- Email: [email protected]
Strongly increasing prevalence of hypertension by increasing overweight in children and adolescents
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Abstracts / Atherosclerosis 252 (2016) e197ee235
determined. Univariate statistics and Partial Least-Squares DiscriminantAnalysis (PLSDA) were conducted to identify a WMLs metabolic profile. Results: HDL-triglycerides levels were significantly increased in the WMLs group (p¼0.023). Cross-Validated PLS-DA models of the NMR and clinical data showed a significant classification capability between groups (p<0.0001). A pro-atherogenic metabolic profile was related to WMLs, presenting an increase of total cholesterol, total triglycerides, LDL and VLDL (cholesterol and triglycerides) and HDL-triglycerides. Patients without WMLs presented a more favourable profile, characterized by increased HDL-cholesterol and LDL-size. In the WMLs group, the proatherogenic pattern was positively associated with inflammatory and oxidative stress parameters. Conclusions: Triglycerides-enrichment of HDL and elevated inflammatory parameters are known to impair reverse cholesterol transport, and might be linked with small-vessel disease by a diminished cholesterol efflux in the subendothelial space of cerebral microvessels.
Methods: PON1 activity was determined by zymogram method that combines gradient gel electrophoresis to separate HDL subclasses and measuring the activity of PON1 in the same gel. This pilot study included 20 patients with chronic kidney disease, 20 patients on hemodialysis and 20 healthy subjects as control. Results: We found significantly decreased PON1 activity in renal patients compared with control (p<0.005). Small HDL3 subclass was significantly higher in renal patients when compared to healthy subjects (p<0.001). Conversely, large HDL2 subclass dominated in controls (p<0.001). In accordance to this, in dialysis patients PON1 activity was higher at HDL3 subclass (p<0.05), while the healthy subjects showed significantly higher PON1 activity at the HDL2 subclass (p<0.05). Conclusions: Chronic kidney disease and hemodialysis lead to changes in the composition and structure of HDL, which causes changes in the distribution of PON1 activity between different subclasses.
EAS16-0910, HYPERTENSION, LIVER AND CHRONIC RENAL DISEASE. ALTERED INFLAMMATORY PARAMETERS AND CHEMERIN LEVELS AFTER RENAL TRANSPLANTATION
EAS16-0530, HYPERTENSION, LIVER AND CHRONIC RENAL DISEASE. HEPATIC TRANSCRIPTOMIC SIGNATURES IN A MOUSE MODEL OF THE METABOLIC SYNDROME
} rincz 1, E.V. Varga 1, A. Szentpe teri 1, P. R. Szentimrei 1, M. Harangi 1, H. Lo € p 1, I. Seres 2, G. Paragh 1. 1 University of Debrecen Faculty of Medicine, Fülo Institute of Medicine, Hungary; 2 Univesity of Debrecen, Department of Medicine, Debrecen, Hungary
D. Nasias 1, 2, I. Evangelakos 1,2, D. Kardassis 1, 2. 1 Foundation for Research and Technology-Hellas, Institute of Molecular Biology and Biotechnology, Heraklion, Greece; 2 Laboratory of Biochemistry, Department of Basic Sciences-University of Crete Medical School, Heraklion, Greece
Objectives: Enhanced lipid peroxidation and dyslipidemia are well known cardiovascular risk factors in end-stage kidney disease. Human serum paraoxonase-1 (PON1) is the most potent HDL-associated antioxidant enzyme and decreased PON1 activity has been reported in renal transplant patients. Chemerin is a recently discovered adipokine with potent proinflammatory effects; however, the impact of renal transplantation on chemerin levels has not been studied yet. Therefore, we aimed to determine lipid and inflammatory parameters as well as chemerin levels in patients undergoing renal transplantation.
Objectives: The metabolic syndrome (MetS) is a cluster of clinical disorders such as dyslipidemia, diabetes and obesity which are associated with increased risk for cardiovascular disease. The etiology of MetS is poorly understood and effective therapeutics are urgently needed. Our main objective was to monitor global changes in the expression of genes in the liver of ApoE3L-CETP mice that were used as a model of MetS.
Methods: Lipid parameters (total cholesterol, LDL-C, HDL-C, triglyceride), inflammatory markers (CRP, procalcitonin) and chemerin levels were measured immediately before and 6 months after renal allograft transplantation in 32 renal transplanted patients (10 females, 22 males). Serum chemerin levels were measured by ELISA, while PON1 paraoxonase and arylesterase activites were determined spectrophotometrically. Results: PON1 paraoxonase and arylesterase activities increased, while serum chemerin and procalcitonin levels decreased significantly after transplantation. Also, significant positive correlations were found between BMI and chemerin concentrations and between LDL-C and chemerin levels before transplantation, respectively. We could not find significant changes in serum lipid and CRP levels. Conclusions: Although there were no quantitative alterations in the serum lipid parameters, renal transplantation significantly improved the HDL-associated antioxidant capacity and attenuated the chronic inflammation in patients with end-stage renal failure.
EAS16-0891, HYPERTENSION, LIVER AND CHRONIC RENAL DISEASE. RENAL DISEASE IS ASSOCIATED WITH MODIFIED PON1 DISTRIBUTION AT HDL SUBCLASSES M. Miljkovic 1, J. Kotur-Stevuljevic 1, A. Stefanovic 1, J. Vekic 1, A. Zeljkovic 1, T. Gojkovic 1, S. Simic-Ogrizovic 2, V. SpasojevicKalimanovska 1, Z. Jelic-Ivanovic 1. 1 Faculty of Pharmacy, Department of Medical biochemistry, Belgrade, Serbia; 2 Clinical Center of Serbia, Clinic of Nephrology, Belgrade, Serbia Objectives: Cardiovascular diseases which present the main cause of death in renal patients are followed with changed composition of lipoproteins. Since the paraoxonase-1(PON1) is mostly attached to HDL, the aim of current study was to investigate whether failure of kidney function leads to alternations in the distribution of PON1 between different HDL subclass.
Methods: Male mice were fed either a High (HFD) or a Low (LFD) Fat Diet for different time periods. Liver RNA was analyzed on Affymetrix Mouse Gene 2.0 ST arrays followed by bioinformatical analysis. Mice were monitored for body weight, total plasma cholesterol and HDL-C levels, blood glucose levels and specific circulating miRNAs. Results: Microarray analysis revealed 126 differentially expressed genes in response to HFD in the 4weeks-group and 219 transcripts in the 8weeks-group. Network analysis revealed that in the 4weeks and the 8weeks groups the peroxisome proliferator activated receptor gamma (Pparg) and the leptin receptor (Lepr) respectively are involved in most interactions with the genes that are clustered in the top network (Energy Production, Lipid Metabolism, Small Molecule Biochemistry). miRNAs previously correlated to metabolic diseases were also found to be differentially expressed in the serum of HFD versus LFD fed mice especially in the longer periods of HFD administration. Conclusions: Our findings are indicative of characteristic hepatic gene and plasma miRNA signatures during the MetS development in ApoE3L-CETPmice which could be exploited further for diagnostic or therapeutic purposes.
EAS16-0392, HYPERTENSION, LIVER AND CHRONIC RENAL DISEASE. STRONGLY INCREASING PREVALENCE OF HYPERTENSION BY INCREASING OVERWEIGHT IN CHILDREN AND ADOLESCENTS G.M. Haas 1, E. Liepold 1, T. Bertsch 2, P. Schwandt 3. 1 Atherosclerosis Prevention Institute, Prevention, Munich, Nuremberg, Germany; 2 General Hospital Nuremberg Paracelsus Medical University, Institute of Clinical Chemistry and Laboratory Medicine, Nuremberg, Germany; 3 Atherosclerosis Prevention Institute and Ludwig-Maximilians University Munich, Prevention, Munich, Nuremberg, Germany Objectives: Because the risk of comorbidities rises steeply at the extremes of body mass index (BMI) we explored associations between weight status and hypertension in female German children and adolescents.
Abstracts / Atherosclerosis 252 (2016) e197ee235
Methods: We measured systolic (SBP) and diastolic (DBP) blood pressure using a non-mercury sphygmomanometer in 10 723 German female children and adolescents aged 3-18 years in cross-sectional surveys of the PEP Family Heart Study Nuremberg. Overweight and obesity were classified into overweight (BMI 85th to <95th percentile), class I obesity (BMI95th to <120 percentile of the 95th percentile), class II obesity (BMI 120% to <140% of the 95th), class III obesity (BMI 140% of the 95th percentile). Results: Among 10 723 (85.7%) non-overweight female youths 5.4% had hypertension (SBP and or DBP 95th percentile) whereas 14.9% of the overweight females were hypertensive. The prevalence of hypertension was nearly twice in grade I obesity (25.5%) and increased further to 36.9% in grade II obesity and to 56% in grade III. Among males with grade III obesity the prevalence was even higher (58.3%).Compared with overweights (odds ratio 2.4; 95% CI 2.0-2.9) the risk of hypertension was 6.2 fold (95% CI 5.1-7.5). Conclusions: An accurate classification of youth with severe obesity may improve the care of this young female population. This is of importance because of the steep increase of severe obesity (over 70% in the USA % since 1994) contrasting the levelling off of overall overweight and obesity in children and adolescents.
EAS16-0021, HYPERTENSION, LIVER AND CHRONIC RENAL DISEASE. ASSOCIATION OF CORONARY ARTERY CALCIFICATION AND ARTERIAL MICRO-CALCIFICATION OF THE VASCULAR ACCESS IN INCIDENT HEMODIALYSIS PATIENTS B.M. Choi, Y.O. Kim, H.C. Song, Y.B. Lee. College of Medicine-The Catholic University of Korea, Department of Internal Medicine, Seoul, Republic of Korea Objectives: Reasons behind increased cardiovascular mortality in arterial micro-calcification (AMC ) are not fully understood, but it is believed that aortic stiffness is a major contributing factor. Whereas, coronary artery calcification (CAC) is quite common in hemodialysis (HD) patients and it is known as predictor of future cardiovascular events and all-cause mortality in HD patients. The aim of this study was to explore the relationship between AMC and CAC in HD patients. Methods: 95 HD patients who received vascular access operation were included. The AMC was diagnosed by pathologic examination of arterial specimen acquired during the operation. All patients underwent a multidetector computed tomography imaging procedure and coronary artery calcium score (CACS) was calculated. Patients were classified into two groups, according to the CACS, as high (100), in 56 patients, and low (<100), in 39 patients. We compared AMC and several parameters between two groups. Results: Mean age was 65.4 ± 12.7 years and the male gender was 63.2% (n¼60). The incidence of AMC was 55.8% (n¼53). The mean CACS was 456.7±697.2 and distributed from zero to 3880. Patients with high CACS group were older (69.6±9.5 vs. 59.4±14.1, p¼0.007), and showed a significantly higher prevalence of diabetes mellitus (75.0% vs. 53.8%, p¼0.027). High CACS group showed high incidence of AMC compared to low CACS group (71.4% vs. 33.3%, p<0.001). By binary logistic regression, AMC was independently associated with high CACS (OR: 4.228, 95% confidence interval [CI]: 1.513-11.817, p¼0.006). Conclusions: The present study suggests that AMC is closely associated with CAC in incident HD patients.
EAS16-0512, HYPERTENSION, LIVER AND CHRONIC RENAL DISEASE. LIVER DISEASE ALTERS HIGH-DENSITY LIPOPROTEIN COMPOSITION, METABOLISM AND FUNCTION M. Trieb 1, V. Stadlbauer 2, R. Birner-Gruenberger 3, G. Marsche 1. 1 Medical University of Graz, Experimental and Clinical Pharmacology, Graz, Austria; 2 Medical University of Graz, Division of Gastroenterology and Hepatology, Graz, Austria; 3 Medical University of Graz, Institute of Pathology, Graz, Austria
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Objectives: Functional impairment of HDL might contribute to the excess mortality experienced by patients with liver disease, but the effect of cirrhosis on HDL metabolism and function remain elusive. In the present study, we assessed several metrics of function of apoB depleted serum HDL of patients with compensated cirrhosis (n¼59), patients with acutely decompensated cirrhosis (n¼21) and healthy controls (n¼20). Methods: Commercial kits were used to assess serum enzyme activities, cholesterol efflux capacity of apoB-depleted serum was assessed using cAMP stimulated RAW264.7 macrophages, arylesterase activity was determined with a photometric assay, endothelial barrier measurements were performed using the Electric Cell-substrate Impedance Sensing system, proteomic profiling of HDL was performed by LC-MS/MS analysis. Results: We observed that sera of cirrhotic patients showed suppressed activities of several enzymes involved in HDL maturation and metabolism. Native gel electrophoresis analyses revealed that cirrhotic serum HDL shifts toward the larger HDL2 subclass. Proteomic assessment of isolated HDL identified several proteins, including apoA-I, apoC-III, apoE, paraoxonase 1 and acute phase serum amyloid A to be significantly altered in cirrhotic patients. With regard to function, these alterations in the composition of isolated HDL were strongly associated with metrics of function of apoB-depleted serum, including cholesterol efflux capability, paraoxonase activity, the ability to inhibit monocyte production of cytokines and endothelial regenerative activities. Conclusions: Alterations in HDL levels, function and composition are linked to several metrics of function of apoB-depleted serum of cirrhotic patients. Our findings may be clinically relevant and improve our ability to monitor cirrhotic patients at high risk.
EAS16-1012, HYPERTENSION, LIVER AND CHRONIC RENAL DISEASE. ENHANCED STATUS OF PROTHROMBOGENESIS AND ITS ASSOCIATION WITH SERUM LDL-C LEVELS IN SUBJECTS WITH FAMILIAL HYPERCHOLESTEROLAEMIA N.A. Mohd Kasim 1, R. Rahmat 1, S. Abdul Razak 1, S. Muid 1, T. Rahman 1, 2, H. Nawawi 1, 2. 1 Universiti Teknologi MARA, Faculty of Medicine, Selangor, Malaysia; 2 Universiti Teknologi MARA, Institute for Pathology-Laboratory and Forensic Medicine I-PPerForM, Selangor, Malaysia Objectives: To compare the biomarkers of prothrombogenesis between subjects with FH and their related unaffected controls(RUC) compared to normal controls(NC), and examine the correlation and association between LDL-c and biomarkers of prothrombogenesis in these subjects. Methods: A total of 360 subjects: 114 FH patients (mean+SD age¼45.8±1.4years, 52.6% females) diagnosed by the Dutch Lipid Clinic Criteria (DLCC), 68 RUC (mean+SD age¼45.8±9.3years, 57.5%females) and 178 NC (mean+SD age¼ 43.7±0.99years, 58.6%females). They were matched for age, gender, ethnicity, smoking status, hypertension and diabetes. Blood samples were analyzed for lipid profiles which run on automated analyser (Integra 400 , Germany), PAI-1, t-PA by ELISA (eBioscience, Austria) while fibrinogen via clotting method (Diagnostic Stago, France) and Lp(a) on immunoassay method( Integra 400, Germany). Results: There were significant increase of PAI-1 (p<0.005), fibrinogen (p<0.001), t-PA (p<0.05), Lp(a) (p<0.001) in FH group compared to NC. The fibrinogen (p<0.001) and Lp(a) (p<0.005) in FH group were found to be significantly elevated compared to RUC. With exception of Lp(a), all prothrombogenic biomarkers in RUC are comparable to NC. There were positive correlation between LDL-c and t-PA (r¼0.132, p<0.05, fibrinogen (r¼0.315, p<0.001), and Lp(a) (r¼0.344, p<0.01). There were significant association between quartiles of LDL-c and quartiles of t-PA (p<0.05), fibrinogen (p<0.001) and Lp(a) (p<0.001). Conclusions: Status of prothrombogenesis is elevated in both FH and RUC compared to NC. In addition, elevated LDL-c levels is associated with enhanced prothrombogenesis. This may be explained by hypercholesterolaemia-induced inflammatory response and endothelial dysfunction leading to enhanced prothrombogenesis and increased risk of coronary events.
Abstracts / Atherosclerosis 252 (2016) e197ee235
determined. Univariate statistics and Partial Least-Squares DiscriminantAnalysis (PLSDA) were conducted to identify a WMLs metabolic profile. Results: HDL-triglycerides levels were significantly increased in the WMLs group (p¼0.023). Cross-Validated PLS-DA models of the NMR and clinical data showed a significant classification capability between groups (p<0.0001). A pro-atherogenic metabolic profile was related to WMLs, presenting an increase of total cholesterol, total triglycerides, LDL and VLDL (cholesterol and triglycerides) and HDL-triglycerides. Patients without WMLs presented a more favourable profile, characterized by increased HDL-cholesterol and LDL-size. In the WMLs group, the proatherogenic pattern was positively associated with inflammatory and oxidative stress parameters. Conclusions: Triglycerides-enrichment of HDL and elevated inflammatory parameters are known to impair reverse cholesterol transport, and might be linked with small-vessel disease by a diminished cholesterol efflux in the subendothelial space of cerebral microvessels.
Methods: PON1 activity was determined by zymogram method that combines gradient gel electrophoresis to separate HDL subclasses and measuring the activity of PON1 in the same gel. This pilot study included 20 patients with chronic kidney disease, 20 patients on hemodialysis and 20 healthy subjects as control. Results: We found significantly decreased PON1 activity in renal patients compared with control (p<0.005). Small HDL3 subclass was significantly higher in renal patients when compared to healthy subjects (p<0.001). Conversely, large HDL2 subclass dominated in controls (p<0.001). In accordance to this, in dialysis patients PON1 activity was higher at HDL3 subclass (p<0.05), while the healthy subjects showed significantly higher PON1 activity at the HDL2 subclass (p<0.05). Conclusions: Chronic kidney disease and hemodialysis lead to changes in the composition and structure of HDL, which causes changes in the distribution of PON1 activity between different subclasses.
EAS16-0910, HYPERTENSION, LIVER AND CHRONIC RENAL DISEASE. ALTERED INFLAMMATORY PARAMETERS AND CHEMERIN LEVELS AFTER RENAL TRANSPLANTATION
EAS16-0530, HYPERTENSION, LIVER AND CHRONIC RENAL DISEASE. HEPATIC TRANSCRIPTOMIC SIGNATURES IN A MOUSE MODEL OF THE METABOLIC SYNDROME
} rincz 1, E.V. Varga 1, A. Szentpe teri 1, P. R. Szentimrei 1, M. Harangi 1, H. Lo € p 1, I. Seres 2, G. Paragh 1. 1 University of Debrecen Faculty of Medicine, Fülo Institute of Medicine, Hungary; 2 Univesity of Debrecen, Department of Medicine, Debrecen, Hungary
D. Nasias 1, 2, I. Evangelakos 1,2, D. Kardassis 1, 2. 1 Foundation for Research and Technology-Hellas, Institute of Molecular Biology and Biotechnology, Heraklion, Greece; 2 Laboratory of Biochemistry, Department of Basic Sciences-University of Crete Medical School, Heraklion, Greece
Objectives: Enhanced lipid peroxidation and dyslipidemia are well known cardiovascular risk factors in end-stage kidney disease. Human serum paraoxonase-1 (PON1) is the most potent HDL-associated antioxidant enzyme and decreased PON1 activity has been reported in renal transplant patients. Chemerin is a recently discovered adipokine with potent proinflammatory effects; however, the impact of renal transplantation on chemerin levels has not been studied yet. Therefore, we aimed to determine lipid and inflammatory parameters as well as chemerin levels in patients undergoing renal transplantation.
Objectives: The metabolic syndrome (MetS) is a cluster of clinical disorders such as dyslipidemia, diabetes and obesity which are associated with increased risk for cardiovascular disease. The etiology of MetS is poorly understood and effective therapeutics are urgently needed. Our main objective was to monitor global changes in the expression of genes in the liver of ApoE3L-CETP mice that were used as a model of MetS.
Methods: Lipid parameters (total cholesterol, LDL-C, HDL-C, triglyceride), inflammatory markers (CRP, procalcitonin) and chemerin levels were measured immediately before and 6 months after renal allograft transplantation in 32 renal transplanted patients (10 females, 22 males). Serum chemerin levels were measured by ELISA, while PON1 paraoxonase and arylesterase activites were determined spectrophotometrically. Results: PON1 paraoxonase and arylesterase activities increased, while serum chemerin and procalcitonin levels decreased significantly after transplantation. Also, significant positive correlations were found between BMI and chemerin concentrations and between LDL-C and chemerin levels before transplantation, respectively. We could not find significant changes in serum lipid and CRP levels. Conclusions: Although there were no quantitative alterations in the serum lipid parameters, renal transplantation significantly improved the HDL-associated antioxidant capacity and attenuated the chronic inflammation in patients with end-stage renal failure.
EAS16-0891, HYPERTENSION, LIVER AND CHRONIC RENAL DISEASE. RENAL DISEASE IS ASSOCIATED WITH MODIFIED PON1 DISTRIBUTION AT HDL SUBCLASSES M. Miljkovic 1, J. Kotur-Stevuljevic 1, A. Stefanovic 1, J. Vekic 1, A. Zeljkovic 1, T. Gojkovic 1, S. Simic-Ogrizovic 2, V. SpasojevicKalimanovska 1, Z. Jelic-Ivanovic 1. 1 Faculty of Pharmacy, Department of Medical biochemistry, Belgrade, Serbia; 2 Clinical Center of Serbia, Clinic of Nephrology, Belgrade, Serbia Objectives: Cardiovascular diseases which present the main cause of death in renal patients are followed with changed composition of lipoproteins. Since the paraoxonase-1(PON1) is mostly attached to HDL, the aim of current study was to investigate whether failure of kidney function leads to alternations in the distribution of PON1 between different HDL subclass.
Methods: Male mice were fed either a High (HFD) or a Low (LFD) Fat Diet for different time periods. Liver RNA was analyzed on Affymetrix Mouse Gene 2.0 ST arrays followed by bioinformatical analysis. Mice were monitored for body weight, total plasma cholesterol and HDL-C levels, blood glucose levels and specific circulating miRNAs. Results: Microarray analysis revealed 126 differentially expressed genes in response to HFD in the 4weeks-group and 219 transcripts in the 8weeks-group. Network analysis revealed that in the 4weeks and the 8weeks groups the peroxisome proliferator activated receptor gamma (Pparg) and the leptin receptor (Lepr) respectively are involved in most interactions with the genes that are clustered in the top network (Energy Production, Lipid Metabolism, Small Molecule Biochemistry). miRNAs previously correlated to metabolic diseases were also found to be differentially expressed in the serum of HFD versus LFD fed mice especially in the longer periods of HFD administration. Conclusions: Our findings are indicative of characteristic hepatic gene and plasma miRNA signatures during the MetS development in ApoE3L-CETPmice which could be exploited further for diagnostic or therapeutic purposes.
EAS16-0392, HYPERTENSION, LIVER AND CHRONIC RENAL DISEASE. STRONGLY INCREASING PREVALENCE OF HYPERTENSION BY INCREASING OVERWEIGHT IN CHILDREN AND ADOLESCENTS G.M. Haas 1, E. Liepold 1, T. Bertsch 2, P. Schwandt 3. 1 Atherosclerosis Prevention Institute, Prevention, Munich, Nuremberg, Germany; 2 General Hospital Nuremberg Paracelsus Medical University, Institute of Clinical Chemistry and Laboratory Medicine, Nuremberg, Germany; 3 Atherosclerosis Prevention Institute and Ludwig-Maximilians University Munich, Prevention, Munich, Nuremberg, Germany Objectives: Because the risk of comorbidities rises steeply at the extremes of body mass index (BMI) we explored associations between weight status and hypertension in female German children and adolescents.
Abstracts / Atherosclerosis 252 (2016) e197ee235
Methods: We measured systolic (SBP) and diastolic (DBP) blood pressure using a non-mercury sphygmomanometer in 10 723 German female children and adolescents aged 3-18 years in cross-sectional surveys of the PEP Family Heart Study Nuremberg. Overweight and obesity were classified into overweight (BMI 85th to <95th percentile), class I obesity (BMI95th to <120 percentile of the 95th percentile), class II obesity (BMI 120% to <140% of the 95th), class III obesity (BMI 140% of the 95th percentile). Results: Among 10 723 (85.7%) non-overweight female youths 5.4% had hypertension (SBP and or DBP 95th percentile) whereas 14.9% of the overweight females were hypertensive. The prevalence of hypertension was nearly twice in grade I obesity (25.5%) and increased further to 36.9% in grade II obesity and to 56% in grade III. Among males with grade III obesity the prevalence was even higher (58.3%).Compared with overweights (odds ratio 2.4; 95% CI 2.0-2.9) the risk of hypertension was 6.2 fold (95% CI 5.1-7.5). Conclusions: An accurate classification of youth with severe obesity may improve the care of this young female population. This is of importance because of the steep increase of severe obesity (over 70% in the USA % since 1994) contrasting the levelling off of overall overweight and obesity in children and adolescents.
EAS16-0021, HYPERTENSION, LIVER AND CHRONIC RENAL DISEASE. ASSOCIATION OF CORONARY ARTERY CALCIFICATION AND ARTERIAL MICRO-CALCIFICATION OF THE VASCULAR ACCESS IN INCIDENT HEMODIALYSIS PATIENTS B.M. Choi, Y.O. Kim, H.C. Song, Y.B. Lee. College of Medicine-The Catholic University of Korea, Department of Internal Medicine, Seoul, Republic of Korea Objectives: Reasons behind increased cardiovascular mortality in arterial micro-calcification (AMC ) are not fully understood, but it is believed that aortic stiffness is a major contributing factor. Whereas, coronary artery calcification (CAC) is quite common in hemodialysis (HD) patients and it is known as predictor of future cardiovascular events and all-cause mortality in HD patients. The aim of this study was to explore the relationship between AMC and CAC in HD patients. Methods: 95 HD patients who received vascular access operation were included. The AMC was diagnosed by pathologic examination of arterial specimen acquired during the operation. All patients underwent a multidetector computed tomography imaging procedure and coronary artery calcium score (CACS) was calculated. Patients were classified into two groups, according to the CACS, as high (100), in 56 patients, and low (<100), in 39 patients. We compared AMC and several parameters between two groups. Results: Mean age was 65.4 ± 12.7 years and the male gender was 63.2% (n¼60). The incidence of AMC was 55.8% (n¼53). The mean CACS was 456.7±697.2 and distributed from zero to 3880. Patients with high CACS group were older (69.6±9.5 vs. 59.4±14.1, p¼0.007), and showed a significantly higher prevalence of diabetes mellitus (75.0% vs. 53.8%, p¼0.027). High CACS group showed high incidence of AMC compared to low CACS group (71.4% vs. 33.3%, p<0.001). By binary logistic regression, AMC was independently associated with high CACS (OR: 4.228, 95% confidence interval [CI]: 1.513-11.817, p¼0.006). Conclusions: The present study suggests that AMC is closely associated with CAC in incident HD patients.
EAS16-0512, HYPERTENSION, LIVER AND CHRONIC RENAL DISEASE. LIVER DISEASE ALTERS HIGH-DENSITY LIPOPROTEIN COMPOSITION, METABOLISM AND FUNCTION M. Trieb 1, V. Stadlbauer 2, R. Birner-Gruenberger 3, G. Marsche 1. 1 Medical University of Graz, Experimental and Clinical Pharmacology, Graz, Austria; 2 Medical University of Graz, Division of Gastroenterology and Hepatology, Graz, Austria; 3 Medical University of Graz, Institute of Pathology, Graz, Austria
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Objectives: Functional impairment of HDL might contribute to the excess mortality experienced by patients with liver disease, but the effect of cirrhosis on HDL metabolism and function remain elusive. In the present study, we assessed several metrics of function of apoB depleted serum HDL of patients with compensated cirrhosis (n¼59), patients with acutely decompensated cirrhosis (n¼21) and healthy controls (n¼20). Methods: Commercial kits were used to assess serum enzyme activities, cholesterol efflux capacity of apoB-depleted serum was assessed using cAMP stimulated RAW264.7 macrophages, arylesterase activity was determined with a photometric assay, endothelial barrier measurements were performed using the Electric Cell-substrate Impedance Sensing system, proteomic profiling of HDL was performed by LC-MS/MS analysis. Results: We observed that sera of cirrhotic patients showed suppressed activities of several enzymes involved in HDL maturation and metabolism. Native gel electrophoresis analyses revealed that cirrhotic serum HDL shifts toward the larger HDL2 subclass. Proteomic assessment of isolated HDL identified several proteins, including apoA-I, apoC-III, apoE, paraoxonase 1 and acute phase serum amyloid A to be significantly altered in cirrhotic patients. With regard to function, these alterations in the composition of isolated HDL were strongly associated with metrics of function of apoB-depleted serum, including cholesterol efflux capability, paraoxonase activity, the ability to inhibit monocyte production of cytokines and endothelial regenerative activities. Conclusions: Alterations in HDL levels, function and composition are linked to several metrics of function of apoB-depleted serum of cirrhotic patients. Our findings may be clinically relevant and improve our ability to monitor cirrhotic patients at high risk.
EAS16-1012, HYPERTENSION, LIVER AND CHRONIC RENAL DISEASE. ENHANCED STATUS OF PROTHROMBOGENESIS AND ITS ASSOCIATION WITH SERUM LDL-C LEVELS IN SUBJECTS WITH FAMILIAL HYPERCHOLESTEROLAEMIA N.A. Mohd Kasim 1, R. Rahmat 1, S. Abdul Razak 1, S. Muid 1, T. Rahman 1, 2, H. Nawawi 1, 2. 1 Universiti Teknologi MARA, Faculty of Medicine, Selangor, Malaysia; 2 Universiti Teknologi MARA, Institute for Pathology-Laboratory and Forensic Medicine I-PPerForM, Selangor, Malaysia Objectives: To compare the biomarkers of prothrombogenesis between subjects with FH and their related unaffected controls(RUC) compared to normal controls(NC), and examine the correlation and association between LDL-c and biomarkers of prothrombogenesis in these subjects. Methods: A total of 360 subjects: 114 FH patients (mean+SD age¼45.8±1.4years, 52.6% females) diagnosed by the Dutch Lipid Clinic Criteria (DLCC), 68 RUC (mean+SD age¼45.8±9.3years, 57.5%females) and 178 NC (mean+SD age¼ 43.7±0.99years, 58.6%females). They were matched for age, gender, ethnicity, smoking status, hypertension and diabetes. Blood samples were analyzed for lipid profiles which run on automated analyser (Integra 400 , Germany), PAI-1, t-PA by ELISA (eBioscience, Austria) while fibrinogen via clotting method (Diagnostic Stago, France) and Lp(a) on immunoassay method( Integra 400, Germany). Results: There were significant increase of PAI-1 (p<0.005), fibrinogen (p<0.001), t-PA (p<0.05), Lp(a) (p<0.001) in FH group compared to NC. The fibrinogen (p<0.001) and Lp(a) (p<0.005) in FH group were found to be significantly elevated compared to RUC. With exception of Lp(a), all prothrombogenic biomarkers in RUC are comparable to NC. There were positive correlation between LDL-c and t-PA (r¼0.132, p<0.05, fibrinogen (r¼0.315, p<0.001), and Lp(a) (r¼0.344, p<0.01). There were significant association between quartiles of LDL-c and quartiles of t-PA (p<0.05), fibrinogen (p<0.001) and Lp(a) (p<0.001). Conclusions: Status of prothrombogenesis is elevated in both FH and RUC compared to NC. In addition, elevated LDL-c levels is associated with enhanced prothrombogenesis. This may be explained by hypercholesterolaemia-induced inflammatory response and endothelial dysfunction leading to enhanced prothrombogenesis and increased risk of coronary events.