Author:
Casas Juan P.,Ninio Ewa,Panayiotou Andrie,Palmen Jutta,Cooper Jackie A.,Ricketts Sally L.,Sofat Reecha,Nicolaides Andrew N.,Corsetti James P.,Fowkes F. Gerry R.,Tzoulaki Ioanna,Kumari Meena,Brunner Eric J.,Kivimaki Mika,Marmot Michael G.,Hoffmann Michael M.,Winkler Karl,März Winfred,Ye Shu,Stirnadel Heide A.,Khaw Kay-Tee,Humphries Steve E.,Sandhu Manjinder S.,Hingorani Aroon D.,Talmud Philippa J.
Abstract
Background—
Higher lipoprotein-associated phospholipase A
2
(Lp-PLA2) activity is associated with increased risk of coronary heart disease (CHD), making Lp-PLA2 a potential therapeutic target.
PLA2G7
variants associated with Lp-PLA2 activity could evaluate whether this relationship is causal.
Methods and Results—
A meta-analysis including a total of 12 studies (5 prospective, 4 case-control, 1 case-only, and 2 cross-sectional studies; n=26 118) was undertaken to examine the association of the following: (1) Lp-PLA2 activity versus cardiovascular biomarkers and risk factors and CHD events (2 prospective studies; n=4884); (2)
PLA2G7
single-nucleotide polymorphisms and Lp-PLA2 activity (3 prospective, 2 case-control, 2 cross-sectional studies; up to n=6094); and (3)
PLA2G7
single-nucleotide polymorphisms and angiographic coronary artery disease (2 case-control, 1 case-only study; n=4971 cases) and CHD events (5 prospective, 2 case-control studies; n=5523). Lp-PLA2 activity correlated with several CHD risk markers. Hazard ratios for CHD events for the top versus bottom quartile of Lp-PLA2 activity were 1.61 (95% confidence interval, 1.31 to 1.99) and 1.17 (95% confidence interval, 0.91 to 1.51) after adjustment for baseline traits. Of 7 single-nucleotide polymorphisms, rs1051931 (A379V) showed the strongest association with Lp-PLA2 activity, with VV subjects having 7.2% higher activity than AAs. Genotype was not associated with risk markers, angiographic coronary disease (odds ratio, 1.03; 95% confidence interval, 0.80 to 1.32), or CHD events (odds ratio, 0.98; 95% confidence interval, 0.82 to 1.17).
Conclusions—
Unlike Lp-PLA2 activity,
PLA2G7
variants associated with modest effects on Lp-PLA2 activity were not associated with cardiovascular risk markers, coronary atheroma, or CHD. Larger association studies, identification of single-nucleotide polymorphisms with larger effects, or randomized trials of specific Lp-PLA2 inhibitors are needed to confirm or refute a contributory role for Lp-PLA2 in CHD.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Physiology (medical),Cardiology and Cardiovascular Medicine