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Background The association of emerging biomarkers such as high-sensitivity C-reactive protein (hs-CRP),homocysteine and fibrinogen with the risk of coronary artery disease (CAD) is still uncertain in Asian population including Koreans and little is known about the combined effect of biomarkers on the risk of CAD.Methods A total of 10 650 subjects (6538 men and 4112 women) were enrolled in this study.A 10-year CAD risk was calculated using Framingham risk score modified by the National Cholesterol Education Program (NCEP) Adult Treatment Panel Ⅲ (ATP Ⅲ ) and levels of circulating hs-CRP,homocysteine and fibrinogen were measured using validated assays.Results The 10-year CAD risk gradually augmented with increase in the circulating levels of hs-CRP,homocysteine and fibrinogen.For the highest quartile of hs-CRP,odds ratio (OR) of high-risk for CAD (10-year risk ≥20%) compared with the lowest quartile was 3.97 (95% C/:2.51-6.29).For homocysteine and fibrinogen,ORs in the highest quartile compared to the lowest quartile were 5.10 (95% Cl:3.05-8.53,P <0.001) and 1.46 (95% Cl:0.69-3.11,P=0.325),respectively.OR of high-risk for CAD in both the highest quartile of hs-CRP and homocysteine was 9.05 (95% CI:5.30-15.45) compared with the below median of hs-CRP and homocysteine.Conclusions The present study demonstrated that hs-CRP and homocysteine are well associated with the 10-year CAD risk estimated using NCEP ATP Ⅲ in Koreans and combination of hs-CRP and homocysteine can have strong synergyin predicting the development of CAD.