Objective To investigate the relationships between the levels of plasma soluble CD40 ligand (sCD40L),fetuin-A and pregnancy-associated plasma protein A (PAPP-A) and carotid plaque in patients with acute ischemic stroke.Methods The patients with acute ischemic stroke were enrolled in the study.Carotid arteries were assessed by using carotid artery ultrasound.The patients were divided into either a carotid artery plaque group or a non-carotid artery plaque group according to the assessment results.The former were further divided into a stable plaque sub-group and an unstable plaque sub-group according the nature of plaque.Enzyme-linked immunosorbent assay was used to detect the levels of plasma sCD40L,fetuin-A and PAPP-A.The demography,previous history,complications,laboratory tests and plasma inflammatory biomarkers between the carotid artery plaque group and the non-carotid artery plaque group and between the stable plaque subgroup and the unstable plaque subgroup were compared.Multivariate logistic regression analysis was used to investigate the relationship between plasma inflammatory biomarkers and carotid plaques.Results A total of 200 patients with acute ischemic stroke were included.Among them,78 were females and 122 were males (aged 33 to 87 years,mean 60.1 ± 10.3 years); 139 patients were in the carotid artery plaque group and 61 were in the non-plaque group; 43 were in the stable plaque subgroup and 96 were in the unstable plaque subgoup.The mean age of the carotid artery plaque subgroup was significantly greater than that in the non-plaque subgroup (63.2 ± 8.7 years vs.50.3 ± 9.5 years; t ＝ 10.179,P =0.000),the constituent ratios of men (68.3％ vs.44.3％;x2＝ 10.336,P＝ 0.001),hypertension (71.2 vs.54.1％;x2=5.540,P=0.019),diabetes (46.8％ vs.29.5％ ;x2 =5.199,P =0.023),and hyperlipidemia (78.4％ vs.37.7％ ;x2 =31.31,P =0.000)in patients of carotid plaque group were significantly higher than those of the non-carotid plaque group.The levels of total cholesterol (5.7 ± 1.1 mmol/L vs.5.3 ± 1.0 mmol/L; t =2.433,P =0.016),low-density lipoprotein cholesterol (4.5 ± 1.0 mmol/L vs.4.1 ±0.9 mmol/L; t =2.683,P =0.008),fasting glucose (7.5 ±2.5 mmol/Lvs.6.4±2.1 mmol/L; t=3.002,P＝0.003),sCD40L (151.4 ± 55.8 pg/mlvs.102.8 ±65.9 pg/ml; t =5.360,P=0.000),fctuin-A (390.1 ± 80.6 μg/ml v.s.352.9 ± 98.6 μg/ml; t =2.591,P =0.011),and PAPP-A (11.49 ±4.67 mIU/L vs.8.46 ± 3.99 mIU/L; t =4.409,P =0.000) were significantly higher than those of the non-carotid plaque group.Multivariate logistic regression analysis showed that hyperlipidemia (odds ratio [OR] 6.582,95％ confidence interval [CI] 2.321-18.662; P =0.000),sCD40L (OR6.372,95％ CI 2.174-18.670;P=0.010),and fetuin-A (OR 4.101,95％ CI 1.012-16.619; P=0.048) were the independent predictors for carotid artery plaques in patients with acute ischemic stroke.The mean age of the stable plaque subgroup was significantly lower than that of the unstable plaque subgroup (59.6 ± 9.3 years vs.64.1 ± 7.2 years; t =3.231,P =0.002).The constituent ratio in patients with hypertension was significantly lower than that of the unstable plaque subgroup (55.8％ vs.78.1％ ; x2 =7.213,P =0.007).The levels of total cholesterol (5.4 ±0.9 mmol/L vs.6.0 ± 1.1 mmol/L; t =3.136,P =0.002),low-density lipoprotein cholesterol (4.0 ± 1.2 mmol/L vs.5.7 ± 1.0 mmol/L; t =8.696,P =0.000),fasting glucose (7.1 ± 2.3 mmol/L vs,7.9 ± 1.9 mmol/L; t =2.147,P =0.034),sCD40L (135.3 ±74.3 pg/ml vs.176.5 ±64.5 pg/ml; t =3.319,P ＝0.001),and PAPP-A (10.96 ± 5.02 mIU/L vs.13.98 ±4.63 mIU/L; t =3.463,P =0.001) were significantly lower than those of the unstable plaque subgroup,while the level of high-density lipoprotein cholesterol was significantly higher than that of the unstable plaque subgroup (1.2 ± 0.2 mmol/L vs.1.1 ± 0.3 mmol/L; t =2.314,P=0.022).Multivariate logistic regression analysis showed that HDL-C (OR 0.234,95％ CI0.060-0.906; P =0.022) was an independent protective factor for unstable plaques,while sCD40L (OR 5.290,95％ CI 1.613-17.351; P =0.029) and PAPP-A (OR4.125,95％ CI 1.281-13.283; P =0.021) were the independent predictors for unstable plaques.Conclusions The levels of sCD40L,PAPP-A,and fetuin-A were associated with the existence and stability of carotid artery plaque.The increased plasma sCD40L and fetuin-A were the independent predictors for carotid artery plaques in patients with acute ischemic stroke,and the increased levels of plasma sCD40L and PAPP-A were the independent predictors for carotid artery plaque instability in patients with acute ischemic stroke.