Imperial College London

Christophe Stevens

Faculty of MedicineSchool of Public Health

Software Engineer/Data Manager
 
 
 
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Stadium HouseWhite City Campus

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Publications

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33 results found

Mulder JWCM, Tromp TR, Al-Khnifsawi M, Blom DJ, Chlebus K, Cuchel M, D'Erasmo L, Gallo A, Hovingh GK, Kim NT, Long J, Raal FJ, Schonck WAM, Soran H, Truong T-H, Boersma E, Roeters van Lennep JE, Homozygous Familial Hypercholesterolemia International Clinical Collaboratorset al., 2024, Sex Differences in Diagnosis, Treatment, and Cardiovascular Outcomes in Homozygous Familial Hypercholesterolemia., JAMA Cardiol, Vol: 9, Pages: 313-322

IMPORTANCE: Homozygous familial hypercholesterolemia (HoFH) is a rare genetic condition characterized by extremely increased low-density lipoprotein (LDL) cholesterol levels and premature atherosclerotic cardiovascular disease (ASCVD). Heterozygous familial hypercholesterolemia (HeFH) is more common than HoFH, and women with HeFH are diagnosed later and undertreated compared to men; it is unknown whether these sex differences also apply to HoFH. OBJECTIVE: To investigate sex differences in age at diagnosis, risk factors, lipid-lowering treatment, and ASCVD morbidity and mortality in patients with HoFH. DESIGN, SETTING, AND PARTICIPANTS: Sex-specific analyses for this retrospective cohort study were performed using data from the HoFH International Clinical Collaborators (HICC) registry, the largest global dataset of patients with HoFH, spanning 88 institutions across 38 countries. Patients with HoFH who were alive during or after 2010 were eligible for inclusion. Data entry occurred between February 2016 and December 2020. Data were analyzed from June 2022 to June 2023. MAIN OUTCOMES AND MEASURES: Comparison between women and men with HoFH regarding age at diagnosis, presence of risk factors, lipid-lowering treatment, prevalence, and onset and incidence of ASCVD morbidity (myocardial infarction [MI], aortic stenosis, and combined ASCVD outcomes) and mortality. RESULTS: Data from 389 women and 362 men with HoFH from 38 countries were included. Women and men had similar age at diagnosis (median [IQR], 13 [6-26] years vs 11 [5-27] years, respectively), untreated LDL cholesterol levels (mean [SD], 579 [203] vs 596 [186] mg/dL, respectively), and cardiovascular risk factor prevalence, except smoking (38 of 266 women [14.3%] vs 59 of 217 men [27.2%], respectively). Prevalence of MI was lower in women (31 of 389 [8.0%]) than men (59 of 362 [16.3%]), but age at first MI was similar (mean [SD], 39 [13] years in women vs 38 [13] years in men). Treated LDL cholesterol levels an

Journal article

Dharmayat KI, Vallejo-Vaz AJ, Stevens CAT, Brandts JM, Lyons ARM, Groselj U, Abifadel M, Aguilar-Salinas CA, Alhabib K, Alkhnifsawi M, Almahmeed W, Alnouri F, Alonso R, Al-Rasadi K, Ashavaid TF, Banach M, Béliard S, Binder C, Bourbon M, Chlebus K, Corral P, Cruz D, Descamps OS, Drogari E, Durst R, Ezhov MV, Genest J, Harada-Shiba M, Holven KB, Humphries SE, Khovidhunkit W, Lalic K, Laufs U, Liberopoulos E, Roeters van Lennep J, Lima-Martinez MM, Lin J, Maher V, März W, Miserez AR, Mitchenko O, Nawawi H, Panayiotou AG, Paragh G, Postadzhiyan A, Reda A, Reiner Ž, Reyes X, Sadiq F, Sahebkar A, Schunkert H, Shek AB, Stroes E, Su T-C, Subramaniam T, Susekov A, Vázquez Cárdenas A, Huong Truong T, Tselepis AD, Vohnout B, Wang L, Yamashita S, Al-Sarraf A, Al-Sayed N, Davletov K, Dwiputra B, Gaita D, Kayikcioglu M, Latkovskis G, Marais AD, Thushara Matthias A, Mirrakhimov E, Nordestgaard BG, Petrulioniene Z, Pojskic B, Sadoh W, Tilney M, Tomlinson B, Tybjærg-Hansen A, Viigimaa M, Catapano AL, Freiberger T, Hovingh GK, Mata P, Soran H, Raal F, Watts GF, Schreier L, Bañares V, Greber-Platzer S, Baumgartner-Kaut M, de Gier C, Dieplinger H, Höllerl F, Innerhofer R, Karall D, Lischka J, Ludvik B, Mäser M, Scholl-Bürgi S, Thajer A, Toplak H, Demeure F, Mertens A, Balligand J-L, Stephenne X, Sokal E, Petrov I, Goudev A, Nikolov F, Tisheva S, Yotov Y, Tzvetkov I, Hegele RA, Gaudet D, Brunham L, Ruel I, McCrindle B, Cuevas A, Perica D, Symeonides P, Trogkanis E, Kostis A, Ioannou A, Mouzarou A, Georgiou A, Stylianou A, Miltiadous G, Iacovides P, Deltas C, Vrablik M, Urbanova Z, Jesina P, Tichy L, Hyanek J, Dvorakova J, Cepova J, Sykora J, Buresova K, Pipek M, Pistkova E, Bartkova I, Sulakova A, Toukalkova L, Spenerova M, Maly J, Benn M, Bendary A, Elbahry A, Ferrières J, Ferrieres D, Peretti N, Bruckert E, Gallo A, Valero R, Mourre F, Aouchiche K, Reynaud R, Tounian P, Lemale J, Boccara F, Moulin P, Charrières S, Di Filippo M, Cariou B, Paillard F, Dourmap C, Pradignac A, Verges Bet al., 2024, Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study, The Lancet, Vol: 403, Pages: 55-66, ISSN: 0140-6736

BackgroundApproximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies.MethodsFor this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia.FindingsOf 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8–13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetica

Journal article

Lyons ARM, Stevens CAT, Dharmayat KI, Vallejo-Vaz DAJ, Ray KKet al., 2023, Overview of a collaborative global effort to address the burden of familial hypercholesterolaemia, Indian Heart Journal, ISSN: 0019-4832

This is an overview of the EAS Familial Hypercholesterolaemia (FH) Studies Collaboration (FHSC) global consortium and registry (established 2015), which broadly addresses the global burden of FH. Eighty-seven National Lead Investigators from 74 countries form this expanding global consortium, and this global registry currently includes pooled data on 70,000 participants from participating countries to facilitate FH surveillance. Published first results from this global registry concluded that FH is diagnosed late, and management of LDL-cholesterol falls below guideline recommendations, and therefore earlier detection of FH and wider use of combination therapy is required. Further FHSC studies will follow on updated data including new countries, participants and variables, and non-DNA genetic information, and on the remaining cohorts in the registry. FHSC cross-sectional collaborative global studies are expected to promote FH detection earlier in life to subsequently initiate early lipid lowering therapy to reduce lifelong exposure to cumulative LDL-cholesterol thus reducing cardiovascular disease risk.

Journal article

Dharmayat K, Stevens C, Elshorbagy A, Brandts J, Lyons A, Catapano A, Freiberger T, Hovingh GK, Mata P, Santos R, Soran H, Watts G, Raal F, Ray K, Vallejo-Vaz Aet al., 2023, APPROACHES TO LDL-C MANAGEMENT IN CHILDREN AND ADOLESCENTS WITH FAMILIAL HYPERCHOLESTEROLAEMIA: ANALYSIS ON OVER 3000 INDIVIDUALS RECEIVING LIPID-LOWERING MEDICATION IN THE FHSC REGISTRY, 91st Annual Meeting of the European-Atherosclerosis-Society (EAS), Publisher: ELSEVIER IRELAND LTD, ISSN: 0021-9150

Conference paper

Barkas F, Vallejo-Vaz A, Elshorbagy A, Stevens C, Lyons A, Dharmayat K, Brandts J, Catapano A, Freiberger T, Hovingh GK, Mata P, Raal F, Santos R, Soran H, Watts G, Ray Ket al., 2023, LIPOPROTEIN (A) AND ATHEROSCLEROTIC CARDIOVASCULAR DISEASE IN ADULTS WITH HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLAEMIA: A CROSS-SECTIONAL STUDY FROM THE EAS FAMILIAL HYPERCHOLESTEROLAEMIA STUDIES COLLABORATION (FHSC), 91st Annual Meeting of the European-Atherosclerosis-Society (EAS), Publisher: ELSEVIER IRELAND LTD, ISSN: 0021-9150

Conference paper

Dharmayat K, Vallejo-Vaz A, Stevens C, Elshorbagy A, Brandts J, Lyons A, Catapano A, Freiberger T, Hovingh GK, Mata P, Santos R, Soran H, Watts G, Raal F, Ray Ket al., 2023, HOW ARE CHILDREN AND ADOLESCENTS WITH FAMILIAL HYPERCHOLESTEROLAEMIA DETECTED GLOBALLY? ANALYSIS FROM THE FHSC REGISTRY ON OVER 11,800 PARTICIPANTS FROM 48 COUNTRIES, 91st Annual Meeting of the European-Atherosclerosis-Society (EAS), Publisher: ELSEVIER IRELAND LTD, ISSN: 0021-9150

Conference paper

Lyons A, Elshorbagy A, Vallejo-Vaz A, Stevens C, Dharmayat K, Brandts J, Catapano A, Freiberger T, Hovingh GK, Mata P, Raal F, Santos R, Soran H, Watts G, Ray Ket al., 2023, OBESITY AND STATIN USE MAY IMPACT THE PREVALENCE OF DIABETES IN FAMILIAL HYPERCHOLESTEROLAEMIA: A WORLDWIDE CROSS-SECTIONAL STUDY BY THE EAS FAMILIAL HYPERCHOLESTEROLAEMIA STUDIES COLLABORATION (FHSC), 91st Annual Meeting of the European-Atherosclerosis-Society (EAS), Publisher: ELSEVIER IRELAND LTD, ISSN: 0021-9150

Conference paper

Elshorbagy A, Vallejo-Vaz A, Barkas F, Stevens C, Lyons A, Dharmayat K, Brandts J, Catapano A, Freiberger T, Hovingh GK, Mata P, Raal F, Santos R, Soran H, Watts G, Ray Ket al., 2023, GLOBAL PREVALENCE OF OVERWEIGHT AND OBESITY AMONG PAEDIATRIC AND ADULT PATIENTS WITH HOMOZYGOUS OR HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLAEMIA, AND ASSOCIATION WITH CORONARY ARTERY DISEASE, 91st Annual Meeting of the European-Atherosclerosis-Society (EAS), Publisher: ELSEVIER IRELAND LTD, ISSN: 0021-9150

Conference paper

Stevens C, Sharabiani M, Chora J, Mahani A, Vallejo-Vaz A, Ray Ket al., 2023, MACHINE LEARNING IDENTIFICATION OF CARRIERS OF PATHOGENIC AND LIKELY PATHOGENIC VARIANTS LINKED TO FAMILIAL HYPERCHOLESTEROLAEMIA IN THE UK BIOBANK, 91st Annual Meeting of the European-Atherosclerosis-Society (EAS), Publisher: ELSEVIER IRELAND LTD, ISSN: 0021-9150

Conference paper

Konnov M, Stevens C, 2023, ASSOCIATION OF PARENTAL OBESITY AND BODY MASS INDEX IN CHILDREN OF PATIENTS WITH EARLY ISCHEMIC HEART DISEASE, 91st Annual Meeting of the European-Atherosclerosis-Society (EAS), Publisher: ELSEVIER IRELAND LTD, Pages: S91-S92, ISSN: 0021-9150

Conference paper

Stevens C, Mahani A, Ray K, Vallejo-Vaz A, Sharabiani Met al., 2023, ENSEMBLE MACHINE LEARNING FOR SCREENING CARDIOVASCULAR DISEASES IN ELECTRONIC HEALTH RECORDS, 91st Annual Meeting of the European-Atherosclerosis-Society (EAS), Publisher: ELSEVIER IRELAND LTD, Pages: S194-S194, ISSN: 0021-9150

Conference paper

Stevens C, Lyons A, Dharmayat K, Mahani A, Ray K, Vallejo-Vaz AJ, Taghavi Azar Sharabiani Met al., 2023, Ensemble machine learning methods in screening electronic health records: a scoping review, Digital Health, Vol: 9, Pages: 1-17, ISSN: 2055-2076

Background:Electronic Health Records (EHRs) provide the opportunity to identify undiagnosed individuals likely to have a given disease using Machine Learning (ML) techniques, and who could then benefit from more medical screening and case finding, reducing the number needed to screen with convenience and healthcare cost savings. Ensemble Machine Learning Models (EMLs) combining multiple prediction estimates into one, are often said to provide better predictive performances than non-ensemble models. Yet, to our knowledge, no literature review summarises the use and performances of different types of EMLs in the context of medical pre-screening. Method:We aimed to conduct a scoping review of the literature reporting the derivation of EMLs for screening of EHRs. We searched EMBASE and MEDLINE databases across all years applying a formal search strategy using terms related to medical screening, EHR and ML. Data were collected, analysed, and reported in accordance with the PRISMA scoping review guideline. Results:A total of 3,355 articles were retrieved, of which 145 articles met our inclusion criteria and were included in this study. EMLs were increasingly employed across several medical specialities and often outperformed non-ensemble approaches. EMLs with complex combination strategies and heterogeneous classifiers often outperformed other types of EMLs but were also less used. EML methodologies, processing steps and data sources were often not clearly described. Conclusions:Our work highlights the importance of deriving and comparing the performances of different types of EMLs when screening EHRs and underscores the need for more comprehensive reporting of ML methodologies employed in clinical research.

Journal article

Stevens C, Mahani A, Ray K, Vallejo-Vaz A, Taghavi Azar Sharabiani Met al., 2022, Use of ensemble machine learning in screening electronic health records: a scoping review, RSS International Conference 2022

Conference paper

Stevens CAT, Lyons ARM, Dharmayat KI, Brandts J, Vallejo-Vaz AJ, Daccord M, Ray KKet al., 2022, FindMyLipidClinic.com: A global Directory of lipid clinics and patient organisations to improve dyslipidemia care: FindMyLipidClinic.com, European Atherosclerosis Journal, Vol: 1, Pages: 37-40, ISSN: 2785-7115

Information available on lipid clinics and patient support and advocacy groups, such as location and services provided, is limited or unknown to patients with dyslipidaemia and their family members who may also be affected, and non-specialist clinicians, hindering accessibility to appropriate healthcare. To overcome this, the European Atherosclerosis Society Familial Hypercholesterolemia Study Collaboration (EAS FHSC) led by Imperial College London has, in collaboration with the European FH Patient Network (FH Europe), developed FindMyLipidClinic.com, a global Directory of lipid clinics and patient support groups in 29 languages. Since its launch in 2020, around 4,000 visitors have conducted 12,000 searches across 1,100 locations, which may have retrieved up to 124 lipid clinics and 29 patient groups currently listed in 39 and 28 countries, respectively. Clinics and patient organisations not currently listed are encouraged to join this directory, and it would also benefit further from collaborations with other existing directories able to contribute.

Journal article

Vallejo-Vaz A, Stevens C, Dharmayat K, Lyons A, Brandts J, Freiberger T, Hovingh GK, Kastelein JJ, Mata P, Raal FJ, Santos R, Soran H, Watts GF, Catapano AL, Ray Ket al., 2022, Identification, characteristics and management of adults with heterozygous Familial Hypercholesterolaemia in high and non-high income countries participating in the EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC), European Atherosclerosis Society Congress 2022, Publisher: Elsevier, Pages: 15-16, ISSN: 0021-9150

Conference paper

Stevens C, Konnov M, Sergienko V, 2022, Predictors of major adverse events of cardiovascular disease in individuals with early ischemic heart disease, European Atherosclerosis Society (EAS) Congress, Publisher: Elsevier, Pages: 261-262, ISSN: 0021-9150

Conference paper

Dharmayat KI, Vallejo-Vaz AJ, Stevens CA, Lyons AR, Catapano AL, Freiberger T, Hovingh GK, Mata P, Santos R, Soran H, Watts GF, Raal FJ, Ray KKet al., 2022, Global perspective of paediatric Familial Hypercholesterolaemia: Analysis from the EAS FHSC registry on over 11,200 children and adolescents with heterozygous Familial Hypercholesterolaemia from 44 countries, 90th European Atherosclerosis Society (EAS) Congress, Publisher: Elsevier, Pages: E13-E13, ISSN: 0021-9150

Conference paper

Tromp TR, Hartgers ML, Hovingh GK, Vallejo-Vaz AJ, Ray KK, Soran H, Freiberger T, Bertolini S, Harada-Shiba M, Blom DJ, Raal FJ, Cuchel Met al., 2022, Worldwide experience of homozygous familial hypercholesterolaemia: retrospective cohort study, The Lancet, Vol: 399, Pages: 719-728, ISSN: 0140-6736

Background:Homozygous familial hypercholesterolaemia (HoFH) is a rare inherited disorder resulting in extremely elevated low-density lipoprotein cholesterol levels and premature atherosclerotic cardiovascular disease (ASCVD). Current guidance about its management and prognosis stems from small studies, mostly from high-income countries. The objective of this study was to assess the clinical and genetic characteristics, as well as the impact, of current practice on health outcomes of HoFH patients globally.Methods:The HoFH International Clinical Collaborators registry collected data on patients with a clinical, or genetic, or both, diagnosis of HoFH using a retrospective cohort study design. This trial is registered with ClinicalTrials.gov, NCT04815005.Findings:Overall, 751 patients from 38 countries were included, with 565 (75%) reporting biallelic pathogenic variants. The median age of diagnosis was 12·0 years (IQR 5·5–27·0) years. Of the 751 patients, 389 (52%) were female and 362 (48%) were male. Race was reported for 527 patients; 338 (64%) patients were White, 121 (23%) were Asian, and 68 (13%) were Black or mixed race. The major manifestations of ASCVD or aortic stenosis were already present in 65 (9%) of patients at diagnosis of HoFH. Globally, pretreatment LDL cholesterol levels were 14·7 mmol/L (IQR 11·6–18·4). Among patients with detailed therapeutic information, 491 (92%) of 534 received statins, 342 (64%) of 534 received ezetimibe, and 243 (39%) of 621 received lipoprotein apheresis. On-treatment LDL cholesterol levels were lower in high-income countries (3·93 mmol/L, IQR 2·6–5·8) versus non-high-income countries (9·3 mmol/L, 6·7–12·7), with greater use of three or more lipid-lowering therapies (LLT; high-income 66% vs non-high-income 24%) and consequently more patients attaining guideline-recommended LDL cholesterol goals (high-income 21% vs non-h

Journal article

Vallejo-Vaz AJ, Stevens CAT, Lyons ARM, Dharmayat KI, Freiberger T, Hovingh GK, Mata P, Raal FJ, Santos RD, Soran H, Watts GF, Abifadel M, Aguilar-Salinas CA, Alhabib KF, Alkhnifsawi M, Almahmeed W, Alnouri F, Alonso R, Al-Rasadi K, Al-Sarraf A, Al-Sayed N, Araujo F, Ashavaid TF, Banach M, Béliard S, Benn M, Binder CJ, Bogsrud MP, Bourbon M, Chlebus K, Corral P, Davletov K, Descamps OS, Durst R, Ezhov M, Gaita D, Genest J, Groselj U, Harada-Shiba M, Holven KB, Kayikcioglu M, Khovidhunkit W, Lalic K, Latkovskis G, Laufs U, Liberopoulos E, Lima-Martinez MM, Lin J, Maher V, Marais AD, März W, Mirrakhimov E, Miserez AR, Mitchenko O, Nawawi H, Nordestgaard BG, Panayiotou AG, Paragh G, Petrulioniene Z, Pojskic B, Postadzhiyan A, Raslova K, Reda A, Reiner Ž, Sadiq F, Sadoh WE, Schunkert H, Shek AB, Stoll M, Stroes E, Su T-C, Subramaniam T, Susekov AV, Tilney M, Tomlinson B, Truong TH, Tselepis AD, Tybjæg-Hansen A, Vázquez Cárdenas A, Viigimaa M, Wang L, Yamashita S, Tokgozoglu L, Catapano AL, Ray KK, Kastelein JJP, Bruckert E, Vohnout B, Schreier L, Pang J, Ebenbichler C, Dieplinger H, Innerhofer R, Winhofer-Stöckl Y, Greber-Platzer S, Krychtiuk K, Speidl W, Toplak H, Widhalm K, Stulnig T, Huber K, Höllerl F, Rega-Kaun G, Kleemann L, Mäser M, Scholl-Bürgi S, Säly C, Mayer FJ, Sablon G, Tarantino E, Nzeyimana C, Pojskic L, Sisic I, Nalbantic AD, Jannes CE, Pereira AC, Krieger JE, Petrov I, Goudev A, Nikolov F, Tisheva S, Yotov Y, Tzvetkov I, Baass A, Bergeron J, Bernard S, Brisson D, Brunham LR, Cermakova L, Couture P, Francis GA, Gaudet D, Hegele RA, Khoury E, Mancini GBJ, McCrindle BW, Paquette M, Ruel I, Cuevas A, Asenjo S, Wang X, Meng K, Song X, Yong Q, Jiang T, Liu Z, Duan Y, Hong J, Ye P, Chen Y, Qi J, Liu Z, Li Y, Zhang C, Peng J, Yang Y, Yu W, Wang Q, Yuan H, Cheng S, Jiang L, Chong M, Jiao J, Wu Y, Wen W, Xu L, Zhang R, Qu Y, He J, Fan X, Wang Z, Chow E, Pećin I, Perica D, Symeonides P, Vrablik M, Ceska R, Soska V, Tichy L, Adamkova V, Franekova J, Cifkova R, Kramet al., 2021, Global perspective of familial hypercholesterolaemia: a cross-sectional study from the EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC), The Lancet, Vol: 398, Pages: 1713-1725, ISSN: 0140-6736

BackgroundThe European Atherosclerosis Society Familial Hypercholesterolaemia Studies Collaboration (FHSC) global registry provides a platform for the global surveillance of familial hypercholesterolaemia through harmonisation and pooling of multinational data. In this study, we aimed to characterise the adult population with heterozygous familial hypercholesterolaemia and described how it is detected and managed globally.MethodsUsing FHSC global registry data, we did a cross-sectional assessment of adults (aged 18 years or older) with a clinical or genetic diagnosis of probable or definite heterozygous familial hypercholesterolaemia at the time they were entered into the registries. Data were assessed overall and by WHO regions, sex, and index versus non-index cases.FindingsOf the 61 612 individuals in the registry, 42 167 adults (21 999 [53·6%] women) from 56 countries were included in the study. Of these, 31 798 (75·4%) were diagnosed with the Dutch Lipid Clinic Network criteria, and 35 490 (84·2%) were from the WHO region of Europe. Median age of participants at entry in the registry was 46·2 years (IQR 34·3–58·0); median age at diagnosis of familial hypercholesterolaemia was 44·4 years (32·5–56·5), with 40·2% of participants younger than 40 years when diagnosed. Prevalence of cardiovascular risk factors increased progressively with age and varied by WHO region. Prevalence of coronary disease was 17·4% (2·1% for stroke and 5·2% for peripheral artery disease), increasing with concentrations of untreated LDL cholesterol, and was about two times lower in women than in men. Among patients receiving lipid-lowering medications, 16 803 (81·1%) were receiving statins and 3691 (21·2%) were on combination therapy, with greater use of more potent lipid-lowering medication in men than in women. Median LDL cholesterol

Journal article

Dharmayat K, Stevens C, Lyons A, Catapano AL, Freiberger T, Hovingh K, Kastelein JJ, Mata P, Raal FJ, Santos RD, Soran H, Watts GF, Ray KK, Vallejo-Vaz AJet al., 2020, Heterozygous familial hypercholesterolaemia in children: preliminary analysis from the eas fhsc global registry on over 7,900 children with familial hypercholesterolaemia, European Atherosclerosis Society Congress, Publisher: Elsevier, Pages: e76-e76, ISSN: 0021-9150

Conference paper

Vallejo-Vaz AJ, Dharmayat K, Stevens C, Lyons A, Brandts J, Catapano AL, Freiberger T, Hovingh K, Kastelein JJ, Mata P, Raal FJ, Santos RD, Soran H, Watts GF, Ray KKet al., 2020, CHARACTERISTICS OF ADULTS WITH HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLAEMIA STRATIFIED BY GENDER: PRELIMINARY ANALYSIS FROM THE EAS FHSC GLOBAL REGISTRY ON OVER 36,000 CASES OF FAMILIAL HYPERCHOLESTEROLAEMIA, Publisher: ELSEVIER IRELAND LTD, Pages: E13-E13, ISSN: 0021-9150

Conference paper

Hu P, Dharmayat KI, Stevens CAT, Sharabiani MTA, Jones RS, Watts GF, Genest J, Ray KK, Vallejo-Vaz AJet al., 2020, Prevalence of familial hypercholesterolemia among the general population and patients with atherosclerotic cardiovascular disease: a systematic review and meta-analysis., Circulation, Vol: 141, Pages: 1742-1759, ISSN: 0009-7322

Background:Contemporary studies suggest that familial hypercholesterolemia (FH) is more frequent than previously reported and increasingly recognized as affecting individuals of all ethnicities and across many regions of the world. Precise estimation of its global prevalence and prevalence across World Health Organization regions is needed to inform policies aiming at early detection and atherosclerotic cardiovascular disease (ASCVD) prevention. The present study aims to provide a comprehensive assessment and more reliable estimation of the prevalence of FH than hitherto possible in the general population (GP) and among patients with ASCVD.Methods:We performed a systematic review and meta-analysis including studies reporting on the prevalence of heterozygous FH in the GP or among those with ASCVD. Studies reporting gene founder effects and focused on homozygous FH were excluded. The search was conducted through Medline, Embase, Cochrane, and Global Health, without time or language restrictions. A random-effects model was applied to estimate the overall pooled prevalence of FH in the general and ASCVD populations separately and by World Health Organization regions.Results:From 3225 articles, 42 studies from the GP and 20 from populations with ASCVD were eligible, reporting on 7 297 363 individuals/24 636 cases of FH and 48 158 patients/2827 cases of FH, respectively. More than 60% of the studies were from Europe. Use of the Dutch Lipid Clinic Network criteria was the commonest diagnostic method. Within the GP, the overall pooled prevalence of FH was 1:311 (95% CI, 1:250–1:397; similar between children [1:364] and adults [1:303], P=0.60; across World Health Organization regions where data were available, P=0.29; and between population-based and electronic health records–based studies, P=0.82). Studies with ≤10 000 participants reported a higher prevalence (1:200–289) compared with larger cohorts (1:365–407; P<0.001). The pooled pre

Journal article

Abar L, Sobiecki JG, Cariolou M, Nanu N, Vieira AR, Stevens C, Aune D, Greenwood DC, Chan DSM, Norat Tet al., 2019, Body size and obesity during adulthood, and risk of lympho-haematopoietic cancers: an update of the WCRF-AICR systematic review of published prospective studies., Ann Oncol, Vol: 30, Pages: 528-541, ISSN: 0923-7534

BACKGROUND: To summarise the evidence on the associations between body mass index (BMI) and BMI in early adulthood, height, waist circumference (WC) and waist-to-hip ratio (WHR), and risk of lympho-haematopoietic cancers. METHOD: We conducted a meta-analysis of prospective studies and identified relevant studies published up to December 2017 by searching PubMed. A random-effects model was used to calculate dose-response summary relative risks (RRs). RESULTS: Our findings showed BMI, and BMI in early adulthood (aged 18-21years) is associated with the risk of Hodgkin's and non-Hodgkin's lymphoma (HL and NHL), diffuse large beta-cell lymphoma (DLBCL), Leukaemia including acute and chronic myeloid lymphoma (AML and CML), and chronic lymphocytic leukaemia (CLL) and multiple myeloma (MM). The summary RR per 5kg/m2 increase in BMI were 1.12 [95% confidence interval (CI): 1.05-1.20] for HL, 1.05 (95% CI: 1.03-1.08) for NHL, 1.11 (95% CI: 1.05-1.16) for DLBCL, 1.06 (95% CI: 1.03-1.09) for ML, 1.09 (95% CI: 1.03-1.15) for leukaemia, 1.13 (95% CI: 1.04-1.24) for AML, 1.13 (95% CI: 1.05-1.22) for CML and 1.04 (95% CI: 1.00-1.09) for CLL, and were1.12 (95% CI: 1.05-1.19) for NHL, 1.22 (95% CI: 1.09-1.37) for DLBCL, and 1.19 (95% CI: 1.03-1.38) for FL for BMI in early adulthood analysis. Results on mortality showed a 15%, 16% and 17% increased risk of NHL, MM and leukaemia, respectively. Greater height increased the risk of NHL by 7%, DLBCL by 10%, FL by 9%, MM by 5% and Leukaemia by 7%. WHR was associated with increased risk of DLBCL by 12%. No association was found between higher WC and risk of MM. CONCLUSION: Our results revealed that general adiposity in adulthood and early adulthood, and greater height may increase the risk of almost all types of lympho-haematopoietic cancers and this adds to a growing body of evidence linking body fatness to several types of cancers.

Journal article

Stevens C, 2018, Value of Information in Health Economics Cost-Effectiveness Analysis

Health Economics(HE) models help decision-making bodies determineoptimal medical treatments based on their respective net benefits.This is done during Cost-Effectiveness analyses(CEA). Often, inputparameters of the model are uncertain and their uncertainty canspread to the result of the CEA. In presence of high uncertainty in theCEA result, decision maker may want to conduct a study to gain newinformation about the model parameters, and thus, avoid making baddecisions. Value of Information analyses(VOI) quantifies decreases inuncertainty due to obtaining perfect or future hypothetical samples.Although these analyses are essential for choosing the right treatments,they are currently underutilised by the HE community because of theircomplexity. This dissertation attempts to resolve this complexity bydescribing VOI calculations in the context of HE CEA analyses. Particularemphasis is placed on calculating the value decrease in uncertaintycaused by a new medical study. This is called Expected Valueof Sample Information(EVSI). In addition, we have developed a simpleonline EVSI calculator that deploys the method presented inStrong, M., Oakley, J. E., Brennan, A., and Breeze, P. (2015). Estimatingthe expected value of sample information using the probabilistic sensitivityanalysis sample: A fast, nonparametric regression-based method.Med DecisMaking, 35(5):570–83.We demonstrate that beside being fast and accurate, this method isalso ideal for automation.

Thesis dissertation

Vallejo-Vaz AJ, De Marco M, Stevens CAT, Akram A, Freiberger T, Hovingh GK, Kastelein JJP, Mata P, Raal FJ, Santos RD, Soran H, Watts GF, Abifadel M, Aguilar-Salinas CA, Al-khnifsawi M, AlKindi FA, Alnouri F, Alonso R, Al-Rasadi K, Al-Sarraf A, Ashavaid TF, Binder CJ, Bogsrud MP, Bourbon M, Bruckert E, Chlebus K, Corral P, Descamps O, Durst R, Ezhov M, Fras Z, Genest J, Groselj U, Harada-Shiba M, Kayikcioglu M, Lalic K, Lam CSP, Latkovskis G, Laufs U, Liberopoulos E, Lin J, Maher V, Majano N, Marais AD, März W, Mirrakhimov E, Miserez AR, Mitchenko O, Nawawi HM, Nordestgaard BG, Paragh G, Petrulioniene Z, Pojskic B, Postadzhiyan A, Reda A, Reiner Ž, Sadoh WE, Sahebkar A, Shehab A, Shek AB, Stoll M, Su T, Subramaniam T, Susekov AV, Symeonides P, Tilney M, Tomlinson B, Truong T, Tselepis AD, Tybjærg-Hansen A, Vázquez-Cárdenas A, Viigimaa M, Vohnout B, Widén E, Yamashita S, Banach M, Gaita D, Jiang L, Nilsson L, Santos LE, Schunkert H, Tokgözoğlu L, Car J, Catapano AL, Ray KKet al., 2018, Overview of the current status of familial hypercholesterolaemia care in over 60 countries - The EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC), Atherosclerosis, Vol: 277, Pages: 234-255, ISSN: 0021-9150

Background and aimsManagement of familial hypercholesterolaemia (FH) may vary across different settings due to factors related to population characteristics, practice, resources and/or policies. We conducted a survey among the worldwide network of EAS FHSC Lead Investigators to provide an overview of FH status in different countries.MethodsLead Investigators from countries formally involved in the EAS FHSC by mid-May 2018 were invited to provide a brief report on FH status in their countries, including available information, programmes, initiatives, and management.Results63 countries provided reports. Data on FH prevalence are lacking in most countries. Where available, data tend to align with recent estimates, suggesting a higher frequency than that traditionally considered. Low rates of FH detection are reported across all regions. National registries and education programmes to improve FH awareness/knowledge are a recognised priority, but funding is often lacking. In most countries, diagnosis primarily relies on the Dutch Lipid Clinics Network criteria. Although available in many countries, genetic testing is not widely implemented (frequent cost issues). There are only a few national official government programmes for FH. Under-treatment is an issue. FH therapy is not universally reimbursed. PCSK9-inhibitors are available in ∼2/3 countries. Lipoprotein-apheresis is offered in ∼60% countries, although access is limited.ConclusionsFH is a recognised public health concern. Management varies widely across countries, with overall suboptimal identification and under-treatment. Efforts and initiatives to improve FH knowledge and management are underway, including development of national registries, but support, particularly from health authorities, and better funding are greatly needed.

Journal article

Abar L, Vieira AR, Aune D, Sobiecki JG, Vingeliene S, Polemiti E, Stevens C, Greenwood DC, Chan DSM, Schlesinger S, Norat Tet al., 2018, Height and body fatness and colorectal cancer risk: an update of the WCRF-AICR systematic review of published prospective studies, European Journal of Nutrition, Vol: 57, Pages: 1701-1720, ISSN: 0044-264X

PurposeThere is no published dose–response meta-analysis on the association between height and colorectal cancer risk (CRC) by sex and anatomical sub-site. We conducted a meta-analysis of prospective studies on the association between height and CRC risk with subgroup analysis and updated evidence on the association between body fatness and CRC risk.MethodsPubMed and several other databases were searched up to November 2016. A random effects model was used to calculate dose–response summary relative risks (RR’s).Results47 studies were included in the meta-analyses including 50,936 cases among 7,393,510 participants. The findings support the existing evidence regarding a positive association of height, general and abdominal body fatness and CRC risk. The summary RR were 1.04 [95% (CI)1.02–1.05, I² = 91%] per 5 cm increase in height, 1.02 [95% (CI)1.01–1.02, I² = 0%] per 5 kg increase in weight, 1.06 [95% (CI)1.04–1.07, I² = 83%] per 5 kg/m2 increase in BMI, 1.02 [95% (CI)1.02–1.03, I² = 4%] per 10 cm increase in waist circumference, 1.03 [95% (CI)1.01–1.05, I² = 16%] per 0.1 unit increase in waist to hip ratio. The significant association for height and CRC risk was similar in men and women. The significant association for BMI and CRC risk was stronger in men than in women.ConclusionThe positive association between height and risk of CRC suggests that life factors during childhood and early adulthood might play a role in CRC aetiology. Higher general and abdominal body fatness during adulthood are risk factors of CRC and these associations are stronger in men than in women.

Journal article

Vingeliene S, Chan DSM, Vieira AR, Polemiti E, Stevens C, Abar L, Rosenblatt DN, Greenwood DC, Norat Tet al., 2017, An update of the WCRF/AICR systematic literature review and meta-analysis on dietary and anthropometric factors and esophageal cancer risk, Annals of Oncology, Vol: 28, Pages: 2409-2419, ISSN: 0923-7534

BackgroundIn the 2007 World Cancer Research Fund/American Institute for Cancer Research Second Expert Report, the expert panel judged that there was strong evidence that alcoholic drinks and body fatness increased esophageal cancer risk, whereas fruits and vegetables probably decreased its risk. The judgments were mainly based on case–control studies. As part of the Continuous Update Project, we updated the scientific evidence accumulated from cohort studies in this topic.MethodsWe updated the Continuous Update Project database up to 10 January 2017 by searching in PubMed and conducted dose–response meta-analyses to estimate summary relative risks (RRs) and 95% confidence intervals (CIs) using random effects model.ResultsA total of 57 cohort studies were included in 13 meta-analyses. Esophageal adenocarcinoma risk was inversely related to vegetable intake (RR per 100 g/day: 0.89, 95% CI: 0.80–0.99, n = 3) and directly associated with body mass index (RR per 5 kg/m2: 1.47, 95% CI: 1.34–1.61, n = 9). For esophageal squamous cell carcinoma, inverse associations were observed with fruit intake (RR for 100 g/day increment: 0.84, 95% CI: 0.75–0.94, n = 3) and body mass index (RR for 5 kg/m2 increment: 0.64, 95% CI: 0.56–0.73, n = 8), and direct associations with intakes of processed meats (RR for 50 g/day increment: 1.59, 95% CI: 1.11–2.28, n = 3), processed and red meats (RR for 100 g/day increment: 1.37, 95% CI: 1.04–1.82, n = 3) and alcohol (RR for 10 g/day increment: 1.25, 95% CI: 1.12–1.41, n = 6). ConclusionsEvidence from cohort studies suggested a protective role of vegetables and body weight control in esophageal adenocarcinomas development. For squamous cell carcinomas, higher intakes of red and processed meats and alcohol may increase the risk, whereas fruits intak

Journal article

Schlesinger S, Chan DSM, Vingeliene S, Vieira AR, Abar L, Polemiti E, Stevens CAT, Greenwood DC, Aune D, Norat Tet al., 2017, Carbohydrates, glycemic index, glycemic load, and breast cancer risk: a systematic review and dose-response meta-analysis of prospective studies, NUTRITION REVIEWS, Vol: 75, Pages: 420-441, ISSN: 0029-6643

Context: The investigation of dose–response associations between carbohydrate intake, glycemic index, glycemic load, and risk of breast cancer stratified by menopausal status, hormone receptor status, and body mass index (BMI) remains inconclusive. Objective: A systematic review and dose–response meta-analyses was conducted to investigate these associations. Data Sources: As part of the World Cancer Research Fund/American Institute for Cancer Research Continuous Update Project, PubMed was searched up to May 2015 for relevant studies on these associations. Study Selection: Prospective studies reporting associations between carbohydrate intake, glycemic index, or glycemic load and breast cancer risk were included. Data Extraction: Two investigators independently extracted data from included studies. Results: Random-effects models were used to summarize relative risks (RRs) and 95%CIs. Heterogeneity between subgroups, including menopausal status, hormone receptor status, and BMI was explored using meta-regression. Nineteen publications were included. The summary RRs (95%CIs) for breast cancer were 1.04 (1.00–1.07) per 10 units/d for glycemic index, 1.01 (0.98–1.04) per 50 units/d for glycemic load, and 1.00 (0.96–1.05) per 50 g/d for carbohydrate intake. For glycemic index, the association appeared slightly stronger among postmenopausal women (summary RR per 10 units/d, 1.06; 95%CI, 1.02–1.10) than among premenopausal women, though the difference was not statistically significant (Pheterogeneity = 0.15). Glycemic load and carbohydrate intake were positively associated with breast cancer among postmenopausal women with estrogen-negative tumors (summary RR for glycemic load, 1.28; 95%CI, 1.08–1.52; and summary RR for carbohydrates, 1.13; 95%CI, 1.02–1.25). No differences in BMI were detected. Conclusions: Menopausal and hormone receptor status, but not BMI, might be potential influencing factors for the associations

Journal article

Vieira AR, Abar L, Chan D, Vingeliene S, Polemiti E, Stevens C, Greenwood D, Norat Tet al., 2017, Foods and beverages and colorectal cancer risk: a systematic review and meta-analysis of cohort studies, an update of the evidence of the WCRF-AICR Continuous Update Project., Annals of Oncology, Vol: 28, Pages: 1788-1802, ISSN: 1569-8041

Objective: As part of the World Cancer Research Fund International Continuous Update Project, we updated the systematic review and meta-analysis of prospective studies to quantify the dose-response between foods and beverages intake and colorectal cancer risk. Data Sources: PubMed and several databases up to May 31 st 2015. Study selection: Prospective studies reporting adjusted relative risk estimates for the association of specific food groups and beverages and risk of colorectal, colon and rectal cancer. Data synthesis: Dose-response meta-analyses using random effect models to estimate summary relative risks (RRs). Results: Results: 400 individual study estimates from 111 unique cohort studies were included. Overall, the risk increase of colorectal cancer is 12% for each 100g/day increase of red and processed meat intake (95%CI=4-21%, I2 =70%, pheterogeneity (ph)<0.01) and 7% for 10 g/day increase of ethanol intake in alcoholic drinks (95%CI=5-9%, I2 =25%, ph =  0.21). Colorectal cancer risk decrease in 17% for each 90g/day increase of whole grains (95%CI=11-21%, I2 =0%, ph =  0.30, 6 studies). For each 400 g/day increase of dairy products intake (95%CI=10-17%, I2 =18%, ph =  0.27, 10 studies). Inverse associations were also observed for vegetables intake (RR per 100 g/day =0.98 (95%CI=0.96-0.99, I2 =0%, ph =  0.48, 11 studies) and for fish intake (RR for 100g/day=0.89(95%CI=0.80-0.99, I2 =0%, ph =  0.52, 11 studies), that were weak for vegetables and driven by one study for fish. Intakes of fruits, coffee, tea, cheese, poultry and legumes were not associated with colorectal cancer risk. Conclusions: Our results reinforce the evidence that high intake of red and processed meat and alcohol increase the risk of colorectal cancer. Milk and whole grains may have a protective role against colorectal cancer. The evidence for vegetables and fish was less convincing.

Journal article

Schlesinger S, Aleksandrova K, Abar L, Vieria AR, Vingeliene S, Polemiti E, Stevens CA, Greenwood DC, Chan DS, Aune D, Norat Tet al., 2017, Adult weight gain and colorectal adenomas - a systematic review and meta-analysis., Annals of Oncology, Vol: 28, ISSN: 1569-8041

Background: Colorectal adenomas are known as precursors for the majority of colorectal carcinomas. While weight gain during adulthood has been identified as a risk factor for colorectal cancer, the association is less clear for colorectal adenomas. We conducted a systematic review and meta-analysis to quantify the evidence on this association. Methods: : We searched MEDLINE up to September 2016 to identify observational (prospective, cross-sectional and retrospective) studies on weight gain during adulthood and colorectal adenoma occurrence and recurrence. We conducted meta-analysis on high weight gain versus stable weight, linear and non-linear dose-response meta-analyses to analyze the association. Summary odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using a random effects model. Results: For colorectal adenoma occurrence, the summary OR was 1.39 (95% CI: 1.17-1.65; I 2 :43%, N =9 studies, cases=5,507) comparing high (midpoint: 17.4 kg) versus stable weight gain during adulthood and with each 5 kg weight gain the odds increased by 7% (2%-11%; I 2 :65%, N =7 studies). Although there was indication of non-linearity ( Pnon-linearity <0.001) there was an increased odds of colorectal adenoma throughout the whole range of weight gain. Three studies were identified investigating the association between weight gain and colorectal adenoma recurrence and data were limited to draw firm conclusions. Conclusions: Even a small amount of adult weight gain was related to a higher odds of colorectal adenoma occurrence. Our findings add to the benefits of weight control in adulthood regarding colorectal adenomas occurrence, which might be relevant for early prevention of colorectal cancer.

Journal article

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