Lipoprotein-associated phospholipase A₂ activity and mass in relation to vascular disease and nonvascular mortality.
OBJECTIVE
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.
Clinical Trial Service Unit, University of Oxford, Oxford, UK. hps@ctsu.ox.ac.uk
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000201:enzymology* / Q000401:mortality; D005260:Female; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D019821:Simvastatin / Q000627:therapeutic use*; D016896:Treatment Outcome
D015415:Biomarkers; D000960:Hypolipidemic Agents; D019821:Simvastatin; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase