Changes in plasma lipids predict pravastatin efficacy in secondary prevention

LIPID Study Investigators

Research output: Contribution to journalArticle

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 lschaemic 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.

Original languageEnglish
Article number128438
Number of pages13
JournalJCI Insight
Volume4
Issue number13
DOIs
Publication statusPublished - 11 Jul 2019

Cite this

LIPID Study Investigators. / Changes in plasma lipids predict pravastatin efficacy in secondary prevention. In: JCI Insight. 2019 ; Vol. 4, No. 13.
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title = "Changes in plasma lipids predict pravastatin efficacy in secondary prevention",
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 lschaemic 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.",
keywords = "LIPOPROTEIN CHOLESTEROL LEVELS, ACUTE CORONARY SYNDROMES, LONG-TERM INTERVENTION, CARDIOVASCULAR EVENTS, DISEASE, RISK, SIMVASTATIN, REDUCTION, DEATH",
author = "{LIPID Study Investigators} and Jayawardana, {Kaushala S.} and Mundra, {Piyushkumar A.} and Corey Giles and Barlow, {Christopher K.} and Nestel, {Paul J.} and Barnes, {Elizabeth H.} and Adrienne Kirby and Peter Thompson and Sullivan, {David R.} and Alshehry, {Zahir H.} and Mellett, {Natalie A.} and Kevin Huynh and McConville, {Malcolm J.} and Sophia Zoungas and Hillis, {Graham S.} and John Chalmers and Mark Woodward and Marschner, {Ian C.} and Gerard Wong and Kingwell, {Bronwyn A.} and John Simes and Tonkin, {Andrew M.} and Meikle, {Peter J.}",
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Changes in plasma lipids predict pravastatin efficacy in secondary prevention. / LIPID Study Investigators.

In: JCI Insight, Vol. 4, No. 13, 128438, 11.07.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Changes in plasma lipids predict pravastatin efficacy in secondary prevention

AU - LIPID Study Investigators

AU - Jayawardana, Kaushala S.

AU - Mundra, Piyushkumar A.

AU - Giles, Corey

AU - Barlow, Christopher K.

AU - Nestel, Paul J.

AU - Barnes, Elizabeth H.

AU - Kirby, Adrienne

AU - Thompson, Peter

AU - Sullivan, David R.

AU - Alshehry, Zahir H.

AU - Mellett, Natalie A.

AU - Huynh, Kevin

AU - McConville, Malcolm J.

AU - Zoungas, Sophia

AU - Hillis, Graham S.

AU - Chalmers, John

AU - Woodward, Mark

AU - Marschner, Ian C.

AU - Wong, Gerard

AU - Kingwell, Bronwyn A.

AU - Simes, John

AU - Tonkin, Andrew M.

AU - Meikle, Peter J.

PY - 2019/7/11

Y1 - 2019/7/11

N2 - 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 lschaemic 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.

AB - 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 lschaemic 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.

KW - LIPOPROTEIN CHOLESTEROL LEVELS

KW - ACUTE CORONARY SYNDROMES

KW - LONG-TERM INTERVENTION

KW - CARDIOVASCULAR EVENTS

KW - DISEASE

KW - RISK

KW - SIMVASTATIN

KW - REDUCTION

KW - DEATH

U2 - 10.1172/jci.insight.128438

DO - 10.1172/jci.insight.128438

M3 - Article

VL - 4

JO - JCI Insight

JF - JCI Insight

SN - 2379-3708

IS - 13

M1 - 128438

ER -