Edinburgh Research Explorer Secretory Phospholipase A2-IIA and Cardiovascular Disease

This study sought to investigate the role of secretory phospholipase A 2 (sPLA 2 )-IIA in cardiovascular disease. Background 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 ef fi cacy. 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. 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% con fi dence 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: