Cardiovascular events with increased lipoprotein-associated phospholipase A 2 and low high-density lipoprotein-cholesterol the veterans affairs HDL intervention trial

Sander J. Robins, Dorothea Collins, Jeanenne J. Nelson, Hanna E. Bloomfield, Bela F. Asztalos

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52 Scopus citations

Abstract

Objective-Lipoprotein-associated phospholipase A 2 (Lp-PLA 2), a proinflammatory enzyme that predominantly circulates with low-density lipoprotein (LDL), has been shown in general populations to predict cardiovascular (CV) events. We sought to determine whether increased Lp-PLA 2 would also predict CV events in the absence of high LDL-cholesterol (LDL-C), in a population with low high-density lipoprotein-cholesterol (HDL-C). Methods and Results-Plasma Lp-PLA 2 activity was measured at baseline and after 6 months on-trial in 1451 men with low HDL-C (mean, 32 mg/dL) and low LDL-C (mean 110 mg/dL), randomized to either placebo or gemfibrozil therapy in the Veterans Affairs HDL Intervention Trial (VA-HIT). Over a quartile range of increasing Lp-PLA 2 there was a significant increase in LDL-C and decrease in HDL-C (P<0.0001), and an increased percentage of myocardial infarction (MI), stroke, or CHD death (P=0.03 for trend). In Cox models, adjusted for major CV risk factors, a 1-SD increase in Lp-PLA 2 was associated with a significant increase in CV events (hazard ratio [HR] 1.17 95% CI 1.04 to 1.32). Although gemfibrozil reduced Lp-PLA 2 only modestly (6.6%), at higher levels OfLp-PLA 2 gemfibrozil produced a significant reduction in CV events. Conclusions-In VA-IIIT, a population with low HDL-C and LDL-C, high Lp-PLA 2 independently predicted CV events that were reduced by gemfibrozil. (Arterioscler Thromb Vase Biol. 2008;28:1172-1178)

Original languageEnglish (US)
Pages (from-to)1172-1178
Number of pages7
JournalArteriosclerosis, thrombosis, and vascular biology
Volume28
Issue number6
DOIs
StatePublished - Jun 1 2008

Keywords

  • Cardiovascular events
  • Gemfibrozil
  • High-density lipoproteins
  • Inflammation
  • Lipoprotein-associated phospholipase A

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