Abstract 18502: Mass and Genetic Polymorphism of Group IIA Secretory Phospholipase A2, Rosuvastatin Therapy, and Risk of Cardiovascular Events: An Analysis From the JUPITER Trial
Background: Although group IIA secretory phospholipase A2 (sPLA2-IIA) is well appraised for its involvement in atherosclerosis by modifying LDL, its role in managing CVD risk in a primary prevention setting with low LDL-C is unknown. Furthermore, the utility of sPLA2-IIA mass for assessing future CVD risk relative to statin therapy in a population free of CVD is unknown.
Methods: We analyzed data from JUPITER (NCT00239681) in which participants with LDL cholesterol <130 mg/dL and hsCRP≥2 mg/L were randomized to rosuvastatin 20mg/day vs placebo. sPLA2-IIA was quantified by sandwich-type ELISA (Cayman) in 11269 participants before and 1 year after randomization. Cox regression was used to examine the association of sPLA2-IIA with CVD. The impact of lifelong reduction in sPLA2-IIA on CVD risk was assessed by Mendelian randomization analysis in 6692 participants.
Results: 313 first CVD events occurred during maximum follow-up of 5.0 (median, 1.9) years. Baseline sPLA2-IIA levels (median, 25th-75th percentile: 3.81, 2.49-6.03 ng/ml) were associated with increased risk of CVD: after adjusting for age, sex, race, treatment, smoking, family history, BMI, blood pressure, glucose, HDL-C, LDL-C, and triglycerides, HR (95%CI, p-value) per SD in sPLA2-IIA was 1.22 (1.08-1.38; p= 0.002). This association was slightly attenuated after additionally adjusting for hsCRP (1.18, 1.04-1.35; p=0.01) and there was no statistical heterogeneity by rosuvastatin therapy. In the rosuvastatin arm, on-treatment sPLA2-IIA levels trended towards an increased residual risk of CVD; HR 1.19 (0.97-1.45; p=0.09) in multivariable adjusted model, this was attenuated after additionally adjusting for hsCRP (HR: 1.08 95% CI 0.87-1.34; p=0.50). rs11573156C in PLA2G2A (encoding sPLA2-IIA) had the strongest effect on sPLA2-IIA levels, median (25th-75th percentile) for the CC and GG genotype were 2.79 (1.97-4.01 ng/mL) and 7.38 (5.38-10.19 ng/mL), respectively; but showed a non-significant association with CVD risk (HR: 1.11, 95% CI 0.89-1.38, p=0.34).
Conclusion: While sPLA2-IIA may be a measurable biomarker to assess the prognostic impact of inflammation on baseline and residual CVD risk, this result do not support sPLA2-IIA as a viable pharmacological target for reducing CVD risk.
Author Disclosures: A.O. Akinkuolie: None. A.Y. Chu: None. M. Caulfield: Employment; Significant; Quest Diagnostics. J. Mu: Employment; Significant; Quest Diagnostics Nichols Institute. H. Eva: Employment; Significant; AstraZeneca. B. Ding: Employment; Significant; AstraZeneca. F. Nyberg: Employment; Significant; AstraZeneca. R.J. Glynn: Research Grant; Significant; has received research support from AstraZeneca and NIH. P.M. Ridker: Research Grant; Significant; Novartis, AstraZeneca, Amgen, Pfizer, NHLBI, NCI. Consultant/Advisory Board; Modest; ISIS, Boston Heart, Genzyme. Other; Modest; Listed as a coinventor on patents held by BWH that relate to the use of inflammatory biomarkers to cardiovascular disease. D.I. Chasman: None. S. Mora: Research Grant; Significant; Atherotech Diagnostics and NHLBI. Consultant/Advisory Board; Modest; Lilly, Pfizer, Cerenis Therapeutics.
- © 2015 by American Heart Association, Inc.