of arterial media layer. No toxicity was observed under LDE-paclitaxel-oleate. Conclusion: This novel therapeutic approach for heart transplantation management is thus a promising strategy to be explored in future clinical studies, since transplant heart vascular disease is the main cause of transplantation failure after the first year and currently has no valid treatment. 778 EFFECTIVITY OF COLESEVELAM IN STATIN INTOLERANT PATIENTS ± EZETIMIBE S. Maierhofer1 , A. deCampo1 , T. Stojakovic2 , H. Jahnel1 , H. Toplak1 . 1 Department of Medicine, 2 Department of Laboratory Diagnostics, Medical University Graz, Graz, Austria Introduction: Statin intolerance is rare but important in clinical practice. Management of cardiovascular risk is restricted to resorption inhibitors and, if indicated, to other drug classes mainly addressing triglyceride levels. We have investigated whether using Colesevelam, a bile acid sequestrant, as monotherapy or add on to Ezetimibe, a selective cholesterol resorption inhibitor, could be of benefit in that subgroup of patients. Methods: Statin intolerant patients with a mean age of 61±9 years (9 women, 6 men) were included in the study. The previously untreated group (A) was treated with Colesevelam-monotherapy (8 patients, 6x625 mg), since Ezetimibe intolerance − additionally to statin intolerance − was already known. Group (B) was pretreated with Ezetimibe (7 patients, 10 mg) and received Colesevelam additionally. Analysis of serum lipid parameters was performed at baseline and after six weeks. Results: Mean inclusion lipid parameters (both groups) were total cholesterol of 267±60, triglycerides of 174±86 and NonHDL-C of 217±60 mg/dl. Starting values and response in both groups were comparable. Results of the study Group
TC
TG
NonHDL-C
HDL-C
LDL-C
A (Colesevelam)
−12.40%*
−15.90%**
−14.40%*
−4.40%
−15.30%
B (add on to Ezetimibe)
−9.50%**
12.40%
−2.20%
−14.90%
−11.00%
*p < 0.05, **p < 0.01, ***p < 0.001.
Conclusion: Therapy with Colesevelam is effective and additive to Ezetimibe. Despite some non-responders (<5% LDL-C reduction) both groups achieved an up to 30% reduction of LDL-cholesterol, which is clinically relevant for patients with statin (± Ezetimibe) intolerance. 779 THE PROGNOSTIC SIGNIFICANCE OF THE FREQUENCY AND THE MORPHOLOGY OF PREMATURE VENTRICULAR CONTRACTIONS DURING AMBULATORY HOLTER MONITORING G. Ephrem1 , M. Levine2 , P. Friedmann3 , P. Schweitzer2 . 1 Department of Medicine, 2 Division of Cardiology, 3 Office of Grants and Research Administration, Beth Israel Medical Center, New York, NY, USA Background: Multiform ventricular premature beats (VPBs) are associated with an adverse prognosis in patients with structural heart disease. Very frequent VPBs are associated with ventricular dysfunction. Our hypothesis is that multiform VPBs confer an adverse prognosis in the general population.
163
Methods: We performed a retrospective cohort study of patients 18 years old referred to our institution for 24-hour Holter monitoring between July 1, 2008 and December 31, 2009. Holters with no VPBs or with non-sustained ventricular tachycardia were excluded. Clinical and adverse event (AE) data ("major adverse cardiovascular event" or new/worsening heart failure) were gathered from chart review. Data was analyzed by VPB frequency (rare, occasional, frequent) and morphology (uniform or multiform). Results: 222 patients (43% male, mean age 55±16 years) were evaluated (median follow-up 7 months (IQR 4−13)). Median frequency was 2 VPB/hr (IQR 1−13). Multiform VPBs were noted in 48%. Patients with multiform VPBs were older, and had a higher prevalence of CAD and CHF. During follow-up, 30 AE were noted. Patients with an AE were younger, had a higher prevalence of HTN, diabetes, CAD and CHF. The multiform group had a higher incidence of AE (23%) compared to the uniform group (5%) (p = 0.0006). Their 1-year event rate was also greater (25% versus 5%) (p = 0.0001). VPB frequency was associated with a higher incidence of AE in the multiform group only. In a Cox regression analysis, multiformity but not frequency predicted AE. Conclusion: Multiform VPBs are associated with AE.
780 ACCURACY AND PRECISION OF POINT-OF-CARE TESTING FOR SERUM CHOLESTEROL, TRIGLYCERIDES AND HDL CHOLESTEROL J.V. Patel1 , G. Thorpe2 , L. Springer3 , E.A. Hughes1 . 1 SMRU, Sandwell and West Birmingham Hospitals NHS Trust, 2 Wolfson Research Laboratories, University of Birmingham, Birmingham, UK , 3 Physician’s Laboratory Advantage Consulting, Glencoe, MN, USA Coronary heart disease (CHD) is the leading preventable cause of death in the UK, and a key strategy for primary prevention is the early detection and reversal of dyslipidaemia − a major correctable cause. The introduction of point-of-care testing (POCT) for serum lipids brings with it the potential to improve patient experiences. However, perceived advantages of better convenience, rapid assessment and consultation could be offset by inaccuracy and unreliability. We were interested to determine the accuracy and precision of total cholesterol (CHOL), triglyceride (TG) and high density lipoprotein cholesterol (HDLc) measures by a nurse on capillary blood using a commercially availible POCT device (Cardiochek, Indianapolis US), and evaluate its performance to discriminate risk categories associated with dyslipidaemia in 160 individuals visiting the outpatient department (Sandwell Hospital) as validated by results obtained from venous serum using a biochemistry analyser (Integra-400+, Roche Diagnostics). Results: Using the Integra-400+, min-max ranges for CHOL, TG and HDLc were 2.4–10.8 mmol/l, 0.6–8.99 mmol/l and 0.6–3.11 mmol/l. CHOL was nonsignificantly 1.4% higher using POCT; a mean bias of 0.07 (sd:0.48) mmol/l. Inaccuracy was greater for HDLc and TG, which were 0.15 (0.20) mmol/l higher (P < 0.001) and 0.08 (0.50) mol/l lower (P = 0.04) using POCT. On ROC analysis, POC testing discriminated the presence of CHOL >5 mmol/l, CHOL:HDLc ratio >6 and TG > 1.7 mmol/l with lower limits of 95% CI for AUC all exceeding 90%). Conclusion: These data for POCT of lipids suggest this approach is appropriate for CHD risk stratification, where the device provides reliable fractionated lipid information − consistent with a traditional clinical chemistry platform.
781 MORE AGGRESSIVE LDL-C AND NON-HDL-C TARGETS MUST BE ACHIEVED IN PATIENTS RECEIVING LIPID-LOWERING THERAPY TO NORMALIZE APOB-CONTAINING LIPOPROTEINS J. Betteridge1 , J.R. Guyton2 , M. Farnier3 , L.A. Leiter4 , J. Lin5 , A. Shah5 , A.O. Johnson-Levonas5 , P. Brudi5 . 1 Royal Free & University College London Medical School, London, UK , 2 Duke University Medical Center, North Carolina, Durham, NC, USA, 3 Point Medical, Dijon, France, 4 Keenan Research Centre in the Li Ka Shing Knowledge Institute of St. Michael’s Hospital, University of Toronto, Toronto, ON, Canada, 5 Merck, Whitehouse Station, NJ, USA Introduction: Statins modify correlations between apoB:LDL-C and nonHDL-C; it is not known if other lipid-lowering therapies have similar effects. Objective: This post-hoc, pooled analysis examined relationships between apoB:LDL-C and apoB:non-HDL-C from 27 randomized, double-blind, activeor placebo-controlled studies in 21794 hypercholesterolemic patients receiving EZE/statin or statin alone, administered as first- or second-line therapy, for 4−24wk. Methods: Simple linear regression analyses calculated LDL-C and non-HDL-C levels corresponding to apoB=90 mg/dL at baseline and endpoint. Results: At baseline in the first-line therapy group, apoB=90 mg/dL corresponded to minimum LDL-C and non-HDL-C goals for high-risk patients (i.e., 100 and 130 mg/dL, respectively). At baseline in the second-line therapy group and following treatment in both the first and second-line groups, apoB=90 mg/dL corresponded to more aggressive LDL-C and non-HDL-C goals (i.e., 70 and 100 mg/dL, respectively).
Atherosclerosis Supplements 12, no. 1 (2011) 13–184
777 A PACLITAXEL DERIVATIVE (PACLITAXEL OLEATE) ASSOCIATED WITH A CHOLESTEROL-RICH NANOEMULSION DECREASES THE TRANSPLANT HEART VASCULAR DISEASE IN RABBIT GRAFT MODEL 1 R. Maranhao ˜ 1,2 , D.D. Louren¸co-Filho1 , C.A. Mendez-Contreras ´ , E.R. Tavares1 , F.R. Freitas1 , N.A. Stolf1 . 1 Heart Institute, Medical School Hospital, University ˜ Paulo, 2 Faculty of Pharmaceutical Science, University of Sao ˜ Paulo, of Sao ˜ Paulo, Brazil Sao Introduction: Previously, cholesterol-rich nanoemulsions (LDE) resembling low-density lipoprotein (LDL) were shown to concentrate in atherosclerotic lesions of rabbits. Lesions were pronouncedly reduced by treatment with paclitaxel-oleate associated to LDE. Objecitve: This study aimed to verify whether LDE-paclitaxel-oleate could concentrate in grafted hearts of rabbits and to ameliorate coronary allograft vasculopathy following the transplantation procedure. Methods: Twenty-one New Zealand rabbits fed 0.5% cholesterol underwent heterotopic heart transplantation at cervical position. All rabbits were treated with cyclosporine A (10 mg/kg/day, os). Eleven rabbits were treated with LDEpaclitaxel-oleate (4 mg/kg body weight paclitaxel/week, I.V.) and 10 control rabbits with saline, for 6 weeks. Four control animals were injected LDE labeled with [14 C]-cholesteryl oleate-ether to determine tissue uptakes. Results: Radioactive LDE uptake by grafts hearts was four fold that of native hearts. Treatment with LDE-paclitaxel-oleate reduced 50% the degree of stenosis in grafted hearts. Arterial lumen area in grafts hearts of LDE-paclitaxeloleate treated group was three-fold larger than in controls and macrophage infiltration was reduced seven-fold. LDE-paclitaxel-oleate also reduced the width of the arterial intima layer and inhibited destruction of arterial media layer. No toxicity was observed under LDE-paclitaxel-oleate. Conclusion: This novel therapeutic approach for heart transplantation management is thus a promising strategy to be explored in future clinical studies, since transplant heart vascular disease is the main cause of transplantation failure after the first year and currently has no valid treatment. 778 EFFECTIVITY OF COLESEVELAM IN STATIN INTOLERANT PATIENTS ± EZETIMIBE S. Maierhofer1 , A. deCampo1 , T. Stojakovic2 , H. Jahnel1 , H. Toplak1 . 1 Department of Medicine, 2 Department of Laboratory Diagnostics, Medical University Graz, Graz, Austria Introduction: Statin intolerance is rare but important in clinical practice. Management of cardiovascular risk is restricted to resorption inhibitors and, if indicated, to other drug classes mainly addressing triglyceride levels. We have investigated whether using Colesevelam, a bile acid sequestrant, as monotherapy or add on to Ezetimibe, a selective cholesterol resorption inhibitor, could be of benefit in that subgroup of patients. Methods: Statin intolerant patients with a mean age of 61±9 years (9 women, 6 men) were included in the study. The previously untreated group (A) was treated with Colesevelam-monotherapy (8 patients, 6x625 mg), since Ezetimibe intolerance − additionally to statin intolerance − was already known. Group (B) was pretreated with Ezetimibe (7 patients, 10 mg) and received Colesevelam additionally. Analysis of serum lipid parameters was performed at baseline and after six weeks. Results: Mean inclusion lipid parameters (both groups) were total cholesterol of 267±60, triglycerides of 174±86 and NonHDL-C of 217±60 mg/dl. Starting values and response in both groups were comparable. Results of the study Group
TC
TG
NonHDL-C
HDL-C
LDL-C
A (Colesevelam)
−12.40%*
−15.90%**
−14.40%*
−4.40%
−15.30%
B (add on to Ezetimibe)
−9.50%**
12.40%
−2.20%
−14.90%
−11.00%
*p < 0.05, **p < 0.01, ***p < 0.001.
Conclusion: Therapy with Colesevelam is effective and additive to Ezetimibe. Despite some non-responders (<5% LDL-C reduction) both groups achieved an up to 30% reduction of LDL-cholesterol, which is clinically relevant for patients with statin (± Ezetimibe) intolerance. 779 THE PROGNOSTIC SIGNIFICANCE OF THE FREQUENCY AND THE MORPHOLOGY OF PREMATURE VENTRICULAR CONTRACTIONS DURING AMBULATORY HOLTER MONITORING G. Ephrem1 , M. Levine2 , P. Friedmann3 , P. Schweitzer2 . 1 Department of Medicine, 2 Division of Cardiology, 3 Office of Grants and Research Administration, Beth Israel Medical Center, New York, NY, USA Background: Multiform ventricular premature beats (VPBs) are associated with an adverse prognosis in patients with structural heart disease. Very frequent VPBs are associated with ventricular dysfunction. Our hypothesis is that multiform VPBs confer an adverse prognosis in the general population.
163
Methods: We performed a retrospective cohort study of patients 18 years old referred to our institution for 24-hour Holter monitoring between July 1, 2008 and December 31, 2009. Holters with no VPBs or with non-sustained ventricular tachycardia were excluded. Clinical and adverse event (AE) data ("major adverse cardiovascular event" or new/worsening heart failure) were gathered from chart review. Data was analyzed by VPB frequency (rare, occasional, frequent) and morphology (uniform or multiform). Results: 222 patients (43% male, mean age 55±16 years) were evaluated (median follow-up 7 months (IQR 4−13)). Median frequency was 2 VPB/hr (IQR 1−13). Multiform VPBs were noted in 48%. Patients with multiform VPBs were older, and had a higher prevalence of CAD and CHF. During follow-up, 30 AE were noted. Patients with an AE were younger, had a higher prevalence of HTN, diabetes, CAD and CHF. The multiform group had a higher incidence of AE (23%) compared to the uniform group (5%) (p = 0.0006). Their 1-year event rate was also greater (25% versus 5%) (p = 0.0001). VPB frequency was associated with a higher incidence of AE in the multiform group only. In a Cox regression analysis, multiformity but not frequency predicted AE. Conclusion: Multiform VPBs are associated with AE.
780 ACCURACY AND PRECISION OF POINT-OF-CARE TESTING FOR SERUM CHOLESTEROL, TRIGLYCERIDES AND HDL CHOLESTEROL J.V. Patel1 , G. Thorpe2 , L. Springer3 , E.A. Hughes1 . 1 SMRU, Sandwell and West Birmingham Hospitals NHS Trust, 2 Wolfson Research Laboratories, University of Birmingham, Birmingham, UK , 3 Physician’s Laboratory Advantage Consulting, Glencoe, MN, USA Coronary heart disease (CHD) is the leading preventable cause of death in the UK, and a key strategy for primary prevention is the early detection and reversal of dyslipidaemia − a major correctable cause. The introduction of point-of-care testing (POCT) for serum lipids brings with it the potential to improve patient experiences. However, perceived advantages of better convenience, rapid assessment and consultation could be offset by inaccuracy and unreliability. We were interested to determine the accuracy and precision of total cholesterol (CHOL), triglyceride (TG) and high density lipoprotein cholesterol (HDLc) measures by a nurse on capillary blood using a commercially availible POCT device (Cardiochek, Indianapolis US), and evaluate its performance to discriminate risk categories associated with dyslipidaemia in 160 individuals visiting the outpatient department (Sandwell Hospital) as validated by results obtained from venous serum using a biochemistry analyser (Integra-400+, Roche Diagnostics). Results: Using the Integra-400+, min-max ranges for CHOL, TG and HDLc were 2.4–10.8 mmol/l, 0.6–8.99 mmol/l and 0.6–3.11 mmol/l. CHOL was nonsignificantly 1.4% higher using POCT; a mean bias of 0.07 (sd:0.48) mmol/l. Inaccuracy was greater for HDLc and TG, which were 0.15 (0.20) mmol/l higher (P < 0.001) and 0.08 (0.50) mol/l lower (P = 0.04) using POCT. On ROC analysis, POC testing discriminated the presence of CHOL >5 mmol/l, CHOL:HDLc ratio >6 and TG > 1.7 mmol/l with lower limits of 95% CI for AUC all exceeding 90%). Conclusion: These data for POCT of lipids suggest this approach is appropriate for CHD risk stratification, where the device provides reliable fractionated lipid information − consistent with a traditional clinical chemistry platform.
781 MORE AGGRESSIVE LDL-C AND NON-HDL-C TARGETS MUST BE ACHIEVED IN PATIENTS RECEIVING LIPID-LOWERING THERAPY TO NORMALIZE APOB-CONTAINING LIPOPROTEINS J. Betteridge1 , J.R. Guyton2 , M. Farnier3 , L.A. Leiter4 , J. Lin5 , A. Shah5 , A.O. Johnson-Levonas5 , P. Brudi5 . 1 Royal Free & University College London Medical School, London, UK , 2 Duke University Medical Center, North Carolina, Durham, NC, USA, 3 Point Medical, Dijon, France, 4 Keenan Research Centre in the Li Ka Shing Knowledge Institute of St. Michael’s Hospital, University of Toronto, Toronto, ON, Canada, 5 Merck, Whitehouse Station, NJ, USA Introduction: Statins modify correlations between apoB:LDL-C and nonHDL-C; it is not known if other lipid-lowering therapies have similar effects. Objective: This post-hoc, pooled analysis examined relationships between apoB:LDL-C and apoB:non-HDL-C from 27 randomized, double-blind, activeor placebo-controlled studies in 21794 hypercholesterolemic patients receiving EZE/statin or statin alone, administered as first- or second-line therapy, for 4−24wk. Methods: Simple linear regression analyses calculated LDL-C and non-HDL-C levels corresponding to apoB=90 mg/dL at baseline and endpoint. Results: At baseline in the first-line therapy group, apoB=90 mg/dL corresponded to minimum LDL-C and non-HDL-C goals for high-risk patients (i.e., 100 and 130 mg/dL, respectively). At baseline in the second-line therapy group and following treatment in both the first and second-line groups, apoB=90 mg/dL corresponded to more aggressive LDL-C and non-HDL-C goals (i.e., 70 and 100 mg/dL, respectively).