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First data from the German cascade screening program for familial hypercholesterolemia – care high
Abstracts / Atherosclerosis 263 (2017) e111ee282
2,5 mmol/l, respectively. 33% of the patients suffered from side effects of the medication.
PO405. TREATMENT PATTERN OF FAMILIAL HYPERCHOLESTEROLEMIA IN SLOVAKIA: TARGETS, TREATMENT AND OBSTACLES IN COMMON PRACTICE Branislav Vohnout1, Lubomira Fabryova2, Alexander Klabnik2, Michaela Kadurova2, Karin Balinth2, Miriam Kozarova2, Inge Buganova2, Jana Raslova1, 2. 1 Coordination Centre for Familial Sirotiakova2, Katarina Hypercholesterolemia and Institute of Nutrition, Slovak Medical University, Bratislava, Slovak Republic; 2 Slovak MedPed FH Collaborative group, Slovak Republic Aim: Maximal dose of potent statins is recommended at first consultation in adult FH patients. Despite of this, a substantial proportion of FH patients are either undertreated or even not treated. The aim of this study was to evaluate treatment of FH patients, proportion of FH patients reaching LDL targets and reasons for not reaching LDL targets in 8 lipid clinics in Slovakia dealing with FH patients.
Methods: Retrospective collection of data on 201 FH patients (50.8±14.9 years old, 55.5% males) who attended the lipid clinics at least three times. The criteria of three visits had been chosen to ensure sufficient time to initiate and/or up-titrate therapy. Results: At first visit 31.3% of patients were treated with statins. At the third visit, 78.1% was treated with statins and 24.4% with ezetimibe. Majority was treated with atorvastatin (75.8%) and rosuvastatin (18.5%), 31.3% of all were treated with atorvastatin 80mg and rosuvastatin 40 mg. However only 11.9% of patients with target LDL level <2.5 mmol/l and 6.9% with target <1.8 mmol/l in fact reached the level, with maximal dose of atorvastatin or rosuvastatin only 7.9% patients reached the targeted LDL level. Reasons for not reaching the target levels were evaluated by physicians in each patient. Side-effects of therapy and non-compliance of patients were responsible for 18% and 30% of cases. Conclusions: Reference of FH patients to lipid clinics in Slovakia improved the treatment, however, almost 25% of the patients were still without statin treatment and majority of patients did not reach target LDL levels.
PO406. THE FIRST RESULTS OF THE LATVIAN REGISTRY OF FAMILIAL HYPERCHOLESTEROLEMIA Gustavs Latkovskis1, 2, 3, Vita Saripo1, 2, 3, Dainus Gilis2, Arta Upena-Roze2, Andrejs Erglis1, 2, 3. 1 University of Latvia, Latvian Institute of Cardiology and Regenerative Medicine, Riga, Latvia; 2 University of Latvia, Faculty of Medicine, Riga, Latvia; 3 Pauls Stradins Clinical University Hospital, Latvian Center of Cardiology, Riga, Latvia Aim: To evaluate clinical characteristics and efficacy of previous management of individuals included in the Latvian Registry of Familial Hypercholesterolemia (LRFH), which was established in February 2015. Methods: Diagnosis of FH was evaluated by Dutch Lipid Clinic Network (DLCN) criteria. Cascade screening of the 1st degree relatives using age and gender specific percentiles of LDL-C was performed in probands with definite and probable FH. Results: One hundred and ninety two adult patients were included in LRFH by November 2016. Majority (n¼151, 79%) were index cases, of whom 36 (24%) had definite, 30 (20%) probable and 58 (38%) possible FH. In cascade screening of eligible relatives LDL-C above 95th percentile was found in 24 of 41 relatives (59%). Thus, altogether 90 patients were diagnosed with FH (mean age 51.9±14.6 years, 30% men). Mean (SD) LDL-C at inclusion was 5.3±2.2 and 5.7±1.3 mmol/l in index cases and relatives, respectively. Only 43 probands (59%) and 5 relatives (21%) were on lipid lowering therapy, and treatment goal was reached in 6 (9%) probands and none of relatives at inclusion. Coronary heart disease (CHD) was diagnosed
e233
in 36 (55%) and 4 (17%) probands and relatives, respectively. Correspondingly onset of CHD was premature in 29 (44%) and 3 (13%) of cases. Conclusions: Within one and a half years we have identified around 1.1% of the estimated number of 8000 FH patients in Latvia. Vast majority had been under-diagnosed and not managed according to international guidelines. There is an urgent need to further develop LRFH.
PO407. CHARACTERISTICS OF LIPID PROFILE IN THE DIFFERENT TYPES OF GLYCOGEN STORAGE DISEASE Natalia Polenova1, 2, Antonina Starodubova1, 2, Tatyana Strokova1,2, Krasilova1, 2, Madlena Bagaeva1, 2. Svetlana Kosyura1, 2, Anastasia 1 Russian Research Institute of Nutrition and Biotechnology, Moscow, Russia; 2 Pirogov Russian National Research Medical University, Moscow, Russia Aim: Aim of our study - to estimate the parameters of lipid profile in patients with the different types of glycogen storage disease (GSD). Methods: 62 patients with GSD (mean age 8.2±0.7) were divided to 3 groups: I-th group - 19 patients with GSD type I (30%), IIth - 16 with GSD type III (25.8%), IIIth - 27 with GSD IV e IX (43.5%). Height, weight, body mass index (BMI), serum levels of total cholesterol (TC), triglycerides (TG), high density cholesterol (HDL)- and low density (LDL) cholesterol were measured. Results: 44 Patients (70.1%) have shown the abnormal lipid profile. The mean TG level was significant higher (p<0.05) in GSD type I and LDL in GSD type III. Level of total cholesterol (TC) were in general group 4,7±0,2 mmol/ l, in I group - 4,9±0,5 mmol/l, in II group - 4,9±0,3 mmol/l, in III group 4,4±0,2 mmol/l. The mean level of HDL were 0,6±0,03 mmol/l in general group, 0,8±0,06 mmol/l in I group, 0,8±0,07 mmol/l in II group and 1,1±0,1 mmol/l in III group. The LDL parameters in the different groups were: general group - 3,1±0,1 mmol/l, I - 2,8±0,2 mmol/l, II - 3,6±0,3 mmol/l, III 0,9±0,06 mmol/l. The means TG-level in general population - 2,2±0,3 mmol/l, in I group - 3,9±0,8 mmol/l, II group - 2,05±0,3mmol/l, III - 1,1±0,1 mmol/l. Conclusions: In this study more, then two-thirds of patients with GSD lipid abnormality were detected. Most prevalence lipid disorder by GSD type I is hypertriglyceridemia, whereas by GSD type III - high LDL-level.
PO408. FIRST DATA FROM THE GERMAN CASCADE SCREENING PROGRAM FOR FAMILIAL HYPERCHOLESTEROLEMIA e CARE HIGH arz2, 3, 4. 1 D-A-CHNina Schmidt1, Alexander Dressel1, Winfried M€ €vention v. Herz-Kreislauf-Erkrankungen e.V., Hamburg, Gesellschaft Pra €t Mannheim der Germany; 2 Medizinische Klinik V, Medizinische Fakulta €t Heidelberg, Mannheim, Germany; 3 Klinisches Institut für Universita €t Medizinische und Chemische Labordiagnostik, Medizinische Universita Graz, Graz, Austria; 4 Synlab Akademie, Synlab Services GmbH, Mannheim/ Augsburg, Germany Aim: Familial hypercholesterolemia (FH) is an inherited disorder of the LDL-cholesterol metabolism, leading to an increased risk of cardiovascular disease, even at young age. This risk can be significantly lowered by early diagnosis and treatment. About 271000 patients affected in Germany are not diagnosed correctly and only a small number is treated properly. To improve FH diagnosis in the general population a cascade screening and registry program was established by us. Methods: Study assistants contact physicians and lipid clinics to introduce the cascade screening and registry. The physicians identify possible FH patients and include them in the study. Patient data is acquired via questionnaires about medical history. Patients meeting at least two inclusion criteria (LDL-C >190 mg/dl; Cholesterol >290 mg/dl; tendon xanthomas; family history of hypercholesterolemia or early myocard infarct) are included in the registry. Family members will be contacted and physicians get feedback about diagnosis and treatment options. Ethical approvals for all German states were collected.
e234
Abstracts / Atherosclerosis 263 (2017) e111ee282
Results: We show initial analysis of the first 300 data sets regarding anamnesis data, comorbidities, state of therapy and target value attainment depending on therapy. Conclusions: Initial analysis of the registry data shows that FH patients in Germany, as expected, are at high risk for early CVD. About 25% of the patients remain untreated and only 15% of the patients attain the LDL cholesterol target value despite lipid lowering therapy. Our data show that FH is still under-diagnosed and under-treated in Germany.
PO409. MUTATION ANALYSIS OF THE HYPERCHOLESTEROLEMIC PATIENTS
LDLR
GENE
IN
CZECH
1, Ales Horinek1, Jaroslav Hubacek2, Lukas Lucie Schwarzova Zlatohlavek1, Martina Vaclova1, Richard Ceska1, Michal Vrablik1. 1 Centre for preventive cardiology, 3rd Dept. of Internal Medicine, 1st Faculty of Medicine, Charles University, Prague, Czech Republic; 2 CEM, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
patient was a female born in 1973. Her plasma lipid levels in 2004 when the diagnosis of FH was established were e TC 10.4, LDL-C 8.3, HDL-C 1.8 and TG 0.6, all in mmol/l. This patient is free of symptomatic cardiovascular or cerebrovascular disease. Conclusions: The most frequent mutation was c.1775G>A (G592E) variant in our group of patients. Six novel variants were detected in these Czech patients. Supported by and AZV CR 15-28277A (Ministry of Health), and UNCE 204022 (Charles University of Prague).
PO410. AORTIC ELASTIC PROPERTIES OF FAMILIAL HYPERCHOLESTEROLEMIA PATIENTS Esra Kaya1, Meral Kayikcioglu2, Serdar Payzin2, Levent Hurkan Can2. 1 Rize Kackar State Hospital, Rize, Turkey; 2 Ege University Medical School Cardiology Department, Izmir, Turkey Aim: Familial hypercholesterolemia (FH) is a genetic disease characterized by premature atherosclerosis due to high cholesterol burden since birth.
Ă
Aim: Familial hypercholesterolemia (FH) and familial defective apoB 100 (FDB) are autosomaly dominant diseases of lipid metabolism, characterized by increased plasma low-density lipoprotein cholesterol (LDL-C) levels, and caused mostly by the mutations within the LDL receptor (FH patients) or the R3500Q mutation in apoB gene (FDB patients). Recently, the prevalence of this disorder has been estimated to be even 1:200, thus making FH the most common inherited metabolic disaease. Methods: 113 Czech Caucasian hypercholesterolemic FDB mutation negative patients were screened by PCR-RFLP for the most common LDL receptor mutation c.1775G>A (G592E). Negative individuals were sequenced by Sanger and/or NGS (Illumina) method in order to reveal mutations within other exons of the gene. Results: We have found 25 mutations of the LDLR gene in the whole set of FH patients. Twenty of these are missense variants, and five are short deletions of one to three bases range. One individual was detected to be homozygous for c.1775G>A mutation within the LDL-receptor gene. The
Aortic stiffness and related elastic properties are associated with subclinical atherosclerosis. We aimed to evaluate the aortic elastic properties in patients with FH. Methods: We studied 84 patients diagnosed as FH according to Simon Broome National Registry and Dutch Lipid Clinic Network Criteria. Systolic and diastolic blood pressure were obtained, aortic systolic and diastolic diameters were measured. Aortic elastic properties were measured by GE Healthcare Vivid 7 Pro Ultrasound System (M4S probe, 1.5-4.3 mHz) and evaluated according to some special formulas including aortic strain, elastic modulus [E(p)] , aortic stiffness index beta and aortic distensibility (Table 1). Results: Mean age was 56 ± 11 years and 51 patients (61% ) were female. Mean aortic strain was 0.12 ± 0.08 while the mean value of elastic modulus [E(p)] was 0.59 ± 0.45. Mean aortic stiffness index beta was 6.4 ± 4.9 and mean aortic distensibility was 5.36 ± 3.9. The mean propagation velocity of descending aorta was 47.4±15.2 (Table 2). Compared to standard norms, all
2,5 mmol/l, respectively. 33% of the patients suffered from side effects of the medication.
PO405. TREATMENT PATTERN OF FAMILIAL HYPERCHOLESTEROLEMIA IN SLOVAKIA: TARGETS, TREATMENT AND OBSTACLES IN COMMON PRACTICE Branislav Vohnout1, Lubomira Fabryova2, Alexander Klabnik2, Michaela Kadurova2, Karin Balinth2, Miriam Kozarova2, Inge Buganova2, Jana Raslova1, 2. 1 Coordination Centre for Familial Sirotiakova2, Katarina Hypercholesterolemia and Institute of Nutrition, Slovak Medical University, Bratislava, Slovak Republic; 2 Slovak MedPed FH Collaborative group, Slovak Republic Aim: Maximal dose of potent statins is recommended at first consultation in adult FH patients. Despite of this, a substantial proportion of FH patients are either undertreated or even not treated. The aim of this study was to evaluate treatment of FH patients, proportion of FH patients reaching LDL targets and reasons for not reaching LDL targets in 8 lipid clinics in Slovakia dealing with FH patients.
Methods: Retrospective collection of data on 201 FH patients (50.8±14.9 years old, 55.5% males) who attended the lipid clinics at least three times. The criteria of three visits had been chosen to ensure sufficient time to initiate and/or up-titrate therapy. Results: At first visit 31.3% of patients were treated with statins. At the third visit, 78.1% was treated with statins and 24.4% with ezetimibe. Majority was treated with atorvastatin (75.8%) and rosuvastatin (18.5%), 31.3% of all were treated with atorvastatin 80mg and rosuvastatin 40 mg. However only 11.9% of patients with target LDL level <2.5 mmol/l and 6.9% with target <1.8 mmol/l in fact reached the level, with maximal dose of atorvastatin or rosuvastatin only 7.9% patients reached the targeted LDL level. Reasons for not reaching the target levels were evaluated by physicians in each patient. Side-effects of therapy and non-compliance of patients were responsible for 18% and 30% of cases. Conclusions: Reference of FH patients to lipid clinics in Slovakia improved the treatment, however, almost 25% of the patients were still without statin treatment and majority of patients did not reach target LDL levels.
PO406. THE FIRST RESULTS OF THE LATVIAN REGISTRY OF FAMILIAL HYPERCHOLESTEROLEMIA Gustavs Latkovskis1, 2, 3, Vita Saripo1, 2, 3, Dainus Gilis2, Arta Upena-Roze2, Andrejs Erglis1, 2, 3. 1 University of Latvia, Latvian Institute of Cardiology and Regenerative Medicine, Riga, Latvia; 2 University of Latvia, Faculty of Medicine, Riga, Latvia; 3 Pauls Stradins Clinical University Hospital, Latvian Center of Cardiology, Riga, Latvia Aim: To evaluate clinical characteristics and efficacy of previous management of individuals included in the Latvian Registry of Familial Hypercholesterolemia (LRFH), which was established in February 2015. Methods: Diagnosis of FH was evaluated by Dutch Lipid Clinic Network (DLCN) criteria. Cascade screening of the 1st degree relatives using age and gender specific percentiles of LDL-C was performed in probands with definite and probable FH. Results: One hundred and ninety two adult patients were included in LRFH by November 2016. Majority (n¼151, 79%) were index cases, of whom 36 (24%) had definite, 30 (20%) probable and 58 (38%) possible FH. In cascade screening of eligible relatives LDL-C above 95th percentile was found in 24 of 41 relatives (59%). Thus, altogether 90 patients were diagnosed with FH (mean age 51.9±14.6 years, 30% men). Mean (SD) LDL-C at inclusion was 5.3±2.2 and 5.7±1.3 mmol/l in index cases and relatives, respectively. Only 43 probands (59%) and 5 relatives (21%) were on lipid lowering therapy, and treatment goal was reached in 6 (9%) probands and none of relatives at inclusion. Coronary heart disease (CHD) was diagnosed
e233
in 36 (55%) and 4 (17%) probands and relatives, respectively. Correspondingly onset of CHD was premature in 29 (44%) and 3 (13%) of cases. Conclusions: Within one and a half years we have identified around 1.1% of the estimated number of 8000 FH patients in Latvia. Vast majority had been under-diagnosed and not managed according to international guidelines. There is an urgent need to further develop LRFH.
PO407. CHARACTERISTICS OF LIPID PROFILE IN THE DIFFERENT TYPES OF GLYCOGEN STORAGE DISEASE Natalia Polenova1, 2, Antonina Starodubova1, 2, Tatyana Strokova1,2, Krasilova1, 2, Madlena Bagaeva1, 2. Svetlana Kosyura1, 2, Anastasia 1 Russian Research Institute of Nutrition and Biotechnology, Moscow, Russia; 2 Pirogov Russian National Research Medical University, Moscow, Russia Aim: Aim of our study - to estimate the parameters of lipid profile in patients with the different types of glycogen storage disease (GSD). Methods: 62 patients with GSD (mean age 8.2±0.7) were divided to 3 groups: I-th group - 19 patients with GSD type I (30%), IIth - 16 with GSD type III (25.8%), IIIth - 27 with GSD IV e IX (43.5%). Height, weight, body mass index (BMI), serum levels of total cholesterol (TC), triglycerides (TG), high density cholesterol (HDL)- and low density (LDL) cholesterol were measured. Results: 44 Patients (70.1%) have shown the abnormal lipid profile. The mean TG level was significant higher (p<0.05) in GSD type I and LDL in GSD type III. Level of total cholesterol (TC) were in general group 4,7±0,2 mmol/ l, in I group - 4,9±0,5 mmol/l, in II group - 4,9±0,3 mmol/l, in III group 4,4±0,2 mmol/l. The mean level of HDL were 0,6±0,03 mmol/l in general group, 0,8±0,06 mmol/l in I group, 0,8±0,07 mmol/l in II group and 1,1±0,1 mmol/l in III group. The LDL parameters in the different groups were: general group - 3,1±0,1 mmol/l, I - 2,8±0,2 mmol/l, II - 3,6±0,3 mmol/l, III 0,9±0,06 mmol/l. The means TG-level in general population - 2,2±0,3 mmol/l, in I group - 3,9±0,8 mmol/l, II group - 2,05±0,3mmol/l, III - 1,1±0,1 mmol/l. Conclusions: In this study more, then two-thirds of patients with GSD lipid abnormality were detected. Most prevalence lipid disorder by GSD type I is hypertriglyceridemia, whereas by GSD type III - high LDL-level.
PO408. FIRST DATA FROM THE GERMAN CASCADE SCREENING PROGRAM FOR FAMILIAL HYPERCHOLESTEROLEMIA e CARE HIGH arz2, 3, 4. 1 D-A-CHNina Schmidt1, Alexander Dressel1, Winfried M€ €vention v. Herz-Kreislauf-Erkrankungen e.V., Hamburg, Gesellschaft Pra €t Mannheim der Germany; 2 Medizinische Klinik V, Medizinische Fakulta €t Heidelberg, Mannheim, Germany; 3 Klinisches Institut für Universita €t Medizinische und Chemische Labordiagnostik, Medizinische Universita Graz, Graz, Austria; 4 Synlab Akademie, Synlab Services GmbH, Mannheim/ Augsburg, Germany Aim: Familial hypercholesterolemia (FH) is an inherited disorder of the LDL-cholesterol metabolism, leading to an increased risk of cardiovascular disease, even at young age. This risk can be significantly lowered by early diagnosis and treatment. About 271000 patients affected in Germany are not diagnosed correctly and only a small number is treated properly. To improve FH diagnosis in the general population a cascade screening and registry program was established by us. Methods: Study assistants contact physicians and lipid clinics to introduce the cascade screening and registry. The physicians identify possible FH patients and include them in the study. Patient data is acquired via questionnaires about medical history. Patients meeting at least two inclusion criteria (LDL-C >190 mg/dl; Cholesterol >290 mg/dl; tendon xanthomas; family history of hypercholesterolemia or early myocard infarct) are included in the registry. Family members will be contacted and physicians get feedback about diagnosis and treatment options. Ethical approvals for all German states were collected.
e234
Abstracts / Atherosclerosis 263 (2017) e111ee282
Results: We show initial analysis of the first 300 data sets regarding anamnesis data, comorbidities, state of therapy and target value attainment depending on therapy. Conclusions: Initial analysis of the registry data shows that FH patients in Germany, as expected, are at high risk for early CVD. About 25% of the patients remain untreated and only 15% of the patients attain the LDL cholesterol target value despite lipid lowering therapy. Our data show that FH is still under-diagnosed and under-treated in Germany.
PO409. MUTATION ANALYSIS OF THE HYPERCHOLESTEROLEMIC PATIENTS
LDLR
GENE
IN
CZECH
1, Ales Horinek1, Jaroslav Hubacek2, Lukas Lucie Schwarzova Zlatohlavek1, Martina Vaclova1, Richard Ceska1, Michal Vrablik1. 1 Centre for preventive cardiology, 3rd Dept. of Internal Medicine, 1st Faculty of Medicine, Charles University, Prague, Czech Republic; 2 CEM, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
patient was a female born in 1973. Her plasma lipid levels in 2004 when the diagnosis of FH was established were e TC 10.4, LDL-C 8.3, HDL-C 1.8 and TG 0.6, all in mmol/l. This patient is free of symptomatic cardiovascular or cerebrovascular disease. Conclusions: The most frequent mutation was c.1775G>A (G592E) variant in our group of patients. Six novel variants were detected in these Czech patients. Supported by and AZV CR 15-28277A (Ministry of Health), and UNCE 204022 (Charles University of Prague).
PO410. AORTIC ELASTIC PROPERTIES OF FAMILIAL HYPERCHOLESTEROLEMIA PATIENTS Esra Kaya1, Meral Kayikcioglu2, Serdar Payzin2, Levent Hurkan Can2. 1 Rize Kackar State Hospital, Rize, Turkey; 2 Ege University Medical School Cardiology Department, Izmir, Turkey Aim: Familial hypercholesterolemia (FH) is a genetic disease characterized by premature atherosclerosis due to high cholesterol burden since birth.
Ă
Aim: Familial hypercholesterolemia (FH) and familial defective apoB 100 (FDB) are autosomaly dominant diseases of lipid metabolism, characterized by increased plasma low-density lipoprotein cholesterol (LDL-C) levels, and caused mostly by the mutations within the LDL receptor (FH patients) or the R3500Q mutation in apoB gene (FDB patients). Recently, the prevalence of this disorder has been estimated to be even 1:200, thus making FH the most common inherited metabolic disaease. Methods: 113 Czech Caucasian hypercholesterolemic FDB mutation negative patients were screened by PCR-RFLP for the most common LDL receptor mutation c.1775G>A (G592E). Negative individuals were sequenced by Sanger and/or NGS (Illumina) method in order to reveal mutations within other exons of the gene. Results: We have found 25 mutations of the LDLR gene in the whole set of FH patients. Twenty of these are missense variants, and five are short deletions of one to three bases range. One individual was detected to be homozygous for c.1775G>A mutation within the LDL-receptor gene. The
Aortic stiffness and related elastic properties are associated with subclinical atherosclerosis. We aimed to evaluate the aortic elastic properties in patients with FH. Methods: We studied 84 patients diagnosed as FH according to Simon Broome National Registry and Dutch Lipid Clinic Network Criteria. Systolic and diastolic blood pressure were obtained, aortic systolic and diastolic diameters were measured. Aortic elastic properties were measured by GE Healthcare Vivid 7 Pro Ultrasound System (M4S probe, 1.5-4.3 mHz) and evaluated according to some special formulas including aortic strain, elastic modulus [E(p)] , aortic stiffness index beta and aortic distensibility (Table 1). Results: Mean age was 56 ± 11 years and 51 patients (61% ) were female. Mean aortic strain was 0.12 ± 0.08 while the mean value of elastic modulus [E(p)] was 0.59 ± 0.45. Mean aortic stiffness index beta was 6.4 ± 4.9 and mean aortic distensibility was 5.36 ± 3.9. The mean propagation velocity of descending aorta was 47.4±15.2 (Table 2). Compared to standard norms, all