The High-Density Lipoprotein Puzzle Why Classic Epidemiology, Genetic Epidemiology, and Clinical Trials Conflict?
Reads0
Chats0
TLDR
In this paper, the authors investigated the relationship between HDL cholesterol and the future risk of myocardial infarction and found that statin therapy interferes with ATP-binding cassette transporter-mediated macrophage cholesterol efflux via miR33 and thus may diminish certain HDL functional properties.Abstract:
Classical epidemiology has established the incremental contribution of the high-density lipoprotein (HDL) cholesterol measure in the assessment of atherosclerotic cardiovascular disease risk; yet, genetic epidemiology does not support a causal relationship between HDL cholesterol and the future risk of myocardial infarction. Therapeutic interventions directed toward cholesterol loading of the HDL particle have been based on epidemiological studies that have established HDL cholesterol as a biomarker of atherosclerotic cardiovascular risk. However, therapeutic interventions such as niacin, cholesteryl ester transfer protein inhibitors increase HDL cholesterol in patients treated with statins, but have repeatedly failed to reduce cardiovascular events. Statin therapy interferes with ATP-binding cassette transporter-mediated macrophage cholesterol efflux via miR33 and thus may diminish certain HDL functional properties. Unraveling the HDL puzzle will require continued technical advances in the characterization and quantification of multiple HDL subclasses and their functional properties. Key mechanistic criteria for clinical outcomes trials with HDL-based therapies include formation of HDL subclasses that improve the efficiency of macrophage cholesterol efflux and compositional changes in the proteome and lipidome of the HDL particle that are associated with improved antioxidant and anti-inflammatory properties. These measures require validation in genetic studies and clinical trials of HDL-based therapies on the background of statins.read more
Citations
More filters
Journal ArticleDOI
Interaction between adipocytes and high-density lipoprotein:new insights into the mechanism of obesity-induced dyslipidemia and atherosclerosis.
TL;DR: The cross-talk between adipocytes and HDL related to cardiovascular disease is summarized, new insights of the potential mechanism underlying obesity and HDL dysfunction are focused on and adipose tissue is targeted for the treatment of HDL metabolism in obesity.
Journal ArticleDOI
Polygenic determinants in extremes of high-density lipoprotein cholesterol.
Jacqueline S. Dron,Jian Wang,Cécile Low-Kam,Sumeet A. Khetarpal,John F. Robinson,Adam D. McIntyre,Matthew R. Ban,Henian Cao,David Rhainds,Marie-Pierre Dubé,Daniel J. Rader,Guillaume Lettre,Jean-Claude Tardif,Robert A. Hegele +13 more
TL;DR: The genetic basis of extreme HDL-C concentrations encountered clinically is frequently polygenic, with contributions from both rare large-effect and common small-effect variants.
Journal ArticleDOI
Genetics, Dyslipidemia, and Cardiovascular Disease: New Insights
TL;DR: Dyslipidemia, especially increased LDL-c and triglyceride levels, continues to play a significant role in CV risk, and the combination of genetic testing and counseling is important in the management of patients with dys Lipidemia of genetic etiology.
Journal ArticleDOI
Lipids, Apolipoproteins, and Risk of Atherosclerotic Cardiovascular Disease in Persons With CKD.
Archna Bajaj,Dawei Xie,Esteban Cedillo-Couvert,Jeanne Charleston,Jing Chen,Rajat Deo,Harold I. Feldman,Alan S. Go,Jiang He,Edward Horwitz,Radhakrishna R. Kallem,Mahboob Rahman,Matthew R. Weir,Amanda H. Anderson,Amanda H. Anderson,Daniel J. Rader,Lawrence J. Appel,John W. Kusek,James P. Lash,Panduranga S. Rao,Raymond R. Townsend +20 more
TL;DR: The findings support future investigations into pharmacologic targeting of lipoproteins beyond LDL-C, such as triglyceride-rich lipopoteins, to reduce residual risk for ASCVD among individuals with CKD.
Journal ArticleDOI
Impact of Diabetes Mellitus.
TL;DR: This review highlights manuscripts published in ATVB within the past 2 years, focusing on novel pathways that might contribute to vascular complications of diabetes mellitus, which is a major healthcare problem that needs to find solutions to.
References
More filters
Journal ArticleDOI
Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial.
Steven E. Nissen,Taro Tsunoda,E. Murat Tuzcu,Paul Schoenhagen,Christopher J. Cooper,Muhammad Yasin,Gregory M. Eaton,Michael A Lauer,W. Scott Sheldon,Cindy L. Grines,Stephen H. Halpern,Tim Crowe,James C. Blankenship,Richard A. Kerensky +13 more
TL;DR: A recombinant ApoA-I Milano/phospholipid complex administered intravenously for 5 doses at weekly intervals produced significant regression of coronary atherosclerosis as measured by IVUS, and results require confirmation in larger clinical trials with morbidity and mortality end points.
Plasma HDL cholesterol and risk of myocardial infarction: a mendelian randomisation study
Benjamin F. Voight,Gina M. Peloso,Marju Orho-Melander,Ruth Frikke-Schmidt,Maja Barbalić,Majken K. Jensen,George Hindy,Hilma Holm,Eric L. Ding,Toby Johnson,Heribert Schunkert,Nilesh J. Samani,Robert Clarke,Jemma C. Hopewell,John F. Thompson,Mingyao Li,Gudmar Thorleifsson,Christopher Newton-Cheh,Kiran Musunuru,James P. Pirruccello,Danish Saleheen,Li Chen,Alexandre F.R. Stewart,Arne Schillert,Unnur Thorsteinsdottir,Gudmundur Thorgeirsson,Sonia S. Anand,James C. Engert,Thomas M. Morgan,John A. Spertus,Monika Stoll,Klaus Berger,Nicola Martinelli,Domenico Girelli,Pascal P. McKeown,Christopher Patterson,Stephen E. Epstein,Joseph M. Devaney,Mary-Susan Burnett,Vincent Mooser,Samuli Ripatti,Ida Surakka,Markku S. Nieminen,Juha Sinisalo,Marja-Liisa Lokki,Markus Perola,Aki S. Havulinna,Ulf de Faire,Bruna Gigante,Erik Ingelsson,Tanja Zeller,Philipp S. Wild,Paul I.W. de Bakker,Olaf H. Klungel,Anke-Hilse Maitland-van der Zee,Bas J M Peters,Anthonius de Boer,Diederick E. Grobbee,Pieter Willem Kamphuisen,Vera H.M. Deneer,Clara C. Elbers,N. Charlotte Onland-Moret,Marten H. Hofker,Cisca Wijmenga,W. M. Monique Verschuren,Jolanda M. A. Boer,Yvonne T. van der Schouw,Asif Rasheed,Philippe M. Frossard,Serkalem Demissie,Cristen J. Willer,Ron Do,Jose M. Ordovas,Gonçalo R. Abecasis,Michael Boehnke,Karen L. Mohlke,Mark J. Daly,Candace Guiducci,Noël P. Burtt,Aarti Surti,Elena Gonzalez,Shaun Purcell,Stacey Gabriel,Jaume Marrugat,John F. Peden,Jeanette Erdmann,Patrick Diemert,Christina Willenborg,Inke R. Koenig,Marcus Fischer,Christian Hengstenberg,Andreas Ziegler,Ian Buysschaert,Diether Lambrechts,Frans Van de Werf,Keith A.A. Fox,Nour Eddine El Mokhtari,Diana Rubin,Juergen Schrezenmeir,Stefan Schreiber,Arne S. Schaefer,John Danesh,Stefan Blankenberg,Robert Roberts,Ruth McPherson,Hugh Watkins,Alistair S. Hall,Kim Overvad,Eric B. Rimm,Eric Boerwinkle,Anne Tybjærg-Hansen,L. Adrienne Cupples,Muredach P. Reilly,Olle Melander,Pier Mannuccio Mannucci,Diego Ardissino,David S. Siscovick,Roberto Elosua,Kari Stefansson,Christopher J. O'Donnell,Veikko Salomaa,Daniel J. Rader,Leena Peltonen,Stephen M. Schwartz,David Altshuler,Sekar Kathiresan +125 more
TL;DR: Mendelian randomisation analyses challenge the concept that raising of plasma HDL cholesterol will uniformly translate into reductions in risk of myocardial infarction.
Journal ArticleDOI
HDL Cholesterol, Very Low Levels of LDL Cholesterol, and Cardiovascular Events
Philip J. Barter,Antonio M. Gotto,John C. LaRosa,Jaman Maroni,Michael Szarek,Scott M. Grundy,John J.P. Kastelein,Vera Bittner,Jean Charles Fruchart +8 more
TL;DR: The HDL cholesterol levels in patients receiving statins was predictive of major cardiovascular events across the TNT study cohort, both when HDL cholesterol was considered as a continuous variable and when subjects were stratified according to quintiles of HDL cholesterol level.
Journal ArticleDOI
Effects of extended-release niacin with laropiprant in high-risk patients.
Martin J Landray,Richard Haynes,Jemma C. Hopewell,Sarah Parish,Theingi Aung,Joseph Tomson,K Wallendszus,Martin Craig,Lixin Jiang,Rory Collins,Jane Armitage +10 more
TL;DR: Among participants with atherosclerotic vascular disease, the addition of extended-release niacin-laropiprant to statin-based LDL cholesterol-lowering therapy did not significantly reduce the risk of major vascular events but did increase therisk of serious adverse events.
Journal ArticleDOI
HDL Cholesterol Efflux Capacity and Incident Cardiovascular Events
Anand Rohatgi,Amit Khera,Jarett D. Berry,Edward G. Givens,Colby Ayers,Kyle E. Wedin,Ian J. Neeland,Ivan S. Yuhanna,Daniel R. Rader,James A. de Lemos,Philip W. Shaul +10 more
TL;DR: Cholesterol efflux capacity, a new biomarker that characterizes a key step in reverse cholesterol transport, was inversely associated with the incidence of cardiovascular events in a population-based cohort.
Related Papers (5)
Plasma HDL cholesterol and risk of myocardial infarction: A mendelian randomisation study
Benjamin F. Voight,Benjamin F. Voight,Benjamin F. Voight,Gina M. Peloso,Gina M. Peloso,Marju Orho-Melander,Ruth Frikke-Schmidt,Maja Barbalić,Majken K. Jensen,George Hindy,Hilma Holm,Eric L. Ding,Toby Johnson,Heribert Schunkert,Nilesh J. Samani,Nilesh J. Samani,Robert Clarke,Jemma C. Hopewell,John F. Thompson,Mingyao Li,Gudmar Thorleifsson,Christopher Newton-Cheh,Kiran Musunuru,Kiran Musunuru,James P. Pirruccello,James P. Pirruccello,Danish Saleheen,Li Chen,Alexandre F.R. Stewart,Arne Schillert,Unnur Thorsteinsdottir,Unnur Thorsteinsdottir,Gudmundur Thorgeirsson,Sonia S. Anand,James C. Engert,Thomas M. Morgan,John A. Spertus,Monika Stoll,Klaus Berger,Nicola Martinelli,Domenico Girelli,Pascal P. McKeown,Christopher Patterson,Stephen E. Epstein,Joseph M. Devaney,Mary Susan Burnett,Vincent Mooser,Samuli Ripatti,Ida Surakka,Markku S. Nieminen,Juha Sinisalo,Marja-Liisa Lokki,Markus Perola,Aki S. Havulinna,Ulf de Faire,Bruna Gigante,Erik Ingelsson,Tanja Zeller,Philipp S. Wild,Paul I.W. de Bakker,Olaf H. Klungel,Anke-Hilse Maitland-van der Zee,Bas J M Peters,Anthonius de Boer,Diederick E. Grobbee,Pieter Willem Kamphuisen,Vera H.M. Deneer,Clara C. Elbers,N. Charlotte Onland-Moret,Marten H. Hofker,Cisca Wijmenga,W. M. Monique Verschuren,Jolanda M. A. Boer,Yvonne T. van der Schouw,Asif Rasheed,Philippe M. Frossard,Serkalem Demissie,Serkalem Demissie,Cristen J. Willer,Ron Do,Jose M. Ordovas,Jose M. Ordovas,Gonçalo R. Abecasis,Michael Boehnke,Karen L. Mohlke,Mark J. Daly,Mark J. Daly,Candace Guiducci,Noël P. Burtt,Aarti Surti,Elena Gonzalez,Shaun Purcell,Shaun Purcell,Stacey Gabriel,Jaume Marrugat,John F. Peden,Jeanette Erdmann,Patrick Diemert,Christina Willenborg,Inke R. König,Marcus Fischer,Christian Hengstenberg,Andreas Ziegler,Ian Buysschaert,Diether Lambrechts,Frans Van de Werf,Keith A.A. Fox,Nour Eddine El Mokhtari,Diana Rubin,Jürgen Schrezenmeir,Stefan Schreiber,Arne Schäfer,John Danesh,Stefan Blankenberg,Robert Roberts,Ruth McPherson,Hugh Watkins,Alistair S. Hall,Kim Overvad,Eric B. Rimm,Eric Boerwinkle,Anne Tybjærg-Hansen,L. Adrienne Cupples,L. Adrienne Cupples,Muredach P. Reilly,Olle Melander,Pier Mannuccio Mannucci,Diego Ardissino,David S. Siscovick,Roberto Elosua,Kari Stefansson,Kari Stefansson,Christopher J. O'Donnell,Christopher J. O'Donnell,Veikko Salomaa,Daniel J. Rader,Leena Peltonen,Leena Peltonen,Stephen M. Schwartz,David Altshuler,Sekar Kathiresan +140 more
Rare variant in scavenger receptor BI raises HDL cholesterol and increases risk of coronary heart disease
Paolo Zanoni,Sumeet A. Khetarpal,Daniel B. Larach,Hancock-Cerutti Wf,John S. Millar,Marina Cuchel,Stephanie DerOhannessian,Anatol Kontush,Praveen Surendran,Danish Saleheen,Stella Trompet,Joop Jukema,De Craen A,Panos Deloukas,Naveed Sattar,Ian Ford,Chris J. Packard,Majumder Aa,Dewan S. Alam,Di Angelantonio E,Gonçalo R. Abecasis,Rajiv Chowdhury,Jeanette Erdmann,Børge G. Nordestgaard,Sune F. Nielsen,Anne Tybjærg-Hansen,Schmidt Rf,Kari Kuulasmaa,Dajiang J. Liu,Markus Perola,Stefan Blankenberg,Salomaa,Satu Männistö,P. Amouyel,Dominique Arveiler,Jean Ferrières,Martina Müller-Nurasyid,Marco M Ferrario,Frank Kee,Cristen J. Willer,Nilesh J. Samani,Heribert Schunkert,Adam S. Butterworth,Joanna M. M. Howson,Gina M. Peloso,Nathan O. Stitziel,John Danesh,Sekar Kathiresan,Daniel J. Rader +48 more
Effects of Dalcetrapib in Patients with a Recent Acute Coronary Syndrome
Gregory G. Schwartz,Anders G. Olsson,Markus Abt,Christie M. Ballantyne,Philip J. Barter,Jochen Brumm,Bernard R. Chaitman,I. Holme,David Kallend,Lawrence A. Leiter,Eran Leitersdorf,John J.V. McMurray,Hardi Mundl,Stephen J. Nicholls,Prediman K. Shah,Jean-Claude Tardif,R. Scott Wright,R. Scott Wright +17 more