OBJECTIVE: To examine the association of lipoprotein-associated phospholipase A2 (Lp-PLA2) mass and activity with calcified coronary plaque in young adults. METHODS AND RESULTS: Nested case-control study among CARDIA participants at the year 15 examination (2000 to 2001, 33 to 45 years old). Cases (n=266) were those with and controls (n=266) those without evidence of calcified coronary plaque by computed tomography matched 1:1 on sex and race. Lp-PLA2 mass and activity were significantly higher in cases (296+/-101 ng/mL and 36.4+/-12.3 nmol/mL per minute) than in controls (267+/-80 ng/mL and 32.9+/-11.8 nmol/mL per minute). In age-adjusted conditional logistic regression, the odds ratio (OR) of calcified coronary plaque per 1 standard deviation (SD) increment was 1.40 (95% CI, 1.17 to 1.67) and 1.39 (95% CI, 1.14 to 1.70) for Lp-PLA2 mass and activity, respectively. After adjusting for multiple covariates including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, and C-reactive protein, a statistically significant association remained for Lp-PLA2 mass (OR, 1.28; 95% CI, 1.03 to 1.60) but not for activity (OR, 1.09; 95% CI, 0.84 to 1.42). No evidence was found for interaction between Lp-PLA2 mass or activity with LDL-C as predictors of calcified coronary plaque. CONCLUSIONS: An independent association of Lp-PLA2 mass with calcified coronary plaque existed in young adults. Therefore, Lp-PLA2 mass may be a useful marker of subclinical cardiovascular risk.