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1. PCSK9 inhibitors on the management of primary and secondary cardiovascular prevention

Author: Victoria Marco-Benedí, Rosa M. Sánchez-Hernández, José Luis Díaz, Estíbaliz Jarauta, Manuel Suárez-Tembra, Xavier Pintó, Carlos Morillas, Núria Plana, Juan Pedro-Botet, and Fernando Civeira
Subjects: PCSK9 inhibitors, Primary prevention, Secondary prevention, LDL-cholesterol, Familial hypercholesterolemia, Nutritional diseases. Deficiency diseases, RC620-627
Abstract: Abstract Background Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) have represented an important change in the management of hypercholesterolemia, although, until now, they have barely been used. Without PCSK9i, many patients with atherosclerotic cardiovascular disease (CVD) or those at very high risk do not reach their therapeutic LDLc objectives. Objective The analysis aimed to examine the clinical and biochemical characteristics of subjects receiving PCSK9i treatment in the Dyslipidemia Registry of the Spanish Atherosclerosis Society. Methods All consecutive subjects aged ≥ 18 years from different Lipid Units included in the Dyslipidemia Registry of the SEA were analyzed. Inclusion criteria consisted of unrelated patients aged ≥ 18 at the time of inclusion with hypercholesterolemia (LDL-C ≥ 130 mg/dL or non-HDL-C ≥ 160 mg/dL after the exclusion of secondary causes) who were studied for at least two years after inclusion. Participants’ baseline and final visit clinical and biochemical characteristics were analyzed based on whether they were on primary or secondary prevention and whether they were taking PCSK9i at the end of follow-up. Results Eight hundred twenty-nine patients were analyzed, 7014 patients in primary prevention and 1281 in secondary prevention at baseline. 4127 subjects completed the required follow-up for the final analysis. The median follow-up duration was 7 years (IQR 3.0–10.0). Five hundred patients (12.1%) were taking PCSK9i at the end of the follow-up. The percentage of PCSK9i use reached 35.6% (n = 201) and 8.7% (n = 318) in subjects with and without CVD, respectively. Subjects on PCSK9i and oral lipid-lowering agents with and without CVD achieved LDLc reductions of 80.3% and 75.1%, respectively, concerning concentrations without lipid-lowering drugs. Factors associated with PCSK9i use included increasing age, LDLc without lipid-lowering drugs and the Dutch Lipid Clinic Network (DLCN) score. However, hypertension, diabetes, smoking, and LDLc after oral lipid-lowering drugs were not independent factors associated with PCSK9i prescription. In subjects with CVD, the use of PCSK9i was higher in men than in women (an odds ratio of 1.613, P = 0.048). Conclusions Approximately one-third of CVD patients received PCSK9i at the end of follow-up. The use of PCSK9i was more focused on baseline LDLc concentrations rather than on CVD risk. Women received less PCSK9i in secondary prevention compared to men.
Published: 2024
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2. OptiMo‐LDLr: An Integrated In Silico Model with Enhanced Predictive Power for LDL Receptor Variants, Unraveling Hot Spot Pathogenic Residues

Author: Asier Larrea‐Sebal, Iñaki Sasiain, Shifa Jebari‐Benslaiman, Unai Galicia‐Garcia, Kepa B. Uribe, Asier Benito‐Vicente, Irene Gracia‐Rubio, Harbil Bediaga‐Bañeres, Sonia Arrasate, Ana Cenarro, Fernando Civeira, Humberto González‐Díaz, and Cesar Martín
Subjects: hot spot, in silico, LDLr, predictive software, Science
Abstract: Abstract Familial hypercholesterolemia (FH) is an inherited metabolic disease affecting cholesterol metabolism, with 90% of cases caused by mutations in the LDL receptor gene (LDLR), primarily missense mutations. This study aims to integrate six commonly used predictive software to create a new model for predicting LDLR mutation pathogenicity and mapping hot spot residues. Six predictive‐software are selected: Polyphen‐2, SIFT, MutationTaster, REVEL, VARITY, and MLb‐LDLr. Software accuracy is tested with the characterized variants annotated in ClinVar and, by bioinformatic and machine learning techniques all models are integrated into a more accurate one. The resulting optimized model presents a specificity of 96.71% and a sensitivity of 98.36%. Hot spot residues with high potential of pathogenicity appear across all domains except for the signal peptide and the O‐linked domain. In addition, translating this information into 3D structure of the LDLr highlights potentially pathogenic clusters within the different domains, which may be related to specific biological function. The results of this work provide a powerful tool to classify LDLR pathogenic variants. Moreover, an open‐access guide user interface (OptiMo‐LDLr) is provided to the scientific community. This study shows that combination of several predictive software results in a more accurate prediction to help clinicians in FH diagnosis.
Published: 2024
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3. Current causes of death in familial hypercholesterolemia

Author: Victoria Marco-Benedí, Ana M. Bea, Ana Cenarro, Estíbaliz Jarauta, Martín Laclaustra, and Fernando Civeira
Subjects: Heterozygous familial hypercholesterolemia phenotype, Parental-offspring, Cardiovascular disease death, Nutritional diseases. Deficiency diseases, RC620-627
Abstract: Abstract Background Familial hypercholesterolemia (FH) is a codominant autosomal disease characterized by high low-density lipoprotein cholesterol (LDLc) and a high risk of premature cardiovascular disease (CVD). The molecular bases have been well defined, and effective lipid lowering is possible. This analysis aimed to study the current major causes of death of genetically defined heterozygous familial hypercholesterolemia (heFH). Methods A case‒control study was designed to analyse life-long mortality in a group of heFH and control families. Data from first-degree family members of cases and controls (nonconsanguineous cohabitants), including deceased relatives, were collected from a questionnaire and review of medical records. Mortality was compared among heFH patients, nonheFH patients, and nonconsanguineous family members. Results A total of 813 family members were analysed, 26.4% of whom were deceased. Among the deceased, the mean age of death was 69.3 years in heFH individuals, 73.5 years in nonheFH individuals, and 73.2 years in nonconsanguineous individuals, without significant differences. CVD was the cause of death in 59.7% of heFH individuals, 37.7% of nonheFH individuals, and 37.4% of nonconsanguineous individuals (P = 0.012). These differences were greater after restricting the analyses to parents. The hazard ratio of dying from CVD was 2.85 times higher (95% CI, (1.73–4.69) in heFH individuals than in individuals in the other two groups (non-FH and nonconsanguineous), who did not differ in their risk. Conclusions CVD mortality in heFH individuals is lower and occurs later than that described in the last century but is still higher than that in non-FH individuals. This improved prognosis of CVD risk is not associated with changes in non-CVD mortality.
Published: 2022
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4. An elevated parametric thyroid feedback quantile-based index is associated with atrial fibrillation

Author: Vanesa Alonso-Ventura, Patricia Campos-Magallon, Belen Moreno-Franco, Pilar Calmarza, Fernando Calvo-Gracia, Jose Manuel Lou-Bonafonte, Patricia de Diego-Garcia, Jose Antonio Casasnovas, Victoria Marco-Benedi, Fernando Civeira, and Martin Laclaustra
Subjects: atrial fibrillation, thyroid regulation, thyrotropin, thyroxine, Parametric Thyroid Feedback Quantile-Based Index, PTFQI, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract: IntroductionAtrial fibrillation is associated with hyperthyroidism. Within the euthyroid range, it is also associated with high thyroxine (fT4), but not with thyrotropin (TSH). We aim to describe differences in thyroid regulation, measured by the Parametric Thyroid Feedback Quantile-Based Index (PTFQI), between patients with atrial fibrillation and the general population.Materials and methodsThyroid parameters (PTFQI, TSH, and fT4) of a sample of 84 euthyroid subjects with atrial fibrillation (cases) were compared to a reference sample of euthyroid healthcare patients (controls). We calculated age and sex adjusted ORs for atrial fibrillation across tertiles of these parameters. Also, within cases, we studied thyroid parameters association with clinical characteristics of the atrial fibrillation.ResultsAfter adjusting for age and sex, fT4 and PTFQI were higher in subjects with atrial fibrillation when compared to the general sample (p
Published: 2023
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5. High consumption of ultra-processed food may double the risk of subclinical coronary atherosclerosis: the Aragon Workers’ Health Study (AWHS)

Author: Henry Montero-Salazar, Carolina Donat-Vargas, Belén Moreno-Franco, Helena Sandoval-Insausti, Fernando Civeira, Martín Laclaustra, and Pilar Guallar-Castillón
Subjects: Ultra-processed food, Subclinical coronary atherosclerosis, Coronary calcium, Cross-sectional cohort study, Nutritional epidemiology, Medicine
Abstract: Abstract Background Ultra-processed food (UPF) consumption, which is increasing worldwide, has recently been associated with an increased risk of death and cardiovascular disease. We aimed to assess whether consumption of UPF is directly associated with subclinical coronary atherosclerosis in middle-aged men. Methods A computed tomography scan was performed on 1876 men from the Aragon Workers’ Health Study, recruited from January 2011 to December 2014, to assess coronary calcium. All participants were free of coronary heart disease. Dietary intake was collected by a validated 136-item semi-quantitative food frequency questionnaire. UPF was defined according to the NOVA classification. Associations between consumption of total energy-adjusted UPF and Coronary Calcium Agatston Score (CACS)—categorized into CACS of 0, > 0 and 0 and
Published: 2020
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6. Obtaining evidence base for the development of Feel4Diabetes intervention to prevent type 2 diabetes – a narrative literature review

Author: Jemina Kivelä, Katja Wikström, Eeva Virtanen, Michael Georgoulis, Greet Cardon, Fernando Civeira, Violeta Iotova, Ernest Karuranga, Winne Ko, Stavros Liatis, Konstantinos Makrilakis, Yannis Manios, Rocío Mateo-Gallego, Anna Nanasi, Imre Rurik, Tsvetalina Tankova, Kaloyan Tsochev, Vicky Van Stappen, Jaana Lindström, and on behalf of the Feel4Diabetes research group
Subjects: Families, Lifestyle intervention, Prevention, Risk factors, Type 2 diabetes, Vulnerable, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract: Abstract Background Feel4Diabetes was a school and community based intervention aiming to promote healthy lifestyle and tackle obesity for the prevention of type 2 diabetes among families in 6 European countries. We conducted this literature review in order to guide the development of evidence-based implementation of the Feel4Diabetes intervention. We focused on type 2 diabetes prevention strategies, including all the phases from risk identification to implementation and maintenance. Special focus was given to prevention among vulnerable groups and people under 45 years. Methods Scientific and grey literature published between January 2000 and January 2015 was searched for relevant studies using electronic databases. To present the literature review findings in a systematic way, we used the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework. A complementary literature search from February 2015 to December 2018 was also conducted. Results The initial review included 27 studies with a follow-up ≥12 months and 9 studies with a follow-up ≥6 months and with a participant mean age
Published: 2020
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7. Two-stage, school and community-based population screening successfully identifies individuals and families at high-risk for type 2 diabetes: the Feel4Diabetes-study

Author: Yannis Manios, Christina Mavrogianni, Christina-Paulina Lambrinou, Greet Cardon, Jaana Lindström, Violeta Iotova, Tsvetalina Tankova, Fernando Civeira, Jemina Kivelä, Zoltán Jancsó, Samyah Shadid, Kaloyan Tsochev, Rocío Mateo-Gallego, Sándorné Radó, George Dafoulas, Konstantinos Makrilakis, Odysseas Androutsos, and on behalf of the Feel4Diabetes-study group
Subjects: Screening, School-based, Vulnerable groups, Type 2 diabetes, Hypertension, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract: Abstract Background The implementation of population screening and early prevention strategies targeting individuals at high-risk for type 2 diabetes (T2D) seems to be a public health priority. The current work aimed to describe the screening procedure applied in the Feel4Diabetes-study and examine its effectiveness in identifying individuals and families at high risk, primarily for T2D and secondarily for hypertension, among vulnerable populations in low to middle-income countries (LMICs) and high-income countries (HICs) across Europe. Methods A two-stage screening procedure, using primary schools as the entry-point to the community, was applied in low socioeconomic status (SES) regions in LMICs (Bulgaria-Hungary), HICs (Belgium-Finland) and HICs under austerity measures (Greece-Spain). During the first-stage screening via the school-setting, a total of 20,501 parents (mothers and/or fathers) of schoolchildren from 11,396 families completed the Finnish Diabetes Risk Score (FINDRISC) questionnaire, while their children underwent anthropometric measurements in the school setting. Parents from the identified “high-risk families” (n = 4484) were invited to participate in the second-stage screening, including the measurement of fasting plasma glucose (FPG) and blood pressure (BP). In total, 3153 parents participated in the second-stage screening (mean age 41.1 ± 5.6 years, 65.8% females). Results Among parents who attended the second-stage screening, the prevalence of prediabetes (as defined by impaired fasting glucose; FPG 100-125 mg/dl) and T2D (FPG > 126 mg/dl) was 23.2 and 3.0% respectively, and it was found to be higher in the higher FINDRISC categories. The percentage of undiagnosed T2D among the participants identified with T2D was 53.5%. The prevalence of high normal BP (systolic BP 130-139 mmHg and/ or diastolic BP 85-89 mmHg) and hypertension (systolic BP ≥ 140 mmHg and/ or diastolic BP ≥ 90 mmHg) was 14 and 18.6% respectively, which was also higher in the higher FINDRISC categories. The percentage of cases not receiving antihypertensive treatment among the participants identified with hypertension was 80.3%. Conclusion The findings of the current study indicate that the two-stage school and community-based screening procedure followed, effectively identified high-risk individuals and families in vulnerable populations across Europe. This approach could be potentially scalable and sustainable and support initiatives for the early prevention of T2D and hypertension. Trial registration The Feel4Diabetes-intervention is registered at https://clinicaltrials.gov/ (NCT02393872; date of trial registration: March 20, 2015).
Published: 2020
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8. Comparative efficacy between atorvastatin and rosuvastatin in the prevention of cardiovascular disease recurrence

Author: Sofía Perez-Calahorra, Martin Laclaustra, Victoria Marco-Benedi, Xavier Pinto, Rosa M. Sanchez-Hernandez, Núria Plana, Emilio Ortega, Francisco Fuentes, and Fernando Civeira
Subjects: Rosuvastatin, Atorvastatin, Secondary prevention, High-potent statin, Nutritional diseases. Deficiency diseases, RC620-627
Abstract: Abstract Background There is no randomized clinical trials with recurrence of atherosclerotic cardiovascular disease (ASCVD) as a major outcome with rosuvastatin. In order to analyze potential differences in the clinical response to atorvastatin and rosuvastatin in secondary ASCVD prevention, we have analyzed the clinical evolution of those subjects of the Dyslipemia Registry of the Spanish Society of Arteriosclerosis (SEA) who at the time of inclusion in the Registry had already suffered an ASCVD. Methods This observational, retrospective, multicenter, national study was designed to determine potential differences between the use of atorvastatin and rosuvastatin in the ASCVD recurrence. Three different follow-up start-times were performed: time of inclusion in the registry; time of first event if this occurred after 2005, and time of first event without date restriction. Results Baseline characteristics were similar between treatment groups. Among atorvastatin or rosuvastatin users, 89 recurrences of ASCVD were recorded (21.9%), of which 85.4% were coronary. At the inclusion of the subject in the registry, 345 participants had not suffered a recurrence yet. These 345 subjects accumulated 1050 person-years in a mean follow-up of 3 years. Event rates were 2.73 (95% CI: 1.63, 4.25) cases/100 person-years and 2.34 (95% CI: 1.17, 4.10) cases/100 person-years in the atorvastatin and rosuvastatin groups, respectively. There were no statistically significant differences between the two groups independently of the follow-up start-time. Conclusions This study does not find differences between high doses of rosuvastatin and atorvastatin in the recurrence of ASCVD, and supports their use as clinically equivalent in secondary prevention of ASCVD.
Published: 2019
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9. APOE Genotypes Modulate Inflammation Independently of Their Effect on Lipid Metabolism

Author: María Civeira-Marín, Ana Cenarro, Victoria Marco-Benedí, Ana M. Bea, Rocío Mateo-Gallego, Belén Moreno-Franco, José M. Ordovás, Martín Laclaustra, Fernando Civeira, and Itziar Lamiquiz-Moneo
Subjects: C-reactive protein, APOE genotype, lipoprotein subclasses, GlycA, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract: The association between APOE genotypes and cardiovascular disease (CVD) is partially mediated by LDL-cholesterol concentration but persists after adjusting for lipid levels and other cardiovascular risk factors. Data from the Aragon Workers Health Study (AWHS) (n = 4159) and the Lipid Unit at the Hospital Universitario Miguel Servet (HUMS) (n = 3705) were used to investigate the relationship between C-reactive protein (CRP) levels and APOE genotype. Lipoprotein particle and GlycA concentrations were analyzed in a subsample from AWHS. APOE genotyping was carried out by the Sanger method in both cohorts. APOE4 carriers had significantly lower levels of CRP than APOE3 carriers. Furthermore, APOE4 carriers had cholesterol-enriched LDL particles compared to APOE2 carriers. APOE4 carriers also had higher concentrations of small, medium, and large LDL particles. CRP levels were not associated with lipoprotein particle number, size, or composition. GlycA levels were not associated with APOE genotypes. However, GlycA levels were significantly associated with the size and the amount of cholesterol contained in HDL, VLDL, and LDL particles. APOE genotype influences CRP concentration regardless of lipid profile. APOE2 carriers showed the highest CRP levels, followed by APOE3 and APOE4. A more atherogenic lipid profile, but not inflammatory markers could partly explain the higher CVD risk observed in APOE4 carriers.
Published: 2022
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10. Effect of the Consumption of Alcohol-Free Beers with Different Carbohydrate Composition on Postprandial Metabolic Response

Author: Itziar Lamiquiz-Moneo, Sofia Pérez-Calahorra, Irene Gracia-Rubio, Alberto Cebollada, Ana M. Bea, Antonio Fumanal, Ana Ferrer-Mairal, Ascensión Prieto-Martín, María Luisa Sanz-Fernández, Ana Cenarro, Fernando Civeira, and Rocio Mateo-Gallego
Subjects: alcohol-free beer, postprandial effect, glucose metabolism, insulin, incretin hormones, Nutrition. Foods and food supply, TX341-641
Abstract: Background: We investigated the postprandial effects of an alcohol-free beer with modified carbohydrate (CH) composition compared to regular alcohol-free beer. Methods: Two randomized crossover studies were conducted. In the first study, 10 healthy volunteers received 25 g of CH in four different periods, coming from regular alcohol-free beer (RB), alcohol-free beer enriched with isomaltulose and a resistant maltodextrin (IMB), alcohol-free beer enriched with resistant maltodextrin (MB), and a glucose-based beverage. In the second study, 20 healthy volunteers were provided with 50 g of CH from white bread (WB) plus water, or with 14.3 g of CH coming from RB, IMB, MB, and extra WB. Blood was sampled after ingestion every 15 min for 2 h. Glucose, insulin, incretin hormones, TG, and NEFAs were determined in all samples. Results: The increase in glucose, insulin, and incretin hormones after the consumption of IMB and MB was significantly lower than after RB. The consumption of WB with IMB and MB showed significantly less increase in glucose levels than WB with water or WB with RB. Conclusions: The consumption of an alcohol-free beer with modified CH composition led to a better postprandial response compared to a conventional alcohol-free beer.
Published: 2022
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11. Association between non-cholesterol sterol concentrations and Achilles tendon thickness in patients with genetic familial hypercholesterolemia

Author: Lucía Baila-Rueda, Itziar Lamiquiz-Moneo, Estíbaliz Jarauta, Rocío Mateo-Gallego, Sofía Perez-Calahorra, Victoria Marco-Benedí, Ana M. Bea, Ana Cenarro, and Fernando Civeira
Subjects: Non-cholesterol sterols, Xanthomas, Familial hypercholesterolemia, Medicine
Abstract: Abstract Background Familial hypercholesterolemia (FH) is a genetic disorder that result in abnormally high low-density lipoprotein cholesterol levels, markedly increased risk of coronary heart disease (CHD) and tendon xanthomas (TX). However, the clinical expression is highly variable. TX are present in other metabolic diseases that associate increased sterol concentration. If non-cholesterol sterols are involved in the development of TX in FH has not been analyzed. Methods Clinical and biochemical characteristics, non-cholesterol sterols concentrations and Aquilles tendon thickness were determined in subjects with genetic FH with (n = 63) and without (n = 40) TX. Student-t test o Mann–Whitney test were used accordingly. Categorical variables were compared using a Chi square test. ANOVA and Kruskal–Wallis tests were performed to multiple independent variables comparison. Post hoc adjusted comparisons were performed with Bonferroni correction when applicable. Correlations of parameters in selected groups were calculated applying the non-parametric Spearman correlation procedure. To identify variables associated with Achilles tendon thickness changes, multiple linear regression were applied. Results Patients with TX presented higher concentrations of non-cholesterol sterols in plasma than patients without xanthomas (P = 0.006 and 0.034, respectively). Furthermore, there was a significant association between 5α-cholestanol, β-sitosterol, desmosterol, 24S-hydroxycholesterol and 27-hydroxycholesterol concentrations and Achilles tendon thickness (p = 0.002, 0.012, 0.020, 0.045 and 0.040, respectively). Conclusions Our results indicate that non-cholesterol sterol concentrations are associated with the presence of TX. Since cholesterol and non-cholesterol sterols are present in the same lipoproteins, further studies would be needed to elucidate their potential role in the development of TX.
Published: 2018
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12. Cataract Surgery in Elderly Subjects with Heterozygous Familial Hypercholesterolemia in Prolonged Treatment with Statins

Author: Victoria Marco-Benedí, Martín Laclaustra, Rosa M. Sánchez-Hernández, Emilio Ortega-Martínez de Victoria, Juan Pedro-Botet, Jose Puzo, and Fernando Civeira
Subjects: cataracts, heterozygous familial hypercholesterolemia, statins, lipid-lowering treatment, Medicine
Abstract: Background: Cataracts are the main cause of blindness and represent one fifth of visual problems worldwide. It is still unknown whether prolonged statin treatment favors the development of cataracts. We aimed to ascertain the prevalence of cataract surgery in elderly subjects with genetically diagnosed heterozygous familial hypercholesterolemia (HeFH) receiving statin treatment for ≥5 years, and compare this with controls. Methods: This is an observational, multicenter, case–control study from five lipid clinics in Spain. We collected data with the following inclusion criteria: age ≥65 years, LDL cholesterol levels ≥220 mg/dL without lipid-lowering drugs, a pathogenic mutation in a candidate gene for HeFH (LDLR, APOB, or PCSK9) and statin treatment for ≥5 years. Controls were selected from relatives of HeFH patients without hypercholesterolemia. Linear and logistic regressions based on generalized linear models and generalized estimating equations (GEE) were used. Cataract surgery was used as a proxy for cataract development. Results: We analyzed 205 subjects, 112 HeFH, and 93 controls, with a mean age of 71.8 (6.5) and 70.0 (7.3) years, respectively. HeFH subjects presented no difference in clinical characteristics, including smoking, hypertension, and type 2 diabetes mellitus, compared with controls. The mean duration of lipid-lowering treatment in HeFH was 22.5 (8.7) years. Cataract surgery prevalence was not significantly different between cases and controls. The presence of cataracts was associated neither with LDLc nor with the length of the statin therapy. Conclusion: In the present study, HeFH was not a risk factor for cataract surgery and prolonged statin treatment did not favor it either. These findings suggest that statin treatment is not related with cataracts.
Published: 2021
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13. SR-B1, a Key Receptor Involved in the Progression of Cardiovascular Disease: A Perspective from Mice and Human Genetic Studies

Author: Irene Gracia-Rubio, César Martín, Fernando Civeira, and Ana Cenarro
Subjects: Scavenger receptor B class 1, cardiovascular disease, mice and human genetic studies, high-density lipoprotein, low-density lipoprotein, Biology (General), QH301-705.5
Abstract: High plasma level of low-density lipoprotein (LDL) is the main driver of the initiation and progression of cardiovascular disease (CVD). Nevertheless, high-density lipoprotein (HDL) is considered an anti-atherogenic lipoprotein due to its role in reverse cholesterol transport and its ability to receive cholesterol that effluxes from macrophages in the artery wall. The scavenger receptor B class type 1 (SR-B1) was identified as the high-affinity HDL receptor, which facilitates the selective uptake of cholesterol ester (CE) into the liver via HDL and is also implicated in the plasma clearance of LDL, very low-density lipoprotein (VLDL) and lipoprotein(a) (Lp(a)). Thus, SR-B1 is a multifunctional receptor that plays a main role in the metabolism of different lipoproteins. The aim of this review is to highlight the association between SR-B1 and CVD risk through mice and human genetic studies.
Published: 2021
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14. Effect of LDL cholesterol, statins and presence of mutations on the prevalence of type 2 diabetes in heterozygous familial hypercholesterolemia

Author: Elisenda Climent, Sofía Pérez-Calahorra, Victoria Marco-Benedí, Nuria Plana, Rosa Sánchez, Emilio Ros, Juan F. Ascaso, Jose Puzo, Fátima Almagro, Carlos Lahoz, Fernando Civeira, and Juan Pedro-Botet
Subjects: Medicine, Science
Abstract: Abstract Patients with heterozygous familial hypercholesterolemia (HeFH) have been reported to be less vulnerable to type 2 diabetes mellitus (T2DM), although the mechanism is unknown. The aims of the present study were to assess the effects of low density lipoprotein (LDL) cholesterol concentration and the presence of FH-causing mutations on T2DM prevalence in HeFH. Data were collected from the Dyslipidemia Registry of the Spanish Arteriosclerosis Society. Inclusion criteria were definite or probable HeFH in patients aged ≥18 years. T2DM prevalence in HeFH patients was compared with data of the general population. 1732 patients were included. The prevalence of T2DM was lower in patients with HeFH compared with the general population (5.94% vs 9.44%; OR: 0.606, 95% CI 0.486–0.755, p
Published: 2017
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15. Effect of Lifestyle Intervention in the Concentration of Adipoquines and Branched Chain Amino Acids in Subjects with High Risk of Developing Type 2 Diabetes: Feel4Diabetes Study

Author: Itziar Lamiquiz-Moneo, Ana M. Bea, Cristian Palacios-Pérez, Pilar De Miguel-Etayo, Esther M. González-Gil, Chuan López-Ariño, Fernando Civeira, Luis A. Moreno, and Rocio Mateo-Gallego
Subjects: feel4diabetes study, branched chain amino acids, retinol-binding protein 4, type 2, diabetes lifestyle intervention, Cytology, QH573-671
Abstract: Introduction: The global prevalence of type 2 diabetes (T2D) is increasing rapidly, especially in low- and middle-income countries and has a high number of associated comorbidities. Plasmatic concentrations of branched chain amino acids (BCAA) and retinol-binding protein 4 (RBP4) have been shown to be elevated in T2D subjects in cross-sectional studies. However, the effect of lifestyle community-based interventions on BCAA and RBP4 concentrations has not yet been analyzed. Material and methods: The Feel4Diabetes study is a school and community-based intervention that identified 360 European families with a high risk of developing T2D according to the FINDRISC questionnaire. Families were randomized in control and intervention groups were followed-up from 2016 to 2018. In the Spanish families, the concentration of BCAA and RBP4 was determined in 266 subjects (115 control and 151 intervention group) that attended the three time-point assessments by colorimetric and ELISA reaction, respectively. Results: Baseline BCAA levels showed positive correlations with the FINDRISC score and glucose impairment (baseline glucose, insulin, and glycated hemoglobin), body mass index, and body weight. The participants receiving the community-based intervention showed a significant decrease in glycated hemoglobin and BCAA levels compared to the control group (p = 0.011 and p < 0.001, respectively). However, baseline RBP4 did not show significant correlations with anthropometric and glycemic parameters, and no significant change was observed in anthropometric parameters and RBP4 concentrations throughout the follow-up. Conclusion: A community-based intervention on lifestyle led to a significant reduction in BCAA levels regardless of weight loss. These findings suggest that this interventional approach could be promising in T2D prevention.
Published: 2020
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16. Lipid Profile Rather Than the LCAT Mutation Explains Renal Disease in Familial LCAT Deficiency

Author: Itziar Lamiquiz-Moneo, Fernando Civeira, Diego Gómez-Coronado, Francisco Blanco-Vaca, Hilda Mercedes Villafuerte-Ledesma, Miriam Gil, Nuria Amigó, Rocío Mateo-Gallego, and Ana Cenarro
Subjects: familial lcat deficiency, fish eye disease, vldl, nmr, fplc, triglycerides, phospholipids, Medicine
Abstract: Renal complications are the major cause of morbidity and mortality in patients with familial lecithin−cholesterol acyltransferase (LCAT) deficiency (FLD). We report three FLD patients, two of them siblings—only one of whom developed renal disease—and the third case being a young man with early renal disease. The aim of this study was to analyze the clinical characteristics and possible mechanisms associated with renal disease in these patients. Plasma lipid levels, LCAT activity, lipoprotein particle profile by NMR and FPLC, free and esterified cholesterol, presence of lipoprotein X (LpX) and DNA sequencing in the three FLD patients have been determined. The three cases presented clinical characteristics of FLD, although only one of the siblings developed renal disease, at 45 years of age, while the other patient developed the disease in his youth. Genetic analysis revealed new missense homozygous mutations, p.(Ile202Thr) in both siblings and p.(Arg171Glu) in the other patient. Lipoprotein particle analysis showed that the two patients with renal disease presented higher numbers of small very low-density lipoprotein (VLDL) and a higher concentration of triglycerides in VLDL. This study reports three new cases of LCAT deficiency, not previously described. Renal disease is not only dependent on LCAT deficiency, and could be due to the presence of VLDL particles, which are rich in triglycerides, free cholesterol and LpX.
Published: 2019
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17. Efficacy and Safety of Alirocumab 150 mg Every 4 Weeks in Patients With Hypercholesterolemia Not on Statin Therapy: The ODYSSEY CHOICE II Study

Author: Erik Stroes, John R. Guyton, Norman Lepor, Fernando Civeira, Daniel Gaudet, Gerald F. Watts, Marie T. Baccara‐Dinet, Guillaume Lecorps, Garen Manvelian, Michel Farnier, and the ODYSSEY CHOICE II Investigators
Subjects: alirocumab, cardiovascular risk, low‐density lipoprotein cholesterol, placebo‐controlled, proprotein convertase subtilisin/kexin type 9, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Background The PCSK9 antibody alirocumab (75 mg every 2 weeks; Q2W) as monotherapy reduced low‐density lipoprotein‐cholesterol (LDL‐C) levels by 47%. Because the option of a monthly dosing regimen is convenient, ODYSSEY CHOICE II evaluated alirocumab 150 mg Q4W in patients with inadequately controlled hypercholesterolemia and not on statin (majority with statin‐associated muscle symptoms), receiving treatment with fenofibrate, ezetimibe, or diet alone. Methods and Results Patients were randomly assigned to placebo, alirocumab 150 mg Q4W or 75 mg Q2W (calibrator arm), with dose adjustment to 150 mg Q2W at week (W) 12 if W8 predefined LDL‐C target levels were not met. The primary efficacy endpoint was LDL‐C percentage change from baseline to W24. Mean baseline LDL‐C levels were 163.9 mg/dL (alirocumab 150 mg Q4W, n=59), 154.5 mg/dL (alirocumab 75 mg Q2W, n=116), and 158.5 mg/dL (placebo, n=58). In the alirocumab 150 mg Q4W and 75 mg Q2W groups (49.1% and 36.0% of patients received dose adjustment, respectively), least‐squares mean LDL‐C changes from baseline to W24 were −51.7% and −53.5%, respectively (placebo [+4.7%]; both groups P
Published: 2016
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18. El hospital universitario del siglo XXI The University Hospital in 21st century

Author: Jesús Millán Núñez-Cortés, Fernando Civeira-Murillo, and José A. Gutiérrez-Fuentes
Subjects: Education (General), L7-991, Medicine (General), R5-920
Published: 2011

19. The genetic basis of familial hypercholesterolemia: inheritance, linkage, and mutations

Author: Isabel De Castro-Orós, Miguel Pocoví, and Fernando Civeira
Subjects: Medicine (General), R5-920, Genetics, QH426-470
Abstract: Isabel De Castro-Orós1, Miguel Pocoví2, Fernando Civeira11Lipid Unit and Laboratorio de Investigación Molecular, Hospital Universitario Miguel Servet, Instituto Aragonés de Ciencias de la Salud (I+CS), Zaragoza, Spain; 2Departamento. Bioquímica y Biología Molecular y Celular. Universidad de Zaragoza, Instituto Aragonés de Ciencias de la Salud (I+CS), Zaragoza, Spain and Ciber de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, SpainAbstract: Familial hypercholesterolemia (FH) is a genetic disorder of lipoprotein metabolism characterized by high plasma concentrations of low-density lipoprotein cholesterol (LDLc), tendon xanthomas, and increased risk of premature coronary heart disease. FH is one of the most common inherited disorders; there are 10,000,000 people with FH worldwide, mainly heterozygotes. The most common FH cause is mutations along the entire gene that encode for LDL receptor (LDLR) protein, but it has been also described that mutations in apolipoprotein B (APOB) and proprotein convertase subtilisin/kexin type 9 genes produce this phenotype. About 17%–33% of patients with a clinical diagnosis of monogenic hypercholesterolemia do not harbor any genetic cause in the known loci. Because FH has been considered as a public health problem, it is very important for an early diagnosis and treatment. Recent studies have demonstrated the influence of the LDLR mutation type in the FH phenotype, associating a more severe clinical phenotype and worse advanced carotid artherosclerosis in patients with null than those with receptor-defective mutations. Since 2004, a molecular FH diagnosis based on a genetic diagnostic platform (Lipochip®; Progenika-Biopharma, Derio, Spain) has been developed. This analysis completes the adequate clinical diagnosis made by physicians. Our group has recently proposed new FH guidelines with the intention to facilitate the FH diagnosis. The treatment for this disease is based on the benefit of lowering LDLc and a healthy lifestyle. Actually, drug therapy is focused on using statins and combined therapy with ezetimibe and statins. This review highlights the recent progress made in genetics, diagnosis, and treatment for FH.Keywords: LDLR, APOB, PCSK9, LDL cholesterol
Published: 2010

20. FABP4 plasma levels are increased in familial combined hyperlipidemia

Author: Anna Cabré, Iolanda Lázaro, Montserrat Cofán, Estibaliz Jarauta, Núria Plana, Angel L. Garcia-Otín, Juan F. Ascaso, Raimón Ferré, Fernando Civeira, Emilio Ros, and Lluís Masana
Subjects: dyslipidemia, FCHL, insulin resistance, obesity, Biochemistry, QD415-436
Abstract: The lipid profile of familial combined hyperlipidemia (FCHL) shares some characteristics with atherogenic dyslipidemia seen in diabetes, metabolic syndrome, and obesity. Adipocyte fatty acid-binding protein 4 (FABP4) appears to be a determinant of atherogenic dyslipidemia. We examined relationships between FABP4 plasma concentrations, dyslipidemia, and metabolic variables in patients with FCHL. We studied 273 unrelated FCHL patients and 118 control subjects. FABP4 was higher in FCHL than controls, with mean levels of 21.8 (10.1) μg/l and 19.2 (9.2) μg/l, respectively (adjusted P= 0.012). In FCHL, FABP4 correlated to body mass index (BMI), waist circumference, insulin levels, and homeostasis model assessment (HOMA) index (all P< 0.05), but not to lipid levels, whereas in obese patients, FABP4 correlated to triglyceride levels (r = 0.303, P= 0.014) and very low density lipoprotein size (r = 0.502, P = 0.001), as determined by nuclear magnetic resonance. Associations of FABP4 with BMI and waist circumference, but not with insulin levels, persisted in this subgroup. Plasma FABP4 does not influence the lipid phenotype of FCHL. In a small subgroup of obese FCHL, FABP4 levels were associated with triglyceride-rich lipoproteins independent of insulin resistance. These results support a hyperlipidemic mechanism of FCHL different from similar metabolic conditions where fat mass is strongly related to FABP4 and hypertriglyceridemia.
Published: 2010
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21. Glycated Hemoglobin, Fasting Insulin and the Metabolic Syndrome in Males. Cross-Sectional Analyses of the Aragon Workers' Health Study Baseline.

Author: Gabriela Saravia, Fernando Civeira, Yamilee Hurtado-Roca, Eva Andres, Montserrat Leon, Miguel Pocovi, Jose Ordovas, Eliseo Guallar, Antonio Fernandez-Ortiz, Jose Antonio Casasnovas, and Martin Laclaustra
Subjects: Medicine, Science
Abstract: Glycated hemoglobin (HbA1c) is currently used to diagnose diabetes mellitus, while insulin has been relegated to research. Both, however, may help understanding the metabolic syndrome and profiling patients. We examined the association of HbA1c and fasting insulin with clustering of metabolic syndrome criteria and insulin resistance as two essential characteristics of the metabolic syndrome.We used baseline data from 3200 non-diabetic male participants in the Aragon Workers' Health Study. We conducted analysis to estimate age-adjusted odds ratios (ORs) across tertiles of HbA1c and insulin. Fasting glucose and Homeostatic model assessment - Insulin Resistance were used as reference. Here we report the uppermost-to-lowest tertile ORs (95%CI).Mean age (SD) was 48.5 (8.8) years and 23% of participants had metabolic syndrome. The ORs for metabolic syndrome criteria tended to be higher across HbA1c than across glucose, except for high blood pressure. Insulin was associated with the criteria more strongly than HbA1c and similarly to Homeostatic model assessment - Insulin Resistance (HOMA-IR). For metabolic syndrome, the OR of HbA1c was 2.68, of insulin, 11.36, of glucose, 7.03, and of HOMA-IR, 14.40. For the clustering of 2 or more non-glycemic criteria, the OR of HbA1c was 2.10, of insulin, 8.94, of glucose, 1.73, and of HOMA-IR, 7.83. All ORs were statistically significant. The areas under the receiver operating characteristics curves for metabolic syndrome were 0.670 (across HbA1c values) and 0.770 (across insulin values), and, for insulin resistance, 0.647 (HbA1c) and 0.995 (insulin). Among non-metabolic syndrome patients, a small insulin elevation identified risk factor clustering.HbA1c and specially insulin levels were associated with metabolic syndrome criteria, their clustering, and insulin resistance. Insulin could provide early information in subjects prone to develop metabolic syndrome.
Published: 2015
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22. El hospital como centro nuclear para mejorar la enseñanza de la medicina

Author: Fernando Civeira Murillo
Subjects: Education (General), L7-991, Medicine (General), R5-920
Published: 2010

23. Implantación de un programa de cribado bioquímico y genético de hipercolesterolemia familiar. Colaboración entre el laboratorio clínico y las unidades de lípidos: diseño del Proyecto ARIAN

Author: Alguacil, Begoña Gallardo, Temprano, Ramon Pérez, Quesada, Mar Martínez, Rico, Miguel Ángel, Herrán, Lourdes Diez, Grijalbo, Ovidio Muñiz, Yun, Purificación García, Villar, Francisca Jiménez-Mena, Pérez, Francisco Morales, Albarrán, Olga González, Puebla, Mercedes Herranz, Robles, Carolina Puertas, Anguila, Silvia Campos, Ruiz, Joan Lima, Ruiz, Armando Raúl Guerra, Hernández, José Luis Hernández, Lario, José Vicente García, Busto, Pablo González, Alemán, Fernando Rodríguez, García, María Mar Águila, Ávila, Fernando Jaén, Benito, Goitzane Marcaida, Gracia, Juan José Tamarit, Cobos, Cristina Gómez, Planella, Juan Ramón Urgeles, Cucalón, Luis Irigoyen, Orna, José Antonio Gimeno, Budría, José Ruiz, Rico, Ignacio Vázquez, Garrido, Jessica Roa, Pérez, Enrique Ruiz, Álvarez, María Maravi, Pereg, Laura de la Maza, García, María Victoria Poncela, Palencia, María Martin, Talavera, David Peñalver, Álvaro, Montaña Jiménez, Duque, Marco Puma, Rodríguez, Almudena Vigil, Alonso, Juan Manuel Fernández, Armas, José Alfredo Martin, Mazorra, Magdalena León, Cabrera, Casimira Domínguez, Gracia, Lidia Esther Ruiz, Foncillas, José Puzo, Sala, Xavier Pintó, Castro, María José Castro, Murillo, Fernando Civeira, Calmarza, Pilar, Hernández, Rosa Sánchez, Ruiz, Marta Riaño, García-Lescun, Camino García, Amor, María Almudena, Alegría, Eduardo, Ferrer, Cristina Soler, Costa, Mercé Montesino, Rus, Antonio, Casañas, Marta, Arrobas Velilla, Teresa, Brea, Ángel, and Valdivielso, Pedro
Published: 2021
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24. Lipoprotein(a) and Benefit of PCSK9 Inhibition in Patients With Nominally Controlled LDL Cholesterol

Author: Schwartz, Gregory G., Gabriel Steg, P.h., Bhatt, Deepak L., Bittner, Vera A., Diaz, Rafael, Goodman, Shaun G., Harrington, Robert A., Jukema, J. Wouter, Szarek, Michael, White, Harvey D., Zeiher, Andreas M., Tricoci, Pierluigi, Roe, Matthew T., Mahaffey, Kenneth W., Edelberg, Jay M., Hanotin, Corinne, Lecorps, Guillaume, Moryusef, Angèle, Pordy, Robert, Sasiela, William J., Tamby, Jean-François, Aylward, Philip E., Drexel, Heinz, Sinnaeve, Peter, Dilic, Mirza, Lopes, Renato D., Gotcheva, Nina N., Prieto, Juan-Carlos, Yong, Huo, López-Jaramillo, Patricio, Pećin, Ivan, Reiner, Zeljko, Ostadal, Petr, Poulsen, Steen Hvitfeldt, Viigimaa, Margus, Nieminen, Markku S., Danchin, Nicolas, Chumburidze, Vakhtang, Marx, Nikolaus, Liberopoulos, Evangelos, Montenegro Valdovinos, Pablo Carlos, Tse, Hung-Fat, Kiss, Robert Gabor, Xavier, Denis, Zahger, Doron, Valgimigli, Marco, Kimura, Takeshi, Kim, Hyo Soo, Kim, Sang-Hyun, Erglis, Andrejs, Laucevicius, Aleksandras, Kedev, Sasko, Yusoff, Khalid, Ramos López, Gabriel Arturo, Alings, Marco, Halvorsen, Sigrun, Correa Flores, Roger M., Sy, Rody G., Budaj, Andrzej, Morais, Joao, Dorobantu, Maria, Karpov, Yuri, Ristic, Arsen D., Chua, Terrance, Murin, Jan, Fras, Zlatko, Dalby, Anthony J., Tuñón, José, Asita de Silva, H., Hagström, Emil, Landmesser, Ulf, Müller, Christian, Chiang, Chern-En, Sritara, Piyamitr, Guneri, Sema, Parkhomenko, Alexander, Ray, Kausik K., Moriarty, Patrick M., Vogel, Robert, Chaitman, Bernard, Kelsey, Sheryl F., Olsson, Anders G., Rouleau, Jean-Lucien, Simoons, Maarten L., Alexander, Karen, Meloni, Chiara, Rosenson, Robert, Sijbrands, Eric J.G., Alexander, John H., Armaganijan, Luciana, Bagai, Akshay, Bahit, Maria Cecilia, Brennan, J. Matthew, Clifton, Shaun, DeVore, Adam D., Deloatch, Shalonda, Dickey, Sheila, Dombrowski, Keith, Ducrocq, Grégory, Eapen, Zubin, Endsley, Patricia, Eppinger, Arleen, Harrison, Robert W., Hess, Connie Ng, Hlatky, Mark A., Jordan, Joseph Dedrick, Knowles, Joshua W., Kolls, Bradley J., Kong, David F., Leonardi, Sergio, Lillis, Linda, Maron, David J., Marcus, Jill, Mathews, Robin, Mehta, Rajendra H., Mentz, Robert J., Moreira, Humberto Graner, Patel, Chetan B., Pereira, Sabrina Bernardez, Perkins, Lynn, Povsic, Thomas J., Puymirat, Etienne, Jones, William Schuyler, Shah, Bimal R., Sherwood, Matthew W., Stringfellow, Kenya, Sujjavanich, Darin, Toma, Mustafa, Trotter, Charlene, van Diepen, Sean F.P., Wilson, Matthew D., Tze-Kay Yan, Andrew, Schiavi, Lilia B., Garrido, Marcelo, Alvarisqueta, Andrés F., Sassone, Sonia A., Bordonava, Anselmo P., Alves De Lima, Alberto E., Schmidberg, Jorge M., Duronto, Ernesto A., Caruso, Orlando C., Novaretto, Leonardo P., Hominal, Miguel Angel, Montaña, Oscar R., Caccavo, Alberto, Gomez Vilamajo, Oscar A., Lorenzatti, Alberto J., Cartasegna, Luis R., Paterlini, Gustavo A., Mackinnon, Ignacio J., Caime, Guillermo D., Amuchastegui, Marcos, Salomone, Oscar, Codutti, Oscar R., Jure, Horacio O., Bono, Julio O.E., Hrabar, Adrian D., Vallejos, Julio A., Ahuad Guerrero, Rodolfo A., Novoa, Federico, Patocchi, Cristian A., Zaidman, Cesar J., Giuliano, Maria E., Dran, Ricardo D., Vico, Marisa L., Carnero, Gabriela S., Guzman, Pablo N., Medrano Allende, Juan C., Garcia Brasca, Daniela F., Bustamante Labarta, Miguel H., Nani, Sebastian, Blumberg, Eduardo D.S., Colombo, Hugo R., Liberman, Alberto, Fuentealba, Victorino, Luciardi, Hector L., Waisman, Gabriel D., Berli, Mario A., Garcia Duran, Ruben O., Cestari, Horacio G., Luquez, Hugo A., Giordano, Jorge A., Saavedra, Silvia S., Zapata, Gerardo, Costamagna, Osvaldo, Llois, Susana, Waites, Jonathon H., Collins, Nicholas, Soward, Allan, Hii, Chris L.S., Shaw, James, Arstall, Margaret A., Horowitz, John, Ninio, Daniel, Rogers, James F., Colquhoun, David, Oqueli Flores, Romulo E., Roberts-Thomson, Philip, Raffel, Owen, Lehman, Sam J., Aroney, Constantine, Coverdale, Steven G.M., Garrahy, Paul J., Starmer, Gregory, Sader, Mark, Carroll, Patrick A., Dick, Ronald, Zweiker, Robert, Hoppe, Uta, Huber, Kurt, Berger, Rudolf, Delle-Karth, Georg, Frey, Bernhard, Faes, Dirk, Hermans, Kurt, Pirenne, Bruno, Leone, Attilio, Hoffer, Etienne, Vrolix, Mathias C.M., De Wolf, Luc, Wollaert, Bart, Castadot, Marc, Dujardin, Karl, Beauloye, Christophe, Vervoort, Geert, Striekwold, Harry, Convens, Carl, Roosen, John, Barbato, Emanuele, Claeys, Marc, Cools, Frank, Terzic, Ibrahim, Barakovic, Fahir, Midzic, Zlatko, Pojskic, Belma, Fazlibegovic, Emir, Durak-Nalbantic, Azra, Kulić, Mehmed, Vulic, Dusko, Muslibegovic, Adis, Goronja, Boris, Reis, Gilmar, Sousa, Luciano, Nicolau, Jose C., Giorgeto, Flavio E., Silva, Ricardo P., Maia, Lilia Nigro, Rech, Rafael, Rossi, Paulo R.F., Cerqueira, Maria José A.G., Duda, Norberto, Kalil, Renato, Kormann, Adrian, Abrantes, José Antonio M., Filho, Pedro Pimentel, Soggia, Ana Priscila, de Santos, Mayler O.N., Neuenschwander, Fernando, Bodanese, Luiz C., Michalaros, Yorghos L., Eliaschewitz, Freddy G., Vidotti, Maria H., Leaes, Paulo E., Botelho, Roberto V., Kaiser, Sergio, Fernandes Manenti, Euler Roberto F., Precoma, Dalton B., Moura Jorge, Jose C., Silva, Pedro, Silveira, Jose A., Saporito, Wladmir, Marin Neto, Jose A., Feitosa, Gilson S., Ritt, Luiz Eduardo F., de Souza, Juliana A., Costa, Fernando, Souza, Weimar K.S.B., Reis, Helder J.L., Machado, Leandro, Aidar Ayoub, José Carlos, Todorov, Georgi V., Nikolov, Fedya P., Velcheva, Elena S., Tzekova, Maria L., Benov, Haralambi O., Petranov, Stanislav L., Tumbev, Haralin S., Shehova-Yankova, Nina S., Markov, Dimitar T., Raev, Dimitar H., Mollov, Mihail N., Kichukov, Kostadin N., Ilieva-Pandeva, Katya A., Ivanova, Raya, Gospodinov, Maryana, Mincheva, Valentina M., Lazov, Petar V., Dimov, Bojidar I., Senaratne, Manohara, Stone, James, Kornder, Jan, Pearce, Stephen, Dion, Danielle, Savard, Daniel, Pesant, Yves, Pandey, Amritanshu, Robinson, Simon, Gosselin, Gilbert, Vizel, Saul, Hoag, Gordon, Bourgeois, Ronald, Morisset, Anne, Sabbah, Eric, Sussex, Bruce, Kouz, Simon, MacDonald, Paul, Diaz, Ariel, Michaud, Nicolas, Fell, David, Leung, Raymond, Vuurmans, Tycho, Lai, Christopher, Nigro, Frank, Davies, Richard, Nogareda, Gustavo, Vijayaraghavan, Ram, Ducas, John, Lepage, Serge, Mehta, Shamir, Cha, James, Dupuis, Robert, Fong, Peter, Lutchmedial, Sohrab, Rodes-Cabau, Josep, Fadlallah, Hussein, Cleveland, David, Huynh, Thao, Bata, Iqbal, Hameed, Adnan, Pincetti, Cristian, Potthoff, Sergio, Prieto, Juan C., Acevedo, Monica, Aguirre, Arnoldo, Vejar, Margarita, Yañez, Mario, Araneda, Guillermo, Fernandez, Mauricio, Perez, Luis, Varleta, Paola, Florenzano, Fernando, Huidobro, Laura, Raffo, Carlos A., Olivares, Claudia, Nahuelpan, Leonardo, Montecinos, Humberto, Chen, Jiyan, Dong, Yugang, Huang, Weijian, Wang, Jianzhong, Huang, Shi'An, Yao, Zhuhua, Li, Xiang, Cui, Lan, Lin, Wenhua, Sun, Yuemin, Wang, Jingfeng, Li, Jianping, Zhang, Xuelian, Zhu, Hong, Chen, Dandan, Huang, Lan, Dong, Shaohong, Su, Guohai, Xu, Biao, Su, Xi, Cheng, Xiaoshu, Lin, Jinxiu, Zong, Wenxia, Li, Huanming, Feng, Yi, Xu, Dingli, Yang, Xinchun, Ke, Yuannan, Lin, Xuefeng, Zhang, Zheng, Zheng, Zeqi, Luo, Zhurong, Chen, Yundai, Ding, Chunhua, Zhong, Yi, Zheng, Yang, Li, Xiaodong, Peng, Daoquan, Zhao, Shuiping, Li, Ying, Liu, Xuebo, Wei, Meng, Liu, Shaowen, Yu, Yihua, Qu, Baiming, Jiang, Weihong, Zhou, Yujie, Zhao, Xingsheng, Yuan, Zuyi, Guo, Ying, Xu, Xiping, Shi, Xubo, Ge, Junbo, Fu, Guosheng, Bai, Feng, Fang, Weiyi, Shou, Xiling, Yang, Xiangjun, Wang, Jian'An, Xiang, Meixiang, Sun, Yingxian, Lu, Qinghua, Zhang, Ruiyan, Zhu, Jianhua, Xu, Yizhou, Fan, Zhongcai, Li, Tianchang, Wu, Chun, Jaramillo, Nicolas, Vallejo, Gregorio Sanchez, Luna Botia, Diana C., Lopez, Rodrigo Botero, Molina De Salazar, Dora I., Cadena Bonfanti, Alberto J., Aroca, Carlos Cotes, Higuera, Juan Diego, Blanquicett, Marco, Barrera Silva, Sandra I., Garcia Lozada, Henry J., Coronel Arroyo, Julian A., Accini Mendoza, Jose L., Fernandez Ruiz, Ricardo L., Quintero Ossa, Alvaro M., Manzur Jatin, Fernando G., Herazo, Aristides Sotomayor, Parada, Jeffrey Castellanos, Arambula, Rafael Suarez, Urina Triana, Miguel A., Fernandez Trujillo, Angela M., Strozzi, Maja, Car, Siniša, Jerić, Melita, Miličić, Davor, Benčić, Martina Lovrić, Pintarić, Hrvoje, Prvulović, Đeiti, Šikić, Jozica, Peršić, Viktor, Mileta, Dean, Štambuk, Kresimir, Babić, Zdravko, Tomulic, Vjekoslav, Lukenda, Josip, Mejic-Krstulovic, Stanka, Starcevic, Boris, Spinar, Jindrich, Horak, David, Velicka, Zdenek, Stasek, Josef, Alan, David, Machova, Vilma, Linhart, Ales, Novotny, Vojtech, Kaucak, Vladimir, Rokyta, Richard, Naplava, Robert, Coufal, Zdenek, Adamkova, Vera, Podpera, Ivo, Zizka, Jiri, Motovska, Zuzana, Marusincova, Ivana, Svab, Premysl, Heinc, Petr, Kuchar, Jiri, Povolny, Petr, Matuska, Jiri, Poulsen, Steen H., Raungaard, Bent, Clemmensen, Peter, Bang, Lia E., May, Ole, Bøttcher, Morten, Hove, Jens D., Frost, Lars, Gislason, Gunnar, Larsen, John, Johansen, Peter Betton, Hald, Flemming, Johansen, Peter, Jeppesen, Jørgen, Nielsen, Tonny, Kristensen, Kjeld S., Walichiewicz, Piotr Maria, Lomholdt, Jens D., Klausen, Ib C., Nielsen, Peter Kaiser, Davidsen, Flemming, Videbaek, Lars, Soots, Mai, Vahula, Veiko, Hedman, Anu, Soopõld, Üllar, Märtsin, Kaja, Jurgenson, Tiina, Kristjan, Arved, Huikuri, Heikki, Pierre Coste, Juhani Airaksinen, Ferrari, Emile, Morel, Olivier, Montalescot, Gilles, Machecourt, Jacques, Barone-Rochette, Gilles, Mansourati, Jacques, Cottin, Yves, Leclercq, Florence, Belhassane, Abdelkader, Delarche, Nicolas, Boccara, Franck, Paganelli, Franck, Clerc, Jérôme, Schiele, Francois, Aboyans, Victor, Probst, Vincent, Berland, Jacques, Lefèvre, Thierry, Citron, Bernard, Khintibidze, Irakli, Shaburishvili, Tamaz, Pagava, Zurab, Ghlonti, Ramaz, Lominadze, Zaza, Khabeishvili, George, Hemetsberger, Rayyan, Edward, Kemala, Rauch-Kröhnert, Ursula, Stratmann, Matthias, Appel, Karl-Friedrich, Schmidt, Ekkehard, Omran, Heyder, Stellbrink, Christoph, Dorsel, Thomas, Lianopoulos, Emmanouil, Vöhringer, Hans Friedrich, Marx, Roger, Zirlik, Andreas, Schellenberg, Detlev, Heitzer, Thomas, Laufs, Ulrich, Werner, Christian, Gielen, Stephan, Nuding, Sebastian, Winkelmann, Bernhard, Behrens, Steffen, Sydow, Karsten, Karakas, Mahir, Simonis, Gregor, Muenzel, Thomas, Werner, Nikos, Leggewie, Stefan, Böcker, Dirk, Braun-Dullaeus, Rüdiger, Toursarkissian, Nicole, Jeserich, Michael, Weißbrodt, Matthias, Schaeufele, Tim, Weil, Joachim, Völler, Heinz, Waltenberger, Johannes, Natour, Mohammed, Schmitt, Susanne, Müller-Wieland, Dirk, Steiner, Stephan, Heidenreich, Lothar, Offers, Elmar, Gremmler, Uwe, Killat, Holger, Rieker, Werner, Patsilinakos, Sotiris, Kartalis, Athanasios, Manolis, Athanassios, Sionis, Dimitrios, Chachalis, Geargios, Skoumas, Ioannis, Athyros, Vasilios, Vardas, Panagiotis, Parthenakis, Frangkiskos, Lekakis, John, Hatzitolios, Apostolos, Fausto Ovando, Sergio R., Arango Benecke, Juan L., Rodriguez De Leon, Edgar R., Yan, Bryan P.Y., Siu, David C.W., Turi, Tibor, Merkely, Bela, Ungi, Imre, Lupkovics, Geza, Nagy, Lajos, Katona, András, Édes, István, Müller, Gábor, Horvath, Iván, Kapin, Tibor, Szigeti, Zsolt, Faluközy, József, Kumbla, Mukund, Sandhu, Manjinder, Annam, Sharath, Proddutur, Naveen Reddy, Regella, Reddy, Premchand, Rajendra K., Mahajan, Ajaykumar, Pawar, Sudhir, Abhyanakar, Atul D., Kerkar, Prafulla, Govinda, Ravishankar A., Oomman, Abraham, Sinha, Dhurjati, Patil, Sachin N., Kahali, Dhiman, Sawhney, Jitendra, Joshi, Abhijeet B., Chaudhary, Sanjeev, Harkut, Pankaj, Guha, Santanu, Porwal, Sanjay, Jujjuru, Srimannarayana, Pothineni, Ramesh B., Monteiro, Minguel R., Khan, Aziz, Iyengar, Shamanna S., Grewal, Jasprakash Singh, Chopda, Manoj, Fulwani, Mahesh C., Patange, Aparna, Sachin, Patil, Chopra, Vijay K., Goyal, Naresh K., Shinde, Rituparna, Manakshe, Gajendra V., Patki, Nitin, Sethi, Sumeet, Munusamy, Vengatesh, Sunil Thanvi, Sunil Karnaand, Adhyapak, Srilakshmi, Patil, Chandrakant, Pandurangi, Ulhas, Mathur, Rishabh, Gupta, Jugal, Kalashetti, Suhas, Bhagwat, Ajit, Raghuraman, Bagirath, Yerra, Shiv Kumar, Bhansali, Prasant, Borse, Rohidas, Rahul, Patil, Das, Srihari, Kumar, Vinay, Abdullakutty, Jabir, Saathe, Shireesh, Palimkar, Priya, Abdullkutty, Jabir, Sathe, Shireesh, Atar, Shaul, Shechter, Michael, Mosseri, Morris, Arbel, Yaron, Ehud, Chorin, Ofer, Havakuk, Lotan, Chaim, Rosenschein, Uri, Katz, Amos, Henkin, Yaakov, Francis, Adi, Klutstein, Marc, Nikolsky, Eugenia, Zukermann, Robert, Turgeman, Yoav, Halabi, Majdi, Marmor, Alon, Kornowski, Ran, Jonas, Michael, Amir, Offer, Hasin, Yonathan, Rozenman, Yoseph, Fuchs, Shmuel, Zvi, Vered, Hussein, Osamah, Gavish, Dov, Vered, Zvi, Caraco, Yoseph, Elias, Mazen, Tov, Naveh, Wolfovitz, Efrat, Lishner, 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Rasmanis, Gundars, Vedin, Ola, Witt, Nils, Mourtzinis, Georgios, Nicol, Peter, Hansen, Ole, Romeo, Stefano, Jensen, Steen Agergaard, Torstensson, Ingemar, Ahremark, Ulf, Sundelin, Torbjörn, Moccetti, Tiziano, Mach, Francois, Binde, Ronald, Gämperli, Oliver, Tsai, Wei-Chuan, Ueng, Kwo-Chang, Lai, Wen-Ter, Liu, Ming-En, Hwang, Juey-Jen, Yin, Wei-Hsian, Hsieh, I-Chang, Hsieh, Ming-Jer, Lin, Wei Hsiang, Kuo, Jen-Yuan, Huang, Tsuei-Yuan, Fang, Chih-Yuan, Kaewsuwanna, Pinij, Soonfuang, Wasant, Jintapakorn, Woravut, Sukonthasarn, Apichard, Wongpraparut, Nattawut, Sastravaha, Krisada, Sansanayudh, Nakarin, Kehasukcharoen, Wirash, Piyayotai, Dilok, Chotnoparatpat, Paiboon, Camsari, Ahmet, Kultursay, Hakan, Mutlu, Bulent, Ersanli, Murat, Demirtas, Mustafa, Kirma, Cevat, Ural, Ertan, Koldas, Lale, Karpenko, Oleksandr, Prokhorov, Alexander, Vakaluyk, Ihor, Myshanych, Halyna, Reshotko, Dmytro, Batushkin, Valeriy, Rudenko, Leonid, Kovalskyi, Ihor, Kushnir, Mykola, Tseluyko, Vira, Mostovoy, Yuriy, 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James, Janik, Matthew, Moran, Joseph, Sumner, Andrew, Kobayashi, John, Davis, William, Yazdani, Shahram, Pasquini, John, Thakkar, Maitreya, Vedere, Amarnath, Leimbach, Wayne, Rider, James, fenton, Sarah, Singh, Narendra, Shah, Anil V., Janosik, Denise, Pepine, Carl, Berman, Brett, Gelormini, Joseph, Daniels, Christopher, Richard, Kerensky, Keating, Friederike, Kondo, Nicholas I., Shetty, Sanjay, Levite, Howard, Waider, Winfried, Takata, Theodore, Abu-Fadel, Mazen, Shah, Vipul, Aggarwal, Rahul, Izzo, Mark, Kumar, Anil, Hattler, Brack, Do, Rose, Link, Chad, Bortnick, Anna, Kinzfogl, George, III, Ghitis, Arnold, Larry, John, Teufel, Edward, Kuhlman, Peter, Mclaurin, Brent, Zhang, Wenwu, Thew, Stephen, Abbas, Jalal, White, Matthew, Islam, Othman, Subherwal, Sumeet, Ranadive, Nandkishore, Vakili, Babak, Gring, Christian, Henderson, David, Schuchard, Timothy, Farhat, Naim, Kline, Geoffrey, Mahal, Sharan, Whitaker, Jack, Speirs, Shawn, Andersen, Rolf, Daboul, Nizar, Horwitz, Phillip, Zahr, 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Published: 2021
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25. El hospital universitario del siglo XXI

Author: Jesús Millán Núñez-Cortés, Fernando Civeira-Murillo, and José A. Gutiérrez-Fuentes
Subjects: Education (General), L7-991, Medicine (General), R5-920

26. Apolipoprotein B, Residual Cardiovascular Risk After Acute Coronary Syndrome, and Effects of Alirocumab

Author: Hagström, Emil, Steg, P. Gabriel, Szarek, Michael, Bhatt, Deepak L., Bittner, Vera A., Danchin, Nicolas, Diaz, Rafael, Goodman, Shaun G., Harrington, Robert A., Jukema, J. Wouter, Liberopoulos, Evangelos, Marx, Nikolaus, McGinniss, Jennifer, Manvelian, Garen, Pordy, Robert, Scemama, Michel, White, Harvey D., Zeiher, Andreas M., Schwartz, Gregory G., Schwartz, Gregory G., Bhatt, Deepak L., Bittner, Vera A., Diaz, Rafael, Goodman, Shaun G., Harrington, Robert A., Jukema, J. Wouter, Szarek, Michael, White, Harvey D., Zeiher, Andreas M., Tricoci, Pierluigi, Roe, Matthew T., Mahaffey, Kenneth W., Edelberg, Jay M., Hanotin, Corinne, Lecorps, Guillaume, Moryusef, Angèle, Pordy, Robert, Sasiela, William J., Tamby, Jean-François, Diaz, Rafael, Aylward, Philip E, Drexel, Heinz, Sinnaeve, Peter, Dilic, Mirza, Lopes, Renato D., Gotcheva, Nina N, Goodman, Shaun G., Prieto, Juan-Carlos, Yong, Huo, López-Jaramillo, Patricio, Pećin, Ivan, Reiner, Zeljko, Ostadal, Petr, Poulsen, Steen Hvitfeldt, Viigimaa, Margus, Nieminen, Markku S, Danchin, Nicolas, Chumburidze, Vakhtang, Marx, Nikolaus, Liberopoulos, Evangelos, Carlos, Pablo, Valdovinos, Montenegro, Tse, Hung-Fat, Kiss, Robert Gabor, Xavier, Denis, Zahger, Doron, Valgimigli, Marco, Kimura, Takeshi, Kim, Hyo Soo, Kim, Sang-Hyun, Erglis, Andrejs, Laucevicius, Aleksandras, Kedev, Sasko, Yusoff, Khalid, Ramos López, Gabriel Arturo, Alings, Marco, White, Harvey D., Halvorsen, Sigrun, Correa Flores, Roger M, Sy, Rody G., Budaj, Andrzej, Morais, Joao, Dorobantu, Maria, Karpov, Yuri, Ristic, Arsen D., Chua, Terrance, Murin, Jan, Fras, Zlatko, Dalby, Anthony J, Tuñón, José, de Silva, H. Asita, Hagström, Emil, Landmesser, Ulf, Müller, Christian, Chiang, Chern-En, Sritara, Piyamitr, Guneri, Sema, Parkhomenko, Alexander, Ray, Kausik K., Moriarty, Patrick M., Roe, Matthew T., Vogel, Robert, Chaitman, Bernard, Kelsey, Sheryl F., Olsson, Anders G., Rouleau, Jean-Lucien, Simoons, Maarten L., Alexander, Karen, Meloni, Chiara, Rosenson, Robert, Sijbrands, Eric J.G., Tricoci, Pierluigi, Alexander, John H., Armaganijan, Luciana, Bagai, Akshay, Bahit, Maria Cecilia, Brennan, J. Matthew, Clifton, Shaun, DeVore, Adam D., Deloatch, Shalonda, Dickey, Sheila, Dombrowski, Keith, Ducrocq, Grégory, Eapen, Zubin, Endsley, Patricia, Eppinger, Arleen, Harrison, Robert W., Hess, Connie Ng, Hlatky, Mark A., Jordan, Joseph Dedrick, Knowles, Joshua W., Kolls, Bradley J., Kong, David F., Leonardi, Sergio, Lillis, Linda, Lopes, Renato D., Maron, David J., Mahaffey, Kenneth W., Marcus, Jill, Mathews, Robin, Mehta, Rajendra H., Mentz, Robert J., Moreira, Humberto Graner, Patel, Chetan B., Pereira, Sabrina Bernardez, Perkins, Lynn, Povsic, Thomas J., Puymirat, Etienne, Roe, Matthew T., Jones, William Schuyler, Shah, Bimal R., Sherwood, Matthew W., Stringfellow, Kenya, Sujjavanich, Darin, Toma, Mustafa, Trotter, Charlene, van Diepen, Sean F.P., Wilson, Matthew D., Tze-Kay Yan, Andrew, Schiavi, Lilia B, Garrido, Marcelo, Alvarisqueta, Andrés F, Sassone, Sonia A, Bordonava, Anselmo P, Alves De Lima, Alberto E, Schmidberg, Jorge M, Duronto, Ernesto A, Caruso, Orlando C, Novaretto, Leonardo P, Hominal, Miguel Angel, Montaña, Oscar R, Caccavo, Alberto, Gomez Vilamajo, Oscar A, Lorenzatti, Alberto J, Cartasegna, Luis R, Paterlini, Gustavo A, Mackinnon, Ignacio J, Caime, Guillermo D, Amuchastegui, Marcos, Salomone, Oscar, Codutti, Oscar R, Jure, Horacio O, Bono, Julio OE, Hrabar, Adrian D, Vallejos, Julio A, Ahuad Guerrero, Rodolfo A, Novoa, Federico, Patocchi, Cristian A, Zaidman, Cesar J, Giuliano, Maria E, Dran, Ricardo D, Vico, Marisa L, Carnero, Gabriela S, Guzman, Pablo N, Medrano Allende, Juan C, Garcia Brasca, Daniela F, Bustamante Labarta, Miguel H, Nani, Sebastian, Blumberg, Eduardo DS, Colombo, Hugo R, Liberman, Alberto, Fuentealba, Victorino, Luciardi, Hector L, Waisman, Gabriel D, Berli, Mario A, Garcia Duran, Ruben O, Cestari, Horacio G, Luquez, Hugo A, Giordano, Jorge A, Saavedra, Silvia S, Zapata, Gerardo, Costamagna, Osvaldo, Llois, Susana, Waites, Jonathon H, Collins, Nicholas, Soward, Allan, Aylward, Philip E, Hii, Chris LS, Aylward, Philip E, Shaw, James, Arstall, Margaret A, Horowitz, John, Ninio, Daniel, Rogers, James F, Colquhoun, David, Oqueli Flores, Romulo E, Roberts-Thomson, Philip, Raffel, Owen, Lehman, Sam J, Aroney, Constantine, Coverdale, Steven GM, Garrahy, Paul J, Starmer, Gregory, Sader, Mark, Carroll, Patrick A, Dick, Ronald, Zweiker, Robert, Hoppe, Uta, Drexel, Heinz, Huber, Kurt, Berger, Rudolf, Delle-Karth, Georg, Frey, Bernhard, Weidinger, Franz, Faes, Dirk, Hermans, Kurt, Pirenne, Bruno, Leone, Attilio, Hoffer, Etienne, Sinnaeve, Peter, Vrolix, Mathias CM, Wolf, Luc De, Wollaert, Bart, Castadot, Marc, Dujardin, Karl, Beauloye, Christophe, Vervoort, Geert, Striekwold, Harry, Convens, Carl, Roosen, John, Barbato, Emanuele, Claeys, Marc, Cools, Frank, Terzic, Ibrahim, Barakovic, Fahir, Midzic, Zlatko, Pojskic, Belma, Fazlibegovic, Emir, Dilic, Mirza, Durak-Nalbantic, Azra, Kulić, Mehmed, Vulic, Dusko, Muslibegovic, Adis, Goronja, Boris, Reis, Gilmar, Sousa, Luciano, Nicolau, Jose C, Giorgeto, Flavio E, Silva, Ricardo P, Maia, Lilia Nigro, Rech, Rafael, Rossi, Paulo RF, Cerqueira, Maria José AG, Duda, Norberto, Kalil, Renato, Kormann, Adrian, Abrantes, José Antonio M, Filho, Pedro Pimentel, Soggia, Ana Priscila, de Santos, Mayler ON, Neuenschwander, Fernando, Bodanese, Luiz C, Michalaros, Yorghos L, Eliaschewitz, Freddy G, Vidotti, Maria H, Leaes, Paulo E, Botelho, Roberto V, Kaiser, Sergio, Manenti, Euler Roberto F Fernandes, Precoma, Dalton B, Moura Jorge, Jose C, Silva, Pedro, Silveira, Jose A, Saporito, Wladmir, Neto, Jose A Marin, Feitosa, Gilson S, Ritt, Luiz Eduardo F, de Souza, Juliana A, Costa, Fernando, Souza, Weimar KSB, Reis, Helder JL, Lopes, Renato D., Machado, Leandro, Aidar Ayoub, José Carlos, Todorov, Georgi V, Nikolov, Fedya P, Velcheva, Elena S, Tzekova, Maria L, Benov, Haralambi O, Petranov, Stanislav L, Tumbev, Haralin S, Shehova-Yankova, Nina S, Markov, Dimitar T, Raev, Dimitar H, Mollov, Mihail N, Kichukov, Kostadin N, Ilieva- Pandeva, Katya A, Gotcheva, Nina N, Ivanova, Raya, Gospodinov, Maryana, Mincheva, Valentina M, Lazov, Petar V, Dimov, Bojidar I, Senaratne, Manohara, Stone, James, Kornder, Jan, Pearce, Stephen, Dion, Danielle, Savard, Daniel, Pesant, Yves, Pandey, Amritanshu, Robinson, Simon, Gosselin, Gilbert, Vizel, Saul, Hoag, Gordon, Bourgeois, Ronald, Morisset, Anne, Sabbah, Eric, Sussex, Bruce, Kouz, Simon, MacDonald, Paul, Diaz, Ariel, Michaud, Nicolas, Fell, David, Leung, Raymond, Vuurmans, Tycho, Lai, Christopher, Nigro, Frank, Davies, Richard, Nogareda, Gustavo, Vijayaraghavan, Ram, Ducas, John, Lepage, Serge, Mehta, Shamir, Cha, James, Dupuis, Robert, Fong, Peter, Lutchmedial, Sohrab, Rodes-Cabau, Josep, Fadlallah, Hussein, Cleveland, David, Huynh, Thao, Bata, Iqbal, Hameed, Adnan, Pincetti, Cristian, Potthoff, Sergio, Prieto, Juan C, Acevedo, Monica, Aguirre, Arnoldo, Vejar, Margarita, Yañez, Mario, Araneda, Guillermo, Fernandez, Mauricio, Perez, Luis, Varleta, Paola, Florenzano, Fernando, Huidobro, Laura, Raffo, Carlos A, Olivares, Claudia, Nahuelpan, Leonardo, Montecinos, Humberto, Chen, Jiyan, Dong, Yugang, Huang, Weijian, Wang, Jianzhong, Huang, Shi’An, Yao, Zhuhua, Li, Xiang, Cui, Lan, Lin, Wenhua, Sun, Yuemin, Wang, Jingfeng, Li, Jianping, Zhang, Xuelian, Zhu, Hong, Chen, Dandan, Huang, Lan, Dong, Shaohong, Su, Guohai, Xu, Biao, Su, Xi, Cheng, Xiaoshu, Lin, Jinxiu, Zong, Wenxia, Li, Huanming, Feng, Yi, Xu, Dingli, Yang, Xinchun, Ke, Yuannan, Lin, Xuefeng, Zhang, Zheng, Zheng, Zeqi, Luo, Zhurong, Chen, Yundai, Ding, Chunhua, Zhong, Yi, Zheng, Yang, Li, Xiaodong, Peng, Daoquan, Zhao, Shuiping, Li, Ying, Liu, Xuebo, Wei, Meng, Liu, Shaowen, Yu, Yihua, Qu, Baiming, Jiang, Weihong, Zhou, Yujie, Zhao, Xingsheng, Yuan, Zuyi, Guo, Ying, Xu, Xiping, Shi, Xubo, Ge, Junbo, Fu, Guosheng, Bai, Feng, Fang, Weiyi, Shou, Xiling, Yang, Xiangjun, Wang, Jian’An, Xiang, Meixiang, Sun, Yingxian, Lu, Qinghua, Zhang, Ruiyan, Zhu, Jianhua, Xu, Yizhou, Fan, Zhongcai, Li, Tianchang, Wu, Chun, Jaramillo, Nicolas, Vallejo, Gregorio Sanchez, Luna Botia, Diana C, Lopez, Rodrigo Botero, De Salazar, Dora I Molina, Bonfanti, Alberto J Cadena, Aroca, Carlos Cotes, Higuera, Juan Diego, Blanquicett, Marco, Barrera Silva, Sandra I, Garcia Lozada, Henry J, Coronel Arroyo, Julian A, Accini Mendoza, Jose L, Fernandez Ruiz, Ricardo L, Quintero Ossa, Alvaro M., Manzur Jatin, Fernando G, Sotomayor Herazo, Aristides, Parada, Jeffrey Castellanos, Arambula, Rafael Suarez, Urina Triana, Miguel A, Trujillo, Angela M Fernandez, Strozzi, Maja, Car, Siniša, Miličić, Davor, Lovrić Benčić, Martina, Pintarić, Hrvoje, Prvulović, Đeiti, Šikić, Jozica, Peršić, Viktor, Mileta, Dean, Štambuk, Kresimir, Babić, Zdravko, Tomulic, Vjekoslav, Lukenda, Josip, Mejic-Krstulovic, Stanka, Starcevic, Boris, Spinar, Jindrich, Horak, David, Velicka, Zdenek, Alan, David, Machova, Vilma, Linhart, Ales, Novotny, Vojtech, Kaucak, Vladimir, Rokyta, Richard, Naplava, Robert, Coufal, Zdenek, Adamkova, Vera, Podpera, Ivo, Zizka, Jiri, Motovska, Zuzana, Marusincova, Ivana, Ostadal, Petr, Heinc, Petr, Kuchar, Jiri, Povolny, Petr, Matuska, Jiri, Poulsen, Steen H, Raungaard, Bent, Clemmensen, Peter, Bang, Lia E, May, Ole, Bøttcher, Morten, Hove, Jens D, Frost, Lars, Gislason, Gunnar, Larsen, John, Johansen, Peter Betton, Hald, Flemming, Johansen, Peter, Jeppesen, Jørgen, Nielsen, Tonny, Kristensen, Kjeld S, Walichiewicz, Piotr Maria, Lomholdt, Jens D, Klausen, Ib C, Nielsen, Peter Kaiser, Davidsen, Flemming, Videbaek, Lars, Viigimaa, Margus, Soots, Mai, Vahula, Veiko, Hedman, Anu, Soopõld, Üllar, Märtsin, Kaja, Jurgenson, Tiina, Kristjan, Arved, Nieminen, Markku S, Vikman, Saila, Huikuri, Heikki, Airaksinen, Juhani, Coste, Pierre, Ferrari, Emile, Danchin, Nicolas, Morel, Olivier, Montalescot, Gilles, Machecourt, Jacques, Barone-Rochette, Gilles, Mansourati, Jacques, Cottin, Yves, Steg, Ph. Gabriel, Leclercq, Florence, Belhassane, Abdelkader, Delarche, Nicolas, Boccara, Franck, Paganelli, Franck, Clerc, Jérôme, Schiele, Francois, Aboyans, Victor, Probst, Vincent, Berland, Jacques, Lefèvre, Thierry, Chumburidze, Vakhtang, Khintibidze, Irakli, Shaburishvili, Tamaz, Pagava, Zurab, Ghlonti, Ramaz, Lominadze, Zaza, Khabeishvili, George, Hemetsberger, Rayyan, Edward, Kemala, Rauch-Kröhnert, Ursula, Stratmann, Matthias, Appel, Karl-Friedrich, Schmidt, Ekkehard, Omran, Heyder, Stellbrink, Christoph, Dorsel, Thomas, Lianopoulos, Emmanouil, Vöhringer, Hans Friedrich, Marx, Roger, Zirlik, Andreas, Schellenberg, Detlev, Heitzer, Thomas, Laufs, Ulrich, Werner, Christian, Marx, Nikolaus, Gielen, Stephan, Nuding, Sebastian, Winkelmann, Bernhard, Behrens, Steffen, Sydow, Karsten, Karakas, Mahir, Simonis, Gregor, Muenzel, Thomas, Werner, Nikos, Leggewie, Stefan, Böcker, Dirk, Braun- Dullaeus, Rüdiger, Toursarkissian, Nicole, Jeserich, Michael, Weißbrodt, Matthias, Schaeufele, Tim, Weil, Joachim, Völler, Heinz, Waltenberger, Johannes, Natour, Mohammed, Schmitt, Susanne, Müller-Wieland, Dirk, Steiner, Stephan, Heidenreich, Lothar, Offers, Elmar, Gremmler, Uwe, Killat, Holger, Rieker, Werner, Patsilinakos, Sotiris, Kartalis, Athanasios, Manolis, Athanassios, Sionis, Dimitrios, Chachalis, Geargios, Liberopoulos, Evangelos, Skoumas, Ioannis, Athyros, Vasilios, Vardas, Panagiotis, Parthenakis, Frangkiskos, Hahalis, Georgios, Lekakis, John, Hatzitolios, Apostolos, Fausto Ovando, Sergio R, Montenegro Valdovinos, Pablo Carlos, Arango Benecke, Juan L, Rodriguez De Leon, Edgar R, Yan, Bryan PY, Siu, David CW, Turi, Tibor, Merkely, Bela, Gabor Kiss, Robert, Ungi, Imre, Lupkovics, Geza, Nagy, Lajos, Katona, András, Édes, István, Müller, Gábor, Horvath, Iván, Kapin, Tibor, Szigeti, Zsolt, Faluközy, József, Kumbla, Mukund, Sandhu, Manjinder, Annam, Sharath, Reddy Proddutur, Naveen, Regella, Reddy, Premchand, Rajendra K, Mahajan, Ajaykumar, Pawar, Sudhir, Abhyanakar, Atul D, Kerkar, Prafulla, Govinda, Ravishankar A, Oomman, Abraham, Sinha, Dhurjati, Patil, Sachin N, Kahali, Dhiman, Sawhney, Jitendra, Joshi, Abhijeet B, Chaudhary, Sanjeev, Harkut, Pankaj, Guha, Santanu, Porwal, Sanjay, Jujjuru, Srimannarayana, Pothineni, Ramesh B, Monteiro, Minguel R, Khan, Aziz, Iyengar, Shamanna S, Grewal, Jasprakash Singh, Chopda, Manoj, Fulwani, Mahesh C, Patange, Dr. Aparna, Sachin, Patil, Chopra, Vijay K, Goyal, Naresh K, Shinde, Rituparna, Manakshe, Gajendra V, Patki, Nitin, Sethi, Sumeet, Munusamy, Vengatesh, Sunil Thanvi, Sunil Karnaand, Adhyapak, Srilakshmi, Patil, Chandrakant, Pandurangi, Ulhas, Mathur, Rishabh, Gupta, Jugal, Kalashetti, Suhas, Bhagwat, Ajit, Raghuraman, Bagirath, Kumar Yerra, Shiv, Bhansali, Prasant, Borse, Rohidas, Rahul, Patil, Das, Srihari, Kumar, Vinay, Abdullakutty, Jabir, Saathe, Shireesh, Palimkar, Priya, Abdullkutty, Jabir, Sathe, Shireesh, Atar, Shaul, Shechter, Michael, Mosseri, Morris, Arbel, Yaron, Ehud, Chorin, Ofer, Havakuk, Lotan, Chaim, Rosenschein, Uri, Katz, Amos, Henkin, Yaakov, Francis, Adi, Klutstein, Marc, Nikolsky, Eugenia, Zukermann, Robert, Turgeman, Yoav, Halabi, Majdi, Marmor, Alon, Kornowski, Ran, Jonas, Michael, Amir, Offer, Hasin, Yonathan, Rozenman, Yoseph, Fuchs, Shmuel, Zvi, Vered, Hussein, Osamah, Gavish, Dov, Vered, Zvi, Caraco, Yoseph, Elias, Mazen, Tov, Naveh, Wolfovitz, Efrat, Lishner, Michael, Elias, Nizar, Piovaccari, Giancarlo, Pellegrin, Annamaria De, Garbelotto, Raffaella, Guardigli, Gabriele, Marco, Valgimigli, Licciardello, Giovanni, Auguadro, Carla, Scalise, Filippo, Cuccia, Claudio, Salvioni, Alessandro, Musumeci, Giuseppe, Senni, Michelle, Calabrò, Paolo, Novo, Salvatore, Faggiano, Pompilio, Metra, Marco, De Cesare, Nicoletta B, Berti, Sergio, Puccioni, Enrico, Galvani, Marcello, Tespili, Maurizio, Piatti, Piermarco, Palvarini, Michela, Luca, Giuseppe De, Violini, Roberto, Leo, Alessandro De, Olivari, Zoran, Filardi, Pasquale Perrone, Ferratini, Maurizio, Racca, Vittorio, Dai, Kazuoki, Shimatani, Yuji, Kamiya, Haruo, Ando, Kenji, Takeda, Yoshihiro, Morino, Yoshihiro, Hata, Yoshiki, Kimura, Kazuo, Kishi, Koichi, Michishita, Ichiro, Uehara, Hiroki, Higashikata, Toshinori, Hirayama, Atsushi, Hirooka, Keiji, Doi, Yasuji, Sakagami, Satoru, Taguchi, Shuichi, Koike, Akihiro, Fujinaga, Hiroyuki, Koba, Shinji, Kozuma, Ken, Kawasaki, Tomohiro, Ono, Yujiro, Shimizu, Masatoshi, Katsuda, Yousuke, Wada, Atsuyuki, Shinke, Toshiro, Kimura, Takeshi, Ako, Junya, Fujii, Kenshi, Takahashi, Toshiyuki, Nakao, Koichi, Furukawa, Yutaka, Sugino, Hiroshi, Tamura, Ritsu, Mano, Toshiaki, Uematsu, Masaaki, Utsu, Noriaki, Ito, Kashima, Haraguchi, Takuya, Sato, Katsuhiko, Ueda, Yasunori, Nishibe, Akira, Fujimoto, Kazuteru, Masutani, Motomaru, Nishibe, Akira, Fujimoto, Kazuteru, Yoon, Jung Han, Kim, Sang-Hyun, Kim, Hack-Lyoung, Sik Park, Hun, Chae, In-Ho, Kim, Moo Hyun, Jeong, Myung Ho, Rha, Seungwoon, Kim, Chongjin, Kim, Hyo-Soo, Kim, Hae Young, Hong, Taekjong, Tahk, Seung-Jea, Kim, Youngkwon, Busmane, Arija, Pontaga, Natalija, Strelnieks, Aldis, Mintale, Iveta, Sime, Iveta, Petrulioniene, Zaneta, Kavaliauskiene, Roma, Jurgaitiene, Ruta, Sakalyte, Gintare, Slapikas, Rimvydas, Norkiene, Sigute, Misonis, Nerijus, Kibarskis, Aleksandras, Kubilius, Raimondas, Bojovski, Stojko, Kedev, Sasko, Lozance, Nensi, Kjovkaroski, Aleksandar, Doncovska, Snezana, Ong, Tiong Kiam, Kasim, Sazzli, Maskon, Oteh, Kandasamy, Balachandran, Yusoff, Khalid, Liew, Houng B, Wan Mohamed, Wan Mohd Izani, Castillo, Armando García, Ramos López, Gabriel Arturo, Calvillo, Jorge Carrillo, Campos, Pedro Fajardo, Núñez Fragoso, Juan Carlos, Bayram Llamas, Edmundo Alfredo, Alcocer Gamba, Marco Antonio, Madrigal, Jaime Carranza, González Salas, Luis Gerardo, Rosas, Enrique López, González Díaz, Belinda, Vázquez, Eduardo Salcido, Nacoud Ackar, Alfredo, Llamas Esperón, Guillermo Antonio, Martínez Sánchez, Carlos Rodolfo, De Leon, María Guerrero, Suarez Otero, Rodrigo, Salmón, Guillermo Fanghänel, Pérez Ríos, Jesús Antonio, Garza Ruíz, José Angel, Alings, Marco, Breedveld, Robert W, Feenema-Aardema, Margriet, Borger-Van Der Burg, Alida, Hoogslag, Pieter AM, Suryapranata, Harry, Oomen, Antonius, Van Haelst, Paulus, Feenema-Aradema, Margriet, Wiersma, Jacobijne J, Basart, Dirk, Van Der Wal, Ruud MA, Zwart, Peter, Monraats, Pascalle, Van Kesteren, Henricus, Karalis, Ioannis, Jukema, Johan, Verdel, Gerardus JE, Brueren, Bart RG, Troquay, Roland PTh, Viergever, Eric P, Al-Windy, Nadea YY, Bartels, Gerard L, Cornel, Jan H, Hermans, Walter RM, Herrman, Johannes PR, Bos, Robert J, Groutars, Reginald GEJ, Van Der Zwaan, Coenraad C, Kaplan, Refik, Ronner, Eelko, Groenemeijer, Bjorn E, Bronzwaer, Patrick NA, Liem, Anho AH, Rensing, Bernard JWM, Bokern, Marcel JJA, Nijmeijer, Remco, Hersbach, Ferry MRJ, Willems, Frank F, Gosselink, Antonius TM, Rasoul, Saman, Elliott, John, Wilkins, Gerard, Fisher, Raewyn, Scott, Douglas, Hart, Hamish, Stewart, Ralph, Harding, Scott, Ternouth, Ian, Fisher, Nicholas, Wilson, Samuel, Aitken, Denise, Anscombe, Russell, Davidson, Laura, Tomala, Tadeusz, Nygård, Ottar, Sparby, Jon Arne, Andersen, Kjell, Gullestad, Lars, Jortveit, Jarle, Munk, Peter S, Singsaas, Erlend gyllensten, Halvorsen, Sigrun, Hurtig, Ulf, Correa Flores, Roger M, Calderon Ticona, Jorge R, Durand Velasquez, Julio R, Negron Miguel, Sandra A, Sanabria Perez, Enrique S, Carrion Chambilla, Jesus M, Chavez Ayala, Carlos A, Castillo Leon, Reynaldo P, Vargas GonzalesC, Rolando J, Hernandez Zuniga, Jose D, Camacho Cosavalente, Luis A, Bravo Mannucci, Jorge E, Landeo, Javier Heredia, Llerena Navarro, Nassip C, Roldan Concha, Yudy M, Rodriguez Chavez, Víctor E, Anchante Hernandez, Henry A, Zea Nunez, Carlos A, Ramos, Walter Mogrovejo, Ferrolino, Arthur, Sy, Rosa Allyn G, Tirador, Louie, Sy, Rody G., Matiga, Generoso, Coching, Raul Martin, Bernan, Alisa, Rogelio, Gregorio, Morales, Dante D., Tan, Edgar, Sulit, Dennis Jose, Wlodarczak, Adrian, Skonieczny, Grzegorz, Pawlowicz, Lidia, Wojewoda, Pawel, Busz-Papiez, Benita, Bednarski, Janusz, Goch, Aleksander, Staneta, Pawel, Dulak, Elzbieta, Budaj, Andrzej, Saminski, Krzysztof, Krasowski, Wlodzimierz, Sudnik, Wanda, Zurakowski, Aleksander, Skorski, Marcin, Lysek, Roman, Miklaszewicz, Beata, Lipko, Jan Andrzej, Kostarska-Srokosz, Edyta, Piepiorka, Marek, Drzewiecka, Anna, Stasiewski, Arkadiusz, Blicharski, Tomasz, Bystryk, Leszek, Szpajer, Michal, Korol, Marek, Czerski, Tomasz, Gniot, Jacek, Lubinski, Andrzej, Gorny, Jerzy, Franek, Edward, Raczak, Grzegorz, Szwed, Hanna, Monteiro, Pedro, Mesquita Bastos, Jose, Pereira, Helder H, Morais, Joao, Seixo, Filipe, Mendonça, Carlos, Botelho, Ana, Caetano, Francisca, Minescu, Bogdan, Istratoaie, Octavian, Tesloianu, Dan N, Dorobantu, Maria, Cristian, Gabriel, Dumitrescu, Silviu, Podoleanu, Cristian GC, Constantinescu, Mircea CA, Bengus, Cristina M, Militaru, Constantin, Rosu, Doina, Parepa, Irinel R, Matei, Adrian V, Alexandru, Tom M, Malis, Mihaela, Coman, Ioan, Shvarts, Yury, Orlikova, Olga, Kobalava, Zhanna, Barbarash, Olga L, Markov, Valentin, Lyamina, Nadezhda, Gordienko, Alexander, Zrazhevsky, Konstantin, Vishnevsky, Alexander Y, Gurevich, Victor, Stryuk, Raisa, Lomakin, Nikita V, Bokarev, Igor, Khlevchuk, Tatiana, Shalaev, Sergey, Khaisheva, Larisa, Chizhov, Petr, Viktorova, Inna, Osokina, Natalya, Shchekotov, Vladimir, Akatova, Evgenia, Chumakova, Galina, Libov, Igor, Voevoda, Mikhail I, Tretyakova, Tatyana V, Baranov, Evgeny, Shustov, Sergey, Yakushin, Sergey, Gordeev, Ivan, Khasanov, Niiaz, Reshetko, Olga, Sotnikova, Tatiana, Molchanova, Olga, Nikolaev, Konstantin, Gapon, Liudmila, Baranova, Elena, Kosmachova, Elena, Karpov, Yuriy, Karpov, Yuri, Povzun, Anton, Egorova, Liudmila, Tyrenko, Vadim V, Ivanov, Igor G, Ilya, Masterov, Kanorsky, Sergey, Simic, Dragan, Ivanovic, Nikola, Davidovic, Goran, Tasic, Nebojsa, Asanin, Milika R., Stojic, Stevo, Apostolovic, Svetlana R., Ilic, Stevan, Tosic, Biljana Putnikovic, Stankovic, Aleksandar, Arandjelovic, Aleksandra, Radovanovic, Slavica, Todic, Branislava, Ristic, Arsen D., Balinovac, Jovan, Dincic, Dragan V., Seferovic, Petar, Karadzic, Ana, Dodic, Slobodan, Dimkovic, Sinisa, Jakimov, Tamara, Poh, Kian-Keong, Yee Ong, Hean, Tang I-Shing, Justin, Micko, Karol, Nociar, Jan, Pella, Daniel, Fulop, Peter, Hranai, Marian, Palka, Juraj, Mazur, Juraj, Majercák, Ivan, Dzupina, Andrej, Fazekas, František, Gonsorcik, Jozef, Bugan, Viliam, Murin, Jan, Selecky, Juraj, Kamensky, Gabriel, Strbova, Jaroslava, Smik, Rudolf, Dukat, Andrej, Olexa, Peter, Žuran, Ivan, Poklukar, Janez, Šuligoj, Nataša Černič, Cevc, Matija, Fras, Zlatko, Cyster, Henry P, Ranjith, Naresh, Corbett, Clive, Bayat, Junaid, Makoali Makotoko, Ellen, du Toit Theron, Hendrik, Kapp, Ilse E, de V Basson, Matthys M, Lottering, Hanlie, Aswegen, Dina Van, Van Zyl, Louis J, Sebastian, Peter J, Pillay, Thayabran, Saaiman, Jan A, Commerford, Patrick J, Cassimjee, Soraya, Riaz, Garda, Ebrahim, Iftikhar O, Sarvan, Mahomed, Mynhardt, Joseph H, Dalby, Anthony J, Reuter, Helmuth, Moodley, Rajendran, Vida, Manuel, Fillat, Angel R. Cequier, Peris, Vicente Bodí, Jimenez, Francisco Fuentes, Marín, Francisco, Cruz Fernández, Jose M, Hidalgo Urbano, Rafael Jesus, Gil-Extremera, Blas, Toledo, Pablo, Worner Diz, Fernando, Garcia-Dorado, David, Iñiguez, Andres, Gonzalez-Juanatey, Jose R, Portales, Javier Fernandez, Murillo, Fernando Civeira, Pericas, Laia Matas, Zamorano, Jose Luis, De Mora Martin, Manuel, Cortada, Jordi Bruguera, Alonso Martin, Joaquin J, Serrano Antolin, Jose Maria, De Berrazueta Fernández, José R, Vázquez de Prada, José Antonio, Díaz Fernández, Jose Francisco, García Lledó, José Alberto, Cosín Sales, Juan, Rodriguez, Javier Botas, Tragant, Gabriel Gusi, Benedicto, Amparo, Gonzalez-Juanatey, Carlos, Camprubí Potau, Mercedes, Perez, Ignacio Plaza, De La Tassa, César Morís, Rincon, Pablo Loma-Osorio, Recena, Javier Balaguer, Escudier, Juan M, Payeras, Antonio Coca, Orcajo, Norberto Alonso, Constantine, Godwin, Haniffa, Ruvaiz, Tissera, Nirmali, Amarasekera, Stanley, Ponnamperuma, Chandrike, Fernando, Nimali, Fernando, Kaputella, Jayawardena, Jayanthimala, Wijeyasingam, Santharaj, Ranasinghe, Gotabhaya, Ekanayaka, Ruvan, Mendis, Sepalika, Senaratne, Vajira, Mayurathan, Gnanamoorthy, Rajapaksha, Ajantha, Sirisena, Thilak, Herath, Jagath I, Amarasena, Naomali, Berglund, Stefan, Rasmanis, Gundars, Hagström, Emil, Vedin, Ola, Witt, Nils, Mourtzinis, Georgios, Nicol, Peter, Hansen, Ole, Romeo, Stefano, Jensen, Steen Agergaard, Torstensson, Ingemar, Ahremark, Ulf, Sundelin, Torbjörn, Moccetti, Tiziano, Müller, Christian, Mach, Francois, Binde, Ronald, Landmesser, Ulf, Gämperli, Oliver, Chiang, Chern-En, Tsai, Wei- Chuan, Ueng, Kwo-Chang, Lai, Wen-Ter, Liu, Ming-En, Hwang, Juey- Jen, Yin, Wei-Hsian, Hsieh, I-Chang, Hsieh, Ming-Jer, Hsiang Lin, Wei, Kuo, Jen-Yuan, Huang, Tsuei-Yuan, Fang, Chih-Yuan, Kaewsuwanna, Pinij, Soonfuang, Wasant, Jintapakorn, Woravut, Sukonthasarn, Apichard, Sritara, Piyamitr, Wongpraparut, Nattawut, Sastravaha, Krisada, Sansanayudh, Nakarin, Kehasukcharoen, Wirash, Piyayotai, Dilok, Chotnoparatpat, Paiboon, Camsari, Ahmet, Kultursay, Hakan, Guneri, Sema, Mutlu, Bulent, Ersanli, Murat, Demirtas, Mustafa, Kirma, Cevat, Ural, Ertan, Koldas, Lale, Karpenko, Oleksandr, Prokhorov, Alexander, Vakaluyk, Ihor, Myshanych, Halyna, Reshotko, Dmytro, Batushkin, Valeriy, Rudenko, Leonid, Kovalskyi, Ihor, Kushnir, Mykola, Tseluyko, Vira, Mostovoy, Yuriy, Stanislavchuk, Mykola, Kyiak, Yulian, Karpenko, Yuriy, Malynovsky, Yaroslav, Klantsa, Andriy, Kutniy, Oles, Amosova, Ekaterina, Tashchuk, Viktor, Leshchuk, Oleh, Parkhomenko, Alexander, Rishko, Mykola, Kopytsya, Mykola, Yagensky, Andriy, Vatutin, Mykola, Bagriy, Andriy, Barna, Olga M, Ushakov, Olexiy, Dzyak, Georgiy, Goloborodko, Borys, Rudenko, Anatolii, Zheleznyy, Volodymyr, Trevelyan, Jasper, Zaman, Azfar, Lee, Kaeng, Moriarty, Andrew, Aggarwal, Rajesh K, Clifford, Piers, Wong, Yuk- Ki, Iqbal, Syed MR, Subkovas, Eduardas, Braganza, Denise, Sarkar, David, Storey, Robert, Griffiths, Huw, Mcclure, Sam, Muthusamy, Rangasamy, Smith, Simon, Kurian, John, Levy, Terry, Barr, Craig, Kadr, Honer, Gerber, Robert, Simaitis, Audrius, Soran, Handrean, Brodison, Adrian, Ayaz, Mohammad, Cheema, Muhammad, Oliver, Richard, Thackray, Simon, Mudawi, Telal, Rahma, Gohar, Sultan, Ayyaz, Reynolds, Timothy, Sharman, David, Spriging, david, Butler, Rob, Wilkinson, Peter, Lip, Gregory YH, Ossei-Gerning, Nicholas, Vardi, Gil, Baldari, Duccio, Brabham, David, Treasure II, Charles, Dahl, Charles, Palmer, Bruce, Wiseman, Alan, Khan, Abul, Puri, Sanjeev, Mohart, Ann Elizabeth, Ince, Carlos, Flores, Enrique, Wright, Scott, Cheng, Shi-Chi, Rosenberg, Michael, Rogers, William, Kosinski, Edward, Forgosh, Les, Waltman, Jonathan, Shoukfeh, Mohammad, Dagher, Georges, Cambier, Patrick, Lieber, Ira, Kumar, Priya, East, Cara, Krichmar, Perry, Hasan, Mian, White, Lindsey, Knickelbine, Thomas, Haldis, Thomas, Gillespie, Eve, Amidon, Thomas, Suh, David, Arif, Imran, Abdallah, mouhamad, Akhter, Faiq, Carlson, Eric, D’Urso, Michael, El- Ahdab, Fadi, Nelson, William, Moriarty, Katie, Harris, Barry, Cohen, Steven, Carter, Luther, Doty, Daniel, Sabatino, Kenneth, Haddad, Tariq, Rao, Sunder, Mulkay, Angel, Jovin, Ion, Klancke, Kim, Malhotra, Vinay, Devarapalli, Sai K, Koren, Michael, Chandna, Harish, Dodds, George, Goraya, Tauqir, Bengston, James, Janik, Matthew, Moran, Joseph, Sumner, Andrew, Kobayashi, John, Davis, William, Yazdani, Shahram, Pasquini, John, Thakkar, Maitreya, Vedere, Amarnath, Leimbach, Wayne, Rider, James, fenton, Sarah, Singh, Narendra, Shah, Anil V, Moriarty, Patrick M., Janosik, Denise, Pepine, Carl, Berman, Brett, Gelormini, Joseph, Daniels, Christopher, Richard, Kerensky, Keating, Friederike, Kondo, Nicholas I, Shetty, Sanjay, Levite, Howard, Waider, Winfried, Takata, Theodore, Abu-Fadel, Mazen, Shah, Vipul, Aggarwal, Rahul, Kumar, Anil, Hattler, Brack, Do, Rose, Link, Chad, Bortnick, Anna, Kinzfogl, George, Ghitis, Arnold, Larry, John, Teufel, Edward, Kuhlman, Peter, Mclaurin, Brent, Zhang, Wenwu, Thew, Stephen, Abbas, Jalal, White, Matthew, Islam, Othman, Subherwal, Sumeet, Ranadive, Nandkishore, Vakili, Babak, Gring, Christian, Henderson, David, Schuchard, Timothy, Farhat, Naim, Kline, Geoffrey, Mahal, Sharan, Whitaker, Jack, Speirs, Shawn, Andersen, Rolf, Daboul, Nizar, Horwitz, Phillip, Zahr, Firas, Ponce, George, Jafar, Zubair, Mcgarvey, Joseph, Panchal, Vipul, Voyce, Stephen, Blok, Thomas, Sheldon, William, Azizad, Masoud M, Schmalfuss, Carsten, Picone, Mark, Pederson, Robert, Herzog, William, Friedman, Keith, Lindsey, Jason, Timothy, Eichenlaub, Leonard, Parilak, Lepor, Norman, El Shahawy, Mahfouz, Weintraub, Howard, Irimpen, Anand, Alonso, Alvaro, May, Wade, Christopher, Daniels, Galski, Thomas, Chu, Alan, Mody, Freny, Ramin, Ebrahimi, Hodes, Zachary, Rossi, Joseph, Rose, Gregory, Fairlamb, James, Lambert, Charles, Raisinghani, Ajit, Abbate, Antonio, Vetrovec, George, King, Marilyn, Carey, Charles, Gerber, Jaime, Younis, Liwa, Park, Hyeun (Tom), Vidovich, Mladen, Knutson, Thomas, Friedman, Dennis, Chaleff, Fred, Loussararian, Arthur, Rozeman, Phillip, Kimmelstiel, Carey, Kuvin, Jeffrey, Silver, Kevin, Foster, Malcolm, Tonnessen, Glen, Espinoza, Andrey, Amlani, Mohamadali, Wali, Andreas, Malozzi, Christopher, Jong, Geert T, Massey, Clara, Wattanakit, Keattiyoat, O’Donnell, Philip J., Singal, Dinesh, Jaffrani, Naseem, Banuru, Sridhar, Fisher, Daniel, Xenakis, Mark, Perlmutter, Neal, Bhagwat, Ravi, Strader, James, Blonder, Ronald, Akyea-Djamson, Ayim, Labroo, Ajay, Lee, Kwan, Marais, H. John, Claxton, Edmund, Weiss, Robert, Kathryn, Rohr, Berk, Martin, Rossi, Peter, Joshi, Parag, Khera, Amit, Khaira, Ajit S, Kumkumian, Greg, Lupovitch, Steven, Purow, Joshua, Welka, Stephen, Hoffman, David, Fischer, Stuart, Soroka, Eugene, Eagerton, Donald, Pancholy, Samir, Ray, Michael, Erenrich, Norman, Farrar, Michael, Pollock, Stewart, French, William J, Diamantis, Steve, Guy, Douglas, Gimple, Lawrence, Neustel, Mark, Schwartz, Steven, Pereira, Edward, Albert, Seals, Spriggs, Douglas, Strain, Janet, Mittal, Suneet, Vo, Anthony, Chane, Majed, Hall, Jason, Vijay, Nampalli, Lotun, Kapildeo, Lester, F. Martin, Nahhas, Ahed, Pope, Theodore, Nager, Paul, Vohra, Rakesh, Sharma, Mukesh, Bashir, Riyaz, Ahmed, Hinan, Berlowitz, Michael, Fishberg, Robert, Barrucco, Robert, Yang, Eric, Radin, Michael, Sporn, Daniel, Stapleton, Dwight, Eisenberg, Steven, Landzberg, Joel, Mcgough, Martin, Turk, Samir, Schwartz, Michael, Sundram, P. Sandy, Jain, Diwakar, Zainea, Mark, Bayron, Carlos, Karlsberg, Ronald, Dohad, Suhail, Lui, Henry, Keen, William, Westerhausen, Donald, Khurana, Sandeep, Agarwal, Himanshu, Birchem, Jessica, Penny, William, Chang, Mark, Murphy, Sherrill, Henry, John, Schifferdecker, Branislav, Gilbert, John M, Chalavarya, Gopal, Eaton, Charles, Schmedtje, John F, Christenson, Stuart, Dotani, Imran, Denham, Douglas, Macdonell, Alexander, Gibson, Paul, Rahman, Aref, Al Joundi, Tammam, Assi, Nizar, Conrad, Gary, Kotha, Purushotham, Love, Michael, Giesler, Gregory, Rubenstein, Howard, Gamil, Dawood, Akright, Laura, Krawczyk, Justine, Cobler, Joanne, Wells, Terry, Welker, James, Foster, Robert, Gilmore, Richard, Anderson, Jay, Jacoby, Douglas, Harris, Bill, Gardner, Geraldine, Dandillaya, Ramprasad, Vora, Kishor, Kostis, John, Hunter, John, Laxson, David, Ball, Eric, Anderson, Jay, Wells, Terry, Vora, Kishor, Ball, Eric, Welker, James, Lopes, Renato D., Egydio, Flavia, Kawakami, Anelise, Oliveira, Janaina, Goodman, Shaun G., Wozniak, Julianna, Matthews, Alexander, Ratky, Caroline, Valiris, Janine, Berdan, Lisa, Hepditch, Anita, Quintero, Kirby, Roe, Matthew T., Rorick, Tyrus, Westbrook, Melissa, Danchin, Nicolas, Bezault, Madeleine, Drouet, Elodie, Simon, Tabassome, White, Harvey D., Alsweiler, Caroline, Sinnaeve, Peter, Luyten, Anne, Aylward, Philip E, Butters, Julie, Griffith, Liddy, Shaw, Michelle, Hagström, Emil, Grunberg, Lena, Szarek, Michael, Islam, Shahidul, Brégeault, Marie-France, Bougon, Nathalie, Faustino, Douglas, Fontecave, Sylvie, Murphy, Judith, Tamby, Jean- Francois, Verrier, Melanie, Agnetti, Veronique, Andersen, Dorthe, Badreddine, Emmy, Bekkouche, Mhamed, Bouancheau, Cecile, Brigui, Imane, Brocklehurst, Maddy, Cianciarulo, Joseph, Devaul, Dawn, Domokos, Szilvia, Gache, Cecile, Gobillot, Caroline, Guillou, Severine, Healy, Jan, Heath, Megan, Jaiwal, Gayatri, Javierre, Carine, Labeirie, Julien, Monier, Myriam, Morales, Ulises, Mrabti, Asmaa, Mthombeni, Bicky, Okan, Betim, Smith, Lucile, Sheller, Jennifer, Sopena, Sebastien, Pellan, Valerie, Benbernou, Fadela, Bengrait, Nafissa, Lamoureux, Maud, Kralova, Katarina, Scemama, Michel, Bejuit, Raphael, Coulange, Anthony, Berthou, Christelle, Repincay, Jérôme, Lorenzato, Christelle, Etienne, Alexis, Gouet, Valerie, Lecorps, Guillaume, Loizeau, Virginie, Normand, Mickael, Ourliac, Anne, Rondel, Christelle, Adamo, Antony, Beltran, Pascale, Barraud, Pauline, Dubois-Gache, Helene, Halle, Benjamin, Metwally, Lamia, Mourgues, Maxime, Sotty, Marc, Vincendet, Marion, Cotruta, Raluca, Chengyue, Zhu, Fournie-Lloret, Dominique, Morrello, Christine, Perthuis, Aurelie, Picault, Patrick, Zobouyan, Isabelle, Colhoun, Helen M., Dempsey, Michael A., and McClanahan, Mark A.
Published: 2022
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27. 859 - DESCRIPCIÓN DEL IMPACTO DE LA DISMINUCIÓN DE LOS LÍPIDOS EN LA COMPOSICIÓN DE LA PLACA DE ATEROMA VALORADO POR ECOGRAFÍA BIDIMENSIONAL

Author: Langarita, Carmen Vicente, primary, Simón, Estíbaliz Jarauta, additional, Hidalgo, María Patricia Solana, additional, Arceiz, Elisa García, additional, Gilaberte, Juan Blas Pérez, additional, Valle, Laura Vela, additional, Giner, Paula López de Turiso, additional, and Murillo, Fernando Civeira, additional
Published: 2023
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28. Contribution of APOE Genetic Variants to Dyslipidemia

Author: Ana M. Bea, Asier Larrea-Sebal, Victoria Marco-Benedi, Kepa B. Uribe, Unai Galicia-Garcia, Itziar Lamiquiz-Moneo, Martín Laclaustra, Belén Moreno-Franco, Pablo Fernandez-Corredoira, Salvador Olmos, Fernando Civeira, César Martin, and Ana Cenarro
Subjects: Cardiology and Cardiovascular Medicine
Abstract: Background: apo (apolipoprotein) E has crucial role in lipid metabolism. The genetic variation in APOE gene is associated with monogenic disorders and contributes to polygenic hypercholesterolemia and to interindividual variability in cholesterol. APOE rare variants may be involved in the phenotype of genetic hyperlipidemias. Methods: Exon 4 of APOE were sequenced in all consecutive unrelated subjects with primary hyperlipidemia from a Lipid Unit (n=3667) and 822 random subjects from the Aragon Workers Health Study. Binding affinity of VLDL (very low-density lipoprotein) to LDL receptor of pathogenic predicted apoE variants was analyzed in vitro. Lipoprotein particle number, size, and composition were studied by nuclear magnetic resonance. Results: In addition to common polymorphisms giving rise to APOE2 and APOE4, 14 gene variants were found in exon 4 of APOE in 65 subjects. p.(Leu167del) in 8 patients with isolated hypercholesterolemia and in 8 patients with combined hyperlipidemia. Subjects with p.(Arg121Trp), p.(Gly145Asp), p.(Arg154Ser), p.(Arg163Cys), p.(Arg165Trp), and p.(Arg168His) variants met dysbetalipoproteinemia lipid criteria and were confirmed by nuclear magnetic resonance. VLDL affinity for the LDL receptor of p.(Arg163Cys) and p.(Arg165Trp) heterozygous carriers had intermedium affinity between APOE2/2 and APOE3/3. p.(Gly145Asp) and p.(Pro220Leu) variants had higher affinity than APOE3/3. Conclusions: APOE genetic variation contributes to the development of combined hyperlipidemia, usually dysbetalipoproteinemia, and familial hypercholesterolemia. The lipid phenotype in heterozygous for dysbetalipoproteinemia-associated mutations is milder than the homozygous APOE2/2-associated phenotype. Subjects with dysbetalipoproteinemia and absence of APOE2/2 are good candidates for the study of pathogenic variants in APOE . However, more investigation is required to elucidate the significance of rarer variants of apoE.
Published: 2023

29. Coordinated overexpression of miR-33a and miR-27b induced by statin-treatment contributes to the development of type 2 diabetes mellitus

Author: Garcia, Unai Galicia, Jebari-Benslaiman, Shifa, Lopez-Ariño, Chuan, Benito-Vicente, Asier, Larrea-Sebal, Asier, Uribe, Kepa Belloso, Gracia-Rubio, Irene, Lagunas, Ana Cenarro, Murillo, Fernando Civeira, and Martin, Cesar
Published: 2024
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30. Randomized, open-label, study comparing efficacy and safety of lerodalcibep to inclisiran in patients with CVD or at high risk for CVD requiring additional LDL-cholesterol reduction

Author: Laufs, Ulrich, Licka, Manuela, Asprusten, Emil, Cariou, Bertrand, Jacobsen, Nicholas, Murillo, Fernando Civeira, Vest, Jeffrey, Kallend, David, and Stein, Evan
Published: 2024
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31. Optimo-LDLr: An integrated in silico model with enhanced predictive power for LDL receptor variants, unraveling hot spot pathogenic residues

Author: Larrea-Sebal, Asier, Sasiain, Iñaki, Jebari-Benslaiman, Shifa, Garcia, Unai Galicia, Uribe, Kepa Belloso, Benito-Vicente, Asier, Fernandez, Jorge, Gracia-Rubio, Irene, Arraste, Sonia, Lagunas, Ana Cenarro, Murillo, Fernando Civeira, Gonzalez-Diaz, Humberto, and Martin, Cesar
Published: 2024
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32. Procedure for the diagnosis of heterozygous familial hypercholesterolemia

Author: Benedi, Victoria Marco, Gassó, Salvador Olmos, Lagunas, Ana Cenarro, Corredoira, Pablo Fernández, Bea Sanz, Ana M., and Murillo, Fernando Civeira
Published: 2024
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33. Association of HDL cholesterol and cardiovascular disease in subjects with familial hypercholesterolemia

Author: Bea Sanz, Ana M., Benedi, Victoria Marco, Lezcano, Ángela, Gonzalez, Rebeca Monjón, Jarauta, Estibaliz, Odriozola, Mónica, Lagunas, Ana Cenarro, and Murillo, Fernando Civeira
Published: 2024
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34. El hospital como centro nuclear para mejorar la enseñanza de la medicina

Author: Fernando Civeira Murillo
Subjects: Education (General), L7-991, Medicine (General), R5-920

35. Diagnosis of Familial Dysbetalipoproteinemia Based on the Lipid Abnormalities Driven by APOE2/E2 Genotype

Author: Ana M Bea, Ana Cenarro, Victoria Marco-Bened, Martn Laclaustra, Csar Martn, Daiana Ibarretxe, Xavier Pint, Teresa Arrobas, Clara Vials, Fernando Civeira, and Salvador Olmos
Subjects: Biochemistry (medical), Clinical Biochemistry
Abstract: Background Familial dysbetalipoproteinemia (FDBL) is a monogenic disease due to variants in APOE with a highly variable phenotype. Current diagnostic lipid-based methods have important limitations. The objective is twofold: to define characteristics of dysbetalipoproteinemia (DBL) based on the analysis of APOE in patients from a lipid unit and in a sample from the general population, and to propose a screening algorithm for FDBL. Methods Lipids and APOE genotype from consecutive unrelated subjects from Miguel Servet University Hospital (MSUH) (n 3603), subjects from the general population participants of the Aragon Workers Health Study (AWHS) (n 4981), and selected subjects from external lipid units (Ext) (n 390) were used to define DBL criteria and to train and validate a screening tool. Results Thirty-five subjects from MSUH, 21 subjects from AWHS, and 31 subjects from Ext were APOE2/2 homozygous. The combination of non high-density lipoprotein cholesterol (non-HDLc)/apoB 1.7 plus triglycerides/apoB 1.35, in mg/dL (non-HDLc [mmol/L]/apolipoprotein B (apoB) [g/L] 4.4 and triglycerides [mmol/L]/apoB [g/L] 3.5), provided the best diagnostic performance for the identification of subjects with hyperlipidemia and APOE2/2 genotype (sensitivity 100 in the 3 cohorts, and specificity 92.8 [MSUH], 80.9 [AWHS], and 77.6 [Ext]). This improves the performance of previous algorithms. Similar sensitivity and specificity were observed in APOE2/2 subjects receiving lipid-lowering drugs. Conclusions The combination of non-HDLc/apoB and triglycerides/apoB ratios is a valuable tool to diagnose DBL in patients with hyperlipidemia with or without lipid-lowering drugs. FDBL diagnosis requires DBL and the presence of a compatible APOE genotype. Most adult APOE2/2 subjects express DBL, making FDBL as common as familial hypercholesterolemia in the population.
Published: 2023

36. Estrategias de tratamiento de las dislipemias en prevención primaria y secundaria. Registro de la Sociedad Española de Arteriosclerosis

Author: Victoria Marco-Benedí, Ana M. Bea, Rosa M. Sánchez Hernández, Núria Plana, Pedro Valdivielso, and Fernando Civeira
Subjects: Pharmacology (medical), Cardiology and Cardiovascular Medicine
Published: 2022

37. A mechanism-based operational definition and classification of hypercholesterolemia

Author: Fernando Civeira, Marcello Arca, Ana Cenarro, and Robert A. Hegele
Subjects: Nutrition and Dietetics, Endocrinology, Diabetes and Metabolism, Internal Medicine, Cardiology and Cardiovascular Medicine
Abstract: In contrast to strong evidence-based clinical recommendations for lipid-lowering treatment, there is no analogous definitive diagnostic definition of hypercholesterolemia and its various subtypes. For many clinicians, guideline indications for hypolipidemic treatment can become broadly conflated with hypercholesterolemia in a non-specific sense. In this statement, we propose a unified definition and mechanism-based classification of hypercholesterolemia, which in turn should help to stratify patients and guide efficient diagnosis without interfering with the current strategies of ASCVD risk reduction.
Published: 2022

38. Absence of the influence of the APOE gene on the incidence of type 2 diabetes mellitus in a cohort of workers: Effect of diet and shift work

Author: Rocío Mateo-Gallego, Sofía Pérez-Calahorra, Ana M. Bea, Irene Gracia-Rubio, Carmen Rodrigo-Carbo, Belen Moreno-Franco, Fernando Civeira, Martín Laclaustra, and Itziar Lamiquiz-Moneo
Subjects: Pharmacology (medical), Cardiology and Cardiovascular Medicine
Published: 2023

39. Alimentos funcionales y nutracéuticos en el tratamiento de la hipercolesterolemia: posicionamiento de la Sociedad Española de Arteriosclerosis 2023

Author: Pablo Pérez-Martínez, Emilio Ros, Juan Pedro-Botet, Fernando Civeira, Vicente Pascual, Carmen Garcés, Rosa Solá, Francisco Pérez-Jiménez, and José M. Mostaza
Subjects: Pharmacology (medical), Cardiology and Cardiovascular Medicine
Published: 2023

40. Implantación de un programa de cribado bioquímico y genético de hipercolesterolemia familiar. Colaboración entre el laboratorio clínico y las unidades de lípidos: diseño del Proyecto ARIAN

Author: Teresa Arrobas Velilla, Ángel Brea, Pedro Valdivielso, Begoña Gallardo Alguacil, Ramon Pérez Temprano, Mar Martínez Quesada, Miguel Ángel Rico, Lourdes Diez Herrán, Ovidio Muñiz Grijalbo, Purificación García Yun, Francisca Jiménez-Mena Villar, Francisco Morales Pérez, Olga González Albarrán, Mercedes Herranz Puebla, Carolina Puertas Robles, Silvia Campos Anguila, Joan Lima Ruiz, Armando Raúl Guerra Ruiz, José Luis Hernández Hernández, José Vicente García Lario, Pablo González Busto, Fernando Rodríguez Alemán, María Mar Águila García, Fernando Jaén Ávila, Goitzane Marcaida Benito, Juan José Tamarit Gracia, Cristina Gómez Cobos, Juan Ramón Urgeles Planella, Luis Irigoyen Cucalón, José Antonio Gimeno Orna, José Ruiz Budría, Ignacio Vázquez Rico, Jessica Roa Garrido, Enrique Ruiz Pérez, María Maravi Álvarez, Laura de la Maza Pereg, María Victoria Poncela García, María Martin Palencia, David Peñalver Talavera, Montaña Jiménez Álvaro, Marco Puma Duque, Almudena Vigil Rodríguez, Juan Manuel Fernández Alonso, José Alfredo Martin Armas, Magdalena León Mazorra, Casimira Domínguez Cabrera, Lidia Esther Ruiz Gracia, José Puzo Foncillas, Xavier Pintó Sala, María José Castro Castro, Fernando Civeira Murillo, Pilar Calmarza, Rosa Sánchez Hernández, Marta Riaño Ruiz, Camino García García-Lescun, María Almudena Amor, Eduardo Alegría, Cristina Soler Ferrer, Mercé Montesino Costa, Antonio Rus, and Marta Casañas
Subjects: Screening programme, 03 medical and health sciences, 0302 clinical medicine, business.industry, Medicine, Pharmacology (medical), 030212 general & internal medicine, 030204 cardiovascular system & hematology, Cardiology and Cardiovascular Medicine, business, Humanities
Abstract: Resumen Introduccion y objetivo La hipercolesterolemia familiar (HF) es el trastorno genetico mas frecuente asociado con enfermedad coronaria prematura debido a la presencia de cLDL incrementado desde el nacimiento. Se encuentra infradiagnosticada e infratratada. El objetivo primario del proyecto ARIAN es determinar el numero de pacientes diagnosticados de HF tras implantar un nuevo procedimiento de cribado desde el laboratorio. Material y metodos Este proyecto se ha disenado como un analisis retrospectivo mediante consulta al sistema informatico. Se seleccionaron de las bases de datos de laboratorio aquellas muestras de suero de pacientes ≥ 18 anos con cLDL directos o calculados > 250 mg/dl, desde el 1 de enero del 2017 hasta el 31 de diciembre del 2018. Una vez descartadas causas secundarias, se comunico al medico de Atencion Primaria solicitante la sospecha de que su paciente pudiera portar una HF y gestionar una cita prioritaria en la unidad de Lipidos. Todos aquellos pacientes con una puntuacion ≥ 6 puntos de los criterios de las Clinicas holandesas se les propuso un estudio genetico. Resultados El protocolo se presento a 55 laboratorios de forma individualizada. Hasta el dia 30 de diciembre del 2020, el numero centros que han remitido resultados es de 24. El numero de muestras analizadas hasta ese momento fue de 3.266.341, lo que representa un 34% de la poblacion atendida en esas areas de salud (9.727.434). Conclusiones La identificacion de nuevos sujetos con HF mediante esta nueva estrategia desde el laboratorio y su remision a las unidades de Lipidos debe incrementar el numero de pacientes tratados en las unidades de Lipidos y permitir iniciar cribados en cascada familiar.
Published: 2021

41. MLb-LDLr

Author: Sonia Arrasate, Kepa B. Uribe, Unai Galicia-Garcia, Shifa Jebari-Benslaiman, Helena Ostolaza, César Martín, Fernando Civeira, Humberto González-Díaz, Ana Cenarro, José Angel Fernández-Higuero, Asier Larrea-Sebal, and Asier Benito-Vicente
Subjects: LNN, linear neural networks, Disease, Cascade screening, Familial hypercholesterolemia, Biology, Machine learning, computer.software_genre, FH, familial hypercholesterolemia, LDL, low-density lipoprotein, machine learning software, medicine, Missense mutation, pathogenicity, EGS, expert-guided selection, ML, machine learning, Gene, AUROC, area under the receiver operating curve, familial hypercholesterolemia, business.industry, nutritional and metabolic diseases, LDL receptor, ESEA, Excel Solver Evolutionary algorithm, prediction, ANN, artificial neural network, Pathogenicity, medicine.disease, LDLr, low-density lipoprotein receptor, UTR, untranslated region, RBF, radial basis function, MLb-LDLr, machine-learning–based low-density lipoprotein receptor software, lipids (amino acids, peptides, and proteins), Artificial intelligence, Preclinical Research, MLP, multilayer perceptron, Cardiology and Cardiovascular Medicine, business, computer, LDA, linear discriminant analysis
Abstract: Visual Abstract, Highlights • A machine-learning model has been developed to improve accuracy on predicting the activity of missense LDLr mutations. • ClinVar was used as database, and the model function was defined by using specific characteristics of the LDLr. • A high-score prediction ML model with specificity of 92.5% and sensitivity of 91.6% has been developed to predict pathogenicity of LDLr variants. • Implementation of high-predicting capacity software constitutes a valuable approach for assessing pathogenicity of LDLr variants to help in the early diagnosis and management of FH disease. • An open-access predictive software (MLb-LDLr) is provided to the scientific community., Summary Untreated familial hypercholesterolemia (FH) leads to atherosclerosis and early cardiovascular disease. Mutations in the low-density lipoprotein receptor (LDLr) gene constitute the major cause of FH, and the high number of mutations already described in the LDLr makes necessary cascade screening or in vitro functional characterization to provide a definitive diagnosis. Implementation of high-predicting capacity software constitutes a valuable approach for assessing pathogenicity of LDLr variants to help in the early diagnosis and management of FH disease. This work provides a reliable machine learning model to accurately predict the pathogenicity of LDLr missense variants with specificity of 92.5% and sensitivity of 91.6%.
Published: 2021

42. Apolipoprotein B, Residual Cardiovascular Risk After Acute Coronary Syndrome, and Effects of Alirocumab

Author: Emil Hagström, P. Gabriel Steg, Michael Szarek, Deepak L. Bhatt, Vera A. Bittner, Nicolas Danchin, Rafael Diaz, Shaun G. Goodman, Robert A. Harrington, J. Wouter Jukema, Evangelos Liberopoulos, Nikolaus Marx, Jennifer McGinniss, Garen Manvelian, Robert Pordy, Michel Scemama, Harvey D. White, Andreas M. Zeiher, Gregory G. Schwartz, Pierluigi Tricoci, Matthew T. Roe, Kenneth W. Mahaffey, Jay M. Edelberg, Corinne Hanotin, Guillaume Lecorps, Angèle Moryusef, William J. Sasiela, Jean-François Tamby, Philip E Aylward, Heinz Drexel, Peter Sinnaeve, Mirza Dilic, Renato D. Lopes, Nina N Gotcheva, Juan-Carlos Prieto, Huo Yong, Patricio López-Jaramillo, Ivan Pećin, Zeljko Reiner, Petr Ostadal, Steen Hvitfeldt Poulsen, Margus Viigimaa, Markku S Nieminen, Vakhtang Chumburidze, Pablo Carlos, Montenegro Valdovinos, Hung-Fat Tse, Robert Gabor Kiss, Denis Xavier, Doron Zahger, Marco Valgimigli, Takeshi Kimura, Hyo Soo Kim, Sang-Hyun Kim, Andrejs Erglis, Aleksandras Laucevicius, Sasko Kedev, Khalid Yusoff, Gabriel Arturo Ramos López, Marco Alings, Sigrun Halvorsen, Roger M Correa Flores, Rody G. Sy, Andrzej Budaj, Joao Morais, Maria Dorobantu, Yuri Karpov, Arsen D. Ristic, Terrance Chua, Jan Murin, Zlatko Fras, Anthony J Dalby, José Tuñón, H. Asita de Silva, Ulf Landmesser, Christian Müller, Chern-En Chiang, Piyamitr Sritara, Sema Guneri, Alexander Parkhomenko, Kausik K. Ray, Patrick M. Moriarty, Robert Vogel, Bernard Chaitman, Sheryl F. Kelsey, Anders G. Olsson, Jean-Lucien Rouleau, Maarten L. Simoons, Karen Alexander, Chiara Meloni, Robert Rosenson, Eric J.G. Sijbrands, John H. Alexander, Luciana Armaganijan, Akshay Bagai, Maria Cecilia Bahit, J. Matthew Brennan, Shaun Clifton, Adam D. DeVore, Shalonda Deloatch, Sheila Dickey, Keith Dombrowski, Grégory Ducrocq, Zubin Eapen, Patricia Endsley, Arleen Eppinger, Robert W. Harrison, Connie Ng Hess, Mark A. Hlatky, Joseph Dedrick Jordan, Joshua W. Knowles, Bradley J. Kolls, David F. Kong, Sergio Leonardi, Linda Lillis, David J. Maron, Jill Marcus, Robin Mathews, Rajendra H. Mehta, Robert J. Mentz, Humberto Graner Moreira, Chetan B. Patel, Sabrina Bernardez Pereira, Lynn Perkins, Thomas J. Povsic, Etienne Puymirat, William Schuyler Jones, Bimal R. Shah, Matthew W. Sherwood, Kenya Stringfellow, Darin Sujjavanich, Mustafa Toma, Charlene Trotter, Sean F.P. van Diepen, Matthew D. Wilson, Andrew Tze-Kay Yan, Lilia B Schiavi, Marcelo Garrido, Andrés F Alvarisqueta, Sonia A Sassone, Anselmo P Bordonava, Alberto E Alves De Lima, Jorge M Schmidberg, Ernesto A Duronto, Orlando C Caruso, Leonardo P Novaretto, Miguel Angel Hominal, Oscar R Montaña, Alberto Caccavo, Oscar A Gomez Vilamajo, Alberto J Lorenzatti, Luis R Cartasegna, Gustavo A Paterlini, Ignacio J Mackinnon, Guillermo D Caime, Marcos Amuchastegui, Oscar Salomone, Oscar R Codutti, Horacio O Jure, Julio OE Bono, Adrian D Hrabar, Julio A Vallejos, Rodolfo A Ahuad Guerrero, Federico Novoa, Cristian A Patocchi, Cesar J Zaidman, Maria E Giuliano, Ricardo D Dran, Marisa L Vico, Gabriela S Carnero, Pablo N Guzman, Juan C Medrano Allende, Daniela F Garcia Brasca, Miguel H Bustamante Labarta, Sebastian Nani, Eduardo DS Blumberg, Hugo R Colombo, Alberto Liberman, Victorino Fuentealba, Hector L Luciardi, Gabriel D Waisman, Mario A Berli, Ruben O Garcia Duran, Horacio G Cestari, Hugo A Luquez, Jorge A Giordano, Silvia S Saavedra, Gerardo Zapata, Osvaldo Costamagna, Susana Llois, Jonathon H Waites, Nicholas Collins, Allan Soward, Chris LS Hii, James Shaw, Margaret A Arstall, John Horowitz, Daniel Ninio, James F Rogers, David Colquhoun, Romulo E Oqueli Flores, Philip Roberts-Thomson, Owen Raffel, Sam J Lehman, Constantine Aroney, Steven GM Coverdale, Paul J Garrahy, Gregory Starmer, Mark Sader, Patrick A Carroll, Ronald Dick, Robert Zweiker, Uta Hoppe, Kurt Huber, Rudolf Berger, Georg Delle-Karth, Bernhard Frey, Franz Weidinger, Dirk Faes, Kurt Hermans, Bruno Pirenne, Attilio Leone, Etienne Hoffer, Mathias CM Vrolix, Luc De Wolf, Bart Wollaert, Marc Castadot, Karl Dujardin, Christophe Beauloye, Geert Vervoort, Harry Striekwold, Carl Convens, John Roosen, Emanuele Barbato, Marc Claeys, Frank Cools, Ibrahim Terzic, Fahir Barakovic, Zlatko Midzic, Belma Pojskic, Emir Fazlibegovic, Azra Durak-Nalbantic, Mehmed Kulić, Dusko Vulic, Adis Muslibegovic, Boris Goronja, Gilmar Reis, Luciano Sousa, Jose C Nicolau, Flavio E Giorgeto, Ricardo P Silva, Lilia Nigro Maia, Rafael Rech, Paulo RF Rossi, Maria José AG Cerqueira, Norberto Duda, Renato Kalil, Adrian Kormann, José Antonio M Abrantes, Pedro Pimentel Filho, Ana Priscila Soggia, Mayler ON de Santos, Fernando Neuenschwander, Luiz C Bodanese, Yorghos L Michalaros, Freddy G Eliaschewitz, Maria H Vidotti, Paulo E Leaes, Roberto V Botelho, Sergio Kaiser, Euler Roberto F Fernandes Manenti, Dalton B Precoma, Jose C Moura Jorge, Pedro Silva, Jose A Silveira, Wladmir Saporito, Jose A Marin Neto, Gilson S Feitosa, Luiz Eduardo F Ritt, Juliana A de Souza, Fernando Costa, Weimar KSB Souza, Helder JL Reis, Leandro Machado, José Carlos Aidar Ayoub, Georgi V Todorov, Fedya P Nikolov, Elena S Velcheva, Maria L Tzekova, Haralambi O Benov, Stanislav L Petranov, Haralin S Tumbev, Nina S Shehova-Yankova, Dimitar T Markov, Dimitar H Raev, Mihail N Mollov, Kostadin N Kichukov, Katya A Ilieva- Pandeva, Raya Ivanova, Maryana Gospodinov, Valentina M Mincheva, Petar V Lazov, Bojidar I Dimov, Manohara Senaratne, James Stone, Jan Kornder, Stephen Pearce, Danielle Dion, Daniel Savard, Yves Pesant, Amritanshu Pandey, Simon Robinson, Gilbert Gosselin, Saul Vizel, Gordon Hoag, Ronald Bourgeois, Anne Morisset, Eric Sabbah, Bruce Sussex, Simon Kouz, Paul MacDonald, Ariel Diaz, Nicolas Michaud, David Fell, Raymond Leung, Tycho Vuurmans, Christopher Lai, Frank Nigro, Richard Davies, Gustavo Nogareda, Ram Vijayaraghavan, John Ducas, Serge Lepage, Shamir Mehta, James Cha, Robert Dupuis, Peter Fong, Sohrab Lutchmedial, Josep Rodes-Cabau, Hussein Fadlallah, David Cleveland, Thao Huynh, Iqbal Bata, Adnan Hameed, Cristian Pincetti, Sergio Potthoff, Juan C Prieto, Monica Acevedo, Arnoldo Aguirre, Margarita Vejar, Mario Yañez, Guillermo Araneda, Mauricio Fernandez, Luis Perez, Paola Varleta, Fernando Florenzano, Laura Huidobro, Carlos A Raffo, Claudia Olivares, Leonardo Nahuelpan, Humberto Montecinos, Jiyan Chen, Yugang Dong, Weijian Huang, Jianzhong Wang, Shi’An Huang, Zhuhua Yao, Xiang Li, Lan Cui, Wenhua Lin, Yuemin Sun, Jingfeng Wang, Jianping Li, Xuelian Zhang, Hong Zhu, Dandan Chen, Lan Huang, Shaohong Dong, Guohai Su, Biao Xu, Xi Su, Xiaoshu Cheng, Jinxiu Lin, Wenxia Zong, Huanming Li, Yi Feng, Dingli Xu, Xinchun Yang, Yuannan Ke, Xuefeng Lin, Zheng Zhang, Zeqi Zheng, Zhurong Luo, Yundai Chen, Chunhua Ding, Yi Zhong, Yang Zheng, Xiaodong Li, Daoquan Peng, Shuiping Zhao, Ying Li, Xuebo Liu, Meng Wei, Shaowen Liu, Yihua Yu, Baiming Qu, Weihong Jiang, Yujie Zhou, Xingsheng Zhao, Zuyi Yuan, Ying Guo, Xiping Xu, Xubo Shi, Junbo Ge, Guosheng Fu, Feng Bai, Weiyi Fang, Xiling Shou, Xiangjun Yang, Jian’An Wang, Meixiang Xiang, Yingxian Sun, Qinghua Lu, Ruiyan Zhang, Jianhua Zhu, Yizhou Xu, Zhongcai Fan, Tianchang Li, Chun Wu, Nicolas Jaramillo, Gregorio Sanchez Vallejo, Diana C Luna Botia, Rodrigo Botero Lopez, Dora I Molina De Salazar, Alberto J Cadena Bonfanti, Carlos Cotes Aroca, Juan Diego Higuera, Marco Blanquicett, Sandra I Barrera Silva, Henry J Garcia Lozada, Julian A Coronel Arroyo, Jose L Accini Mendoza, Ricardo L Fernandez Ruiz, Alvaro M. Quintero Ossa, Fernando G Manzur Jatin, Aristides Sotomayor Herazo, Jeffrey Castellanos Parada, Rafael Suarez Arambula, Miguel A Urina Triana, Angela M Fernandez Trujillo, Maja Strozzi, Siniša Car, Davor Miličić, Martina Lovrić Benčić, Hrvoje Pintarić, Đeiti Prvulović, Jozica Šikić, Viktor Peršić, Dean Mileta, Kresimir Štambuk, Zdravko Babić, Vjekoslav Tomulic, Josip Lukenda, Stanka Mejic-Krstulovic, Boris Starcevic, Jindrich Spinar, David Horak, Zdenek Velicka, David Alan, Vilma Machova, Ales Linhart, Vojtech Novotny, Vladimir Kaucak, Richard Rokyta, Robert Naplava, Zdenek Coufal, Vera Adamkova, Ivo Podpera, Jiri Zizka, Zuzana Motovska, Ivana Marusincova, Petr Heinc, Jiri Kuchar, Petr Povolny, Jiri Matuska, Steen H Poulsen, Bent Raungaard, Peter Clemmensen, Lia E Bang, Ole May, Morten Bøttcher, Jens D Hove, Lars Frost, Gunnar Gislason, John Larsen, Peter Betton Johansen, Flemming Hald, Peter Johansen, Jørgen Jeppesen, Tonny Nielsen, Kjeld S Kristensen, Piotr Maria Walichiewicz, Jens D Lomholdt, Ib C Klausen, Peter Kaiser Nielsen, Flemming Davidsen, Lars Videbaek, Mai Soots, Veiko Vahula, Anu Hedman, Üllar Soopõld, Kaja Märtsin, Tiina Jurgenson, Arved Kristjan, Saila Vikman, Heikki Huikuri, Juhani Airaksinen, Pierre Coste, Emile Ferrari, Olivier Morel, Gilles Montalescot, Jacques Machecourt, Gilles Barone-Rochette, Jacques Mansourati, Yves Cottin, Ph. Gabriel Steg, Florence Leclercq, Abdelkader Belhassane, Nicolas Delarche, Franck Boccara, Franck Paganelli, Jérôme Clerc, Francois Schiele, Victor Aboyans, Vincent Probst, Jacques Berland, Thierry Lefèvre, Irakli Khintibidze, Tamaz Shaburishvili, Zurab Pagava, Ramaz Ghlonti, Zaza Lominadze, George Khabeishvili, Rayyan Hemetsberger, Kemala Edward, Ursula Rauch-Kröhnert, Matthias Stratmann, Karl-Friedrich Appel, Ekkehard Schmidt, Heyder Omran, Christoph Stellbrink, Thomas Dorsel, Emmanouil Lianopoulos, Hans Friedrich Vöhringer, Roger Marx, Andreas Zirlik, Detlev Schellenberg, Thomas Heitzer, Ulrich Laufs, Christian Werner, Stephan Gielen, Sebastian Nuding, Bernhard Winkelmann, Steffen Behrens, Karsten Sydow, Mahir Karakas, Gregor Simonis, Thomas Muenzel, Nikos Werner, Stefan Leggewie, Dirk Böcker, Rüdiger Braun- Dullaeus, Nicole Toursarkissian, Michael Jeserich, Matthias Weißbrodt, Tim Schaeufele, Joachim Weil, Heinz Völler, Johannes Waltenberger, Mohammed Natour, Susanne Schmitt, Dirk Müller-Wieland, Stephan Steiner, Lothar Heidenreich, Elmar Offers, Uwe Gremmler, Holger Killat, Werner Rieker, Sotiris Patsilinakos, Athanasios Kartalis, Athanassios Manolis, Dimitrios Sionis, Geargios Chachalis, Ioannis Skoumas, Vasilios Athyros, Panagiotis Vardas, Frangkiskos Parthenakis, Georgios Hahalis, John Lekakis, Apostolos Hatzitolios, Sergio R Fausto Ovando, Pablo Carlos Montenegro Valdovinos, Juan L Arango Benecke, Edgar R Rodriguez De Leon, Bryan PY Yan, David CW Siu, Tibor Turi, Bela Merkely, Imre Ungi, Geza Lupkovics, Lajos Nagy, András Katona, István Édes, Gábor Müller, Iván Horvath, Tibor Kapin, Zsolt Szigeti, József Faluközy, Mukund Kumbla, Manjinder Sandhu, Sharath Annam, Naveen Reddy Proddutur, Reddy Regella, Rajendra K Premchand, Ajaykumar Mahajan, Sudhir Pawar, Atul D Abhyanakar, Prafulla Kerkar, Ravishankar A Govinda, Abraham Oomman, Dhurjati Sinha, Sachin N Patil, Dhiman Kahali, Jitendra Sawhney, Abhijeet B Joshi, Sanjeev Chaudhary, Pankaj Harkut, Santanu Guha, Sanjay Porwal, Srimannarayana Jujjuru, Ramesh B Pothineni, Minguel R Monteiro, Aziz Khan, Shamanna S Iyengar, Jasprakash Singh Grewal, Manoj Chopda, Mahesh C Fulwani, Dr. Aparna Patange, Patil Sachin, Vijay K Chopra, Naresh K Goyal, Rituparna Shinde, Gajendra V Manakshe, Nitin Patki, Sumeet Sethi, Vengatesh Munusamy, Sunil Karnaand Sunil Thanvi, Srilakshmi Adhyapak, Chandrakant Patil, Ulhas Pandurangi, Rishabh Mathur, Jugal Gupta, Suhas Kalashetti, Ajit Bhagwat, Bagirath Raghuraman, Shiv Kumar Yerra, Prasant Bhansali, Rohidas Borse, Patil Rahul, Srihari Das, Vinay Kumar, Jabir Abdullakutty, Shireesh Saathe, Priya Palimkar, Jabir Abdullkutty, Shireesh Sathe, Shaul Atar, Michael Shechter, Morris Mosseri, Yaron Arbel, Chorin Ehud, Havakuk Ofer, Chaim Lotan, Uri Rosenschein, Amos Katz, Yaakov Henkin, Adi Francis, Marc Klutstein, Eugenia Nikolsky, Robert Zukermann, Yoav Turgeman, Majdi Halabi, Alon Marmor, Ran Kornowski, Michael Jonas, Offer Amir, Yonathan Hasin, Yoseph Rozenman, Shmuel Fuchs, Vered Zvi, Osamah Hussein, Dov Gavish, Zvi Vered, Yoseph Caraco, Mazen Elias, Naveh Tov, Efrat Wolfovitz, Michael Lishner, Nizar Elias, Giancarlo Piovaccari, Annamaria De Pellegrin, Raffaella Garbelotto, Gabriele Guardigli, Valgimigli Marco, Giovanni Licciardello, Carla Auguadro, Filippo Scalise, Claudio Cuccia, Alessandro Salvioni, Giuseppe Musumeci, Michelle Senni, Paolo Calabrò, Salvatore Novo, Pompilio Faggiano, Marco Metra, Nicoletta B De Cesare, Sergio Berti, Enrico Puccioni, Marcello Galvani, Maurizio Tespili, Piermarco Piatti, Michela Palvarini, Giuseppe De Luca, Roberto Violini, Alessandro De Leo, Zoran Olivari, Pasquale Perrone Filardi, Maurizio Ferratini, Vittorio Racca, Kazuoki Dai, Yuji Shimatani, Haruo Kamiya, Kenji Ando, Yoshihiro Takeda, Yoshihiro Morino, Yoshiki Hata, Kazuo Kimura, Koichi Kishi, Ichiro Michishita, Hiroki Uehara, Toshinori Higashikata, Atsushi Hirayama, Keiji Hirooka, Yasuji Doi, Satoru Sakagami, Shuichi Taguchi, Akihiro Koike, Hiroyuki Fujinaga, Shinji Koba, Ken Kozuma, Tomohiro Kawasaki, Yujiro Ono, Masatoshi Shimizu, Yousuke Katsuda, Atsuyuki Wada, Toshiro Shinke, Junya Ako, Kenshi Fujii, Toshiyuki Takahashi, Koichi Nakao, Yutaka Furukawa, Hiroshi Sugino, Ritsu Tamura, Toshiaki Mano, Masaaki Uematsu, Noriaki Utsu, Kashima Ito, Takuya Haraguchi, Katsuhiko Sato, Yasunori Ueda, Akira Nishibe, Kazuteru Fujimoto, Motomaru Masutani, Jung Han Yoon, Hack-Lyoung Kim, Hun Sik Park, In-Ho Chae, Moo Hyun Kim, Myung Ho Jeong, Seungwoon Rha, Chongjin Kim, Hyo-Soo Kim, Hae Young Kim, Taekjong Hong, Seung-Jea Tahk, Youngkwon Kim, Arija Busmane, Natalija Pontaga, Aldis Strelnieks, Iveta Mintale, Iveta Sime, Zaneta Petrulioniene, Roma Kavaliauskiene, Ruta Jurgaitiene, Gintare Sakalyte, Rimvydas Slapikas, Sigute Norkiene, Nerijus Misonis, Aleksandras Kibarskis, Raimondas Kubilius, Stojko Bojovski, Nensi Lozance, Aleksandar Kjovkaroski, Snezana Doncovska, Tiong Kiam Ong, Sazzli Kasim, Oteh Maskon, Balachandran Kandasamy, Houng B Liew, Wan Mohd Izani Wan Mohamed, Armando García Castillo, Jorge Carrillo Calvillo, Pedro Fajardo Campos, Juan Carlos Núñez Fragoso, Edmundo Alfredo Bayram Llamas, Marco Antonio Alcocer Gamba, Jaime Carranza Madrigal, Luis Gerardo González Salas, Enrique López Rosas, Belinda González Díaz, Eduardo Salcido Vázquez, Alfredo Nacoud Ackar, Guillermo Antonio Llamas Esperón, Carlos Rodolfo Martínez Sánchez, María Guerrero De Leon, Rodrigo Suarez Otero, Guillermo Fanghänel Salmón, Jesús Antonio Pérez Ríos, José Angel Garza Ruíz, Robert W Breedveld, Margriet Feenema-Aardema, Alida Borger-Van Der Burg, Pieter AM Hoogslag, Harry Suryapranata, Antonius Oomen, Paulus Van Haelst, Margriet Feenema-Aradema, Jacobijne J Wiersma, Dirk Basart, Ruud MA Van Der Wal, Peter Zwart, Pascalle Monraats, Henricus Van Kesteren, Ioannis Karalis, Johan Jukema, Gerardus JE Verdel, Bart RG Brueren, Roland PTh Troquay, Eric P Viergever, Nadea YY Al-Windy, Gerard L Bartels, Jan H Cornel, Walter RM Hermans, Johannes PR Herrman, Robert J Bos, Reginald GEJ Groutars, Coenraad C Van Der Zwaan, Refik Kaplan, Eelko Ronner, Bjorn E Groenemeijer, Patrick NA Bronzwaer, Anho AH Liem, Bernard JWM Rensing, Marcel JJA Bokern, Remco Nijmeijer, Ferry MRJ Hersbach, Frank F Willems, Antonius TM Gosselink, Saman Rasoul, John Elliott, Gerard Wilkins, Raewyn Fisher, Douglas Scott, Hamish Hart, Ralph Stewart, Scott Harding, Ian Ternouth, Nicholas Fisher, Samuel Wilson, Denise Aitken, Russell Anscombe, Laura Davidson, Tadeusz Tomala, Ottar Nygård, Jon Arne Sparby, Kjell Andersen, Lars Gullestad, Jarle Jortveit, Peter S Munk, Erlend gyllensten Singsaas, Ulf Hurtig, Jorge R Calderon Ticona, Julio R Durand Velasquez, Sandra A Negron Miguel, Enrique S Sanabria Perez, Jesus M Carrion Chambilla, Carlos A Chavez Ayala, Reynaldo P Castillo Leon, Rolando J Vargas GonzalesC, Jose D Hernandez Zuniga, Luis A Camacho Cosavalente, Jorge E Bravo Mannucci, Javier Heredia Landeo, Nassip C Llerena Navarro, Yudy M Roldan Concha, Víctor E Rodriguez Chavez, Henry A Anchante Hernandez, Carlos A Zea Nunez, Walter Mogrovejo Ramos, Arthur Ferrolino, Rosa Allyn G Sy, Louie Tirador, Generoso Matiga, Raul Martin Coching, Alisa Bernan, Gregorio Rogelio, Dante D. Morales, Edgar Tan, Dennis Jose Sulit, Adrian Wlodarczak, Grzegorz Skonieczny, Lidia Pawlowicz, Pawel Wojewoda, Benita Busz-Papiez, Janusz Bednarski, Aleksander Goch, Pawel Staneta, Elzbieta Dulak, Krzysztof Saminski, Wlodzimierz Krasowski, Wanda Sudnik, Aleksander Zurakowski, Marcin Skorski, Roman Lysek, Beata Miklaszewicz, Jan Andrzej Lipko, Edyta Kostarska-Srokosz, Marek Piepiorka, Anna Drzewiecka, Arkadiusz Stasiewski, Tomasz Blicharski, Leszek Bystryk, Michal Szpajer, Marek Korol, Tomasz Czerski, Jacek Gniot, Andrzej Lubinski, Jerzy Gorny, Edward Franek, Grzegorz Raczak, Hanna Szwed, Pedro Monteiro, Jose Mesquita Bastos, Helder H Pereira, Filipe Seixo, Carlos Mendonça, Ana Botelho, Francisca Caetano, Bogdan Minescu, Octavian Istratoaie, Dan N Tesloianu, Gabriel Cristian, Silviu Dumitrescu, Cristian GC Podoleanu, Mircea CA Constantinescu, Cristina M Bengus, Constantin Militaru, Doina Rosu, Irinel R Parepa, Adrian V Matei, Tom M Alexandru, Mihaela Malis, Ioan Coman, Yury Shvarts, Olga Orlikova, Zhanna Kobalava, Olga L Barbarash, Valentin Markov, Nadezhda Lyamina, Alexander Gordienko, Konstantin Zrazhevsky, Alexander Y Vishnevsky, Victor Gurevich, Raisa Stryuk, Nikita V Lomakin, Igor Bokarev, Tatiana Khlevchuk, Sergey Shalaev, Larisa Khaisheva, Petr Chizhov, Inna Viktorova, Natalya Osokina, Vladimir Shchekotov, Evgenia Akatova, Galina Chumakova, Igor Libov, Mikhail I Voevoda, Tatyana V Tretyakova, Evgeny Baranov, Sergey Shustov, Sergey Yakushin, Ivan Gordeev, Niiaz Khasanov, Olga Reshetko, Tatiana Sotnikova, Olga Molchanova, Konstantin Nikolaev, Liudmila Gapon, Elena Baranova, Elena Kosmachova, Yuriy Karpov, Anton Povzun, Liudmila Egorova, Vadim V Tyrenko, Igor G Ivanov, Masterov Ilya, Sergey Kanorsky, Dragan Simic, Nikola Ivanovic, Goran Davidovic, Nebojsa Tasic, Milika R. Asanin, Stevo Stojic, Svetlana R. Apostolovic, Stevan Ilic, Biljana Putnikovic Tosic, Aleksandar Stankovic, Aleksandra Arandjelovic, Slavica Radovanovic, Branislava Todic, Jovan Balinovac, Dragan V. Dincic, Petar Seferovic, Ana Karadzic, Slobodan Dodic, Sinisa Dimkovic, Tamara Jakimov, Kian-Keong Poh, Hean Yee Ong, Justin Tang I-Shing, Karol Micko, Jan Nociar, Daniel Pella, Peter Fulop, Marian Hranai, Juraj Palka, Juraj Mazur, Ivan Majercák, Andrej Dzupina, František Fazekas, Jozef Gonsorcik, Viliam Bugan, Juraj Selecky, Gabriel Kamensky, Jaroslava Strbova, Rudolf Smik, Andrej Dukat, Peter Olexa, Ivan Žuran, Janez Poklukar, Nataša Černič Šuligoj, Matija Cevc, Henry P Cyster, Naresh Ranjith, Clive Corbett, Junaid Bayat, Ellen Makoali Makotoko, Hendrik du Toit Theron, Ilse E Kapp, Matthys M de V Basson, Hanlie Lottering, Dina Van Aswegen, Louis J Van Zyl, Peter J Sebastian, Thayabran Pillay, Jan A Saaiman, Patrick J Commerford, Soraya Cassimjee, Garda Riaz, Iftikhar O Ebrahim, Mahomed Sarvan, Joseph H Mynhardt, Helmuth Reuter, Rajendran Moodley, Manuel Vida, Angel R. Cequier Fillat, Vicente Bodí Peris, Francisco Fuentes Jimenez, Francisco Marín, Jose M Cruz Fernández, Rafael Jesus Hidalgo Urbano, Blas Gil-Extremera, Pablo Toledo, Fernando Worner Diz, David Garcia-Dorado, Andres Iñiguez, Jose R Gonzalez-Juanatey, Javier Fernandez Portales, Fernando Civeira Murillo, Laia Matas Pericas, Jose Luis Zamorano, Manuel De Mora Martin, Jordi Bruguera Cortada, Joaquin J Alonso Martin, Jose Maria Serrano Antolin, José R De Berrazueta Fernández, José Antonio Vázquez de Prada, Jose Francisco Díaz Fernández, José Alberto García Lledó, Juan Cosín Sales, Javier Botas Rodriguez, Gabriel Gusi Tragant, Amparo Benedicto, Carlos Gonzalez-Juanatey, Mercedes Camprubí Potau, Ignacio Plaza Perez, César Morís De La Tassa, Pablo Loma-Osorio Rincon, Javier Balaguer Recena, Juan M Escudier, Antonio Coca Payeras, Norberto Alonso Orcajo, Godwin Constantine, Ruvaiz Haniffa, Nirmali Tissera, Stanley Amarasekera, Chandrike Ponnamperuma, Nimali Fernando, Kaputella Fernando, Jayanthimala Jayawardena, Santharaj Wijeyasingam, Gotabhaya Ranasinghe, Ruvan Ekanayaka, Sepalika Mendis, Vajira Senaratne, Gnanamoorthy Mayurathan, Ajantha Rajapaksha, Thilak Sirisena, Jagath I Herath, Naomali Amarasena, Stefan Berglund, Gundars Rasmanis, Ola Vedin, Nils Witt, Georgios Mourtzinis, Peter Nicol, Ole Hansen, Stefano Romeo, Steen Agergaard Jensen, Ingemar Torstensson, Ulf Ahremark, Torbjörn Sundelin, Tiziano Moccetti, Francois Mach, Ronald Binde, Oliver Gämperli, Wei- Chuan Tsai, Kwo-Chang Ueng, Wen-Ter Lai, Ming-En Liu, Juey- Jen Hwang, Wei-Hsian Yin, I-Chang Hsieh, Ming-Jer Hsieh, Wei Hsiang Lin, Jen-Yuan Kuo, Tsuei-Yuan Huang, Chih-Yuan Fang, Pinij Kaewsuwanna, Wasant Soonfuang, Woravut Jintapakorn, Apichard Sukonthasarn, Nattawut Wongpraparut, Krisada Sastravaha, Nakarin Sansanayudh, Wirash Kehasukcharoen, Dilok Piyayotai, Paiboon Chotnoparatpat, Ahmet Camsari, Hakan Kultursay, Bulent Mutlu, Murat Ersanli, Mustafa Demirtas, Cevat Kirma, Ertan Ural, Lale Koldas, Oleksandr Karpenko, Alexander Prokhorov, Ihor Vakaluyk, Halyna Myshanych, Dmytro Reshotko, Valeriy Batushkin, Leonid Rudenko, Ihor Kovalskyi, Mykola Kushnir, Vira Tseluyko, Yuriy Mostovoy, Mykola Stanislavchuk, Yulian Kyiak, Yuriy Karpenko, Yaroslav Malynovsky, Andriy Klantsa, Oles Kutniy, Ekaterina Amosova, Viktor Tashchuk, Oleh Leshchuk, Mykola Rishko, Mykola Kopytsya, Andriy Yagensky, Mykola Vatutin, Andriy Bagriy, Olga M Barna, Olexiy Ushakov, Georgiy Dzyak, Borys Goloborodko, Anatolii Rudenko, Volodymyr Zheleznyy, Jasper Trevelyan, Azfar Zaman, Kaeng Lee, Andrew Moriarty, Rajesh K Aggarwal, Piers Clifford, Yuk- Ki Wong, Syed MR Iqbal, Eduardas Subkovas, Denise Braganza, David Sarkar, Robert Storey, Huw Griffiths, Sam Mcclure, Rangasamy Muthusamy, Simon Smith, John Kurian, Terry Levy, Craig Barr, Honer Kadr, Robert Gerber, Audrius Simaitis, Handrean Soran, Adrian Brodison, Mohammad Ayaz, Muhammad Cheema, Richard Oliver, Simon Thackray, Telal Mudawi, Gohar Rahma, Ayyaz Sultan, Timothy Reynolds, David Sharman, david Spriging, Rob Butler, Peter Wilkinson, Gregory YH Lip, Nicholas Ossei-Gerning, Gil Vardi, Duccio Baldari, David Brabham, Charles Treasure II, Charles Dahl, Bruce Palmer, Alan Wiseman, Abul Khan, Sanjeev Puri, Ann Elizabeth Mohart, Carlos Ince, Enrique Flores, Scott Wright, Shi-Chi Cheng, Michael Rosenberg, William Rogers, Edward Kosinski, Les Forgosh, Jonathan Waltman, Mohammad Shoukfeh, Georges Dagher, Patrick Cambier, Ira Lieber, Priya Kumar, Cara East, Perry Krichmar, Mian Hasan, Lindsey White, Thomas Knickelbine, Thomas Haldis, Eve Gillespie, Thomas Amidon, David Suh, Imran Arif, mouhamad Abdallah, Faiq Akhter, Eric Carlson, Michael D’Urso, Fadi El- Ahdab, William Nelson, Katie Moriarty, Barry Harris, Steven Cohen, Luther Carter, Daniel Doty, Kenneth Sabatino, Tariq Haddad, Sunder Rao, Angel Mulkay, Ion Jovin, Kim Klancke, Vinay Malhotra, Sai K Devarapalli, Michael Koren, Harish Chandna, George Dodds III, Tauqir Goraya, James Bengston, Matthew Janik, Joseph Moran, Andrew Sumner, John Kobayashi, William Davis, Shahram Yazdani, John Pasquini, Maitreya Thakkar, Amarnath Vedere, Wayne Leimbach, James Rider, Sarah fenton, Narendra Singh, Anil V Shah, Denise Janosik, Carl Pepine, Brett Berman, Joseph Gelormini, Christopher Daniels, Kerensky Richard, Friederike Keating, Nicholas I Kondo, Sanjay Shetty, Howard Levite, Winfried Waider, Theodore Takata, Mazen Abu-Fadel, Vipul Shah, Rahul Aggarwal, Anil Kumar, Brack Hattler, Rose Do, Chad Link, Anna Bortnick, George Kinzfogl III, Arnold Ghitis, John Larry, Edward Teufel, Peter Kuhlman, Brent Mclaurin, Wenwu Zhang, Stephen Thew, Jalal Abbas, Matthew White, Othman Islam, Sumeet Subherwal, Nandkishore Ranadive, Babak Vakili, Christian Gring, David Henderson, Timothy Schuchard, Naim Farhat, Geoffrey Kline, Sharan Mahal, Jack Whitaker, Shawn Speirs, Rolf Andersen, Nizar Daboul, Phillip Horwitz, Firas Zahr, George Ponce, Zubair Jafar, Joseph Mcgarvey, Vipul Panchal, Stephen Voyce, Thomas Blok, William Sheldon, Masoud M Azizad, Carsten Schmalfuss, Mark Picone, Robert Pederson, William Herzog, Keith Friedman, Jason Lindsey, Eichenlaub Timothy, Parilak Leonard, Norman Lepor, Mahfouz El Shahawy, Howard Weintraub, Anand Irimpen, Alvaro Alonso, Wade May, Daniels Christopher, Thomas Galski, Alan Chu, Freny Mody, Ebrahimi Ramin, Zachary Hodes, Joseph Rossi, Gregory Rose, James Fairlamb, Charles Lambert, Ajit Raisinghani, Antonio Abbate, George Vetrovec, Marilyn King, Charles Carey, Jaime Gerber, Liwa Younis, Hyeun (Tom) Park, Mladen Vidovich, Thomas Knutson, Dennis Friedman, Fred Chaleff, Arthur Loussararian, Phillip Rozeman, Carey Kimmelstiel, Jeffrey Kuvin, Kevin Silver, Malcolm Foster, Glen Tonnessen, Andrey Espinoza, Mohamadali Amlani, Andreas Wali, Christopher Malozzi, Geert T Jong, Clara Massey, Keattiyoat Wattanakit, Philip J. O’Donnell, Dinesh Singal, Naseem Jaffrani, Sridhar Banuru, Daniel Fisher, Mark Xenakis, Neal Perlmutter, Ravi Bhagwat, James Strader, Ronald Blonder, Ayim Akyea-Djamson, Ajay Labroo, Kwan Lee, H. John Marais, Edmund Claxton, Robert Weiss, Rohr Kathryn, Martin Berk, Peter Rossi, Parag Joshi, Amit Khera, Ajit S Khaira, Greg Kumkumian, Steven Lupovitch, Joshua Purow, Stephen Welka, David Hoffman, Stuart Fischer, Eugene Soroka, Donald Eagerton, Samir Pancholy, Michael Ray, Norman Erenrich, Michael Farrar, Stewart Pollock, William J French, Steve Diamantis, Douglas Guy, Lawrence Gimple, Mark Neustel, Steven Schwartz, Edward Pereira, Seals Albert, Douglas Spriggs, Janet Strain, Suneet Mittal, Anthony Vo, Majed Chane, Jason Hall, Nampalli Vijay, Kapildeo Lotun, F. Martin Lester, Ahed Nahhas, Theodore Pope, Paul Nager, Rakesh Vohra, Mukesh Sharma, Riyaz Bashir, Hinan Ahmed, Michael Berlowitz, Robert Fishberg, Robert Barrucco, Eric Yang, Michael Radin, Daniel Sporn, Dwight Stapleton, Steven Eisenberg, Joel Landzberg, Martin Mcgough, Samir Turk, Michael Schwartz, P. Sandy Sundram, Diwakar Jain, Mark Zainea, Carlos Bayron, Ronald Karlsberg, Suhail Dohad, Henry Lui, William Keen, Donald Westerhausen, Sandeep Khurana, Himanshu Agarwal, Jessica Birchem, William Penny, Mark Chang, Sherrill Murphy, John Henry, Branislav Schifferdecker, John M Gilbert, Gopal Chalavarya, Charles Eaton, John F Schmedtje, Stuart Christenson, Imran Dotani, Douglas Denham, Alexander Macdonell, Paul Gibson, Aref Rahman, Tammam Al Joundi, Nizar Assi, Gary Conrad, Purushotham Kotha, Michael Love, Gregory Giesler, Howard Rubenstein, Dawood Gamil, Laura Akright, Justine Krawczyk, Joanne Cobler, Terry Wells, James Welker, Robert Foster, Richard Gilmore, Jay Anderson, Douglas Jacoby, Bill Harris, Geraldine Gardner, Ramprasad Dandillaya, Kishor Vora, John Kostis, John Hunter, David Laxson, Eric Ball, Flavia Egydio, Anelise Kawakami, Janaina Oliveira, Julianna Wozniak, Alexander Matthews, Caroline Ratky, Janine Valiris, Lisa Berdan, Anita Hepditch, Kirby Quintero, Tyrus Rorick, Melissa Westbrook, Madeleine Bezault, Elodie Drouet, Tabassome Simon, Caroline Alsweiler, Anne Luyten, Julie Butters, Liddy Griffith, Michelle Shaw, Lena Grunberg, Shahidul Islam, Marie-France Brégeault, Nathalie Bougon, Douglas Faustino, Sylvie Fontecave, Judith Murphy, Jean- Francois Tamby, Melanie Verrier, Veronique Agnetti, Dorthe Andersen, Emmy Badreddine, Mhamed Bekkouche, Cecile Bouancheau, Imane Brigui, Maddy Brocklehurst, Joseph Cianciarulo, Dawn Devaul, Szilvia Domokos, Cecile Gache, Caroline Gobillot, Severine Guillou, Jan Healy, Megan Heath, Gayatri Jaiwal, Carine Javierre, Julien Labeirie, Myriam Monier, Ulises Morales, Asmaa Mrabti, Bicky Mthombeni, Betim Okan, Lucile Smith, Jennifer Sheller, Sebastien Sopena, Valerie Pellan, Fadela Benbernou, Nafissa Bengrait, Maud Lamoureux, Katarina Kralova, Raphael Bejuit, Anthony Coulange, Christelle Berthou, Jérôme Repincay, Christelle Lorenzato, Alexis Etienne, Valerie Gouet, Virginie Loizeau, Mickael Normand, Anne Ourliac, Christelle Rondel, Antony Adamo, Pascale Beltran, Pauline Barraud, Helene Dubois-Gache, Benjamin Halle, Lamia Metwally, Maxime Mourgues, Marc Sotty, Marion Vincendet, Raluca Cotruta, Zhu Chengyue, Dominique Fournie-Lloret, Christine Morrello, Aurelie Perthuis, Patrick Picault, Isabelle Zobouyan, Helen M. Colhoun, Michael A. Dempsey, Mark A. McClanahan, Roe, Matthew T., Blicharski, Tomasz, Bystryk, Leszek, Szpajer, Michal, Korol, Marek, Czerski, Tomasz, Gniot, Jacek, Lubinski, Andrzej, Gorny, Jerzy, Franek, Edward, Raczak, Grzegorz, Vogel, Robert, Szwed, Hanna, Monteiro, Pedro, Mesquita Bastos, Jose, Pereira, Helder H., Morais, Joao, Seixo, Filipe, Mendonça, Carlos, Botelho, Ana, Caetano, Francisca, Minescu, Bogdan, Chaitman, Bernard, Istratoaie, Octavian, Tesloianu, Dan N., Dorobantu, Maria, Cristian, Gabriel, Dumitrescu, Silviu, Podoleanu, Cristian Gc, Constantinescu, Mircea Ca, Bengus, Cristina M., Militaru, Constantin, Rosu, Doina, Kelsey, Sheryl F., Parepa, Irinel R., Matei, Adrian V., Alexandru, Tom M., Malis, Mihaela, Coman, Ioan, Shvarts, Yury, Orlikova, Olga, Kobalava, Zhanna, Barbarash, Olga L., Markov, Valentin, Olsson, Anders G., Lyamina, Nadezhda, Gordienko, Alexander, Zrazhevsky, Konstantin, Vishnevsky, Alexander Y., Gurevich, Victor, Stryuk, Raisa, Lomakin, Nikita V., Bokarev, Igor, Khlevchuk, Tatiana, Shalaev, Sergey, Rouleau, Jean-Lucien, Khaisheva, Larisa, Chizhov, Petr, Viktorova, Inna, Osokina, Natalya, Shchekotov, Vladimir, Akatova, Evgenia, Chumakova, Galina, Libov, Igor, Voevoda, Mikhail I., Tretyakova, Tatyana V., Simoons, Maarten L., Baranov, Evgeny, Shustov, Sergey, Yakushin, Sergey, Gordeev, Ivan, Khasanov, Niiaz, Reshetko, Olga, Sotnikova, Tatiana, Molchanova, Olga, Nikolaev, Konstantin, Gapon, Liudmila, Alexander, Karen, Baranova, Elena, Kosmachova, Elena, Karpov, Yuriy, Karpov, Yuri, Povzun, Anton, Egorova, Liudmila, Tyrenko, Vadim V., Ivanov, Igor G., Ilya, Masterov, Kanorsky, Sergey, Meloni, Chiara, Simic, Dragan, Ivanovic, Nikola, Davidovic, Goran, Tasic, Nebojsa, Asanin, Milika R., Stojic, Stevo, Apostolovic, Svetlana R., Ilic, Stevan, Tosic, Biljana Putnikovic, Stankovic, Aleksandar, Rosenson, Robert, Arandjelovic, Aleksandra, Radovanovic, Slavica, Todic, Branislava, Ristic, Arsen D., Balinovac, Jovan, Dincic, Dragan V., Seferovic, Petar, Karadzic, Ana, Dodic, Slobodan, Dimkovic, Sinisa, Sijbrands, Eric J. G., Jakimov, Tamara, Poh, Kian-Keong, Yee Ong, Hean, Tang I-Shing, Justin, Micko, Karol, Nociar, Jan, Pella, Daniel, Fulop, Peter, Hranai, Marian, Palka, Juraj, Tricoci, Pierluigi, Mazur, Juraj, Majercák, Ivan, Dzupina, Andrej, Fazekas, František, Gonsorcik, Jozef, Bugan, Viliam, Murin, Jan, Selecky, Juraj, Kamensky, Gabriel, Strbova, Jaroslava, Alexander, John H., Smik, Rudolf, Dukat, Andrej, Olexa, Peter, Žuran, Ivan, Poklukar, Janez, Šuligoj, Nataša Černič, Cevc, Matija, Fras, Zlatko, Cyster, Henry P., Ranjith, Naresh, Armaganijan, Luciana, Corbett, Clive, Bayat, Junaid, Makoali Makotoko, Ellen, du Toit Theron, Hendrik, Kapp, Ilse E., de V Basson, Matthys M., Lottering, Hanlie, Van Aswegen, Dina, Van Zyl, Louis J., Sebastian, Peter J., Bagai, Akshay, Pillay, Thayabran, Saaiman, Jan A., Commerford, Patrick J., Cassimjee, Soraya, Riaz, Garda, Ebrahim, Iftikhar O., Sarvan, Mahomed, Mynhardt, Joseph H., Dalby, Anthony J., Reuter, Helmuth, Bahit, Maria Cecilia, Moodley, Rajendran, Vida, Manuel, Fillat, Angel R. Cequier, Peris, Vicente Bodí, Jimenez, Francisco Fuentes, Marín, Francisco, Cruz Fernández, Jose M., Hidalgo Urbano, Rafael Jesus, Gil-Extremera, Blas, Toledo, Pablo, Brennan, J. Matthew, Worner Diz, Fernando, Garcia-Dorado, David, Iñiguez, Andres, Gonzalez-Juanatey, Jose R., Portales, Javier Fernandez, Murillo, Fernando Civeira, Pericas, Laia Matas, Zamorano, Jose Luis, De Mora Martin, Manuel, Cortada, Jordi Bruguera, Clifton, Shaun, Alonso Martin, Joaquin J., Serrano Antolin, Jose Maria, De Berrazueta Fernández, José R., Vázquez de Prada, José Antonio, Díaz Fernández, Jose Francisco, García Lledó, José Alberto, Cosín Sales, Juan, Rodriguez, Javier Botas, Tragant, Gabriel Gusi, Benedicto, Amparo, DeVore, Adam D., Gonzalez-Juanatey, Carlos, Camprubí Potau, Mercedes, Perez, Ignacio Plaza, De La Tassa, César Morís, Rincon, Pablo Loma-Osorio, Recena, Javier Balaguer, Escudier, Juan M., Payeras, Antonio Coca, Orcajo, Norberto Alonso, Constantine, Godwin, Deloatch, Shalonda, Haniffa, Ruvaiz, Tissera, Nirmali, Amarasekera, Stanley, Ponnamperuma, Chandrike, Fernando, Nimali, Fernando, Kaputella, Jayawardena, Jayanthimala, Wijeyasingam, Santharaj, Ranasinghe, Gotabhaya, Ekanayaka, Ruvan, Dickey, Sheila, Mendis, Sepalika, Senaratne, Vajira, Mayurathan, Gnanamoorthy, Rajapaksha, Ajantha, Sirisena, Thilak, Herath, Jagath I., Amarasena, Naomali, Berglund, Stefan, Rasmanis, Gundars, Hagström, Emil, Dombrowski, Keith, Vedin, Ola, Witt, Nils, Mourtzinis, Georgios, Nicol, Peter, Hansen, Ole, Romeo, Stefano, Jensen, Steen Agergaard, Torstensson, Ingemar, Ahremark, Ulf, Sundelin, Torbjörn, Ducrocq, Grégory, Moccetti, Tiziano, Müller, Christian, Mach, Francois, Binde, Ronald, Landmesser, Ulf, Gämperli, Oliver, Chiang, Chern-En, Tsai, Wei-Chuan, Ueng, Kwo-Chang, Lai, Wen-Ter, Eapen, Zubin, Liu, Ming-En, Hwang, Juey-Jen, Yin, Wei-Hsian, Hsieh, I.-Chang, Hsieh, Ming-Jer, Hsiang Lin, Wei, Kuo, Jen-Yuan, Huang, Tsuei-Yuan, Fang, Chih-Yuan, Kaewsuwanna, Pinij, Endsley, Patricia, Soonfuang, Wasant, Jintapakorn, Woravut, Sukonthasarn, Apichard, Sritara, Piyamitr, Wongpraparut, Nattawut, Sastravaha, Krisada, Sansanayudh, Nakarin, Kehasukcharoen, Wirash, Piyayotai, Dilok, Chotnoparatpat, Paiboon, Eppinger, Arleen, Camsari, Ahmet, Kultursay, Hakan, Guneri, Sema, Mutlu, Bulent, Ersanli, Murat, Demirtas, Mustafa, Kirma, Cevat, Ural, Ertan, Koldas, Lale, Karpenko, Oleksandr, Harrison, Robert W., Prokhorov, Alexander, Vakaluyk, Ihor, Myshanych, Halyna, Reshotko, Dmytro, Batushkin, Valeriy, Rudenko, Leonid, Kovalskyi, Ihor, Kushnir, Mykola, Tseluyko, Vira, Mostovoy, Yuriy, Hess, Connie Ng, Stanislavchuk, Mykola, Kyiak, Yulian, Karpenko, Yuriy, Malynovsky, Yaroslav, Klantsa, Andriy, Kutniy, Oles, Amosova, Ekaterina, Tashchuk, Viktor, Leshchuk, Oleh, Parkhomenko, Alexander, Hlatky, Mark A., Rishko, Mykola, Kopytsya, Mykola, Yagensky, Andriy, Vatutin, Mykola, Bagriy, Andriy, Barna, Olga M., Ushakov, Olexiy, Dzyak, Georgiy, Goloborodko, Borys, Rudenko, Anatolii, Jordan, Joseph Dedrick, Zheleznyy, Volodymyr, Trevelyan, Jasper, Zaman, Azfar, Lee, Kaeng, Moriarty, Andrew, Aggarwal, Rajesh K., Clifford, Piers, Wong, Yuk-ki, Iqbal, Syed Mr, Subkovas, Eduardas, Knowles, Joshua W., Braganza, Denise, Sarkar, David, Storey, Robert, Griffiths, Huw, Mcclure, Sam, Muthusamy, Rangasamy, Smith, Simon, Kurian, John, Levy, Terry, Barr, Craig, Kolls, Bradley J., Kadr, Honer, Gerber, Robert, Simaitis, Audrius, Soran, Handrean, Brodison, Adrian, Ayaz, Mohammad, Cheema, Muhammad, Oliver, Richard, Thackray, Simon, Mudawi, Telal, Kong, David F., Rahma, Gohar, Sultan, Ayyaz, Reynolds, Timothy, Sharman, David, Spriging, David, Butler, Rob, Wilkinson, Peter, Lip, Gregory Yh, Ossei-Gerning, Nicholas, Vardi, Gil, Leonardi, Sergio, Baldari, Duccio, Brabham, David, Treasure Ii, Charles, Dahl, Charles, Palmer, Bruce, Wiseman, Alan, Khan, Abul, Puri, Sanjeev, Mohart, Ann Elizabeth, Ince, Carlos, Lillis, Linda, Flores, Enrique, Wright, Scott, Cheng, Shi-Chi, Rosenberg, Michael, Rogers, William, Kosinski, Edward, Forgosh, Les, Waltman, Jonathan, Shoukfeh, Mohammad, Dagher, Georges, Lopes, Renato D., Cambier, Patrick, Lieber, Ira, Kumar, Priya, East, Cara, Krichmar, Perry, Hasan, Mian, White, Lindsey, Knickelbine, Thomas, Haldis, Thomas, Gillespie, Eve, Maron, David J., Amidon, Thomas, Suh, David, Arif, Imran, Abdallah, Mouhamad, Akhter, Faiq, Carlson, Eric, D'Urso, Michael, El-Ahdab, Fadi, Nelson, William, Moriarty, Katie, Mahaffey, Kenneth W., Harris, Barry, Cohen, Steven, Carter, Luther, Doty, Daniel, Sabatino, Kenneth, Haddad, Tariq, Rao, Sunder, Mulkay, Angel, Jovin, Ion, Klancke, Kim, Marcus, Jill, Malhotra, Vinay, Devarapalli, Sai K., Koren, Michael, Chandna, Harish, Dodds Iii, George, Goraya, Tauqir, Bengston, James, Janik, Matthew, Moran, Joseph, Sumner, Andrew, Mathews, Robin, Kobayashi, John, Davis, William, Yazdani, Shahram, Pasquini, John, Thakkar, Maitreya, Vedere, Amarnath, Leimbach, Wayne, Rider, James, Fenton, Sarah, Singh, Narendra, Mehta, Rajendra H., Shah, Anil V., Moriarty, Patrick M., Janosik, Denise, Pepine, Carl, Berman, Brett, Gelormini, Joseph, Daniels, Christopher, Richard, Kerensky, Keating, Friederike, Kondo, Nicholas I., Mentz, Robert J., Shetty, Sanjay, Levite, Howard, Waider, Winfried, Takata, Theodore, Abu-Fadel, Mazen, Shah, Vipul, Aggarwal, Rahul, Kumar, Anil, Hattler, Brack, Do, Rose, Moreira, Humberto Graner, Link, Chad, Bortnick, Anna, Kinzfogl Iii, George, Ghitis, Arnold, Larry, John, Teufel, Edward, Kuhlman, Peter, Mclaurin, Brent, Zhang, Wenwu, Thew, Stephen, Patel, Chetan B., Abbas, Jalal, White, Matthew, Islam, Othman, Subherwal, Sumeet, Ranadive, Nandkishore, Vakili, Babak, Gring, Christian, Henderson, David, Schuchard, Timothy, Farhat, Naim, Pereira, Sabrina Bernardez, Kline, Geoffrey, Mahal, Sharan, Whitaker, Jack, Speirs, Shawn, Andersen, Rolf, Daboul, Nizar, Horwitz, Phillip, Zahr, Firas, Ponce, George, Jafar, Zubair, Perkins, Lynn, Mcgarvey, Joseph, Panchal, Vipul, Voyce, Stephen, Blok, Thomas, Sheldon, William, Azizad, Masoud M., Schmalfuss, Carsten, Picone, Mark, Pederson, Robert, Herzog, William, Povsic, Thomas J., Friedman, Keith, Lindsey, Jason, Timothy, Eichenlaub, Leonard, Parilak, Lepor, Norman, El Shahawy, Mahfouz, Weintraub, Howard, Irimpen, Anand, Alonso, Alvaro, May, Wade, Puymirat, Etienne, Christopher, Daniels, Galski, Thomas, Chu, Alan, Mody, Freny, Ramin, Ebrahimi, Hodes, Zachary, Rossi, Joseph, Rose, Gregory, Fairlamb, James, Lambert, Charles, Raisinghani, Ajit, Abbate, Antonio, Vetrovec, George, King, Marilyn, Carey, Charles, Gerber, Jaime, Younis, Liwa, Park, Hyeun Tom, Vidovich, Mladen, Knutson, Thomas, Jones, William Schuyler, Friedman, Dennis, Chaleff, Fred, Loussararian, Arthur, Rozeman, Phillip, Kimmelstiel, Carey, Kuvin, Jeffrey, Silver, Kevin, Foster, Malcolm, Tonnessen, Glen, Espinoza, Andrey, Shah, Bimal R., Amlani, Mohamadali, Wali, Andreas, Malozzi, Christopher, Jong, Geert T., Massey, Clara, Wattanakit, Keattiyoat, O'Donnell, Philip J., Singal, Dinesh, Jaffrani, Naseem, Banuru, Sridhar, Sherwood, Matthew W., Fisher, Daniel, Xenakis, Mark, Perlmutter, Neal, Bhagwat, Ravi, Strader, James, Blonder, Ronald, Akyea-Djamson, 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John, Stringfellow, Kenya, Claxton, Edmund, Weiss, Robert, Kathryn, Rohr, Berk, Martin, Rossi, Peter, Joshi, Parag, Khera, Amit, Khaira, Ajit S., Kumkumian, Greg, Lupovitch, Steven, Sujjavanich, Darin, Purow, Joshua, Welka, Stephen, Hoffman, David, Fischer, Stuart, Soroka, Eugene, Eagerton, Donald, Pancholy, Samir, Ray, Michael, Erenrich, Norman, Farrar, Michael, Toma, Mustafa, Pollock, Stewart, French, William J., Diamantis, Steve, Guy, Douglas, Gimple, Lawrence, Neustel, Mark, Schwartz, Steven, Pereira, Edward, Albert, Seals, Spriggs, Douglas, Trotter, Charlene, Strain, Janet, Mittal, Suneet, Vo, Anthony, Chane, Majed, Hall, Jason, Vijay, Nampalli, Lotun, Kapildeo, Lester, F. Martin, Nahhas, Ahed, Pope, Theodore, van Diepen, Sean F. 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Fernandes, Precoma, Dalton B., Moura Jorge, Jose C., Silva, Pedro, Silveira, Jose A., Saporito, Wladmir, Neto, Jose A. 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Molina, Bonfanti, Alberto J. Cadena, Aroca, Carlos Cotes, Higuera, Juan Diego, Blanquicett, Marco, Barrera Silva, Sandra I., Garcia Lozada, Henry J., Prieto, Juan-Carlos, Coronel Arroyo, Julian A., Accini Mendoza, Jose L., Fernandez Ruiz, Ricardo L., Quintero Ossa, Alvaro M., Manzur Jatin, Fernando G., Sotomayor Herazo, Aristides, Parada, Jeffrey Castellanos, Arambula, Rafael Suarez, Urina Triana, Miguel A., Trujillo, Angela M. Fernandez, Yong, Huo, Strozzi, Maja, Car, Siniša, Miličić, Davor, Lovrić Benčić, Martina, Pintarić, Hrvoje, Prvulović, Đeiti, Šikić, Jozica, Peršić, Viktor, Mileta, Dean, Štambuk, Kresimir, López-Jaramillo, Patricio, Babić, Zdravko, Tomulic, Vjekoslav, Lukenda, Josip, Mejic-Krstulovic, Stanka, Starcevic, Boris, Spinar, Jindrich, Horak, David, Velicka, Zdenek, Alan, David, Machova, Vilma, Pećin, Ivan, Linhart, Ales, Novotny, Vojtech, Kaucak, Vladimir, Rokyta, Richard, Naplava, Robert, Coufal, Zdenek, Adamkova, Vera, Podpera, Ivo, Zizka, Jiri, Motovska, Zuzana, Reiner, Zeljko, Marusincova, Ivana, Ostadal, Petr, Heinc, Petr, Kuchar, Jiri, Povolny, Petr, Matuska, Jiri, Poulsen, Steen H., Raungaard, Bent, Clemmensen, Peter, Bang, Lia E., May, Ole, Bøttcher, Morten, Hove, Jens D., Frost, Lars, Gislason, Gunnar, Larsen, John, Johansen, Peter Betton, Hald, Flemming, Johansen, Peter, Jeppesen, Jørgen, Poulsen, Steen Hvitfeldt, Nielsen, Tonny, Kristensen, Kjeld S., Walichiewicz, Piotr Maria, Lomholdt, Jens D., Klausen, Ib C., Nielsen, Peter Kaiser, Davidsen, Flemming, Videbaek, Lars, Viigimaa, Margus, Soots, Mai, Vahula, Veiko, Hedman, Anu, Soopõld, Üllar, Märtsin, Kaja, Jurgenson, Tiina, Kristjan, Arved, Nieminen, Markku S., Vikman, Saila, Huikuri, Heikki, Airaksinen, Juhani, Coste, Pierre, Ferrari, Emile, Morel, Olivier, Montalescot, Gilles, Machecourt, Jacques, Barone-Rochette, Gilles, Mansourati, Jacques, Cottin, Yves, Steg, Ph Gabriel, Leclercq, Florence, Belhassane, Abdelkader, Delarche, Nicolas, Boccara, Franck, Paganelli, Franck, Clerc, Jérôme, Schiele, Francois, Aboyans, Victor, Probst, Vincent, Berland, Jacques, Chumburidze, Vakhtang, Lefèvre, Thierry, Khintibidze, Irakli, Shaburishvili, Tamaz, Pagava, Zurab, Ghlonti, Ramaz, Lominadze, Zaza, Khabeishvili, George, Hemetsberger, Rayyan, Edward, Kemala, Marx, Nikolaus, Rauch-Kröhnert, Ursula, Stratmann, Matthias, Appel, Karl-Friedrich, Schmidt, Ekkehard, Omran, Heyder, Stellbrink, Christoph, Dorsel, Thomas, Lianopoulos, Emmanouil, Vöhringer, Hans Friedrich, Marx, Roger, Liberopoulos, Evangelos, Zirlik, Andreas, Schellenberg, Detlev, Heitzer, Thomas, Laufs, Ulrich, Werner, Christian, Gielen, Stephan, Nuding, Sebastian, Winkelmann, Bernhard, Behrens, Steffen, Carlos, Pablo, Sydow, Karsten, Karakas, Mahir, Simonis, Gregor, Muenzel, Thomas, Werner, Nikos, Leggewie, Stefan, Böcker, Dirk, Braun-Dullaeus, Rüdiger, Toursarkissian, Nicole, Jeserich, Michael, Valdovinos, Montenegro, Weißbrodt, Matthias, Schaeufele, Tim, Weil, Joachim, Völler, Heinz, Waltenberger, Johannes, Natour, Mohammed, Schmitt, Susanne, Müller-Wieland, Dirk, Steiner, Stephan, Heidenreich, Lothar, Tse, Hung-Fat, Offers, Elmar, Gremmler, Uwe, Killat, Holger, Rieker, Werner, Patsilinakos, Sotiris, Kartalis, Athanasios, Manolis, Athanassios, Sionis, Dimitrios, Chachalis, Geargios, Kiss, Robert Gabor, Skoumas, Ioannis, Athyros, Vasilios, Vardas, Panagiotis, Parthenakis, Frangkiskos, Hahalis, Georgios, Lekakis, John, Hatzitolios, Apostolos, Fausto Ovando, Sergio R., Montenegro Valdovinos, Pablo Carlos, Arango Benecke, Juan L., Xavier, Denis, Rodriguez De Leon, Edgar R., Yan, Bryan Py, Siu, David Cw, Turi, Tibor, Merkely, Bela, Gabor Kiss, Robert, Ungi, Imre, Lupkovics, Geza, Nagy, Lajos, Katona, András, Zahger, Doron, Édes, István, Müller, Gábor, Horvath, Iván, Kapin, Tibor, Szigeti, Zsolt, Faluközy, József, Kumbla, Mukund, Sandhu, Manjinder, Annam, Sharath, Reddy Proddutur, Naveen, Valgimigli, Marco, Regella, Reddy, Premchand, Rajendra K., Mahajan, Ajaykumar, Pawar, Sudhir, Abhyanakar, Atul D., Kerkar, Prafulla, Govinda, Ravishankar A., Oomman, Abraham, Sinha, Dhurjati, Patil, Sachin N., Kimura, Takeshi, Kahali, Dhiman, Sawhney, Jitendra, Joshi, Abhijeet B., Chaudhary, Sanjeev, Harkut, Pankaj, Guha, Santanu, Porwal, Sanjay, Jujjuru, Srimannarayana, Pothineni, Ramesh B., Monteiro, Minguel R., Kim, Hyo Soo, Khan, Aziz, Iyengar, Shamanna S., Grewal, Jasprakash Singh, Chopda, Manoj, Fulwani, Mahesh C., Patange, Dr 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Gavish, Dov, Ramos López, Gabriel Arturo, Vered, Zvi, Caraco, Yoseph, Elias, Mazen, Tov, Naveh, Wolfovitz, Efrat, Lishner, Michael, Elias, Nizar, Piovaccari, Giancarlo, De Pellegrin, Annamaria, Garbelotto, Raffaella, Alings, Marco, Guardigli, Gabriele, Marco, Valgimigli, Licciardello, Giovanni, Auguadro, Carla, Scalise, Filippo, Cuccia, Claudio, Salvioni, Alessandro, Musumeci, Giuseppe, Senni, Michelle, Calabrò, Paolo, Novo, Salvatore, Faggiano, Pompilio, Metra, Marco, De Cesare, Nicoletta B., Berti, Sergio, Puccioni, Enrico, Galvani, Marcello, Tespili, Maurizio, Piatti, PierMarco, Palvarini, Michela, Halvorsen, Sigrun, De Luca, Giuseppe, Violini, Roberto, De Leo, Alessandro, Olivari, Zoran, Filardi, Pasquale Perrone, Ferratini, Maurizio, Racca, Vittorio, Dai, Kazuoki, Shimatani, Yuji, Kamiya, Haruo, Correa Flores, Roger M., Ando, Kenji, Takeda, Yoshihiro, Morino, Yoshihiro, Hata, Yoshiki, Kimura, Kazuo, Kishi, Koichi, Michishita, Ichiro, Uehara, Hiroki, Higashikata, Toshinori, Hirayama, Atsushi, Sy, Rody G., Hirooka, Keiji, Doi, Yasuji, Sakagami, Satoru, Taguchi, Shuichi, Koike, Akihiro, Fujinaga, Hiroyuki, Koba, Shinji, Kozuma, Ken, Kawasaki, Tomohiro, Ono, Yujiro, Budaj, Andrzej, Shimizu, Masatoshi, Katsuda, Yousuke, Wada, Atsuyuki, Shinke, Toshiro, Ako, Junya, Fujii, Kenshi, Takahashi, Toshiyuki, Nakao, Koichi, Furukawa, Yutaka, Sugino, Hiroshi, Tamura, Ritsu, Mano, Toshiaki, Uematsu, Masaaki, Utsu, Noriaki, Ito, Kashima, Haraguchi, Takuya, Sato, Katsuhiko, Ueda, Yasunori, Nishibe, Akira, Fujimoto, Kazuteru, Masutani, Motomaru, Yoon, Jung Han, Kim, Hack-Lyoung, Sik Park, Hun, Chae, In-Ho, Kim, Moo Hyun, Jeong, Myung Ho, Rha, Seungwoon, Kim, Chongjin, Kim, Hyo-Soo, Kim, Hae Young, Hong, Taekjong, Tahk, Seung-Jea, Kim, Youngkwon, Busmane, Arija, Pontaga, Natalija, Strelnieks, Aldis, Mintale, Iveta, Sime, Iveta, Petrulioniene, Zaneta, Kavaliauskiene, Roma, Jurgaitiene, Ruta, Sakalyte, Gintare, Slapikas, Rimvydas, Norkiene, Sigute, Misonis, Nerijus, Chua, Terrance, Kibarskis, Aleksandras, Kubilius, Raimondas, Bojovski, Stojko, Lozance, Nensi, Kjovkaroski, Aleksandar, Doncovska, Snezana, Ong, Tiong Kiam, Kasim, Sazzli, Maskon, Oteh, Kandasamy, Balachandran, Liew, Houng B., Wan Mohamed, Wan Mohd Izani, Castillo, Armando García, Calvillo, Jorge Carrillo, Campos, Pedro Fajardo, Núñez Fragoso, Juan Carlos, Bayram Llamas, Edmundo Alfredo, Alcocer Gamba, Marco Antonio, Madrigal, Jaime Carranza, González Salas, Luis Gerardo, Rosas, Enrique López, González Díaz, Belinda, Vázquez, Eduardo Salcido, Nacoud Ackar, Alfredo, Llamas Esperón, Guillermo Antonio, Martínez Sánchez, Carlos Rodolfo, De Leon, María Guerrero, Suarez Otero, Rodrigo, Salmón, Guillermo Fanghänel, Pérez Ríos, Jesús Antonio, Garza Ruíz, José Angel, Breedveld, Robert W., Feenema-Aardema, Margriet, Borger-Van Der Burg, Alida, Hoogslag, Pieter Am, Suryapranata, Harry, Tuñón, José, Oomen, Antonius, Van Haelst, Paulus, Feenema-Aradema, Margriet, Wiersma, Jacobijne J., Basart, Dirk, Van Der Wal, Ruud Ma, Zwart, Peter, Monraats, Pascalle, Van Kesteren, Henricus, Karalis, Ioannis, de Silva, H. Asita, Jukema, Johan, Verdel, Gerardus Je, Brueren, Bart Rg, Troquay, Roland P. Th, Viergever, Eric P., Al-Windy, Nadea Yy, Bartels, Gerard L., Cornel, Jan H., Hermans, Walter Rm, Herrman, Johannes Pr, Bos, Robert J., Groutars, Reginald Gej, Van Der Zwaan, Coenraad C., Kaplan, Refik, Ronner, Eelko, Groenemeijer, Bjorn E., Bronzwaer, Patrick Na, Liem, Anho Ah, Rensing, Bernard Jwm, Bokern, Marcel Jja, Nijmeijer, Remco, Hersbach, Ferry Mrj, Willems, Frank F., Gosselink, Antonius Tm, Rasoul, Saman, Elliott, John, Wilkins, Gerard, Fisher, Raewyn, Scott, Douglas, Hart, Hamish, Stewart, Ralph, Harding, Scott, Ternouth, Ian, Fisher, Nicholas, Wilson, Samuel, Aitken, Denise, Anscombe, Russell, Davidson, Laura, Tomala, Tadeusz, Nygård, Ottar, Sparby, Jon Arne, Andersen, Kjell, Gullestad, Lars, Jortveit, Jarle, Munk, Peter S., Singsaas, Erlend Gyllensten, Hurtig, Ulf, Calderon Ticona, Jorge R., Durand Velasquez, Julio R., Negron Miguel, Sandra A., Sanabria Perez, Enrique S., Carrion Chambilla, Jesus M., Chavez Ayala, Carlos A., Castillo Leon, Reynaldo P., Vargas GonzalesC, Rolando J., Hernandez Zuniga, Jose D., Camacho Cosavalente, Luis A., Bravo Mannucci, Jorge E., Landeo, Javier Heredia, Llerena Navarro, Nassip C., Roldan Concha, Yudy M., Rodriguez Chavez, Víctor E., Anchante Hernandez, Henry A., Zea Nunez, Carlos A., Ramos, Walter Mogrovejo, Ferrolino, Arthur, Sy, Rosa Allyn G., Tirador, Louie, Matiga, Generoso, Coching, Raul Martin, Bernan, Alisa, Rogelio, Gregorio, Morales, Dante D., Tan, Edgar, Sulit, Dennis Jose, Wlodarczak, Adrian, Skonieczny, Grzegorz, Ray, Kausik K., Pawlowicz, Lidia, Wojewoda, Pawel, Busz-Papiez, Benita, Bednarski, Janusz, Goch, Aleksander, Staneta, Pawel, Dulak, Elzbieta, Saminski, Krzysztof, Krasowski, Wlodzimierz, Sudnik, Wanda, Zurakowski, Aleksander, Skorski, Marcin, Lysek, Roman, Miklaszewicz, Beata, Lipko, Jan Andrzej, Kostarska-Srokosz, Edyta, Piepiorka, Marek, Drzewiecka, Anna, Stasiewski, Arkadiusz, Bhatt, Deepak L, Bittner, Vera A, Goodman, Shaun G, Harrington, Robert A, Jukema, J Wouter, White, Harvey D, Zeiher, Andreas M, Roe, Matthew T, Mahaffey, Kenneth W, Edelberg, Jay M, Sasiela, William J, Aylward, Philip E, Lopes, Renato D, Gotcheva, Nina N, Nieminen, Markku S, Laucevičius, Aleksandras, Correa Flores, Roger M, Sy, Rody G, Ristic, Arsen D, Dalby, Anthony J, de Silva, H Asita, Ray, Kausik K, Moriarty, Patrick M, Kelsey, Sheryl F, Olsson, Anders G, Simoons, Maarten L, Sijbrands, Eric J G, Alexander, John H, Brennan, J Matthew, DeVore, Adam D, Harrison, Robert W, Hlatky, Mark A, Knowles, Joshua W, Kolls, Bradley J, Kong, David F, Maron, David J, Mehta, Rajendra H, Mentz, Robert J, Patel, Chetan B, Povsic, Thomas J, Shah, Bimal R, Sherwood, Matthew W, van Diepen, Sean F P, Wilson, Matthew D, Schiavi, Lilia B, Alvarisqueta, Andrés F, Sassone, Sonia A, Bordonava, Anselmo P, Alves De Lima, Alberto E, Schmidberg, Jorge M, Duronto, Ernesto A, Caruso, Orlando C, Novaretto, Leonardo P, Montaña, Oscar R, Gomez Vilamajo, Oscar A, Lorenzatti, Alberto J, Cartasegna, Luis R, Paterlini, Gustavo A, Mackinnon, Ignacio J, Caime, Guillermo D, Codutti, Oscar R, Jure, Horacio O, Hrabar, Adrian D, Vallejos, Julio A, Ahuad Guerrero, Rodolfo A, Patocchi, Cristian A, Zaidman, Cesar J, Giuliano, Maria E, Dran, Ricardo D, Vico, Marisa L, Carnero, Gabriela S, Guzman, Pablo N, Medrano Allende, Juan C, Garcia Brasca, Daniela F, Bustamante Labarta, Miguel H, Colombo, Hugo R, Luciardi, Hector L, Waisman, Gabriel D, Berli, Mario A, Garcia Duran, Ruben O, Cestari, Horacio G, Luquez, Hugo A, Giordano, Jorge A, Saavedra, Silvia S, Waites, Jonathon H, Arstall, Margaret A, Rogers, James F, Oqueli Flores, Romulo E, Lehman, Sam J, Garrahy, Paul J, Carroll, Patrick A, Wolf, Luc De, Nicolau, Jose C, Giorgeto, Flavio E, Silva, Ricardo P, Abrantes, José Antonio M, Bodanese, Luiz C, Michalaros, Yorghos L, Eliaschewitz, Freddy G, Vidotti, Maria H, Leaes, Paulo E, Botelho, Roberto V, Manenti, Euler Roberto F Fernandes, Precoma, Dalton B, Moura Jorge, Jose C, Silveira, Jose A, Neto, Jose A Marin, Feitosa, Gilson S, Ritt, Luiz Eduardo F, de Souza, Juliana A, Todorov, Georgi V, Nikolov, Fedya P, Velcheva, Elena S, Tzekova, Maria L, Benov, Haralambi O, Petranov, Stanislav L, Tumbev, Haralin S, Shehova-Yankova, Nina S, Markov, Dimitar T, Raev, Dimitar H, Mollov, Mihail N, Kichukov, Kostadin N, Ilieva-Pandeva, Katya A, Mincheva, Valentina M, Lazov, Petar V, Dimov, Bojidar I, Prieto, Juan C, Raffo, Carlos A, Luna Botia, Diana C, De Salazar, Dora I Molina, Bonfanti, Alberto J Cadena, Barrera Silva, Sandra I, Garcia Lozada, Henry J, Coronel Arroyo, Julian A, Accini Mendoza, Jose L, Fernandez Ruiz, Ricardo L, Quintero Ossa, Alvaro M, Manzur Jatin, Fernando G, Urina Triana, Miguel A, Trujillo, Angela M Fernandez, Poulsen, Steen H, Bang, Lia E, Hove, Jens D, Kristensen, Kjeld S, Lomholdt, Jens D, Klausen, Ib C, Fausto Ovando, Sergio R, Arango Benecke, Juan L, Rodriguez De Leon, Edgar R, Premchand, Rajendra K, Abhyanakar, Atul D, Govinda, Ravishankar A, Patil, Sachin N, Joshi, Abhijeet B, Pothineni, Ramesh B, Monteiro, Minguel R, Iyengar, Shamanna S, Fulwani, Mahesh C, Chopra, Vijay K, Goyal, Naresh K, Manakshe, Gajendra V, Pellegrin, Annamaria De, De Cesare, Nicoletta B, Piatti, Piermarco, Luca, Giuseppe De, Leo, Alessandro De, Petrulionienė, Žaneta, Šakalytė, Gintarė, Šlapikas, Rimvydas, Liew, Houng B, Breedveld, Robert W, Wiersma, Jacobijne J, Troquay, Roland PTh, Viergever, Eric P, Bartels, Gerard L, Cornel, Jan H, Bos, Robert J, Van Der Zwaan, Coenraad C, Groenemeijer, Bjorn E, Willems, Frank F, Munk, Peter S, Calderon Ticona, Jorge R, Durand Velasquez, Julio R, Negron Miguel, Sandra A, Sanabria Perez, Enrique S, Carrion Chambilla, Jesus M, Chavez Ayala, Carlos A, Castillo Leon, Reynaldo P, Vargas GonzalesC, Rolando J, Hernandez Zuniga, Jose D, Camacho Cosavalente, Luis A, Bravo Mannucci, Jorge E, Llerena Navarro, Nassip C, Roldan Concha, Yudy M, Rodriguez Chavez, Víctor E, Anchante Hernandez, Henry A, Zea Nunez, Carlos A, Sy, Rosa Allyn G, Morales, Dante D, Pereira, Helder H, Tesloianu, Dan N, Bengus, Cristina M, Parepa, Irinel R, Matei, Adrian V, Alexandru, Tom M, Barbarash, Olga L, Vishnevsky, Alexander Y, Lomakin, Nikita V, Voevoda, Mikhail I, Tretyakova, Tatyana V, Tyrenko, Vadim V, Ivanov, Igor G, Asanin, Milika R, Apostolovic, Svetlana R, Dincic, Dragan V, Cyster, Henry P, Kapp, Ilse E, de V Basson, Matthys M, Aswegen, Dina Van, Van Zyl, Louis J, Sebastian, Peter J, Saaiman, Jan A, Commerford, Patrick J, Ebrahim, Iftikhar O, Mynhardt, Joseph H, Fillat, Angel R Cequier, Cruz Fernández, Jose M, Gonzalez-Juanatey, Jose R, Alonso Martin, Joaquin J, De Berrazueta Fernández, José R, Escudier, Juan M, Herath, Jagath I, Hsieh, I-Chang, Barna, Olga M, Aggarwal, Rajesh K, Wong, Yuk-Ki, Devarapalli, Sai K, Shah, Anil V, Kondo, Nicholas I, Azizad, Masoud M, Jong, Geert T, O'Donnell, Philip J, Marais, H John, Khaira, Ajit S, French, William J, Lester, F Martin, Sundram, P Sandy, Gilbert, John M, Schmedtje, John F, Colhoun, Helen M, Dempsey, Michael A, and McClanahan, Mark A
Subjects: Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use, Anticholesteremic Agents/adverse effects, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], prevention & control, heart disease risk factors, diagnosis [Cardiovascular Diseases], Antibodies, Monoclonal, Humanized, PCSK9 inhibitors, acute coronary syndrome, apolipoproteins B, LDL cholesterol, Antibodies, acute coronary syndrome, LDL, drug therapy [Atherosclerosis], Risk Factors, Physiology (medical), therapeutic use [Hydroxymethylglutaryl-CoA Reductase Inhibitors], Monoclonal, Humans, Cardiac and Cardiovascular Systems, Humanized, Cardiovascular Diseases/diagnosis, Apolipoproteins B, Kardiologi, diagnosis [Acute Coronary Syndrome], Anticholesteremic Agents, PCSK9 inhibitors, apolipoproteins B, cholesterol, LDL, cholesterol, Atherosclerosis/drug therapy, Cholesterol, LDL, Atherosclerosis, Acute Coronary Syndrome/diagnosis, drug therapy, Cholesterol, Treatment Outcome, Cardiovascular Diseases, Heart Disease Risk Factors, epidemiology, adverse effects [Anticholesteremic Agents], Hydroxymethylglutaryl-CoA Reductase Inhibitors, Cardiology and Cardiovascular Medicine
Abstract: Circulation : an official journal of the American Heart Association / ed.-in-chief Ephraim Donosco 146(9), 657-672 (2022). doi:10.1161/CIRCULATIONAHA.121.057807, Published by Ovid, [Erscheinungsort nicht ermittelbar]
Published: 2022

43. Hipercolesterolemia familiar en Gran Canaria: mutación con efecto fundador y alta frecuencia de diabetes

Author: Ana M. Wägner, Rosa M. Sánchez-Hernández, Ana M. González-Lleó, Mauro Boronat, Antonio Tugores, Fernando Civeira, and Yeray Brito-Casillas
Subjects: Gynecology, medicine.medical_specialty, business.industry, 030209 endocrinology & metabolism, Familial hypercholesterolemia, 030204 cardiovascular system & hematology, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, Diabetes mellitus, medicine, Pharmacology (medical), Cardiology and Cardiovascular Medicine, business, Founder mutation
Abstract: Resumen Introduccion Gran Canaria es una region de aislamiento genetico para hipercolesterolemia familiar, debido a una mutacion fundadora, p.[Tyr400_Phe402del], en el gen del receptor de LDL (LDLR). Datos iniciales indican que sus portadores podrian tener una alta prevalencia de diabetes. Material y metodos Se recluto a los pacientes mayores de 30 anos con hipercolesterolemia familiar y mutacion confirmada en LDLR en un hospital de tercer nivel de Gran Canaria y se comparo la prevalencia de diabetes y otros datos clinicos entre los portadores de p.[Tyr400_Phe402del] y los de otras mutaciones en LDLR. Resultados El 76,4% de los 89 participantes era portador de p.[Tyr400_Phe402del]. En ese grupo la prevalencia de diabetes fue significativamente mas alta (25 vs. 4%, p = 0,045). Dichos casos tambien tenian mayor prevalencia de enfermedad cardiovascular y niveles mas altos de colesterol LDL y trigliceridos. No hubo diferencias en edad, peso, indice de masa corporal, cintura, edad de inicio y tiempo de tratamiento con estatinas. Sin embargo, si precisaban mas a menudo inhibidores de PCSK9 (51,5 vs. 24%, p = 0,027). Conclusiones La mutacion p.[Tyr400_Phe402del] se asocia a una elevada prevalencia de diabetes, no explicada por factores de riesgo clasicos, como la edad, la obesidad o el uso prolongado de estatinas.
Published: 2021

44. Rendimiento diagnóstico de la secuenciación de genes de hipercolesterolemia familiar en sujetos con hipercolesterolemia primaria

Author: Itziar Lamiquiz-Moneo, Belén Moreno-Franco, Fernando Civeira, Martín Laclaustra, César Martín, Lourdes Palacios, Rocío Mateo-Gallego, María Teresa Tejedor, Ana Cenarro, Gobierno de Aragón, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), and European Commission
Subjects: Apolipoprotein E, medicine.medical_specialty, Candidate gene, Apolipoprotein B, Hypercholesterolemia, FH prevalence, Disease, Familial hypercholesterolemia, 030204 cardiovascular system & hematology, Hyperlipoproteinemia Type II, PCSK9, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Humans, Medicine, Mutation in candidate genes, Allele, FH suspicion criteria, STAP1, LDLR | Lipoprotein(a), biology, business.industry, General Medicine, Lipoprotein(a), Middle Aged, medicine.disease, Spain, Mutation, biology.protein, lipids (amino acids, peptides, and proteins), Proprotein Convertase 9, business
Abstract: [EN] [Introduction and objectives] Our objective was to approximate the prevalence of mutations in candidate genes for familial hypercholesterolemia (FH) in a middle-aged Spanish population and to establish the predictive value of criteria for clinical suspicion in the detection of causative mutations., [EN] [Methods] Unrelated individuals aged ≥ 18 years from the Aragon Workers’ Health Study (AWHS) with high low-density lipoprotein cholesterol (LDL-C) and clinical suspicion of FH (participants with LDL-C concentrations above the 95th percentile, participants with premature cardiovascular disease and/or participants with high LDL-C [130 mg/dL] under statin therapy), assuming that any participant with FH exhibits at leats 1 trait, were selected and the LDLR, APOB, PCSK9, APOE, STAP1 and LDLRAP1 genes were sequenced by next generation sequencing technology., [EN] [Results] Of 5400 individuals from the AWHS, 4514 had complete data on lipid levels and lipid-lowering drugs, 255 participants (5.65%) met the criteria for suspicion of FH, 24 of them (9.41%) were diagnosed with hyperlipoproteinemia(a), and 16 (6.27% of those sequenced) were found to carry causative mutations in candidate genes: 12 participants carried 11 different pathogenic LDLR alleles and 4 participants carried 1 pathogenic mutation in PCSK9. LDL-C concentrations > 220 mg/dL and LDL-C > 130 mg/dL despite statin therapy showed the strongest association with the presence of mutations (P = .011)., [EN] [Conclusions] Our results show that the prevalence of FH in Spain is 1:282 and suggest that the combination of high untreated LDL-C and high levels of LDL-C despite statin therapy are the best predictors of a positive FH genetic test., [ES] [Introducción y objetivos] Nuestro objetivo fue aproximar la prevalencia de mutaciones en los genes candidatos de hipercolesterolemia familiar (HF) en una población española de mediana edad, y determinar el valor predictivo de los criterios clínicos de sospecha de HF en la detección de mutaciones causales., [ES] [Métodos] Se seleccionaron individuos mayores de 18 años no relacionados de la cohorte Estudio de Salud de los Trabajadores de Aragón (AWHS) con colesterol unido a lipoproteínas de baja densidad (cLDL) > percentil 95, con enfermedad cardiovascular prematura o con cLDL > 130 mg/dl con tratamiento hipolipemiante, asumiendo que al menos una de las características estará presente en todos los individuos con HF. En estos participantes se secuenciaron los genes LDLR, APOB, PCSK9, APOE, STAP1 y LDLRAP1 mediante secuenciación masiva., [ES] [Resultados] De 5.400 individuos del AWHS, 4.514 tenían datos lipídicos y registro farmacológico hipolipemiante completo, 255 participantes (5,65%) cumplían los criterios de sospecha de HF, 24 de ellos (9,41%) fueron diagnosticados de hiperlipoproteinemia(a) y 16 (6,27% de los secuenciados) presentaron alguna mutación causal en genes candidatos: 12 participantes portaban 11 alelos patogénicos diferentes en LDLR y 4 participantes portaban una mutación patogénica en PCSK9. Las concentraciones de cLDL > 220 mg/dl y el cLDL > 130 mg/dl a pesar del tratamiento con estatinas mostraron la mayor asociación con la presencia de mutación (p = 0,011)., [ES] [Conclusiones] Nuestros resultados muestran que la prevalencia española de HF es 1:282 y sugieren que una concentración de cLDL elevado, y niveles altos de cLDL a pesar de la terapia con estatinas son los mejores predictores para un diagnóstico genético positivo de HF., Este trabajo contó con el apoyo de subvenciones del Gobierno de Aragón, B14-7R, España y del Ministerio de Economía y Competitividad de España PI15/01983, PI18/01777 y CIBERCV. Estos proyectos son cofinanciados por el Instituto de Salud Carlos III y el Fondo Europeo de Desarrollo Regional (FEDER) de la Unión Europea «Una manera de hacer Europa».
Published: 2021

45. Leu22_Leu23 Duplication at the Signal Peptide of PCSK9 Promotes Intracellular Degradation of LDLr and Autosomal Dominant Hypercholesterolemia

Author: Asier Benito-Vicente, Kepa B. Uribe, Asier Larrea-Sebal, Lourdes Palacios, Ana Cenarro, Xabier Calle, Unai Galicia-Garcia, Shifa Jebari-Benslaiman, Rosa M. Sánchez-Hernández, Marianne Stef, Gilles Lambert, Fernando Civeira, Cesar Martín, Eusko Jaurlaritza, Instituto de Salud Carlos III, Fundación Biofísica Bizkaia, and Universidad del País Vasco
Subjects: Hyperlipoproteinemia Type II, Leucine repetition, Cholesterol, Metabolism, Receptors, LDL, Leucine, Lipoproteins, Hypercholesterolemia, Humans, Cholesterol, LDL, Proprotein Convertase 9, Protein Sorting Signals, Cardiology and Cardiovascular Medicine
Abstract: [Background] PCSK9 (Proprotein convertase subtilisin/kexin type 9) regulates LDL-C (low-density lipoprotein cholesterol) metabolism by targeting LDLr (LDL receptor) for lysosomal degradation. PCSK9 gain-of-function variants cause autosomal dominant hypercholesterolemia by reducing LDLr levels, the D374Y variant being the most severe, while loss-of-function variants are associated with low LDL-C levels. Gain-of-function and loss-of-function activities have also been attributed to variants occurring in the PCSK9 signal peptide. Among them, L11 is a very rare PCSK9 variant that seems to increase LDL-C values in a moderate way causing mild hypercholesterolemia., [Methods] Using molecular biology and biophysics methodologies, activities of L8 and L11 variants, both located in the leucine repetition stretch of the signal peptide, have been extensively characterized in vitro., [Results] L8 variant is not associated with increased LDLr activity, whereas L11 activity is increased by ≈20% compared with wt PCSK9. The results suggest that the L11 variant reduces LDLr levels intracellularly by a process resulting from impaired cleavage of the signal peptide. This would lead to less efficient LDLr transport to the cell membrane and promote LDLr intracellular degradation., [Conclusions] Deletion of a leucine in the signal peptide in L8 variant does not affect PCSK9 activity, whereas the leucine duplication in the L11 variant enhances LDLr intracellular degradation. These findings highlight the importance of deep in vitro characterization of PCSK9 genetic variants to determine pathogenicity and improve clinical diagnosis and therapy of inherited familial hypercholesterolemia disease., This work was supported by the Basque Government (Grupos Consolidados IT-1264-19) and Instituto de Salud Carlos III: CIBERCV and FIS PI19/0069. U. Galicia-Garcia was supported by Fundación Biofísica Bizkaia. A. Benito-Vicente was supported by Programa de especialización de Personal Investigador Doctor en la UPV/EHU (2019) 2019-2020. S. Jebari-Benslaiman and A. Larrea-Sebal were supported by a grant PIF (2017–2018) and (2019-2020), Gobierno Vasco, respectively. A.L-S was partially supported by Fundación Biofísica Bizkaia.
Published: 2022

46. Disbetalipoproteinemia y otras alteraciones relacionadas con la apolipoproteína E

Author: I. Gracia-Rubio, Fernando Civeira, Ana Cenarro, and Ana M. Bea
Subjects: Apolipoprotein E, medicine.medical_specialty, Very low-density lipoprotein, Apolipoprotein B, 030204 cardiovascular system & hematology, Atheromatosis, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, medicine, Pharmacology (medical), 030212 general & internal medicine, Fenofibrate, biology, business.industry, Cholesterol, nutritional and metabolic diseases, Endocrinology, chemistry, biology.protein, lipids (amino acids, peptides, and proteins), Cardiology and Cardiovascular Medicine, business, medicine.drug, Lipoprotein, Chylomicron
Abstract: Dysbetalipoproteinaemia (or type III hyperlipoproteinaemia) is a severe mixed hyperlipidaemia resulting from the accumulation of remnant chylomicron and VLDL particles in plasma, also called β-VLDL. It is caused by a defect in the recognition by hepatic LDL and lipoprotein receptor-related protein (LRP) of β-VLDL. Mutations in the APOE gene, especially in subjects homozygous for the ɛ2/ɛ2 allele, are responsible for this lack of receptor recognition. Dysbetalipoproteinaemia represents 2-5% of the mixed dyslipidaemias seen in Lipid Units, is highly atherogenic and predisposes to diffuse atheromatosis, either coronary, peripheral vascular, or carotid, so early diagnosis and treatment is necessary. The presence of hypertriglyceridaemia, with non-HDL cholesterol/apolipoprotein B ratios>1.43 (in mg/dL) followed by APOE genotyping is the method of choice in the diagnosis of dysbetalipoproteinaemia. It is a dyslipidaemia that responds well to hygienic-dietary treatment, although the combination of statin and fenofibrate is often necessary to achieve optimal control.
Published: 2021

47. Carga de enfermedad. Cálculo del riesgo cardiovascular y objetivos terapéuticos

Author: Estíbaliz Jarauta, Victoria Marco-Benedí, Fernando Civeira, and Martín Laclaustra
Subjects: medicine.medical_specialty, business.industry, Intensive treatment, Disease, Arteriosclerosis, 030204 cardiovascular system & hematology, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, Ezetimibe, Internal medicine, Maximum tolerated dose, Cohort, medicine, Pharmacology (medical), Lifetime risk, 030212 general & internal medicine, Statin therapy, Cardiology and Cardiovascular Medicine, business, medicine.drug
Abstract: Therapeutic intervention should be determined by the risk of developing atheromatous cardiovascular disease (CVD). The higher the risk, the more intense the action should be. This is the reason for the stratification of patient risk. In primary prevention, the two main guidelines used, the American Heart Association and the American College of Cardiology (ACC/AHA) use the Pooled cohort equations (PCE) and the guidelines of the European societies use the SCORE tables. The PCE calculates the risk of fatal and non-fatal CVD, and the SCORE calculates risk of fatal CVD only. In young people, it is useful to consider the lifetime risk calculation. The Spanish Society of Arteriosclerosis (SEA) recommends the SCORE system in Spain. SCORE and PCE calculate the risk for people up to 70 and 75 years of age. Prediction and potentials are available for 80 years of age and above, with the data available being much more scarce. Risk stratification in secondary prevention may be useful to identify the subgroup of patients who may benefit from more intensive treatment. Imaging tests, especially coronary calcium scans and vascular ultrasound, can help to better the profile risk. European guidelines identify LDL cholesterol as a therapeutic target. They recommend initiating treatment with statins, and increasing dose and potency until targets are achieved, and then to treatment with potent statins at a maximum tolerated dose, and ezetimibe if targets are not achieved. As a third step, PCSK9 inhibitors are indicated. They set very ambitious targets, as low as 40 mg/dL in those subjects with recurrences before two years of CVD despite high-intensity statin therapy, and below 55 mg/dL for all very high-risk subjects.
Published: 2021

48. Triglyceride Metabolism Modifies Lipoprotein(a) Plasma Concentration

Author: Maria Ramos-Cáceres, Itziar Lamiquiz-Moneo, Ana Cenarro, Pilar Calmarza, Victoria Marco-Benedí, Ana M Bea, Rocio Mateo-Gallego, Jose Puzo, Jose M Ordovas, Fernando Civeira, and Martin Laclaustra
Subjects: Apolipoprotein E2, Endocrinology, Diabetes and Metabolism, Biochemistry (medical), Clinical Biochemistry, Lipoproteins, VLDL, Nutrition Surveys, Biochemistry, Endocrinology, Apolipoproteins E, Cross-Sectional Studies, Humans, Cardiology and Cardiovascular Medicine, Triglycerides, Apolipoproteins B, Lipoprotein(a)
Abstract: Background Lipoprotein(a) (Lp(a)) is a significant cardiovascular risk factor. Knowing the mechanisms that regulate its concentration can facilitate the development of Lp(a)-lowering drugs. This study analyzes the relationship between triglycerides (TGs) and Lp(a) concentrations, cross-sectionally and longitudinally, and the influence of the number and composition of TG-rich lipoproteins, and the APOE genotype. Methods Data from Aragon Workers Health Study (AWHS) (n = 5467), National Health and Nutrition Examination Survey III phase 2 (n = 3860), and Hospital Universitario Miguel Servet (HUMS) (n = 2079) were used for cross-sectional TG and Lp(a) relationship. Lp(a) intrasubject variation was studied in AWHS participants and HUMS patients with repeated measurements. TG-rich lipoproteins were quantified by nuclear magnetic resonance in a subsample from AWHS. Apolipoproteins B and E were quantified by Luminex in very low-density lipoprotein (VLDL) isolated by ultracentrifugation, from HUMS samples. APOE genotyping was carried in AWHS and HUMS participants. Regression models adjusted for age and sex were used to study the association. Results The 3 studies showed an inverse relationship between TG and Lp(a). Increased VLDL number, size, and TG content were associated with significantly lower Lp(a). There was an inverse association between the apoE concentration in VLDL and Lp(a). No significant association was observed for apolipoprotein (apo)B. Subjects carrying the apoE2/E2 genotype had significantly lower levels of Lp(a). Conclusion Our results show an inverse relationship Lp(a)-TG. Subjects with larger VLDL size have lower Lp(a), and lower values of Lp(a) were present in patients with apoE-rich VLDL and apoE2/E2 subjects. Our results suggest that bigger VLDLs and VLDLs enriched in apoE are inversely involved in Lp(a) plasma concentration.
Published: 2022

49. Maternally inherited hypercholesterolemia does not modify the cardiovascular phenotype in familial hypercholesterolemia

Author: Núria Plana, Ana M. Bea, Martín Laclaustra, Ángel Brea, Rosa M. Sánchez-Hernández, Victoria Marco-Benedí, Manuel Suárez-Tembra, Fernando Civeira, and Xavier Pintó
Subjects: Adult, Male, 0301 basic medicine, medicine.medical_specialty, Hypercholesterolemia, Familial hypercholesterolemia, Disease, 030204 cardiovascular system & hematology, Hyperlipoproteinemia Type II, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Diabetes mellitus, medicine, Humans, Pregnancy, business.industry, Maternal effect, Cholesterol, LDL, medicine.disease, Obesity, Cross-Sectional Studies, Phenotype, 030104 developmental biology, Spain, Female, Maternal Inheritance, Age of onset, Cardiology and Cardiovascular Medicine, business, Dyslipidemia
Abstract: Background and aims Familial hypercholesterolemia (FH) is a codominant autosomal disease characterized by a high risk of cardiovascular disease when not in lipid-lowering treatment. However, there is a large variability in the clinical presentation in heterozygous subjects (HeFH). Maternal hypercholesterolemia has been proposed as a cardiometabolic risk factor later in life. Whether this phenotype variability depends on the mother or father origin of hypercholesterolemia is unknown. The objective of this study was to analyze potential differences in anthropometry, superficial lipid deposits, comorbidities, and lipid concentrations depending on the parental origin of hypercholesterolemia within a large group of HeFH. Methods This is a cross-sectional observational, multicenter, nation-wide study in Spain. We recruited adults with HeFH to study clinical differences according to the parental origin. Data on HeFH patients were obtained from the Dyslipidemia Registry of the Spanish Atherosclerosis Society. Results HeFH patients were grouped in 1231 HeFH-mother-offspring aged 45.7 (16.3) years and 1174 HeFH-father-offspring aged 44.8 (16.7) years. We did not find any difference in lipid parameters (total cholesterol, triglycerides, LDLc, HDLc, and Lp(a)), nor in the comorbidities studied (cardiovascular disease prevalence, age of onset of cardiovascular disease, obesity, diabetes, and hypertension) between groups. Lipid-lowering treatment did not differ between groups. The prevalence of comorbidities did not show differences when they were studied by age groups. Conclusions Our research with a large group of subjects with HeFH shows that a potential maternal effect is not relevant in FH. However, due to the size of our sample, potential differences between genders cannot be completely ruled out. This implies that severe maternal hypercholesterolemia during pregnancy is not associated with additional risk in the FH affected offspring.
Published: 2021

50. Glycerol kinase deficiency in adults: Description of 4 novel cases, systematic review and development of a clinical diagnostic score

Author: Ana M. Bea, Jacinto Fernández-Pardo, Itziar Lamiquiz-Moneo, Estíbaliz Jarauta, Victoria Marco-Benedí, C. López-Ariño, Rocío Mateo-Gallego, Fernando Civeira, Ana Cenarro, and Lia Ferraro
Subjects: Adult, Male, 0301 basic medicine, medicine.medical_specialty, Lipoproteins, 030204 cardiovascular system & hematology, Lipoprotein particle, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Glycerol Kinase, Diabetes mellitus, Internal medicine, medicine, Humans, Triglycerides, Hypertriglyceridemia, biology, business.industry, Cholesterol, Genetic disorder, Glycerol kinase deficiency, medicine.disease, Clinical Practice, Phenotype, 030104 developmental biology, chemistry, Hyperglycerolemia, biology.protein, Cardiology and Cardiovascular Medicine, business
Abstract: Background and aims Glycerol kinase deficiency (GKD) is a rare genetic disorder characterized by hyperglycerolemia and glyceroluria, which could be misdiagnosed as a moderate to severe hypertriglyceridemia (HTG). We aimed to describe four novel cases of GKD, to complete a systematic review of all cases of isolated GKD published so far, and to develop a suspicion clinical diagnostic score for GKD. Methods We reported four cases with suspicion of GKD and compared their phenotype with 584 males with triglycerides (TG) > 300 mg/dL, selected as control group (HTG non-GKD). The GK gene was sequenced in all cases. Lipoprotein particle concentrations were measured in all cases with GKD. The systematic review involved a PubMed, Cochrane and Scopus databases search to identify anthropometric and biochemical characteristics of all described cases with GKD. Results The systematic review retrieved a total of 15 articles involving 39 subjects with GKD. GKD cases reported a history of high TG levels resistant to lipid-lowering therapy. Compared to GKD subjects (n = 43), HTG non-GKD subjects (n = 584) showed significantly higher BMI, total cholesterol, non-HDL cholesterol and gamma-glutamyltransferase, significantly lower HDL cholesterol and TG, and higher prevalence of diabetes. The proposed diagnostic score was significantly higher in GKD than in HTG non-GKD subjects. Conclusions This is the first systematic review that compiles all GKD cases reported to date including 4 novel cases, and examine the differential GKD phenotype compared to other types of HTG. The proposed score would have a broad utility in clinical practice to avoid unwarranted lipid lowering treatment in GKD patients.
Published: 2020

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