Background:Recent clinical studies showed that lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ) is a predictor for incident atherosclerotic disease. We have previously shown that among the LDL subfractions, Lp-PLA 2 activity is preferentially associated with the atherogenic small, dense (sdLDL) particles in vitro. We investigated whether Lp-PLA 2 could be a marker of sdLDL in human plasma. Methods: One hundred and seventy-six individuals participated in the study. LDL subclass analysis was performed by polyacrylamide gel electrophoresis. Lp-PLA 2 activity and mass were determined in total plasma and in apolipoprotein B-depleted plasma (HDL-Lp-PLA 2 ). Non-HDL-Lp-PLA 2 activity and mass were calculated by subtracting the HDL-Lp-PLA 2 from total plasma Lp-PLA 2 . Results: On the basis of the LDL subclass analysis, participants were categorized into phenotype A and non-A (total cholesterol mass of the sdLDL subfractions <0.155 and >0.155 mmol/L, respectively). Unlike total plasma Lp-PLA 2 mass, total plasma Lp-PLA 2 activity and non-HDL-Lp-PLA 2 activity and mass were significantly higher in persons with phenotype non-A compared with persons with phenotype A, whereas HDLLp-PLA 2 activity and mass were lower in persons with phenotype non-A compared with phenotype A. Total plasma activity and non-HDL-Lp-PLA 2 activity and mass, but not Lp-PLA 2 mass, were correlated with sdLDL-cholesterol mass, proportion, and mean LDL