近期皮质下小梗死患者外周动脉僵硬度与脑小血管病总负荷程度的相关性研究OA
Correlation between peripheral arterial stiffness and total cerebral small vessel disease burden in patients with recent small subcortical infarction
目的 探讨近期皮质下小梗死(RSSI)患者的外周动脉僵硬度与脑小血管病(CSVD)总负荷程度的相关性,并构建 RSSI 患者 CSVD 总负荷程度的预测模型.方法 回顾性连续纳入2025 年3 月至2025 年11 月南京医科大学第三附属医院(常州市第二人民医院)神经内科收治的RSSI 患者.收集所有患者的临床资料,包括人口学资料(年龄、性别)、体质量指数(BMI)、入院血压(收缩压、舒张压)、入院美国国立卫生研究院卒中量表(NIHSS)评分、既往史(高血压病、糖尿病、高脂血症、冠心病、心房颤动)、吸烟史、饮酒史、入院或次日实验室检查指标[总胆固醇、三酰甘油、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、尿素氮、肌酐、尿酸、同型半胱氨酸(Hcy)].依据 CSVD总负荷评分结果将 RSSI 患者分为 CSVD 总负荷轻度(0~1 分)组、中度(2 分)组和重度(3~4 分)组,采用外周动脉僵硬度检测装置(ADS-6000B)检测三组患者的外周动脉僵硬度指标肱-踝脉搏波速度(baPWV)和踝肱指数.比较三组患者的临床资料并对组间比较差异有统计学意义的变量进行事后多重比较、共线性分析,排除存在共线性(方差膨胀因子≥10)的变量后行多因素有序 Logistic 回归分析,探索影响 RSSI 患者 CSVD 总负荷程度(轻、中、重度)的因素.以 baPWV 为自变量,CSVD 总负荷程度(轻、中、重度)为因变量,Hcy 为中介变量进行中介效应分析.将三组间比较差异有统计学意义的变量采用向后逐步法纳入多因素有序 Logistic 回归分析筛选出有统计学意义的变量,且进行平行线检验(以 P>0.05 为比例优势假设成立);使用限制性立方样条图分析纳入模型构建的连续变量与结局之间是否存在非线性关系(以 P≤0.05 为存在非线性关系),并采用有序 Logistic 回归分析分别以中、重度 CSVD 总负荷为临床结局输出二者的累积概率为最终临床结局,构建预测 RSSI患者中、重度 CSVD 总负荷的(发生中、重度 CSVD 总负荷的累积概率)预测模型,并进行列线图可视化,绘制校准曲线和决策曲线评估该模型的预测效能.绘制该模型预测 RSSI 患者 CSVD 总负荷程度的受试者工作特征曲线以评估模型预测 RSSI 患者中、重度 CSVD 总负荷的区分度,曲线下面积(AUC)0.5~0.7 为区分度较低,>0.7~0.8 为区分度中等,>0.8~0.9 为区分度优秀,>0.9为区分度极好.拟合不含 baPWV 的基础有序 Logistic 回归预测模型,使用 nricens 包计算加入baPWV 后模型的综合判别改善指数(IDI),IDI>0 且95%CI 不包含0 则提示加入 baPWV 的预测模型相较于基础预测模型判别能力提高.结果 (1)共纳入 RSSI 患者 101 例,男 67 例,女34 例,年龄45~91 岁,中位年龄67(61,75)岁,入院 NIHSS 评分0~8 分,中位入院 NIHSS 评分2(1,2)分,CSVD 总负荷评分0~4 分,中位 CSVD 总负荷评分2(1,3)分,其中轻度组28 例,中度组53 例,重度组20 例.(2)三组年龄、高血压病患者比例、入院收缩压、Hcy、baPWV 差异均有统计学意义(均 P≤0.05);多重比较结果显示,重度组年龄、高血压病患者比例、入院收缩压均高于轻度组,中度组入院收缩压高于轻度组,三组 Hcy、baPWV 两两比较差异均有统计学意义(均 P≤0.05).(3)多因素有序 Logistic 回归分析结果显示,入院收缩压(OR=1.028,95%CI:1.007~1.051,P=0.010)、Hcy(OR=1.186,95%CI:1.057~1.334,P=0.004)、baPWV(OR=1.409,95%CI:1.142~1.738,P=0.001)均为 RSSI 患者 CSVD 总负荷程度的影响因素.(4)中介效应分析结果显示,baPWV 对 CSVD总负荷程度的总效应值为0.436,在纳入血 Hcy 后,其间接效应值为0.136,占总效应值的31.19%.(5)以 RSSI 患者的 CSVD 总负荷程度为因变量,将三组间比较差异有统计学意义的指标年龄、高血压病、入院收缩压、Hcy 及 baPWV(方差膨胀因子均≤10)采用向后逐步法纳入有序 Logistic 回归,最终纳入模型构建的变量为入院收缩压、Hcy 及 baPWV,模型比例优势假设成立(P=0.796);构建有序 Logistic 回归预测模型为:logit[P(Y≤1)]=10.160-(0.025×入院收缩压+0.164×Hcy+0.298×baPWV);logit[P(Y≤2)]=13.752-(0.025×入院收缩压+0.164×Hcy+0.298×baPWV).(6)基于有序 Logistic 回归模型,分别以中、重度 CSVD 总负荷为临床结局输出二者的累积概率为最终临床结局,构建预测 RSSI 患者发生中、重度 CSVD 总负荷累积概率的列线图预测模型,经 Boostrap校正后该模型预测 RSSI 患者中、重度CSVD 总负荷的AUC 为0.821(95%CI:0.749~0.908),区分度优秀,校准度良好.IDI 分析显示,纳入 baPWV 后模型判别能力较不含 baPWV 的基础有序Logistic 回归预测模型提升(IDI=0.065,95%CI:0.003~0.192,P=0.019).决策曲线显示,在高风险阈值范围内(0.2~0.7)该模型均具有较高净获益.结论 RSSI 患者入院收缩压、Hcy 及baPWV 与 CSVD 总负荷程度独立相关,且 Hcy 在 baPWV 与 CSVD 总负荷程度之间发挥部分中介作用.基于入院收缩压、Hcy 及 baPWV 构建的预测模型可对 RSSI 患者的中、重度 CSVD 总负荷进行分层预测,且具有较好的实用价值.
Objective To investigate the correlation between peripheral arterial stiffness and total cerebral small vessel disease(CSVD)burden in patients with recent small subcortical infarction(RSSI),and to establish a prediction model for total CSVD burden in RSSI patients.Methods Consecutive RSSI patients admitted to the Department of Neurology,the Third Affiliated Hospital of Nanjing Medical University(the Second People's Hospital of Changzhou)from March 2025 to November 2025 were retrospectively enrolled.Clinical data were collected,including demographic characteristics(age,sex),body mass index(BMI),admission blood pressure(systolic and diastolic blood pressure),National Institutes of Health stroke scale(NIHSS)score at admission,medical history(hypertension,diabetes mellitus,hyperlipidemia,coronary heart disease,atrial fibrillation),smoking history,drinking history,and laboratory tests on admission or the next day(total cholesterol,triglyceride,high-density lipoprotein cholesterol,low-density lipoprotein cholesterol,urea nitrogen,creatinine,uric acid,homocysteine[Hcy]).According to total CSVD burden scores,all RSSI patients were divided into mild(0-1points),moderate(2points),and severe(3-4points)groups.Brachial-ankle pulse wave velocity(baPWV)and ankle-brachial index were measured using an arterial stiffness detector(ADS-6000B).Clinical characteristics were compared among the three groups,post hoc multiple comparisons and collinearity analysis were performed for variables with significant differences,variables with collinearity(variance inflation factor≥10)were excluded,and the remaining variables were entered into multivariate ordinal Logistic regression to identify independent risk factors for total CSVD burden(mild,moderate,severe)of RSSI patients.Mediation analysis was performed with baPWV as the independent variable,total CSVD burden(mild,moderate,severe)as the dependent variable,and Hcy as the mediator.Variables with significant intergroup differences were selected by backward stepwise multivariate ordinal Logistic regression to construct a prediction model for total CSVD burden,and the parallel lines test was used(P>0.05 indicated that the proportional odds assumption was satisfied).Restricted cubic splines were used to explore nonlinear relationships between continuous variables and the outcome(P≤0.05 indicated a nonlinear relationship).Ordinal Logistic regression was performed,with cumulative probability of moderate and severe CSVD burden used as the primary clinical endpoint to establish a prediction model for RSSI patients with moderate to severe CSVD burden(the cumulative probability of moderate-to-severe CSVD burden)prediction.The model was visualized using a nomogram and its performance was evaluated with calibration curves and decision curve analysis(DCA).Receiver operating characteristic(ROC)curves of the total CSVD burden level of the RSSI patients were plotted to assess the model's discrimination in predicting the total moderate and severe CSVD burden,with area under the curve(AUC)values of0.5-0.7 as low,>0.7-0.8 as moderate,>0.8-0.9 as excellent,and>0.9 as outstanding.Fit a baseline ordinal Logistic regression model excluding baPWV,and calculate the integrated discrimination improvement(IDI)using the nricens package;IDI>0 and 95%CI not crossing 0 suggested adding baPWV improved the model discrimination compared with the baseline model.Results(1)A total of 101 RSSI patients were enrolled,including 67 males and 34 females,aged 45-91 years with a median age of 67(61,75)years.The NIHSS score was between 0-8,with median NIHSS score at admission was 2(1,2).The total CSVD burden score was between0-4,and median total CSVD burden score was 2(1,3).There were 28 patients in the mild group,53 in the moderate group,and 20 in the severe group.(2)Significant differences were observed among the three groups in age,prevalence of hypertension,admission systolic blood pressure,Hcy,and baPWV(all P≤0.05).Post hoc analysis showed that age,hypertension prevalence,and admission systolic blood pressure were higher in the severe group than those in the mild group;admission systolic blood pressure was higher in the moderate group than that in the mild group;and Hcy and baPWV differed significantly in all pairwise comparisons between groups(all P≤0.05).(3)Multivariable ordinal Logistic regression showed that admission systolic blood pressure(OR,1.028,95%CI 1.007-1.051,P=0.010),Hcy(OR,1.186,95%CI 1.057-1.334,P=0.004),and baPWV(OR,1.409,95%CI 1.142-1.738,P=0.001)were independent influencing factors for total CSVD burden in the RSSI patients.(4)Mediation analysis showed that the total effect of baPWV on CSVD burden was 0.436,and the indirect effect mediated by Hcy was 0.136,accounting for 31.19%of the total effect.(5)Using the total CSVD burden in RSSI patients as dependent variable,enter all variables with significant statistical differences between the three groups(age,hypertension,admission systolic blood pressure,Hcy,and baPWV[all variance inflation factors≤10])into backward stepwise ordinal Logistic regression.Admission systolic blood pressure,Hcy,and baPWV were ultimately included in the model,and the proportional odds assumption was satisfied(P=0.796).The ordinal Logistic regression prediction model was established as following:logit(P[Y≤1])=10.160-(0.025×admission systolic blood pressure+0.164×Hcy+0.298×baPWV);logit(P[Y≤2])=13.752-(0.025×admission systolic blood pressure+0.164×Hcy+0.298×baPWV).(6)Based on the ordinal Logistic regression model(with cumulative probability of moderate and severe CSVD burden used as the primary clinical endpoint),establish the alignment diagram prediction model.After Bootstrap correction,the AUC obtained from predicting RSSI patients with moderate and severe CSVD was 0.821(95%CI 0.749-0.908),indicating good model discrimination and calibration.IDI analysis showed that adding baPWV significantly improved model performance(IDI=0.065,95%CI 0.003-0.192,P=0.019).DCA demonstrated high net benefit within a threshold range of 0.2-0.7,the model demonstrated a high net benefit.Conclusions Admission systolic blood pressure,Hcy,and baPWV are independently associated with total CSVD burden in RSSI patients,and Hcy partially mediates the relationship between baPWV and total CSVD burden.The prediction model based on admission systolic blood pressure,Hcy,and baPWV can effectively stratify moderate-to-severe CSVD burden in RSSI patients and shows favorable clinical utility.
吴辰龙;项艰波;张敏;恽文伟
213000 南京医科大学第三附属医院(常州市第二人民医院)神经内科213000 南京医科大学第三附属医院(常州市第二人民医院)影像科213000 南京医科大学第三附属医院(常州市第二人民医院)神经内科213000 南京医科大学第三附属医院(常州市第二人民医院)神经内科
近期皮质下小梗死动脉僵硬度脑小血管病总负荷肱-踝脉搏波速度预测模型
Recent subcortical small infarctionArterial stiffnessTotal cerebral small vessel disease burdenBrachial-ankle pulse wave velocityPrediction model
《中国脑血管病杂志》 2026 (4)
219-230,12
常州市卫生健康委员会拔尖人才项目(2022CZBJ055)
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