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512 ETHNIC DIFFERENCES IN CIRCULATING MARKERS OF ANGIOGENESIS AND THEIR ASSOCIATION WITH CARDIOVASCULAR RISK FACTORS AND PERIPHERAL ARTERIAL DISEASE
79th EAS Congress
Atherosclerosis Supplements 12, no. 1 (2011) 13–184
Conclusion: in our patients, the strong association between platelet count and PAD was independent of the ferritin levels and the inflammatory background. 511 HIGH LIPOPROTEIN (A) IN CHILDREN OF PATIENTS WITH PREMATURE CORONARY HEART DISEASE. RELATION TO OWN AND PARENTAL RISK FACTORS M. Konnov, L. Dobordzhginidze, A. Deev, N. Gratsiansky. Center for Atherosclerosis, Institute of Physico-Chemical Medicine, Moscow, Russia Purpose: To elucidate associations between high level of lipoprotein(a) [Lp(a)] in children of patients with premature (onset <55 years, men; <60 years, women) coronary heart disease (PCHD) with their own and parental characteristics. Methods: We examined members of 133 families: 122 probands, their 95 consorts, 177 children aged 5−34 years. Characteristics studied included demographics, standard risk factors (RF), apoB, apoA1, fibrinogen, plasminogen activator inhibitor-1, plasminogen, alpha-2 antiplasmin, antithrombin-III, proteinC, serum glucose, insulin, homeostasis model assessment of insulin resistance, glucose tolerance, presence of diabetes, atherogenic dyslipidemia (high TG + low HDL-C) (ADLP), metabolic syndrome. High Lp(a) was defined as 30 mg/dl. Predictors were selected by sex, age adjusted logistic regression (inivariate with subsequent multivariate analysis). Associations were assessed separately in younger and adult children. Results: Lp(a) was high in 21/83 children aged 5−17 years. Characteristics independently associated with high Lp(a) were apoB (OR 1.03, p = 0.025), plasminogen (1.03, p = 0.027) of children; high Lp(a) (12.3, p = 0.0007), high vs non-high education (5.59, p = 0.017), aDLP (0.16, p = 0.019) of proband; high Lp(a) (8.92, p = 0.0044), apoB (1.03, p = 0.047) of consort. Lp(a) was high in 25/94 children aged 18−34 years. Its independent predictors were own LDL-C (1.71, p = 0.019); high Lp(a) (26.9, p = 0.0001), aDLP (0.13, p = 0.030) of proband; high Lp(a) (13.6, p = 0.0033), LDL-C (3.38, p = 0.014) of consort. Conclusion: High Lp(a) in children of PCHD patients was associated with elevated Lp(a) of both parents. Some other predictors were plausible, while inverse association with parental ADLP required confirmation, and proband’s higher education possibly reflected some unaccounted factors. 512 ETHNIC DIFFERENCES IN CIRCULATING MARKERS OF ANGIOGENESIS AND THEIR ASSOCIATION WITH CARDIOVASCULAR RISK FACTORS AND PERIPHERAL ARTERIAL DISEASE P.C. Bennett1 , S.H. Silverman2 , P.S. Gill3 , A.D. Blann1 , G.Y. Lip1 . 1 Haemostasis, Thrombosis & Vascular Biology Unit, University of Birmingham, 2 Vascular Surgery, Sandwell and West Birmingham Hospitals NHS Trust, 3 Primary Care Clinical Sciences, University of Birmingham, Birmingham, UK Objective: To determine whether ethnic differences exist in circulating markers of angiogenesis (Angiopoietin-1 (Ang-1), Angiopoietin-2 (Ang-2), soluble Tie-2 receptor (sTie-2) and Angiogenin) between South Asians and Blacks and Whites. To determine associations between these markers and cardiovascular risk factors and Peripheral arterial disease (PAD). Patients and Methods: We recruited 255 subjects (86 South Asians, 81 Blacks and 79 Whites). Subjects were separated into symptomatic PAD (radiologically confirmed disease attending intermittent claudication clinics or for vascular surgery), risk factor controls (evidence of at least one cardiovascular risk factor with Ankle Brachial Pressure Index (ABPI) > 1) and healthy volunteers (No cardiovascular risk factors with ABPI > 1). All subjects completed an interviewer led questionnaire, anthrompometric measurements were taken and blood sampling was performed. Enzyme linked immunoassay (ELISA) was used to quantify angiogenic markers. Results: Whites had lower angiogenin concentration than both South Asians and Blacks (p = 0.0217 and p = 0.003 respectively). Angiogenin was higher in diabetics than non-diabetics (p = 0.0338). Ang-1 and Ang-2 were correlated with Age (p = 0.007 and p = 0.006 respectively). Ang-2 was higher overall in subjects with coronary artery disease (p = 0.0176) and PAD (p = 0.0018). The association between Ang-2 and PAD was apparent in both South Asians (p = 0.0084) and Whites (p = 0.0484). Conclusions: Ethnic differences are evident in circulating markers of angiogenesis, which may reflect susceptibility of particular groups to a greater predilection to PAD. Of the angiogenic markers, Ang-2 was higher in symptomatic PAD and its levels increased with advancing disease, reflecting ongoing angiogenesis occurring in the progression of atherosclerosis. 513 BIOMARKERS ASSOCIATED WITH LONG TERM CARDIOVASCULAR EVENTS IN PATIENTS WITH TYPE 2 DIABETES MELLITUS H. Tria Bianco, M.C. Izar, T. Helfenstein, H.R. Fonseca, S.C. Fischer, C.E. Ferreira, S.P. Barbosa, R.M. Povoa, F.A. Fonseca, Gold Investigators. ˜ Paulo, Sao ˜ Paulo, Brazil Medicine, Federal University of Sao Background: Cardiovascular events in patients with diabetes have twice the incidence than in non-diabetic subjects, even after adjustment for classic risk
109
factors. We examined biomarkers that could be associated with cardiovascular events in these patients. Methods: A prospective, multicentre study, evaluated 323 patients of both genders, 35−80 y, from a cohort of type two diabetes (DM2) subjects followed for a period of 10 years (median). High-sensitivity C-reactive protein (immunoturbidimetry), high-sensitivity troponin (immune assay), homocystein (HPLC), and the presence of left ventricle hypertrophy (LVH) on 12-lead ECG (Perugia criteria), were performed at baseline for the occurrence of combined clinical events (acute coronary syndrome, stroke, cardiovascular death and total mortality) in a 10-year follow-up. Cumulative survival curves, analyzed by Logrank/Mantel-Cox test, were compared on basis of baseline biomarkers, categorized as follows (cut-offs): hs-CRP 3 mg/dL, troponin 0.02 mg/L, homocystein 17 micromol/L and presence of LVH. Results: In the 323 patients followed by 10 y, there were 76 events. Previous myocardial infarction (hazard ratio: 68.4, p < 0.0001), LVH (hazard ratio: 9.1, p = 0.03) and troponin (hazard ratio: 5.1, p = 0.024) were associated with higher event rates in 10 years. Higher levels of hs-CRP (hazard ratio: 3.6, p = 0.058) and homocystein (hazard ratio: 3.2, p = 0.075) presented a trend to higher event rate. Conclusions: Previous myocardial infarction and biomarkers of myocardial function identified subgroups of patients with type 2 diabetes at higher risk for cardiovascular events. 514 LOW ANKLE-BRACHIAL INDEX IS ASSOCIATED WITH CHRONIC KIDNEY DISEASE P. Wohlfahrt, J. Bruthans, V. Adamkov ´ a, ´ R. C´ıfkova, ´ The Czech post-MONICA. IKEM, Prague, Czech Republic Introduction: Low ankle brachial index (ABI) is diagnostic for peripheral arterial disease (PAD) and is associated with increased cardiovascular risk. Chronic kidney disease (CKD) is also an important cardiovascular risk factor. Weather asymptomatic PAD in general population is associated with CKD is not clear. The purpose of our study was to assess the association between ABI and CKD. Methods: A total of 837 individuals from the Czech post-MONICA study (a randomly selected 1% representative population sample, aged 54±13.5 years, 47% men) were examined. Individuals were categorized according to ABI to low (<1.0), normal (1.0−1.4), and high (>1.4) ABI groups. Glomerular filtration (GFR) was estimated using MDRD formula, CKD was defined as GFR <60 ml/min/1.73m2 . Results: Among 837 subjects 27 (3.2%) had low and 19 (2.2%) high ABI. Individuals with low ABI had lover GFR than normal ABI individuals (67.3±13.6 vs. 75.4±12.4, p < 0.01), while there was no difference between low and high ABI groups (67.3±13.6 vs. 73.0±8.9, p = 0.28). CKD was more prevalent in individuals with PAD than in normal ABI individuals (28.6% vs. 8.3%, p < 0.01). In a model adjusted for age, sex, hypertension and diabetes, low ABI (OR 1.98, 95% CI 1.21−4.8, p < 0.05) remained independently associated with CKD. Conclusion: Chronic kidney disease is highly prevalent in individuals with asymptomatic peripheral arterial disease among general population suggesting, that renal function needs to be closely monitored in individuals with PAD. 515 SMALL DENSE LDL-CHOLESTEROL IS SUPERIOR TO LDL-CHOLESTEROL FOR DETERMINING SEVERE CORONARY ATHEROSCLEROSIS Y. Meguro1 , Y. Ito1 , S. Koba2 , Y. Yokota2 , T. Hirano3 , Y. Ban2 , F. Tsunoda2 , T. Sato2 , M. Shoji2 , H. Suzuki2 , E. Geshi2 , Y. Kobayashi2 , T. Katagiri2 . 1 Research and Development Department, Denka Seiken Co., Ltd., Niigata, 2 Department of Medicine, Division of Cardiology, 3 Department of Medicine, Division of Diabetes, Metabolism and Endocrinology, Showa University School of Medicine, Tokyo, Japan Background and Aims: The aim of this study is to determine whether small dense LDL-cholesterol (sd-LDL-C) is superior to LDL-C and/or non-lipid biomarkers of coronary heart disease (CHD) progression among non-CHD and stable CHD subjects. Methods: The study enrolled 482 stable CHD patients and 389 non-CHD who were not receiving any lipid-lowering drugs. LDL particle size was determined by gradient gel electrophoresis and sd-LDL-C concentration was measured by a rapid assay with modified heparin-magnesium precipitation method. Results: Both male and female CHD patients had significantly smaller LDL particles and lower large-LDL (Lb LDL)-C concentrations, and significantly higher sd-LDL-C concentrations than the control subjects. LDL-C concentrations were modestly higher and sd-LDL-C concentrations were significantly higher in 258 patients with angiographically documented severe CHD than in the patients with mild CHD irrespective of treatment by LDL-lowering drugs and history of myocardial infarction and/or coronary revascularization. Lb-LDL-C concentrations, in contrast, were similar between the two groups. Multivariate logistic regression analysis revealed that sd-LDL-C levels were significantly associated with severe CHD independently of LDL-C. Conclusion: sd-LDL-C concentration is closely related to the severity independently of classical coronary risk factors. These results suggest that the
Atherosclerosis Supplements 12, no. 1 (2011) 13–184
Conclusion: in our patients, the strong association between platelet count and PAD was independent of the ferritin levels and the inflammatory background. 511 HIGH LIPOPROTEIN (A) IN CHILDREN OF PATIENTS WITH PREMATURE CORONARY HEART DISEASE. RELATION TO OWN AND PARENTAL RISK FACTORS M. Konnov, L. Dobordzhginidze, A. Deev, N. Gratsiansky. Center for Atherosclerosis, Institute of Physico-Chemical Medicine, Moscow, Russia Purpose: To elucidate associations between high level of lipoprotein(a) [Lp(a)] in children of patients with premature (onset <55 years, men; <60 years, women) coronary heart disease (PCHD) with their own and parental characteristics. Methods: We examined members of 133 families: 122 probands, their 95 consorts, 177 children aged 5−34 years. Characteristics studied included demographics, standard risk factors (RF), apoB, apoA1, fibrinogen, plasminogen activator inhibitor-1, plasminogen, alpha-2 antiplasmin, antithrombin-III, proteinC, serum glucose, insulin, homeostasis model assessment of insulin resistance, glucose tolerance, presence of diabetes, atherogenic dyslipidemia (high TG + low HDL-C) (ADLP), metabolic syndrome. High Lp(a) was defined as 30 mg/dl. Predictors were selected by sex, age adjusted logistic regression (inivariate with subsequent multivariate analysis). Associations were assessed separately in younger and adult children. Results: Lp(a) was high in 21/83 children aged 5−17 years. Characteristics independently associated with high Lp(a) were apoB (OR 1.03, p = 0.025), plasminogen (1.03, p = 0.027) of children; high Lp(a) (12.3, p = 0.0007), high vs non-high education (5.59, p = 0.017), aDLP (0.16, p = 0.019) of proband; high Lp(a) (8.92, p = 0.0044), apoB (1.03, p = 0.047) of consort. Lp(a) was high in 25/94 children aged 18−34 years. Its independent predictors were own LDL-C (1.71, p = 0.019); high Lp(a) (26.9, p = 0.0001), aDLP (0.13, p = 0.030) of proband; high Lp(a) (13.6, p = 0.0033), LDL-C (3.38, p = 0.014) of consort. Conclusion: High Lp(a) in children of PCHD patients was associated with elevated Lp(a) of both parents. Some other predictors were plausible, while inverse association with parental ADLP required confirmation, and proband’s higher education possibly reflected some unaccounted factors. 512 ETHNIC DIFFERENCES IN CIRCULATING MARKERS OF ANGIOGENESIS AND THEIR ASSOCIATION WITH CARDIOVASCULAR RISK FACTORS AND PERIPHERAL ARTERIAL DISEASE P.C. Bennett1 , S.H. Silverman2 , P.S. Gill3 , A.D. Blann1 , G.Y. Lip1 . 1 Haemostasis, Thrombosis & Vascular Biology Unit, University of Birmingham, 2 Vascular Surgery, Sandwell and West Birmingham Hospitals NHS Trust, 3 Primary Care Clinical Sciences, University of Birmingham, Birmingham, UK Objective: To determine whether ethnic differences exist in circulating markers of angiogenesis (Angiopoietin-1 (Ang-1), Angiopoietin-2 (Ang-2), soluble Tie-2 receptor (sTie-2) and Angiogenin) between South Asians and Blacks and Whites. To determine associations between these markers and cardiovascular risk factors and Peripheral arterial disease (PAD). Patients and Methods: We recruited 255 subjects (86 South Asians, 81 Blacks and 79 Whites). Subjects were separated into symptomatic PAD (radiologically confirmed disease attending intermittent claudication clinics or for vascular surgery), risk factor controls (evidence of at least one cardiovascular risk factor with Ankle Brachial Pressure Index (ABPI) > 1) and healthy volunteers (No cardiovascular risk factors with ABPI > 1). All subjects completed an interviewer led questionnaire, anthrompometric measurements were taken and blood sampling was performed. Enzyme linked immunoassay (ELISA) was used to quantify angiogenic markers. Results: Whites had lower angiogenin concentration than both South Asians and Blacks (p = 0.0217 and p = 0.003 respectively). Angiogenin was higher in diabetics than non-diabetics (p = 0.0338). Ang-1 and Ang-2 were correlated with Age (p = 0.007 and p = 0.006 respectively). Ang-2 was higher overall in subjects with coronary artery disease (p = 0.0176) and PAD (p = 0.0018). The association between Ang-2 and PAD was apparent in both South Asians (p = 0.0084) and Whites (p = 0.0484). Conclusions: Ethnic differences are evident in circulating markers of angiogenesis, which may reflect susceptibility of particular groups to a greater predilection to PAD. Of the angiogenic markers, Ang-2 was higher in symptomatic PAD and its levels increased with advancing disease, reflecting ongoing angiogenesis occurring in the progression of atherosclerosis. 513 BIOMARKERS ASSOCIATED WITH LONG TERM CARDIOVASCULAR EVENTS IN PATIENTS WITH TYPE 2 DIABETES MELLITUS H. Tria Bianco, M.C. Izar, T. Helfenstein, H.R. Fonseca, S.C. Fischer, C.E. Ferreira, S.P. Barbosa, R.M. Povoa, F.A. Fonseca, Gold Investigators. ˜ Paulo, Sao ˜ Paulo, Brazil Medicine, Federal University of Sao Background: Cardiovascular events in patients with diabetes have twice the incidence than in non-diabetic subjects, even after adjustment for classic risk
109
factors. We examined biomarkers that could be associated with cardiovascular events in these patients. Methods: A prospective, multicentre study, evaluated 323 patients of both genders, 35−80 y, from a cohort of type two diabetes (DM2) subjects followed for a period of 10 years (median). High-sensitivity C-reactive protein (immunoturbidimetry), high-sensitivity troponin (immune assay), homocystein (HPLC), and the presence of left ventricle hypertrophy (LVH) on 12-lead ECG (Perugia criteria), were performed at baseline for the occurrence of combined clinical events (acute coronary syndrome, stroke, cardiovascular death and total mortality) in a 10-year follow-up. Cumulative survival curves, analyzed by Logrank/Mantel-Cox test, were compared on basis of baseline biomarkers, categorized as follows (cut-offs): hs-CRP 3 mg/dL, troponin 0.02 mg/L, homocystein 17 micromol/L and presence of LVH. Results: In the 323 patients followed by 10 y, there were 76 events. Previous myocardial infarction (hazard ratio: 68.4, p < 0.0001), LVH (hazard ratio: 9.1, p = 0.03) and troponin (hazard ratio: 5.1, p = 0.024) were associated with higher event rates in 10 years. Higher levels of hs-CRP (hazard ratio: 3.6, p = 0.058) and homocystein (hazard ratio: 3.2, p = 0.075) presented a trend to higher event rate. Conclusions: Previous myocardial infarction and biomarkers of myocardial function identified subgroups of patients with type 2 diabetes at higher risk for cardiovascular events. 514 LOW ANKLE-BRACHIAL INDEX IS ASSOCIATED WITH CHRONIC KIDNEY DISEASE P. Wohlfahrt, J. Bruthans, V. Adamkov ´ a, ´ R. C´ıfkova, ´ The Czech post-MONICA. IKEM, Prague, Czech Republic Introduction: Low ankle brachial index (ABI) is diagnostic for peripheral arterial disease (PAD) and is associated with increased cardiovascular risk. Chronic kidney disease (CKD) is also an important cardiovascular risk factor. Weather asymptomatic PAD in general population is associated with CKD is not clear. The purpose of our study was to assess the association between ABI and CKD. Methods: A total of 837 individuals from the Czech post-MONICA study (a randomly selected 1% representative population sample, aged 54±13.5 years, 47% men) were examined. Individuals were categorized according to ABI to low (<1.0), normal (1.0−1.4), and high (>1.4) ABI groups. Glomerular filtration (GFR) was estimated using MDRD formula, CKD was defined as GFR <60 ml/min/1.73m2 . Results: Among 837 subjects 27 (3.2%) had low and 19 (2.2%) high ABI. Individuals with low ABI had lover GFR than normal ABI individuals (67.3±13.6 vs. 75.4±12.4, p < 0.01), while there was no difference between low and high ABI groups (67.3±13.6 vs. 73.0±8.9, p = 0.28). CKD was more prevalent in individuals with PAD than in normal ABI individuals (28.6% vs. 8.3%, p < 0.01). In a model adjusted for age, sex, hypertension and diabetes, low ABI (OR 1.98, 95% CI 1.21−4.8, p < 0.05) remained independently associated with CKD. Conclusion: Chronic kidney disease is highly prevalent in individuals with asymptomatic peripheral arterial disease among general population suggesting, that renal function needs to be closely monitored in individuals with PAD. 515 SMALL DENSE LDL-CHOLESTEROL IS SUPERIOR TO LDL-CHOLESTEROL FOR DETERMINING SEVERE CORONARY ATHEROSCLEROSIS Y. Meguro1 , Y. Ito1 , S. Koba2 , Y. Yokota2 , T. Hirano3 , Y. Ban2 , F. Tsunoda2 , T. Sato2 , M. Shoji2 , H. Suzuki2 , E. Geshi2 , Y. Kobayashi2 , T. Katagiri2 . 1 Research and Development Department, Denka Seiken Co., Ltd., Niigata, 2 Department of Medicine, Division of Cardiology, 3 Department of Medicine, Division of Diabetes, Metabolism and Endocrinology, Showa University School of Medicine, Tokyo, Japan Background and Aims: The aim of this study is to determine whether small dense LDL-cholesterol (sd-LDL-C) is superior to LDL-C and/or non-lipid biomarkers of coronary heart disease (CHD) progression among non-CHD and stable CHD subjects. Methods: The study enrolled 482 stable CHD patients and 389 non-CHD who were not receiving any lipid-lowering drugs. LDL particle size was determined by gradient gel electrophoresis and sd-LDL-C concentration was measured by a rapid assay with modified heparin-magnesium precipitation method. Results: Both male and female CHD patients had significantly smaller LDL particles and lower large-LDL (Lb LDL)-C concentrations, and significantly higher sd-LDL-C concentrations than the control subjects. LDL-C concentrations were modestly higher and sd-LDL-C concentrations were significantly higher in 258 patients with angiographically documented severe CHD than in the patients with mild CHD irrespective of treatment by LDL-lowering drugs and history of myocardial infarction and/or coronary revascularization. Lb-LDL-C concentrations, in contrast, were similar between the two groups. Multivariate logistic regression analysis revealed that sd-LDL-C levels were significantly associated with severe CHD independently of LDL-C. Conclusion: sd-LDL-C concentration is closely related to the severity independently of classical coronary risk factors. These results suggest that the