New scores for prediction of left atrial thrombus/spontaneous echo contrast in patients with nonvalvular atrial fibrillation: A single-center retrospective analysis
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摘要: 目的探索预测左房血栓(left atrial thrombus，LAT)/自发显影(spontaneous echo contrast，SEC)的新因素，比较CHADS2/CHADS2-VASc加入新的危险因素后，新的模型预测LAT/SEC的能力是否提升；并探索新因素对于CHADS2/CHADS2-VASc模型中的低风险患者LAT/SEC的预测。方法回顾过去10年我院接受经食管超声检查的非瓣膜性心房颤动患者，筛选LAT/SEC的患者，以年龄及性别1∶1匹配左房未见LAT/SEC的患者。使用二元logistic回归分析识别影响LAT/SEC的危险因素。将新的因素纳入CHADS2及CHADS2-VASc模型，利用ROC曲线评价模型预测LAT/SEC的能力是否有所提升。并在低风险患者中(CHADS2-VASc男性0分，女性1分)，利用ROC曲线评价新因素对这部分患者LAT/SEC的预测能力。结果研究共纳入了1270例非瓣膜性房颤患者，其中LAT/SEC 635例，左房未见LAT/SEC 635例。回归分析提示左房增大(LAE)、血尿酸增高(HSUA)及血纤维蛋白原(FIB)是LAT/SEC的独立危险因素。CHADS2+LAE、CHADS2+HSUA、CHASD2+FIB、CHADS2+LAE+HSUA+FIB预测LAT/SEC的ROC曲线下面积(AUC)分别为：0.739、0.647、0.654、0.767，较原模型CHADS2(AUC=0.614)提高(P* < 0.05)。CAHDS2-VASc+LAE、CHADS2-VASc+HSUA、CHADS2-VASc+FIB、CHADS2-VASc+LAE+HSUA+FIB预测LAT/SEC的ROC AUC分别为0.785、0.719、0.710、0.801，较原模型CHADS2-VASc(AUC=0.695)提高(P* < 0.05)。在整组患者中，LAE+HSUA+FIB预测LAT/SEC的ROC AUC为0.756(P < 0.05)，在CHADS2-VASc评分为0(男性)或1(女性)分患者中，LAE+HSUA+FIB*预测LAT/SEC的ROC AUC为0.752(P < 0.05)。结论① LAE、HSUA、FIB是LAT/SEC的独立危险因素。②分别加入LAE、HSUA、FIB后，CHADS2及CHADS2-VASc模型预测能力均有提升。其中，以单独加入LAE带来的提升最显著；三者均加入时，模型预测更准确。③LAE、HSUA、FIB三者可预测CHADS2-VASc评分为0(男)或1分(女)患者中LAT/SEC的发生，有助于筛选真正的低风险患者。Abstract: ObjectiveTo explore new risk factors for predicting left atrial thrombus(LAT)/ Spontaneous echo contrast(SEC), to compare whether the ability of CHADS2 and CHADS2-VASc plus new risk factors to predict LAT/SEC was improved, and explore new factors for the prediction of LAT/SEC in low-risk patients in the CHADS2/CHADS2-VASc model.MethodsWe reviewed patients who had undergone a transesophageal echocardiography exam over the past 10 years, with those descriptions contained"echo contrast". The patients without LAT/SEC were matched 1: 1 by age and sex. Binary logistic regression analysis was used to identify risk markers. The new markers were incorporated into the CHADS2 and CHADS2-VASc scales, and the ROC curve was used to evaluate the predictive power of those new scales. And in patients with a CHADS2-VASc score of 0(male) or 1(female), the ability of new factors to predict LAT/SEC was evaluated.ResultsA total of 1270 patients were included in the study, 635 of them had LAT/SEC. Regression analysis revealed left atrial enlargement(LAE), high serum uric acid level(HSUA), and fibrinogen level(FIB) were the independent risk markers for LAT/SEC. Receiver operating characteristic analysis showed that area under the curve(AUC) of CHADS2+LAE, CHADS2+ HSUA, CHADS2+FIB and CHADS2+LAE+ ISUA +FIB scores were 0.739, 0.647, 0.654 and 0.767, respectively, compared with CHADS2(AUC=0.614), all P* < 0.05. And the AUC of CHADS2-VASc+LAE, CHADS2-VASc + HSUA, CHADS2-VASc +FIB and CHADS2-VASc+LAE+ HSUA +FIB scores were 0.785, 0.719, 0.710 and 0.801, respectively, compared with CHADS2-VASc(AUC=0.695), all P* < 0.05. In all patients, the AUC of LAE+HSUA+FIB scores was 0.756, compared with null hypothesis: true area=0.5, P < 0.05, and in patients with CHADS2-VASc score of 0(male) or 1(female), the receiver operating characteristic curve analysis showed that area under the curve(AUC) of LAE+ ISUA +FIB* scores were 0.752, compared with null hypothesis: true area=0.5, P < 0.05.Conclusion① LAE, HSUA, FIB were independent risk markers for LAT/SEC. ②After adding LAE, HSUA and FIB respectively, the prediction power of CHADS2 and CHADS2-VASc models were all improved. Among them, the most significant improvement was brought by adding LAE alone; when all three are added, the model prediction is most accurate. ③LAE, HSUA, and FIB can predict the occurrence of LAT/SEC in patients with CHADS2-VASc score of 0 or 1(female), which is helpful for screening truly low-risk patients.
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表 1 基线资料
Table 1. General data
例(%), X±S 变量 阳性组 阴性组 P值 年龄/岁 65.7±9.6 65.7±9.6 1.000 ≥75岁 122(19.2) 122(19.2) 1.000 ≥65岁 248(39.1) 248(39.1) 1.000 女性 306(48.2) 306(48.2) 1.000 高血压 358(56.4) 319(50.2) 0.028 糖尿病 111(17.5) 94(14.8) 0.195 充血性心衰 66(10.4) 11(1.7) < 0.001 血管病 94(14.8) 77(12.1) 0.162 卒中/TIA/血栓事件 92(14.5) 51(8.0) < 0.001 抗凝 182(28.7) 148(23.3) 0.015 CHADS2 1.3±1.2 0.8±0.9 < 0.001 CHADS2-VASc 2.5±1.7 1.5±1.1 < 0.001 CHADS2-VASc评分为0或1(女) 112(17.6) 245(38.6) < 0.001 Vmax 0.3±0.2 0.4±0.3 < 0.001 左房直径/mm 44.9±5.9 38.7±6.0 < 0.001 LAE 523(82.4) 273(43.0) < 0.001 LVEF/% 58.8±10.5 64.3±7.4 < 0.001 URIC/(μmol· L-1) 378.3±100.4 344.0±85.7 < 0.001 HSUA 205(32.3) 111(17.5) < 0.001 FIB/(g·L-1) 3.0±0.8 2.7±0.7 < 0.001 注：Vmax：左心耳排空速度；LVEF：左室射血分数。 
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表 2 LAT/SEC单因素logistic回归
Table 2. Univariate logistic regression
因素 OR 95%CI P值 高血压 1.280 1.027~1.597 0.028 糖尿病 1.219 0.903~1.645 0.195 充血性心衰 6.580 3.441~12.583 < 0.001 血管病 1.259 0.911~1.740 0.163 卒中/TIA/血栓事件 1.940 1.351~2.785 < 0.001 抗凝 1.363 1.061~1.752 0.015 LAE 6.192 4.786~8.011 < 0.001 HSUA 2.251 1.729~2.930 < 0.001 FIB 1.682 1.433~1.973 < 0.001
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表 3 LAT/SEC多因素logistic回归
Table 3. Multivariate logistic regression
因素 OR 95%CI P值 高血压 1.047 0.808~1.357 0.729 充血性心衰 3.158 1.545~6.454 0.002 卒中/TIA/血栓事件 1.817 1.198~2.756 0.005 抗凝 1.119 0.839~1.493 0.445 LAE 5.573 4.232~7.338 0.000 HSUA 1.884 1.396~2.544 0.000 FIB 1.600 1.337~1.913 0.000
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表 4 模型预测LAT/SEC效能比较
Table 4. Comparison of thrombosis/spontaneous imaging performance predictive model
模型 AUC P 95%CI P* CHADS2 0.614 < 0.001 0.586~0.640 CHADS2+LAE 0.739 < 0.001 0.713~0.763 < 0.0001 CHADS2+HSUA 0.647 < 0.001 0.620~0.674 0.0002 CHADS2+FIB 0.654 < 0.001 0.627~0.680 < 0.0001 CHADS2+LAE+HSUA+FIB 0.767 < 0.001 0.743~0.790 < 0.0001 CHADS2-VASc 0.695 < 0.001 0.668~0.720 CHADS2-VASc+LAE 0.785 < 0.001 0.761~0.807 < 0.0001 CHADS2-VASc+HSUA 0.719 < 0.001 0.694~0.744 0.0003 CHADS2-VASc+FIB 0.710 < 0.001 0.684~0.735 0.0016 CHADS2-VASc+LAE+HSUA+FIB 0.801 < 0.001 0.778~0.823 0.0001 注：CHADS2+LAE表示将LAE纳入CHADS2后的新模型，CHADS2-VASc+LAE表示将LAE纳入CHADS2-VASc后的新模型。P表示与原假设AUC为0.5相比，P < 0.05，则拒绝原假设，提示模型可区分阳性组及阴性组。P*表示CHADS2/CHADS2-VASc模型与其相关新模型AUC值的比较(如：CHADS2与CHADS2+LAE的AUC相比，CHADS2-VASc与CHADS2-VASc与CHADS2-VASc+LAE的AUC相比，以此类推)，P*值< 0.05有意义。
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表 5 CHADS2/CHADS2-VASc与LAE+HSUA+FIB预测LAT/SEC效能比较
Table 5. Comparison of Thrombosis/Spontaneous Imaging Efficacy
模型 AUC P 95%CI P* CHADS2 0.614 0.0149 0.587~0.642 < 0.0001 CHADS2-VASc 0.694 0.0145 0.668~0.720 0.001 LAE+HSUA+FIB 0.756 0.0137 0.731~0.780 注：P表示与原假设ROC曲线下面积为0.5相比，P < 0.05，提示拒绝原假设，模型可区分LAT/SEC及阴性。P*表示模型LAE+HSUA+FIB与模型CHADS2/CHADS2-VASc模型与AUC值的比较，P* < 0.05。
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