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
UR - http://www.scopus.com/inward/record.url?scp=85070659111&partnerID=8YFLogxK
UR - https://www.scopus.com/pages/publications/85070659111
U2 - 10.1172/jci.insight.128438
DO - 10.1172/jci.insight.128438
M3 - Article
C2 - 31292301
SN - 2379-3708
VL - 4
JO - JCI Insight
JF - JCI Insight
IS - 13
M1 - :e12843
ER -
