第一部分 慢性冠脉综合征患者新型脂质代谢指标与PCI术后不良预后的相关性研究

 

摘  要

研究背景

冠状动脉疾病(coronary artery disease, CAD)是严重威胁我国居民健康的重大公共卫生问题。慢性冠脉综合征(chronic coronary syndrome, CCS)是CAD的主要构成部分，涵盖除急性冠脉综合征(acute coronary syndrome, ACS)以外所有CAD临床情况。CCS是一动态变化的疾病过程，与ACS具有不同的远期风险。由于目前针对CCS的研究证据有限，尚无法根据个体化危险因素水平，提供确切的治疗及预防建议。经皮冠状动脉介入术(percutaneous coronary intervention, PCI)是CCS的主要治疗手段，其相关不良预后再次血运重建和支架内再狭窄(in-stent restenosis, ISR)不仅可增大患者疾病负担，还可作为心血管事件的独立危险因素，对患者预后与康复构成威胁。近来研究发现，新型脂质代谢指标甘油三酯-葡萄糖指数(triglyceride glucose index, TyG)、单核细胞/高密度脂蛋白胆固醇比值(monocyte-to-high-density lipoprotein-cholesterol ratio, MHR)和残余胆固醇(remnant cholesterol, RC)可对具有不同临床表现的CAD人群的主要不良心血管事件展开预测。然而，目前尚无关于此类新型脂质代谢指标与PCI术后CCS患者不良预后相关性的研究。

 

研究目的

本研究旨在探讨新型脂质代谢指标TyG、MHR和RC与PCI术后CCS患者不良预后的相关性，从而为PCI术后CCS人群风险管理与潜在防控靶点提供初步研究证据。

 

研究方法

本研究采用回顾性队列研究设计。连续入组于2017年3月至12月在我院住院并接受冠状动脉造影检查的疑诊CAD患者。使用TyG、MHR和RC的三分位数作为指标高中低水平的分组标准，其中，TyG分组设置为T₁(≤8.6023)、T₂(8.6023-9.0899)和T₃(>9.0899)，MHR分组设置为M₁(≤0.2900)、M₂(0.2900-0.4200)和M₃(>0.4200)，RC分组设置为R₁(≤0.3518)、R₂(0.3518-0.5600)和R₃(>0.5600)。主要研究结局为PCI术后不良预后复合终点，包括再次血运重建与ISR。采用Kaplan-Meier和Log-rank检验分析组间结局事件发生率差异。采用多因素COX比例风险回归分析估计观察指标与研究结局之间关联的风险比(hazard ratio, HR)和95%置信区间(confidence interval, CI)。采用限制性立方样条(restricted cubic spline, RCS)探索观察指标与研究结局之间的线性关联。

 

研究结果

在经入选及排除标准核定后，共计纳入1471例CCS患者。中位随访时间为59.57月(四分位数间距: 26.37-64.33)。共计577名(39.20%)患者发生主要研究结局事件。

在以TyG为观察指标的分析中，三组患者的结局事件发生率具有显著性差异(Log-rank检验, P值=0.0037)。组间比较显示，T₂及T₃组的结局事件发生率均高于T₁组(Log-rank检验，矫正后T₂和T₁的P值=0.0230，T₃和T₁的P值=0.0010)，而T₂与T₃之间则无显著性差异。多因素COX分析显示，在完全矫正混杂后，TyG每单位水平的增高可导致结局发生风险升高26.40%(HR, 1.2640; 95%CI: 1.1080-1.4420; P<0.001)。相比T₁组，T₂及T₃组患者的结局发生风险分别升高25.90%(HR, 1.2590; 95%CI: 1.0220-1.5520; P<0.001)和40.00%(HR, 1.4000; 95%CI: 1.1340-1.7190; P<0.001)。RCS结果显示，在完全矫正混杂后，TyG与主要研究结局为线性相关(整体P值=0.0017, 非线性P值=0.2359)。

在以MHR为观察指标的分析中，三组患者的结局事件发生率无显著性差异。多因素COX分析显示，在完全矫正混杂后，MHR每单位水平的增高可导致结局发生风险增高50.40%(HR, 1.5040; 95%CI: 1.1140-2.0310; P=0.0080)。而在MHR分组比较中，各项分析均显示无统计学意义。

在以RC为观察指标的分析中，三组患者的结局事件发生率存在显著性差异(Log-rank检验，P值=0.0024)，其中，R₃组的结局事件发生率显著高于R₁组及R₂组(Log-rank检验，矫正后R₃和R₁的P值=0.0010；R₃和R₂的P值=0.0290)，而R₂组与R₁组则无明显差异。多因素COX分析显示，相比R₁组，R₃组的结局发生风险在完全校正后可升高37.80%(HR, 1.3780; 95%CI: 1.1260-1.6870; P=0.0020)。RCS分析显示，RC与结局事件的关联为非线性，提示RC的致风险作用或存在效应阈值(整体P值=0.0105, 非线性P值=0.0163)。

 

研究结论

本研究表明新型脂质代谢指标TyG和RC是PCI术后CCS患者再次血运重建和ISR的独立危险因素。测量评估CCS患者的基线TyG和RC水平可帮助识别PCI术后不良预后风险升高的高危人群。

 

关键词：慢性冠脉综合征，经皮冠状动脉介入术，新型脂质代谢指标，不良预后

第二部分  基于新型脂质代谢指标的中医药干预PCI术后慢性冠脉综合征患者不良预后的疗效评价

 

摘  要

研究背景

脂质代谢异常是冠状动脉疾病(coronary artery disease, CAD)的重要病理生理机制，除直接参与冠状动脉粥样硬化形成外，还可与胰岛素抵抗(insulin resistance, IR)、炎症反应和高血压等心血管危险因素发挥联合效应，在CAD的发展和不良预后中扮演关键角色。基于这一联系开发的新型脂质代谢指标已在多项研究中被证实可独立预测不同临床表现的CAD患者的不良心血管事件发生风险。在第一部分研究中，本研究还发现新型脂质代谢指标甘油三酯-葡萄糖指数（triglyceride glucose index, TyG)和残余胆固醇(remnant cholesterol, RC)可实现对PCI术后不良预后发生风险增高的慢性冠脉综合征(chronic coronary syndrome, CCS)人群的分层与定位。中医药(traditional Chinese medicine, TCM)干预联合指南推荐药物治疗(guideline-directed medical treatment, GDMT)的中西医结合治疗策略是CAD临床防治的重要途径，可在常规西药基础上进一步改善患者整体预后。因此，通过联合TCM干预实现CCS现有治疗方案的优化，是降低PCI术后CCS患者不良预后发生风险从而预防不良心血管事件的有效手段。然而，目前中医药干预在PCI术后CCS患者不良预后中疗效的研究证据有限，中西医结合治疗能否进一步改善高风险人群相关预后也尚无明确结论。

 

研究目的

本研究旨在评价中西医结合治疗在PCI术后CCS患者不良预后中的疗效，并在第一部份研究结果基础上，评估中西医结合治疗在以TyG和RC为指导的高风险人群中的作用。

 

研究方法

本研究为一项大样本、前瞻性、观察性队列研究的二次分析。研究暴露因素为是否使用TCM+GDMT治疗，TCM定义为使用CAD相关中药累积大于6个月/年。主要研究结局为PCI术后不良预后的复合终点，包括再次血运重建和支架内再狭窄(in-stent restenosis, ISR)。采用第一部分中TyG和RC分组标准作为高中低风险人群分层的依据。采用Kaplan-Meier和Log-rank检验分析组间结局发生率差异。采用多因素COX比例风险回归分析估计研究暴露因素与研究结局之间关联的风险比(hazard ratio, HR)和95%置信区间(confidence interval, CI)。

 

研究结果

在经入选和排除标准核定后，最终纳入分析患者2274例，TCM+GDMT组患者共计1119例，GDMT组患者1155例。研究的中位随访时长为60.45个月(四分位数间距: 16.47-68.00)，共计1054名(46.40%)患者发生终点事件，其中，GDMT+TCM组有479名(42.80%)患者，GDMT组有575名(49.80%)患者。Kaplan-Meier分析结果显示，GDMT+TCM组患者的结局发生率显著性低于GDMT组(Log-rank检验，P值<0.001)。多因素COX分析结果显示，在完全矫正混杂后，相比GDMT组患者，GDMT+TCM组患者的结局发生风险可降低达23.10%(HR, 0.769; 95%CI: 0.680-0.871; P<0.001)。

在以TyG指导风险分组的分析中，多因素COX分析显示，在结局事件发生风险最低的T₁组中，GDMT组患者与GDMT+TCM组患者的研究结局发生风险无显著性差异(P值均＞0.05)。在T₂组患者中，GDMT+TCM治疗组相较GDMT组可降低主要结局发生风险达36.10%(HR, 0.639; 95%CI: 0.515-0.793; P<0.001)。而在T3组患者中，GDMT+TCM治疗组的主要研究结局发生风险则是GDMT组的0.805倍(HR, 0.805; 95%CI: 0.656-0.987; P=0.037)。在以RC指导风险分组的分析中，多因素COX分析显示，相比GDMT组患者，接受GDMT+TCM干预可在R₂及R₃组中分别降低主要研究结局发生风险达23.60%(HR, 0.764; 95%CI: 0.612-0.954; P=0.017)和23.60%(HR, 0.764; 95%CI: 0.621-0.939; P=0.011)。

 

研究结论

本研究证实中医药干预可有效降低PCI术后CCS患者不良预后的发生风险，并可在新型脂质代谢指标TyG和RC指导下，进一步降低高风险CCS人群相关不良预后的发生风险。

 

关键词：慢性冠脉综合征，经皮冠状动脉介入术，中西医结合治疗，不良预后

第三部分 中医药干预联合新型脂质代谢指标的临床预测模型构建与评价

 

摘  要

研究背景

中医药(traditional Chinese medicine, TCM)干预是冠状动脉疾病(coronary artery disease, CAD)临床防治的重要途径，其疗效已在诸多研究中得到证实。慢性冠脉综合征(chronic coronary syndrome, CCS)是CAD的主要构成部分，具有病程动态变化，心血管不良事件风险个体差异大的特点。第一部分研究中，我们已对CCS的潜在危险因素进行了探究，发现新型脂质代谢指标甘油三酯-葡萄糖指数(triglyceride glucose index, TyG)和残余胆固醇是PCI术后CCS患者再次血运重建和支架内再狭窄(in-stent restenosis, ISR)的独立危险因素。第二部分研究中，我们证实TCM干预可有效降低PCI术后CCS患者再次血运重建和ISR的发生风险，并可在TyG和RC指导下，进一步改善高风险人群的相关不良预后。因此，如何在以上研究成果基础上，为TCM在CCS中的应用提供进一步研究证据，从而促进TCM应用，成为了亟待解决的问题。

临床预测模型是通过整合与结局及预后相关的影响因素，对患者疾病风险与治疗获益进行评估并量化的工具。多项研究表明，基于人口学特征及心血管危险因素的临床预测模型可实现对主要心血管不良事件的高危CCS人群筛选与定位，从而指导预防措施及治疗决策。然而，目前尚无研究对TCM干预作为基线评估因素整合进入临床预测模型的应用价值进行探索。

 

研究目的

构建并评价TCM干预联合新型脂质代谢指标在PCI术后CCS人群不良预后中的临床预测模型，从而为促进TCM在CCS中的临床应用提供新的解决办法与思路。

 

研究方法

本研究为一项大样本、前瞻性、观察性队列研究的二次分析。研究暴露因素为是否使用TCM+指南推荐药物治疗(guideline-directed medical treatment, GDMT)，TCM定义为使用CAD相关中药累积大于6个月/年。研究结局为PCI术后不良预后的复合终点，包括再次血运重建和ISR。采用交叉Lasso回归筛选临床预测模型的自变量。采用列线图对已筛选变量进行优化并对模型进行可视化。采用Bootstrap重复抽样法对模型进行内部验证。采用Calibration校准曲线对模型一致性进行评价。采用一致性指数(concordance index, C-index)以及时间依存受试者工作特征曲线和时间依存曲线下面积(time-dependent area under curve, time-AUC)对模型一致性进行敏感性分析。

 

研究结果

研究最终纳入分析患者2274例，TCM+GDMT组患者共计1119例，GDMT组患者1155例。研究的中位随访时长为60.45个月(四分位数间距: 16.47-68.00)，共计1054名(46.40%)患者发生终点事件。

在经交叉Lasso回归筛选和列线图优化后，GDMT+TCM治疗、TyG、支架植入个数、靶病变≥20mm、高敏C反应蛋白(high-sensitive CRP, hs-CRP)、多支病变及既往PCI可作为自变量构建针对PCI术后CCS患者不良预后的临床预测模型。其中，GDMT+TCM是研究结局发生风险的独立保护因素，量化得分后，其分值相比不接受GDMT+TCM减少约10分，对应结局减少风险可达10%。此外，支架植入个数、靶病变≥20 mm、TyG水平增加、hs-CRP含量上升、多支病变和既往PCI是研究结局发生风险的显著危险因素，在结局发生风险中具有不同贡献分值。Bootstrap重复1500次抽样内部验证后，获取得到Calibration校准曲线，结果显示临床预测模型对主要研究结局发生风险估计值与实际观察值具有良好一致性。敏感性分析显示，该模型对主要研究结局的3年发生风险C-index为59.2%，五年发生风险C-index为60.1%，且其3年和5年time-AUC估计值分别为0.624(95%CI: 0.601-0.641)和0.664(95%CI: 0.648-0.687)。

 

研究结论

通过建立临床预测模型，本研究首次实现了将TCM干预整合进入心血管危险因素评分模型，不仅证实TCM干预是PCI术后CCS患者不良预后的独立保护因素，还发现中西医结合治疗可联同多种常见心血管危险因素对CCS患者再次血运重建和ISR的发生风险展开预测。本研究结果为促进TCM临床应用提供了新思路，在简化TCM临床治疗决策路径和扩大TCM临床应用场景等方面具有显著创新性意义。

 

关键词：慢性冠脉综合征，经皮冠状动脉介入术，中西医结合治疗，临床预测模型

综述 慢性冠脉综合征中西医结合治疗研究进展

 

摘要：冠状动脉疾病(coronary artery disease, CAD)是心血管疾病死亡的首要原因，具有高患病率、高发病率和高死亡率的流行病学特点，严重威胁人类健康。慢性冠脉综合征(chronic coronary syndrome, CCS)是CAD主要构成部分，其临床亚型具有不同心血管风险，是一动态变化的疾病过程。本文主要介绍CCS在最新指南下各亚型的诊断流程及治疗方案，重点介绍中医药在CCS各临床亚型中的治疗原则和研究进展，旨在通过对CCS的中西医结合治疗研究进展的简述为相关治疗策略的优化和研究提供参考。

 

Part I

 

Association between Novel Lipid Metabolism Indicators and Adverse Prognosis in Patients with Chronic Coronary Syndrome after PCI

 

Abstract

Background

Coronary artery disease (CAD) is a major public health issue that poses a serious threat to the health of residents in our country. Chronic coronary syndrome (CCS) is a major component of CAD, covering all clinical manifestations of CAD except for acute coronary syndrome (ACS). CCS is a dynamic process with different long-term risk compared to ACS. Due to the limited research evidence currently available for CCS, it is not possible to provide specific treatment and prevention recommendations based on individual risk factor levels. Percutaneous coronary intervention (PCI) is the primary treatment for CCS. Its related adverse prognosis, such as repeat revascularization and in-stent restenosis (ISR), can not only increase the disease burden but also act as independent risk factors for cardiovascular events, posing a threat to the prognosis and rehabilitation of patients. Recent studies have found that novel lipid metabolism indicators, such as the triglyceride glucose index (TyG), monocyte-to-high-density lipoprotein-cholesterol ratio (MHR), and remnant cholesterol (RC), can predict major adverse cardiovascular events in CAD populations with different clinical characteristics. However, there are currently no studies on the association between these novel lipid metabolism indicators and the adverse prognosis of CCS patients after PCI.

 

Aims

This study aims to explore the association between the novel lipid metabolism indicators including TyG, MHR, and RC, and the adverse prognosis after PCI in patients with CCS, thereby providing preliminary research evidence for risk management and prevention targets following PCI in CCS.

 

Methods

This study was conducted using a retrospective cohort design. Patients who were consecutively admitted to our hospital from March to December 2017 and underwent coronary angiography for suspected CAD were included. The tertiles of TyG, MHR, and RC were used as the criteria for dividing patients into high, medium, and low levels. Specifically, the TyG groups were set as T1 (≤8.6023), T2 (8.6023-9.0899), and T3 (>9.0899); the MHR groups as M1 (≤0.2900), M2 (0.2900-0.4200), and M3 (>0.4200); and the RC groups as R1 (≤0.3518), R2 (0.3518-0.5600), and R3 (>0.5600). The primary outcome was a composite endpoint of adverse prognosis after PCI, including repeat revascularization and ISR. The differences in the incidence of outcome between groups were analyzed using the Log-rank test and Kaplan-Meier analysis. Multivariate COX proportional hazards regression analysis was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for the association between the indicators and outcomes. Restricted Cubic Spline (RCS) was used to explore the linear relationship between indicators and outcomes.

 

Results

A total of 1471 patients with CCS were included. The median duration of follow-up was 59.57 months (Interquartile Range: 26.37-64.33). During the follow-up, 577 (39.20%) patients experienced outcome events.

In the analyses using the TyG as the indicator, there cumulative incidences of outcome were significantly different among the three groups (Log-rank test, P=0.0037). Inter-group comparisons showed that T₂ and T₃ had higher cumulative incidence of outcome compared to the T₁ (Log-rank test, adjusted P-value for T₂ and T₁=0.0230, T₃ and T₁=0.0010) while no significant difference between T₂ and T₃ was observed. In the multivariate Cox analyses, per-unit increase in TyG was associated with increased risk of outcome (HR, 1.2640; 95% CI: 1.1080-1.4420; P<0.0010). Compared to the T₁, the fully adjusted HR for outcome in T₂ and T₃ was 1.2590 (HR, 1.2590; 95% CI: 1.0220-1.5520; P<0.0010) and 1.4000 (HR, 1.4000; 95% CI: 1.1340-1.7190; P<0.0010), respectively. RCS analyses showed a linear correlation between TyG and the primary outcome after fully adjusted for confounders (overall P=0.0017, nonlinearity P=0.2359).

In the analysis using MHR as the indicator, there was no significant difference in the cumulative incidence of outcome among the groups. Multivariate Cox analyses showed that per-unit increase in MHR led to a 50.40% increase in the risk of outcomes after full adjustment for confounders (HR, 1.5040; 95% CI: 1.1140-2.0310; P=0.0080). However, no statistical significance was found in the analyses when categorizing MHR.

In the analysis using RC as the indicator, there were significant differences in the cumulative incidence of outcome among the three groups (Log-rank test, P=0.0024). The patients in R3 had a significantly higher cumulative incidence of outcome than R₁ and R₂ (Log-rank test, adjusted P-value for R₃ and R₁=0.0010; R₃ and R₂=0.0290), with no significant difference between R₂ and R₁. Multivariate Cox analyses indicated that, compared to the R₁ group, the risk of outcome in the R₃ group increased by 37.80% after full adjustment (HR, 1.3780; 95% CI: 1.1260-1.6870; P=0.0020). RCS analyses suggested a nonlinear correlation between RC and outcome, indicating a possible threshold effect in the risk contribution of RC (overall P=0.0105, nonlinearity P=0.0163).

 

Conclusion

This study indicates that TyG and RC are independent risk factors for repeat revascularization and ISR in patients with CCS. Measuring and assessing the baseline TyG and RC levels in CCS patients can identify high-risk individuals with an elevated risk of adverse prognosis of PCI.

 

Keywords: Chronic coronary syndrome, percutaneous coronary intervention, novel metabolism indicator, adverse prognosis

Part II

Evaluation of the Efficacy of Traditional Chinese Medicine in Preventing Adverse Prognosis among Patients with Chronic Coronary Syndrome after PCI based on Novel Lipid Metabolism Indicators

 

Abstract

Background

Disturbed lipid metabolism is the key pathophysiological mechanism in coronary artery disease (CAD). Except for directly contributing to the formation of atherosclerosis, it also interacts with other cardiovascular risk factors such as insulin resistance (IR), inflammatory responses, and hypertension, playing a crucial role in the development and adverse prognosis of CAD. Based on these relationships, novel lipid metabolic indicators have been proven in multiple studies to independently predict the risk of adverse cardiovascular events in CAD patients with different clinical manifestations. In the first part of the study, we also found that the novel lipid metabolic indicators, the triglyceride glucose index (TyG) and remnant cholesterol (RC), can be used to stratify and identify individuals with chronic coronary syndrome (CCS) at increased risk of adverse outcomes of percutaneous coronary intervention (PCI). The integration of traditional Chinese medicine (TCM) with guideline-directed medical treatment (GDMT) is an important approach in the clinical prevention and treatment of CAD, potentially improving overall patient prognosis beyond conventional Western medicine. Therefore, optimizing the existing treatment regimen for CCS through the integration of TCM is an effective means to reduce the risk of adverse outcomes and prevent adverse cardiovascular events in CCS patients. However, current evidence on the efficacy of TCM in improving adverse outcomes in CCS patients after PCI is limited, and whether the integration of TCM and Western medicine can further improve prognosis in high-risk groups remains unclear.

 

Aims

This study aims to evaluate the efficacy of integrative Chinese and Western medicine in treating patients with CCS after PCI, and to assess its role in high-risk populations guided by TyG and RC according to the findings of the first part of the study.

 

Methods

This study is a secondary analysis of a large-scale, prospective, observational cohort study. The exposure factor was whether patients received treatment with TCM plus GDMT. TCM was defined as using CAD-related herbal medicine for more than 6 months per year. The primary study outcome was a composite endpoint of PCI, including repeat revascularization and in-stent restenosis (ISR). The TyG index and RC tertile values from the first part of the study were used for risk stratification into high, medium, and low-risk groups. Differences in outcome incidence between groups were analyzed using the Log-rank test and Kaplan-Meier survival analysis. The association between the exposure factor and study outcomes was estimated using a multivariate Cox proportional hazards regression model to calculate the hazard ratio (HR) and 95% confidence intervals (CI).

 

Results

After patients were screened with inclusion and exclusion criteria, a total of 2274 patients were included in the final analysis with 1119 patients in the TCM+GDMT group and 1155 patients in the GDMT group. The median follow-up duration was 60.45 months (interquartile range: 16.47-68.00), and 1054 patients (46.40%) experienced endpoints. Among these, 479 patients (42.80%) were in the GDMT+TCM group, and 575 patients (49.80%) were in the GDMT group. Kaplan-Meier analysis showed that the incidence of outcomes in the GDMT+TCM group was significantly lower than that in the GDMT group (Log-rank test, P<0.001). Multivariate Cox regression analysis revealed that, after full adjustment for confounders, the risk of study outcome in the GDMT+TCM group was reduced by 23.10% compared to the GDMT group (HR, 0.769; 95%CI: 0.680-0.871; P<0.001).

In analyses using TyG for risk grouping, multivariate Cox analysis showed no significant difference in the risk of study outcomes between GDMT and GDMT+TCM groups in the T₁ group (P values>0.05). In the T₂ group, the GDMT+TCM treatment group reduced the risk of study outcome by 36.10% compared to the GDMT group (HR, 0.639; 95%CI: 0.515-0.793; P<0.001). In the T₃ group, the risk of study outcome for the GDMT+TCM treatment group was 0.805 times that of the GDMT group (HR, 0.805; 95%CI: 0.656-0.987; P=0.037). In the analysis using RC for risk grouping, multivariate Cox analysis indicated that GDMT+TCM intervention could reduce the risk of major study outcomes by 23.60% in both R₂ and R₃ groups compared to the GDMT group (HR, 0.764; 95%CI: 0.612-0.954; P=0.017 and HR, 0.764; 95%CI: 0.621-0.939; P=0.011, respectively).

 

Conclusion

This study confirms that TCM intervention can effectively reduce the risk of adverse prognosis of PCI in patients with CCS. It also demonstrates that the integrative medicine could lead to further reduction of risk in high-risk CCS populations under the guidance of novel lipid metabolism indicators.

 

Key words: Chronic coronary syndrome, percutaneous coronary intervention, integrative medicine, adverse prognosis

Part III

 

Construction and Evaluation of Clinical Prediction Model Combining Traditional Chinese Medicine with Novel Lipid Metabolism Indicators

 

Abstract

Background

Traditional Chinese medicine (TCM) is an important approach in the clinical prevention and treatment of coronary artery disease (CAD) with their efficacy confirmed in many studies. Chronic coronary syndrome (CCS) is the primary component of CAD, characterized by dynamic changes in the course of the disease and a large individual variation in the risk of cardiovascular adverse events. In the first part of our study, we explored potential risk factors for CCS and identified novel lipid metabolism indicators such as the triglyceride glucose index (TyG) and remnant cholesterol (RC) as independent risk factors for repeat revascularization and in-stent restenosis (ISR) in patients with CCS after percutaneous coronary intervention (PCI). In the second part of our study, we confirmed that TCM can effectively reduce the risk of repeat revascularization and ISR in patients with CCS after PCI, and can further improve the adverse prognosis in high-risk groups under the guidance of TyG and RC. Therefore, how to provide further research evidence for the application of TCM in CCS, and thereby promote the application of TCM, has become an urgent issue to be addressed.

Clinical prediction models are tools for quantifying patient risk and benefit by integrating risk factors affecting prognosis. Numerous studies have demonstrated that clinical prediction models based on demographic characteristics and cardiovascular risk factors can effectively screen and identify high-risk CCS populations for major cardiovascular adverse events, thereby guiding preventive measures and treatment decisions. However, no studies to date have explored the application value of integrating TCM as baseline assessment factors into clinical prediction models.

 

Aims

Construct and evaluate a clinical prediction model using TCM intervention combined with novel lipid metabolism indicators for adverse prognosis in the CCS population after PCI, thereby providing new solutions and ideas for promoting the clinical application of TCM in CCS.

 

Methods

This study is a secondary analysis of a large-scale, prospective, observational cohort study. The exposure factor is the use of TCM+ Guideline-Directed Medical Treatment (GDMT), where TCM is defined as the use of CAD-related herbal medicines for more than 6 months per year. The study outcome is a composite endpoint of adverse prognosis of PCI, including repeat revascularization and ISR. Cross Lasso regression was used to screen the independent variables of the clinical prediction model. Nomogram was used to optimize the screened variables and visualize the multivariate prediction model. Bootstrap resampling was applied for internal validation of the model. Calibration curves were used to evaluate the consistency of the model. The concordance index (C-index), time-dependent receiver operating characteristic curves, and the time-dependent area under the curve (time-AUC) were used for sensitivity analysis.

Results

A total of 2274 patients were included in the final analysis. 1119 patients were in the TCM+GDMT group, and 1155 patients were in the GDMT group. The median follow-up duration was 60.45 months (interquartile range: 16.47-68.00), and 1054 patients (46.40%) experienced endpoint events.

After cross Lasso regression screening and nomogram optimization, GDMT+TCM treatment, TyG, number of implanted stents , target lesion ≥20mm, high-sensitive CRP (hs-CRP), multivessel disease, and history of percutaneous coronary intervention (PCI) could be used as independent variables to construct a clinical risk prediction model for adverse prognosis after PCI in CCS patients. Among them, GDMT+TCM was an independent protective factor for the risk of major study outcomes. After quantification, its score reduced by about 10 points compared to not receiving GDMT+TCM, corresponding to a reduction in risk of outcomes by about 10%. Additionally, number of implanted stents, target lesion ≥20mm, increased TyG level, elevated hs-CRP, multivessel disease, and history of PCI were significant risk factors for the risk of primary study outcome, contributing different values to the risk of outcomes. After internal validation with 1500 bootstrap resampling, the Calibration curve showed that the constructed clinical prediction model was consistent with actual observations for the risk of primary study outcome. Sensitivity analysis showed that the model had a 3-year C-index for major study outcomes of 59.2%, a 5-year C-index of 60.1%, and 3-year and 5-year time-AUC estimates of 0.624 (95%CI: 0.601-0.641) and 0.664 (95%CI: 0.648-0.687), respectively.

Conclusion

By establishing a clinical prediction model, this research is the first to integrate TCM intervention into the cardiovascular risk scoring system. It not only confirms that TCM interventions are an independent protective factor against adverse prognosis of PCI in CCS patients but also finds that the integration of Chinese and Western medicine can predict the risk of revascularization and ISR in CCS patients with various cardiovascular risk factors. The results of this study provide robust evidence for the improvement of TCM intervention in adverse prognosis of CCS patients after PCI and provide new insights into promoting the clinical application of TCM. This study is notably innovative in simplifying TCM clinical decision-making and expanding the clinical scenarios of TCM.

 

Key words: Chronic coronary syndrome, percutaneous coronary intervention, integrative medicine, clinical prediction model

Review Research progress of integrated traditional Chinese medicine and western medicine in the treatment of chronic coronary syndrome

 

Abstract: Coronary artery disease (CAD) is the leading cause of cardiovascular mortality with epidemiological characteristics of high prevalence, high incidence and high mortality, posing great threat to human health. Chronic coronary syndrome (CCS) is the primary component of CAD which are associated with different cardiovascular risk according to its subtypes. CCS is a dynamic clinical process. This review summarizes the diagnostic procedure and treatment of CCS based on the latest guideline, meanwhile emphasizes the treatment principles and research progress of traditional Chinese medicine in CCS and its subtypes, thus aiming to provide reference in optimizing the treatment and research of integrated traditional Chinese medicine and western medicine in CCS.