- Email: [email protected]
Screening for LDLR gene mutations responsible for hypocholesterolemia in Russian population
e138
Abstracts / Atherosclerosis 241 (2015) e72ee148
University of Edinburgh, Edinburgh, United Kingdom; 2 Centre for Inflammation Research, University of Edinburgh, Edinburgh, United Kingdom; 3 Division of Cardiology, David Geffen School of Medicine at UCLA, Los Angeles, USA
* Corresponding author. Aim: Particulate matter in air pollution is associated with cardiovascular disease. Diesel exhaust particulate (DEP) is a common source of nanoparticles in urban environments, however, the constituents and mechanisms that drive its detrimental actions have yet to be established. Here we explore both the acute and chronic vascular actions of DEP, exploring the role of oxidative stress and whether removal of water-soluble components from DEP can ameliorate these effects. Methods & results: Electron paramagnetic resonance showed that suspensions of DEP generated superoxide free radicals. Direct addition of DEP to isolated aortic rings attenuated endothelial-mediated relaxation, which could be prevented by co-incubation with superoxide dismutase. Western diet-fed apolipoprotein-E knockout mice were used to determine whether chronic pulmonary exposure to DEP (10mg twice weekly for 4 weeks) increased lesion formation. Atherosclerotic burden was increased (P¼0.017) in DEP-treated mice (59±10% area of media) compared with vehicle-treated controls (32±7%). These changes were paralleled by an increase in antioxidant gene expression (haemoxygenase-1, NRF-2, NQO1) in the liver. Removal of the aqueous-soluble constituents of DEP diminished its ability to impair arterial function and promote lesion development. Conclusions: DEP directly impairs vascular function through generation of superoxide free radicals. Pulmonary exposure to DEP promoted the development of atherosclerosis in mice, an effect that coincided with systemic oxidative stress. Washing DEP with aqueous buffer attenuated both the acute and chronic vascular actions of DEP. Strategies that remove the water-soluble redox-active constituents of DEP may represent a novel means to reduce the cardiovascular actions of this common air pollutant.
EAS-0808. OBESE, SMOKER, AND OBESE SMOKER: IS THERE A GENERAL LIFESTYLE GRADIENT? T. Lohse 1, *, S. Rohrmann 1, M. Bopp 1, A. Chiolero 2, D. Faeh 1. 1 Chronic Disease Epidemiology, Epidemiology Biostatistics and Prevention Institute (EBPI), Zurich, Switzerland; 2 Chronic Diseases, Institute of Social and Preventive Medicine (IUMSP), Lausanne, Switzerland
* Corresponding author. Aim: Obesity and smoking are major CVD risk factors and may be associated with other unfavourable lifestyle behaviours. Our aim was to investigate the significance of obesity, heavy smoking, and both combined in terms of prevalence trends and their relationship with other lifestyle factors. Methods: We used data from the population-based cross-sectional Swiss Health Survey (5 waves, 1992-2012) comprising 85,575 individuals aged 18 years. Height, weight, and smoking status were self-reported. We used multinomial logistic regression to analyse differences in lifestyle for the combinations of BMI category and smoking status, focusing on obese and heavy smokers. We defined normal-weight never smokers as reference. Results: The lifestyle of obese never smoker differed least from reference. Normal weight smokers had particularly high odds of infrequent fruit and vegetable consumption [men, odds ratio: 1.80 (95% confidence interval: 1.59-2.02); women, 2.43 (2.15-2.75)] and of frequent alcohol consumption [2.49 (2.15-2.88); 3.21 (2.77-3.74)]. The odds of an unfavourable behaviour among obese smokers were increased for all lifestyle factors considered, and it was particularly high for physical inactivity [3.29 (2.36-4.58); 2.14 (1.35-3.38)]. While the prevalence of smoking has decreased and of obesity has increased in the Swiss population, the prevalence of obese smokers
remained relatively stable in men but doubled in women between 1992 and 2012. Conclusion: All three CVD risk groups showed considerable potential for improvement of general lifestyle. In normal-weight smokers attention should be paid on diet and alcohol consumption, whereas in obese smokers promotion of physical activity should have the highest priority.
EAS-0827. APOB/APOA-I RATIO, AND MAJOR CARDIOVASCULAR RISK FACTORS IN AZORES AND LISBON POPULATIONS e A COMPARISON STUDY R. Ferin 1, *, A. Lima 1, J. Baptista 1, A.C. Alves 2, 3, M. Bourbon 2,3, M.L. ~o e Recursos Naturais, Universidade ~o 1. 1 DCTD/Centro de Investigaça Pava ~o dos Açores, Ponta Delgada 9501-801, Portugal; 2 Grupo de investigaça ~o da Saúde e Cardiovascular Unidade I&D Departamento de Promoça ~o da doenças na ~o Transmissíveis Instituto Nacional de Saúde Dr. Prevença Ricardo Jorge, Lisboa 1649-040, Portugal; 3 Centre for Biodiversity Functional and Integrative Genomics (BioFIG) Faculty of Sciences University of Lisboa, Lisboa 1749-016, Portugal
* Corresponding author. Aim: Death rate from coronary artery disease (CAD) is two-fold higher in the Azores archipelago than in mainland Portugal. There is not a registered database on the prevalente risk factors for cardiovascular diseases (CVD) in Azores. Those can diverge in different populations, due to genetic and/or environmental factors. The aim was to compare the apoB/apoA-I ratio and major risk factors for atherosclerosis between the populations of Azores and Lisbon. Methods: This study involved 439 Azorean volunteers and 166 from Lisbon (from e_COR study). Participants (aged 20-70 years) were asymptomatic for CAD and free of chronic diseases (except hypertension). The Azores population was split into two groups: Azores-1-sub~o jects born and living in three more geographically isolated islands (Sa ~o Miguel Jorge, Graciosa and Flores), and Azores-2esubjects from Sa island. Results: Prevalence of obesity and hypertension was higher (36% and 23%;P<0.05) in the Azores group (mean age 40±10 years;41% male) than in Lisbon population (42±15 years;52% male). Total cholesterol, HDLcholesterol, apoA-I, and apoB concentrations in the Azores were higher (P<0.01) than in Lisbon. Except for HDL-cholesterol and apoA-I levels, which were lower, all other parameters were significantly increased in Azores-1 as compared with Azores-2 or Lisbon. Also, Azores-1 subjects exhibited a higher apoB/apoA-I ratio than those in Azores-2or Lisbon, mainly men (0.93±0.41 vs 0.62±0.18;P<0.001). Conclusion: As expressed by apoB/apoA-I ratio Azores-1 subjects are at high risk of developing a CVD event, which is in agreement with the respective island death rate for CVD. Azores-2 might be a reference population for CVD studies in Azores.
EAS-0835. SCREENING FOR LDLR GENE MUTATIONS RESPONSIBLE HYPOCHOLESTEROLEMIA IN RUSSIAN POPULATION
FOR
E. Shakhtshneider 1, *, D. Ivanoshchuk 1, I. Pilipenko 2, Y. Nikitin 3, S. Malyutina 3, M. Voevoda 1. 1 Laboratory of Medical Genetics, Federal State Budgetary Institution of Internal and Preventive Medicine SB RAMS, Novosibirsk, Russia; 2 Laboratory of Molecular Epidemiology and Human Evolution, Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia; 3 Laboratory of Therapy, Federal State Budgetary Institution of Internal and Preventive Medicine SB RAMS, Novosibirsk, Russia
* Corresponding author. Background and aims: The aim of this study was to identification of the spectrum of mutations in low-density lipoproteins receptor (LDLR) gene in
Abstracts / Atherosclerosis 241 (2015) e72ee148
a population sample of Russian patients with hypocholesterolemia and normocholesterolemia. Methods: The patients included in the analysis were selected based on total cholesterol level from population sample surveyed in frame of HAPIEE project (9360 participants, aged 45-69). Totally 10 men and 10 women aged 45-49 with lowest total cholesterol level in this age group were included in the analysis. Total cholesterol level was <200mg/dl and mean total cholesterol level e 144±6mg/dl. The plasma lipid levels were determined by standard enzymatic assays. All patients were of Caucasian. For each patient all exons and flanking splicing regions of LDLR gene were sequenced. Results: rs2228671, IVSþ10, rs5929 in twenty unrelated patients with hypocholesterolemia were identified. We found rs2228671 (C/T) in exon 2 in 7 patients in heterozygous variation. IVSþ10 (G/C) was described in 9 patients. We found rs5929 (C/T) in exon 11 in 5 patients in heterozygous variation. Conclusions: Population sample of Russian patients with hypocholesterolemia significantly differs from clinically selected patients with familial hypercholesterolemia by the spectrum of mutations in LDLR gene. The reported study was partially supported by RFBR, research project N1404-01594a.
EAS-0852. NON-LIPID RISK FACTORS IN CHILDREN WITH PARENTAL EARLY CORONARY ARTERY DISEASE. ASSOCIATIONS WITH CHARACTERISTICS OF THEIR PARENT WITHOUT CORONARY ARTERY DISEASE M. Konnov*, A.D. Deev, N.A. Gratsiansky. Laboratory of Clinical Cardiology, Research Institute of Physical-Chemical Medicine, Moscow, Russia
* Corresponding author. Objective: To elucidate relationships between non-lipid risk factors (RF) in children of patients with early (E) CAD and characteristics of their CADfree parents. Methods: The study of families of ECAD patients contained 200 CAD-free proband's spouses (16.8% men) and 268 their children (5-34 y, 56.7% men). Recorded non-lipid RF were: smoking, metabolic syndrome (MS) (16 y); in children 5-17 y e excess weight; large (75 percentile) waist circumference (WC), pre-diabetes; in offsprings 18-34 y e hypertension (HT), PreDM, obesity. Associations with parental RF and level of education were assessed in two age groups (5-17, n¼127, 18-34 y, n¼141) (except smoking and MS). Results: Among young children 20.8% were overweight, 23.1% e had large WC. Smoking, HT, obesity, prediabetes, MS were found in 30.8, 14.4,12.3, 10.3, 12.4% of adult children, respectively. Characteristics of CAD free parents independently associated with non-lipid RF of offsprings are shown in the table. Conclusion: These associations reflect contribution of CAD-free parents to formation of modifiable non-lipid RF in offsprings of ECAD patients.
e139
EAS-0854. FIRST GLOBAL, LONGITUDINAL, PHARMACO-EPIDEMIOLOGIC, OBSERVATIONAL REGISTRY ON GENE THERAPY IN THE MANAGEMENT OF LIPOPROTEIN LIPASE DEFICIENCY (GENIALL) E. Steinhagen-Thiessen 1, E. Stroes 2, H. Soran 3, C. Johnson 4, G. Iotti 5, *, M. Zibellini 5, B. Ossenkoppele 6, M. Dippel 7, M.R. Averna 8. 1 Lipid Clinic at the Interdisciplinary Metabolism Center, Charit e University Hospital, Berlin, Germany; 2 Department of Vascular Medicine, Amsterdam Medical Center, Amsterdam, Netherlands; 3 Cardiovascular Trials Unit, Central Manchester University Hospitals NHS Foundation Trust, Manchester, United Kingdom; 4 Hospital, University, Southampton, United Kingdom; 5 Medical Affairs, Chiesi Farmaceutici, Parma, Italy; 6 Clinical Operations, uniQure, Amsterdam, Netherlands; 7 Medical Affairs, uniQure, Amsterdam, Netherlands; 8 Centro regionale delle malattie rare del metabolismo dell' adulto (CERMMET), Policlinico Giaccone, Palermo, Italy
* Corresponding author. Background: A good understanding of the natural history of rare diseases is a pre-requisite for successful patient management. Disease registries have been helpful in this regard. Lipoprotein Lipase Deficiency (LPLD) is a rare, autosomal-recessive disease resulting in chylomicronemia and increased risk of pancreatitis. Limited data is available on its natural course and no consensus exists on its management. Alipogene tiparvovec (Glybera®) - the first gene therapy to receive Marketing Authorization in the EU - introduces a LPL gain-of-function allele in an AAV1-vector. Clinical experience has shown a long term expression of LPL-protein in injected muscles, improved postprandial chylomicron metabolism, and a decreased incidence and severity of pancreatitis. As part of the risk management plan for Glybera® a 15-year registry was launched in 2014. The registry includes collection of data on the natural course of the disease, as well as efficacy and safety outcomes on Glybera®-treated patients. Aim: To introduce a gene therapy disease registry for LPLD (GENIALL). Method: GENIALL is an international, multicenter, prospective, longitudinal, observational study. Data collection consists of relevant laboratory, safety and clinical outcome information, including dietary adherence, pancreatitis episodes, adverse events, and quality of life, amongst others. Results: To-date GENIALL has received regulatory approval in 10 sites (Berlin, Hamburg, Vienna, Palermo, Rome, Padova, Manchester, Lyon, Stockholm, Amsterdam). Five out of 200 targeted LPLD-patients have been consented within the first 5 months. Conclusion: Successful start-up of the GENIALL-Registry underlines the need for broad collection of data in LPLD, which will help to guide LPLDmanagement in the future.
EAS-0859. SMOKING IN CHILDREN OF PATIENTS WITH EARLY CORONARY ARTERY DISEASE: RELATION TO OWN AND PARENTAL CHARACTERISTICS M. Konnov*, A.D. Deev, N.A. Gratsiansky. Laboratory of Clinical Cardiology, Research Institute of Physical-Chemical Medicine, Moscow, Russia
* Corresponding author. Non-lipid RF of children, age group Current smoking, 12-34 years
Characteristic of CAD-free parent
Smoking Lower education HT, 18-34 years Higher education Excess weight, 5-17 years WC, cm Obesity, 18-34 year MS HDL-cholesterol, mmol/l WC 75 percentile, 5-17 years WC, cm Prediabetes,18-34 years MS Basal glucose, mmol/l MS,16-34 years MS
OR
CI
p
2.75 1.60 2.20 1.05 8.22 0.42
1.33-5.70 1.08-2.39 1.11-4.40 1.01-1.08 2.15-31.4 0.00-0.40
0.006 0.021 0.025 0.006 0.002 0.006
1.07 6.61 3.40 6.66
1.03-1.10 1.78-24.6 1.47-7.88 2.07-21.4
0.000 0.005 0.004 0.001
Despite risk inherent in parental early coronary artery disease (ECAD) offsprings of patients with ECAD smoke. Purpose: To elucidate associations between current smoking (CS) in children of patients with ECAD with their own and parental characteristics. Methods: We examined 246 probands with ECAD, their consorts (n¼168) and children (n¼316). We registered habits, weight at birth, breastfeeding duration, BMI, waist circumference (WC), heart rate, BP, triglycerides (TG), high and low density cholesterol (HDL-C, LDL-C), basal glycemia, glucose tolerance, diabetes (D), pre-/hypertension, metabolic syndrome. Education grading e elementary, post-primary, secondary, undergraduate, higher (15 points). Predictors of CS were selected in 2 groups according to median age.
Abstracts / Atherosclerosis 241 (2015) e72ee148
University of Edinburgh, Edinburgh, United Kingdom; 2 Centre for Inflammation Research, University of Edinburgh, Edinburgh, United Kingdom; 3 Division of Cardiology, David Geffen School of Medicine at UCLA, Los Angeles, USA
* Corresponding author. Aim: Particulate matter in air pollution is associated with cardiovascular disease. Diesel exhaust particulate (DEP) is a common source of nanoparticles in urban environments, however, the constituents and mechanisms that drive its detrimental actions have yet to be established. Here we explore both the acute and chronic vascular actions of DEP, exploring the role of oxidative stress and whether removal of water-soluble components from DEP can ameliorate these effects. Methods & results: Electron paramagnetic resonance showed that suspensions of DEP generated superoxide free radicals. Direct addition of DEP to isolated aortic rings attenuated endothelial-mediated relaxation, which could be prevented by co-incubation with superoxide dismutase. Western diet-fed apolipoprotein-E knockout mice were used to determine whether chronic pulmonary exposure to DEP (10mg twice weekly for 4 weeks) increased lesion formation. Atherosclerotic burden was increased (P¼0.017) in DEP-treated mice (59±10% area of media) compared with vehicle-treated controls (32±7%). These changes were paralleled by an increase in antioxidant gene expression (haemoxygenase-1, NRF-2, NQO1) in the liver. Removal of the aqueous-soluble constituents of DEP diminished its ability to impair arterial function and promote lesion development. Conclusions: DEP directly impairs vascular function through generation of superoxide free radicals. Pulmonary exposure to DEP promoted the development of atherosclerosis in mice, an effect that coincided with systemic oxidative stress. Washing DEP with aqueous buffer attenuated both the acute and chronic vascular actions of DEP. Strategies that remove the water-soluble redox-active constituents of DEP may represent a novel means to reduce the cardiovascular actions of this common air pollutant.
EAS-0808. OBESE, SMOKER, AND OBESE SMOKER: IS THERE A GENERAL LIFESTYLE GRADIENT? T. Lohse 1, *, S. Rohrmann 1, M. Bopp 1, A. Chiolero 2, D. Faeh 1. 1 Chronic Disease Epidemiology, Epidemiology Biostatistics and Prevention Institute (EBPI), Zurich, Switzerland; 2 Chronic Diseases, Institute of Social and Preventive Medicine (IUMSP), Lausanne, Switzerland
* Corresponding author. Aim: Obesity and smoking are major CVD risk factors and may be associated with other unfavourable lifestyle behaviours. Our aim was to investigate the significance of obesity, heavy smoking, and both combined in terms of prevalence trends and their relationship with other lifestyle factors. Methods: We used data from the population-based cross-sectional Swiss Health Survey (5 waves, 1992-2012) comprising 85,575 individuals aged 18 years. Height, weight, and smoking status were self-reported. We used multinomial logistic regression to analyse differences in lifestyle for the combinations of BMI category and smoking status, focusing on obese and heavy smokers. We defined normal-weight never smokers as reference. Results: The lifestyle of obese never smoker differed least from reference. Normal weight smokers had particularly high odds of infrequent fruit and vegetable consumption [men, odds ratio: 1.80 (95% confidence interval: 1.59-2.02); women, 2.43 (2.15-2.75)] and of frequent alcohol consumption [2.49 (2.15-2.88); 3.21 (2.77-3.74)]. The odds of an unfavourable behaviour among obese smokers were increased for all lifestyle factors considered, and it was particularly high for physical inactivity [3.29 (2.36-4.58); 2.14 (1.35-3.38)]. While the prevalence of smoking has decreased and of obesity has increased in the Swiss population, the prevalence of obese smokers
remained relatively stable in men but doubled in women between 1992 and 2012. Conclusion: All three CVD risk groups showed considerable potential for improvement of general lifestyle. In normal-weight smokers attention should be paid on diet and alcohol consumption, whereas in obese smokers promotion of physical activity should have the highest priority.
EAS-0827. APOB/APOA-I RATIO, AND MAJOR CARDIOVASCULAR RISK FACTORS IN AZORES AND LISBON POPULATIONS e A COMPARISON STUDY R. Ferin 1, *, A. Lima 1, J. Baptista 1, A.C. Alves 2, 3, M. Bourbon 2,3, M.L. ~o e Recursos Naturais, Universidade ~o 1. 1 DCTD/Centro de Investigaça Pava ~o dos Açores, Ponta Delgada 9501-801, Portugal; 2 Grupo de investigaça ~o da Saúde e Cardiovascular Unidade I&D Departamento de Promoça ~o da doenças na ~o Transmissíveis Instituto Nacional de Saúde Dr. Prevença Ricardo Jorge, Lisboa 1649-040, Portugal; 3 Centre for Biodiversity Functional and Integrative Genomics (BioFIG) Faculty of Sciences University of Lisboa, Lisboa 1749-016, Portugal
* Corresponding author. Aim: Death rate from coronary artery disease (CAD) is two-fold higher in the Azores archipelago than in mainland Portugal. There is not a registered database on the prevalente risk factors for cardiovascular diseases (CVD) in Azores. Those can diverge in different populations, due to genetic and/or environmental factors. The aim was to compare the apoB/apoA-I ratio and major risk factors for atherosclerosis between the populations of Azores and Lisbon. Methods: This study involved 439 Azorean volunteers and 166 from Lisbon (from e_COR study). Participants (aged 20-70 years) were asymptomatic for CAD and free of chronic diseases (except hypertension). The Azores population was split into two groups: Azores-1-sub~o jects born and living in three more geographically isolated islands (Sa ~o Miguel Jorge, Graciosa and Flores), and Azores-2esubjects from Sa island. Results: Prevalence of obesity and hypertension was higher (36% and 23%;P<0.05) in the Azores group (mean age 40±10 years;41% male) than in Lisbon population (42±15 years;52% male). Total cholesterol, HDLcholesterol, apoA-I, and apoB concentrations in the Azores were higher (P<0.01) than in Lisbon. Except for HDL-cholesterol and apoA-I levels, which were lower, all other parameters were significantly increased in Azores-1 as compared with Azores-2 or Lisbon. Also, Azores-1 subjects exhibited a higher apoB/apoA-I ratio than those in Azores-2or Lisbon, mainly men (0.93±0.41 vs 0.62±0.18;P<0.001). Conclusion: As expressed by apoB/apoA-I ratio Azores-1 subjects are at high risk of developing a CVD event, which is in agreement with the respective island death rate for CVD. Azores-2 might be a reference population for CVD studies in Azores.
EAS-0835. SCREENING FOR LDLR GENE MUTATIONS RESPONSIBLE HYPOCHOLESTEROLEMIA IN RUSSIAN POPULATION
FOR
E. Shakhtshneider 1, *, D. Ivanoshchuk 1, I. Pilipenko 2, Y. Nikitin 3, S. Malyutina 3, M. Voevoda 1. 1 Laboratory of Medical Genetics, Federal State Budgetary Institution of Internal and Preventive Medicine SB RAMS, Novosibirsk, Russia; 2 Laboratory of Molecular Epidemiology and Human Evolution, Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia; 3 Laboratory of Therapy, Federal State Budgetary Institution of Internal and Preventive Medicine SB RAMS, Novosibirsk, Russia
* Corresponding author. Background and aims: The aim of this study was to identification of the spectrum of mutations in low-density lipoproteins receptor (LDLR) gene in
Abstracts / Atherosclerosis 241 (2015) e72ee148
a population sample of Russian patients with hypocholesterolemia and normocholesterolemia. Methods: The patients included in the analysis were selected based on total cholesterol level from population sample surveyed in frame of HAPIEE project (9360 participants, aged 45-69). Totally 10 men and 10 women aged 45-49 with lowest total cholesterol level in this age group were included in the analysis. Total cholesterol level was <200mg/dl and mean total cholesterol level e 144±6mg/dl. The plasma lipid levels were determined by standard enzymatic assays. All patients were of Caucasian. For each patient all exons and flanking splicing regions of LDLR gene were sequenced. Results: rs2228671, IVSþ10, rs5929 in twenty unrelated patients with hypocholesterolemia were identified. We found rs2228671 (C/T) in exon 2 in 7 patients in heterozygous variation. IVSþ10 (G/C) was described in 9 patients. We found rs5929 (C/T) in exon 11 in 5 patients in heterozygous variation. Conclusions: Population sample of Russian patients with hypocholesterolemia significantly differs from clinically selected patients with familial hypercholesterolemia by the spectrum of mutations in LDLR gene. The reported study was partially supported by RFBR, research project N1404-01594a.
EAS-0852. NON-LIPID RISK FACTORS IN CHILDREN WITH PARENTAL EARLY CORONARY ARTERY DISEASE. ASSOCIATIONS WITH CHARACTERISTICS OF THEIR PARENT WITHOUT CORONARY ARTERY DISEASE M. Konnov*, A.D. Deev, N.A. Gratsiansky. Laboratory of Clinical Cardiology, Research Institute of Physical-Chemical Medicine, Moscow, Russia
* Corresponding author. Objective: To elucidate relationships between non-lipid risk factors (RF) in children of patients with early (E) CAD and characteristics of their CADfree parents. Methods: The study of families of ECAD patients contained 200 CAD-free proband's spouses (16.8% men) and 268 their children (5-34 y, 56.7% men). Recorded non-lipid RF were: smoking, metabolic syndrome (MS) (16 y); in children 5-17 y e excess weight; large (75 percentile) waist circumference (WC), pre-diabetes; in offsprings 18-34 y e hypertension (HT), PreDM, obesity. Associations with parental RF and level of education were assessed in two age groups (5-17, n¼127, 18-34 y, n¼141) (except smoking and MS). Results: Among young children 20.8% were overweight, 23.1% e had large WC. Smoking, HT, obesity, prediabetes, MS were found in 30.8, 14.4,12.3, 10.3, 12.4% of adult children, respectively. Characteristics of CAD free parents independently associated with non-lipid RF of offsprings are shown in the table. Conclusion: These associations reflect contribution of CAD-free parents to formation of modifiable non-lipid RF in offsprings of ECAD patients.
e139
EAS-0854. FIRST GLOBAL, LONGITUDINAL, PHARMACO-EPIDEMIOLOGIC, OBSERVATIONAL REGISTRY ON GENE THERAPY IN THE MANAGEMENT OF LIPOPROTEIN LIPASE DEFICIENCY (GENIALL) E. Steinhagen-Thiessen 1, E. Stroes 2, H. Soran 3, C. Johnson 4, G. Iotti 5, *, M. Zibellini 5, B. Ossenkoppele 6, M. Dippel 7, M.R. Averna 8. 1 Lipid Clinic at the Interdisciplinary Metabolism Center, Charit e University Hospital, Berlin, Germany; 2 Department of Vascular Medicine, Amsterdam Medical Center, Amsterdam, Netherlands; 3 Cardiovascular Trials Unit, Central Manchester University Hospitals NHS Foundation Trust, Manchester, United Kingdom; 4 Hospital, University, Southampton, United Kingdom; 5 Medical Affairs, Chiesi Farmaceutici, Parma, Italy; 6 Clinical Operations, uniQure, Amsterdam, Netherlands; 7 Medical Affairs, uniQure, Amsterdam, Netherlands; 8 Centro regionale delle malattie rare del metabolismo dell' adulto (CERMMET), Policlinico Giaccone, Palermo, Italy
* Corresponding author. Background: A good understanding of the natural history of rare diseases is a pre-requisite for successful patient management. Disease registries have been helpful in this regard. Lipoprotein Lipase Deficiency (LPLD) is a rare, autosomal-recessive disease resulting in chylomicronemia and increased risk of pancreatitis. Limited data is available on its natural course and no consensus exists on its management. Alipogene tiparvovec (Glybera®) - the first gene therapy to receive Marketing Authorization in the EU - introduces a LPL gain-of-function allele in an AAV1-vector. Clinical experience has shown a long term expression of LPL-protein in injected muscles, improved postprandial chylomicron metabolism, and a decreased incidence and severity of pancreatitis. As part of the risk management plan for Glybera® a 15-year registry was launched in 2014. The registry includes collection of data on the natural course of the disease, as well as efficacy and safety outcomes on Glybera®-treated patients. Aim: To introduce a gene therapy disease registry for LPLD (GENIALL). Method: GENIALL is an international, multicenter, prospective, longitudinal, observational study. Data collection consists of relevant laboratory, safety and clinical outcome information, including dietary adherence, pancreatitis episodes, adverse events, and quality of life, amongst others. Results: To-date GENIALL has received regulatory approval in 10 sites (Berlin, Hamburg, Vienna, Palermo, Rome, Padova, Manchester, Lyon, Stockholm, Amsterdam). Five out of 200 targeted LPLD-patients have been consented within the first 5 months. Conclusion: Successful start-up of the GENIALL-Registry underlines the need for broad collection of data in LPLD, which will help to guide LPLDmanagement in the future.
EAS-0859. SMOKING IN CHILDREN OF PATIENTS WITH EARLY CORONARY ARTERY DISEASE: RELATION TO OWN AND PARENTAL CHARACTERISTICS M. Konnov*, A.D. Deev, N.A. Gratsiansky. Laboratory of Clinical Cardiology, Research Institute of Physical-Chemical Medicine, Moscow, Russia
* Corresponding author. Non-lipid RF of children, age group Current smoking, 12-34 years
Characteristic of CAD-free parent
Smoking Lower education HT, 18-34 years Higher education Excess weight, 5-17 years WC, cm Obesity, 18-34 year MS HDL-cholesterol, mmol/l WC 75 percentile, 5-17 years WC, cm Prediabetes,18-34 years MS Basal glucose, mmol/l MS,16-34 years MS
OR
CI
p
2.75 1.60 2.20 1.05 8.22 0.42
1.33-5.70 1.08-2.39 1.11-4.40 1.01-1.08 2.15-31.4 0.00-0.40
0.006 0.021 0.025 0.006 0.002 0.006
1.07 6.61 3.40 6.66
1.03-1.10 1.78-24.6 1.47-7.88 2.07-21.4
0.000 0.005 0.004 0.001
Despite risk inherent in parental early coronary artery disease (ECAD) offsprings of patients with ECAD smoke. Purpose: To elucidate associations between current smoking (CS) in children of patients with ECAD with their own and parental characteristics. Methods: We examined 246 probands with ECAD, their consorts (n¼168) and children (n¼316). We registered habits, weight at birth, breastfeeding duration, BMI, waist circumference (WC), heart rate, BP, triglycerides (TG), high and low density cholesterol (HDL-C, LDL-C), basal glycemia, glucose tolerance, diabetes (D), pre-/hypertension, metabolic syndrome. Education grading e elementary, post-primary, secondary, undergraduate, higher (15 points). Predictors of CS were selected in 2 groups according to median age.