Changes in lipoprotein-Associated phospholipase A2 activity predict coronary events and partly account for the treatment effect of pravastatin: results from the Long-Term Intervention with Pravastatin in Ischemic Disease study

Harvey White; John Simes; Ralph Stewart; Stefan Blankenberg; Elizabeth Barnes; Ian Marschner; Peter Thompson; Malcolm West; Tanja Zeller; David Colquhoun; Paul Nestel; Anthony Keech; David Sullivan; David Hunt; Andrew Tonkin

doi:10.1161/JAHA.113.000360

Changes in lipoprotein-Associated phospholipase A2 activity predict coronary events and partly account for the treatment effect of pravastatin: results from the Long-Term Intervention with Pravastatin in Ischemic Disease study

Harvey White, John Simes, Ralph Stewart, Stefan Blankenberg, Elizabeth Barnes, Ian Marschner, Peter Thompson, Malcolm West, Tanja Zeller, David Colquhoun, Paul Nestel, Anthony Keech, David Sullivan, David Hunt, Andrew Tonkin

Research output: Contribution to journal › Article › peer-review

45 Citations (Scopus)

Abstract

Background--Lipoprotein-associated phospholipase A2 (Lp-PLA ₂) levels are associated with coronary heart disease (CHD) in healthy individuals and in patients who have had ischemic events. Methods and Results--The Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) study randomized 9014 patients with cholesterol levels of 4.0 to 7.0 mmol/L to placebo or pravastatin 3 to 36 months after myocardial infarction or unstable angina and showed a reduction in CHD and total mortality. We assessed the value of baseline and change in Lp-PLA ₂ activity to predict outcomes over a 6-year follow-up, the effect of pravastatin on Lp-PLA ₂ levels, and whether pravastatin treatment effect was related to Lp-PLA ₂ activity change. Lp-PLA ₂ was measured at randomization and 1 year, and levels were grouped as quartiles. The prespecified end point was CHD death or nonfatal myocardial infarction. Baseline Lp-PLA ₂ activity was positively associated with CHD events (P<0.001) but not after adjustment for 23 baseline factors (P=0.66). In 6518 patients who were event free at 1 year, change in Lp-PLA ₂ was a significant independent predictor of subsequent CHD events after adjustment for these risk factors, including LDL cholesterol and LDL cholesterol changes (P<0.001). Pravastatin reduced Lp-PLA ₂ by 16% compared with placebo (P<0.001). After adjustment for Lp-PLA ₂ change, the pravastatin treatment effect was reduced from 23% to 10% (P=0.26), with 59% of the treatment effect accounted for by changes in Lp-PLA ₂. Similar reductions in treatment effect were seen after adjustment for LDL cholesterol change. Conclusion--Reduction in Lp-PLA ₂ activity during the first year was a highly significant predictor of CHD events, independent of change in LDL cholesterol, and may account for over half of the benefits of pravastatin in the LIPID study.

Original language	English
Pages (from-to)	1-13
Number of pages	13
Journal	Journal of the American Heart Association
Volume	2
Issue number	5
DOIs	https://doi.org/10.1161/JAHA.113.000360
Publication status	Published - 14 Dec 2013

Keywords

Biomarkers
Lipid
Lp-PLA
Pravastatin

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White, H., Simes, J., Stewart, R., Blankenberg, S., Barnes, E., Marschner, I., Thompson, P., West, M., Zeller, T., Colquhoun, D., Nestel, P., Keech, A., Sullivan, D., Hunt, D., & Tonkin, A. (2013). Changes in lipoprotein-Associated phospholipase A2 activity predict coronary events and partly account for the treatment effect of pravastatin: results from the Long-Term Intervention with Pravastatin in Ischemic Disease study. Journal of the American Heart Association, 2(5), 1-13. https://doi.org/10.1161/JAHA.113.000360

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title = "Changes in lipoprotein-Associated phospholipase A2 activity predict coronary events and partly account for the treatment effect of pravastatin: results from the Long-Term Intervention with Pravastatin in Ischemic Disease study",

abstract = "Background--Lipoprotein-associated phospholipase A2 (Lp-PLA 2) levels are associated with coronary heart disease (CHD) in healthy individuals and in patients who have had ischemic events. Methods and Results--The Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) study randomized 9014 patients with cholesterol levels of 4.0 to 7.0 mmol/L to placebo or pravastatin 3 to 36 months after myocardial infarction or unstable angina and showed a reduction in CHD and total mortality. We assessed the value of baseline and change in Lp-PLA 2 activity to predict outcomes over a 6-year follow-up, the effect of pravastatin on Lp-PLA 2 levels, and whether pravastatin treatment effect was related to Lp-PLA 2 activity change. Lp-PLA 2 was measured at randomization and 1 year, and levels were grouped as quartiles. The prespecified end point was CHD death or nonfatal myocardial infarction. Baseline Lp-PLA 2 activity was positively associated with CHD events (P<0.001) but not after adjustment for 23 baseline factors (P=0.66). In 6518 patients who were event free at 1 year, change in Lp-PLA 2 was a significant independent predictor of subsequent CHD events after adjustment for these risk factors, including LDL cholesterol and LDL cholesterol changes (P<0.001). Pravastatin reduced Lp-PLA 2 by 16% compared with placebo (P<0.001). After adjustment for Lp-PLA 2 change, the pravastatin treatment effect was reduced from 23% to 10% (P=0.26), with 59% of the treatment effect accounted for by changes in Lp-PLA 2. Similar reductions in treatment effect were seen after adjustment for LDL cholesterol change. Conclusion--Reduction in Lp-PLA 2 activity during the first year was a highly significant predictor of CHD events, independent of change in LDL cholesterol, and may account for over half of the benefits of pravastatin in the LIPID study. ",

keywords = "Biomarkers, Lipid, Lp-PLA, Pravastatin",

author = "Harvey White and John Simes and Ralph Stewart and Stefan Blankenberg and Elizabeth Barnes and Ian Marschner and Peter Thompson and Malcolm West and Tanja Zeller and David Colquhoun and Paul Nestel and Anthony Keech and David Sullivan and David Hunt and Andrew Tonkin",

year = "2013",

month = dec,

day = "14",

doi = "10.1161/JAHA.113.000360",

language = "English",

volume = "2",

pages = "1--13",

journal = "Journal of the American Heart Association",

issn = "2047-9980",

publisher = "AHA Journals",

number = "5",

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White, H, Simes, J, Stewart, R, Blankenberg, S, Barnes, E, Marschner, I, Thompson, P, West, M, Zeller, T, Colquhoun, D, Nestel, P, Keech, A, Sullivan, D, Hunt, D & Tonkin, A 2013, 'Changes in lipoprotein-Associated phospholipase A2 activity predict coronary events and partly account for the treatment effect of pravastatin: results from the Long-Term Intervention with Pravastatin in Ischemic Disease study', Journal of the American Heart Association, vol. 2, no. 5, pp. 1-13. https://doi.org/10.1161/JAHA.113.000360

Changes in lipoprotein-Associated phospholipase A2 activity predict coronary events and partly account for the treatment effect of pravastatin: results from the Long-Term Intervention with Pravastatin in Ischemic Disease study. / White, Harvey; Simes, John; Stewart, Ralph et al.
In: Journal of the American Heart Association, Vol. 2, No. 5, 14.12.2013, p. 1-13.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Changes in lipoprotein-Associated phospholipase A2 activity predict coronary events and partly account for the treatment effect of pravastatin: results from the Long-Term Intervention with Pravastatin in Ischemic Disease study

AU - White, Harvey

AU - Simes, John

AU - Stewart, Ralph

AU - Blankenberg, Stefan

AU - Barnes, Elizabeth

AU - Marschner, Ian

AU - Thompson, Peter

AU - West, Malcolm

AU - Zeller, Tanja

AU - Colquhoun, David

AU - Nestel, Paul

AU - Keech, Anthony

AU - Sullivan, David

AU - Hunt, David

AU - Tonkin, Andrew

PY - 2013/12/14

Y1 - 2013/12/14

N2 - Background--Lipoprotein-associated phospholipase A2 (Lp-PLA 2) levels are associated with coronary heart disease (CHD) in healthy individuals and in patients who have had ischemic events. Methods and Results--The Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) study randomized 9014 patients with cholesterol levels of 4.0 to 7.0 mmol/L to placebo or pravastatin 3 to 36 months after myocardial infarction or unstable angina and showed a reduction in CHD and total mortality. We assessed the value of baseline and change in Lp-PLA 2 activity to predict outcomes over a 6-year follow-up, the effect of pravastatin on Lp-PLA 2 levels, and whether pravastatin treatment effect was related to Lp-PLA 2 activity change. Lp-PLA 2 was measured at randomization and 1 year, and levels were grouped as quartiles. The prespecified end point was CHD death or nonfatal myocardial infarction. Baseline Lp-PLA 2 activity was positively associated with CHD events (P<0.001) but not after adjustment for 23 baseline factors (P=0.66). In 6518 patients who were event free at 1 year, change in Lp-PLA 2 was a significant independent predictor of subsequent CHD events after adjustment for these risk factors, including LDL cholesterol and LDL cholesterol changes (P<0.001). Pravastatin reduced Lp-PLA 2 by 16% compared with placebo (P<0.001). After adjustment for Lp-PLA 2 change, the pravastatin treatment effect was reduced from 23% to 10% (P=0.26), with 59% of the treatment effect accounted for by changes in Lp-PLA 2. Similar reductions in treatment effect were seen after adjustment for LDL cholesterol change. Conclusion--Reduction in Lp-PLA 2 activity during the first year was a highly significant predictor of CHD events, independent of change in LDL cholesterol, and may account for over half of the benefits of pravastatin in the LIPID study.

AB - Background--Lipoprotein-associated phospholipase A2 (Lp-PLA 2) levels are associated with coronary heart disease (CHD) in healthy individuals and in patients who have had ischemic events. Methods and Results--The Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) study randomized 9014 patients with cholesterol levels of 4.0 to 7.0 mmol/L to placebo or pravastatin 3 to 36 months after myocardial infarction or unstable angina and showed a reduction in CHD and total mortality. We assessed the value of baseline and change in Lp-PLA 2 activity to predict outcomes over a 6-year follow-up, the effect of pravastatin on Lp-PLA 2 levels, and whether pravastatin treatment effect was related to Lp-PLA 2 activity change. Lp-PLA 2 was measured at randomization and 1 year, and levels were grouped as quartiles. The prespecified end point was CHD death or nonfatal myocardial infarction. Baseline Lp-PLA 2 activity was positively associated with CHD events (P<0.001) but not after adjustment for 23 baseline factors (P=0.66). In 6518 patients who were event free at 1 year, change in Lp-PLA 2 was a significant independent predictor of subsequent CHD events after adjustment for these risk factors, including LDL cholesterol and LDL cholesterol changes (P<0.001). Pravastatin reduced Lp-PLA 2 by 16% compared with placebo (P<0.001). After adjustment for Lp-PLA 2 change, the pravastatin treatment effect was reduced from 23% to 10% (P=0.26), with 59% of the treatment effect accounted for by changes in Lp-PLA 2. Similar reductions in treatment effect were seen after adjustment for LDL cholesterol change. Conclusion--Reduction in Lp-PLA 2 activity during the first year was a highly significant predictor of CHD events, independent of change in LDL cholesterol, and may account for over half of the benefits of pravastatin in the LIPID study.

KW - Biomarkers

KW - Lipid

KW - Lp-PLA

KW - Pravastatin

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U2 - 10.1161/JAHA.113.000360

DO - 10.1161/JAHA.113.000360

M3 - Article

SN - 2047-9980

VL - 2

SP - 1

EP - 13

JO - Journal of the American Heart Association

JF - Journal of the American Heart Association

IS - 5

ER -

White H, Simes J, Stewart R, Blankenberg S, Barnes E, Marschner I et al. Changes in lipoprotein-Associated phospholipase A2 activity predict coronary events and partly account for the treatment effect of pravastatin: results from the Long-Term Intervention with Pravastatin in Ischemic Disease study. Journal of the American Heart Association. 2013 Dec 14;2(5):1-13. doi: 10.1161/JAHA.113.000360

Changes in lipoprotein-Associated phospholipase A2 activity predict coronary events and partly account for the treatment effect of pravastatin: results from the Long-Term Intervention with Pravastatin in Ischemic Disease study

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