Cardiovascular Diabetology (Jun 2019)
The selective peroxisome proliferator-activated receptor alpha modulator (SPPARMα) paradigm: conceptual framework and therapeutic potential
- Jean-Charles Fruchart,
- Raul D. Santos,
- Carlos Aguilar-Salinas,
- Masanori Aikawa,
- Khalid Al Rasadi,
- Pierre Amarenco,
- Philip J. Barter,
- Richard Ceska,
- Alberto Corsini,
- Jean-Pierre Després,
- Patrick Duriez,
- Robert H. Eckel,
- Marat V. Ezhov,
- Michel Farnier,
- Henry N. Ginsberg,
- Michel P. Hermans,
- Shun Ishibashi,
- Fredrik Karpe,
- Tatsuhiko Kodama,
- Wolfgang Koenig,
- Michel Krempf,
- Soo Lim,
- Alberto J. Lorenzatti,
- Ruth McPherson,
- Jesus Millan Nuñez-Cortes,
- Børge G. Nordestgaard,
- Hisao Ogawa,
- Chris J. Packard,
- Jorge Plutzky,
- Carlos I. Ponte-Negretti,
- Aruna Pradhan,
- Kausik K. Ray,
- Željko Reiner,
- Paul M. Ridker,
- Massimiliano Ruscica,
- Shaukat Sadikot,
- Hitoshi Shimano,
- Piyamitr Sritara,
- Jane K. Stock,
- Ta-Chen Su,
- Andrey V. Susekov,
- André Tartar,
- Marja-Riitta Taskinen,
- Alexander Tenenbaum,
- Lale S. Tokgözoğlu,
- Brian Tomlinson,
- Anne Tybjærg-Hansen,
- Paul Valensi,
- Michal Vrablík,
- Walter Wahli,
- Gerald F. Watts,
- Shizuya Yamashita,
- Koutaro Yokote,
- Alberto Zambon,
- Peter Libby
Affiliations
- Jean-Charles Fruchart
- R3i Foundation
- Raul D. Santos
- Hospital Israelita Albert Einstein, and Lipid Clinic, Heart Institute (InCor) University of Sao Paulo Medical School Hospital
- Carlos Aguilar-Salinas
- Unidad de Investigacion de Enfermedades Metabolicas, Department of Endocrinolgy and Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
- Masanori Aikawa
- Center for Interdisciplinary Cardiovascular Sciences and Center for Excellence in Vascular Biology, Division of Cardiovascular Medicine and Channing Division of Network Medicine, Brigham and Women’s Hospital, Harvard Medical School
- Khalid Al Rasadi
- Department of Clinical Biochemistry, Sultan Qaboos University Hospital
- Pierre Amarenco
- Department of Neurology and Stroke Center, Paris-Diderot-Sorbonne University
- Philip J. Barter
- Lipid Research Group, School of Medical Sciences, University of New South Wales
- Richard Ceska
- IIIrd Dept Int. Med, Center for Preventive Cardiology, 3rd Internal Medicine Clinic, University General Hospital and Charles University
- Alberto Corsini
- Department of Pharmacological and Biomolecular Sciences, Università Degli Studi di Milano
- Jean-Pierre Després
- Centre de recherche sur les soins et les services de première ligne-Université Laval du CIUSSS de la Capitale-Nationale, Department of Kinesiology, Faculty of Medicine, Université Laval
- Patrick Duriez
- INSERM, CHU Lille, U1171-Degenerative & Vascular Cognitive Disorders, University of Lille, Faculty of Pharmacy, University of Lille, UDSL
- Robert H. Eckel
- Division of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Colorado School of Medicine
- Marat V. Ezhov
- Laboratory of Lipid Disorders, National Cardiology Research Center
- Michel Farnier
- Lipid Clinic, Point Médical and Department of Cardiology, CHU Dijon-Bourgogne
- Henry N. Ginsberg
- Columbia University Vagelos College of Physicians and Surgeons
- Michel P. Hermans
- Division of Endocrinology and Nutrition, Cliniques Universitaires St-Luc and Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain
- Shun Ishibashi
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Jichi Medical University
- Fredrik Karpe
- OCDEM, University of Oxford and the NIHR Oxford Biomedical Research Centre, OUH Foundation Trust, Churchill Hospital
- Tatsuhiko Kodama
- Laboratory for System Biology and Medicine Research Center for Advanced Science and Technology, The University of Tokyo
- Wolfgang Koenig
- Deutsches Herzzentrum München, Technische Universitat München, Germany; DZHK (German Centre for Cardiovascular Research)
- Michel Krempf
- Mass Spectrometry Core facility of West Human Nutrition Research Center (CRNHO), Hotel Dieu Hospital
- Soo Lim
- Department of Internal Medicine, Seoul National University Bundang Hospital and Seoul National University College of Medicine
- Alberto J. Lorenzatti
- DAMIC Medical Institute/Rusculleda Foundation for Research
- Ruth McPherson
- Ruddy Canadian Cardiovascular Genetics Centre, University of Ottawa Heart Institute
- Jesus Millan Nuñez-Cortes
- Internal Medicine, Lipids Unit, Gregorio Marañón University Hospital
- Børge G. Nordestgaard
- Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital
- Hisao Ogawa
- National Cerebral and Cardiovascular Center
- Chris J. Packard
- Institute of Cardiovascular and Medical Sciences, University of Glasgow
- Jorge Plutzky
- Cardiovascular Medicine, Brigham and Women’s Hospital, Harvard Medical School
- Carlos I. Ponte-Negretti
- Unidad de Prevención Cardiometabólica Cardiocob. Servicio de Cardiología Hospital el Pino Santiago de Chile, Sociedad Inter Americana de Cardiología SIAC Chairman Cardiovascular Prevention Comite
- Aruna Pradhan
- Division of Cardiovascular Medicine, VA Boston Medical Center
- Kausik K. Ray
- Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, Imperial College London
- Željko Reiner
- Department of Internal Medicine, University Hospital Centre Zagreb, School of Medicine, Zagreb University
- Paul M. Ridker
- Division of Cardiovascular Medicine and Center for Cardiovascular Disease Prevention, Brigham and Women’s Hospital, Harvard Medical School
- Massimiliano Ruscica
- Department of Pharmacological and Biomolecular Sciences, Università Degli Studi di Milano
- Shaukat Sadikot
- Department of Endocrinology/Diabetology, Jaslok Hospital and Research Centre
- Hitoshi Shimano
- Department of Internal Medicine (Endocrinology and Metabolism), Faculty of Medicine, University of Tsukuba
- Piyamitr Sritara
- Department of Medicine, Ramathibodi Hospital, Mahidol University
- Jane K. Stock
- R3i Foundation
- Ta-Chen Su
- Departments of Internal Medicine and Environmental and Occupational Medicine, National Taiwan University; Institute of Occupational Medicine and Industrial Hygiene, National Taiwan University College of Public Health
- Andrey V. Susekov
- Faculty of Clinical Pharmacology and Therapeutics, Academy for Postgraduate Continuous Medical Education
- André Tartar
- Faculté de Pharmacie de Lille
- Marja-Riitta Taskinen
- Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki and Clinical Research Institute, HUCH Ltd.
- Alexander Tenenbaum
- Sackler Faculty of Medicine, Tel Aviv University
- Lale S. Tokgözoğlu
- Department of Cardiology, Faculty of Medicine, Hacettepe University
- Brian Tomlinson
- Department of Medicine & Theraputics, The Chinese University of Hong Kong
- Anne Tybjærg-Hansen
- Department of Clinical Biochemistry, Rigshospitalet; Copenhagen University Hospital, Faculty of Health and Medical Sciences, University of Copenhagen
- Paul Valensi
- Department of Endocrinology, Diabetology and Nutrition, Jean-Verdier Hospital (AP-HP)
- Michal Vrablík
- 3rd Department of Medicine, 1st Faculty of Medicine of Charles University and General University Hospital in Prague
- Walter Wahli
- Lee Kong Chian School of Medicine, Nanyang Technological University Singapore
- Gerald F. Watts
- Lipid Disorders Clinic, Department of Cardiology, Royal Perth Hospital, School of Medicine, University of Western Australia
- Shizuya Yamashita
- Rinku General Medical Center
- Koutaro Yokote
- Department of Endocrinology, Hematology and Gerontology, Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine
- Alberto Zambon
- Department of Medicine-DIMED, University of Padua
- Peter Libby
- Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School
- DOI
- https://doi.org/10.1186/s12933-019-0864-7
- Journal volume & issue
-
Vol. 18,
no. 1
pp. 1 – 20
Abstract
Abstract In the era of precision medicine, treatments that target specific modifiable characteristics of high-risk patients have the potential to lower further the residual risk of atherosclerotic cardiovascular events. Correction of atherogenic dyslipidemia, however, remains a major unmet clinical need. Elevated plasma triglycerides, with or without low levels of high-density lipoprotein cholesterol (HDL-C), offer a key modifiable component of this common dyslipidemia, especially in insulin resistant conditions such as type 2 diabetes mellitus. The development of selective peroxisome proliferator-activated receptor alpha modulators (SPPARMα) offers an approach to address this treatment gap. This Joint Consensus Panel appraised evidence for the first SPPARMα agonist and concluded that this agent represents a novel therapeutic class, distinct from fibrates, based on pharmacological activity, and, importantly, a safe hepatic and renal profile. The ongoing PROMINENT cardiovascular outcomes trial is testing in 10,000 patients with type 2 diabetes mellitus, elevated triglycerides, and low levels of HDL-C whether treatment with this SPPARMα agonist safely reduces residual cardiovascular risk.
Keywords
- Residual cardiovascular risk
- Visceral obesity
- Diabetes
- Atherogenic dyslipidemia
- Triglycerides
- Remnant cholesterol
