National Institute Public Health and Environm, Netherlands
Stephens, Jeffrey W. (författare)
Swansea University, Wales
Hofker, Marten H. (författare)
University of Groningen, Netherlands
Tedgui, Alain (författare)
INSERM, France
Hofman, Albert (författare)
Erasmus MC, Netherlands
Uitterlinden, Andre G. (författare)
Erasmus MC, Netherlands
Adamkova, Vera (författare)
Institute Clin and Expt Med, Czech Republic
Pitha, Jan (författare)
Institute Clin and Expt Med, Czech Republic
Onland-Moret, Charlotte N. (författare)
University of Medical Centre Utrecht, Netherlands
Cramer, Maarten J. (författare)
University of Medical Centre Utrecht, Netherlands
Nathoe, Hendrik M. (författare)
University of Medical Centre Utrecht, Netherlands
Spiering, Wilko (författare)
University of Medical Centre Utrecht, Netherlands
Klungel, Olaf H. (författare)
University of Utrecht, Netherlands
Kumari, Meena (författare)
UCL, England
Whincup, Peter H. (författare)
University of London, England
Morrow, David A. (författare)
Brigham and Womens Hospital, MA USA
Braund, Peter S. (författare)
University of Leicester, England
Hall, Alistair S. (författare)
University of Leeds, England
Olsson, Anders G. (författare)
Östergötlands Läns Landsting,Linköpings universitet,Avdelningen för kardiovaskulär medicin,Hälsouniversitetet,Endokrinmedicinska kliniken,Stockholm Heart Centre, Sweden
Doevendans, Pieter A. (författare)
University of Medical Centre Utrecht, Netherlands
Trip, Mieke D. (författare)
University of Amsterdam, Netherlands
Tobin, Martin D. (författare)
University of Leicester, England
Hamsten, Anders (författare)
Karolinska Institute, Sweden
Watkins, Hugh (författare)
University of Oxford, England
Koenig, Wolfgang (författare)
University of Ulm Medical Centre, Germany
Nicolaides, Andrew N. (författare)
University of London Imperial Coll Science Technology and Med, England
Objectives This study sought to investigate the role of secretory phospholipase A(2) (sPLA(2))-IIA in cardiovascular disease. less thanbrgreater than less thanbrgreater thanBackground Higher circulating levels of sPLA(2)-IIA mass or sPLA(2) 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 sPLA(2) inhibitor (varespladib) was stopped prematurely for lack of efficacy. less thanbrgreater than less thanbrgreater thanMethods 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 sPLA(2)-IIA isoenzyme, as an instrumental variable. less thanbrgreater than less thanbrgreater thanResults PLA2G2A rs11573156 C allele associated with lower circulating sPLA(2)-IIA mass (38% to 44%) and sPLA(2) 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 sPLA(2)-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. less thanbrgreater than less thanbrgreater thanConclusions Reducing sPLA(2)-IIA mass is unlikely to be a useful therapeutic goal for preventing cardiovascular events.