Evaluation of lipoprotein(a) in the prevention and management of atherosclerotic cardiovascular disease: A survey among the Lipid Clinics Network

The Lipid Clinics Network (LCN) project is a network promoted by the European Atherosclerosis Society (EAS) to create European-wide standards for diagnosis, management, and treatment of patients affected by lipid metabolism disorders, based on the 2019 ESC/EAS guidelines on management of dyslipidemias and the following EAS updates and consensus statements [,]. The LCN provides not only an infrastructure for online educational activities and training within all members via EAS digital platform but also for local webinars and global surveys to identify and address gaps in knowledge and needs by exchange of knowledge and best practice (https://eas-society.org/collaborations-outreach/lipid-clinic-network/). At December 14, 2022, the Lipid Clinics Network account for about 290 lipid clinics distributed in 34 countries. In each country, an expert national lipidologist (National Coordinator) locally selected other national lipid clinics to join the Network.

The structure and spread of the established LCN make possible to explore the different approaches in the management of patients with dyslipidaemias and to compare experiences in the different national territories. One of the topics that appeared to be of interest to the participants in the network was lipoprotein(a) [Lp(a)] and its role in determining the cardiovascular risk.

So far, evidence from literature emphasizes that Lp(a) is one of the strongest genetically determined risk factors for cardiovascular disease (CVD) []. Besides an LDL-like particle, it contains an additional (apo)lipoprotein that is called apolipoprotein(a) [apo(a)], which shows a high homology with plasminogen, albeit devoid of any plasminogen-like activity []. Plasma apolipoprotein(a) [apo(a)] shows considerable size heterogeneity, existing as discrete glycoprotein isoform variants containing from less than 17 to greater than 30 tandemly repeated kringle units, resulting in a range in apparent molecular mass from approximately 400 to 800 kDa, and therefore in a high heterogeneity of serum Lp(a) particles []. After more than 50 years of research, however, the physiological function of Lp(a) is still unexplained []. Probably also for this reason, as well as the lack of standardised measurements and lab reports, the routine use of the Lp(a) measurement is still scarce [].

Therefore, an online survey for the “Evaluation of Lipoprotein(a) in European Lipid Clinics” was conducted to understand how widely lipoprotein(a) is routinely evaluated within the European lipid clinics, and the criteria used by the clinics to determine whether or not to test for Lp(a) and the practical factors considered in the decision to test for Lp(a), in order to gather useful information to determine resource, process, infrastructure and funding requirements for Lp(a) evaluation to become a standard practice also in centres where its evaluation is not available and further investigate the impact and benefit of identifying patients with high Lp(a) levels.

In 2022, the EAS decided to take advantage of the LCN structured Network to conduct an online survey on Lp(a) and its role in determining the cardiovascular risk. A total of 226 LCN members of 27 countries have been invited to join the survey and 151 of them accepted and completed the questionnaire from May 2022 to September 2022. The survey included 20 questions in English, most of which involved a multiple response (Supplementary materials). The respondents were given a list of possible options, but they were free to respond in their own words if the provided options did not adequately describe the situation in their local clinical practice.

The questionnaire was divided into three primary areas of inquiry.

• -
  background and clinical setting information of clinicians;
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  specific questions for doctors who claimed not to measure Lp(a) in the clinical practice, in order to understand what were the reasons or clinical barriers for not ordering the Lp(a) test routinely;
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  specific questions for doctors who claimed to measure Lp(a) in the clinical practice, to further investigate the approach for the management of patients at higher CVD risk in the clinical setting.

The physicians were informed about the questionnaire prior to participating and the participation was voluntary. Consent was implied on the return of a completed questionnaire. The estimate time for survey completion was 10 min.

All the answers have been handled anonymously before analysis. Results were summarized using frequencies and percentages. Stratified analyses were conducted base on clinicians clinical setting or specialty. Statistical analyses were performed using the Statistical Analysis System Software (version 9.4; SAS Institute, Cary, NC, USA).

This survey included a total of 151 centres clinicians, most of which declared to practice mainly in the university hospital (79%), and about 70% of them were cardiologists or lipidologists (Table 1). Geographical origin of centres participating in the survey is shown in Supplementary Fig. 1.

According to the respondents' personal experiences, the proportion of clinicians who routinely measure Lp(a) in clinical practice was 75.5% (Fig. 1), with no marked variation according to the different clinical setting (63.6% general hospital; 73.3% other specialised hospital; 75.0% private practice; 77.3% university hospital). The stratified analysis by countries is reported in Supplementary Table 1, while the stratified analysis by Eastern and Western European countries is reported in Supplementary Fig. 2.

Among clinicians who do not measure Lp(a) in their clinical practice (N = 37), the most common reasons for not ordering the Lp(a) test were the lack of reimbursement or of treatment options for elevated Lp(a), the non-availability of Lp(a) test, and the high cost of performing the laboratory test (Fig. 2A). Among them, the availability of therapies targeting this lipoprotein would result in a greater propensity of clinicians to start testing Lp(a) (Fig. 2B).

Among those (N = 114) declared to routinely measure Lp(a), most frequently, the Lp(a) measurement is required to further stratify patients' cardiovascular risk (Fig. 3). Regarding the type of patients, they considered eligible to Lp(a) test (Fig. 4), 96 (84.2%) reported they would measure Lp(a) in case of diagnosis of familial hypercholesterolemia and 90 (78.9%) in patients with recurrent CV events despite LDL-C lowering; finally, 78 (68.4%) declared they would measure Lp(a) at least once in each adult person's lifetime.

Despite the reported routine measure of Lp(a), only 42.1% of those clinicians reported that almost all (80–100%) of patients in their clinic have Lp(a) measured. This answer was provided by 26.7% of endocrinologists, 31.3% of cardiologists, and 52.1% of lipidologists. Considering the type of patients (Supplementary Table 2), 54.4% of clinicians reported that almost all of patients with prior myocardial infarction have Lp(a) measured, 74.6% reported that almost all of patients with familial hypercholesterolemia have Lp(a) measured, while 43.0% reported that almost all of patients with prior stroke have Lp(a) measured.

Half of clinicians who routinely measure Lp(a) in clinical practice recognized in 50 mg/dL (approx. 110 nmol/L) the threshold for increased cardiovascular risk due to elevated Lp(a) level (Fig. 4), and the majority of them declared that in case of elevated Lp(a), firstly they intensify lipid-lowering treatment. Almost all clinicians (96.5%) reported that they discuss the Lp(a) test result with the patient, explain the clinical consequences of elevated Lp(a), and 85% recommend Lp(a) testing in family members.

To our knowledge, this is the first international survey to address the use of Lp(a) measurement in clinical practice in more than 150 specialised lipid clinics distributed throughout the European territory, investigating its importance and perception by physicians, hurdles, and potential for its implementation. In this setting, 75.5% of clinicians reported to routinely measure Lp(a) in clinical practice. Our responders showed also to be aware of the potential of Lp(a) measurement for CV risk stratification, and of the importance of familial screening in case of high Lp(a) levels. Patients who are recommended for testing are those at increased CV risk, such as those with FH, those with ACS or heart attack, but only 68% of the participants answered that they would measure Lp(a) at least once in each adult person's lifetime.

Indeed, a role for Lp(a) in promoting atherosclerosis and increasing cardiovascular risk has been suggested several years ago [], but has only been consolidated in recent years []. The growing importance of this lipoprotein has been stated by the recently published American Heart Association (AHA) statement []. Recently the EAS consensus has highlighted the available evidence for elevated Lp(a) concentration as a causal risk factor for atherosclerotic cardiovascular disease (ASCVD), irrespective of gender and ethnicity, as well as for aortic valve stenosis, and provides practical guidance on testing and treating high Lp(a) levels and on how to asses Lp(a) contribution to ASCVD [].

Measurement of Lp(a) is a routine that guidelines recommend at least once in a lifetime [], also due to the good stability of this parameter in adulthood []. Although it has not yet become part of normal clinical activities widely, this practice has several potentials. First of all, the Lp(a) assay can be useful in cardiovascular risk stratification. Mendelian randomization studies have consistently demonstrated that lifelong exposure to higher Lp(a) levels is strongly and causally associated with an increased risk of ASCVD [,]. The Copenhagen Heart Study showed that patients with higher Lp(a) levels have increased risk of myocardial infarction []. The EPIC-Norfolk demonstrated that patients with high Lp(a) levels have two-fold increase in CVD []. Lp(a) values has been shown to predict CVD outcomes and improve CVD risk prediction both in intermediate risk category [], and in patients at higher CV risk as the ones affected by familial hypercholesterolemia (FH) patients []. Therefore, individuals with higher Lp(a) levels present an additional risk factor, independent of other CV risk factors, that makes them eligible for a more intensive lipid-lowering intervention, also given the current unavailability of drugs directed specifically against Lp(a) []. Moreover, elevated Lp(a) is predominantly a monogenic cardiovascular risk determinant, with 70–90% of inter-individual heterogeneity in levels being genetically determined []. Given the strong gene determinism of Lp(a) plasma levels, the identification of a subject with high Lp(a) would allow to investigate the presence of this risk factor in relatives of the index case, following the typical model of the cascade screening proposed for FH [,].

In our survey, however, the percentage of clinics measuring Lp(a), considering the specialised setting, should be considered far from being optimal [], confirming that measurement of Lp(a) remains an underused practice, suggesting that the implementation of Lp(a) measurement in general practice will be even more discouraging. Data quantifying the use of Lp(a) measurement in different national contexts are scanty. In many national and international surveys, such as the SANTORINI study (AL Catapano and K Ray, personal communication) or the EUROASPIRE V survey [], Lp(a) was very seldom measured, or not measured at all. From our survey, three main reasons emerged.

First, the test is often not reimbursed and therefore poorly recommended by clinicians. Indeed, despite the evidence collected till now, many payers have not yet included Lp(a) in the traditional lipid panel for cardiovascular risk assessment. A recent review, however, clearly showed that the cost for Lp(a) determination is comparable to the standard lipid panel that includes estimates of other lipoprotein subfractions (even lower if compared to the genetic test for FH diagnosis). Moreover, considering the overall economic burden of CVD, the test appears to be cost-effective [].

Second, the challenges in the standardization of Lp(a) measurement (the units is only an example of this) have somehow discouraged the use of measured Lp(a) levels in the context of CVD risk. The EAS consensus recommends the use of a robust method with antibodies apo(a) isoform-insensitive, to avoid the interference of the kringle IV2 repeats. Much more efforts are needed to implement a standardized Lp(a) measurement worldwide.

Third, the absence of specific and effective Lp(a) lowering therapy leads the clinician to consider Lp(a) measurement to be not very relevant. However, in addition to the above benefits, it is important to disseminate the concept that the increased risk resulting from high Lp(a) levels can be counteracted with more intensive interventions on modifiable risk factors.

In conclusion, our survey shows that 3 out of 4 clinicians working in the lipid clinics state that Lp(a) value among is included in their routine measurements. They showed to be fairly aware about the threshold for higher CV risk, about the potential interventions, and the cascade screening in family. However, it must be considered that this result is partly dependent on the specialist setting within which the survey was conducted, suggesting that the generalisation of the results is not warranted. Nevertheless, this survey allowed to obtain a picture of how different European clinics approach Lp(a) evaluation as part of cardiovascular risk assessment, shedding light on current clinical practice in specializes Lipid clinics included in the Network. These results warrant for a great deal of effort from scientific societies to support the decisions of health policy makers and to educate health personnel, as well as to raise awareness among the general population. An important role may be played by the Lipid Clinics Network, with the aim of facilitating interaction and education, and advancing the work of clinical lipidologists, enabling them to exchange clinical experience in patient management and approaches to barriers to sub-optimal patient care.

A.L.C., L.T, M.B., and K.K.R. were responsible for the study concept and design. M.G. and E.O. were responsible for data collection. E.O. and M.C. provided methodological and statistical knowledge and performed the analysis. A.L.C., L.T, M.B., and K.K.R. contributed to the interpretation of the results. E.O., M.G., and M.C. wrote the article. A.L.C., L.T, M.B., and K.K.R. critically revised for important intellectual content and approved the final article.

The survey is an initiative of the European Atherosclerosis Society within the Lipid Clinic Network, supported by an unconditional research grant from Novartis.

Alaa ABDELRAZIK (University Hospital of North Midland, United Kingdom); Alberto MELLO E SILVA (Sociedade Portuguesa de Aterosclerose, Portugal); Alexander VONBANK (VIVIT Institute, Austria); Alexandros D TSELEPIS (Dept of Chemistry, Atherothrombosis Research Center, University of Ioannina, Greece); Alper SONMEZ (Department of Endocrinology and Metabolism, Ankara Guven Hospital, Turkey); Angelina PASSARO (Department of Translational Medicine, University of Ferrara & Center for the Study and Treatment of Metabolic Diseases, Atherosclerosis, and Clinical Nutrition, University Hospital of Ferrara Arcispedale Sant’Anna, Italy); Anja VOGT (Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Germany); Ann MERTENS (Clinical and Experimental Endocrinology, KU Leuven, Leuven, Belgium); Ann VERHAEGEN (Antwerp University Hospital, Belgium); Arman S POSTADZHIYAN (Medical University of Sofia, Saint Anna University Hospital, Departement of Cardiology, Bulgaria); BAHADIR KIRILMAZ (Canakkale Onsekiz Mart University, Medical Faculty Cardiology Dept, Turkey); Baris GUNGOR (University of Health Sciences Dr. Siyami Ersek Hospital, Turkey); Berit S HEDEGAARD (Aalborg University, Denmark); Bertrand CARIOU (Nantes Université, CHU NANTES, CNRS, INSERM, l'institut du thorax, Nantes, France); Britta OTTE (Universitätsklinikum Münster, Lipidambulanz, Germany); Buğra ÖZKAN (Mersin University, Turkey); Christ BERGE (Dept. of cardiology, Haukeland. Unversity Hopsital, Norway); Christoph F EBENBICHLER (Department for Internal Medicine I, Medical University Innsbruck, Austria); Christoph J BINDER (Medical University of Vienna, Austria); Christoph OLIVIER (Department of Cardiology and Angiology, University Heart Center Freiburg-Bad Krozingen, Faculty of Medicine, University of Freiburg, Germany); Conrad AZZOPARDI (Mater Dei Hospital, Malta); Cristina SOLER (Lipid Unit, Hospital de Sta Caterina, Spain); Dan GAITA (Universitatea de Medicina si Farmacie Victor Babes din Timisoara & Clinica de Cardiologie, Institutul de Boli Cardiovasculare Timisoara, Romania); Daniel WEGHUBER (Department of Pediatrics, Paracelsus Medical University, Austria); Dilek URAL (Koç University School of Medicine Department of Cardiology, Turkey); Diogo CRUZ (Hospital de Cascais - Dr.José de Almeida, Portugal); Dragos VINEREANU (University of Medicine and Pharmacy "Carol Davila", University and Emergency Hospital, Bucharest, Romania); Elena D PENCU (Grand Hôpital de Charleroi GHDC, Belgium); Emil HAGSTRÖM (Dept of medical sciences, Uppsala University, Sweden); Erik B SCHMIDT (Aalborg University, Denmark); Erik S STROES (Dept of vascular medicine, AmsterdamUMC, The Netherlands); Evangelos LIBEROPOULOS (1st Department of Propedeutic Medicine, School of Medicine, National and Kapodistrian University of Athens, General Hospital of Athens Laiko, Greece); Fabian DEMEURE (CHU UCL Namur - Site Godinne, Belgium); Fabio FIMIANI (Azienda Ospedaliera di Rilievo Nazionale AORN Dei Colli, “V.Monaldi”, Unit of Inherited and Rare Cardiovascular Diseases, Italy ); Fabio PELLEGATTA (Center for the Study of Atherosclerosis. Bassini Hospital. Cinisello Balsamo, Italy); Fahri BAYRAM (Erciyes University, Turkey); Finn L HENRIKSEN (Department of Cardiology Odense University Hospital, Denmark); Florian HÖLLERL (1st Medical Department, Landstrasse Clinic, Vienna Health Association, Austria); Francesco CIPOLLONE (Clinica Medica Institute of "SS. Annunziata" Hospital, Department of Medicine and Aging Sciences, “G. d'Annunzio” University, Italy); Francisco ARAÚJO (Hospital Lusíadas, Portugal); Franck BOCCARA (Sorbonne Université, Groupe de Recherche Clinique number 22, C2MV—Complications Cardiovasculaires et Métaboliques chez les Patients Vivant avec le Virus de l’Immunodéficience Humaine; Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche S 938; Centre de Recherche Saint-Antoine, Institut Hospital Universitaire de Cardio-métabolisme et Nutrition Cardiologie; Hôpital Saint Antoine Assistance Publique–Hôpitaux de Paris, Paris, France); François PAILLARD (Cardiologie et Centre Clinico-Biologique des Lipides et Athérosclérose, CHU Rennes, France); Gabor SIMONYI (DBC St. Imre University Teaching Hospital, Metabolic Center, Lipid Center, Hungary); Gabriella IANNUZZO (Department of Clinical Medicine and Surgery. University of Naples Federico II, Italy); Giuseppe MANDRAFFINO (Department of Clinical and Experimental Medicine - Lipid Center, University of Messina, Italy); Graham BAYLY (Dept Clinical Biochemistry, University Hospitals Bristol, United Kingdom); Gustavs LATKOVSKIS (Institute of Cardiology and Regenerative Medicine, University of Latvia & Latvian Center of Cardiology, Pauls Stradins Clinical University Hospital & Faculty of Medicine, University of Latvia, Latvia); György PARAGH (Division of Metabolic Disorders, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary); Hana ROSOLOVA (Charles University Prague Medical Hospital in Pilsen, Czech Republic); Handrean SORAN (Central Manchester University Hospital NHS Foundation Trust, United Kingdom); Helle KANSTRUP (Department of cardiology, Aarhus University hospital, Denmark); Hermann TOPLAK (Department of Medicine, Division of Endocrinology and Diabetology, Medical University Graz, Austria); Hülya ÇIÇEKÇIOĞLU (ankara bilkent city hospital, Turkey); Inanc ARTAC (Department of Cardiology, Kafkas University Hospital, Faculty of Medicine, Turkey); Ioanna GOUNI-BERTHOLD (Center for Endocrinology, Diabetes and Preventive Medicine, University of Cologne, Faculty of Medicine and University Hospital Cologne, Germany); Irfan V DUZEN (Gaziantep University, Faculty of Medicine, Cardiology Department, Turkey); Isabel M PALMA (CHUPORTO - Centro Hospitalar Universitário do Porto, Portugal); Istvan REIBER (Szent Gyorgy University Teaching Hospital of Fejer County, Hungary); Iveta DZIVITE-KRISANE (Children’s University Hospital, Latvia); Jeanine E ROETERS VAN LENNEP (Department of Internal medicine, Erasmus MC University Medical Center, The Netherlands); Jean-Luc J BALLIGAND (Institut de Recherche Expérimentale et Clinique, Universite catholique de Louvain, Bruxelles); Joao C PORTO (CHUC, Portugal); João S DUARTE (Hospital Egas Moniz, Lisboa, Portugal); Johan DE SUTTER (AZ Maria Middelares Hospital Gent, Belgium); José LÓPEZ-MIRANDA (Lipid and Arteriosclerosis Unit. Department of Internal Medicine. Hospital Universitario Reina Sofia. IMIBIC. University of Cordoba. CiberOBN, Spain); Jose M MOSTAZA (Hospital La Paz-Carlos III, Spain); Jurgita PLISIENE (Lithuanian University of Health sciences, Lithuania); Kadir U MERT (Eskişehir Osmangazi University, Faculty of Medicine, Department of Cardiology, Turkey); Kirsten B HOLVEN (Department of Nutrition, University of Oslo and National Advisory unit on FH, Oslo University Hospital, Norway); Kjetil RETTERSTØL (The Lipid Clinic, Oslo University Hospital and Department of Nutrition, University of Oslo, Norway); Kristian K THOMSEN (University Hospital of South Denmark, Esbjerg, Denmark); Lale TOKGOZOGLU (Hacettepe University, Turkey); Laszlo BAJNOK (1st Department of Medicine, Medical School, University of Pecs, Hungary); Lia E BANG (Copenhagen University Hospital, Denmark); Liliana GRIGORE (IRCCS Multimedica, Italy); Lluís MASANA (Hospital Universitari Sant Joan. Universitat Rovira i Virgili. CIBERDEM. Reus, Spain); Loukianos S RALLIDIS (University General Hospital Attikon, Greece); Maciej BANACH (Department of Preventive Cardiology and Lipidology, Medical University of Lodz, Poland); Małgorzata WALUŚ-MIARKA (Jagiellonian University Medical College, Dept. Of Metabolic Diseases and Diabetology, Poland); Manuel CASTRO CABEZAS (Franciscus Gasthuis & Vlietland Rotterdam, The Netherlands); Marcello ARCA (Sapienza University of Rome, Italy); Margus VIIGIMAA (North Estonia Medical Centre, Tallinn University of Technology, Estonia); Martin P BOGSRUD (Unit for Cardiac and Cardiovascular Genetics, Oslo University Hospital, Norway); Matej MLINARIČ (Department of Endocrinology, Diabetes and Metabolism, University Children's Hospital, University Medical Centre Ljubljana, Slovenia); Matteo PIRRO (Section of Internal Medicine, Angiology and Arteriosclerosis Diseases, Italy); Maurizio AVERNA (Department PROMISE-University of Palermo & Istituto di Biofisica, Consiglio Nazionale delle Ricerche, Palermo, Italy); Meral KAYIKCIOGLU (Ege University Medical School Department of Cardiology, Turkey); Merete HEITMANN (Bispebjerg-Frederiksberg University Hospital, Denmark); Mette MOURIDSEN (Department of Cardiology, Herlev and Gentofte Hospital, University of Copenhagen, Denmark); Michal VRABLIK (3rd Department of Internal Medicine, General University Hospital and 1st Medical Faculty, Charles University, Prague, Czech Republic); Michel FARNIER (PEC2, University of Bourgogne Franche-Comté, France); Michel R LANGLOIS (Dept. Laboratory Medicine, AZ St.Jan Hospital, Belgium); Milad KHEDR (Department of Clinical Biochemistry and Metabolic Medicine, Royal Liverpool University Hospital, United Kingdom); Muge ILDIZLI DEMIRBAS (Kartal Kosuyolu Research and Training Hospital, Turkey); Myra TILNEY (Lipid Clinic, Mater Dei Hospital & Dept of Medicine, University of Malta Medical School, Malta); Nadia CITRONI (Internal Medicine, APSS Trento Hospital, Italy); Niels P RIKSEN (Dept. Of Internal Medicine, Radboud university medical center, The Netherlands); Nikolay M RUNEV (UMHAT Alexandrovska, Bulgaria); Nora KUPSTYTE-KRISTAPONE (Hospital of Lithuanian University of Health Sciences Kaunas Clinics, Lithuania); Olena MITCHENKO (NSC "Institute of Cardiology, Clinical and Regenerative Medicine of the NAMS of Ukraine", Ukraine); Oliver WEINGÄRTNER (Universitätsklinikum Jena, Department of Internal Medicine I, Germany); Oner OZDOGAN (University of Health Sciences, Izmir Faculty of Medicine, Tepecik Training and Research Hospital, Department of Cardiology, Turkey); Ovidio MUÑIZ-GRIJALVO (Hospital Virgen del Rocío, Spain); Ozcan BASARAN (Mugla Sitki Kocman University, Faculty of Medicine, Cardiology Department, Turkey); Pankaj GUPTA (University Hospitals of Leicester, United Kingdom); Paolo PARINI (Cardio Metabolic Unit, Karolinska Institutet, and Theme Inflammation and Ageing, Karolinska University Hospital Huddinge, Sweden); Patrizia SUPPRESSA (Department of Internal Medicine and rare disease Centre "C. Frugoni" University Hospital of Bari, Bari, Italy); Paul DOWNIE (Salisbury NHS Foundation trust, United Kingdom); Pavel JESINA (Metabolic Center General University Hospital, Czech Republic); Pavel KRAML (Dept.of Internal Medicine, Third Faculty of Medicine, Charles University and Královské Vinohrady University Hospital Prague, Czech Republic); Pawel BURCHARDT (Department of Cardiology, Cardiovascular Unit, J. Struś Hospital, Poznań & Department of Hypertension, Angiology and Internal Medicine, Poznan University of Medical Sciences, Poznań, Poland); Pedro VALDIVIELSO (Hospital VIRGEN DE LA VICTORIA, Spain); Pedro VON HAFE (Instituto Cuf, Portugal); Peter FASCHING (5th Med. Dept, Clinic Ottakring, Austria); Philippe MOULIN (Hospices civils de Lyon/INSERM/Université Lyon1, Hôpital Louis Pradel, Fédération d'endocrinologie, France); Quitéria RATO (Sociedade Portuguesa de Aterosclerose , Portugal); Reinhold INNERHOFER (Medical University Vienna, Austria); Renata CÍFKOVÁ (Center for Cardiovascular Prevention, Charles University in Prague, First Faculty of Medicine and Thomayer University Hospital, Prague, Czech Republic); Rene VALERO (Aix Marseille Univ, APHM, INSERM, INRAE, C2VN, University Hospital La Conception, Department of Nutrition, Metabolic Diseases and Endocrinology, France); Roberto SCICALI (Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy); Robin URBÁNEK (Internal medicine, Obezita-Ormiga s.r.o, Czech Republic); Roma KAVALIAUSKIENE (Klaipėda Seamen's Hospital, Lituania); Roman CIBULKA (Department of paramedic science, medical diagnostics studies and public health, Faculty of Health Care Studies, University of West Bohemia, Czech Republic); Sabina ZAMBON (Department of Medicine - DIMED, University of Padova, Italy); Sergio D'ADDATO (University of Bologna. IRCCS S.Orsola Bologna , Italy); Stanislav ZEMEK (Lipidova ambulance, Czech Republic); Stefano ROMEO (Gothenburg University, Sweden); Stephanie KÖNEMANN (Department of Internal Medicine B, University Medicine Greifswald, DZHK (German Centre for Cardiovascular Research), Germany); Susanne GREBER-PLATZER (Clinical Division of Pediatric Pulmonology, Allergology and Endocrinology, Department of Pediatrics and Adolescent Medicine, Medical University Vienna, Austria); Thomas STULNIG (Clinical Division of Endocrinology and Metabolism, Department of Medicine III, Medical University Vienna & Third Medical Department and Karl Landsteiner Institute for Metabolic Diseases and Nephrology, Clinic Hietzing, Vienna, Austria); Thomas MUHR (Dept of Cardiology, Linköping University Hospital, Sweden); Tina Z KHAN (Consultant Cardiologist, Royal Brompton and Harefield Hospitals Part of Guy’s and St Thomas' NHS Foundation Trust, United Kingdom); Tomas FREIBERGER (Centre of Cardiovascular Surgery and Transplantation, Brno & Medical Faculty, Masaryk University, Brno, Czech Republic); Tomáš ŠÁLEK (Metabolic Clinic, Tomas Bata Hospital, Zlín, Czech Republic); Tomas VASYLIUS (Republican Panevezys hospital, Dep. Of Cardiology, Lithuania); Ulrich LAUFS (Klinik und Poliklinik für Kardiologie, Universitätsklinikum Leipzig, Germany); Ulrike SCHATZ (University Hospital Carl Gustav Carus Dresden at the Technical University Dresden, Department of Internal Medicine III, Germany); Urh GROSELJ (UMC - University Children's Hospital Ljubljana; University of Ljubljana, Faculty of Medicine, Slovenia); Victoria MARCO-BENEDI (Hospital Universitario Miguel Servet, IISA, CIBERCV, Spain); Vincent MAHER (Advanced Lipid Management and Research ALMAR centre, Tallaght University Hospital, Ireland); Vladimír BLAHA (University Hospital Hradec Králové and Charles University, Faculty of Medicine in Hradec Králové, 3rd Department of Internal Medicine - Metabolism and Gerontology, Czech Republic); Vladimir SOSKA (Department of Clinical Biochemistry, St. Anne's University Hospital Brno; 2nd Clinic of Internal Medicine, Faculty of Medicine, Masaryk University Brno, Czech Republic); Volker JJ SCHETTLER (Centre of Nephrology Göttingen, Germany); Wolfgang REINHARDT (SUS Malmoe, Sweden); Xavier PINTÓ (Hospital Universitari de Bellvitge-Idibell-UB-CiberObn, Spain); Yoto YOTOV (Second Cardiology Clinic, University Hospital Sv. Marina, Medical University of Varna, Bulgaria); Zaneta PETRULIONIENE (Vilnius University Medical Faculty; Vilnius University Hospital Santaros klinikos, Lithuania); Željko REINER (Department for Metabolic Diseases, University Hospital Center Zagreb, Croatia).

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