- Email: [email protected]
Lipoprotein(a) concentrations and apolipoprotein-E isoforms
Abstracts / Atherosclerosis 241 (2015) e72ee148
in children exposed to Lp(a) hyperlipidemia (Lp(a)-HLP) and high non-HDL cholesterol levels than in those with only one cardiovascular risk factor. We retrospectively studied 47 children, aged 6-17yr (median 10.5), who underwent a noninvasive assessment of subclinical atherosclerosis because of high non-HDL cholesterol (defined as >3.75 mmol/l) and/or high Lp(a) (defined as >300 mg/l) levels. Data on family history of premature atherosclerosis, age, gender, body mass index (BMI) and blood pressure were collected. Biological data (lipid profile, apoB, apoA1 and Lp(a) levels) were measured on the same fasting blood sample. Arterial intima-media thickness (IMT) and flow-mediated dilation (FMD) were assessed by high-resolution ultrasound. We found a positive family history of premature atherosclerosis in 55.3% of our subjects. After adjustment for age and gender, 75% of them had BMI in the normal range. 40.4% had isolated high non-HDL cholesterol, 51.1 % combined high non-HDL cholesterol and Lp(a)-HLP and 8.5 % isolated Lp(a)-HLP. We found a significant positive correlation between Lp(a) levels and IMT, but not with FMD. Surprisingly, the group with isolated Lp(a)-HLP showed the highest IMT measurements, reaching statistical signification. The only variable significantly correlated to FMD was blood pressure. In conclusion, isolated Lp(a)-HLP has a stronger impact on premature atherosclerosis than when combined with hypercholesterolemia in dyslipidemic children. EAS-0574. LIPOPROTEIN (A): CONCENTRATION, ISOFORMS, POLYMORPHISMS AND ASSOCIATION WITH PRECLINICAL ATHEROSCLEROSIS C. Pavanello 1, *, C. Vitali 2, C. Tarlarini 3, S. Penco 3, L. Calabresi 2, G. Mombelli 1, C.R. Sirtori 1. 1 Centro Dislipidemie, A.O. Ospedale Niguarda Ca Granda, Milan, Italy; 2 Dipartimento di Scienze Farmacologiche e degli Studi di Milano, Biomolecolari, Via Balzaretti 9 20133, Universita Milan, Italy; 3 Dipartimento di Medicina di Laboratorio Genetica Medica, Granda, Milan, Italy A.O. Ospedale Niguarda Ca
* Corresponding author. Lipoprotein(a) [Lp(a)] is a plasma lipoprotein consisting of a cholesterolrich LDL particle with one molecule of apolipoprotein B100 and an additional protein, apolipoprotein(a) [apo(a)], attached via a disulfide bond. Its levels remain relatively constant throughout an individual's lifespan and are mainly attributed to genetic variation within the apo(a) gene (LPA). Increased levels of Lp(a) are a risk factor for coronary artery disease. We included 60 subjects, aged between 18 and 75 years, in primary prevention and with Lp(a) > 35 mg/dL. Eligible participants had data for Lp(a) concentrations, LPA kringle IV type 2 (KIV-2) sums of repeats (affecting isoform size) and carrier status for the LPA single-nucleotide polymorphisms rs10455872 and rs3798220 (affecting concentrations in plasma). Lp(a) was quantified by ELISA test and apo(a) isoforms were designated as F, B, S1, S2, S3, S4 according to their relative electrophoretic mobility on SDS-PAGE compared with apoB100. Mean plasmatic Lp(a) level was 117 mg/dL (35-387 mg/dL). We found an inverse correlation with isoform size and Lp(a) concentrations. An association with the presence of the two SNPs (28% of the subjects were carriers of the rs10455872 and 17% of the rs3798220) and elevated Lp(a) levels were also observed. Finally we investigated the association of Lp(a) levels with carotid intimal medial thickness (IMT) as an early marker of atherosclerosis and we found that IMT increased with increase quartiles of Lp(a) levels (p< 0.05). The results suggest an associations between high serum Lp(a) levels and atherosclerosis.
e101
Complex, Moscow, Russia; 2 Institute of Clinical Cardiology, Russian Cardiology Research and Production Complex, Moscow, Russia
* Corresponding author. Aim: Being a risk factor for atherosclerosis lipoprotein(a) [Lp(a)] may participate in inflammatory reactions in the vessel wall. The aim was to examine the relationship between the blood levels of Lp(a), autoantibodies (AAb) to Lp(a) and the parameters of cell immunity in patients with stable CHD. Methods: 104 men with different stages of coronary atherosclerosis according to CAG were enrolled. Group 1 had intact coronary arteries. Group 2 and Group 3 had undergone coronary stenting; in Group 2 no coronary atherosclerosis progression was found and Group 3 had disease progression in non-invaded coronary arteries (new stenosis above 50%). Group 4 had multivessel coronary disease. Lp(a) and AAb levels were determined by intralaboratory ELISA kit, lipids were measured by commercial kits. Lymphocyte subsets (CD4þFoxP3þTregs and CD4þIL17þTh17) were counted in PBMC using direct immunofluorescence and flow cytometry, lymphocyte activation marker sCD25 in serum via Immulite. Results: The Lp(a) level was significantly higher in Group 4 (38.3±8.5 mg/ dL) compare Group 1 (12.3±3.0 mg/dL), p Conclusion: The identified patterns may indicate the participation of Lp(a) in autoimmune inflammation in atherosclerosis. EAS-0791. LIPOPROTEIN(A) AND SMALL DENSE LOW DENSITY LIPOPROTEIN SUBFRACTIONS AS CARDIOVASCULAR RISK FACTORS O. Afanasieva 1, E. Utkina 1, N. Artemieva 2, M. Ezhov 2, *, Y. Matchin 2, I. Adamova 1, S. Pokrovsky 1. 1 Institute of Experimental Cardiology, Russian Cardiology Research and Production Complex, Moscow, Russia; 2 Institute of Clinical Cardiology, Russian Cardiology Research and Production Complex, Moscow, Russia
* Corresponding author. Aim: To examine the relationship of lipoprotein(a) [Lp(a)] and lipoprotein subfractions with cardiovascular risk in patients with and without coronary artery disease. Methods: 228 patients on statins medication (73% men) and undergoing CAG were included in retrospective study. The Lp(a) concentration was measured by ELISA non-sensitive to apo(a) polymorphism. Lipids and lipoprotein subfractions were determined by reagent's kits «Biocon» (Germany) and «Lipoprint® System», (Quantimetrix », USA), respectively. Results: All patients were enrolled into two group according to CAG results: the Group 1 - patients with diseased coronary arteries (n¼190) and Group 2 - with intact vessels (n¼38). Groups differed in the Lp(a) level (61.0±3.5 mg/dL and 33.4±6.9 md/dL, p¼0.002) and small dense LDL (sdLDL) concentration (4.5±0.5 mg/dL and 2.1±0.4 mg/dL, p¼0.03), other parameters were comparable. Lp(a) concentrations correlated with small intermediate density lipoprotein subfraction (IDL-A) (r¼0.15, p Conclusion: Lp(a) is independent risk factor for CHD, sdLDL potentiates the risk of coronary diseases, associated with high Lp(a) level.
EAS-0813. LIPOPROTEIN(A) ISOFORMS
CONCENTRATIONS
AND
APOLIPOPROTEIN-E
E. Waldmann 1, *, R.G. Stark 2, J. Altenhofer 1, K. Henze 1, K.G. Parhofer 1. 1 Medical Department 2, Hospital of the University of Munich €konomie und (LMU), München, Germany; 2 Institut für Gesundheitso Management im Gesundheitswesen, Helmholtz Zentrum, München, Germany
EAS-0753. LP(A), AUTOANTIBODIES TO LP(A) AND MINOR T-CELL SUBPOPULATIONS IN PATIENTS WITH CORONARY ATHEROSCLEROSIS
* Corresponding author.
E. Klesareva 1, E. Pylaeva 2, *, A. Potekhina 2, T. Krasnikova 1, M. Afanasieva 1, V. Masenko 2, T. Arefieva 1, O. Afanasieva 1. 1 Institute of Experimental Cardiology, Russian Cardiology Research and Production
Although lipoprotein(a) is an established risk factor for cardiovascular disease its metabolism is largely unknown. Apolipoprotein E (apoE) is present on many lipoproteins and is an important mediator of lipoprotein metabolism. The various isoforms of apoE (E2, E3, E4) result in 6 common apoE
e102
Abstracts / Atherosclerosis 241 (2015) e72ee148
phenotypes (apoE2/E2; apoE2/E3; apoE2/E4; apoE3/E3; apoE3/E4; apoE4/ E4) with apoE3/E3 being the most common normal variant. It is unclear whether and how the apoE phenotype is associated with lipoprotein(a) concentrations. We evaluated lipoprotein(a) concentrations in subjects with different apoE phenotypes (apoE2/E2: n¼81; apoE2/E3: n¼188; apoE2/E4: n¼58; apoE3/E3: n¼132; apoE3/E4: n¼182; apoE4/E4: n¼68). Using a general linear model we found that the groups differ significantly (p¼0.04) regarding lipoprotein(a) concentration (apoE2/E2: 28±41 (mean±SD) mg/dl; apoE2/E3: 30±53 mg/dl, apoE2/E4:34±54 mg/dl; apoE3/E3: 49±65 mg/dl; apoE3/E4: 41±64 mg/dl; apoE4/E4: 39±51 mg/dl). After adjusting for age, gender, BMI, log-triglyceride, LDL-cholesterol and HDL-cholesterol the association was no longer significant (p¼0.14). In a second step we analyzed the effect of single isoforms on lipoprotein(a) concentrations. We therefore compared any apoE2 (heterozygous or homozygous) vs. any apoE4 vs. apoE3/E3 (phenotype apoE2/E4 was excluded). Although apoE isoforms are overall not significantly associated with lipoprotein(a) (p¼0.10) after adjusting for age, gender, BMI, log- triglycerides, LDL-cholesterol and HDLcholesterol, the apoE2 isoform is associated with significantly lower lipoprotein(a) concentrations compared to E3/E3, (p¼0.03), while apoE4 was not different from E3/E3. These data indicate that apoE may be directly or indirectly involved in the metabolism of lipoprotein(a). The underlying mechanisms remain to be determined. EAS-0862. PLASMA PROPROTEIN CONVERTASE SUBTILISIN/KEXIN TYPE 9 (PCSK9) IS ASSOCIATED WITH LP(A) IN TYPE 2 DIABETIC PATIENTS Y. Nekaies 1, B. Baudin 2, *, M. Sakly 1, N. Attia 1. 1 Research Unit of Integrated Physiology (UR11ES33), University of Carthage Faculty of Sciences of Bizerte, Bizerte, Tunisia; 2 Biochemistry Department, Biology and Pathology Pole Saint-Antoine Hospital and Faculty of Pharmacy Chatenay Malabry, Paris, France
* Corresponding author. Objective: Type 2 diabetes mellitus (T2DM) is associated with elevated plasma apolipoprotein B, Lp(a), triglycerides and reduced HDL-C. The present study was conducted to investigate whether plasma proprotein convertase subtilisin/kexin type 9 (PCSK9), a regulator of LDL-receptor (LDLr) expression in hepatocytes, was associated with diabetic dyslipidemia. Methods: We developed a sandwich ELISA using recombinant human PCSK9 protein and a polyclonal antibody pre-coated onto a microplate specific directed against human PCSK9. We measured circulating PCSK9 concentrations in a cohort of patients with T2DM (n ¼ 50) compared to an age- and sex-matched control group (n¼50). Plasma apolipoprotein B, Lp(a) triglycerides, LDL-C, HDL-C and LDL-r were measured in both groups. Results: Plasma PCSK9 levels were significantly elevated in T2DM compared to controls (44.61±14.44 and 33.22 ± 11.79 ng/mL respectively, p<0.0001). However, LDL-r levels did not differ between the two groups. No significant correlation of PCSK9 with lipid parameters was found. Remarkably PCSK9 was positively correlated with Lp(a) in whole population (r¼ þ0.254, p<0.0138) and in T2DM group (r¼ þ0287, p¼ 0.0474) but not in controls. Conclusion: Lp(a) levels has been proposed as a contributing factor to the accelerated development of macrovascular complications in T2DM and the synergic effect with PCSK9 may explain the enhanced atherogenicity in type 2 diabetic patients.
TG rich lipoproteins EAS-0857. SERUM APOLIPOPROTEIN B-48 CORRELATES IN PATIENTS WITH FAMILIAL HYPERCHOLESTEROLEMIA M. Walus-Miarka 1, *, B. Idzior-Walus 1, P. Miarka 2, M. Kapusta 3. 1 Metabolic Diseases, Jagiellonian University Medical College, Krakow, Poland; 2 Department of Nephrology, Jagiellonian University Medical College, Krakow, Poland; 3 Department of Biochemistry, Jagiellonian University Medical College, Krakow, Poland
* Corresponding author. Apolipoprotein B-48 (apoB-48) is known to be the only specific marker of intestinal chylomicron particles. In humans ApoB-48 is synthesized only by the intestine. In this study we aimed to examine factors associated with fasting apoB-48 in patients with familial hypercholesterolemia (FH). Material included 130 patients with FH, diagnosed using Simon Broome criteria, 100 adult patients and 30 children and adolescents (< 18 yrs). Apo B48 serum concentration was determined by ELISA, serum lipids by enzymatic methods, carotid intima-media thickness (IMT) by ultrasonography. Mean values of apo B-48 were higher in men than in women (3552.3þ/ 2126.0 vs 2744.0þ/-1473.2 ng/ml, p¼0.03). In the whole group of patients mean apoB-48 correlated significantly with age (-0.19), systolic blood pressure (-0.18), triglycerides (0.27), apo A1 (-0.23) and IMT (-0.21). 74.7% of adult patients were treated with statins. In adult patients apoB-48 correlated with total cholesterol, LDL-C, triglycerides and apoA1 ( r¼ 0.24, 0.24, 0.34, and-0.21 respectively). In FH patients not treated with statins, apoB-48 correlated positively with waist to hip ratio ( r¼0.42). In FH women treated with statins apo B-48 correlated with total, LDL-cholesterol and triglycerides (r ¼ 0.33, 0.36 and 0.40 respectively). Only in FH men not treated with statins strong positive correlation between apo B-48 and IMT was found ( r¼.75), while in men treated with statin, unexpectedly, negative correlation was observed ( r¼ -0.47). The results of the study suggest, that, in patients not treated with statins apo B-48 might be a marker of subclinical atherosclerosis measured as IMT.
Post prandial lipoproteins EAS-0014. EFFECT OF FAT COMPOSITION OF A MEAL POSTPRANDIAL INFLAMMATORY RESPONSE
ON
THE
ACUTE
I. Shapira 1, *, O. Raz 2. 1 Directorate, Tel Aviv Sourasky Medical Center, TelAviv, Israel; 2 Nutrition, Tel Aviv Sourasky Medical Center, Tel-Aviv, Israel
* Corresponding author. Introduction: The presence of low grade, internal inflammation is one of the main causes for development of insulin resistance, type 2 diabetes mellitus and atherosclerosis. Consumption of long lasting diets with various compositions affects the inflammatory response. Aim: In this study we investigated the effect of a single meal, composed of different type of fatty acids (saturated; SFA versus mono-unsaturated fatty acids; MUFA) on the development of inflammation. Methods: 50 healthy subjects, were randomly chosen to eat two isocaloric meals with similar amounts of fat, either high in SFA or in MUFA, given as breakfast. Following three weeks each participant was given the alternate meal. Blood samples were taken following an overnight fast, and 2, 4 hours following the meal. Results: High SFA meal, but not MUFA increases erythrocyte sedimentation rate, fibrinogen, leukocytes, CRP and IL-6 concentration. In addition, the results indicate that high BMI subjects are less sensitive to the effect of the SFA meal, and the increase in the inflammatory response is more moderate. Conclusion: A single high SFA meal induces immediate postprandial inflammatory response. This study emphasizes the importance of consuming diet with anti-inflammatory effects, showing the harm influence of a single unfavorable meal. EAS-0593. COMPARISON OF EFFECTS OF DIABETIC ENTERAL NUTRITION AND STANDARD ENTERAL NUTRITION ON POSTPRANDIAL LEVEL OF FREE FATTY ACIDS e A PILOT STUDY , L. Sobotka, V. Bla ha. IIIrd Dept. Metabolic Care and J. Vísek*, A. Ticha lov Gerontology, University Hospital, Hradec Kra e, Czech Republic
* Corresponding author.
in children exposed to Lp(a) hyperlipidemia (Lp(a)-HLP) and high non-HDL cholesterol levels than in those with only one cardiovascular risk factor. We retrospectively studied 47 children, aged 6-17yr (median 10.5), who underwent a noninvasive assessment of subclinical atherosclerosis because of high non-HDL cholesterol (defined as >3.75 mmol/l) and/or high Lp(a) (defined as >300 mg/l) levels. Data on family history of premature atherosclerosis, age, gender, body mass index (BMI) and blood pressure were collected. Biological data (lipid profile, apoB, apoA1 and Lp(a) levels) were measured on the same fasting blood sample. Arterial intima-media thickness (IMT) and flow-mediated dilation (FMD) were assessed by high-resolution ultrasound. We found a positive family history of premature atherosclerosis in 55.3% of our subjects. After adjustment for age and gender, 75% of them had BMI in the normal range. 40.4% had isolated high non-HDL cholesterol, 51.1 % combined high non-HDL cholesterol and Lp(a)-HLP and 8.5 % isolated Lp(a)-HLP. We found a significant positive correlation between Lp(a) levels and IMT, but not with FMD. Surprisingly, the group with isolated Lp(a)-HLP showed the highest IMT measurements, reaching statistical signification. The only variable significantly correlated to FMD was blood pressure. In conclusion, isolated Lp(a)-HLP has a stronger impact on premature atherosclerosis than when combined with hypercholesterolemia in dyslipidemic children. EAS-0574. LIPOPROTEIN (A): CONCENTRATION, ISOFORMS, POLYMORPHISMS AND ASSOCIATION WITH PRECLINICAL ATHEROSCLEROSIS C. Pavanello 1, *, C. Vitali 2, C. Tarlarini 3, S. Penco 3, L. Calabresi 2, G. Mombelli 1, C.R. Sirtori 1. 1 Centro Dislipidemie, A.O. Ospedale Niguarda Ca Granda, Milan, Italy; 2 Dipartimento di Scienze Farmacologiche e degli Studi di Milano, Biomolecolari, Via Balzaretti 9 20133, Universita Milan, Italy; 3 Dipartimento di Medicina di Laboratorio Genetica Medica, Granda, Milan, Italy A.O. Ospedale Niguarda Ca
* Corresponding author. Lipoprotein(a) [Lp(a)] is a plasma lipoprotein consisting of a cholesterolrich LDL particle with one molecule of apolipoprotein B100 and an additional protein, apolipoprotein(a) [apo(a)], attached via a disulfide bond. Its levels remain relatively constant throughout an individual's lifespan and are mainly attributed to genetic variation within the apo(a) gene (LPA). Increased levels of Lp(a) are a risk factor for coronary artery disease. We included 60 subjects, aged between 18 and 75 years, in primary prevention and with Lp(a) > 35 mg/dL. Eligible participants had data for Lp(a) concentrations, LPA kringle IV type 2 (KIV-2) sums of repeats (affecting isoform size) and carrier status for the LPA single-nucleotide polymorphisms rs10455872 and rs3798220 (affecting concentrations in plasma). Lp(a) was quantified by ELISA test and apo(a) isoforms were designated as F, B, S1, S2, S3, S4 according to their relative electrophoretic mobility on SDS-PAGE compared with apoB100. Mean plasmatic Lp(a) level was 117 mg/dL (35-387 mg/dL). We found an inverse correlation with isoform size and Lp(a) concentrations. An association with the presence of the two SNPs (28% of the subjects were carriers of the rs10455872 and 17% of the rs3798220) and elevated Lp(a) levels were also observed. Finally we investigated the association of Lp(a) levels with carotid intimal medial thickness (IMT) as an early marker of atherosclerosis and we found that IMT increased with increase quartiles of Lp(a) levels (p< 0.05). The results suggest an associations between high serum Lp(a) levels and atherosclerosis.
e101
Complex, Moscow, Russia; 2 Institute of Clinical Cardiology, Russian Cardiology Research and Production Complex, Moscow, Russia
* Corresponding author. Aim: Being a risk factor for atherosclerosis lipoprotein(a) [Lp(a)] may participate in inflammatory reactions in the vessel wall. The aim was to examine the relationship between the blood levels of Lp(a), autoantibodies (AAb) to Lp(a) and the parameters of cell immunity in patients with stable CHD. Methods: 104 men with different stages of coronary atherosclerosis according to CAG were enrolled. Group 1 had intact coronary arteries. Group 2 and Group 3 had undergone coronary stenting; in Group 2 no coronary atherosclerosis progression was found and Group 3 had disease progression in non-invaded coronary arteries (new stenosis above 50%). Group 4 had multivessel coronary disease. Lp(a) and AAb levels were determined by intralaboratory ELISA kit, lipids were measured by commercial kits. Lymphocyte subsets (CD4þFoxP3þTregs and CD4þIL17þTh17) were counted in PBMC using direct immunofluorescence and flow cytometry, lymphocyte activation marker sCD25 in serum via Immulite. Results: The Lp(a) level was significantly higher in Group 4 (38.3±8.5 mg/ dL) compare Group 1 (12.3±3.0 mg/dL), p Conclusion: The identified patterns may indicate the participation of Lp(a) in autoimmune inflammation in atherosclerosis. EAS-0791. LIPOPROTEIN(A) AND SMALL DENSE LOW DENSITY LIPOPROTEIN SUBFRACTIONS AS CARDIOVASCULAR RISK FACTORS O. Afanasieva 1, E. Utkina 1, N. Artemieva 2, M. Ezhov 2, *, Y. Matchin 2, I. Adamova 1, S. Pokrovsky 1. 1 Institute of Experimental Cardiology, Russian Cardiology Research and Production Complex, Moscow, Russia; 2 Institute of Clinical Cardiology, Russian Cardiology Research and Production Complex, Moscow, Russia
* Corresponding author. Aim: To examine the relationship of lipoprotein(a) [Lp(a)] and lipoprotein subfractions with cardiovascular risk in patients with and without coronary artery disease. Methods: 228 patients on statins medication (73% men) and undergoing CAG were included in retrospective study. The Lp(a) concentration was measured by ELISA non-sensitive to apo(a) polymorphism. Lipids and lipoprotein subfractions were determined by reagent's kits «Biocon» (Germany) and «Lipoprint® System», (Quantimetrix », USA), respectively. Results: All patients were enrolled into two group according to CAG results: the Group 1 - patients with diseased coronary arteries (n¼190) and Group 2 - with intact vessels (n¼38). Groups differed in the Lp(a) level (61.0±3.5 mg/dL and 33.4±6.9 md/dL, p¼0.002) and small dense LDL (sdLDL) concentration (4.5±0.5 mg/dL and 2.1±0.4 mg/dL, p¼0.03), other parameters were comparable. Lp(a) concentrations correlated with small intermediate density lipoprotein subfraction (IDL-A) (r¼0.15, p Conclusion: Lp(a) is independent risk factor for CHD, sdLDL potentiates the risk of coronary diseases, associated with high Lp(a) level.
EAS-0813. LIPOPROTEIN(A) ISOFORMS
CONCENTRATIONS
AND
APOLIPOPROTEIN-E
E. Waldmann 1, *, R.G. Stark 2, J. Altenhofer 1, K. Henze 1, K.G. Parhofer 1. 1 Medical Department 2, Hospital of the University of Munich €konomie und (LMU), München, Germany; 2 Institut für Gesundheitso Management im Gesundheitswesen, Helmholtz Zentrum, München, Germany
EAS-0753. LP(A), AUTOANTIBODIES TO LP(A) AND MINOR T-CELL SUBPOPULATIONS IN PATIENTS WITH CORONARY ATHEROSCLEROSIS
* Corresponding author.
E. Klesareva 1, E. Pylaeva 2, *, A. Potekhina 2, T. Krasnikova 1, M. Afanasieva 1, V. Masenko 2, T. Arefieva 1, O. Afanasieva 1. 1 Institute of Experimental Cardiology, Russian Cardiology Research and Production
Although lipoprotein(a) is an established risk factor for cardiovascular disease its metabolism is largely unknown. Apolipoprotein E (apoE) is present on many lipoproteins and is an important mediator of lipoprotein metabolism. The various isoforms of apoE (E2, E3, E4) result in 6 common apoE
e102
Abstracts / Atherosclerosis 241 (2015) e72ee148
phenotypes (apoE2/E2; apoE2/E3; apoE2/E4; apoE3/E3; apoE3/E4; apoE4/ E4) with apoE3/E3 being the most common normal variant. It is unclear whether and how the apoE phenotype is associated with lipoprotein(a) concentrations. We evaluated lipoprotein(a) concentrations in subjects with different apoE phenotypes (apoE2/E2: n¼81; apoE2/E3: n¼188; apoE2/E4: n¼58; apoE3/E3: n¼132; apoE3/E4: n¼182; apoE4/E4: n¼68). Using a general linear model we found that the groups differ significantly (p¼0.04) regarding lipoprotein(a) concentration (apoE2/E2: 28±41 (mean±SD) mg/dl; apoE2/E3: 30±53 mg/dl, apoE2/E4:34±54 mg/dl; apoE3/E3: 49±65 mg/dl; apoE3/E4: 41±64 mg/dl; apoE4/E4: 39±51 mg/dl). After adjusting for age, gender, BMI, log-triglyceride, LDL-cholesterol and HDL-cholesterol the association was no longer significant (p¼0.14). In a second step we analyzed the effect of single isoforms on lipoprotein(a) concentrations. We therefore compared any apoE2 (heterozygous or homozygous) vs. any apoE4 vs. apoE3/E3 (phenotype apoE2/E4 was excluded). Although apoE isoforms are overall not significantly associated with lipoprotein(a) (p¼0.10) after adjusting for age, gender, BMI, log- triglycerides, LDL-cholesterol and HDLcholesterol, the apoE2 isoform is associated with significantly lower lipoprotein(a) concentrations compared to E3/E3, (p¼0.03), while apoE4 was not different from E3/E3. These data indicate that apoE may be directly or indirectly involved in the metabolism of lipoprotein(a). The underlying mechanisms remain to be determined. EAS-0862. PLASMA PROPROTEIN CONVERTASE SUBTILISIN/KEXIN TYPE 9 (PCSK9) IS ASSOCIATED WITH LP(A) IN TYPE 2 DIABETIC PATIENTS Y. Nekaies 1, B. Baudin 2, *, M. Sakly 1, N. Attia 1. 1 Research Unit of Integrated Physiology (UR11ES33), University of Carthage Faculty of Sciences of Bizerte, Bizerte, Tunisia; 2 Biochemistry Department, Biology and Pathology Pole Saint-Antoine Hospital and Faculty of Pharmacy Chatenay Malabry, Paris, France
* Corresponding author. Objective: Type 2 diabetes mellitus (T2DM) is associated with elevated plasma apolipoprotein B, Lp(a), triglycerides and reduced HDL-C. The present study was conducted to investigate whether plasma proprotein convertase subtilisin/kexin type 9 (PCSK9), a regulator of LDL-receptor (LDLr) expression in hepatocytes, was associated with diabetic dyslipidemia. Methods: We developed a sandwich ELISA using recombinant human PCSK9 protein and a polyclonal antibody pre-coated onto a microplate specific directed against human PCSK9. We measured circulating PCSK9 concentrations in a cohort of patients with T2DM (n ¼ 50) compared to an age- and sex-matched control group (n¼50). Plasma apolipoprotein B, Lp(a) triglycerides, LDL-C, HDL-C and LDL-r were measured in both groups. Results: Plasma PCSK9 levels were significantly elevated in T2DM compared to controls (44.61±14.44 and 33.22 ± 11.79 ng/mL respectively, p<0.0001). However, LDL-r levels did not differ between the two groups. No significant correlation of PCSK9 with lipid parameters was found. Remarkably PCSK9 was positively correlated with Lp(a) in whole population (r¼ þ0.254, p<0.0138) and in T2DM group (r¼ þ0287, p¼ 0.0474) but not in controls. Conclusion: Lp(a) levels has been proposed as a contributing factor to the accelerated development of macrovascular complications in T2DM and the synergic effect with PCSK9 may explain the enhanced atherogenicity in type 2 diabetic patients.
TG rich lipoproteins EAS-0857. SERUM APOLIPOPROTEIN B-48 CORRELATES IN PATIENTS WITH FAMILIAL HYPERCHOLESTEROLEMIA M. Walus-Miarka 1, *, B. Idzior-Walus 1, P. Miarka 2, M. Kapusta 3. 1 Metabolic Diseases, Jagiellonian University Medical College, Krakow, Poland; 2 Department of Nephrology, Jagiellonian University Medical College, Krakow, Poland; 3 Department of Biochemistry, Jagiellonian University Medical College, Krakow, Poland
* Corresponding author. Apolipoprotein B-48 (apoB-48) is known to be the only specific marker of intestinal chylomicron particles. In humans ApoB-48 is synthesized only by the intestine. In this study we aimed to examine factors associated with fasting apoB-48 in patients with familial hypercholesterolemia (FH). Material included 130 patients with FH, diagnosed using Simon Broome criteria, 100 adult patients and 30 children and adolescents (< 18 yrs). Apo B48 serum concentration was determined by ELISA, serum lipids by enzymatic methods, carotid intima-media thickness (IMT) by ultrasonography. Mean values of apo B-48 were higher in men than in women (3552.3þ/ 2126.0 vs 2744.0þ/-1473.2 ng/ml, p¼0.03). In the whole group of patients mean apoB-48 correlated significantly with age (-0.19), systolic blood pressure (-0.18), triglycerides (0.27), apo A1 (-0.23) and IMT (-0.21). 74.7% of adult patients were treated with statins. In adult patients apoB-48 correlated with total cholesterol, LDL-C, triglycerides and apoA1 ( r¼ 0.24, 0.24, 0.34, and-0.21 respectively). In FH patients not treated with statins, apoB-48 correlated positively with waist to hip ratio ( r¼0.42). In FH women treated with statins apo B-48 correlated with total, LDL-cholesterol and triglycerides (r ¼ 0.33, 0.36 and 0.40 respectively). Only in FH men not treated with statins strong positive correlation between apo B-48 and IMT was found ( r¼.75), while in men treated with statin, unexpectedly, negative correlation was observed ( r¼ -0.47). The results of the study suggest, that, in patients not treated with statins apo B-48 might be a marker of subclinical atherosclerosis measured as IMT.
Post prandial lipoproteins EAS-0014. EFFECT OF FAT COMPOSITION OF A MEAL POSTPRANDIAL INFLAMMATORY RESPONSE
ON
THE
ACUTE
I. Shapira 1, *, O. Raz 2. 1 Directorate, Tel Aviv Sourasky Medical Center, TelAviv, Israel; 2 Nutrition, Tel Aviv Sourasky Medical Center, Tel-Aviv, Israel
* Corresponding author. Introduction: The presence of low grade, internal inflammation is one of the main causes for development of insulin resistance, type 2 diabetes mellitus and atherosclerosis. Consumption of long lasting diets with various compositions affects the inflammatory response. Aim: In this study we investigated the effect of a single meal, composed of different type of fatty acids (saturated; SFA versus mono-unsaturated fatty acids; MUFA) on the development of inflammation. Methods: 50 healthy subjects, were randomly chosen to eat two isocaloric meals with similar amounts of fat, either high in SFA or in MUFA, given as breakfast. Following three weeks each participant was given the alternate meal. Blood samples were taken following an overnight fast, and 2, 4 hours following the meal. Results: High SFA meal, but not MUFA increases erythrocyte sedimentation rate, fibrinogen, leukocytes, CRP and IL-6 concentration. In addition, the results indicate that high BMI subjects are less sensitive to the effect of the SFA meal, and the increase in the inflammatory response is more moderate. Conclusion: A single high SFA meal induces immediate postprandial inflammatory response. This study emphasizes the importance of consuming diet with anti-inflammatory effects, showing the harm influence of a single unfavorable meal. EAS-0593. COMPARISON OF EFFECTS OF DIABETIC ENTERAL NUTRITION AND STANDARD ENTERAL NUTRITION ON POSTPRANDIAL LEVEL OF FREE FATTY ACIDS e A PILOT STUDY , L. Sobotka, V. Bla ha. IIIrd Dept. Metabolic Care and J. Vísek*, A. Ticha lov Gerontology, University Hospital, Hradec Kra e, Czech Republic
* Corresponding author.