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521 RAPID AND EFFICIENT IMMUNOCHROMATOGRAPHIC FATTY ACID BINDING PROTEIN ASSAY FOR EARLY DIAGNOSIS OF MYOCARDIAL INFARCTION
79th EAS Congress
Atherosclerosis Supplements 12, no. 1 (2011) 13–184
Conclusions: This pilot study didn’t show significant impact of two COX-1 polymorphisms (−707A>G and 10742C>A) on aspirin efficacy in the setting of PCI. These data could be used for power calculations of a larger study evaluating role of −707G allele as non-signicant difference could be due to insufficiant power of the current study. 521 RAPID AND EFFICIENT IMMUNOCHROMATOGRAPHIC FATTY ACID BINDING PROTEIN ASSAY FOR EARLY DIAGNOSIS OF MYOCARDIAL INFARCTION M. Voevoda1 , V. Shulman2 , L. Polikarpov2 , O. Shtegman2 , K. Nikolaev1 . 1 Institute of Internal Medicine SB RAMS, Novosibirsk, 2 Krasnoyarsk State Medical University, Krasnoyarsk, Russia Objective: The study was aimed at the estimation of the efficiency of rapid immunochromatographic measuring of fatty acid binding protein (FABP) level in the blood for early diagnosis of myocardial infarction (MI). The concentration of FABP in blood is a well-known marker of myocardial infarction. Methods: A novel, sensitive immunochromatographic assay which is based on immunochromatographic strip technique has been recently developed for rapid qualitative detection of FABP in whole blood (BioTest Co., Novosibirsk, Russia, http://www.biotst.ru/ru/). The procedure requires ~100 mkl of whole blood and can be completed in 20 min without any equipment and in any setting. Test detects FABP level equal or exceeding 15 ng/mkl. Assay was completed in 98 patients admitted to emergence department with diagnosis of definite MI or acute coronary syndrome. Result: MI was detected in 71 patients according to standard criterion, including troponin I measuring. Overall sensitivity of the FABP assay for 24 hours in comparison with standard criterion was 93.4% and specificity 93%. In comparison at the same time sensitivity and specificity of troponin I assay was 89% and 74% accordingly. It is important that FABP assay demonstrated high sensitivity and specificity in first 3 hours of MI (86% and 100% accordingly). Conclusions: Express immunochromatographic FABP assay is a new and very efficient tool for early diagnosis of MI. Particularly important is its high sensitivity and specificity in first 3 hours of MI allowing early and optimal treatment using conventional and new therapeutic approaches. 522 THE IMPORTANCE OF INFLAMMATORY MARKERS FOR EARLY DIAGNOSTIC IN ADOLESCENTS WITH METABOLIC DISEASES V. Negrean, M. Adam, T. Alexescu, S. Tarmure, F. Tomesc, D. Sturzu, A. Nemes. UMF Iuliu Hatieganu Cluj-Napoca Clinica Medicala IV, Cluj-Napoca, Romania Introduction: The purpose of this study was to determine the relationship between the inflammatory markers (fibrinogen, CRP, TNF alpha, IL6, IL8) and the early diagnosis of atherosclerosis in teenagers suffering from metabolic diseases − diabetes mellitus, obesity, dyslipidaemia, hyperuricaemia. Material and Methods: The study included 4052 teenagers studying at 56 various high schools from Cluj that were asked to answer a list of 30 questions concerning the following matters: anthropometrical data, metabolic risk factors, metabolic diseases genetic backgrounds, personal medical history of metabolic disorders. The subjects were divided into 2 groups, a control group and an experimental group. The experimental group consisted of 251 patients diagnosed with metabolic diseases that were tested for inflammatory markers and ultrasound examined in order to determinate the carotid intima-media thickness. Results: 251 (16.01%) out of the 4052 teenagers had metabolic diseases, and 141 (56%) of those had at least one inflammatory marker impaired and 84 (33.6%) had all of the markers impaired. The sedentary life style was positive in 248 cases, the metabolic genetic background in 239 cases, the use of alcohol in 131 cases and smoking in 201 cases. Conclusions: Metabolic diseases are frequent in adolescents and inflammatory markers can be used for early diagnosis of atherosclerosis. 523 THE IMPACT OF PLASMA ADIPOCYTE FATTY ACID-BINDING PROTEIN ON RENAL INSUFFICIENCY AND CORONARY LESION SEVERITY IN DIABETIC PATIENTS T. Miyoshi1 , M. Doi2 , K. Takeda2 , S. Usui3 , K. Nakamura1 , S. Kusachi3 , K. Kusano1 , H. Ito1 . 1 Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Okayama, 2 Department of Cardiology, Kagawa Prefectural Central Hospital, Takamatsu, 3 Department of Medical Technology, Okayama University Graduate School of Medicine, Okayama, Japan Background: Renal insufficiency is associated with cardiovascular events. Adipocyte fatty acid-binding protein (A-FABP) has been shown to play a critical role in metabolic syndrome and atherosclerosis. We investigated whether plasma A-FABP could correlate with renal insufficiency and severity of coronary artery lesion in patients with type 2 diabetes. Methods: The consecutive 191 patients with suspected coronary artery disease were enrolled after coronary angiogram. Renal function was assed just before
111
coronary angiogram. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2 . The severity of coronary stenosis was assessed using the scoring system. Plasma A-FABP was measured by ELISA. Results: In diabetic patients (n = 86), plasma A-FABP was significantly associated with eGFR (r = −0.43, p < 0.01) and coronary plaque severity (r = −0.29, p < 0.01). In non-diabetic subjects (n = 95), the correlation of plasma A-FABP with eGFR remained significant, but not with coronary plaque severity. The prevalence of CKD and multi-coronary vessel disease In diabetic patients with higher A-FABP (>20.3ng/mL) was significantly greater than those with lower A-FABP (67% vs. 20%, p = 0.02 and 39% vs. 4%, p < 0.01, respectively). Multiple logistic analysis in diabetic patients demonstrated that plasma A-FABP (per doubling) was independently associated with CKD (OR 6.21 [1.78–21.67]; p < 0.01) and multi-coronary vessel disease (odds ratio [OR] 1.89 [95% CI 1.02– 3.45]; p = 0.04). Conclusion: Plasma A-FABP could be a new biomarker which involved in the interplay between renal dysfunction and coronary artery disease in type 2 diabetic patients. 524 EVALUATION OF SERA BIOMARKERS FOR CORONARY ARTERY DISEASE AND DIABETES N. Ivanova1 , A. Postadzhiyan2 , B. Finkov2 , M. Apostolova1 . 1 Institute of Molecular Biology, BAS, 2 University Hospital “St. Anna”, Sofia, Bulgaria Introduction: Cardiovascular diseases are the most common cause of death in developed countries. Among them atherosclerosis is a leader in morbidity and mortality. The proteomic analyses facilitate protein separation, identification, and characterization, this makes it ideal for documenting protein modifications due to this particular disease. Aim: The aim of this study was to investigate the participation of proteins in the progression of the atherosclerotic plaques and to clarify the molecular mechanisms of action in sera from patients with coronary artery disease. Materials and Methods: Proteome analysis was conducted for sera from 293 patients with the following diagnoses: Stable Angina Pectoris − SAP (n = 59), Unstable Angina Pectoris UAP (n = 120), diabetes type I (n = 114) and for sera from 131 healthy controls. The proteome analysis includes: 2D electrophoresis, immunoblotting, mass-spectrometry and bioinformatics analysis: OPHID database and Ingenuity Pathway Analysis, Ingenuity Systems. Results: The identified proteins changed over the threshold in patients with UAP, SAP and diabetes type I participate in 6 different signal transduction pathways. Ingenuity Pathway Analysis identified 6 specific potential biomarkers for patients with UAP, 6 for patients with diabetes and 5 for SAP. Conclusion: The changes of expression of the chosen biomarkers probably can determine the differences in the characteristic and progression of the disease in the patients studied. 525 ASSOCIATION OF ANGIOTENSIN II TYPE 1 RECEPTOR +1166 A/C GENE POLYMORPHISM WITH HUMAN CAROTID PLAQUE VULNERABILITY A. Kolakovic1 , M. Zivkovic1 , D. Radak2 , I. Koncar3 , T. Djuric1 , L. Davidovic3 , ˇ Institute of Nuclear Sciences, Laboratory D. Alavantic1 , A. Stankovic1 . 1 VINCA for Radiobiology and Molecular Genetics, 2 Cardiovascular Institute Dedinje, 3 Institute for Cardiovascular Diseases, Belgrade, Serbia Background and Aim: Angiotensin II is a potent vasoconstrictor and plays a pivotal role in regulation of blood pressure homeostasis and atherogenesis through its binding to the angiotensin II type 1 receptor (AGTR1). Beyond its hemodynamic effect Ang II modulates the atherosclerotic phenotype by balance between intravascular clot formation and fibrinolotyc potential, promoting the induction of plaque vulnerability. AGTR1 +1166 A/C gene polymorphism has been investigated in correlation with carotid IMT and associated with increased cardiovascular disease risk. In this study we investigate possible association of AGT1R +1166 A/C gene polymorphism with plaque stability in patients with carotid atherosclerosis from Serbia. Methods: Study group was consisted of 400 patients with carotid atherosclerosis (278 pts. with stable and 122 pts. with ustable plaques). The AGTR1 sequence containing the A1166C site at nucleotide position 1166 in the 3 untranslated region was amplified by PCR and genotypes were determined by RFLP analysis. Results: We have found significance difference in genotype frequency between patients with stable and unstable carotid plaques according to the genotype model considering C allele as dominant (CC+CA vs. AA; stable plaque: 39.93% vs. 60.07%, unstable plaque 51.64% vs. % 48.36, respectively, p = 0.03). Carriers of genotypes containing C allele had 1.63 fold increased risk for unstable plaque development, adjusted for hypertension and smoking status (OR = 1.63, 95% CI 1.05–2.51, p = 0.03). Conclusion: In this study our data demonstrate that AGTR1 +A1166C gene polymorphism contributes to the variability in interindividual risk for plaque instability in patients with carotid atherosclerosis from Serbia.
Atherosclerosis Supplements 12, no. 1 (2011) 13–184
Conclusions: This pilot study didn’t show significant impact of two COX-1 polymorphisms (−707A>G and 10742C>A) on aspirin efficacy in the setting of PCI. These data could be used for power calculations of a larger study evaluating role of −707G allele as non-signicant difference could be due to insufficiant power of the current study. 521 RAPID AND EFFICIENT IMMUNOCHROMATOGRAPHIC FATTY ACID BINDING PROTEIN ASSAY FOR EARLY DIAGNOSIS OF MYOCARDIAL INFARCTION M. Voevoda1 , V. Shulman2 , L. Polikarpov2 , O. Shtegman2 , K. Nikolaev1 . 1 Institute of Internal Medicine SB RAMS, Novosibirsk, 2 Krasnoyarsk State Medical University, Krasnoyarsk, Russia Objective: The study was aimed at the estimation of the efficiency of rapid immunochromatographic measuring of fatty acid binding protein (FABP) level in the blood for early diagnosis of myocardial infarction (MI). The concentration of FABP in blood is a well-known marker of myocardial infarction. Methods: A novel, sensitive immunochromatographic assay which is based on immunochromatographic strip technique has been recently developed for rapid qualitative detection of FABP in whole blood (BioTest Co., Novosibirsk, Russia, http://www.biotst.ru/ru/). The procedure requires ~100 mkl of whole blood and can be completed in 20 min without any equipment and in any setting. Test detects FABP level equal or exceeding 15 ng/mkl. Assay was completed in 98 patients admitted to emergence department with diagnosis of definite MI or acute coronary syndrome. Result: MI was detected in 71 patients according to standard criterion, including troponin I measuring. Overall sensitivity of the FABP assay for 24 hours in comparison with standard criterion was 93.4% and specificity 93%. In comparison at the same time sensitivity and specificity of troponin I assay was 89% and 74% accordingly. It is important that FABP assay demonstrated high sensitivity and specificity in first 3 hours of MI (86% and 100% accordingly). Conclusions: Express immunochromatographic FABP assay is a new and very efficient tool for early diagnosis of MI. Particularly important is its high sensitivity and specificity in first 3 hours of MI allowing early and optimal treatment using conventional and new therapeutic approaches. 522 THE IMPORTANCE OF INFLAMMATORY MARKERS FOR EARLY DIAGNOSTIC IN ADOLESCENTS WITH METABOLIC DISEASES V. Negrean, M. Adam, T. Alexescu, S. Tarmure, F. Tomesc, D. Sturzu, A. Nemes. UMF Iuliu Hatieganu Cluj-Napoca Clinica Medicala IV, Cluj-Napoca, Romania Introduction: The purpose of this study was to determine the relationship between the inflammatory markers (fibrinogen, CRP, TNF alpha, IL6, IL8) and the early diagnosis of atherosclerosis in teenagers suffering from metabolic diseases − diabetes mellitus, obesity, dyslipidaemia, hyperuricaemia. Material and Methods: The study included 4052 teenagers studying at 56 various high schools from Cluj that were asked to answer a list of 30 questions concerning the following matters: anthropometrical data, metabolic risk factors, metabolic diseases genetic backgrounds, personal medical history of metabolic disorders. The subjects were divided into 2 groups, a control group and an experimental group. The experimental group consisted of 251 patients diagnosed with metabolic diseases that were tested for inflammatory markers and ultrasound examined in order to determinate the carotid intima-media thickness. Results: 251 (16.01%) out of the 4052 teenagers had metabolic diseases, and 141 (56%) of those had at least one inflammatory marker impaired and 84 (33.6%) had all of the markers impaired. The sedentary life style was positive in 248 cases, the metabolic genetic background in 239 cases, the use of alcohol in 131 cases and smoking in 201 cases. Conclusions: Metabolic diseases are frequent in adolescents and inflammatory markers can be used for early diagnosis of atherosclerosis. 523 THE IMPACT OF PLASMA ADIPOCYTE FATTY ACID-BINDING PROTEIN ON RENAL INSUFFICIENCY AND CORONARY LESION SEVERITY IN DIABETIC PATIENTS T. Miyoshi1 , M. Doi2 , K. Takeda2 , S. Usui3 , K. Nakamura1 , S. Kusachi3 , K. Kusano1 , H. Ito1 . 1 Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Okayama, 2 Department of Cardiology, Kagawa Prefectural Central Hospital, Takamatsu, 3 Department of Medical Technology, Okayama University Graduate School of Medicine, Okayama, Japan Background: Renal insufficiency is associated with cardiovascular events. Adipocyte fatty acid-binding protein (A-FABP) has been shown to play a critical role in metabolic syndrome and atherosclerosis. We investigated whether plasma A-FABP could correlate with renal insufficiency and severity of coronary artery lesion in patients with type 2 diabetes. Methods: The consecutive 191 patients with suspected coronary artery disease were enrolled after coronary angiogram. Renal function was assed just before
111
coronary angiogram. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2 . The severity of coronary stenosis was assessed using the scoring system. Plasma A-FABP was measured by ELISA. Results: In diabetic patients (n = 86), plasma A-FABP was significantly associated with eGFR (r = −0.43, p < 0.01) and coronary plaque severity (r = −0.29, p < 0.01). In non-diabetic subjects (n = 95), the correlation of plasma A-FABP with eGFR remained significant, but not with coronary plaque severity. The prevalence of CKD and multi-coronary vessel disease In diabetic patients with higher A-FABP (>20.3ng/mL) was significantly greater than those with lower A-FABP (67% vs. 20%, p = 0.02 and 39% vs. 4%, p < 0.01, respectively). Multiple logistic analysis in diabetic patients demonstrated that plasma A-FABP (per doubling) was independently associated with CKD (OR 6.21 [1.78–21.67]; p < 0.01) and multi-coronary vessel disease (odds ratio [OR] 1.89 [95% CI 1.02– 3.45]; p = 0.04). Conclusion: Plasma A-FABP could be a new biomarker which involved in the interplay between renal dysfunction and coronary artery disease in type 2 diabetic patients. 524 EVALUATION OF SERA BIOMARKERS FOR CORONARY ARTERY DISEASE AND DIABETES N. Ivanova1 , A. Postadzhiyan2 , B. Finkov2 , M. Apostolova1 . 1 Institute of Molecular Biology, BAS, 2 University Hospital “St. Anna”, Sofia, Bulgaria Introduction: Cardiovascular diseases are the most common cause of death in developed countries. Among them atherosclerosis is a leader in morbidity and mortality. The proteomic analyses facilitate protein separation, identification, and characterization, this makes it ideal for documenting protein modifications due to this particular disease. Aim: The aim of this study was to investigate the participation of proteins in the progression of the atherosclerotic plaques and to clarify the molecular mechanisms of action in sera from patients with coronary artery disease. Materials and Methods: Proteome analysis was conducted for sera from 293 patients with the following diagnoses: Stable Angina Pectoris − SAP (n = 59), Unstable Angina Pectoris UAP (n = 120), diabetes type I (n = 114) and for sera from 131 healthy controls. The proteome analysis includes: 2D electrophoresis, immunoblotting, mass-spectrometry and bioinformatics analysis: OPHID database and Ingenuity Pathway Analysis, Ingenuity Systems. Results: The identified proteins changed over the threshold in patients with UAP, SAP and diabetes type I participate in 6 different signal transduction pathways. Ingenuity Pathway Analysis identified 6 specific potential biomarkers for patients with UAP, 6 for patients with diabetes and 5 for SAP. Conclusion: The changes of expression of the chosen biomarkers probably can determine the differences in the characteristic and progression of the disease in the patients studied. 525 ASSOCIATION OF ANGIOTENSIN II TYPE 1 RECEPTOR +1166 A/C GENE POLYMORPHISM WITH HUMAN CAROTID PLAQUE VULNERABILITY A. Kolakovic1 , M. Zivkovic1 , D. Radak2 , I. Koncar3 , T. Djuric1 , L. Davidovic3 , ˇ Institute of Nuclear Sciences, Laboratory D. Alavantic1 , A. Stankovic1 . 1 VINCA for Radiobiology and Molecular Genetics, 2 Cardiovascular Institute Dedinje, 3 Institute for Cardiovascular Diseases, Belgrade, Serbia Background and Aim: Angiotensin II is a potent vasoconstrictor and plays a pivotal role in regulation of blood pressure homeostasis and atherogenesis through its binding to the angiotensin II type 1 receptor (AGTR1). Beyond its hemodynamic effect Ang II modulates the atherosclerotic phenotype by balance between intravascular clot formation and fibrinolotyc potential, promoting the induction of plaque vulnerability. AGTR1 +1166 A/C gene polymorphism has been investigated in correlation with carotid IMT and associated with increased cardiovascular disease risk. In this study we investigate possible association of AGT1R +1166 A/C gene polymorphism with plaque stability in patients with carotid atherosclerosis from Serbia. Methods: Study group was consisted of 400 patients with carotid atherosclerosis (278 pts. with stable and 122 pts. with ustable plaques). The AGTR1 sequence containing the A1166C site at nucleotide position 1166 in the 3 untranslated region was amplified by PCR and genotypes were determined by RFLP analysis. Results: We have found significance difference in genotype frequency between patients with stable and unstable carotid plaques according to the genotype model considering C allele as dominant (CC+CA vs. AA; stable plaque: 39.93% vs. 60.07%, unstable plaque 51.64% vs. % 48.36, respectively, p = 0.03). Carriers of genotypes containing C allele had 1.63 fold increased risk for unstable plaque development, adjusted for hypertension and smoking status (OR = 1.63, 95% CI 1.05–2.51, p = 0.03). Conclusion: In this study our data demonstrate that AGTR1 +A1166C gene polymorphism contributes to the variability in interindividual risk for plaque instability in patients with carotid atherosclerosis from Serbia.