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MS183 LONG-TERM EFFECT OF STATINS ON THE RISK OF NEW-ONSET DIABETES – A RETROSPECTIVE COHORT STUDY
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Atherosclerosis Supplements 11, no. 2 (2010) 109–222
MS180 SYSTEM INFLAMMATION MARKERS AND MARKERS OF ENDOTHELIAL FUNCTION IN PATIENTS WITH CORONARY ARTERY DISEASE (UNSTABLE AND STABLE ANGINA) I. Golikova. Atherosclerosis and CAD, NSC “N.D. Strazhesko Institute of Cardiology”, Kyiv, Ukraine Aim: To study the system inflammation markers and endothelial function at the patients with the stable and unstable angina pectoris. Diagnosis of coronary artery disease (CAD) confirmed by the results of coronaroangiography (CAG) with flow of disease. Methods: 100 patients were inspected, middle ages 54.5±3.8 years. Patients were divided onto 2 groups: with the stable flow of disease (n = 64) and unstable angina (n = 36). All patients with the unstable angina had the signs of destruction of atherosclerotic plaque on results of CAG. Results: The reliable increase of level of von Willebrand factor (vWF) was marked for patients with unstable angina comparing with stable patients (91.5±3.4% vs 75.4±2.8%, p < 0.05). A tendency of higher level of endothelin-1 (E-1) was found in patients with unstable angina (11.2±1.1 pg/ml vs 10.6±0.6 pg/m). Significant increase of inflammation markers (C-reactive protein: 20.9±2.7 mg/l vs 12.3±0.8 mg/l, p < 0.05; pro-inflammatory cytokines: IL-6 26.8±2.5 pg/ml vs 13.8±1.0 pg/ml, p < 0.001; IL-8 1745±92 pg/ml vs 1066±86 pg/ml, p < 0.001) and decrease of antyinflammatory cytokines (IL-4 14.7±2.1 pg/ml vs 22.4±1.6 pg/ml, p < 0.05; IL-10 11.0±1.5 pg/ml vs 19.0±1.4 pg/ml, p < 0.05) was exposed at the patients with unstable angina also. Conclusion: At the patients with unstable angina and angiographic signs of destruction of atherosclerotic plaque the increase activity of a system inflammation is marked and more expressed endothelial dysfunction comparing with the patients with the stable CAD. MS181 THE HAPTOGLOBIN 2−2 GENOTYPE IS ASSOCIATED WITH CAROTID ATHEROSCLEROSIS IN 64-YEAR OLD WOMEN WITH ESTABLISHED DIABETES M. Ryndel, C.J. Behre, G. Brohall, U. Prahl, C. Schmidt, G. Bergstrom, ¨ B. Fagerberg, F.J. Olson. Sahlgrenska Center for Cardiovascular and Metabolic Research, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden Introduction: Haptoglobin polymorphism generates three common human genotypes: Hp1−1, Hp2−1 and Hp2−2. Among subjects with diabetes, Hp2−2 is associated with an elevated risk to develop cardiovascular disease. The impact of haptoglobin genotype on subclinical carotid atherosclerosis is not known. We hypothesised that Hp2−2 was associated with increased occurrence of carotid atherosclerosis in subjects with diabetes. Methods: We studied a population-based sample of 64-year old women with diabetes (n = 226), either established diabetes known before study entry (n = 116) or new diabetes detected at study screening. Haptoglobin genotype was determined by PCR. Carotid atherosclerosis was assessed by ultrasound imaging. Results: In the entire diabetes cohort, no differences were observed in carotid intima-media thickness (IMT) or plaque prevalence between the genotype groups. However, among those with established diabetes, Hp2−2 was associated with higher plaque prevalence and larger carotid IMT compared with the Hp2−1 and Hp1−1 genotypes. Common cardiovascular risk factors did not differ between the genotype groups. Conclusions: The Hp2−2 genotype was associated with increased occurrence of subclinical carotid atherosclerosis in 64-year old women with established diabetes. This association was not explained by traditional risk factors for cardiovascular disease. These results extend previous observations that Hp2−2 is associated with clinical cardiovascular disease in diabetes. MS182 NO EVIDENCE OF IMPAIRED ENDOTHELIAL FUNCTION OR ALTERED INFLAMMATORY STATE IN PATIENTS WITH FAMILIAL HYPERCHOLESTEROLEMIA USING STATINS I. Aagnes, A. Hovland, J.H. Flage, O.-L. Brekke, K.T. Lappegard. ˚ Nordland Hospital, Bodø, Norway Object of study: Familial hypercholesterolemia (FH) is associated with an increased risk of premature atherosclerosis; the latter is associated with inflammation and endothelial dysfunction. We wanted to investigate whether endothelial function and inflammation were altered in patients with familial hypercholesterolemia treated with statins. Methods: Patients with FH on statins (n = 14), as well as 11 healthy age- and gender-matched controls without statins participated in the study. Endothelial function was evaluated using the Endo-PAT® system from Itamar Medical Ltd, Caesarea, Israel. Fasting blood samples were drawn and 27 different cytokines, chemokines and growth factors were analyzed in addition to standard laboratory tests. Results: There were no statistically significant differences between the FH group and the control group regarding age, weight, blood pressure or BMI. In vivo measurement of endothelial function was assessed through the EndoPAT-system, and mean reactive hyperemia index (RHI) was 1.58 and 1.93
Memory Stick Presentations
(p = n.s.) in the control and FH groups, respectively. There were no differences between the groups in TNF 32 vs. 26 pg/ml, IL-10 8 vs. 7, IL-6 17 vs. 9, IL-10 8 vs. 7, IL-1b 1.9 vs. 1.2, IL-1ra 88 vs. 101, MCP-1 35 vs. 45 (all p = n.s.) or any of the other inflammatory markers tested. There were no significant differences in HDL-cholesterol, LDL-cholesterol, triglycerides, APO A, APO B, Lp(a), homocysteine, HbA1c, trombocytes and fibrinogen between the groups. Conclusions: Endothelial function and inflammatory state assessed by RHPAT or inflammatory biomarkers were not different in FH patients on statins compared to healthy controls. MS183 LONG-TERM EFFECT OF STATINS ON THE RISK OF NEW-ONSET DIABETES − A RETROSPECTIVE COHORT STUDY G.-P. Jong1 , L. Tien2 , T. Ma3 . 1 Division of Cardiology, Armed Forces Taichung General Hospital, 2 Central Region Branch, Bureau of National Health Insurance, 3 Department of the Health Service Management, China Medical University, Taichung, Taiwan R.O.C. Statins have been linked to new-onset diabetes (NOD); however, data on the effect of these drugs on the development of NOD in hyperlipidemic patients has not been well determined. We aimed to investigate the association between statins and NOD. This was a retrospective cohort study performed using data from claim forms provided to the central region branch of the Bureau of National Health Insurance in Taiwan from January 2004 to December 2008. Prescriptions for statins before the index date were retrieved from a prescription database. We estimated the hazards ratios (HRs) of NOD associated with statins use; nondiabetic subjects served as the reference group. A total of 1250 NOD cases were identified in 19014 hyperlipidemic patients during the study period. The risk of NOD after adjusting sex and age was higher among users of lovastatins (HR, 1.22; 95% confidence interval (CI), 1.07–1.38) than among non-users. Patients who take fluvaststins (HR, 0.61; 95% CI, 0.44–0.84) are at a lower risk of developing NOD than non-users. Pravastatins, simvastatins, and atorvastatins were not associated with risk of NOD. The results of this study suggest that hyperlipidemic patients who take fluvaststins are at lower risk of NOD. Lovastatins were associated with a significant increase in the risk of NOD. MS184 ADULTHOOD TELEVISION VIEWING RELATES INDEPENDENTLY TO CARDIOMETABOLIC RISK PROFILE IN EARLY MIDDLE AGE E. Stamatakis1 , M. Hamer1 , G. Mishra1,2 . 1 Epidemiology & Public Health, University College London, 2 Medical Research Council, London, UK Introduction: There is little research examining the longitudinal associations of sedentary behaviour and cardiovascular risk. Objective: To examine the independent associations between TV viewing in early adulthood and cardiometabolic risk in middle age. Design: The study sample comprised 5629 members (2683 men) of the 1958 British Birth Cohort. TV watching/exercise frequency were measured at age 23 and daily TV and weekly moderate to vigorous physical activity (MVPA) at age 44, as well as 15 biological cardiometabolic risk factors. Factor analysis revealed three risk factor components (explaining 57% of the risk variance: a metabolic (C1: triglycerides, HDL, BMI, waist, blood pressure), a haemostatic/inflammatory (C2: fibrinogen, von Willebrand factor, d-dimer, c-reactive protein), and a cholesterol (C3: total cholesterol, LDL). Results: TV at age 23 showed strong multivariable-adjusted associations with C1 (: Generalized linear model coefficient: 0.26, 95% CI: 0.16 to 0.37, p < 0.001), C2 (0.20, 0.9 to 0.32, p < 0.001), but not with C3 (0.05, −0.17 to 0.1, p = 0.9). For C1 and C2, associations remained strong following adjustments for physical activity and TV watching at age 44 (C1: 0.17, 0.01 to 0.29, p < 0.001; C2: 0.13, 0.02 to 0.25, p = 0.01). Among physically active participants, TV watching had linear associations with C1 (0.14, 0.02 to 0.25, p = 0.02) and C2 (0.23, 0.11 to 0.35, p < 0.001). Conclusions: TV watching during early to mid adulthood was associated independently with the metabolic and haemostatic risk factor profiles at age 44. MS185 TF AND TFPI POLYMORPHISMS IN CORONARY HEART DISEASE AND DIABETES TYPE 2 1 ˚ Pettersen1 , S. Akra ˚ T. Opstad1 , A.A. , T. Weiss1 , H. Arnesen1,2 , I. Seljeflot1,2 , Center for Clinical Heart Research. 1 Department of Cardiology, Center for Clinical Heart Research, Oslo University Hospital, Ulleval, 2 University of Oslo, Oslo, Norway Introduction: Tissue factor (TF) and its endogenous inhibitor (TFPI) are the main regulators of the initiation of the coagulation process, important in atherothrombosis. Objectives: To compare the frequency of six known single nucleotide polymorphisms (SNPs) in the genes coding for TF and TFPI in CHD patients as compared to healthy individuals. Genotypes and phenotypes were evaluated with special emphasis on diabetes and gender differences in the CHD population.
Atherosclerosis Supplements 11, no. 2 (2010) 109–222
MS180 SYSTEM INFLAMMATION MARKERS AND MARKERS OF ENDOTHELIAL FUNCTION IN PATIENTS WITH CORONARY ARTERY DISEASE (UNSTABLE AND STABLE ANGINA) I. Golikova. Atherosclerosis and CAD, NSC “N.D. Strazhesko Institute of Cardiology”, Kyiv, Ukraine Aim: To study the system inflammation markers and endothelial function at the patients with the stable and unstable angina pectoris. Diagnosis of coronary artery disease (CAD) confirmed by the results of coronaroangiography (CAG) with flow of disease. Methods: 100 patients were inspected, middle ages 54.5±3.8 years. Patients were divided onto 2 groups: with the stable flow of disease (n = 64) and unstable angina (n = 36). All patients with the unstable angina had the signs of destruction of atherosclerotic plaque on results of CAG. Results: The reliable increase of level of von Willebrand factor (vWF) was marked for patients with unstable angina comparing with stable patients (91.5±3.4% vs 75.4±2.8%, p < 0.05). A tendency of higher level of endothelin-1 (E-1) was found in patients with unstable angina (11.2±1.1 pg/ml vs 10.6±0.6 pg/m). Significant increase of inflammation markers (C-reactive protein: 20.9±2.7 mg/l vs 12.3±0.8 mg/l, p < 0.05; pro-inflammatory cytokines: IL-6 26.8±2.5 pg/ml vs 13.8±1.0 pg/ml, p < 0.001; IL-8 1745±92 pg/ml vs 1066±86 pg/ml, p < 0.001) and decrease of antyinflammatory cytokines (IL-4 14.7±2.1 pg/ml vs 22.4±1.6 pg/ml, p < 0.05; IL-10 11.0±1.5 pg/ml vs 19.0±1.4 pg/ml, p < 0.05) was exposed at the patients with unstable angina also. Conclusion: At the patients with unstable angina and angiographic signs of destruction of atherosclerotic plaque the increase activity of a system inflammation is marked and more expressed endothelial dysfunction comparing with the patients with the stable CAD. MS181 THE HAPTOGLOBIN 2−2 GENOTYPE IS ASSOCIATED WITH CAROTID ATHEROSCLEROSIS IN 64-YEAR OLD WOMEN WITH ESTABLISHED DIABETES M. Ryndel, C.J. Behre, G. Brohall, U. Prahl, C. Schmidt, G. Bergstrom, ¨ B. Fagerberg, F.J. Olson. Sahlgrenska Center for Cardiovascular and Metabolic Research, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden Introduction: Haptoglobin polymorphism generates three common human genotypes: Hp1−1, Hp2−1 and Hp2−2. Among subjects with diabetes, Hp2−2 is associated with an elevated risk to develop cardiovascular disease. The impact of haptoglobin genotype on subclinical carotid atherosclerosis is not known. We hypothesised that Hp2−2 was associated with increased occurrence of carotid atherosclerosis in subjects with diabetes. Methods: We studied a population-based sample of 64-year old women with diabetes (n = 226), either established diabetes known before study entry (n = 116) or new diabetes detected at study screening. Haptoglobin genotype was determined by PCR. Carotid atherosclerosis was assessed by ultrasound imaging. Results: In the entire diabetes cohort, no differences were observed in carotid intima-media thickness (IMT) or plaque prevalence between the genotype groups. However, among those with established diabetes, Hp2−2 was associated with higher plaque prevalence and larger carotid IMT compared with the Hp2−1 and Hp1−1 genotypes. Common cardiovascular risk factors did not differ between the genotype groups. Conclusions: The Hp2−2 genotype was associated with increased occurrence of subclinical carotid atherosclerosis in 64-year old women with established diabetes. This association was not explained by traditional risk factors for cardiovascular disease. These results extend previous observations that Hp2−2 is associated with clinical cardiovascular disease in diabetes. MS182 NO EVIDENCE OF IMPAIRED ENDOTHELIAL FUNCTION OR ALTERED INFLAMMATORY STATE IN PATIENTS WITH FAMILIAL HYPERCHOLESTEROLEMIA USING STATINS I. Aagnes, A. Hovland, J.H. Flage, O.-L. Brekke, K.T. Lappegard. ˚ Nordland Hospital, Bodø, Norway Object of study: Familial hypercholesterolemia (FH) is associated with an increased risk of premature atherosclerosis; the latter is associated with inflammation and endothelial dysfunction. We wanted to investigate whether endothelial function and inflammation were altered in patients with familial hypercholesterolemia treated with statins. Methods: Patients with FH on statins (n = 14), as well as 11 healthy age- and gender-matched controls without statins participated in the study. Endothelial function was evaluated using the Endo-PAT® system from Itamar Medical Ltd, Caesarea, Israel. Fasting blood samples were drawn and 27 different cytokines, chemokines and growth factors were analyzed in addition to standard laboratory tests. Results: There were no statistically significant differences between the FH group and the control group regarding age, weight, blood pressure or BMI. In vivo measurement of endothelial function was assessed through the EndoPAT-system, and mean reactive hyperemia index (RHI) was 1.58 and 1.93
Memory Stick Presentations
(p = n.s.) in the control and FH groups, respectively. There were no differences between the groups in TNF 32 vs. 26 pg/ml, IL-10 8 vs. 7, IL-6 17 vs. 9, IL-10 8 vs. 7, IL-1b 1.9 vs. 1.2, IL-1ra 88 vs. 101, MCP-1 35 vs. 45 (all p = n.s.) or any of the other inflammatory markers tested. There were no significant differences in HDL-cholesterol, LDL-cholesterol, triglycerides, APO A, APO B, Lp(a), homocysteine, HbA1c, trombocytes and fibrinogen between the groups. Conclusions: Endothelial function and inflammatory state assessed by RHPAT or inflammatory biomarkers were not different in FH patients on statins compared to healthy controls. MS183 LONG-TERM EFFECT OF STATINS ON THE RISK OF NEW-ONSET DIABETES − A RETROSPECTIVE COHORT STUDY G.-P. Jong1 , L. Tien2 , T. Ma3 . 1 Division of Cardiology, Armed Forces Taichung General Hospital, 2 Central Region Branch, Bureau of National Health Insurance, 3 Department of the Health Service Management, China Medical University, Taichung, Taiwan R.O.C. Statins have been linked to new-onset diabetes (NOD); however, data on the effect of these drugs on the development of NOD in hyperlipidemic patients has not been well determined. We aimed to investigate the association between statins and NOD. This was a retrospective cohort study performed using data from claim forms provided to the central region branch of the Bureau of National Health Insurance in Taiwan from January 2004 to December 2008. Prescriptions for statins before the index date were retrieved from a prescription database. We estimated the hazards ratios (HRs) of NOD associated with statins use; nondiabetic subjects served as the reference group. A total of 1250 NOD cases were identified in 19014 hyperlipidemic patients during the study period. The risk of NOD after adjusting sex and age was higher among users of lovastatins (HR, 1.22; 95% confidence interval (CI), 1.07–1.38) than among non-users. Patients who take fluvaststins (HR, 0.61; 95% CI, 0.44–0.84) are at a lower risk of developing NOD than non-users. Pravastatins, simvastatins, and atorvastatins were not associated with risk of NOD. The results of this study suggest that hyperlipidemic patients who take fluvaststins are at lower risk of NOD. Lovastatins were associated with a significant increase in the risk of NOD. MS184 ADULTHOOD TELEVISION VIEWING RELATES INDEPENDENTLY TO CARDIOMETABOLIC RISK PROFILE IN EARLY MIDDLE AGE E. Stamatakis1 , M. Hamer1 , G. Mishra1,2 . 1 Epidemiology & Public Health, University College London, 2 Medical Research Council, London, UK Introduction: There is little research examining the longitudinal associations of sedentary behaviour and cardiovascular risk. Objective: To examine the independent associations between TV viewing in early adulthood and cardiometabolic risk in middle age. Design: The study sample comprised 5629 members (2683 men) of the 1958 British Birth Cohort. TV watching/exercise frequency were measured at age 23 and daily TV and weekly moderate to vigorous physical activity (MVPA) at age 44, as well as 15 biological cardiometabolic risk factors. Factor analysis revealed three risk factor components (explaining 57% of the risk variance: a metabolic (C1: triglycerides, HDL, BMI, waist, blood pressure), a haemostatic/inflammatory (C2: fibrinogen, von Willebrand factor, d-dimer, c-reactive protein), and a cholesterol (C3: total cholesterol, LDL). Results: TV at age 23 showed strong multivariable-adjusted associations with C1 (: Generalized linear model coefficient: 0.26, 95% CI: 0.16 to 0.37, p < 0.001), C2 (0.20, 0.9 to 0.32, p < 0.001), but not with C3 (0.05, −0.17 to 0.1, p = 0.9). For C1 and C2, associations remained strong following adjustments for physical activity and TV watching at age 44 (C1: 0.17, 0.01 to 0.29, p < 0.001; C2: 0.13, 0.02 to 0.25, p = 0.01). Among physically active participants, TV watching had linear associations with C1 (0.14, 0.02 to 0.25, p = 0.02) and C2 (0.23, 0.11 to 0.35, p < 0.001). Conclusions: TV watching during early to mid adulthood was associated independently with the metabolic and haemostatic risk factor profiles at age 44. MS185 TF AND TFPI POLYMORPHISMS IN CORONARY HEART DISEASE AND DIABETES TYPE 2 1 ˚ Pettersen1 , S. Akra ˚ T. Opstad1 , A.A. , T. Weiss1 , H. Arnesen1,2 , I. Seljeflot1,2 , Center for Clinical Heart Research. 1 Department of Cardiology, Center for Clinical Heart Research, Oslo University Hospital, Ulleval, 2 University of Oslo, Oslo, Norway Introduction: Tissue factor (TF) and its endogenous inhibitor (TFPI) are the main regulators of the initiation of the coagulation process, important in atherothrombosis. Objectives: To compare the frequency of six known single nucleotide polymorphisms (SNPs) in the genes coding for TF and TFPI in CHD patients as compared to healthy individuals. Genotypes and phenotypes were evaluated with special emphasis on diabetes and gender differences in the CHD population.