Abstract 17485: Decreases in Plasma Phosphatidylinositol Species Partially Explain the Reduction in Cardiovascular Events After Pravastatin Therapy in Secondary Prevention
Introduction: Statin therapy in secondary prevention leads to a reduced risk of future cardiovascular disease (CVD) events. This is explained, in part, by the dramatic reduction in circulating low density lipoprotein cholesterol (LDL-C). However, the effect of statins on circulating lipid species and the independent effect on risk reduction are less well defined. Lipidomic studies on large clinical cohorts can help to define these effects.
Methods: Plasma lipids (345 species) were measured using mass spectrometry on baseline and one year follow up samples from an unbiased subcohort (n=4991) from the Long-Term Intervention with Pravastatin in Ischemic Disease (LIPID) Study. The pravastatin treatment effect on future CVD events and CVD death (from year 1) was calculated using a Cox regression model with treatment as the predictor and adjusting for 21 baseline clinical risk factors. The proportion of the treatment effect explained by baseline levels and changes in individual lipid species, changes in LDL-C or both was determined by subsequent adjustment for these covariates. Within the treatment group, Cox regression was used to identify changes in lipid species associated with future CVD events and CVD death adjusting for the clinical risk factors.
Results: The pravastatin treatment effect was 22.6% for CVD events. Baseline levels and reduction in the phosphatidylinositol species PI(36:2) and PI(36:3) accounted for the greatest reduction in the pravastatin treatment effect (from 22.6% to 10.5% and 13.6% respectively) corresponding to 53.5% and 39.5% of the treatment effect accounted for by these phosphatidylinositol species. Larger reductions in treatment effect were seen after also adjusting for the change in LDL-C (82.2% and 67.7% respectively). Stronger effects were observed for CVD death. The changes in PI(36:2) and PI(36:3) were associated with future CVD events after adjustment for clinical risk factors.
Conclusion: Reduction of phosphatidylinositol species during the first year of treatment were associated with CVD events and accounted for over half of the benefit of pravastatin in the LIPID study. Participants in who the levels of phosphatidylinositol were not reduced by treatment with pravastatin were at increased risk of future events.
Author Disclosures: P.A. Mundra: None. C.K. Barlow: None. P.J. Nestel: None. E.H. Barnes: None. A. Kirby: None. P. Thompson: None. D.R. Sullivan: None. Z.H. Alshehry: None. N.A. Mellett: None. K. Huynh: None. M.J. McConville: None. G. Wong: None. B.A. Kingwell: None. J. Simes: None. A.M. Tonkin: None. P.J. Meikle: Other; Modest; Zora Biosciences.
- © 2016 by American Heart Association, Inc.