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Changes in plasma lipids predict pravastatin efficacy in secondary prevention
Kaushala S. Jayawardana, … , Peter J. Meikle, on behalf of the LIPID Study Investigators
Kaushala S. Jayawardana, … , Peter J. Meikle, on behalf of the LIPID Study Investigators
Published July 11, 2019
Citation Information: JCI Insight. 2019;4(13):e128438. https://doi.org/10.1172/jci.insight.128438.
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Clinical Medicine Clinical trials Metabolism

Changes in plasma lipids predict pravastatin efficacy in secondary prevention

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Abstract

BACKGROUND Statins have pleiotropic effects on lipid metabolism. The relationship between these effects and future cardiovascular events is unknown. We characterized the changes in lipids upon pravastatin treatment and defined the relationship with risk reduction for future cardiovascular events.METHODS Plasma lipids (n = 342) were measured in baseline and 1-year follow-up samples from a Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) study subcohort (n = 4991). The associations of changes in lipids with treatment and cardiovascular outcomes were investigated using linear and Cox regression. The effect of treatment on future cardiovascular outcomes was examined by the relative risk reduction (RRR).RESULTS Pravastatin treatment was associated with changes in 206 lipids. Species containing arachidonic acid were positively associated while phosphatidylinositol species were negatively associated with pravastatin treatment. The RRR from pravastatin treatment for cardiovascular events decreased from 23.5% to 16.6% after adjustment for clinical risk factors and change in LDL-cholesterol (LDL-C) and to 3.0% after further adjustment for the change in the lipid ratio PI(36:2)/PC(38:4). Change in PI(36:2)/PC(38:4) mediated 58% of the treatment effect. Stratification of patients into quartiles of change in PI(36:2)/PC(38:4) indicated no benefit of pravastatin in the fourth quartile.CONCLUSION The change in PI(36:2)/PC(38:4) predicted benefit from pravastatin, independent of change in LDL-C, demonstrating its potential as a biomarker for monitoring the clinical benefit of statin treatment in secondary prevention.TRIAL REGISTRATION Australian New Zealand Clinical Trials Registry identifier ACTRN12616000535471.FUNDING Bristol-Myers Squibb; NHMRC grants 211086, 358395, and 1029754; NHMRC program grant 1149987; NHMRC fellowship 108026; and the Operational Infrastructure Support Program of the Victorian government of Australia.

Authors

Kaushala S. Jayawardana, Piyushkumar A. Mundra, Corey Giles, Christopher K. Barlow, Paul J. Nestel, Elizabeth H. Barnes, Adrienne Kirby, Peter Thompson, David R. Sullivan, Zahir H. Alshehry, Natalie A. Mellett, Kevin Huynh, Malcolm J. McConville, Sophia Zoungas, Graham S. Hillis, John Chalmers, Mark Woodward, Ian C. Marschner, Gerard Wong, Bronwyn A. Kingwell, John Simes, Andrew M. Tonkin, Peter J. Meikle, on behalf of the LIPID Study Investigators

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Figure 1

Association of pravastatin treatment with change in the concentration of lipid species (n = 4991).

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Association of pravastatin treatment with change in the concentration of...
Linear regression analysis of the percentage change in each lipid species against statin treatment, adjusted for age, sex, BMI, and percentage change in cholesterol, HDL-C, and triglycerides, was performed. The β-coefficient denotes the difference in percentage changes (from baseline to follow-up) between treatment and placebo groups. DG, diacylglycerol; HexCer, monohexosylceramide; LPC, lysophosphatidylcholine; LPE, lysophosphatidylethanolamine; LPI, lysophosphatidylinositol; PC, phosphatidylcholine; PI, phosphatidylinositol.

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