BACKGROUND: Coronary artery disease (CAD) is the leading cause of death and disability worldwide. Lipoprotein associated phospholipase A (Lp-PLA) is an emerging biomarker for inflammation that has shown association with CAD. Its significance in the Asian Indian population is not clearly known. We sought to compare the possible association of various biomarkers of atherosclerosis along with Lp-PLA, in symptomatic individuals with CAD vs. healthy controls in Asian South-Indians. METHODS: We conducted a cross-sectional case control study at three centers in a South Indian population. A total of 100 CAD patients with acute coronary syndrome (ACS), 100 age and gender matched healthy controls participated, of which, 166 subjects or 83 case-control pairs with complete data for both participants were identified for the statistical analysis. Lp-PLA concentration and activity were measured using PLAC test and PLAC activity assay respectively (diaDexus Inc., San Francisco, CA, USA), while all other parameters were measured using standard commercially available kits. RESULTS: We enrolled a total of 200 subjects (mean age 50.7±9.6 years, 87.5% males). A total of 83 subjects completed the study in the CAD group (mean age 51 ±8.9 years, 85% males) and 83 subjects in the control group (mean age 50±8.9 years, 86.5% males). In the CAD group, Lp-PLA concentration positively correlated with TC (ρ=0.19, P=0.02), non-HDL-C (ρ=0.20, P=0.02), Lp-PLA activity (ρ=0.27, P=0.001) and Lp(a) (r=0.25, P=0.02). Lp-PLA activity correlated positively with TC (ρ=0.28, P=0.001), LDL-C (ρ=0.30, P<0.001), non-HDL-C (ρ=0.35, P<0.001), ApoB (ρ=0.35, P<0.001) and negatively correlated to HDL-C (ρ=-0.24, P=0.004). Cox proportionality hazards model revealed Lp-PLA concentration (β=0.006, SE =0.002, P=0.009) to have positive association with the event of CAD, while negative association was observed for ApoA1 (β=-0.06, SE =0.02, P=0.001). ROC analysis revealed that the highest quartile of Lp-PLA concentration to have area under curve (AUC) of 0.80 (95% CI, 0.65-0.9; P<0.001) with cut off value of >427 ng/mL and ApoA1 with AUC of 0.78 (95% CI, 0.70-0.85; P<0.001) with cut off value of ≤129.6 mg/dL with the optimum balance of sensitivity and specificity. CONCLUSIONS: In this study population, circulating plasma Lp-PLA was found to be elevated in CAD group. ApoA1 showed negative association and Lp-PLA concentration showed positive association with risk for CAD. In the highest quartile, Lp-PLA concentration had the best diagnostic utility. Our results support the hypothesis that Lp-PLA may be a potential risk marker for CAD in Asian Indians.