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P101 AORTIC STIFFNESS AS A RISK FACTOR FOR RECURRENT CARDIOVASCULAR EVENTS IN VERY HIGH RISK DIABETIC MEN
78th EAS Congress
Atherosclerosis Supplements 11, no. 2 (2010) 17–108
(TIMI) frame count and aggregation and deformability of erythrocytes were measured by Laser-assisted Optical Rotational Cell Analyser. Plasma viscosity was measured by a cone-plate viscometer. Erythrocyte aggregation was represented by aggregation half-time, aggregation amplitude, and aggregation index, whereas elongation index was used for expression of deformability. Results: Aggregation half-time, aggregation index, elongation index, and plasma viscosity were similar between two groups, however, significant difference was found in aggregation amplitude, which was in favour of an increased aggregability in SCF patients compared to controls (22.5±4.7au vs. 17.5±7.5au, respectively, p = 0.028). In the study group, correlation analysis revealed a significant relationship between the TIMI frame count for left anterior descending artery and aggregation amplitude (r = 0.307, p = 0.045). Conclusion: These findings suggest that erythrocyte aggregability, but not deformability or plasma viscosity may contribute to the pathophysiology of SCF presumably via adversely affecting blood flow in the coronary microcirculation. P98 INVOLVEMENT OF Na+ –Ca2+ EXCHANGER IN THE ENDOTHELIUM-INDEPENDENT VASORELAXATION INDUCED BY Curcuma longa L. IN RAT MESENTERIC ARTERY O. Adaramoye1 , I.A. Medeiros2 . 1 Biochemistry, University of Ibadan, Ibadan, Nigeria, 2 LTF, Universidade Federal da Para´ıba (UFPB), Joao Pessoa, Brazil Objective: Previous studies confirmed that the methanolic extract from Curcuma longa L. (CLME) lowers arterial blood pressure and heart rate in rats. In this study, we investigated the involvement of Na+ −Ca2+ exchanger (NCE) in the vasorelaxation by CLME in rat mesenteric arteries. Methods: Mesenteric arteries were obtained from rats and cut into rings. In some rings, the endothelium was removed by gently rubbing the surface with a moist finger. The rings were suspended in organ baths containing Tyrode’s solution (37ºC, 95% O2 + 5% CO2). Rings were stabilized with a resting tension of 0.75 g for 60 minutes, and different drugs were administered. Results: CLME (1–1000 mg/mL) concentration-dependently relaxed phenylephrine (PHE) (10 mM) pre-contracted rings with intact-or denuded-endothelium, suggesting that the removal of endothelium has no effect on vasorelaxation by CLME. CLME (30, 100 and 300 mg/mL) inhibited the cumulative concentrationresponse curves to PHE (10−8 −10−5 M) in a concentration-dependent manner. Treatment with ouabain 100 mM (selective blocker of Na±K+ ATPase) has no effect on the relaxant responses of CLME. However, treatment with nickel chloride (NiCl2) (100, 300 and 400 mM), a putative NCE inhibitor, concentrationdependently reduced the vasorelaxant responses of CLME. CLME (100 mg/mL) produced less relaxant effect with decreasing extracellular Na+ concentration. CLME-induced vasorelaxation was abolished in a Na+-free Tyrode’s solution, a condition that eliminates the influence of the forward mode of the exchanger. Conclusions: The results provide indirect evidence that the stimulation of the forward mode of NCE may contribute to the vasorelaxation by CLME. P99 BODY MASS INDEX IS A MAJOR DETERMINANT FOR NON-ALCOHOLIC STEATOHEPATITIS IN NON-DIABETIC HYPERTENSION PATIENTS C.-H. Chou1 , W.-C. Tsai2 . 1 Internal Medicine, Sinlau Christian Hospital, 2 Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan R.O.C. Purpose: Non-alcoholic steatohepatitis (NASH) was associated with cardiovascular risk. Metabolic syndrome was associated with NASH. However, factors for development of NASH were not well study in hypertension. Methods: We included 220 non-diabetic essential hypertension patient (mean age 41±8 years, 149 men) in this study. All patients did not have viral or alcoholic liver diseases. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and adiponectin were measured. NASH was defined as if ALT or AST >30 U/L in men or >19 U/L in women. Homeostasis model assessment (HOMA) index was used for degree of insulin resistance. Results: NASH was noted in 99 patients (45%). Patients with NASH had significantly higher glucose, triglyceride, cholesterol, body mass index (BMI), HOMA index, and lower adiponectin. Status of statin usage was not associated with NASH. After multivariate analysis controlling glucose, triglyceride, cholesterol, BMI, HOMA index, and adiponectin, only BMI was significantly associated with NASH (HR 1.179, 95% CI 1.059–1.313, p = 0.003), and cholesterol was borderline significantly associated with NASH (HR 1.010, 95% CI 1.000–1.019, p = 0.053). Conclusion: BMI is an independent factor associated with NASH in hypertension.
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P100 INCREASED LEVELS OF ADMA AS MEASURE OF ENDOTHELIAL DYSFUNCTION IN ELDERLY PATIENTS WITH ATRIAL FIBRILLATION I. Seljeflot1 , S. Ulimoen2 , S. Enger2 , H. Arnesen1 , A. Tveit2 . 1 Center for ˚ Clinical Heart Research, Dept of Cardiology, Oslo University Hospital, Ulleval, Oslo, 2 Medicine, Asker & Bærum Hospital, Sandvika, Norway Several independent risk factors for AF have been identified, however, the importance of endothelial dysfunction is still not clarified. The aim of the present study was to evaluate the levels of L-arginine, the substrate for nitric oxide (NO) and the asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO-synthase, as related to the presence of AF. Material and Methods: The study population consists of 75-year old subjects with permanent AF (n = 62) and control subjects in sinus rhythm (n = 124), matched for gender. Clinical data were obtained and fasting blood samples were prepared for measurement of L-arginine and ADMA, performed by an HPLCmethod. Group differences were compared by t-test and Chi-square was used for trend analysis through quartiles. Multiple regression models were performed for estimation of independency. Results: Means (SD) are given. Levels of ADMA were elevated in AF vs controls (0.69 (0.13) vs 0.62 (0.12) umol/L, p < 0.001) and the L-arginine/ADMA ratios were lower (114 (23) vs 124 (27), p = 0.015), still significant after adjustment for relevant covariates (creatinine, hypertension, body mass index, diabetes, ischemic heart disease, LDL-cholesterol) (p = 0.007 and p = 0.037, respectively). When dividing the ADMA levels into quartiles there was a significant trend for having AF with increasing levels of ADMA (p = 0.001) with a clear cut-off at the 25th percentile (< 0.54umol/L), giving an OR for having AF of 7.16 (95% CI 2.43–21.09) with higher levels. Conclusion: Elevated levels of ADMA are significantly predicting the presence of atrial fibrillation in the elderly, elucidating the importance of endothelial dysfunction in such patients. P101 AORTIC STIFFNESS AS A RISK FACTOR FOR RECURRENT CARDIOVASCULAR EVENTS IN VERY HIGH RISK DIABETIC MEN D. Levisianou1 , A. Melidonis1 , S. Foussas1 , E. Adamopoulou1 , E. Skopelitis2 , A. Destounis2 , T. Xenopoulou2 , I. Skoularigis3 , G. Koukoulis3 , F. Triposkiadis3 . 1 Tzanio General Hospital, Piraeus, 2 Agios Panteleimon General Hospital, Nikea, 3 University of Thessaly, Larissa, Greece Background and Aims: Aortic stiffness (AS) has been shown to correlate with the possibility of recurrence of coronary events in non-diabetic patients. Its predictive value for cardiovascular morbidity in diabetics with ischaemic heard disease isn’t established. The aim of this prospective study was to test the hypothesis that estimating AS could predict cardiovascular morbidity in diabetic patients. Materials and Methods: One hundred consecutive diabetic men with no history of cardiovascular disease, admitted to the coronary care unit, were evaluated for arterial stiffness by calculating carotid-femoral pulse wave velocity (PWV). Follow-up telephone interviews at 12 months after discharge assessed the primary endpoints: unstable angina, revascularization, myocardial infarction, stroke or death. Cox proportional hazard models were used to estimate causespecific hazards of the end-points. To facilitate analysis, PWV values were divided into two halves, upper and lower. Results: Overall 12 cardiovascular events and 2 deaths were recorded during follow-up period. Those in the upper compared to those in the lower half of PWV were older (68.22±7.18 vs. 58.96±10.36 years, p < 0.001), had a longer diabetes duration (13.6±10.43 vs. 6.71±5.95 years, p = 0.003), and more increased TC (178.26±52.50 vs. 216.66±56.7 mg/dl, p = 0.025). After adjustment for age, diabetes duration, TC, and smoking, PWV was independently associated with the risk for recurrent cardiovascular events (hazard ratio=2.408, 95% CI =1.313–6.88, p = 0.032). Conclusion: Increased AS was associated with increased one-year risk for recurrent cardiovascular event in diabetic men. We propose that AS could be routinely used for risk stratification in the management of diabetic men after the first coronary event. P102 GENETIC VARIATION AT THE CD36 LOCUS AND RISK OF CORONARY HEART DISEASE IN WOMEN AND MEN M.K. Jensen1 , K.J. Mukamal2 , C.J. Girman3 , C. Chen1 , A. Handberg4 , K.M. Rexrode5 , E.B. Rimm1 . 1 Harvard School of Public Health, 2 Beth Israel Deaconess Medical Center, Boston, MA, 3 Merck Research Labs, Noth Wales, PA, USA, 4 Aarhus University Hospital, Aarhus, Denmark, 5 Brigham and Women’s Hospital, Boston, MA, USA Introduction: CD36 is a scavenger receptor that is important for the differentiation of macrophages into foam cells. Genetic variation at this locus has been associated with lipids and risk of CAD, especially among men. Aim: We examined whether genetic variation at this locus was associated with risk of CHD in two prospective studies of women and men.
Atherosclerosis Supplements 11, no. 2 (2010) 17–108
(TIMI) frame count and aggregation and deformability of erythrocytes were measured by Laser-assisted Optical Rotational Cell Analyser. Plasma viscosity was measured by a cone-plate viscometer. Erythrocyte aggregation was represented by aggregation half-time, aggregation amplitude, and aggregation index, whereas elongation index was used for expression of deformability. Results: Aggregation half-time, aggregation index, elongation index, and plasma viscosity were similar between two groups, however, significant difference was found in aggregation amplitude, which was in favour of an increased aggregability in SCF patients compared to controls (22.5±4.7au vs. 17.5±7.5au, respectively, p = 0.028). In the study group, correlation analysis revealed a significant relationship between the TIMI frame count for left anterior descending artery and aggregation amplitude (r = 0.307, p = 0.045). Conclusion: These findings suggest that erythrocyte aggregability, but not deformability or plasma viscosity may contribute to the pathophysiology of SCF presumably via adversely affecting blood flow in the coronary microcirculation. P98 INVOLVEMENT OF Na+ –Ca2+ EXCHANGER IN THE ENDOTHELIUM-INDEPENDENT VASORELAXATION INDUCED BY Curcuma longa L. IN RAT MESENTERIC ARTERY O. Adaramoye1 , I.A. Medeiros2 . 1 Biochemistry, University of Ibadan, Ibadan, Nigeria, 2 LTF, Universidade Federal da Para´ıba (UFPB), Joao Pessoa, Brazil Objective: Previous studies confirmed that the methanolic extract from Curcuma longa L. (CLME) lowers arterial blood pressure and heart rate in rats. In this study, we investigated the involvement of Na+ −Ca2+ exchanger (NCE) in the vasorelaxation by CLME in rat mesenteric arteries. Methods: Mesenteric arteries were obtained from rats and cut into rings. In some rings, the endothelium was removed by gently rubbing the surface with a moist finger. The rings were suspended in organ baths containing Tyrode’s solution (37ºC, 95% O2 + 5% CO2). Rings were stabilized with a resting tension of 0.75 g for 60 minutes, and different drugs were administered. Results: CLME (1–1000 mg/mL) concentration-dependently relaxed phenylephrine (PHE) (10 mM) pre-contracted rings with intact-or denuded-endothelium, suggesting that the removal of endothelium has no effect on vasorelaxation by CLME. CLME (30, 100 and 300 mg/mL) inhibited the cumulative concentrationresponse curves to PHE (10−8 −10−5 M) in a concentration-dependent manner. Treatment with ouabain 100 mM (selective blocker of Na±K+ ATPase) has no effect on the relaxant responses of CLME. However, treatment with nickel chloride (NiCl2) (100, 300 and 400 mM), a putative NCE inhibitor, concentrationdependently reduced the vasorelaxant responses of CLME. CLME (100 mg/mL) produced less relaxant effect with decreasing extracellular Na+ concentration. CLME-induced vasorelaxation was abolished in a Na+-free Tyrode’s solution, a condition that eliminates the influence of the forward mode of the exchanger. Conclusions: The results provide indirect evidence that the stimulation of the forward mode of NCE may contribute to the vasorelaxation by CLME. P99 BODY MASS INDEX IS A MAJOR DETERMINANT FOR NON-ALCOHOLIC STEATOHEPATITIS IN NON-DIABETIC HYPERTENSION PATIENTS C.-H. Chou1 , W.-C. Tsai2 . 1 Internal Medicine, Sinlau Christian Hospital, 2 Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan R.O.C. Purpose: Non-alcoholic steatohepatitis (NASH) was associated with cardiovascular risk. Metabolic syndrome was associated with NASH. However, factors for development of NASH were not well study in hypertension. Methods: We included 220 non-diabetic essential hypertension patient (mean age 41±8 years, 149 men) in this study. All patients did not have viral or alcoholic liver diseases. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and adiponectin were measured. NASH was defined as if ALT or AST >30 U/L in men or >19 U/L in women. Homeostasis model assessment (HOMA) index was used for degree of insulin resistance. Results: NASH was noted in 99 patients (45%). Patients with NASH had significantly higher glucose, triglyceride, cholesterol, body mass index (BMI), HOMA index, and lower adiponectin. Status of statin usage was not associated with NASH. After multivariate analysis controlling glucose, triglyceride, cholesterol, BMI, HOMA index, and adiponectin, only BMI was significantly associated with NASH (HR 1.179, 95% CI 1.059–1.313, p = 0.003), and cholesterol was borderline significantly associated with NASH (HR 1.010, 95% CI 1.000–1.019, p = 0.053). Conclusion: BMI is an independent factor associated with NASH in hypertension.
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P100 INCREASED LEVELS OF ADMA AS MEASURE OF ENDOTHELIAL DYSFUNCTION IN ELDERLY PATIENTS WITH ATRIAL FIBRILLATION I. Seljeflot1 , S. Ulimoen2 , S. Enger2 , H. Arnesen1 , A. Tveit2 . 1 Center for ˚ Clinical Heart Research, Dept of Cardiology, Oslo University Hospital, Ulleval, Oslo, 2 Medicine, Asker & Bærum Hospital, Sandvika, Norway Several independent risk factors for AF have been identified, however, the importance of endothelial dysfunction is still not clarified. The aim of the present study was to evaluate the levels of L-arginine, the substrate for nitric oxide (NO) and the asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO-synthase, as related to the presence of AF. Material and Methods: The study population consists of 75-year old subjects with permanent AF (n = 62) and control subjects in sinus rhythm (n = 124), matched for gender. Clinical data were obtained and fasting blood samples were prepared for measurement of L-arginine and ADMA, performed by an HPLCmethod. Group differences were compared by t-test and Chi-square was used for trend analysis through quartiles. Multiple regression models were performed for estimation of independency. Results: Means (SD) are given. Levels of ADMA were elevated in AF vs controls (0.69 (0.13) vs 0.62 (0.12) umol/L, p < 0.001) and the L-arginine/ADMA ratios were lower (114 (23) vs 124 (27), p = 0.015), still significant after adjustment for relevant covariates (creatinine, hypertension, body mass index, diabetes, ischemic heart disease, LDL-cholesterol) (p = 0.007 and p = 0.037, respectively). When dividing the ADMA levels into quartiles there was a significant trend for having AF with increasing levels of ADMA (p = 0.001) with a clear cut-off at the 25th percentile (< 0.54umol/L), giving an OR for having AF of 7.16 (95% CI 2.43–21.09) with higher levels. Conclusion: Elevated levels of ADMA are significantly predicting the presence of atrial fibrillation in the elderly, elucidating the importance of endothelial dysfunction in such patients. P101 AORTIC STIFFNESS AS A RISK FACTOR FOR RECURRENT CARDIOVASCULAR EVENTS IN VERY HIGH RISK DIABETIC MEN D. Levisianou1 , A. Melidonis1 , S. Foussas1 , E. Adamopoulou1 , E. Skopelitis2 , A. Destounis2 , T. Xenopoulou2 , I. Skoularigis3 , G. Koukoulis3 , F. Triposkiadis3 . 1 Tzanio General Hospital, Piraeus, 2 Agios Panteleimon General Hospital, Nikea, 3 University of Thessaly, Larissa, Greece Background and Aims: Aortic stiffness (AS) has been shown to correlate with the possibility of recurrence of coronary events in non-diabetic patients. Its predictive value for cardiovascular morbidity in diabetics with ischaemic heard disease isn’t established. The aim of this prospective study was to test the hypothesis that estimating AS could predict cardiovascular morbidity in diabetic patients. Materials and Methods: One hundred consecutive diabetic men with no history of cardiovascular disease, admitted to the coronary care unit, were evaluated for arterial stiffness by calculating carotid-femoral pulse wave velocity (PWV). Follow-up telephone interviews at 12 months after discharge assessed the primary endpoints: unstable angina, revascularization, myocardial infarction, stroke or death. Cox proportional hazard models were used to estimate causespecific hazards of the end-points. To facilitate analysis, PWV values were divided into two halves, upper and lower. Results: Overall 12 cardiovascular events and 2 deaths were recorded during follow-up period. Those in the upper compared to those in the lower half of PWV were older (68.22±7.18 vs. 58.96±10.36 years, p < 0.001), had a longer diabetes duration (13.6±10.43 vs. 6.71±5.95 years, p = 0.003), and more increased TC (178.26±52.50 vs. 216.66±56.7 mg/dl, p = 0.025). After adjustment for age, diabetes duration, TC, and smoking, PWV was independently associated with the risk for recurrent cardiovascular events (hazard ratio=2.408, 95% CI =1.313–6.88, p = 0.032). Conclusion: Increased AS was associated with increased one-year risk for recurrent cardiovascular event in diabetic men. We propose that AS could be routinely used for risk stratification in the management of diabetic men after the first coronary event. P102 GENETIC VARIATION AT THE CD36 LOCUS AND RISK OF CORONARY HEART DISEASE IN WOMEN AND MEN M.K. Jensen1 , K.J. Mukamal2 , C.J. Girman3 , C. Chen1 , A. Handberg4 , K.M. Rexrode5 , E.B. Rimm1 . 1 Harvard School of Public Health, 2 Beth Israel Deaconess Medical Center, Boston, MA, 3 Merck Research Labs, Noth Wales, PA, USA, 4 Aarhus University Hospital, Aarhus, Denmark, 5 Brigham and Women’s Hospital, Boston, MA, USA Introduction: CD36 is a scavenger receptor that is important for the differentiation of macrophages into foam cells. Genetic variation at this locus has been associated with lipids and risk of CAD, especially among men. Aim: We examined whether genetic variation at this locus was associated with risk of CHD in two prospective studies of women and men.