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Record W1583413364 · doi:10.1016/j.jacc.2013.06.044

Secretory Phospholipase A2-IIA and Cardiovascular Disease

2013· review· en· W1583413364 on OpenAlex
Michael V. Holmes, Tabassome Simon, Holly Exeter, Lasse Folkersen, Folkert W. Asselbergs, Montse Guardiola, Jackie A. Cooper, Jutta Palmen, Jaroslav A. Hubáček, Kathryn Carruthers, Benjamin D. Horne, Kimberly D. Brunisholz, Jessica L. Mega, Erik P.A. van Iperen, Mingyao Li, Maarten Leusink, Stella Trompet, Jeffrey J. W. Verschuren, G. Kees Hovingh, Abbas Dehghan, Christopher P. Nelson, Salma Kotti, Nicolas Danchin, Markus Scholz, Christiane L. Haase, Dietrich Rothenbacher, Daniel I. Swerdlow, Karoline Kuchenbaecker, Eleonora Staines-Urias, Anuj Goel, Ferdinand van 't Hooft, Karl Gertow, Ulf dé Fairé, Andrie G. Panayiotou, Elena Tremoli, Damiano Baldassarre, Fabrizio Veglia, Lesca M. Holdt, Frank Beutner, Ron T. Gansevoort, Gerjan Navis, Irene Mateo Leach, Lutz P. Breitling, Hermann Brenner, Joachim Thiery, Dhayana Dallmeier, Anders Franco‐Cereceda, Jolanda M.A. Boer, Jeffrey W. Stephens, Marten H. Hofker, Alain Tedgui, Albert Hofman, André G. Uitterlinden, Věra Adámková, Jan Piťha, N. Charlotte Onland‐Moret, Maarten J. Cramer, Hendrik M. Nathoe, Wilko Spiering, Olaf H. Klungel, Meena Kumari, Peter H. Whincup, David A. Morrow, Peter S. Braund, Alistair S. Hall, Anders Olsson, Pieter A. Doevendans, Mieke D. Trip, Martin D. Tobin, Anders Hamsten, Hugh Watkins, Wolfgang Köenig, Andrew Nicolaides, Daniel Teupser, Ian N.M. Day, John F. Carlquist, Tom R. Gaunt, Ian Ford, Naveed Sattar, Sotirios Tsimikas, Gregory G. Schwartz, Debbie A. Lawlor, Richard Morris, Manjinder S. Sandhu, R. Poledne, Anke H. Maitland‐van der Zee, Kay‐Tee Khaw, Brendan J. Keating, Pim van der Harst, Jackie F. Price, Shamir R. Mehta, Salim Yusuf, J. C. M. Witteman, Oscar H. Franco, J. Wouter Jukema, Peter de Knijff, Anne Tybjærg‐Hansen, Daniel J. Rader, Martin Farrall, Nilesh J. Samani, Mika Kivimäki, Keith A.A. Fox, Steve E. Humphries, J. L. Ross Anderson, S. Matthijs Boekholdt, Tom Palmer, Per Eriksson, Guillaume Paré, Aroon D. Hingorani, Marc S. Sabatine, Ziad Mallat, Juan P. Casas, Philippa J. Talmud

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
fundA Canadian funder is recorded on the work.

Bibliographic record

VenueJournal of the American College of Cardiology · 2013
Typereview
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicProtein Kinase Regulation and GTPase Signaling
Canadian institutionsHamilton Health SciencesMcMaster UniversityPopulation Health Research Institute
FundersNational Heart, Lung, and Blood InstituteNational Institute on AgingEconomic and Social Research CouncilServierMedical Research CouncilNational Institutes of HealthSanofiTop Institute PharmaStockholms Läns LandstingAgence Nationale de la RechercheHjärt-LungfondenAbbott LaboratoriesAstellas PharmaVetenskapsrådetEisaiGentofte HospitalNederlandse Organisatie voor Wetenschappelijk OnderzoekDaiichi-SankyoBritish Heart FoundationBundesministerium für Bildung und ForschungRigshospitaletErasmus Universiteit RotterdamDaiichi Sankyo EuropeKarolinska InstitutetZonMwHeart and Stroke Foundation of CanadaTorsten Söderbergs StiftelseResearch Promotion FoundationKnut och Alice Wallenbergs StiftelseUniversity of BristolDiabetes UKMinistero della SaluteAntheraNational Institute for Health and Care ResearchWellcome TrustIntarcia TherapeuticsCancer Research UKErasmus Medisch CentrumHealth and Safety ExecutiveBoston Scientific CorporationUniversity of California, San DiegoSundhed og Sygdom, Det Frie ForskningsrådBrigham and Women's HospitalPfizerGlaxoSmithKlineEuropean CommissionAstraZenecaBristol-Myers SquibbJohn D. and Catherine T. MacArthur FoundationEli Lilly and CompanyAmgen
KeywordsMedicineDiseasePhospholipase A2Internal medicineBiochemistryEnzyme

Abstract

fetched live from OpenAlex

OBJECTIVES: This study sought to investigate the role of secretory phospholipase A2 (sPLA2)-IIA in cardiovascular disease. BACKGROUND: Higher circulating levels of sPLA2-IIA mass or sPLA2 enzyme activity have been associated with increased risk of cardiovascular events. However, it is not clear if this association is causal. A recent phase III clinical trial of an sPLA2 inhibitor (varespladib) was stopped prematurely for lack of efficacy. METHODS: We conducted a Mendelian randomization meta-analysis of 19 general population studies (8,021 incident, 7,513 prevalent major vascular events [MVE] in 74,683 individuals) and 10 acute coronary syndrome (ACS) cohorts (2,520 recurrent MVE in 18,355 individuals) using rs11573156, a variant in PLA2G2A encoding the sPLA2-IIA isoenzyme, as an instrumental variable. RESULTS: PLA2G2A rs11573156 C allele associated with lower circulating sPLA2-IIA mass (38% to 44%) and sPLA2 enzyme activity (3% to 23%) per C allele. The odds ratio (OR) for MVE per rs11573156 C allele was 1.02 (95% confidence interval [CI]: 0.98 to 1.06) in general populations and 0.96 (95% CI: 0.90 to 1.03) in ACS cohorts. In the general population studies, the OR derived from the genetic instrumental variable analysis for MVE for a 1-log unit lower sPLA2-IIA mass was 1.04 (95% CI: 0.96 to 1.13), and differed from the non-genetic observational estimate (OR: 0.69; 95% CI: 0.61 to 0.79). In the ACS cohorts, both the genetic instrumental variable and observational ORs showed a null association with MVE. Instrumental variable analysis failed to show associations between sPLA2 enzyme activity and MVE. CONCLUSIONS: Reducing sPLA2-IIA mass is unlikely to be a useful therapeutic goal for preventing cardiovascular events.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.969
Threshold uncertainty score0.822

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0020.002
Bibliometrics0.0000.000
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.018
GPT teacher head0.265
Teacher spread0.248 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it