- Email: [email protected]
Ratios of serum eicosapentaenoic (EPA) and docosahexaenoic (DHA) acid to arachidonic acid (AA) and coronary and aortic plaque instability
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Abstracts / Atherosclerosis 235 (2014) e192–e301
51 - Novel risk factors and biomarkers EAS-0864. COMPARISON OF SERUM TIMP-2, NGAL AND ANGIOPOIETIN-2 LEVELS TO IDENTIFY CORONARY ARTERY STENOSIS H. Jooa, Y. Hana, H. Seoa, S. Choia, J. Parka, C. Yua, S. Honga, D. Lima a
Department of Cardiology Cardiovascular Center, Korea University Anam Hospital, Seoul, Korea Objectives: Coronary artery artherosclerosis involves lipid metabolism as well as vascular inflammation/activation. We aimed to compare the diagnostic values of new biomarkers regarding vascular inflammation/ activation (NGAL, TIMP2, IL-8, GRO alpha, angiopoietin-2, bFGF and EGF) to identify angiographically significant coronary artery stenosis. Methods: Serum levels of NGAL, TIMP2, IL-8, GRO alpha, angiopoietin-2, bFGF, EGF and hsCRP were measured in 70 patients who undertook coronary angiography. Results: Serum TIMP-2, NGAL and angiopoietin-2 levels were significantly elevated in patients with coronary artery stenosis (p ¼ 0.002, p ¼ 0.01 and p ¼ 0.01, respectively). They were also statistically correlated with the numbers of the stenotic coronary artery and its angiographical severities based on the modified Gensini score. Receiver operating characteristic curves of TIMP-2, NGAL and angiopoietin-2 showed significantly increased area under the curve (0.795, 0.728, 0.722, respectively). Multivariate analysis revealed that the elevated serum angiopoietin-2 level, old age and current smoking were statistically strong predictors for coronary artery stenosis (p ¼ 0.22, p ¼ 0.006 and p ¼ 0.004, respectively). Conclusion: Serum TIMP-2, NGAL and angiopoietin-2 levels were useful predictors for the presence and severity of coronary artery stenosis. 51 - Novel risk factors and biomarkers EAS-0403. CIRCULATING PRO-ATHEROGENIC OXIDIZED-LDL/b2-GLYCOPROTEIN I COMPLEXES ARE DETECTED IN ARTERIAL AND VENOUS DISEASES AND ARE INDEPENDENT PREDICTORS OF CAROTID ARTERIAL DISEASE L.R. Lopeza, E. Matsuurab, K.E. Guyerc, C.B. Rockmand, J.S. Bergere a Medical Department, Corgenix Inc., Broomfield, USA; b Collaborative Research Center for Okayama Medical Innovation Center (OMIC) and Department of Cell Chemistry, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama, Japan; c Department of Chemistry, Indiana University South Bend, South Bend, USA; d Department of Surgery Division of Vascular Surgery, New York University School of Medicine, New York, USA; e Department of Medicine Divisions of Cardiology and Hematology, New York University School of Medicine, New York, USA
Objectives: Statin-modifiable and pro-atherogenic oxLDL/b2GPI complexes have been implicated in the initiation and progression of atherosclerotic CVD and associated with disease severity and adverse outcomes. However, the presence and significance of these complexes in idiopathic venous disease (IVD) have not been evaluated. Methods: 146 study subjects recruited from a vascular surgery outpatient clinic were enrolled: 61 had arterial disease (21 CarAD, 17 PAD, and 23 AAA), 32 had IVD, and 53 were healthy controls. Serum was obtained to measure oxLDL/b2GPI by ELISA and the results were expressed in U/mL (meanSD). Results: One-hundred subjects not taking statins were further studied. OxLDL/b2GPI levels were significantly elevated in arterial (0.690.50, p¼0.004) and venous groups (0.540.37, p¼0.025) compared to controls (0.390.33). Among arterial disease patients, oxLDL/b2GPI levels were 0.850.59 for CarAD, 0.720.54 for PAD and 0.520.38 for AAA. There was a significant positive association of oxLDL/b2GPI with the following demographic and clinical variables: sex (male 0.55 vs female 0.26, p¼0.005);
age (r¼0.299, p¼0.002); hypertension (0.54 vs 0.27, p¼0.024) and history of previous thrombotic episodes (0.95 vs 0.37, p¼0.035). Subjects with oxLDL/b2GPI levels above the median (0.25 U/mL) were significantly more likely to have arterial disease (OR 4.5, 1.54-13.14, p¼0.004) and venous disease (OR 4.1, 1.38-11.99, p¼0.008). Multivariate regression models with oxLDL/b2GPI as a dependent variable indicated male gender (t¼2.34, p¼0.021), high cholesterol (t¼-2.58, p¼0.011) and the CarAD phenotype (t¼2.32, p¼0.023) were significant predictors of oxLDL/b2GPI. Excluding venous disease, only CarAD remained as a significant independent predictor of oxLDL/b2GPI levels. Conclusion: The coexistence of oxLDL/b2GPI complexes in arterial and venous disease suggests a common underlying oxidative inflammatory mechanism that is particularly significant as an independent predictor for CarAD. 51 - Novel risk factors and biomarkers EAS-0594. LIPOSCALE: A NOVEL ADVANCED LIPOPROTEIN TEST BASED ON 2D DIFFUSION-ORDERED 1H NMR SPECTROSCOPY R. Mallola, N. Amigóa, A. Cabréb, M.A. Rodrígueza, M. Herasb, M. Vinaixaa, N. Planac, E. Rockd, J. Ribaltab, L. Masanab, X. Correiga Centre for Omic Sciences, Universitat Rovira i Virgili, Reus, Spain; b Lipid and Atherosclerosis Research Unit, Universitat Rovira i Virgili, Reus, Spain; c Lipid and Atherosclerosis Research Unit, Sant Joan University Hospital, Reus, Spain; d INRA-Theix, UMMM, Saint Genès Champanelle, France a
Objectives: Type 2 diabetic subjects (T2DM) tend to present atherogenic dyslipidemia (AD), characterized by high triglycerides, low HDL cholesterol (HDL-C) levels, and a preponderance of small LDL particles. Moreover, the number of LDL particles (LDL-P) has been suggested to be a better predictor of cardiovascular risk than LDL cholesterol (LDL-C) in patients with high cardiometabolic risk. We developed a novel advanced lipoprotein test (ALT) based on 2D diffusion-ordered 1H NMR spectroscopy (DOSY) to compare the lipid and lipoprotein profiles of T2DM subjects with and without AD. Methods: First, we used a cohort of 177 subjects to set up a novel ALT based on DOSY. This methodology allows the determination of particle size and particle concentration of different lipoprotein classes and subclasses. These samples were also analyzed with a reference technique for validation purposes. Second, we used a cohort of 323 subjects to define the lipid and lipoprotein profile of AD. To associate these profiles with cardiovascular risk, we measured the intima media thickness (IMT). Results: VLDL particles were higher in T2DM subjects with AD, while medium HDL particles and total HDL-C were decreased. Despite we found no difference in LDL-C levels, mean levels of total LDL-P were higher in T2DM subjects with AD. We further analyzed the cases when these measures were discordant on the basis of population percentiles, i.e., when LDL-C was increased and LDL-P was normal (cholesterol-enriched particles predominate) and when LDL-P was increased but LDL-C was normal (cholesterol-depleted particles predominate). For those individuals with cholesterol-depleted LDL particles, only LDL-P was associated with IMT (r¼0.29). Conclusion: We used a novel ALT that permitted a profound characterization of AD in T2DM subjects. For individuals with cholesterol-depleted LDL particles, the LDL-attributable atherosclerotic risk was associated with LDL-P but not with LDL-C. 51 - Novel risk factors and biomarkers EAS-0097. RATIOS OF SERUM EICOSAPENTAENOIC (EPA) AND DOCOSAHEXAENOIC (DHA) ACID TO ARACHIDONIC ACID (AA) AND CORONARY AND AORTIC PLAQUE INSTABILITY Y. Momiyamaa, R. Ohmorib, R. Katoc, H. Taniguchic, F. Ohsuzuc a b
Department of Cardiology, NHO Tokyo Medical Center, Tokyo, Japan; Faculty of Education, Utsunomiya University, Utsunomiya, Japan; c First
Abstracts / Atherosclerosis 235 (2014) e192–e301
Department of Internal Medicine, National Defense Medical College, Saitama, Japan Objectives: Low EPA/AA ratio is suggested to be a biomarker for cardiovascular risk. Methods: To elucidate the associations between coronary (myocardial infarction and complex lesions) and aortic (complex plaques) plaque instability and EPA, DHA and AA levels and EPA/AA and DHA/AA ratios, black-blood aortic MRI was performed in 127 patients undergoing coronary angiography. On coronary angiograms, the degree of coronary atherosclerosis was represented as number of stenotic vessels. Complex lesions were defined by Ambrose classification. Regarding MRI, transverse aortic images (9 slices of thoracic, 9 slices of abdominal) were obtained at 12-mm intervals. The degree of aortic atherosclerosis was represented as sum of scores in each slice. Complex plaque was defined as one with irregular surface and thickening >4mm. Serum EPA, DHA and AA levels were measured by gas chromatography. Study patients were divided into tertiles by EPA, DHA, AA levels and EPA/AA and DHA/AA ratios. Results: The prevalence of CAD and the number of stenotic vessels were similar among tertiles of EPA, DHA and AA levels and EPA/AA and DHA/AA ratios. The prevalence of coronary plaque instability tended to be highest in lowest EPA tertile (50%(T1), 37%(T2) and 29%(T3)), lowest DHA tertile (48%(T1), 35%(T2) and 33%(T2)), and highest AA tertile (43%(T1), 30%(T2) and 43%(T3))(P¼NS). Coronary plaque instability was significantly most prevalent in lowest EPA/AA tertile (52%(T1), 35%(T2) and 29%(T3), P<0.05), but the difference among DHA/AA tertiles did not reach statistical significance (48%(T1), 35%(T2) and 33%(T3)). Regarding aortic atherosclerosis, the prevalence of aortic plaques and plaque score were similar among tertiles. The prevalence of complex aortic plaques was not different among tertiles of EPA (17%, 19% and 19%), DHA (14%, 16% and 24%), AA (19%, 12% and 24%), EPA/AA (21%, 14% and 19%) and DHA/AA (19%, 7% and 29%)(P¼NS). Conclusion: Only low EPA/AA ratio was associated with coronary, but not aortic, plaque instability. 51 - Novel risk factors and biomarkers EAS-0672. NUMBER OF CORONARY RISK FACTORS IS ASSOCIATED WITH BLOOD THROMBOGENICITY T. Nemotoa, Y. Uedaa a
Cardiovascular Division, Osaka Police Hospital, Osaka, Japan
Objectives: Increased blood thrombogenicity is considered one of the most important factors that are associated with cardiovascular events, and may play an important role for the onset of ACS. Blood thrombogenicity would be determined by blood rheology, coagulation system, and platelet functions. We examined the association between blood thrombogenicity and the amount of coronary risk factors. Methods: Consecutive patients (n¼898) who received coronary angiography were enrolled from January 2009 to January 2011. Blood thrombogenicity was evaluated by blood vulnerability index (BVI) calculated from the time-volume curve of whole blood run through and occlude the microchannels by thrombus formation in Micro-Channel Array Flow Analyzer (MC-FAN). Coronary risk factors included were hypertension, diabetes mellitus, dyslipidemia, high body mass index, and current smoking. Results: Study patients were male in 640 (71%) patients; were 68 years old in average; had mean body mass index of 24.4; had hypertension in 740 (82%), diabetes mellitus in 382 (43%), dyslipidemia in 725 (81%), and current smoking in 143 (16%) patients. BVI was significantly (p<0.01) higher in the patients with more coronary risk factors. Mean BVI in the patients with each number of risk factors was 2405 (risk factor¼0; n¼28), 2324 (1; n¼111), 2335 (2; n¼263), 2334 (3; n¼294), 2494 (4; n¼185), 2658 (5; n¼17). Conclusion: Blood thrombogenicity was higher in the patients with more coronary risk factors.
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51 - Novel risk factors and biomarkers EAS-0730. FOCUS ON RELEASED EXTRACELLULAR MATRIX COMPONENTS FROM CAROTID PLAQUE CORE: INTACT PROTEINS OR FRAGMENTS? S. Rocchicciolia, G. Pelosia, S. Rosinia, N. Ucciferria, M. Marconib, M. Ferrarib, A. Cecchettinic a IFC, Istituto di Fisiologia Clinica-CNR, pisa, Italy; b Unit of Vascular Surgery, University of Pisa, pisa, Italy; c Department of Clinical and Experimental Medicine, University of Pisa, pisa, Italy
Objectives: Carotid plaque rupture, leading to atherothrombosis, is the third most common cause of death and it is responsible for 20% of all strokes. Plaque core-specific molecular factors or fragments that are released into the blood flow, can be identified by proteomics analysis of extracellular matrix and may be exploited as clinically relevant specific biomarkers of vulnerability. Aim of this study was to map proteins and fragmented ECM products from the secretome of complicated carotid plaque specimens. Methods: The secretome profile of atherosclerotic internal carotid artery (ICA) derived from endoarterectomy was obtained by using HPLC coupled with mass spectrometry (LC-MSMS). ICA samples were left for 24 hours at 37 C in a serum free culture medium and a LC-MSMS analysis was carried out on collected secretomes. Additionally, secreted proteins were also analyzed to identify fragmented ECM proteins. Immunohistochemistry and histology analyses were performed to plaque core. Results: The LC-MSMS approach enabled the identification of 150 ECM and ECM associated proteins. Of relevance it was the observation that apo(A) and apo(E) were manly fragmented, indicating a strong activity of MMPs into plaque core. Proteoglycans and collagens were also identified and their fragmentation indicates an intense intraplaque enzyme activity, relatable to impending hemorrhage and/or rupture. Conclusion: An optimized workflow, allowing the first detailed matrix protein profile of carotid plaque secretome, may assist and improve biomarker discovery of molecular factors specifically related to disease complication. The proportion between intact protein and its fragments into the ECM plaque core could represent a quantitative indirect measure of intralesional protease activity and therefore provide a clinically novel and potentially more reliable index of rupture risk for vulnerable plaques. 51 - Novel risk factors and biomarkers EAS-0143. LIPOPROTEIN-ASSOCIATED PHOSPHOLIPASE A2 SERUM LEVELS IN PATIENTS FROM DIFFERENT CATEGORIES OF CARDIOVASCULAR RISK A. Semenovaa, D. Nozadzea, I. Sergienkoa, T. Vlasikb, V. Kukharchuka a Atherosclerosis Department, Russian Cardiology Research Complex, Moscow, Russia; b Laboratory of Cell Engineering, Russian Cardiology Research Complex, Moscow, Russia
Objectives: The aim was to compare the lipoprotein-associated phospholipase A2 (Lp-PLA2) serum levels in patients from different cardiovascular risk categories. Methods: 519 patients from Moscow prospective study database were divided into 4 cardiovascular risk categories according to present clinical recommendations (low, moderate, high, very high). Blood samples were taken for the Lp-PLA2 mass and activity levels determination. The serum levels of total cholesterol (TC), low-density lipoprotein-cholesterol (LDLC), high-density lipoprotein-cholesterol (HDL-C), triglycerides (TG), lipoprotein (a) (Lp(a)), high sensitive C-reactive protein (hsCRP) and uric acid were also detected. Results: After preliminary analysis the results were more prominent with the exclusion of patients who received statins and patients with diabetes
Abstracts / Atherosclerosis 235 (2014) e192–e301
51 - Novel risk factors and biomarkers EAS-0864. COMPARISON OF SERUM TIMP-2, NGAL AND ANGIOPOIETIN-2 LEVELS TO IDENTIFY CORONARY ARTERY STENOSIS H. Jooa, Y. Hana, H. Seoa, S. Choia, J. Parka, C. Yua, S. Honga, D. Lima a
Department of Cardiology Cardiovascular Center, Korea University Anam Hospital, Seoul, Korea Objectives: Coronary artery artherosclerosis involves lipid metabolism as well as vascular inflammation/activation. We aimed to compare the diagnostic values of new biomarkers regarding vascular inflammation/ activation (NGAL, TIMP2, IL-8, GRO alpha, angiopoietin-2, bFGF and EGF) to identify angiographically significant coronary artery stenosis. Methods: Serum levels of NGAL, TIMP2, IL-8, GRO alpha, angiopoietin-2, bFGF, EGF and hsCRP were measured in 70 patients who undertook coronary angiography. Results: Serum TIMP-2, NGAL and angiopoietin-2 levels were significantly elevated in patients with coronary artery stenosis (p ¼ 0.002, p ¼ 0.01 and p ¼ 0.01, respectively). They were also statistically correlated with the numbers of the stenotic coronary artery and its angiographical severities based on the modified Gensini score. Receiver operating characteristic curves of TIMP-2, NGAL and angiopoietin-2 showed significantly increased area under the curve (0.795, 0.728, 0.722, respectively). Multivariate analysis revealed that the elevated serum angiopoietin-2 level, old age and current smoking were statistically strong predictors for coronary artery stenosis (p ¼ 0.22, p ¼ 0.006 and p ¼ 0.004, respectively). Conclusion: Serum TIMP-2, NGAL and angiopoietin-2 levels were useful predictors for the presence and severity of coronary artery stenosis. 51 - Novel risk factors and biomarkers EAS-0403. CIRCULATING PRO-ATHEROGENIC OXIDIZED-LDL/b2-GLYCOPROTEIN I COMPLEXES ARE DETECTED IN ARTERIAL AND VENOUS DISEASES AND ARE INDEPENDENT PREDICTORS OF CAROTID ARTERIAL DISEASE L.R. Lopeza, E. Matsuurab, K.E. Guyerc, C.B. Rockmand, J.S. Bergere a Medical Department, Corgenix Inc., Broomfield, USA; b Collaborative Research Center for Okayama Medical Innovation Center (OMIC) and Department of Cell Chemistry, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama, Japan; c Department of Chemistry, Indiana University South Bend, South Bend, USA; d Department of Surgery Division of Vascular Surgery, New York University School of Medicine, New York, USA; e Department of Medicine Divisions of Cardiology and Hematology, New York University School of Medicine, New York, USA
Objectives: Statin-modifiable and pro-atherogenic oxLDL/b2GPI complexes have been implicated in the initiation and progression of atherosclerotic CVD and associated with disease severity and adverse outcomes. However, the presence and significance of these complexes in idiopathic venous disease (IVD) have not been evaluated. Methods: 146 study subjects recruited from a vascular surgery outpatient clinic were enrolled: 61 had arterial disease (21 CarAD, 17 PAD, and 23 AAA), 32 had IVD, and 53 were healthy controls. Serum was obtained to measure oxLDL/b2GPI by ELISA and the results were expressed in U/mL (meanSD). Results: One-hundred subjects not taking statins were further studied. OxLDL/b2GPI levels were significantly elevated in arterial (0.690.50, p¼0.004) and venous groups (0.540.37, p¼0.025) compared to controls (0.390.33). Among arterial disease patients, oxLDL/b2GPI levels were 0.850.59 for CarAD, 0.720.54 for PAD and 0.520.38 for AAA. There was a significant positive association of oxLDL/b2GPI with the following demographic and clinical variables: sex (male 0.55 vs female 0.26, p¼0.005);
age (r¼0.299, p¼0.002); hypertension (0.54 vs 0.27, p¼0.024) and history of previous thrombotic episodes (0.95 vs 0.37, p¼0.035). Subjects with oxLDL/b2GPI levels above the median (0.25 U/mL) were significantly more likely to have arterial disease (OR 4.5, 1.54-13.14, p¼0.004) and venous disease (OR 4.1, 1.38-11.99, p¼0.008). Multivariate regression models with oxLDL/b2GPI as a dependent variable indicated male gender (t¼2.34, p¼0.021), high cholesterol (t¼-2.58, p¼0.011) and the CarAD phenotype (t¼2.32, p¼0.023) were significant predictors of oxLDL/b2GPI. Excluding venous disease, only CarAD remained as a significant independent predictor of oxLDL/b2GPI levels. Conclusion: The coexistence of oxLDL/b2GPI complexes in arterial and venous disease suggests a common underlying oxidative inflammatory mechanism that is particularly significant as an independent predictor for CarAD. 51 - Novel risk factors and biomarkers EAS-0594. LIPOSCALE: A NOVEL ADVANCED LIPOPROTEIN TEST BASED ON 2D DIFFUSION-ORDERED 1H NMR SPECTROSCOPY R. Mallola, N. Amigóa, A. Cabréb, M.A. Rodrígueza, M. Herasb, M. Vinaixaa, N. Planac, E. Rockd, J. Ribaltab, L. Masanab, X. Correiga Centre for Omic Sciences, Universitat Rovira i Virgili, Reus, Spain; b Lipid and Atherosclerosis Research Unit, Universitat Rovira i Virgili, Reus, Spain; c Lipid and Atherosclerosis Research Unit, Sant Joan University Hospital, Reus, Spain; d INRA-Theix, UMMM, Saint Genès Champanelle, France a
Objectives: Type 2 diabetic subjects (T2DM) tend to present atherogenic dyslipidemia (AD), characterized by high triglycerides, low HDL cholesterol (HDL-C) levels, and a preponderance of small LDL particles. Moreover, the number of LDL particles (LDL-P) has been suggested to be a better predictor of cardiovascular risk than LDL cholesterol (LDL-C) in patients with high cardiometabolic risk. We developed a novel advanced lipoprotein test (ALT) based on 2D diffusion-ordered 1H NMR spectroscopy (DOSY) to compare the lipid and lipoprotein profiles of T2DM subjects with and without AD. Methods: First, we used a cohort of 177 subjects to set up a novel ALT based on DOSY. This methodology allows the determination of particle size and particle concentration of different lipoprotein classes and subclasses. These samples were also analyzed with a reference technique for validation purposes. Second, we used a cohort of 323 subjects to define the lipid and lipoprotein profile of AD. To associate these profiles with cardiovascular risk, we measured the intima media thickness (IMT). Results: VLDL particles were higher in T2DM subjects with AD, while medium HDL particles and total HDL-C were decreased. Despite we found no difference in LDL-C levels, mean levels of total LDL-P were higher in T2DM subjects with AD. We further analyzed the cases when these measures were discordant on the basis of population percentiles, i.e., when LDL-C was increased and LDL-P was normal (cholesterol-enriched particles predominate) and when LDL-P was increased but LDL-C was normal (cholesterol-depleted particles predominate). For those individuals with cholesterol-depleted LDL particles, only LDL-P was associated with IMT (r¼0.29). Conclusion: We used a novel ALT that permitted a profound characterization of AD in T2DM subjects. For individuals with cholesterol-depleted LDL particles, the LDL-attributable atherosclerotic risk was associated with LDL-P but not with LDL-C. 51 - Novel risk factors and biomarkers EAS-0097. RATIOS OF SERUM EICOSAPENTAENOIC (EPA) AND DOCOSAHEXAENOIC (DHA) ACID TO ARACHIDONIC ACID (AA) AND CORONARY AND AORTIC PLAQUE INSTABILITY Y. Momiyamaa, R. Ohmorib, R. Katoc, H. Taniguchic, F. Ohsuzuc a b
Department of Cardiology, NHO Tokyo Medical Center, Tokyo, Japan; Faculty of Education, Utsunomiya University, Utsunomiya, Japan; c First
Abstracts / Atherosclerosis 235 (2014) e192–e301
Department of Internal Medicine, National Defense Medical College, Saitama, Japan Objectives: Low EPA/AA ratio is suggested to be a biomarker for cardiovascular risk. Methods: To elucidate the associations between coronary (myocardial infarction and complex lesions) and aortic (complex plaques) plaque instability and EPA, DHA and AA levels and EPA/AA and DHA/AA ratios, black-blood aortic MRI was performed in 127 patients undergoing coronary angiography. On coronary angiograms, the degree of coronary atherosclerosis was represented as number of stenotic vessels. Complex lesions were defined by Ambrose classification. Regarding MRI, transverse aortic images (9 slices of thoracic, 9 slices of abdominal) were obtained at 12-mm intervals. The degree of aortic atherosclerosis was represented as sum of scores in each slice. Complex plaque was defined as one with irregular surface and thickening >4mm. Serum EPA, DHA and AA levels were measured by gas chromatography. Study patients were divided into tertiles by EPA, DHA, AA levels and EPA/AA and DHA/AA ratios. Results: The prevalence of CAD and the number of stenotic vessels were similar among tertiles of EPA, DHA and AA levels and EPA/AA and DHA/AA ratios. The prevalence of coronary plaque instability tended to be highest in lowest EPA tertile (50%(T1), 37%(T2) and 29%(T3)), lowest DHA tertile (48%(T1), 35%(T2) and 33%(T2)), and highest AA tertile (43%(T1), 30%(T2) and 43%(T3))(P¼NS). Coronary plaque instability was significantly most prevalent in lowest EPA/AA tertile (52%(T1), 35%(T2) and 29%(T3), P<0.05), but the difference among DHA/AA tertiles did not reach statistical significance (48%(T1), 35%(T2) and 33%(T3)). Regarding aortic atherosclerosis, the prevalence of aortic plaques and plaque score were similar among tertiles. The prevalence of complex aortic plaques was not different among tertiles of EPA (17%, 19% and 19%), DHA (14%, 16% and 24%), AA (19%, 12% and 24%), EPA/AA (21%, 14% and 19%) and DHA/AA (19%, 7% and 29%)(P¼NS). Conclusion: Only low EPA/AA ratio was associated with coronary, but not aortic, plaque instability. 51 - Novel risk factors and biomarkers EAS-0672. NUMBER OF CORONARY RISK FACTORS IS ASSOCIATED WITH BLOOD THROMBOGENICITY T. Nemotoa, Y. Uedaa a
Cardiovascular Division, Osaka Police Hospital, Osaka, Japan
Objectives: Increased blood thrombogenicity is considered one of the most important factors that are associated with cardiovascular events, and may play an important role for the onset of ACS. Blood thrombogenicity would be determined by blood rheology, coagulation system, and platelet functions. We examined the association between blood thrombogenicity and the amount of coronary risk factors. Methods: Consecutive patients (n¼898) who received coronary angiography were enrolled from January 2009 to January 2011. Blood thrombogenicity was evaluated by blood vulnerability index (BVI) calculated from the time-volume curve of whole blood run through and occlude the microchannels by thrombus formation in Micro-Channel Array Flow Analyzer (MC-FAN). Coronary risk factors included were hypertension, diabetes mellitus, dyslipidemia, high body mass index, and current smoking. Results: Study patients were male in 640 (71%) patients; were 68 years old in average; had mean body mass index of 24.4; had hypertension in 740 (82%), diabetes mellitus in 382 (43%), dyslipidemia in 725 (81%), and current smoking in 143 (16%) patients. BVI was significantly (p<0.01) higher in the patients with more coronary risk factors. Mean BVI in the patients with each number of risk factors was 2405 (risk factor¼0; n¼28), 2324 (1; n¼111), 2335 (2; n¼263), 2334 (3; n¼294), 2494 (4; n¼185), 2658 (5; n¼17). Conclusion: Blood thrombogenicity was higher in the patients with more coronary risk factors.
e219
51 - Novel risk factors and biomarkers EAS-0730. FOCUS ON RELEASED EXTRACELLULAR MATRIX COMPONENTS FROM CAROTID PLAQUE CORE: INTACT PROTEINS OR FRAGMENTS? S. Rocchicciolia, G. Pelosia, S. Rosinia, N. Ucciferria, M. Marconib, M. Ferrarib, A. Cecchettinic a IFC, Istituto di Fisiologia Clinica-CNR, pisa, Italy; b Unit of Vascular Surgery, University of Pisa, pisa, Italy; c Department of Clinical and Experimental Medicine, University of Pisa, pisa, Italy
Objectives: Carotid plaque rupture, leading to atherothrombosis, is the third most common cause of death and it is responsible for 20% of all strokes. Plaque core-specific molecular factors or fragments that are released into the blood flow, can be identified by proteomics analysis of extracellular matrix and may be exploited as clinically relevant specific biomarkers of vulnerability. Aim of this study was to map proteins and fragmented ECM products from the secretome of complicated carotid plaque specimens. Methods: The secretome profile of atherosclerotic internal carotid artery (ICA) derived from endoarterectomy was obtained by using HPLC coupled with mass spectrometry (LC-MSMS). ICA samples were left for 24 hours at 37 C in a serum free culture medium and a LC-MSMS analysis was carried out on collected secretomes. Additionally, secreted proteins were also analyzed to identify fragmented ECM proteins. Immunohistochemistry and histology analyses were performed to plaque core. Results: The LC-MSMS approach enabled the identification of 150 ECM and ECM associated proteins. Of relevance it was the observation that apo(A) and apo(E) were manly fragmented, indicating a strong activity of MMPs into plaque core. Proteoglycans and collagens were also identified and their fragmentation indicates an intense intraplaque enzyme activity, relatable to impending hemorrhage and/or rupture. Conclusion: An optimized workflow, allowing the first detailed matrix protein profile of carotid plaque secretome, may assist and improve biomarker discovery of molecular factors specifically related to disease complication. The proportion between intact protein and its fragments into the ECM plaque core could represent a quantitative indirect measure of intralesional protease activity and therefore provide a clinically novel and potentially more reliable index of rupture risk for vulnerable plaques. 51 - Novel risk factors and biomarkers EAS-0143. LIPOPROTEIN-ASSOCIATED PHOSPHOLIPASE A2 SERUM LEVELS IN PATIENTS FROM DIFFERENT CATEGORIES OF CARDIOVASCULAR RISK A. Semenovaa, D. Nozadzea, I. Sergienkoa, T. Vlasikb, V. Kukharchuka a Atherosclerosis Department, Russian Cardiology Research Complex, Moscow, Russia; b Laboratory of Cell Engineering, Russian Cardiology Research Complex, Moscow, Russia
Objectives: The aim was to compare the lipoprotein-associated phospholipase A2 (Lp-PLA2) serum levels in patients from different cardiovascular risk categories. Methods: 519 patients from Moscow prospective study database were divided into 4 cardiovascular risk categories according to present clinical recommendations (low, moderate, high, very high). Blood samples were taken for the Lp-PLA2 mass and activity levels determination. The serum levels of total cholesterol (TC), low-density lipoprotein-cholesterol (LDLC), high-density lipoprotein-cholesterol (HDL-C), triglycerides (TG), lipoprotein (a) (Lp(a)), high sensitive C-reactive protein (hsCRP) and uric acid were also detected. Results: After preliminary analysis the results were more prominent with the exclusion of patients who received statins and patients with diabetes