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Keywords:

  • biomarker;
  • cardiovascular disease;
  • lipoprotein-associated phospholipase A2;
  • risk factors

Abstract.  Heart Protection Study Collaborative Group (Clinical Trial Service Unit, University of Oxford, Oxford, UK) Lipoprotein-associated phospholipase A2 activity and mass in relation to vascular disease and nonvascular mortality. J Intern Med 2010; 268:348–358.

Objectives.  To assess whether associations of circulating lipoprotein-associated phospholipase A2 (Lp-PLA2) with vascular disease are independent of other risk factors.

Methods.  Lp-PLA2 activity and mass, lipids and other characteristics were measured at baseline in 19 037 individuals at high risk of vascular disease in a randomized trial of simvastatin with 5-year average follow-up.

Results.  Lp-PLA2 activity and mass were correlated with each other (r = 0.56), lipids and other vascular risk factors. The moderate association of Lp-PLA2 activity with occlusive coronary events (n = 2531) in analyses adjusted for nonlipid factors (hazard ratio per 1 SD [HR] 1.11, 95% CI 1.06–1.15) became nonsignificant after further adjustment for apolipoproteins (HR 1.02, 0.97–1.06). Such adjustment also attenuated HRs with Lp-PLA2 mass from 1.08 (1.03–1.12) to 1.05 (1.01–1.09). By contrast, the HR with apolipoprotein-B100 of 1.15 (1.10–1.19) was only slightly attenuated to 1.14 (1.09–1.19) after further adjustment for apolipoprotein A1 and Lp-PLA2. Age- and sex-adjusted HRs for other cardiac events (n = 1007) with either Lp-PLA2 activity or mass were about 1.20, but HRs reduced after adjustment for nonlipid factors (activity: 1.11, 1.04–1.18; mass: 1.08, 1.02–1.15). Adjusted HRs for ischaemic stroke (n = 900) were weak and nonsignificant and for nonvascular mortality (n = 1040) were 1.01 (0.94–1.09) with activity and 1.12 (1.05–1.19) with mass. Simvastatin reduced Lp-PLA2 levels by about one-quarter, but simvastatin’s vascular protection did not vary with baseline Lp-PLA2 concentration.

Conclusions.  Associations of Lp-PLA2 with occlusive coronary events depend considerably on lipid levels, whereas those with other cardiac events appear to reflect confounding from cardiovascular medication and prior vascular disease.