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719 COMPARISON OF THE NEW UNIFIED CRITERIA FOR METABOLIC SYNDROME WITH CONVENTIONAL IDF CRITERIA: RISK FOR DEVELOPING CARDIOVASCULAR DISEASE
79th EAS Congress
Atherosclerosis Supplements 12, no. 1 (2011) 13–184
2. patients with recent ischemic symptoms (within 2 months) had higher YKL40 mRNAlevels in carotid plaque than other patients; 3. in vitro, releasate from activated platelets significantly increased the expression of YKL-40 in THP-1 monocytes and 4. in vitro, YKL-40 increased matrix metalloproteinase-9 expression and activity in THP-1 monocytes. Conclusions: Our findings suggest that YKL-40 might be a marker of plaque instability, potentially reflecting macrophage activation and matrix degradation within the atherosclerotic lesion. 718 STRUCTURE AND CYTOKINE PATTERN OF CAROTID PLAQUES IN ELDERLY PATIENTS H. Grufman1,2 , A. Edsfeldt2 , A. Persson2 , M. Nitulescu2 , M. Nilsson2 , J. Nilsson2 , I. Goncalves1,2 . 1 Department of Cardiology, Skane University Hospital, 2 Experimental Cardiovascular Research Group, Clinical Research ¨ Sweden Center, Clinical Sciences, Lund University, Malmo, Background and Purpose: Age is a strong risk factor for atherosclerotic disease. The purpose of this study is to investigate whether atherosclerotic plaques from elderly have more vulnerable features when compared with those from younger patients both regarding histology and content of chemokines and inflammatory cytokines. We also compared the levels of cytokines in blood between elderly and younger patients. Methods: Carotid plaques were collected from 150 patients, half of which were 70 years or older. On the day before carotid endarterectomy a plasma sample was collected. The most stenotic part of the plaque was used for histology and immunohistochemistry. The rest of the plaque was homogenized. Eotaxin, fractalkine, IL-6, IL-10, IL-12(p70), IL-12(p40), MIP-1beta, PDGFAB/BB, RANTES, VEGF, IFNgamma, TNFalpha, MCP-1, IL-1beta and sCD40L were analyzed in plaque homogenate and plasma. Results: Macrophage content of carotid plaques from patients 70 years and older was significantly higher than in plaques from younger patients. The level of IFNgamma was significantly lower in plaques from elderly. Further, RANTES and MCP-1 were significantly higher in plaques from elderly. Cytokine levels in plasma did not differ between elderly and younger. Conclusion: Atherosclerotic plaques from elderly patients are richer in macrophages, and so possibly more vulnerable than plaques from younger patients. INFgamma is lower in plaques from elderly whereas MCP-1 and RANTES are higher than in the younger. This suggests that elderly patients have more chemoattractant, and less inflammatory ability in their plaques than younger patients. These differences are not reflected in circulating cytokine levels. 719 COMPARISON OF THE NEW UNIFIED CRITERIA FOR METABOLIC SYNDROME WITH CONVENTIONAL IDF CRITERIA: RISK FOR DEVELOPING CARDIOVASCULAR DISEASE J. Suwa. Preventive Medicine, St. Luke’s International Hospital, Tokyo, Japan Aims: The new unified criteria (NUC) for metabolic syndrome (MS) was proposed in 2009 by several major organizations. Central obesity was not an obligatory component in the new criteria. The aim of this study was to compare NUC with conventional IDF (International Diabetes Federation) criteria with regard to the risk of developing cardiovascular disease (CVD). Methods: 13,839 individuals (6813 men, mean age 49.2 years; 7026 women, mean age 47.5 years) who underwent annual health checks at our institution in 2002 were enrolled in this retrospective cohort study. Individuals with a history of coronary heart disease (CHD) or stroke or those treated with medications for diabetes, hypertension or dyslipidemia were excluded. Central obesity was defined as waist circumference 90 cm for men, 80 cm for women. Results: Per NUC and IDF criteria respectively, the prevalence of MS was 14.7% versus 9.0% in men, and 6.2% versus 4.4% in women. During followup (mean 4.0±1.4 years), there were 108 new CVD diagnoses (71 men, 37 women; 58 CHDs, 50 strokes). Age-adjusted multivariable hazard ratios for CVD associated with MS were 1.612 (95% CI; 0.924–2.812, p = 0.093) and 2.389 (95% CI; 1.308–4.362, p = 0.005) in men, per NUC and IDF criteria respectively. For women, these were 1.911 (95% CI; 0.821–4.450, p = 0.133) and 2.501 (95% CI; 1.026–6.096, p = 0.044) respectively. Conclusions: Our findings suggest that conventional IDF criteria including central obesity as an obligatory component is more closely associated with cardiovascular risk than the NUC. 720 CEREBRAL MICROBLEEDS IS ASSOCIATED WITH ARTERIAL CALCIFICATION K.-Y. Park1 , P.-W. Chung2 . 1 Neurology, Chung-Ang University Hospital, 2 Kangbuk Samsung Hospital, Seoul, Republic of Korea Background: The aim of the present study was to investigate the association between cerebral artery calcification and cerebral microbleeds (CMB). Methods: We identified 110 consecutive patients with acute ischemic stroke who underwent CT angiography within seven days of symptom onset.
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Calcifications of the intracranial internal carotid artery (I-ICA) were graded and CMBs were also counted according to their location. Correlation between I-ICA calcification and CMB was tested by using Pearson’s correlation and multiple linear regression analysis. Results: The stroke patients ranged in age from 26 to 95 years (67±13 years). I-ICA calcification was found in 162 arteries (73.6%) and CMB was detected in 26 patients (23.6%). Univariate analysis revealed that I-ICA calcification was correlated with total CMB (correlation coefficient r = 0.41, p < 0.001) and CMB in deep gray matter (r = 0.339, p < 0.001), but not with CMB in lobar region (r = 0.139, p = 0.053). Multiple linear regression showed that I-ICA calcification was independent determinants of CMB in deep gray matter (B = 0.291, p = 0.043), but not total CMB (B = 0.313, p = 0.466) and CMB in lobar region (B = −0.377, p = 0.363). Conclusions: I-ICA calcification is common in patients with acute ischemic stroke and is an independent predictor for CMB in the deep gray matter rather than total CMB or CMB in lobar region. 721 RELATIONSHIP BETWEEN PLASMA ADMA LEVELS AND CAROTID NARROWING DEGREE IN CAROTID ENDARTERECTOMY (CEA) PATIENTS A. Zinellu1 , M.A. Casu2 , F. Piredda2 , P. Porcu3 , L. Deiana1 , C. Carru1 . 1 Biomedical Sciences, 2 Chair of Vascular Surgery, University of Sassari, Sassari, Italy, 3 Department of Cardiac Surgery, Grenoble University Hospital, CHU La Tronche, Grenoble, France The possibility that ADMA may contributes to the development of restenosis in CEA patients is consistent with the ability of this molecule to provoke endothelial damage via NOS (nitric oxide synthase) inhibition. We investigate about the relationship between plasma ADMA levels and carotid narrowing in a cohort of patients underwent to surgical intervention of CEA. A total of 64 consecutive patients (15 women, 49 men) aged 45−78, has been enrolled for the study. Between 6−96 months after CEA intervention patients has been reviewed. Arginine, ADMA and symmetric dimethylarginine (SDMA) were measured by capillary electrophoresis. Morphological analysis and stenosis evaluation of the carotid measurement was performed by duplex ultra-sonography. Mean values for ADMA, SDMA and Arg in patients were respectively 0.599±0.109 mmol/L, 0.484±147 mmol/L and 84.9±21.3 mmol/L. During the follow-up period the patients showed a normal carotid narrowing degree (CND=27.9%) and only one subject presented clinical evidence of restenosis (CND > 70%). We found a positive correlation between CND% and plasma ADMA concentrations (r = 0.37, P = 0.003). No relationship were found between CND% and SDMA or Arg. Stepwise multiple linear regression with CND% as the dependent variable and ADMA, age, MFI, creatinine and smoking as independent variables confirmed that ADMA was positively associated with CND% (t = 2.34, P = 0.023) whilst age was inversely related to CND% (t = −2.50, p < 0.015). In conclusion we found that asymmetric dimethylarginine is correlated to the carotid narrowing degree after CEA intervention, thus suggesting a possible role of ADMA in events which bring to restenosis in subjects undergone this surgery treatment. 722 COMPREHENSIVE METABOLIC PROFILING IN RISK STRATIFICATION OF HUMAN CAROTID ATHEROSCLEROSIS J. Shalhoub1 , P.A. Vorkas2 , C. Monaco3 , E.J. Want2 , M.R. Lewis2 , A.H. Davies1 , E. Holmes2 , J.K. Nicholson2 . 1 Academic Section of Vascular Surgery, 2 Biomolecular Medicine, 3 Cytokine Biology of Atherosclerosis, Imperial College London, London, UK Introduction: Biomarker or biomarker ‘signature’ discovery is sought for the risk stratification of atherosclerosis. To date, human atherosclerotic tissue has not been subject to metabolic profiling, which further has the potential to elucidate disease mechanisms. Objectives: To investigate metabolic profiling in the context of human carotid atherosclerosis and it’s utility in separating high-risk from low-risk atherosclerosis. Methods: Ten carotid plaques (5 asymptomatic, 5 responsible for recent focal neurological symptoms pertaining the ipsilateral anterior cerebral circulation) were fresh frozen for batch metabolite extraction. Both polar and organic extracts were subject to nuclear magnetic resonance (NMR; Bruker 600MHz; NOESY and CPMG sequences) and ultra performance liquid chromatography mass spectrometry (UPLC-MS; Q-TOF Premier, Waters Technologies). Two biological replicates were analysed for each specimen. Principal components analysis (PCA) was employed using Matlab for NMR and SIMCA-P+ for UPLCMS data. Results: PCA from aqueous and organic phase extracts analysed using NMR did not provide clear separation between the symptomatic and asymptomatic groups. Organic phase NMR PCA presented a clear group comprising two samples with both their biological replicates. PCA from the organic phase UPLC-MS data provided good separation between the two groups.
Atherosclerosis Supplements 12, no. 1 (2011) 13–184
2. patients with recent ischemic symptoms (within 2 months) had higher YKL40 mRNAlevels in carotid plaque than other patients; 3. in vitro, releasate from activated platelets significantly increased the expression of YKL-40 in THP-1 monocytes and 4. in vitro, YKL-40 increased matrix metalloproteinase-9 expression and activity in THP-1 monocytes. Conclusions: Our findings suggest that YKL-40 might be a marker of plaque instability, potentially reflecting macrophage activation and matrix degradation within the atherosclerotic lesion. 718 STRUCTURE AND CYTOKINE PATTERN OF CAROTID PLAQUES IN ELDERLY PATIENTS H. Grufman1,2 , A. Edsfeldt2 , A. Persson2 , M. Nitulescu2 , M. Nilsson2 , J. Nilsson2 , I. Goncalves1,2 . 1 Department of Cardiology, Skane University Hospital, 2 Experimental Cardiovascular Research Group, Clinical Research ¨ Sweden Center, Clinical Sciences, Lund University, Malmo, Background and Purpose: Age is a strong risk factor for atherosclerotic disease. The purpose of this study is to investigate whether atherosclerotic plaques from elderly have more vulnerable features when compared with those from younger patients both regarding histology and content of chemokines and inflammatory cytokines. We also compared the levels of cytokines in blood between elderly and younger patients. Methods: Carotid plaques were collected from 150 patients, half of which were 70 years or older. On the day before carotid endarterectomy a plasma sample was collected. The most stenotic part of the plaque was used for histology and immunohistochemistry. The rest of the plaque was homogenized. Eotaxin, fractalkine, IL-6, IL-10, IL-12(p70), IL-12(p40), MIP-1beta, PDGFAB/BB, RANTES, VEGF, IFNgamma, TNFalpha, MCP-1, IL-1beta and sCD40L were analyzed in plaque homogenate and plasma. Results: Macrophage content of carotid plaques from patients 70 years and older was significantly higher than in plaques from younger patients. The level of IFNgamma was significantly lower in plaques from elderly. Further, RANTES and MCP-1 were significantly higher in plaques from elderly. Cytokine levels in plasma did not differ between elderly and younger. Conclusion: Atherosclerotic plaques from elderly patients are richer in macrophages, and so possibly more vulnerable than plaques from younger patients. INFgamma is lower in plaques from elderly whereas MCP-1 and RANTES are higher than in the younger. This suggests that elderly patients have more chemoattractant, and less inflammatory ability in their plaques than younger patients. These differences are not reflected in circulating cytokine levels. 719 COMPARISON OF THE NEW UNIFIED CRITERIA FOR METABOLIC SYNDROME WITH CONVENTIONAL IDF CRITERIA: RISK FOR DEVELOPING CARDIOVASCULAR DISEASE J. Suwa. Preventive Medicine, St. Luke’s International Hospital, Tokyo, Japan Aims: The new unified criteria (NUC) for metabolic syndrome (MS) was proposed in 2009 by several major organizations. Central obesity was not an obligatory component in the new criteria. The aim of this study was to compare NUC with conventional IDF (International Diabetes Federation) criteria with regard to the risk of developing cardiovascular disease (CVD). Methods: 13,839 individuals (6813 men, mean age 49.2 years; 7026 women, mean age 47.5 years) who underwent annual health checks at our institution in 2002 were enrolled in this retrospective cohort study. Individuals with a history of coronary heart disease (CHD) or stroke or those treated with medications for diabetes, hypertension or dyslipidemia were excluded. Central obesity was defined as waist circumference 90 cm for men, 80 cm for women. Results: Per NUC and IDF criteria respectively, the prevalence of MS was 14.7% versus 9.0% in men, and 6.2% versus 4.4% in women. During followup (mean 4.0±1.4 years), there were 108 new CVD diagnoses (71 men, 37 women; 58 CHDs, 50 strokes). Age-adjusted multivariable hazard ratios for CVD associated with MS were 1.612 (95% CI; 0.924–2.812, p = 0.093) and 2.389 (95% CI; 1.308–4.362, p = 0.005) in men, per NUC and IDF criteria respectively. For women, these were 1.911 (95% CI; 0.821–4.450, p = 0.133) and 2.501 (95% CI; 1.026–6.096, p = 0.044) respectively. Conclusions: Our findings suggest that conventional IDF criteria including central obesity as an obligatory component is more closely associated with cardiovascular risk than the NUC. 720 CEREBRAL MICROBLEEDS IS ASSOCIATED WITH ARTERIAL CALCIFICATION K.-Y. Park1 , P.-W. Chung2 . 1 Neurology, Chung-Ang University Hospital, 2 Kangbuk Samsung Hospital, Seoul, Republic of Korea Background: The aim of the present study was to investigate the association between cerebral artery calcification and cerebral microbleeds (CMB). Methods: We identified 110 consecutive patients with acute ischemic stroke who underwent CT angiography within seven days of symptom onset.
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Calcifications of the intracranial internal carotid artery (I-ICA) were graded and CMBs were also counted according to their location. Correlation between I-ICA calcification and CMB was tested by using Pearson’s correlation and multiple linear regression analysis. Results: The stroke patients ranged in age from 26 to 95 years (67±13 years). I-ICA calcification was found in 162 arteries (73.6%) and CMB was detected in 26 patients (23.6%). Univariate analysis revealed that I-ICA calcification was correlated with total CMB (correlation coefficient r = 0.41, p < 0.001) and CMB in deep gray matter (r = 0.339, p < 0.001), but not with CMB in lobar region (r = 0.139, p = 0.053). Multiple linear regression showed that I-ICA calcification was independent determinants of CMB in deep gray matter (B = 0.291, p = 0.043), but not total CMB (B = 0.313, p = 0.466) and CMB in lobar region (B = −0.377, p = 0.363). Conclusions: I-ICA calcification is common in patients with acute ischemic stroke and is an independent predictor for CMB in the deep gray matter rather than total CMB or CMB in lobar region. 721 RELATIONSHIP BETWEEN PLASMA ADMA LEVELS AND CAROTID NARROWING DEGREE IN CAROTID ENDARTERECTOMY (CEA) PATIENTS A. Zinellu1 , M.A. Casu2 , F. Piredda2 , P. Porcu3 , L. Deiana1 , C. Carru1 . 1 Biomedical Sciences, 2 Chair of Vascular Surgery, University of Sassari, Sassari, Italy, 3 Department of Cardiac Surgery, Grenoble University Hospital, CHU La Tronche, Grenoble, France The possibility that ADMA may contributes to the development of restenosis in CEA patients is consistent with the ability of this molecule to provoke endothelial damage via NOS (nitric oxide synthase) inhibition. We investigate about the relationship between plasma ADMA levels and carotid narrowing in a cohort of patients underwent to surgical intervention of CEA. A total of 64 consecutive patients (15 women, 49 men) aged 45−78, has been enrolled for the study. Between 6−96 months after CEA intervention patients has been reviewed. Arginine, ADMA and symmetric dimethylarginine (SDMA) were measured by capillary electrophoresis. Morphological analysis and stenosis evaluation of the carotid measurement was performed by duplex ultra-sonography. Mean values for ADMA, SDMA and Arg in patients were respectively 0.599±0.109 mmol/L, 0.484±147 mmol/L and 84.9±21.3 mmol/L. During the follow-up period the patients showed a normal carotid narrowing degree (CND=27.9%) and only one subject presented clinical evidence of restenosis (CND > 70%). We found a positive correlation between CND% and plasma ADMA concentrations (r = 0.37, P = 0.003). No relationship were found between CND% and SDMA or Arg. Stepwise multiple linear regression with CND% as the dependent variable and ADMA, age, MFI, creatinine and smoking as independent variables confirmed that ADMA was positively associated with CND% (t = 2.34, P = 0.023) whilst age was inversely related to CND% (t = −2.50, p < 0.015). In conclusion we found that asymmetric dimethylarginine is correlated to the carotid narrowing degree after CEA intervention, thus suggesting a possible role of ADMA in events which bring to restenosis in subjects undergone this surgery treatment. 722 COMPREHENSIVE METABOLIC PROFILING IN RISK STRATIFICATION OF HUMAN CAROTID ATHEROSCLEROSIS J. Shalhoub1 , P.A. Vorkas2 , C. Monaco3 , E.J. Want2 , M.R. Lewis2 , A.H. Davies1 , E. Holmes2 , J.K. Nicholson2 . 1 Academic Section of Vascular Surgery, 2 Biomolecular Medicine, 3 Cytokine Biology of Atherosclerosis, Imperial College London, London, UK Introduction: Biomarker or biomarker ‘signature’ discovery is sought for the risk stratification of atherosclerosis. To date, human atherosclerotic tissue has not been subject to metabolic profiling, which further has the potential to elucidate disease mechanisms. Objectives: To investigate metabolic profiling in the context of human carotid atherosclerosis and it’s utility in separating high-risk from low-risk atherosclerosis. Methods: Ten carotid plaques (5 asymptomatic, 5 responsible for recent focal neurological symptoms pertaining the ipsilateral anterior cerebral circulation) were fresh frozen for batch metabolite extraction. Both polar and organic extracts were subject to nuclear magnetic resonance (NMR; Bruker 600MHz; NOESY and CPMG sequences) and ultra performance liquid chromatography mass spectrometry (UPLC-MS; Q-TOF Premier, Waters Technologies). Two biological replicates were analysed for each specimen. Principal components analysis (PCA) was employed using Matlab for NMR and SIMCA-P+ for UPLCMS data. Results: PCA from aqueous and organic phase extracts analysed using NMR did not provide clear separation between the symptomatic and asymptomatic groups. Organic phase NMR PCA presented a clear group comprising two samples with both their biological replicates. PCA from the organic phase UPLC-MS data provided good separation between the two groups.