The selective peroxisome proliferator-activated receptor alpha modulator (SPPARM) paradigm: conceptual framework and therapeutic potential: A consensus statement from the International Atherosclerosis Society (IAS) and the Residual Risk Reduction Initiative (R3i) Foundation

被引：107

作者：

Fruchart, Jean-Charles ^{[1
]}

Santos, Raul D. ^{[2
,3
]}

Aguilar-Salinas, Carlos ^{[4
,5
]}

Aikawa, Masanori ^{[6
,7
,8
]}

Al Rasadi, Khalid ^{[9
]}

Amarenco, Pierre ^{[10
,11
]}

Barter, Philip J. ^{[12
]}

Ceska, Richard ^{[13
,14
]}

Corsini, Alberto ^{[15
]}

Despres, Jean-Pierre ^{[16
]}

Duriez, Patrick ^{[17
]}

Eckel, Robert H. ^{[18
]}

Ezhov, Marat V. ^{[19
]}

Farnier, Michel ^{[20
,21
]}

Ginsberg, Henry N. ^{[22
]}

Hermans, Michel P. ^{[23
,24
]}

Ishibashi, Shun ^{[25
]}

Karpe, Fredrik ^{[26
,27
]}

Kodama, Tatsuhiko ^{[28
]}

Koenig, Wolfgang ^{[29
,30
,31
]}

Krempf, Michel ^{[32
,33
,34
]}

Lim, Soo ^{[35
,36
]}

Lorenzatti, Alberto J. ^{[37
,38
]}

McPherson, Ruth ^{[39
]}

Millan Nunez-Cortes, Jesus ^{[40
,41
,42
]}

Nordestgaard, Borge G. ^{[43
,44
,45
,46
]}

Ogawa, Hisao ^{[47
]}

Packard, Chris J. ^{[48
]}

Plutzky, Jorge ^{[49
]}

Ponte-Negretti, Carlos I. ^{[50
]}

Pradhan, Aruna ^{[51
,52
]}

Ray, Kausik K. ^{[53
]}

Reiner, Zeljko ^{[54
]}

Ridker, Paul M. ^{[55
,56
]}

Ruscica, Massimiliano ^{[15
]}

Sadikot, Shaukat ^{[57
]}

Shimano, Hitoshi ^{[58
]}

Sritara, Piyamitr ^{[59
]}

Stock, Jane K. ^{[1
]}

Su, Ta-Chen ^{[60
,61
]}

Susekov, Andrey V. ^{[62
]}

Tartar, Andre ^{[63
]}

Taskinen, Marja-Riitta ^{[64
,65
]}

Tenenbaum, Alexander ^{[66
,67
]}

Tokgozoglu, Lale S. ^{[68
]}

Tomlinson, Brian ^{[69
]}

Tybjaerg-Hansen, Anne ^{[70
,71
,72
,73
]}

Valensi, Paul ^{[74
]}

Vrablik, Michal ^{[75
,76
]}

Wahli, Walter ^{[77
,78
,79
]}

机构：

[1] R3i Fdn, Picassopl 8, CH-4010 Basel, Switzerland

[2] Univ Sao Paulo, Hosp Israelita Albert Einstein, Med Sch Hosp, Sao Paulo, Brazil

[3] Univ Sao Paulo, Med Sch Hosp, Heart Inst InCor, Lipid Clin, Sao Paulo, Brazil

[4] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Endocrinolgy & Metab, Unidad Invest Enfermedades Metabol, Mexico City, DF, Mexico

[5] Escuela Med & Ciencias Salud, Tecnol Monterrey, Monterrey, Mexico

[6] Harvard Med Sch, Brigham & Womens Hosp, Ctr Interdisciplinary Cardiovasc Sci, Boston, MA 02115 USA

[7] Harvard Med Sch, Brigham & Womens Hosp, Div Cardiovasc Med, Ctr Excellence Vasc Biol, Boston, MA 02115 USA

[8] Harvard Med Sch, Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA

[9] Sultan Qaboos Univ Hosp, Dept Clin Biochem, Muscat, Oman

[10] Paris Diderot Sorbonne Univ, Dept Neurol, Paris, France

[11] Paris Diderot Sorbonne Univ, Stroke Ctr, Paris, France

[12] Univ New South Wales, Sch Med Sci, Lipid Res Grp, Sydney, NSW, Australia

[13] Univ Gen Hosp, Internal Med Clin 3, Ctr Prevent Cardiol, Dept Int Med 3, Prague, Czech Republic

[14] Charles Univ Prague, Prague, Czech Republic

[15] Univ Milan, Dept Pharmacol & Biomol Sci, Milan, Italy

[16] Univ Laval, Univ Laval CIUSSS Capitale Natl, Ctr Rech Soins & Serv Premiere Ligne, Dept Kinesiol,Fac Med, Quebec City, PQ, Canada

[17] Univ Lille, CHU Lille, INSERM,UDSL, U1171 Degenerat & Vasc Cognit Disorders,Fac Pharm, Lille, France

[18] Univ Colorado, Sch Med, Dept Med, Div Endocrinol Metab & Diabet, Anschutz Med Campus, Aurora, CO USA

[19] Natl Cardiol Res Ctr, Lab Lipid Disorders, Moscow, Russia

[20] CHU Dijon Bourgogne, Lipid Clin, Point Med, Dijon, France

[21] CHU Dijon Bourgogne, Dept Cardiol, Dijon, France

[22] Columbia Univ, Vagelos Coll Physicians & Surg, New York, NY USA

[23] Catholic Univ Louvain, Clin Univ St Luc, Div Nutr & Endocrinol, Brussels, Belgium

[24] Catholic Univ Louvain, IREC, Brussels, Belgium

[25] Jichi Med Univ, Dept Internal Med, Div Endocrinol & Metab, Shimotsuke, Tochigi, Japan

[26] Univ Oxford, OCDEM, Oxford, England

[27] Churchill Hosp, OUH Fdn Trust, NIHR Oxford Biomed Res Ctr, Oxford, England

[28] Univ Tokyo, Ctr Adv Sci & Technol, Lab Syst Biol & Med Res, Tokyo, Japan

[29] Tech Univ Munich, Deutsch Herzzentrum Munchen, Munich, Germany

[30] DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Munich, Germany

[31] Univ Ulm, Inst Epidemiol & Med Biometry, Ulm, Germany

[32] Hop Hotel Dieu, West Human Nutr Res Ctr CRNHO, Mass Spectrometry Core facil, Nantes, France

[33] INRA, UMR 1280, Physiol Adaptat Nutr, Nantes, France

[34] G&R Laennec Hosp, Dept Endocrinol Metab Dis & Nutr, Nantes, France

[35] Seoul Natl Univ, Bundang Hosp, Dept Internal Med, Seongnam, South Korea

[36] Seoul Natl Univ, Coll Med, Seongnam, South Korea

[37] Rusculleda Fdn Res, DAMIC Med Inst, Cordoba, Argentina

[38] Cordoba Hosp, Cardiol Dept, Cordoba, Argentina

[39] Univ Ottawa, Heart Inst, Ruddy Canadian Cardiovasc Genet Ctr, Ottawa, ON, Canada

[40] Gregorio Maranon Univ Hosp, Lipids Unit, Internal Med, Madrid, Spain

[41] Univ Complutense Madrid, Sch Med, Dept Med, Madrid, Spain

[42] Inst Invest Sanitarias Gregorio Maranon, Madrid, Spain

[43] Dept Clin Biochem, Herlev, Denmark

[44] Copenhagen Univ Hosp, Gentofte Hosp, Herlev, Denmark

[45] Copenhagen Gen Populat Study, Herlev, Denmark

[46] Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark

[47] Natl Cerebral & Cardiovasc Ctr, Suita, Osaka, Japan

[48] Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland

[49] Harvard Med Sch, Brigham & Womens Hosp, Cardiovasc Med, Boston, MA 02115 USA

[50] Hosp El Pino Santiago Chile, Serv Cardiol, Unidad Prevenc Cardiometab Cardiocob, Soc Inter Amer Cardiol SIAC Chairma Cardiovasc Pr, Santiago, Chile

来源：

CARDIOVASCULAR DIABETOLOGY | 2019年 / 18卷 / 1期

关键词：

Residual cardiovascular risk; Visceral obesity; Diabetes; Atherogenic dyslipidemia; Triglycerides; Remnant cholesterol; Selective peroxisome proliferator-activated receptor alpha modulator; SPPARMalpha; Pemafibrate (K-877); Inflammation; PROMINENT; DENSITY-LIPOPROTEIN CHOLESTEROL; FATTY LIVER-DISEASE; ISCHEMIC-HEART-DISEASE; ALL-CAUSE MORTALITY; TRIGLYCERIDE-RICH LIPOPROTEINS; COMBINATION LIPID THERAPY; TISSUE FACTOR EXPRESSION; ACUTE-CORONARY-SYNDROME; OF-FUNCTION MUTATIONS; CARDIOVASCULAR-DISEASE;

D O I：

10.1186/s12933-019-0864-7

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 (SPPARM) offers an approach to address this treatment gap. This Joint Consensus Panel appraised evidence for the first SPPARM 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 SPPARM agonist safely reduces residual cardiovascular risk.

引用

页数：20

共 148 条

[61] Apolipoprotein CIII is a new player in diabetes [J].

Juntti-Berggren, Lisa ;

Berggren, Per-Olof .

CURRENT OPINION IN LIPIDOLOGY, 2017, 28 (01) :27-31

[62] Lipids, apolipoproteins, and their ratios in relation to cardiovascular events with statin treatment [J].

Kastelein, John J. P. ;

van der Steeg, Wim A. ;

Holme, Ingar ;

Gaffney, Michael ;

Cater, Nilo B. ;

Barter, Philip ;

Deedwania, Prakash ;

Olsson, Anders G. ;

Boekholdt, S. Matthijs ;

Demicco, David A. ;

Szarek, Michael ;

LaRosa, John C. ;

Pedersen, Terje R. ;

Grundy, Scott M. .

CIRCULATION, 2008, 117 (23) :3002-3009

[63] Effect of fenofibrate on the need for laser treatment for diabetic retinopathy (FIELD study): a randomised controlled trial [J].

Keech, A. C. ;

Mitchell, P. ;

Summonen, P. A. ;

O'Day, J. ;

Davis, T. M. E. ;

Moffitt, M. S. ;

Taskinen, M. R. ;

Simes, R. J. ;

Tse, D. ;

Williamson, E. ;

Merrifield, A. ;

Laatikainen, L. T. ;

d'Emden, M. C. ;

Crimet, D. C. ;

O'Connell, R. L. ;

Colman, P. G. .

LANCET, 2007, 370 (9600) :1687-1697

[64] Angiopoietin-like 3 in lipoprotein metabolism [J].

Kersten, Sander .

NATURE REVIEWS ENDOCRINOLOGY, 2017, 13 (12) :731-739

[65] FGF21 Revolutions: Recent Advances Illuminating FGF21 Biology and Medicinal Properties [J].

Kharitonenkov, Alexei ;

DiMarchi, Richard .

TRENDS IN ENDOCRINOLOGY AND METABOLISM, 2015, 26 (11) :608-617

[66] Association of Rare and Common Variation in the Lipoprotein Lipase Gene With Coronary Artery Disease [J].

Khera, Amit V. ;

Won, Hong-Hee ;

Peloso, Gina M. ;

O'Dushlaine, Colm ;

Liu, Dajiang ;

Stitziel, Nathan O. ;

Natarajan, Pradeep ;

Nomura, Akihiro ;

Emdin, Connor A. ;

Gupta, Namrata ;

Borecki, Ingrid B. ;

Asselta, Rosanna ;

Duga, Stefano ;

Merlini, Piera Angelica ;

Correa, Adolfo ;

Kessler, Thorsten ;

Wilson, James G. ;

Bown, Matthew J. ;

Hall, Alistair S. ;

Braund, Peter S. ;

Carey, David J. ;

Murray, Michael F. ;

Kirchner, H. Lester ;

Leader, Joseph B. ;

Lavage, Daniel R. ;

Manus, J. Neil ;

Hartzel, Dustin N. ;

Samani, Nilesh J. ;

Schunkert, Heribert ;

Marrugat, Jaume ;

Elosua, Roberto ;

McPherson, Ruth ;

Farrall, Martin ;

Watkins, Hugh ;

Lander, Eric S. ;

Rader, Daniel J. ;

Danesh, John ;

Ardissino, Diego ;

Gabriel, Stacey ;

Willer, Cristen ;

Abecasis, Goncalo R. ;

Saleheen, Danish ;

Dewey, Frederick E. ;

Kathiresan, Sekar .

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2017, 317 (09) :937-946

[67] Elevated Triglyceride Level Is Independently Associated With Increased All-Cause Mortality in Patients With Established Coronary Heart Disease Twenty-Two-Year Follow-Up of the Bezafibrate Infarction Prevention Study and Registry [J].

Klempfner, Robert ;

Erez, Aharon ;

Sagit, Ben-Zekry ;

Goldenberg, Ilan ;

Fisman, Enrique ;

Kopel, Eran ;

Shlomo, Nir ;

Israel, Ariel ;

Tenenbaum, Alexander .

CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES, 2016, 9 (02) :100-108

[68]

Krishnan V, 2000, Vitam Horm, V60, P123, DOI 10.1016/S0083-6729(00)60018-3

[69] Liver fat content, non-alcoholic fatty liver disease, and ischaemic heart disease: Mendelian randomization and meta-analysis of 279 013 individuals [J].

Lauridsen, Bo Kobbero ;

Stender, Stefan ;

Kristensen, Thomas Skarup ;

Kofoed, Klaus Fuglsang ;

Kober, Lars ;

Nordestgaard, Borge G. ;

Tybjaerg-Hansen, Anne .

EUROPEAN HEART JOURNAL, 2018, 39 (05) :385-393

[70] Selective estrogen receptor modulators (SERMs): Mechanisms of anticarcinogenesis and drug resistance [J].

Lewis, JS ;

Jordan, VC .

MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS, 2005, 591 (1-2) :247-263

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