Hyperlipoproteinemia affects cytokine production in whole blood samples ex vivo. The influence of lipid-lowering therapy

A specific and robust immunoassay for the lipoprotein-associated phospholipase A₂ (Lp-PLA₂), platelet-activating factor acetylhydrolase, is described for the first time. The immunoassay was used to evaluate possible links between plasma Lp-PLA₂ levels and atherosclerosis risk amongst susceptible individuals. Such an investigation was important because Lp-PLA₂ participates in the oxidative modification of low density lipoprotein by cleaving oxidised phosphatidylcholines, generating lysophosphatidylcholine and oxidised free fatty acids. The majority of Lp-PLA₂ was found associated with LDL (approximately 80%) and, as expected, enzyme levels were significantly positively correlated to LDL cholesterol. Plasma Lp-PLA₂ levels were significantly elevated in patients with angiographically proven coronary artery disease (CAD) when compared with age-matched controls, even though LDL cholesterol levels did not differ significantly. Indeed, when included in a general linear model with LDL cholesterol and other risk factors, Lp-PLA₂ appeared to be an independent predictor of disease status. We propose, therefore, that plasma Lp-PLA₂ mass should be viewed as a potential novel risk factor for CAD that provides information related to but additional to traditional lipoprotein measurements.