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Changes in plasma lipids predict pravastatin efficacy in secondary prevention.

Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia. National Health and Medical Research Council of Australia (NHMRC) Clinical Trials Centre, University of Sydney, Sydney, New South Wales, Australia. Sir Charles Gairdner Hospital, Perth, Western Australia, Australia. Royal Prince Alfred Hospital, Sydney, New South Wales, Australia. King Fahad Medical City, Riyadh, Saudi Arabia. Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, Victoria, Australia. The George Institute for Global Health, Sydney, New South Wales, Australia. Monash University, Melbourne, Victoria, Australia. The Royal Perth Hospital and University of Western Australia, Perth, Western Australia, Australia. The George Institute for Global Health, University of Oxford, England. Department of Mathematics and Statistics, Macquarie University, Sydney, New South Wales, Australia.

JCI insight. 2019;(13)
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Abstract

BACKGROUNDStatins 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.METHODSPlasma 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).RESULTSPravastatin 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.CONCLUSIONThe 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 REGISTRATIONAustralian New Zealand Clinical Trials Registry identifier ACTRN12616000535471.FUNDINGBristol-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.

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MeSH terms : Secondary Prevention