- Email: [email protected]
S21-3 GINKGO BILOBA EXTRACT UPREGULATES ENDOTHELIAL NITRIC OXIDE SYNTHASE AND HEME OXYGENASE-1 EXPRESSION IN HIGH GLUCOSE-STIMULATED HUMAN AORTIC ENDOTHELIAL CELLS
Abstract of the 16th Asian Pacific Congress of Cardiology, Taipei, Taiwan, 13–16 December, 2007 recipients especially those with lower BMI. Our results may give a new insight into VGC usage against CMV infection.
S20-7 ONE STAGE OPERATION OF TOTAL ARCH REPAIR WITH STENT GRAFT IMPLANTATION AT REVERSE SLEEVE GRAFT FOR RESIDUAL TYPE A DISSECTING AORTIC ANEURYSM
I-Ming Chen, Hsiao-Huang Chang, Chiao-Po Hsu, Shiau-Ting Lai, Chun-Che Shih. Division of Cardiovascular Surgery, Department of surgery, Taipei Veterans General Hospital, Taipei, Taiwan Residual type A dissecting aortic aneurysm may develop in patients who had underwent ascending aorta repair because of acute type A aortic dissection. This kind of dissecting aneurysm remained challenging for surgeons not only due to extensive aneurysm formation but also high risk of redo sternotomy and prolonged operation time. We entered mediastinal cavity via redo sternotomy. The operation was accomplished under cardiopulmonary bypass and short period of circulatory arrest with modified trifurcated graft, elephant trunk procedure with reverse sleeve graft and stent graft implantation at reverse sleeve graft simultaneously. We successfully performed this operation in one stage for 3 patients with residual type A dissecting aortic aneurysm in recent 2 months.
SYMPOSIUM 21
GENERAL S21-1 STATINS IN INTERMITTENT CLAUDICATION: A META-ANALYSIS
Arnold S. De Guzman, Ma. Paz Mildred F. Luque. Heart Institute, St. Luke’s Medical Center, Philippines Background: Intermittent claudication is always been bothersome to patients with peripheral arterial disease. These patients suffer lower limb pain limiting their activity and independence. The benefit of statins among claudicants still remains unclear. The objective of this meta-analysis is to determine the efficacy of statin treatment among patients with intermittent claudication. Methods: Clinical trials were identified from Medline search, PUBMED, and Cochrane collaboration databases 1999 to 2006 using the following keywords: statins, claudication, peripheral arterial disease, peripheral vascular disease, randomized controlled trials and MESH terms Hydroxymethylglutaryl-Coa Reductase Inhibitors, peripheral vascular disease, and intermittent claudication. A total of 12 articles were queried, 8 of which are RCTs and were subjected to data extraction and quality scale. Independent quality assessment scale and the inclusion criteria were strictly applied. A total of 3 trials were included in the study. All included studies were randomized controlled trials involving a total of 380 PAD patients with intermittent claudication (Fontaine class II) and an Ankle-Brachial index of less than 0.90. Patients with previous surgery/angioplasty for PAOD, any condition that limits their ability to perform exercise test like previous MI patients/CABG within 6 months, unstable angina, neurologic disease, arthritis, uncontrolled hypertension, DVT before 3 months of randomization. Patients who had previously been treated with statins or other cholesterol lowering drugs were also excluded. Main results: The analysis of the mean walking distance showed a significant improvement from baseline as compared with the placebo at 95% CI (2.31, df – 1) P:<0.00001. The analysis in terms of pain-free walking distance also showed a significant improvement in the pain-free walking distance from baseline as compared with the placebo at 95% CI (0.04, df – 2) P<0.00001. Conclusions: Statins are beneficial among claudicant patients with significant improvement of mean walking distance and increase in pain-free walking distance with treatment duration of 6 to 12 months. Reviever’s Conclusion: Indeed, among PAD patients, the use of statins in intermittent claudication significantly improves the pain and experience comfort thus promoting independence and quality of life.
41
S21-2 MEASUREMENT OF CORONARY SINUS BLOOD FLOW AFTER FIRST ANTERIOR MYOCARDIAL INFARCTION WITH TRANSTHORACIC ECHOCARDIOGRAPHY AND ITS ASSOCIATION WITH WALL MOTION SCORING INDEX
M. Toufan, J. Samadikhah, A. Alizadeh Asl, R. Azarfarin, A.R. Yaghoobi. Shaheed Madani Heart Center, Iran Background: Coronary sinus blood flow (CSBF) and coronary sinus velocity time integral (CSVTI) are appropriate criteria for efficacy of myocardial perfusion. But standard methods for its measurement are invasive. The aim of this study was measuring of CSBF and CSVTI via transthoracic echocardiography (TTE) in patients (pts) with acute myocardial infarction (AMI) in association with left ventricular ejection fraction (LVEF), wall motion scoring index (WMSI) and in-hospital mortality. Material and Methods: In this cohort study 20 pts with anterior AMI and 20 healthy individuals as controls, studied in 6 months period (in 2005) in Madani heart center in Tabriz(Iran). All of pts received same drugs for AMI treatment (e.g. fibrinolytic). CSBF, CSVTI, WMSI and tissue Doppler imaging (TDI) data were obtained via TTE and Compared between the 2 groups. Results: Baseline variables were similar between 2 groups (p>0.05). CSBF in AMI group was 287.8±128 ml/min and in control group was 415±127 ml/min (p=0.001).Also CSVTI was significantly lower in AMI group than control group (11.16±2.85 and 17.56±2.72 mm, respectively; p=0.003). There was significant correlation between CSBF and LVEF (r=0.52, p=0.01), WMSI (r=−0.77, p=0.0001) and in-hospital mortality (r=0.58 p=0.03), also between CSVTI and LVEF (r=0.85, p=0.0001), WMSI (r=−0.57, p=0.0009) and in hospital-mortality rate (r=0.69, p=0.02). CSBF and CSVTI had good correlation with TDI findings: Em (peak early diastolic velocity in the myocardium) and Sm (peak systolic velocity in the myocardium). Conclusion: Our study demonstrated good correlation between measured CSBF and CSVTI by 2D, Doppler TTE and LVEF, WMSI, in-hospital mortality and also TDI findings; Also we found that CSBF and CSVTI were independent predictors in AMI pts. Keywords: Myocardial infarction, Transthoracic echocardiography, Coronary sinus, Wall motion scoring index, Tissue doppler imaging.
S21-3 GINKGO BILOBA EXTRACT UPREGULATES ENDOTHELIAL NITRIC OXIDE SYNTHASE AND HEME OXYGENASE-1 EXPRESSION IN HIGH GLUCOSE-STIMULATED HUMAN AORTIC ENDOTHELIAL CELLS
Hsiao-Ya Tsai 1,3 , Yung-Hsiang Chen 4 , Feng-Yen Lin 6 , Jia-Hsiung Chen 2,3 , Shin-Jong Lin 1,3 , Jaw-Wen Chen 2,3 . 1 Institute of Clinical Medicine, 2 Institute and department of Pharmacology and 3 Cardiovascular Research Center, National Yang-Ming University; the 4 Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital; 5 Graduate Institute of Integrated Medicine, 6 China Medicine University, Graduate Institute of Medical Sciences, Taipei Medical University, Taipei, Taiwan, ROC. High glucose is suggested as one of major risk factors for cardiovascular diseases, which may impair vascular cells by increasing intracellular oxidative stress. Heme oxygenase-1 (HO-1) is a cytoprotective enzyme with anti-inflammatory and antioxidative properties. Ginkgo biloba extract (GBE), a Chinese herbal medicine with anti-oxidative and anti-inflammatory properties, could inhibit cytokineinduced endothelial adhesiveness to monocytes/mononuclear cells (MNCs), a pivotal sign of atherogenesis. Whether GBE may exert its endothelial protection by modify HO-1 expression under high glucose stimulation was not known. This study was aimed to explore the direct protective effects of GBE on high glucose-stimulated human aortic endothelial cells (HAECs). It was shown that GBE (100 µg/ml for 18 hours) could significantly attenuate high glucose (25mM for 4 days)-induced endothelial cell death, reactive oxygen species production, expression of intercellular adhesion molecule (ICAM)-1 and the adhesiveness of to monocytes/MNCs. Attenuation of endothelial nitric oxide synthase (eNOS) expression by high glucose could also be reversed by GBE treatment. Sn-protoporphyrinIX (SnPPIX), an inhibitor of HO-1, could block most of the above effects of GBE except ICAM-1expression, suggesting that GBE could, largely by upregulating HO-1expression, reverse high glucose-induced
42
Abstracts of the 16th Asian Pacific Congress of Cardiology, Taipei, Taiwan, 13-16 December, 2007
endothelial dysfunction. Other experiments showed that the mechanisms might also involve anti-oxidant activity and JNK pathways. Accordingly, GBE could protect endothelial cells from high glucose-induced injury by enhancing eNOS and activating HO-1 expression, suggesting the possibility of a novel strategy for vascular protection in chronic hyperglycemia such as that in patients with poorly controlled diabetes mellitus. Further in vivo and clinical studies should be done to verify these issues.
homocysteine levels probably due to antiproliferative activity or it might be due to antioxidant or vasodilator activity. Keywords: H2 S [Hydrogensulfide], homocysteine, atherosclerosis, NaHS, left carotid artery, atherogenic diet, injury, carotid artery lesion index.
S21-6 PROGRESSION OF ATHEROSCLEROSIS – ROLE OF ENDOTOXIN
S21-4 SCREENING FOR SUBCLINICAL CORONARY ATHEROSCLEROSIS IN UNCOMPLICATED TYPE 2 DIABETES
Meng-Huan Lei, Yu-Cheng Hsu, Chao-Chin Chen, Sheng-Liang Chung. Lo-Tung Poh-Ai Hospital, I-Lan, Taiwan Background: Cardiovascular disease is the cause of death in 65-75% of diabetic patients. Generally, diabetic patients have more extensive atherosclerosis with a higher prevalence of multi-vessel coronary artery disease (CAD), frequent silent myocardial ischemia and infarction with a poorer prognosis as compared with non-diabetic counterparts.Early detection of coronary artery disease may helprefine the management of asymptomatic diabetic patients. The aim of this study was to determine the prevalence and clinical predictors of subclinical coronary atherosclerosis measured by multi-detector computerized tomography (MDCT) in uncomplicated type2 diabetes (T2DM). Methods: This study recruited 1866 T2DM patients (age between 40 to 80 years old mean 65.0±9.3,48.4% male) without prior cardiovascular disease from ILan Diabetes Care Network over a 9-month period. The duration of diabetes and HbA1c were 6.7±5.9 years, 7.9±1.9% respectively. Aspirin was prescribed in 32.3% of patients. Established risk factors (smoking, hypertension, hypercholesterolemia, family history of premature CAD, macro/microalbuminuria) and coronary artery calcium (CAC) scores were determined. Results: The extents of CAC were variable in this diabetic cohorts, 89.2% patients with one or more risk factor:no calcification in 23.1% , minimal (≤10AU) in 14.9%, mild (11-100AU) in 25.9%, moderate (101-400AU) in 20.3%, severe (4011000AU) in 9.3%, and extensive (≤1000AU) in 6.5%. In multivariable logistic regression model, the predictors of CAC include age, male gender, hypertension, duration of diabetes and hypercholesterolemia. There was no difference in the severity of CAC in patients with 2 or less risk factors. Only clustering of 3 or more risk factors predicts higher degree of CAC (odds ratio 1.64, 2.38: p value 0.028,0.008 respectively). Conclusions: Significant subclinical coronary atherosclerosis is common in uncomplicated T2DM as measured by MDCT, which was not fairly predicted by the number of established risk factors. Risk stratification and short-term outcome in this CAD risk-equivalent T2DM population will be prospectively evaluated according to CAC scores.
S21-5 TO STUDY THE ROLE OF H2 S IN THE INITIAL STAGE OF ATHEROSCLEROSIS
Sarita G. Barsainya, Gaurang B. Shah. Dept. of Pharmacology, K.B. Institute of Pharmaceutical Education and Research, Gandhinagar, INDIA Background: H2 S [Hydrogensulfide] was recently suggested to be a possible endogenous gasotransmitter in physiological concentration produced from homocysteine. For the purpose of understanding its possible role in pathogenesis of atherosclerosis, we explored the effect of H2 S on carotid artery injured rats. Objective: To study the role of H2 S in the initial stage of atherosclerosis in rats. Materials and Methods: Rats fed on atherogenic diet for 1 week underwent left carotid artery injury induced by thin metallic wire. Atherogenic diet was continued and on the next day of injury, treatment of NaHS [H2S donor] was given for another 3 weeks. Total 4 weeks later, blood was collected and carotid artery was removed for various observations. Results: Carotid artery lesion index was significantly less in H2 S treated group [0.13±0.09] when compared with control group [3.94±0.89] P value < 0.05 Mean serum homocysteine levels were significantly higher in H2 S treated group [7.85±0.19 µmol/L] when compared with control group [5.45±0.065 µmol/L] P value<0.005 Conclusion: H2 S is directly acting as a antiatherosclerotic in the presence of high
N.A. Bylova, G.P. Arutyunov, L.I. Kafarskaya, T.K. Chrenyavskaya. Russian State Medical University, Russian Federation Background and aim: One of possible causes of development of atherosclerosis is a high level of proinflammatory cytokines. High level of endotoxin may leads to increase of systemic inflammation. The goal of the trial was to evaluate the effect of different concentration of endotoxin on development of atherosclerosis (carotid intima-media thickness (CIMT). Methods: study was approved by local ethical committee of Russian State medical University. 300 asymptomatic patients with moderately elevated cholesterol and low risk of cardiovascular disease were enrolled in the study (LDL 120-190 mg/dl, HDL-C ≤60 mg/dl; triglicerides < 500 mg/dl) and evidence of thickening of the walls of the extracranial carotid arteries, as measured by B-mode ultrasound (at baseline and at 24 month). Exclusion criteria were infectious diseases. In all patients we also measured a level of endotoxin in plasma (LAL-test). Results: at baseline we find patients with endotoxin level 0,25±0,03 UE/l (first group, n=110) and 0,41±0,05 UE/l (second group, n=100). Mean CIMT in first group was 1.16±0.05 mm and in second group 1.163±0.07 mm. Average LDL levels were 150±4 mg/dl and 151±2 mg/dl, respectively. After 24 months of follow up no significant changes were find in cholesterol levels. Mean CIMT in first group had no changes 1.16±0.09 mm, but in second group increased significantly – 1.65±0.04 mm (p=0.002). Conclusion: among asymptomatic patients at low risk for cardiovascular disease high levels of endotoxin in plasma was associated with an increase in CIMT.
S21-7 IDENTIFICATION OF POTENTIALLY ATHEROGENIC ELECTRONEGATIVE LDL IN PATIENTS WITH CORONARY ARTERY DISEASE OR CAD RISK FACTORS
Po-Yuan Chang 1 , Yi-Jie Chen 1 , Shao-Chun Lu 1 , Jen-Kuang Lee 1 , Chao-Yuh Yang 2 , Chu-Huang Chen 2 , Yuan-Teh Lee 1 , Ming-Fong Chen 1 . 1 National Taiwan University Medical Center, Taipei, Taiwan, and 2 Baylor College of Medicine, Houston, Texas, USA Background: L5, a highly electronegative LDL originally isolated from hypercholesterolemic human plasma, exhibits a spectrum of atherogenic effects on cultured vascular cells. To evaluate its clinical implication, we assess its prevalence in patients with coronary artery disease (CAD) or CAD risk factors in comparison with subjects without these risk factors. Methods and Results: Fasting blood samples were collected from adult patients with angiographically evidenced CAD (stenosis> =50%; n=10), asymptomatic hypercholesterolemia (LDL cholesterol> =160 mg/dL; n=10), type 2 diabetes mellitus (HbA1c> =8.0; n=10), history of chronic smoking (n=10), and healthy subjects without these risk factors (n=10). In consistence with our previous findings, plasma LDL was divided by ion-exchange chromatography into 5 subfractions, L1–L5, with increasing electronegativity, in all hypercholesterolemic samples (n=10/10; L5/LDL=0.8-4.0%). Irrespective of the plasma cholesterol concentrations, L5 was also found in all diabetic (n=10/10; L5/LDL=1.0-5.3%) and most CAD patients (n=7/10; L5/LDL=0.6-2.8%) and chronic smokers (n=3/5; L5/LDL=0.7-2.1%). In contrast, ion-exchange chromatography failed to yield L5 in any of the healthy subjects without CAD risk factors. Regardless of their origins, all L5 specimens were able to induce human arterial endothelial cell (EC) apoptosis and inhibit EC proliferation by inhibiting fibroblast growth factor-2 expression. L1-L4 had no effects. Conclusions: EC apoptosis contributes to both atherosclerosis and thrombosis. Thus, L5’s prevalence in patients with CAD or CAD risk factors but not in riskfree healthy subjects implicates a clinical correlation. Large-scale epidemiologic survey and prospective investigations are warranted to confirm L5’s atherogenic role and hence identifying it as a novel therapeutic target.
S20-7 ONE STAGE OPERATION OF TOTAL ARCH REPAIR WITH STENT GRAFT IMPLANTATION AT REVERSE SLEEVE GRAFT FOR RESIDUAL TYPE A DISSECTING AORTIC ANEURYSM
I-Ming Chen, Hsiao-Huang Chang, Chiao-Po Hsu, Shiau-Ting Lai, Chun-Che Shih. Division of Cardiovascular Surgery, Department of surgery, Taipei Veterans General Hospital, Taipei, Taiwan Residual type A dissecting aortic aneurysm may develop in patients who had underwent ascending aorta repair because of acute type A aortic dissection. This kind of dissecting aneurysm remained challenging for surgeons not only due to extensive aneurysm formation but also high risk of redo sternotomy and prolonged operation time. We entered mediastinal cavity via redo sternotomy. The operation was accomplished under cardiopulmonary bypass and short period of circulatory arrest with modified trifurcated graft, elephant trunk procedure with reverse sleeve graft and stent graft implantation at reverse sleeve graft simultaneously. We successfully performed this operation in one stage for 3 patients with residual type A dissecting aortic aneurysm in recent 2 months.
SYMPOSIUM 21
GENERAL S21-1 STATINS IN INTERMITTENT CLAUDICATION: A META-ANALYSIS
Arnold S. De Guzman, Ma. Paz Mildred F. Luque. Heart Institute, St. Luke’s Medical Center, Philippines Background: Intermittent claudication is always been bothersome to patients with peripheral arterial disease. These patients suffer lower limb pain limiting their activity and independence. The benefit of statins among claudicants still remains unclear. The objective of this meta-analysis is to determine the efficacy of statin treatment among patients with intermittent claudication. Methods: Clinical trials were identified from Medline search, PUBMED, and Cochrane collaboration databases 1999 to 2006 using the following keywords: statins, claudication, peripheral arterial disease, peripheral vascular disease, randomized controlled trials and MESH terms Hydroxymethylglutaryl-Coa Reductase Inhibitors, peripheral vascular disease, and intermittent claudication. A total of 12 articles were queried, 8 of which are RCTs and were subjected to data extraction and quality scale. Independent quality assessment scale and the inclusion criteria were strictly applied. A total of 3 trials were included in the study. All included studies were randomized controlled trials involving a total of 380 PAD patients with intermittent claudication (Fontaine class II) and an Ankle-Brachial index of less than 0.90. Patients with previous surgery/angioplasty for PAOD, any condition that limits their ability to perform exercise test like previous MI patients/CABG within 6 months, unstable angina, neurologic disease, arthritis, uncontrolled hypertension, DVT before 3 months of randomization. Patients who had previously been treated with statins or other cholesterol lowering drugs were also excluded. Main results: The analysis of the mean walking distance showed a significant improvement from baseline as compared with the placebo at 95% CI (2.31, df – 1) P:<0.00001. The analysis in terms of pain-free walking distance also showed a significant improvement in the pain-free walking distance from baseline as compared with the placebo at 95% CI (0.04, df – 2) P<0.00001. Conclusions: Statins are beneficial among claudicant patients with significant improvement of mean walking distance and increase in pain-free walking distance with treatment duration of 6 to 12 months. Reviever’s Conclusion: Indeed, among PAD patients, the use of statins in intermittent claudication significantly improves the pain and experience comfort thus promoting independence and quality of life.
41
S21-2 MEASUREMENT OF CORONARY SINUS BLOOD FLOW AFTER FIRST ANTERIOR MYOCARDIAL INFARCTION WITH TRANSTHORACIC ECHOCARDIOGRAPHY AND ITS ASSOCIATION WITH WALL MOTION SCORING INDEX
M. Toufan, J. Samadikhah, A. Alizadeh Asl, R. Azarfarin, A.R. Yaghoobi. Shaheed Madani Heart Center, Iran Background: Coronary sinus blood flow (CSBF) and coronary sinus velocity time integral (CSVTI) are appropriate criteria for efficacy of myocardial perfusion. But standard methods for its measurement are invasive. The aim of this study was measuring of CSBF and CSVTI via transthoracic echocardiography (TTE) in patients (pts) with acute myocardial infarction (AMI) in association with left ventricular ejection fraction (LVEF), wall motion scoring index (WMSI) and in-hospital mortality. Material and Methods: In this cohort study 20 pts with anterior AMI and 20 healthy individuals as controls, studied in 6 months period (in 2005) in Madani heart center in Tabriz(Iran). All of pts received same drugs for AMI treatment (e.g. fibrinolytic). CSBF, CSVTI, WMSI and tissue Doppler imaging (TDI) data were obtained via TTE and Compared between the 2 groups. Results: Baseline variables were similar between 2 groups (p>0.05). CSBF in AMI group was 287.8±128 ml/min and in control group was 415±127 ml/min (p=0.001).Also CSVTI was significantly lower in AMI group than control group (11.16±2.85 and 17.56±2.72 mm, respectively; p=0.003). There was significant correlation between CSBF and LVEF (r=0.52, p=0.01), WMSI (r=−0.77, p=0.0001) and in-hospital mortality (r=0.58 p=0.03), also between CSVTI and LVEF (r=0.85, p=0.0001), WMSI (r=−0.57, p=0.0009) and in hospital-mortality rate (r=0.69, p=0.02). CSBF and CSVTI had good correlation with TDI findings: Em (peak early diastolic velocity in the myocardium) and Sm (peak systolic velocity in the myocardium). Conclusion: Our study demonstrated good correlation between measured CSBF and CSVTI by 2D, Doppler TTE and LVEF, WMSI, in-hospital mortality and also TDI findings; Also we found that CSBF and CSVTI were independent predictors in AMI pts. Keywords: Myocardial infarction, Transthoracic echocardiography, Coronary sinus, Wall motion scoring index, Tissue doppler imaging.
S21-3 GINKGO BILOBA EXTRACT UPREGULATES ENDOTHELIAL NITRIC OXIDE SYNTHASE AND HEME OXYGENASE-1 EXPRESSION IN HIGH GLUCOSE-STIMULATED HUMAN AORTIC ENDOTHELIAL CELLS
Hsiao-Ya Tsai 1,3 , Yung-Hsiang Chen 4 , Feng-Yen Lin 6 , Jia-Hsiung Chen 2,3 , Shin-Jong Lin 1,3 , Jaw-Wen Chen 2,3 . 1 Institute of Clinical Medicine, 2 Institute and department of Pharmacology and 3 Cardiovascular Research Center, National Yang-Ming University; the 4 Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital; 5 Graduate Institute of Integrated Medicine, 6 China Medicine University, Graduate Institute of Medical Sciences, Taipei Medical University, Taipei, Taiwan, ROC. High glucose is suggested as one of major risk factors for cardiovascular diseases, which may impair vascular cells by increasing intracellular oxidative stress. Heme oxygenase-1 (HO-1) is a cytoprotective enzyme with anti-inflammatory and antioxidative properties. Ginkgo biloba extract (GBE), a Chinese herbal medicine with anti-oxidative and anti-inflammatory properties, could inhibit cytokineinduced endothelial adhesiveness to monocytes/mononuclear cells (MNCs), a pivotal sign of atherogenesis. Whether GBE may exert its endothelial protection by modify HO-1 expression under high glucose stimulation was not known. This study was aimed to explore the direct protective effects of GBE on high glucose-stimulated human aortic endothelial cells (HAECs). It was shown that GBE (100 µg/ml for 18 hours) could significantly attenuate high glucose (25mM for 4 days)-induced endothelial cell death, reactive oxygen species production, expression of intercellular adhesion molecule (ICAM)-1 and the adhesiveness of to monocytes/MNCs. Attenuation of endothelial nitric oxide synthase (eNOS) expression by high glucose could also be reversed by GBE treatment. Sn-protoporphyrinIX (SnPPIX), an inhibitor of HO-1, could block most of the above effects of GBE except ICAM-1expression, suggesting that GBE could, largely by upregulating HO-1expression, reverse high glucose-induced
42
Abstracts of the 16th Asian Pacific Congress of Cardiology, Taipei, Taiwan, 13-16 December, 2007
endothelial dysfunction. Other experiments showed that the mechanisms might also involve anti-oxidant activity and JNK pathways. Accordingly, GBE could protect endothelial cells from high glucose-induced injury by enhancing eNOS and activating HO-1 expression, suggesting the possibility of a novel strategy for vascular protection in chronic hyperglycemia such as that in patients with poorly controlled diabetes mellitus. Further in vivo and clinical studies should be done to verify these issues.
homocysteine levels probably due to antiproliferative activity or it might be due to antioxidant or vasodilator activity. Keywords: H2 S [Hydrogensulfide], homocysteine, atherosclerosis, NaHS, left carotid artery, atherogenic diet, injury, carotid artery lesion index.
S21-6 PROGRESSION OF ATHEROSCLEROSIS – ROLE OF ENDOTOXIN
S21-4 SCREENING FOR SUBCLINICAL CORONARY ATHEROSCLEROSIS IN UNCOMPLICATED TYPE 2 DIABETES
Meng-Huan Lei, Yu-Cheng Hsu, Chao-Chin Chen, Sheng-Liang Chung. Lo-Tung Poh-Ai Hospital, I-Lan, Taiwan Background: Cardiovascular disease is the cause of death in 65-75% of diabetic patients. Generally, diabetic patients have more extensive atherosclerosis with a higher prevalence of multi-vessel coronary artery disease (CAD), frequent silent myocardial ischemia and infarction with a poorer prognosis as compared with non-diabetic counterparts.Early detection of coronary artery disease may helprefine the management of asymptomatic diabetic patients. The aim of this study was to determine the prevalence and clinical predictors of subclinical coronary atherosclerosis measured by multi-detector computerized tomography (MDCT) in uncomplicated type2 diabetes (T2DM). Methods: This study recruited 1866 T2DM patients (age between 40 to 80 years old mean 65.0±9.3,48.4% male) without prior cardiovascular disease from ILan Diabetes Care Network over a 9-month period. The duration of diabetes and HbA1c were 6.7±5.9 years, 7.9±1.9% respectively. Aspirin was prescribed in 32.3% of patients. Established risk factors (smoking, hypertension, hypercholesterolemia, family history of premature CAD, macro/microalbuminuria) and coronary artery calcium (CAC) scores were determined. Results: The extents of CAC were variable in this diabetic cohorts, 89.2% patients with one or more risk factor:no calcification in 23.1% , minimal (≤10AU) in 14.9%, mild (11-100AU) in 25.9%, moderate (101-400AU) in 20.3%, severe (4011000AU) in 9.3%, and extensive (≤1000AU) in 6.5%. In multivariable logistic regression model, the predictors of CAC include age, male gender, hypertension, duration of diabetes and hypercholesterolemia. There was no difference in the severity of CAC in patients with 2 or less risk factors. Only clustering of 3 or more risk factors predicts higher degree of CAC (odds ratio 1.64, 2.38: p value 0.028,0.008 respectively). Conclusions: Significant subclinical coronary atherosclerosis is common in uncomplicated T2DM as measured by MDCT, which was not fairly predicted by the number of established risk factors. Risk stratification and short-term outcome in this CAD risk-equivalent T2DM population will be prospectively evaluated according to CAC scores.
S21-5 TO STUDY THE ROLE OF H2 S IN THE INITIAL STAGE OF ATHEROSCLEROSIS
Sarita G. Barsainya, Gaurang B. Shah. Dept. of Pharmacology, K.B. Institute of Pharmaceutical Education and Research, Gandhinagar, INDIA Background: H2 S [Hydrogensulfide] was recently suggested to be a possible endogenous gasotransmitter in physiological concentration produced from homocysteine. For the purpose of understanding its possible role in pathogenesis of atherosclerosis, we explored the effect of H2 S on carotid artery injured rats. Objective: To study the role of H2 S in the initial stage of atherosclerosis in rats. Materials and Methods: Rats fed on atherogenic diet for 1 week underwent left carotid artery injury induced by thin metallic wire. Atherogenic diet was continued and on the next day of injury, treatment of NaHS [H2S donor] was given for another 3 weeks. Total 4 weeks later, blood was collected and carotid artery was removed for various observations. Results: Carotid artery lesion index was significantly less in H2 S treated group [0.13±0.09] when compared with control group [3.94±0.89] P value < 0.05 Mean serum homocysteine levels were significantly higher in H2 S treated group [7.85±0.19 µmol/L] when compared with control group [5.45±0.065 µmol/L] P value<0.005 Conclusion: H2 S is directly acting as a antiatherosclerotic in the presence of high
N.A. Bylova, G.P. Arutyunov, L.I. Kafarskaya, T.K. Chrenyavskaya. Russian State Medical University, Russian Federation Background and aim: One of possible causes of development of atherosclerosis is a high level of proinflammatory cytokines. High level of endotoxin may leads to increase of systemic inflammation. The goal of the trial was to evaluate the effect of different concentration of endotoxin on development of atherosclerosis (carotid intima-media thickness (CIMT). Methods: study was approved by local ethical committee of Russian State medical University. 300 asymptomatic patients with moderately elevated cholesterol and low risk of cardiovascular disease were enrolled in the study (LDL 120-190 mg/dl, HDL-C ≤60 mg/dl; triglicerides < 500 mg/dl) and evidence of thickening of the walls of the extracranial carotid arteries, as measured by B-mode ultrasound (at baseline and at 24 month). Exclusion criteria were infectious diseases. In all patients we also measured a level of endotoxin in plasma (LAL-test). Results: at baseline we find patients with endotoxin level 0,25±0,03 UE/l (first group, n=110) and 0,41±0,05 UE/l (second group, n=100). Mean CIMT in first group was 1.16±0.05 mm and in second group 1.163±0.07 mm. Average LDL levels were 150±4 mg/dl and 151±2 mg/dl, respectively. After 24 months of follow up no significant changes were find in cholesterol levels. Mean CIMT in first group had no changes 1.16±0.09 mm, but in second group increased significantly – 1.65±0.04 mm (p=0.002). Conclusion: among asymptomatic patients at low risk for cardiovascular disease high levels of endotoxin in plasma was associated with an increase in CIMT.
S21-7 IDENTIFICATION OF POTENTIALLY ATHEROGENIC ELECTRONEGATIVE LDL IN PATIENTS WITH CORONARY ARTERY DISEASE OR CAD RISK FACTORS
Po-Yuan Chang 1 , Yi-Jie Chen 1 , Shao-Chun Lu 1 , Jen-Kuang Lee 1 , Chao-Yuh Yang 2 , Chu-Huang Chen 2 , Yuan-Teh Lee 1 , Ming-Fong Chen 1 . 1 National Taiwan University Medical Center, Taipei, Taiwan, and 2 Baylor College of Medicine, Houston, Texas, USA Background: L5, a highly electronegative LDL originally isolated from hypercholesterolemic human plasma, exhibits a spectrum of atherogenic effects on cultured vascular cells. To evaluate its clinical implication, we assess its prevalence in patients with coronary artery disease (CAD) or CAD risk factors in comparison with subjects without these risk factors. Methods and Results: Fasting blood samples were collected from adult patients with angiographically evidenced CAD (stenosis> =50%; n=10), asymptomatic hypercholesterolemia (LDL cholesterol> =160 mg/dL; n=10), type 2 diabetes mellitus (HbA1c> =8.0; n=10), history of chronic smoking (n=10), and healthy subjects without these risk factors (n=10). In consistence with our previous findings, plasma LDL was divided by ion-exchange chromatography into 5 subfractions, L1–L5, with increasing electronegativity, in all hypercholesterolemic samples (n=10/10; L5/LDL=0.8-4.0%). Irrespective of the plasma cholesterol concentrations, L5 was also found in all diabetic (n=10/10; L5/LDL=1.0-5.3%) and most CAD patients (n=7/10; L5/LDL=0.6-2.8%) and chronic smokers (n=3/5; L5/LDL=0.7-2.1%). In contrast, ion-exchange chromatography failed to yield L5 in any of the healthy subjects without CAD risk factors. Regardless of their origins, all L5 specimens were able to induce human arterial endothelial cell (EC) apoptosis and inhibit EC proliferation by inhibiting fibroblast growth factor-2 expression. L1-L4 had no effects. Conclusions: EC apoptosis contributes to both atherosclerosis and thrombosis. Thus, L5’s prevalence in patients with CAD or CAD risk factors but not in riskfree healthy subjects implicates a clinical correlation. Large-scale epidemiologic survey and prospective investigations are warranted to confirm L5’s atherogenic role and hence identifying it as a novel therapeutic target.