Amit V Khera
Boston, USA
Amit V. Khera, MD MSc, is a cardiologist, human geneticist, and population biologist at Massachusetts General Hospital (MGH), group leader within the MGH Center for Genomic Medicine, Associate Director of the Program in Medical and Population Genetics and Merkin Institute Fellow at the Broad Institute of MIT and Harvard, and Assistant Professor at Harvard Medical School.
He received his MD with Alpha Omega Alpha distinction from the Perelman School of Medicine at the University of Pennsylvania and went on to complete clinical training in Internal Medicine and cardiology at Brigham and Women’s Hospital and MGH. He completed a Masters of Science at the Harvard School of Public Health and a postdoctoral research fellowship with Dr. Sekar Kathiresan in human genetics at the Broad Institute of MIT and Harvard.
His research program (kheralab.org) uses genetic variation as a tool to uncover new biology and enable enhanced clinical care informed by inherited susceptibility.
He has developed expertise in epidemiology, clinical medicine, and human genetics. Among his scientific contributions, he pioneered use of a new approach to quantify genetic risk (‘genome-wide polygenic scores’) for common diseases, developed biomarkers that provide new biologic insights, and analyzed large-scale gene sequencing data to highlight key pathways driving risk and identify molecular subtypes of cardiometabolic diseases.
Dr. Khera has authored more than 90 scientific publications, including lead or senior-authored publications in the New England Journal of Medicine, Journal of the American Medical Association, Cell, Nature Reviews Genetics, Nature Genetics, Journal of the American College of Cardiology, and Circulation. His work has been recognized as among the top ten research advances by the American Heart Association (in both 2016 and 2018), and the National Human Genome Research Institute (in 2020), and he is the 2019 recipient of the Douglas P. Zipes Distinguished Young Scientist Award from the American College of Cardiology.
In tandem with his research efforts, he founded and is co-leading a Preventive Genomics Clinic at MGH to provide a clinical infrastructure for genome-first medicine.
Monday 23 May
Implementing genetics scores in clinical practice
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Alberico Catapano
Alberico Catapano
Milan, ItalyFull Professor of Pharmacology, Director of the Center of Epidemiology and Preventive Pharmacology (SEFAP) as well as Director of the Laboratory of Lipoproteins, Immunity and Atherosclerosis at the University of Milan (Department of Pharmacological and Biomolecular
Sciences) and PhD coordinator from 2017 to 2020.
Moreover he is Director of the Center for the Study, Prevention and Therapy of Atherosclerosis of the University of Milan, at the Bassini Hospital, Head of Cardiovascular Research Line at Multimedica IRCCS Sesto San Giovanni (Mi), President of the Italian Society of Clinical and Sperimental Therapy (SITeCS) and General Director of the SISA Foundation
His main research, from 1972, interests include the study of atherosclerosis, lipids, lipoproteins and genetic dyslipidaemias, and he has made landmark observations regarding heat shock proteins and pentraxins in atherogenesis, on high-density lipoproteins in the modulation of the immune response, and on the identification of possible therapeutic targets by exploiting genetic information. Past President of the European Atherosclerosis Society (EAS), Professor Catapano is currently Co- Chairman of the EAS/European Society of Cardiology (ESC) guidelines for the treatment of dyslipoproteinaemias. Editor of Atherosclerosis Supplements, Co-editor of Atherosclerosis and Associate Editor of other scientific journals, he has authored more than 590 scientific papers in peer-reviewed journals (I.F. 10.929) and is among the highly cited scientists in 2019, 2020 and 2021 according to Clarivate -
Kausik Ray
Kausik Ray
London, United KingdomKausik Ray is currently Professor of Public Health, Deputy Director of Imperial Clinical Trials Unit and Head of Commercial Trials within the Department of Public Health and Primary Care, School of Public Health, Imperial College London, Consultant Cardiologist and Chief Clinical Officer and Head of Trials –Discover Now as well as NIHR ARC National Lead of Cardiovascular Disease. Professor Ray received his medical education (MB ChB, 1991) at the University of Birmingham Medical School, his MD (2004) at the University of Sheffield, a post-doctoral fellowship at Harvard Medical School and finally an MPhil in epidemiology (2007) from the University of Cambridge.
A Fellow of the American College of Cardiology, the European Society of Cardiology, the American Heart Association and the Royal College of Physicians, Kausik Ray is also a member of the British Cardiovascular Society and President of the European Atherosclerosis Society, also serving on the EAS Consensus panel and EAS Executive Committee. Professor Ray has either been the National Lead Investigator, Principal Investigator, or served on committees for several major medical trials, as well as international registries and is currently involved in 8 ongoing trials in lipids and diabetes and the PI for ORION 1, 3, 11 assessing PCSK9 inhibition through RNA interference and BETONMACE assessing BET protein inhibition in patients with ACS.
Professor Ray’s research interests have focused on the prevention of coronary disease with a focus on lipids, diabetes, biomarkers and risk prediction. He has an H index of 87, an i10 of 220 and over 92,000 citations for his work in journals such as New England Journal of Medicine, The Lancet, JAMA, European Heart Journal, Circulation and JACC. He has also been included in the Clarivate Analytics’ list of the top 1% most cited authors in all of global medicine in 2018, 2019 and 2020. Key original contributions which have influenced European and American guidelines include demonstrating the early benefits of statin therapy post ACS, the impact of more/less intensive glycaemic control on CVD and the risks/benefits of aspirin therapy in primary prevention. Recently, his work on statins and diabetes risk led to a global label change for statins by the FDA and EMEA. Currently Professor Ray leads the EAS FH Studies collaboration which is the first global registry of FH which includes 70 countries and 62,000 cases, as well as being the Senior PI for the TOGETHER study looking at cardiometabolic risk in the vascular health checks in 250,000 people in London.
Genetic risk scores offer great potential in the delivery of precision cardiovascular medicine, across primary and early secondary prevention settings, with the opportunity to intervene earlier to inform treatment choices and reduce the likelihood of clinical disease. Integration of genetic risk scores within clinical practice also has wider impact, in optimising healthcare resource use to individuals most likely to be benefit from specific interventions.
While widely applied in research studies, the clinical utility of genetic risk scores has yet to be established. There are also important challenges to their implementation. Key amongst these is the need for further validation to ensure accuracy and reliability, barriers to implementation and to the interpretation of information, education of healthcare personnel, and reimbursement issues. There are also ethical issues relating to how such information is used and the paucity of representation from different ethnicities. These challenges underline the need for further validation within each population ancestry group; definition of the added clinical value from the use of the score; consideration of benefits versus harms in research studies; and assessment of relevant social, ethical and legal issues that may impact reimbursement and health policy. Successful implementation will most likely be in personalising preventive measures and informing treatment choice.
Key references
Patel AP, Wang M, Kartoun U, Ng K, Khera AV. Quantifying and understanding the higher risk of atherosclerotic cardiovascular disease among South Asian individuals: results from the UK Biobank Prospective Cohort Study. Circulation 2021;144:410-422.
Kim MS, Kim WJ, Khera AV, Kim JY, Yon DK, Lee SW, Shin JI, Won HH. Association between adiposity and cardiovascular outcomes: an umbrella review and meta-analysis of observational and Mendelian randomization studies. Eur Heart J 2021;42:3388-3403.
Hindy G, Aragam KG, Ng K, Chaffin M, Lotta LA, Baras A; Regeneron Genetics Center, Drake I, Orho-Melander M, Melander O, Kathiresan S, Khera AV. Genome-wide polygenic score, clinical risk factors, and long-term trajectories of coronary artery disease. Arterioscler Thromb Vasc Biol 2020;40:2738-2746.
