Heart Protection Study Collaborative Group are listed in the Contributors section
Lipoprotein-associated phospholipase A2 activity and mass in relation to vascular disease and nonvascular mortality
Article first published online: 7 JUL 2010
© 2010 The Association for the Publication of the Journal of Internal Medicine
Journal of Internal Medicine
Volume 268, Issue 4, pages 348–358, October 2010
How to Cite
Heart Protection Study Collaborative Group (2010), Lipoprotein-associated phospholipase A2 activity and mass in relation to vascular disease and nonvascular mortality. Journal of Internal Medicine, 268: 348–358. doi: 10.1111/j.1365-2796.2010.02258.x
- Issue published online: 1 SEP 2010
- Article first published online: 7 JUL 2010
- 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.