- Email: [email protected]
International comparison of services and facilities for the care of familial hypercholesterolaemia (FH)
e28
Abstracts / Atherosclerosis 252 (2016) e1ee196
when assessed against the DLCC. The SB Register criteria, the US MEDPED and the JFHMC had low diagnostic sensitivity (51.1% vs. 25.3% vs. 47.0% respectively). However, the SB Register criteria showed better diagnostic performance than the other criteria with 98.8% specificity, 28.6% efficiency, 98.1% and 62.3% for positive and negative predictive values respectively. Conclusions: All the other criteria have low sensitivity compared to the DLCC implying that there are less suited for screening of FH cases. However, the SB Register criterion is comparable with the DLCC in terms of specificity. Therefore, the DLCC appear to be better at clinically screening FH cases whilst both DLCC and SB Register criteria are more useful in identifying the positive cases to be confirmed by genetic testing.
EAS16-0757, DYSLIPIDEMIAS: DYSLIPIDEMIAS, SCREENING AND TREATMENT. DUTCH SCORE AND “CASCADE SCREENING” FOR THE IDENTIFICATION OF PATIENTS AFFECTED BY HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA S. Sperlongano 1, C. Garaffa 1, F. Natale 1, F. Fimiani 1, E. Garaffa 2, L. D'Acierno 1, M. Laringe 2, G. Limongelli 1, G. Piccinocchi 2, P. 1. 1 Second University of Naples, Monaldi Hospital, Naples, Italy; Calabro 2 CO.ME.GEN, General pratictioners, Naples, Italy Aim: to identify and analyse families of people with homozygous familial hypercholesterolemia (FH), to focus our attention on this rare disease, characterized by a very high cardiovascular risk and too often underdiagnosed and undertreated. Methods: We extrapolated from a total of 3250 patients from our ward and clinics (subjects with suspected characteristics of FH, e.g. premature coronary heart disease, very high level of LDL Cholesterol, tendon xanthomas) and adopted Dutch Lipid Clinic Network (DLCN) criteria to establish the clinical diagnosis of FH. For the early identification of new FH subjects, we performed a cascade screening of family members of probands with a definite or probable diagnosis of FH (DLCN > 5), analysing pedigrees of families with FH. Results: Between October 2014 and September 2015 we selected 7 probands, of whom 4 got DLCN > 8 (definite diagnosis of FH) and 3 got DLCN between 6 and 8 (probable diagnosis). Finally, we obtained 7 families of patients with definite or probable diagnosis of FH according to their clinical and/or genetic characteristics. One of the probands has also a genetic diagnosis of homozygous FH. Conclusions: Dutch Score is a very useful instrument to make diagnosis of FH. An early diagnosis is essential to readily adopt a treatment whit traditional and novel cholesterol-lowering medication to attenuate development of atherosclerosis and to prevent cardiovascular diseases.
EAS16-0761, DYSLIPIDEMIAS: DYSLIPIDEMIAS, SCREENING AND TREATMENT. RETROSPECTIVE OBSERVATIONAL STUDY ON THE DIAGNOSIS AND THERAPY OF THE FH ON A SAMPLE OF REAL WORLD POPULATION C. Garaffa 1, F. Natale 1, S. Sperlongano 1, F. Fimiani 1, M. Laringe 2, L. D'Acierno 1, E. Garaffa 2, G. Limongelli 1, G. Piccinocchi 2, P. 1. 1 Second University of Naples, Monaldi Hospital, Naples, Italy; Calabro 2 CO.ME.GEN, General pratictioners, Naples, Italy Objectives: FH is a genetic disorder underdiagnosed and therefore undertreated. In Italy, as in the majority of the European countries, the diagnosis is less than1% of cases. Aim: to highlight the real prevalence of FH, the management of the latter by the GPs and the correlation between FH and CV accidents. Methods: we used a DB containing the medical records of 174.459 patients of a cooperative of 130 GPs (CO.ME.GEN.) all operating in the City of Naples. The parameters of the queries used were: an value of total cholesterol 310 or of LDL cholesterol 200. The final study population obtained was of 1832 patients.
Results: with regard to the inclusion in a diagnostic category it was evidenced that it was given a diagnosis according to the criteria ICD9 only to 1089 patients (59.44%). Of a total of 174.459 patients, 109 (0,06%) had a diagnosis of FH. Of the tested sample, only 946 patients (51.6%) were treated. Of these, only 29 (3%) reached target levels of total cholesterol and none target of LDL as recommended by the guidelines. Moreover from the analysis of 22015 deaths it has been pointed out a direct relationship between death from CV causes and cholesterol 310. Conclusions: the analysis of the data base of a cooperative of GPs operating in the city of Naples resulted in the evidence of a clear under diagnosis of the FH in a real world population and a further analysis could lead to an improvement in the management of patients with FH.
EAS16-1049, DYSLIPIDEMIAS: DYSLIPIDEMIAS, SCREENING AND TREATMENT. INTERNATIONAL COMPARISON OF PRIMARY CARE KNOWLEDGE AND PRACTICES OF FAMILIAL HYPERCHOLESTEROLAEMIA (FH) G.F. Watts. University of Western Australia, Medicine and Pharmacology, Perth, Australia Objectives: To determine primary care physicians (PCPs)' awareness, knowledge and practices regarding the care of FH. Methods: A formal questionnaire was anonymously completed by physicians in 10 different countries (Australia, Japan, Malaysia, Vietnam, India, the Philippines, United Kingdom, China, South Africa and South Korea). The survey sought responses relating to general familiarity, awareness of management guidelines, identification (clinical characteristics and lipid profile), prevalence and inheritance, extent of elevation in risk of cardiovascular disease (CVD), and practice on screening and treatment. Results: 1,433 physicians completed the questionnaire with only 33% considered themselves to be familiar with FH. 76% correctly defined FH and 65% identified the typical lipid profile, with a higher proportion of physicians from United Kingdom, China and Japan selected the correct FH definition and lipid profile compared with those from South Korea, India and Vietnam. However, less than half of the physician across the 10 countries were aware of national or international management guidelines (38%), or correctly defined the prevalence (27%), inheritance (41%), and CVD risk of FH (11%). 56% suggested PCPs as the most effective health professional to detect FH. The majority of the physicians also considered laboratory interpretative comments are useful (82%) and statin therapy is an appropriate cholesterol-lowering therapy (91%) for FH management. Conclusions: The study identified substantial deficits in the awareness and knowledge of FH among physicians in the region. Implementation of country-specific guidelines and extensive work in FH education and awareness programs are imperative to improve the care of FH.
EAS16-1050, DYSLIPIDEMIAS: DYSLIPIDEMIAS, SCREENING AND TREATMENT. INTERNATIONAL COMPARISON OF SERVICES AND FACILITIES FOR THE CARE OF FAMILIAL HYPERCHOLESTEROLAEMIA (FH) G.F. Watts. University of Western Australia, Medicine and Pharmacology, Perth, Australia Objectives: To describe existing health services, facilities and resources for the care of FH in countries in the Asia-Pacific region, South Africa, Brazil and United Kingdom. Methods: A formal questionnaire that investigates the six key elements of a desirable FH model of care (availability of national guidelines and protocols, lipid clinic network, DNA testing facilities, paediatric and cardiovascular imaging services, and apheresis facilities) was completed by leading experts in FH from 15 countries (Australia, Brazil, China, Hong Kong, India, Japan, Malaysia, New Zealand, the Philippines, Singapore, South Africa, South Korea, Taiwan, United Kingdom and Vietnam). Results: 94 leading experts in FH completed the questionnaires. Of the 15 countries or regions studied, 45% had established national guidelines and
Abstracts / Atherosclerosis 252 (2016) e1ee196
protocols for FH management. Only 30% had a network of lipid clinics. More than half of the countries provided genetic (53%) and paediatric services (66%) to FH patients. Formal LDL apheresis service was only available in 7 countries (45%). All 15 countries or regions had cardiovascular imaging facilities available for FH patients. Australia, United Kingdom and Japan are the three countries providing all six services and facilities to FH patients. In contrast, the care of FH in Vietnam and the Philippines is suboptimal with less than three services and facilities available in their countries. Conclusions: This survey has identified important gaps in services and facilities for FH management. Further focus on implementation of national management guidelines, lipid clinic network and apheresis facilities are required, particularly in less developed countries.
EAS16-0680, DYSLIPIDEMIAS: DYSLIPIDEMIAS, SCREENING AND TREATMENT. SWITCH TO ROSUVASTATIN VERSUS ADDITION OF EZETIMIBE IN PATIENTS RECEIVING ATORVASTATIN: EFFECT ON URINE 8ISOPROSTANE LEVELS E. Klouras 1, C. Tellis 2, F. Barkas 1, E. Liberopoulos 1, M. Elisaf 1, A. Tselepis 2. 1 School of Medicine - University of Ioannina, Department of Internal Medicine, Ioannina, Greece; 2 Department of Chemistry- University of Ioannina, Atherothrombosis Research Centre / Laboratory of Biochemistry, Ioannina, Greece Objectives: Oxidative stress is an essential part of atherosclerosis, while statin treatment exhibit significant antioxidant activity. Urine 8-isoprostane, a non-enzymatic product of phospholipids’ oxidation, is a reliable marker of oxidative stress. The aim of the present study is to assess the effect of switch to rosuvastatin or addition of ezetimibe on urine 8-isoprostane levels of dyslipidemic patients receiving atorvastatin. Methods: Study’s population consisted of dyslipidemic patients taking atorvastatin (10 or 20 mg daily for at least three months) and not attaining the LDL-cholesterol targets according to European Society of Cardiology/ European Atherosclerosis Society (ESC/EAS) guidelines (n¼28). Thirteen subjects were assigned to rosuvastatin (20 or 40 mg daily, respectively) and 15 to ezetimibe (10 mg daily) on top of atorvastatin. After three months of treatment, we assessed the change of urine 8-isoprostane levels (expressed as urine 8-isoprostane/urine creatine ratio), quantificated with enzyme immunoassay (Cayman Chemical’s ACE EIA Kits), in the two groups. Results: In the group switching from atorvastatin to higher dose of rosuvastatin, urine 8-isoprostane levels reduced significantly by 43.5% (from 14.15 ± 9.47 ng/mmol to 8.00 ± 3.08 ng/mmol, p¼0.03). On the other hand, a non-significant change of urine 8-isoprostane levels was found after the addition of ezetimibe (from 14.16 ± 12.3 ng/mmol to 9.02 ± 5.99 ng/mmol, NS). Conclusions: Switching to higher dose of rosuvastatin significantly reduces urine 8-isoprostane levels in dyslipidemic subjects receiving atorvastatin, an effect which is not observed after a three month addition of ezetimibe to atorvastatin.
EAS16-0415, DYSLIPIDEMIAS: DYSLIPIDEMIAS, SCREENING AND TREATMENT. CASCADE GENETIC SCREENING FOR FAMILIAL HYPERCHOLESTEROLEMIA IN WEST SIBERIA E. Shakhtshneider 1, K. Makarenkova 2, D. Ivanoshchuk 1, P. Orlov 1, Y. Ragino 3, M. Voevoda 1. 1 Institute of Internal and Preventive Medicine, Laboratory of medical genetics, Novosibirsk, Russia; 2 Institute of Internal and Preventive Medicine, Clinical department, Novosibirsk, Russia; 3 Institute of Internal and Preventive Medicine, Laboratory of bichemistry, Novosibirsk, Russia Objectives: Familial hypercholesterolemia (FH) is one of the most common congenital metabolic disorders. Aim of study is examine of patients with FH using the principle of a cascade genetic screening in West Siberia.
e29
Methods: The study was performed in patients with a clinical diagnosis of definite FH (The Simon Broom Register Group and Dutch Lipid Clinic Network Criteria). 32 patients with total cholesterol level > 7 mmol/l were examined in clinical department in 2015 year. Definite FH according clinical criteria was identified in 12 patients, 47±14 age. It was 10 unrelated patients and 2 patients from one family (mother and son). The plasma lipid levels were determined by standard enzymatic assays. The LDLR gene was analyzed by targeted high-throughput sequencing (NimbleGen SeqCap Target Enrichment; GS Junior, Roche). Results: Mean TC level was 8±1,8 mmol/l in patients with FH. 50% of patients used statins. 42% of patients with FH had xanthomas. We found rs5930 and rs121908038 of LDLR that were associated with the FH in previous studies. Missense mutation Cys340Phe (rs755757866) has been identified as damaging (PolyPhen2, Score of 1.000). All of non-synonymous SNP were presented in heterozygous state. All patients had synonymous SNPs in LDLR and a lot of SNPs in introns of LDLR. Conclusions: In 10 of 12 patients with FH (83.3%) were identified changes in structure LDLR, which may lead to a change in the function of the LDL receptor. This study confirmed genetic heterogeneity of the spectrum of structural modifications of LDLR in FH patients. The study supported by RHF, N14-06-00867.
EAS16-0129, DYSLIPIDEMIAS: DYSLIPIDEMIAS, SCREENING AND TREATMENT. LIPID CLINIC EXPERIENCE OF GENOTYPING FOR FAMILIAL HYPERCHOLESTEROLAEMIA K. Shipman, R. Cramb. University Hospitals Birmingham NHS Foundation Trust, Department of Clinical Chemistry, Birmingham, United Kingdom Objectives: In the West Midlands commissioners have refused to fund widespread genotyping of possible familial hypercholesterolaemia (FH) cases therefore clinics have performed testing only when the data may help management of the case and their family. It is hoped that a cascade screening service will soon start in the region so clinic data were assessed to see if standard criteria would be suitable to select cases for screening. Methods: Six months of data from a large secondary care lipid clinic were examined, via laboratory systems and electronic notes. Results: Not all data were available but in total 21 patients were tested: 6 were heterozygous (5 LDLR and 1 ApoB), two were homozygous for LDLR mutations and one was compound heterozygous for LDLR and ApoB mutations (43% positive rate). Three patients were part of cascade screening; 2 were positive. Of the genotype negative 11 (92%) had documented family history of high lipids and all had a family history of premature cardiovascular disease except for 2, and 3 who had nothing on family history documented. The average total cholesterol was higher in the gene positive (11.5 mmol/L) versus the gene negative (8.0 mmol/L) but some numbers were estimated based on letters stating pre-treatment values. Only 1 had tendon xanthomata, the homozygous LDLR patient. Conclusions: Despite very selective testing, with only 3 of the 21 being for cascade screening, the mutation positive rate was only 43%. Higher cholesterol is more likely to be associated with a positive mutation in this cohort.
EAS16-0144, DYSLIPIDEMIAS: DYSLIPIDEMIAS, SCREENING AND TREATMENT. CAROTID PLAQUES AND INTIMA-MEDIA THICKNESS-ARE THE SAME RISK FACTORS IN MEN AND WOMEN WITH FAMILIAL HYPERCHOLESTEROLEMIA? M. Walus-Miarka 1, B. Idzior-Walus 1, D. Czarnecka 2, M. KlochBadełek 2, W. Wojciechowska 2, M. Kapusta 3. 1 Jagiellonian University Medical College, Metabolic Diseases, Krakow, Poland; 2 Jagiellonian University Medical College, I Department of Cardiology, Krakow, Poland; 3 Jagiellonian University Medical College, Biochemistry, Krakow, Poland Objectives: Familial hypercholesterolemia (FH) is strongly associated with premature coronary heart disease. It is autosomal dominant disorder and
Abstracts / Atherosclerosis 252 (2016) e1ee196
when assessed against the DLCC. The SB Register criteria, the US MEDPED and the JFHMC had low diagnostic sensitivity (51.1% vs. 25.3% vs. 47.0% respectively). However, the SB Register criteria showed better diagnostic performance than the other criteria with 98.8% specificity, 28.6% efficiency, 98.1% and 62.3% for positive and negative predictive values respectively. Conclusions: All the other criteria have low sensitivity compared to the DLCC implying that there are less suited for screening of FH cases. However, the SB Register criterion is comparable with the DLCC in terms of specificity. Therefore, the DLCC appear to be better at clinically screening FH cases whilst both DLCC and SB Register criteria are more useful in identifying the positive cases to be confirmed by genetic testing.
EAS16-0757, DYSLIPIDEMIAS: DYSLIPIDEMIAS, SCREENING AND TREATMENT. DUTCH SCORE AND “CASCADE SCREENING” FOR THE IDENTIFICATION OF PATIENTS AFFECTED BY HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA S. Sperlongano 1, C. Garaffa 1, F. Natale 1, F. Fimiani 1, E. Garaffa 2, L. D'Acierno 1, M. Laringe 2, G. Limongelli 1, G. Piccinocchi 2, P. 1. 1 Second University of Naples, Monaldi Hospital, Naples, Italy; Calabro 2 CO.ME.GEN, General pratictioners, Naples, Italy Aim: to identify and analyse families of people with homozygous familial hypercholesterolemia (FH), to focus our attention on this rare disease, characterized by a very high cardiovascular risk and too often underdiagnosed and undertreated. Methods: We extrapolated from a total of 3250 patients from our ward and clinics (subjects with suspected characteristics of FH, e.g. premature coronary heart disease, very high level of LDL Cholesterol, tendon xanthomas) and adopted Dutch Lipid Clinic Network (DLCN) criteria to establish the clinical diagnosis of FH. For the early identification of new FH subjects, we performed a cascade screening of family members of probands with a definite or probable diagnosis of FH (DLCN > 5), analysing pedigrees of families with FH. Results: Between October 2014 and September 2015 we selected 7 probands, of whom 4 got DLCN > 8 (definite diagnosis of FH) and 3 got DLCN between 6 and 8 (probable diagnosis). Finally, we obtained 7 families of patients with definite or probable diagnosis of FH according to their clinical and/or genetic characteristics. One of the probands has also a genetic diagnosis of homozygous FH. Conclusions: Dutch Score is a very useful instrument to make diagnosis of FH. An early diagnosis is essential to readily adopt a treatment whit traditional and novel cholesterol-lowering medication to attenuate development of atherosclerosis and to prevent cardiovascular diseases.
EAS16-0761, DYSLIPIDEMIAS: DYSLIPIDEMIAS, SCREENING AND TREATMENT. RETROSPECTIVE OBSERVATIONAL STUDY ON THE DIAGNOSIS AND THERAPY OF THE FH ON A SAMPLE OF REAL WORLD POPULATION C. Garaffa 1, F. Natale 1, S. Sperlongano 1, F. Fimiani 1, M. Laringe 2, L. D'Acierno 1, E. Garaffa 2, G. Limongelli 1, G. Piccinocchi 2, P. 1. 1 Second University of Naples, Monaldi Hospital, Naples, Italy; Calabro 2 CO.ME.GEN, General pratictioners, Naples, Italy Objectives: FH is a genetic disorder underdiagnosed and therefore undertreated. In Italy, as in the majority of the European countries, the diagnosis is less than1% of cases. Aim: to highlight the real prevalence of FH, the management of the latter by the GPs and the correlation between FH and CV accidents. Methods: we used a DB containing the medical records of 174.459 patients of a cooperative of 130 GPs (CO.ME.GEN.) all operating in the City of Naples. The parameters of the queries used were: an value of total cholesterol 310 or of LDL cholesterol 200. The final study population obtained was of 1832 patients.
Results: with regard to the inclusion in a diagnostic category it was evidenced that it was given a diagnosis according to the criteria ICD9 only to 1089 patients (59.44%). Of a total of 174.459 patients, 109 (0,06%) had a diagnosis of FH. Of the tested sample, only 946 patients (51.6%) were treated. Of these, only 29 (3%) reached target levels of total cholesterol and none target of LDL as recommended by the guidelines. Moreover from the analysis of 22015 deaths it has been pointed out a direct relationship between death from CV causes and cholesterol 310. Conclusions: the analysis of the data base of a cooperative of GPs operating in the city of Naples resulted in the evidence of a clear under diagnosis of the FH in a real world population and a further analysis could lead to an improvement in the management of patients with FH.
EAS16-1049, DYSLIPIDEMIAS: DYSLIPIDEMIAS, SCREENING AND TREATMENT. INTERNATIONAL COMPARISON OF PRIMARY CARE KNOWLEDGE AND PRACTICES OF FAMILIAL HYPERCHOLESTEROLAEMIA (FH) G.F. Watts. University of Western Australia, Medicine and Pharmacology, Perth, Australia Objectives: To determine primary care physicians (PCPs)' awareness, knowledge and practices regarding the care of FH. Methods: A formal questionnaire was anonymously completed by physicians in 10 different countries (Australia, Japan, Malaysia, Vietnam, India, the Philippines, United Kingdom, China, South Africa and South Korea). The survey sought responses relating to general familiarity, awareness of management guidelines, identification (clinical characteristics and lipid profile), prevalence and inheritance, extent of elevation in risk of cardiovascular disease (CVD), and practice on screening and treatment. Results: 1,433 physicians completed the questionnaire with only 33% considered themselves to be familiar with FH. 76% correctly defined FH and 65% identified the typical lipid profile, with a higher proportion of physicians from United Kingdom, China and Japan selected the correct FH definition and lipid profile compared with those from South Korea, India and Vietnam. However, less than half of the physician across the 10 countries were aware of national or international management guidelines (38%), or correctly defined the prevalence (27%), inheritance (41%), and CVD risk of FH (11%). 56% suggested PCPs as the most effective health professional to detect FH. The majority of the physicians also considered laboratory interpretative comments are useful (82%) and statin therapy is an appropriate cholesterol-lowering therapy (91%) for FH management. Conclusions: The study identified substantial deficits in the awareness and knowledge of FH among physicians in the region. Implementation of country-specific guidelines and extensive work in FH education and awareness programs are imperative to improve the care of FH.
EAS16-1050, DYSLIPIDEMIAS: DYSLIPIDEMIAS, SCREENING AND TREATMENT. INTERNATIONAL COMPARISON OF SERVICES AND FACILITIES FOR THE CARE OF FAMILIAL HYPERCHOLESTEROLAEMIA (FH) G.F. Watts. University of Western Australia, Medicine and Pharmacology, Perth, Australia Objectives: To describe existing health services, facilities and resources for the care of FH in countries in the Asia-Pacific region, South Africa, Brazil and United Kingdom. Methods: A formal questionnaire that investigates the six key elements of a desirable FH model of care (availability of national guidelines and protocols, lipid clinic network, DNA testing facilities, paediatric and cardiovascular imaging services, and apheresis facilities) was completed by leading experts in FH from 15 countries (Australia, Brazil, China, Hong Kong, India, Japan, Malaysia, New Zealand, the Philippines, Singapore, South Africa, South Korea, Taiwan, United Kingdom and Vietnam). Results: 94 leading experts in FH completed the questionnaires. Of the 15 countries or regions studied, 45% had established national guidelines and
Abstracts / Atherosclerosis 252 (2016) e1ee196
protocols for FH management. Only 30% had a network of lipid clinics. More than half of the countries provided genetic (53%) and paediatric services (66%) to FH patients. Formal LDL apheresis service was only available in 7 countries (45%). All 15 countries or regions had cardiovascular imaging facilities available for FH patients. Australia, United Kingdom and Japan are the three countries providing all six services and facilities to FH patients. In contrast, the care of FH in Vietnam and the Philippines is suboptimal with less than three services and facilities available in their countries. Conclusions: This survey has identified important gaps in services and facilities for FH management. Further focus on implementation of national management guidelines, lipid clinic network and apheresis facilities are required, particularly in less developed countries.
EAS16-0680, DYSLIPIDEMIAS: DYSLIPIDEMIAS, SCREENING AND TREATMENT. SWITCH TO ROSUVASTATIN VERSUS ADDITION OF EZETIMIBE IN PATIENTS RECEIVING ATORVASTATIN: EFFECT ON URINE 8ISOPROSTANE LEVELS E. Klouras 1, C. Tellis 2, F. Barkas 1, E. Liberopoulos 1, M. Elisaf 1, A. Tselepis 2. 1 School of Medicine - University of Ioannina, Department of Internal Medicine, Ioannina, Greece; 2 Department of Chemistry- University of Ioannina, Atherothrombosis Research Centre / Laboratory of Biochemistry, Ioannina, Greece Objectives: Oxidative stress is an essential part of atherosclerosis, while statin treatment exhibit significant antioxidant activity. Urine 8-isoprostane, a non-enzymatic product of phospholipids’ oxidation, is a reliable marker of oxidative stress. The aim of the present study is to assess the effect of switch to rosuvastatin or addition of ezetimibe on urine 8-isoprostane levels of dyslipidemic patients receiving atorvastatin. Methods: Study’s population consisted of dyslipidemic patients taking atorvastatin (10 or 20 mg daily for at least three months) and not attaining the LDL-cholesterol targets according to European Society of Cardiology/ European Atherosclerosis Society (ESC/EAS) guidelines (n¼28). Thirteen subjects were assigned to rosuvastatin (20 or 40 mg daily, respectively) and 15 to ezetimibe (10 mg daily) on top of atorvastatin. After three months of treatment, we assessed the change of urine 8-isoprostane levels (expressed as urine 8-isoprostane/urine creatine ratio), quantificated with enzyme immunoassay (Cayman Chemical’s ACE EIA Kits), in the two groups. Results: In the group switching from atorvastatin to higher dose of rosuvastatin, urine 8-isoprostane levels reduced significantly by 43.5% (from 14.15 ± 9.47 ng/mmol to 8.00 ± 3.08 ng/mmol, p¼0.03). On the other hand, a non-significant change of urine 8-isoprostane levels was found after the addition of ezetimibe (from 14.16 ± 12.3 ng/mmol to 9.02 ± 5.99 ng/mmol, NS). Conclusions: Switching to higher dose of rosuvastatin significantly reduces urine 8-isoprostane levels in dyslipidemic subjects receiving atorvastatin, an effect which is not observed after a three month addition of ezetimibe to atorvastatin.
EAS16-0415, DYSLIPIDEMIAS: DYSLIPIDEMIAS, SCREENING AND TREATMENT. CASCADE GENETIC SCREENING FOR FAMILIAL HYPERCHOLESTEROLEMIA IN WEST SIBERIA E. Shakhtshneider 1, K. Makarenkova 2, D. Ivanoshchuk 1, P. Orlov 1, Y. Ragino 3, M. Voevoda 1. 1 Institute of Internal and Preventive Medicine, Laboratory of medical genetics, Novosibirsk, Russia; 2 Institute of Internal and Preventive Medicine, Clinical department, Novosibirsk, Russia; 3 Institute of Internal and Preventive Medicine, Laboratory of bichemistry, Novosibirsk, Russia Objectives: Familial hypercholesterolemia (FH) is one of the most common congenital metabolic disorders. Aim of study is examine of patients with FH using the principle of a cascade genetic screening in West Siberia.
e29
Methods: The study was performed in patients with a clinical diagnosis of definite FH (The Simon Broom Register Group and Dutch Lipid Clinic Network Criteria). 32 patients with total cholesterol level > 7 mmol/l were examined in clinical department in 2015 year. Definite FH according clinical criteria was identified in 12 patients, 47±14 age. It was 10 unrelated patients and 2 patients from one family (mother and son). The plasma lipid levels were determined by standard enzymatic assays. The LDLR gene was analyzed by targeted high-throughput sequencing (NimbleGen SeqCap Target Enrichment; GS Junior, Roche). Results: Mean TC level was 8±1,8 mmol/l in patients with FH. 50% of patients used statins. 42% of patients with FH had xanthomas. We found rs5930 and rs121908038 of LDLR that were associated with the FH in previous studies. Missense mutation Cys340Phe (rs755757866) has been identified as damaging (PolyPhen2, Score of 1.000). All of non-synonymous SNP were presented in heterozygous state. All patients had synonymous SNPs in LDLR and a lot of SNPs in introns of LDLR. Conclusions: In 10 of 12 patients with FH (83.3%) were identified changes in structure LDLR, which may lead to a change in the function of the LDL receptor. This study confirmed genetic heterogeneity of the spectrum of structural modifications of LDLR in FH patients. The study supported by RHF, N14-06-00867.
EAS16-0129, DYSLIPIDEMIAS: DYSLIPIDEMIAS, SCREENING AND TREATMENT. LIPID CLINIC EXPERIENCE OF GENOTYPING FOR FAMILIAL HYPERCHOLESTEROLAEMIA K. Shipman, R. Cramb. University Hospitals Birmingham NHS Foundation Trust, Department of Clinical Chemistry, Birmingham, United Kingdom Objectives: In the West Midlands commissioners have refused to fund widespread genotyping of possible familial hypercholesterolaemia (FH) cases therefore clinics have performed testing only when the data may help management of the case and their family. It is hoped that a cascade screening service will soon start in the region so clinic data were assessed to see if standard criteria would be suitable to select cases for screening. Methods: Six months of data from a large secondary care lipid clinic were examined, via laboratory systems and electronic notes. Results: Not all data were available but in total 21 patients were tested: 6 were heterozygous (5 LDLR and 1 ApoB), two were homozygous for LDLR mutations and one was compound heterozygous for LDLR and ApoB mutations (43% positive rate). Three patients were part of cascade screening; 2 were positive. Of the genotype negative 11 (92%) had documented family history of high lipids and all had a family history of premature cardiovascular disease except for 2, and 3 who had nothing on family history documented. The average total cholesterol was higher in the gene positive (11.5 mmol/L) versus the gene negative (8.0 mmol/L) but some numbers were estimated based on letters stating pre-treatment values. Only 1 had tendon xanthomata, the homozygous LDLR patient. Conclusions: Despite very selective testing, with only 3 of the 21 being for cascade screening, the mutation positive rate was only 43%. Higher cholesterol is more likely to be associated with a positive mutation in this cohort.
EAS16-0144, DYSLIPIDEMIAS: DYSLIPIDEMIAS, SCREENING AND TREATMENT. CAROTID PLAQUES AND INTIMA-MEDIA THICKNESS-ARE THE SAME RISK FACTORS IN MEN AND WOMEN WITH FAMILIAL HYPERCHOLESTEROLEMIA? M. Walus-Miarka 1, B. Idzior-Walus 1, D. Czarnecka 2, M. KlochBadełek 2, W. Wojciechowska 2, M. Kapusta 3. 1 Jagiellonian University Medical College, Metabolic Diseases, Krakow, Poland; 2 Jagiellonian University Medical College, I Department of Cardiology, Krakow, Poland; 3 Jagiellonian University Medical College, Biochemistry, Krakow, Poland Objectives: Familial hypercholesterolemia (FH) is strongly associated with premature coronary heart disease. It is autosomal dominant disorder and