基于Lasso-Logistic回归模型拟合NRS 2002评分、CONUT评分和RDW-SD、ALB评估肺结核患者静脉血栓栓塞症风险的价值
doi: 10.12259/j.issn.2095-610X.S20250805
The Value of Fitting NRS 2002 ，CONUT ，RDW-SD and ALB in Assessing the Risk of Venous Thromboembolism in Patients with the Pulmonary Tuberculosis Based on Lasso-Logistic Regression Model
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摘要:
目的 评估营养参数在肺结核患者中发生静脉血栓栓塞症（venous thromboembolism，VTE）风险的关系，寻找血栓形成的危险因素及预测因素，协助早期识别肺结核并发VTE的高危因素。 方法 收集2021年8月至2023年8月在昆明市第三人民医院住院确诊为肺结核的323例患者，根据非手术患者VTE风险评估分为VTE评分高危组（n = 116）例和低危组（n = 207）例，两组之间差异有统计学意义的营养指标Lasso回归进行变量筛选，采用多因素Logistic回归筛选肺结核患者VTE评分高危的独立危险因素，并构建列线图预测模型；采用受试者工作特征曲线（receiver operating characteristic，ROC）、校准曲线、决策曲线、影响曲线评价预测模型。 结果 两组间比较，高危组患者年龄明显大于低危组（59 vs. 41，P < 0.001），原发性高血压病、性别、2型糖尿病病史均无组间差异（P值分别为0.084、0.724和0.488）。组间比较和Lasso回归筛选出ALB、HCT、NRS 2002评分、HBDH、RDW-SD、RDW-CV、TG、CONUT评分、NEFA共9个变量。多因素Logistic回归分析显示， ALB、NRS 2002评分、RDW-SD、CONUT评分是肺结核患者VTE评分高危的独立影响因素（P < 0.005）。ROC曲线下面积显示：联合因子预测肺结核患者VTE评分高危的AUC（0.892）大于ALB（0.803）、NRS 2002评分（0.735）、RDW-SD（0.685）、CONUT评分（0.774）。拟合预测模型：Logit（P）：Y=0.433×NRS-0.136×ALB+0.411×CONUT评分+0.072×RDW-SD-1.770，P＝1/（1+ｅ-Y）（Y：预测指数，P：预测概率）。校准曲线显示模型预测与实际结果趋于一致（U：> 0.05），决策曲线、影响曲线显示模型能够临床获益。 结论 ALB、NRS 2002评分、RDW-SD、CONUT评分是肺结核患者VTE评分高危的独立影响因素，可以指导临床，尽早改善这些指标、降低VTE评分，减少血栓风险。同时，该预测模型在验证队列中表现出色，其区分能力、校准精度和临床实用性（决策曲线分析）均达到较好水平。 -
关键词:
- 肺结核 /
- 静脉血栓栓塞 /
- 营养风险筛查2002 /
- 控制营养评分 /
- 红细胞分布宽度标准差 /
- 血清白蛋白 /
- 营养评价
Abstract:Objective To evaluate the relationship between nutritional parameters and the risk of venous thromboembolicism （VTE） in patients with tuberculosis so as to identify the risk factors and predictors of thrombosis and assist in the early identification of high-risk factors for VTE in patients with the pulmonary tuberculosis. Methods A total of 323 patients diagnosed with the pulmonary tuberculosis and hospitalized in Kunming Third People’s Hospital from August 2021 to August 2023 were collected. According to the VTE risk assessment of non-operative patients, they were divided into the high-risk group and the low-risk group respectively with 116 and 207 in each group. The nutritional indicators with statistically significant differences between the two groups were screened by Lasso regression. Multivariate Logistic regression was used to screen the independent risk factors for high VTE risk in pulmonary tuberculosis patients, and a nomogram prediction model was constructed. The prediction model was evaluated by receiver operating characteristic curve （ROC）, calibration curve, decision curve, and influence curve. Results Patients in the high-risk group were significantly older than those in the low-risk group （59 vs.41, P < 0.001）, hypertension, gender, and Type 2 diabetes did not differ significantly （P values were 0.084, 0.724 and 0.488, respectively）. 9 variables were selected from the inter-group comparison and Lasso regression, including ALB, HCT, NRS2002 scores, HBDH, RDW-SD, RDW-CV, TG, CONUT scores, and NEFA. Multivariate Logistic regression analysis showed that ALB, NRS2002 scores, RDW-SD, and CONUT scores were independent influencing factors for the high risk of VTE scores in patients with tuberculosis （P < 0.005）. Area under the ROC curve showed that the AUC （0.892） for high-risk VTE scores in patients with the pulmonary tuberculosis was greater than that of ALB （0.803）, NRS2002 score （0.735）, RDW-SD （0.685）, and CONUT score （0.774）. Fitting prediction model: Logit （P）: Y=0.433×NRS-0.136×ALB+0.411×CONUT score+0.072×RDW-SD-1.770, P = 1/（1+e-Y） （Y: prediction index, P: prediction probability）. Calibration curve showed that the model prediction tended to be consistent with the actual results （U: > 0.05）, and the decision curve and influence curve showed that the model can bring clinical benefits. Conclusion ALB, NRS2002 scores, RDW-SD, and CONUT scores are independent influencing factors for the high risk of VTE scores in patients with tuberculosis. They can guide the clinical practice, improve these indicators as soon as possible, reduce VTE scores, and reduce the thrombosis risk. At the same time, the prediction model performs well in the verification cohort, with its discrimination ability, calibration accuracy and clinical utility （decision curve analysis） all reaching a satisfactory level. -
Key words:
- Tuberculosis pulmonary /
- Venous thromboembolism /
- NRS 2002 /
- CONUT /
- RDW-SD /
- Serum albumin /
- Nutrition assessment
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图 1 高危组和低危组营养相关指标LASSO回归系数图和参数图
A：LASSO系数路径（22个变量）；B：10倍交叉验证结果。
Figure 1. LASSO regression coefficient and parameter diagram of nutrition-related indicators of high-risk groups and low-risk groups
图 2 独立诊断指标及联合因子预测肺结核患者VTE评分高危的ROC曲线
注：model表示基于二元logistic回归方程建立预测模型；*P < 0.005。
Figure 2. The ROC curve of independent diagnostic indicators and combined factorspredicts high risk of VTE scores in patients with tuberculosis
图 3 肺结核患者VTE评分高危预测模型列线图
**P < 0.01，***P < 0.001。
Figure 3. Nomenclature of high-risk prediction model for VTE scores in patients with tuberculosis
图 4 肺结核患者VTE高危风险预测模型曲线
A：Calibration校准曲线；B：DCA曲线；C：影响曲线。
Figure 4. The high risk prediction model curve of VTE in patients with tuberculosis
表 1 肺结核患者VTE评分高危组和低危组基线资料的单因素分析 [M（P25，P75）/n（%）/（$\bar x \pm s $）]
Table 1. Univariate analysis of baseline data of VTE scores in high-risk groups and low-risk groups in tuberculosis patients [M（P25，P75）/n（%）/（$\bar x \pm s $）]
指标 高危组（n=116） 低危组（n=207） Z/χ2/t P 年龄（岁） 59（47，74） 47（32，60） −5.359a <0.001* 男性 89（76.72） 140（67.63） 2.978b 0.084 2型糖尿病 15（12.93） 24（11.59） 0.125b 0.724 高血压病 22（18.97） 33（15.94） 0.481b 0.488 体脂率 22.06±8.28 22.84±7.58 0.870c 0.385 体重（Kg） 58（47，74） 56（49，65） −3.181a 0.001* BMI（Kg/m2） 19.21（16.73，22.32） 20.76（18.61，23.6） −3.637a <0.001* NRS 2002评分 3（2，4） 1（1，2） −7.490 a <0.001* PNI 34.2（28.3，39.45） 45.75（39.2，50.6） −9.491a <0.001* GNRI 2609 （2440 ，2764 ）2605 （2395 ，2605 ）−0.982a 0.326 CONUT评分 5（3，7） 2（0，3） −8.279a <0.001* 总蛋白（g/L） 62.95（54.43，66.98） 66（61.9，72.3） −5.406a <0.001* 白蛋白（g/L） 30.5（26.33，34.50） 35.9（33.6，38.2） −9.033a <0.001* 球蛋白（g/L） 30.15（25.85，35.48） 28.7（25，32.8） −1.928a 0.054 白球比 1.03（0.76，1.23） 1.30（1.08，1.64） −6.645a <0.001* 前白蛋白（mg/L） 136.65（91.43，177.08） 195（150.2，244） −6.481a <0.001* а-羟丁酸（U/L） 163.45（129.78，214.78） 131（115.6，159.6） −5.202a <0.001* β-羟丁酸（mmol/L） 0.11（0.05，0.44） 0.06（0.04，0.13） −4.299a <0.001* 游离脂肪酸（mmol/L） 0.58（0.3，0.91） 0.42（0.25，0.61） −3.906a <0.001* 甘油三脂（mmol/L） 1.37（0.91，2.72） 1.95（1.01，3.59） −2.890a 0.004* 总胆固醇（mmol/L） 3.60（2.85，4.56） 4.24（3.55，5.15） −3.838a <0.001* 尿酸（umol/L） 345（208.75，507） 363（271，516） −1.447a 0.148 红细胞（10×12/L） 3.85（3.38，4.33） 4.52（4.02，4.90） −6.183a <0.001* 血红蛋白（g/L） 111（94，128.75） 134（121，147） −6.994a <0.001* HCT（L/L） 34.2（29.7，39.8） 41.2（37.4，45） −7.346a <0.001* MCV（fL） 89.3（84.3，96.5） 91.2（88.3，95.2） −2.059a <0.001* MCH（pg） 29.1（27，31.2） 30（28.5，31.4） −2.271a 0.023* MCHC（g/L） 322（313，333） 326（319，333） −2.266a 0.023* RDW-SD（fL） 48.3（44.2，54.5） 44.3（41.9，47.9） −5.528a <0.001* RDW-CV（%） 14.95（13.6，17） 13.2（12.5，14.5） −7.184a <0.001* BMI：体重指数；NRS 2002评分：营养风险评分2002；PNI：预后营养指数；GNRI：老年营养风险指数；CONUT评分：控制营养评分；HCT：红细胞压积；MCV：红细胞平均体积；MCH：平均血红蛋白含量；MCHC：平均血红蛋白浓度；RDW-SD：红细胞分布宽度标准差；RDW-CV：红细胞分布宽度变异系数；a：统计量Z；b：统计量χ2；c：统计量t；*P < 0.005。 
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表 2 肺结核患者VTE评分高危的多因素分析
Table 2. Multivariate analysis of high risk of VTE scores in patients with tuberculosis
变量 B SE Wald OR（95%CI） P ALB −0.136 0.027 24.957 0.873（0.828～0.921） <0.001* NRS 2002评分 0.433 0.125 11.964 1.542（1.207～1.972） 0.001* RDW-SD 0.072 0.024 9.057 1.075（1.026～1.127） 0.003* CONUT评分 0.411 0.069 35.571 1.509（1.318～1.727） <0.001* *P < 0.05。
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表 3 独立诊断指标及联合因子预测肺结核患者VTE评分高危的ROC曲线分析
Table 3. Analysis of ROC curves for independent diagnostic indicators and combined factors predicting high risk of VTE scores in patients with tuberculosis
变量 AUC（95%CI） 最佳截断值 灵敏度（%） 特异度（%） 约登指数 P ALB 0.803（0.756～0.850） 36.4 61.4 87.9 0.493 <0.001* NRS 2002 0.735（0.673～0.797） 1.966 78.4 72.9 0.513 <0.001* RDW-SD 0.685（0.623～0.748） 50.05 39.7 90.3 0.300 <0.001* CONUT 0.774（0.720～0.829） 3.50 64.7 79.2 0.439 <0.001* modle 0.892（0.857～0.926） 0.300 89.7 75.9 0.655 <0.001* *P < 0.05。
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