Lipoprotein-associated phospholipase A₂, inflammatory biomarkers, and risk of cardiovascular disease in the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER)

Abstract 

Objective

Lipoprotein-associated phospholipase A₂ (Lp-PLA₂) is an inflammatory biomarker that circulates mainly bound to LDL. We evaluated the association of Lp-PLA₂ with vascular events in the elderly where the importance of LDL is diminished as a risk factor for coronary disease.

Methods

Mass and activity of Lp-PLA₂ were related to risk over 3.2 years for vascular events (definite or suspected death from CHD, non-fatal MI, fatal or non-fatal stroke) in the 2804 men and 3000 women age 70–82 years in the Prospective Study of Pravastatin in the Elderly (PROSPER).

Results

Lp-PLA₂ showed a moderate, positive association with risk of a vascular event with hazard ratios of 1.25 (confidence interval (CI) 1.02–1.54) for mass and 1.39 (CI 1.14–1.70) for activity for top versus bottom quartile. Risk associations were attenuated when classical risk factors, lipids and inflammatory markers – C-reactive protein and white cell count – were included in the models. Lp-PLA₂ was unrelated to stroke risk. Inclusion of all three inflammatory markers in multivariate models negated the association of HDL cholesterol with risk (hazard ratio 0.98; CI 0.88–1.10) and increased prediction of coronary events; the C statistic rose from 63.2% to 64.4% (P<0.001).

Conclusion

In elderly people Lp-PLA₂, alongside other inflammatory indices, is a potential biomarker for vascular events, particularly CHD.

Keywords: Lipoprotein-associated phospholipids A2, Elderly, Prosper, Inflammatory markers, Coronary heart disease risk