Standard
Harvard
Holmes, MV, Simon, T, Exeter, HJ, Folkersen, L, Asselbergs, FW, Guardiola, M, Cooper, JA, Palmen, J, Hubacek, JA, Carruthers, KF, Horne, BD, Brunisholz, KD, Mega, JL, van Iperen, EPA, Li, M, Leusink, M, Trompet, S, Verschuren, JJW, Hovingh, GK, Dehghan, A, Nelson, CP, Kotti, S, Danchin, N, Scholz, M, Haase, CL, Rothenbacher, D, Swerdlow, DI, Kuchenbaecker, KB, Staines-Urias, E, Goel, A, van 't Hooft, F, Gertow, K, de Faire, U, Panayiotou, AG, Tremoli, E, Baldassarre, D, Veglia, F, Holdt, LM, Beutner, F, Gansevoort, RT, Navis, GJ, Mateo Leach, I, Breitling, LP, Brenner, H, Thiery, J, Dallmeier, D, Franco-Cereceda, A, Boer, JMA, Stephens, JW, Hofker, MH, Tedgui, A, Hofman, A, Uitterlinden, AG, Adamkova, V, Pitha, J, Onland-Moret, NC, Cramer, MJ, Nathoe, HM, Spiering, W, Klungel, OH, Kumari, M, Whincup, PH, Morrow, DA, Braund, PS, Hall, AS, Olsson, AG, Doevendans, PA, Trip, MD, Tobin, MD, Hamsten, A, Watkins, H, Koenig, W, Nicolaides, AN, Teupser, D, Day, INM, Carlquist, JF, Gaunt, TR, Ford, I, Sattar, N, Tsimikas, S, Schwartz, GG, Lawlor, DA, Morris, RW, Sandhu, MS, Poledne, R, Maitland-van der Zee, AH, Khaw, K-T, Keating, BJ, van der Harst, P, Price, JF, Mehta, SR, Yusuf, S, Witteman, JCM, Franco, OH, Jukema, JW, de Knijff, P, Tybjaerg-Hansen, A, Rader, DJ, Farrall, M, Samani, NJ, Kivimaki, M, Fox, KAA, Humphries, SE, Anderson, JL, Boekholdt, SM
, Palmer, TM, Eriksson, P, Paré, G, Hingorani, AD, Sabatine, MS, Mallat, Z, Casas, JP & Talmud, PJ 2013, '
Secretory phospholipase A(2)-IIA and cardiovascular disease: a mendelian randomization study',
Journal of the American College of Cardiology, vol. 62, no. 21, pp. 1966-1976.
https://doi.org/10.1016/j.jacc.2013.06.044APA
Holmes, M. V., Simon, T., Exeter, H. J., Folkersen, L., Asselbergs, F. W., Guardiola, M., Cooper, J. A., Palmen, J., Hubacek, J. A., Carruthers, K. F., Horne, B. D., Brunisholz, K. D., Mega, J. L., van Iperen, E. P. A., Li, M., Leusink, M., Trompet, S., Verschuren, J. J. W., Hovingh, G. K., ... Talmud, P. J. (2013).
Secretory phospholipase A(2)-IIA and cardiovascular disease: a mendelian randomization study.
Journal of the American College of Cardiology,
62(21), 1966-1976.
https://doi.org/10.1016/j.jacc.2013.06.044Vancouver
Author
Bibtex
@article{f697571987ef4253b0758c4689a87ae0,
title = "Secretory phospholipase A(2)-IIA and cardiovascular disease: a mendelian randomization study",
abstract = "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.",
keywords = "Alleles, Cardiovascular Diseases, DNA, Gene Expression Regulation, Global Health, Humans, Incidence, Mendelian Randomization Analysis, Phospholipases A2, Secretory",
author = "Holmes, {Michael V.} and Tabassome Simon and Exeter, {Holly J.} and Lasse Folkersen and Asselbergs, {Folkert W.} and Montse Guardiola and Cooper, {Jackie A.} and Jutta Palmen and Hubacek, {Jaroslav A.} and Carruthers, {Kathryn F.} and Horne, {Benjamin D.} and Brunisholz, {Kimberly D.} and Mega, {Jessica L.} and {van Iperen}, {Erik P. A.} and Mingyao Li and Maarten Leusink and Stella Trompet and Verschuren, {Jeffrey J. W.} and Hovingh, {G. Kees} and Abbas Dehghan and Nelson, {Christopher P.} and Salma Kotti and Nicolas Danchin and Markus Scholz and Haase, {Christiane L.} and Dietrich Rothenbacher and Swerdlow, {Daniel I.} and Kuchenbaecker, {Karoline B.} and Eleonora Staines-Urias and Anuj Goel and {van 't Hooft}, Ferdinand and Karl Gertow and {de Faire}, Ulf and Panayiotou, {Andrie G.} and Elena Tremoli and Damiano Baldassarre and Fabrizio Veglia and Holdt, {Lesca M.} and Frank Beutner and Gansevoort, {Ron T.} and Navis, {Gerjan J.} and {Mateo Leach}, Irene and Breitling, {Lutz P.} and Hermann Brenner and Joachim Thiery and Dhayana Dallmeier and Anders Franco-Cereceda and Boer, {Jolanda M. A.} and Stephens, {Jeffrey W.} and Hofker, {Marten H.} and Alain Tedgui and Albert Hofman and Uitterlinden, {Andr{\'e} G.} and Vera Adamkova and Jan Pitha and Onland-Moret, {N. Charlotte} and Cramer, {Maarten J.} and Nathoe, {Hendrik M.} and Wilko Spiering and Klungel, {Olaf H.} and Meena Kumari and Whincup, {Peter H.} and Morrow, {David A.} and Braund, {Peter S.} and Hall, {Alistair S.} and Olsson, {Anders G.} and Doevendans, {Pieter A.} and Trip, {Mieke D.} and Tobin, {Martin D.} and Anders Hamsten and Hugh Watkins and Wolfgang Koenig and Nicolaides, {Andrew N.} and Daniel Teupser and Day, {Ian N. M.} and Carlquist, {John F.} and Gaunt, {Tom R.} and Ian Ford and Naveed Sattar and Sotirios Tsimikas and Schwartz, {Gregory G.} and Lawlor, {Debbie A.} and Morris, {Richard W.} and Sandhu, {Manjinder S.} and Rudolf Poledne and {Maitland-van der Zee}, {Anke H.} and Kay-Tee Khaw and Keating, {Brendan J.} and {van der Harst}, Pim and Price, {Jackie F.} and Mehta, {Shamir R.} and Salim Yusuf and Witteman, {Jaqueline C. M.} and Franco, {Oscar H.} and Jukema, {J. Wouter} and {de Knijff}, Peter and Anne Tybjaerg-Hansen and Rader, {Daniel J.} and Martin Farrall and Samani, {Nilesh J.} and Mika Kivimaki and Fox, {Keith A. A.} and Humphries, {Steve E.} and Anderson, {Jeffrey L.} and Boekholdt, {S. Matthijs} and Palmer, {Tom M.} and Per Eriksson and Guillaume Par{\'e} and Hingorani, {Aroon D.} and Sabatine, {Marc S.} and Ziad Mallat and Casas, {Juan P.} and Talmud, {Philippa J.}",
note = "Copyright {\textcopyright} 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.",
year = "2013",
month = nov,
day = "19",
doi = "10.1016/j.jacc.2013.06.044",
language = "English",
volume = "62",
pages = "1966--1976",
journal = "Journal of the American College of Cardiology",
issn = "1558-3597",
publisher = "Elsevier USA",
number = "21",
}
RIS
TY - JOUR
T1 - Secretory phospholipase A(2)-IIA and cardiovascular disease
T2 - a mendelian randomization study
AU - Holmes, Michael V.
AU - Simon, Tabassome
AU - Exeter, Holly J.
AU - Folkersen, Lasse
AU - Asselbergs, Folkert W.
AU - Guardiola, Montse
AU - Cooper, Jackie A.
AU - Palmen, Jutta
AU - Hubacek, Jaroslav A.
AU - Carruthers, Kathryn F.
AU - Horne, Benjamin D.
AU - Brunisholz, Kimberly D.
AU - Mega, Jessica L.
AU - van Iperen, Erik P. A.
AU - Li, Mingyao
AU - Leusink, Maarten
AU - Trompet, Stella
AU - Verschuren, Jeffrey J. W.
AU - Hovingh, G. Kees
AU - Dehghan, Abbas
AU - Nelson, Christopher P.
AU - Kotti, Salma
AU - Danchin, Nicolas
AU - Scholz, Markus
AU - Haase, Christiane L.
AU - Rothenbacher, Dietrich
AU - Swerdlow, Daniel I.
AU - Kuchenbaecker, Karoline B.
AU - Staines-Urias, Eleonora
AU - Goel, Anuj
AU - van 't Hooft, Ferdinand
AU - Gertow, Karl
AU - de Faire, Ulf
AU - Panayiotou, Andrie G.
AU - Tremoli, Elena
AU - Baldassarre, Damiano
AU - Veglia, Fabrizio
AU - Holdt, Lesca M.
AU - Beutner, Frank
AU - Gansevoort, Ron T.
AU - Navis, Gerjan J.
AU - Mateo Leach, Irene
AU - Breitling, Lutz P.
AU - Brenner, Hermann
AU - Thiery, Joachim
AU - Dallmeier, Dhayana
AU - Franco-Cereceda, Anders
AU - Boer, Jolanda M. A.
AU - Stephens, Jeffrey W.
AU - Hofker, Marten H.
AU - Tedgui, Alain
AU - Hofman, Albert
AU - Uitterlinden, André G.
AU - Adamkova, Vera
AU - Pitha, Jan
AU - Onland-Moret, N. Charlotte
AU - Cramer, Maarten J.
AU - Nathoe, Hendrik M.
AU - Spiering, Wilko
AU - Klungel, Olaf H.
AU - Kumari, Meena
AU - Whincup, Peter H.
AU - Morrow, David A.
AU - Braund, Peter S.
AU - Hall, Alistair S.
AU - Olsson, Anders G.
AU - Doevendans, Pieter A.
AU - Trip, Mieke D.
AU - Tobin, Martin D.
AU - Hamsten, Anders
AU - Watkins, Hugh
AU - Koenig, Wolfgang
AU - Nicolaides, Andrew N.
AU - Teupser, Daniel
AU - Day, Ian N. M.
AU - Carlquist, John F.
AU - Gaunt, Tom R.
AU - Ford, Ian
AU - Sattar, Naveed
AU - Tsimikas, Sotirios
AU - Schwartz, Gregory G.
AU - Lawlor, Debbie A.
AU - Morris, Richard W.
AU - Sandhu, Manjinder S.
AU - Poledne, Rudolf
AU - Maitland-van der Zee, Anke H.
AU - Khaw, Kay-Tee
AU - Keating, Brendan J.
AU - van der Harst, Pim
AU - Price, Jackie F.
AU - Mehta, Shamir R.
AU - Yusuf, Salim
AU - Witteman, Jaqueline C. M.
AU - Franco, Oscar H.
AU - Jukema, J. Wouter
AU - de Knijff, Peter
AU - Tybjaerg-Hansen, Anne
AU - Rader, Daniel J.
AU - Farrall, Martin
AU - Samani, Nilesh J.
AU - Kivimaki, Mika
AU - Fox, Keith A. A.
AU - Humphries, Steve E.
AU - Anderson, Jeffrey L.
AU - Boekholdt, S. Matthijs
AU - Palmer, Tom M.
AU - Eriksson, Per
AU - Paré, Guillaume
AU - Hingorani, Aroon D.
AU - Sabatine, Marc S.
AU - Mallat, Ziad
AU - Casas, Juan P.
AU - Talmud, Philippa J.
N1 - Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
PY - 2013/11/19
Y1 - 2013/11/19
N2 - 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.
AB - 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.
KW - Alleles
KW - Cardiovascular Diseases
KW - DNA
KW - Gene Expression Regulation
KW - Global Health
KW - Humans
KW - Incidence
KW - Mendelian Randomization Analysis
KW - Phospholipases A2, Secretory
U2 - 10.1016/j.jacc.2013.06.044
DO - 10.1016/j.jacc.2013.06.044
M3 - Journal article
C2 - 23916927
VL - 62
SP - 1966
EP - 1976
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
SN - 1558-3597
IS - 21
ER -
