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210 The number of very early endothelial progenitor cell colonies correlates with atherosclerosis burden in acute coronary syndromes
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Abstracts
Canadian Cardiovascular Society (CCS) CCS163 Poster INSIGHTS INTO DISEASE MECHANISMS AND MANAGEMENT OF CVD Monday, October 24, 2011 209 CIRCULATING CD28- LYMPHOCYTES ARE ASSOCIATED WITH CEREBROVASCULAR SYMPTOMATOLOGY, SEX, AND CAROTID PLAQUE TEXTURE RJ Doonan, E Hitschfeld, M Genest, S Chatur, C Tsoukas, SS Daskalopoulou
CD28- T-cells are found in greater amounts in patients with cerebrovascular symptomatology and in men. This suggests a role for CD28- T-cells in the development of unstable carotid plaques and the pathogenesis of cerebrovascular disease, which is in line with previous studies that investigated coronary events. Furthermore, even in this small sample size we found significant inverse associations between circulating CD28- Tcells and carotid plaque heterogeneity and positively associated with plaque area. Further studies including assessment of plaque structure on histology are currently being performed by our group to confirm these results.
Montréal, Québec BACKGROUND: Circulating CD28- T-cells have previously been
found to be higher in patients with myocardial infarction and to be associated with carotid intima-media thickness. However, the association between CD28- T-cells and cerebrovascular events or carotid plaque have never been investigated. Furthermore, whether there are sex differences in circulating CD28- T-cell levels as well as association with carotid plaque texture (heterogeneity), assessed on ultrasound, have yet to be elucidated. METHODS: Symptomatic (n ⫽ 13) and asymptomatic (n ⫽ 7) patients referred for carotid endarterectomy were recruited preoperatively. Information on patient symptomatology and medical history were obtained from a patient interview and medical charts. A fasting blood sample was obtained pre-operatively. Flow cytometry was performed on whole blood using either a CD3, CD4, CD28 or CD3, CD8, CD28 antibody mix (eBioscience, San Diego, United States) and a BD Bioscience (Mississauga, Canada) flow cytometer. Data was acquired as percentage of CD4⫹CD28- and CD8⫹CD28- T-cells. Preoperative ultrasound was performed on each patient by a specifically trained vascular ultrasonographer. Using a commercially available sophisticated software, image brightness normalization and digital image analysis was performed. The software provides 51 different features of both plaque echodensity (brightness) and texture (heterogeneity). Pearson’s correlation coefficients were calculated for image analysis parameters and circulating CD28- T-cell percentages. RESULTS: Symptomatic patients were found to have a higher percentage of CD4⫹CD28- (6.9 ⫾ 7.3 vs. 1.2 ⫾ 0.95%, P ⬍ 0.05) and CD8⫹CD28- T-cells (37.8 ⫾ 25.9 vs. 19.6 ⫾ 11.2%, P ⬍ 0.05). Men also had higher percentages of CD4⫹CD28- (6.9 ⫾ 7.2 vs. 0.98 ⫾ 0.0.42%, P ⬍ 0.05) and CD8⫹CD28- T-cells (41.1 ⫾ 22.5 vs. 10.45 ⫾ 8.45, P ⬍ 0.05). CD4⫹CD28- T-cell percentage was inversely correlated with two parameters of plaque heterogeneity: Spatial Grey Level Dependence Contrast (r ⫽ -0.460, P ⬍ 0.05) and Grey Level Dependence Matrices Contrast (r ⫽ -0.465, P ⬍ 0.05). CD8⫹CD28-T-cell percentage was correlated inversely with Spatial Grey Level Dependence Angular Second Moment (r ⫽ -0.434, P ⬍ 0.05) and positively with plaque area (r ⫽ 0.435, P ⬍ 0.05). CONCLUSION: This is the first study to show that circulating
210 THE NUMBER OF VERY EARLY ENDOTHELIAL PROGENITOR CELL COLONIES CORRELATES WITH ATHEROSCLEROSIS BURDEN IN ACUTE CORONARY SYNDROMES R Kouz, C Berry, E Rheaume, G Brand, A Kernaleguen, J Grégoire, R Ibrahim, J Lespérance, P L’Allier, S Noble, P Meyer, M Guertin, J Tardif Montréal, Québec BACKGROUND: Endothelial progenitor cells (EPCs) have been shown to promote repair of damaged endothelium and to promote neovascularization in ischemic areas. While EPCs have been shown to correlate with numbers of cardiovascular risk factors, their association to atherosclerosis burden has been disputed. Previous studies did not use an objective measure of atherosclerosis like quantitative coronary angiography (QCA) and have not linked atherosclerosis burden with very early EPCs. METHODS: EPCs were measured by flow cytometry (CD34⫹/ KDR⫹) and by colony forming units (CFU) after 4 days of culture. QCA was used to assess the cumulative coronary stenosis score, which is calculated by adding all percent diameter stenoses. RESULTS: We studied 160 patients, 105 presenting with an acute coronary syndrome and 55 presenting with stable angina. Mean age was 59 years, with 8% diabetics and 80% men. EPC CFU, but not EPC counts by flow cytometry, were inversely correlated with the cumulative coronary stenosis score (respectively r ⫽ -0.224, P ⫽ 0.004 and r ⫽ -0.102, P ⫽ 0.265). The relationship was observed in patients presenting with an acute coronary syndrome (n ⫽ 105: EPC CFU r ⫽ -0.343 P ⬍ 0.001 and r ⫽ -0.186 P ⫽ 0.099 for EPC count) but not in the stable angina population (n ⫽ 55: EPC CFU r ⫽ 0.112, P ⫽ 0.418, EPC count r ⫽ 0.017, P ⫽ 0.918). In a multivariate analysis of all patients, EPC CFU was the only predictor (P ⬍ 0.05) of the cumulative coronary stenosis score in a model that included known cardiovascular risk factors (age, gender, diabetes, hypertension, dyslipidemia, BMI, angina, prior MI). CONCLUSION: This is the first report of an association between an objective QCA measurement of atherosclerosis burden and very early EPC CFU counts. The association is independent of traditional cardiovascular risk factors and is seen in patients presenting with an acute coronary syndrome.
Abstracts
Canadian Cardiovascular Society (CCS) CCS163 Poster INSIGHTS INTO DISEASE MECHANISMS AND MANAGEMENT OF CVD Monday, October 24, 2011 209 CIRCULATING CD28- LYMPHOCYTES ARE ASSOCIATED WITH CEREBROVASCULAR SYMPTOMATOLOGY, SEX, AND CAROTID PLAQUE TEXTURE RJ Doonan, E Hitschfeld, M Genest, S Chatur, C Tsoukas, SS Daskalopoulou
CD28- T-cells are found in greater amounts in patients with cerebrovascular symptomatology and in men. This suggests a role for CD28- T-cells in the development of unstable carotid plaques and the pathogenesis of cerebrovascular disease, which is in line with previous studies that investigated coronary events. Furthermore, even in this small sample size we found significant inverse associations between circulating CD28- Tcells and carotid plaque heterogeneity and positively associated with plaque area. Further studies including assessment of plaque structure on histology are currently being performed by our group to confirm these results.
Montréal, Québec BACKGROUND: Circulating CD28- T-cells have previously been
found to be higher in patients with myocardial infarction and to be associated with carotid intima-media thickness. However, the association between CD28- T-cells and cerebrovascular events or carotid plaque have never been investigated. Furthermore, whether there are sex differences in circulating CD28- T-cell levels as well as association with carotid plaque texture (heterogeneity), assessed on ultrasound, have yet to be elucidated. METHODS: Symptomatic (n ⫽ 13) and asymptomatic (n ⫽ 7) patients referred for carotid endarterectomy were recruited preoperatively. Information on patient symptomatology and medical history were obtained from a patient interview and medical charts. A fasting blood sample was obtained pre-operatively. Flow cytometry was performed on whole blood using either a CD3, CD4, CD28 or CD3, CD8, CD28 antibody mix (eBioscience, San Diego, United States) and a BD Bioscience (Mississauga, Canada) flow cytometer. Data was acquired as percentage of CD4⫹CD28- and CD8⫹CD28- T-cells. Preoperative ultrasound was performed on each patient by a specifically trained vascular ultrasonographer. Using a commercially available sophisticated software, image brightness normalization and digital image analysis was performed. The software provides 51 different features of both plaque echodensity (brightness) and texture (heterogeneity). Pearson’s correlation coefficients were calculated for image analysis parameters and circulating CD28- T-cell percentages. RESULTS: Symptomatic patients were found to have a higher percentage of CD4⫹CD28- (6.9 ⫾ 7.3 vs. 1.2 ⫾ 0.95%, P ⬍ 0.05) and CD8⫹CD28- T-cells (37.8 ⫾ 25.9 vs. 19.6 ⫾ 11.2%, P ⬍ 0.05). Men also had higher percentages of CD4⫹CD28- (6.9 ⫾ 7.2 vs. 0.98 ⫾ 0.0.42%, P ⬍ 0.05) and CD8⫹CD28- T-cells (41.1 ⫾ 22.5 vs. 10.45 ⫾ 8.45, P ⬍ 0.05). CD4⫹CD28- T-cell percentage was inversely correlated with two parameters of plaque heterogeneity: Spatial Grey Level Dependence Contrast (r ⫽ -0.460, P ⬍ 0.05) and Grey Level Dependence Matrices Contrast (r ⫽ -0.465, P ⬍ 0.05). CD8⫹CD28-T-cell percentage was correlated inversely with Spatial Grey Level Dependence Angular Second Moment (r ⫽ -0.434, P ⬍ 0.05) and positively with plaque area (r ⫽ 0.435, P ⬍ 0.05). CONCLUSION: This is the first study to show that circulating
210 THE NUMBER OF VERY EARLY ENDOTHELIAL PROGENITOR CELL COLONIES CORRELATES WITH ATHEROSCLEROSIS BURDEN IN ACUTE CORONARY SYNDROMES R Kouz, C Berry, E Rheaume, G Brand, A Kernaleguen, J Grégoire, R Ibrahim, J Lespérance, P L’Allier, S Noble, P Meyer, M Guertin, J Tardif Montréal, Québec BACKGROUND: Endothelial progenitor cells (EPCs) have been shown to promote repair of damaged endothelium and to promote neovascularization in ischemic areas. While EPCs have been shown to correlate with numbers of cardiovascular risk factors, their association to atherosclerosis burden has been disputed. Previous studies did not use an objective measure of atherosclerosis like quantitative coronary angiography (QCA) and have not linked atherosclerosis burden with very early EPCs. METHODS: EPCs were measured by flow cytometry (CD34⫹/ KDR⫹) and by colony forming units (CFU) after 4 days of culture. QCA was used to assess the cumulative coronary stenosis score, which is calculated by adding all percent diameter stenoses. RESULTS: We studied 160 patients, 105 presenting with an acute coronary syndrome and 55 presenting with stable angina. Mean age was 59 years, with 8% diabetics and 80% men. EPC CFU, but not EPC counts by flow cytometry, were inversely correlated with the cumulative coronary stenosis score (respectively r ⫽ -0.224, P ⫽ 0.004 and r ⫽ -0.102, P ⫽ 0.265). The relationship was observed in patients presenting with an acute coronary syndrome (n ⫽ 105: EPC CFU r ⫽ -0.343 P ⬍ 0.001 and r ⫽ -0.186 P ⫽ 0.099 for EPC count) but not in the stable angina population (n ⫽ 55: EPC CFU r ⫽ 0.112, P ⫽ 0.418, EPC count r ⫽ 0.017, P ⫽ 0.918). In a multivariate analysis of all patients, EPC CFU was the only predictor (P ⬍ 0.05) of the cumulative coronary stenosis score in a model that included known cardiovascular risk factors (age, gender, diabetes, hypertension, dyslipidemia, BMI, angina, prior MI). CONCLUSION: This is the first report of an association between an objective QCA measurement of atherosclerosis burden and very early EPC CFU counts. The association is independent of traditional cardiovascular risk factors and is seen in patients presenting with an acute coronary syndrome.