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 D., Simes, John, Stewart, Ralph A. H., Blankenberg, Stefan, Barnes, Elizabeth H., Marschner, Ian C., Thompson, Peter, West, Malcolm, Zeller, Tanja, Colquhoun, David M., Nestel, Paul, Keech, Anthony C., Sullivan, David R., Hunt, David and Tonkin, Andrew (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: e000360.1-e000360.12. doi:10.1161/JAHA.113.000360

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Author White, Harvey D.
Simes, John
Stewart, Ralph A. H.
Blankenberg, Stefan
Barnes, Elizabeth H.
Marschner, Ian C.
Thompson, Peter
West, Malcolm
Zeller, Tanja
Colquhoun, David M.
Nestel, Paul
Keech, Anthony C.
Sullivan, David R.
Hunt, David
Tonkin, Andrew
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
Journal name Journal of the American Heart Association   Check publisher's open access policy
ISSN 2047-9980
Publication date 2013-10-01
Sub-type Article (original research)
DOI 10.1161/JAHA.113.000360
Open Access Status DOI
Volume 2
Issue 5
Start page e000360.1
End page e000360.12
Total pages 12
Place of publication Hoboken, NJ, United States
Publisher Wiley-Blackwell
Language eng
Formatted abstract
Background: Lipoprotein-associated phospholipase A2 (Lp-PLA2) 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-PLA2 activity to predict outcomes over a 6-year follow-up, the effect of pravastatin on Lp-PLA2 levels, and whether pravastatin treatment effect was related to Lp-PLA2 activity change. Lp-PLA2was 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-PLA2 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-PLA2 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-PLA2 by 16% compared with placebo (P<0.001). After adjustment for Lp-PLA2 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-PLA2. Similar reductions in treatment effect were seen after adjustment for LDL cholesterol change.

Conclusion: Reduction in Lp-PLA2 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. 
Keyword Biomarkers
LIPID
Lp-PLA(2)
Pravastatin
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Medicine Publications
 
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