第一部分：冠心病患者动脉硬化的影响因素分析

目的：臂踝脉搏波传导速度（brachial-ankle pulse wave velocity, baPWV）作为评估动脉僵硬度的重要临床指标，在冠心病的发生与发展过程中具有显著的预测价值。本研究旨在深入探讨冠心病患者群体中影响动脉硬化的独立危险因素，以期为临床预防和治疗提供依据。

方法：本研究回顾性纳入了2014年1月至2022年11月期间因冠心病住院的3703例患者，所有患者均接受baPWV测量。根据预设的baPWV临界值，将患者分别分为baPWV ≤ 14 m/s与baPWV > 14 m/s、baPWV ≤ 18 m/s与baPWV > 18 m/s各两组。通过多因素Logistic回归模型分析baPWV > 14 m/s与baPWV > 18 m/s的独立影响因素，结果以比值比（odds ratio, OR）和95%置信区间（confidence interval, CI）来表示。

结果：本研究中患者平均年龄58.46 ± 10.26岁，男性3111人（84%），baPWV > 14m/s组2377人（64.2%），baPWV > 18m/s组660人（17.8%）。分析结果显示，年龄增长（OR = 1.09，95%CI 1.08～1.10，p < 0.001）、高血压史（OR = 1.32，95%CI 1.08～1.61，p = 0.006）、糖尿病史（OR = 1.36，95%CI 1.07～1.73，p = 0.012）、收缩压升高（OR = 1.04，95%CI 1.03～1.04，p < 0.001）、心率（OR = 1.01，95%CI 1.01～1.02，p = 0.002）及血沉增快（OR = 1.02，95%CI 1.01～1.03，p < 0.001）是baPWV轻度升高（baPWV > 14m/s）的独立影响因素，身体质量指数升高（OR = 0.95，95%CI 0.92～0.98，p = 0.001）与baPWV降低相关。对于baPWV明显升高（baPWV > 18m/s），独立影响因素包括年龄增加（OR = 1.10，95%CI 1.09～1.12，p < 0.001）、高血压史（OR = 1.79，95%CI 1.36～2.37，p < 0.001）、糖尿病史（OR = 1.48，95%CI 1.12～1.96，p = 0.006）、收缩压升高（OR = 1.02，95%CI 1.02～1.03，p < 0.001）、心率加快（OR = 1.03，95%CI 1.02～1.04，p < 0.001）、空腹血糖升高（OR = 1.06，95%CI 1.00～1.12，p = 0.036）以及血沉加快（OR = 1.01，95%CI 1.00～1.02，p = 0.014），而男性（OR = 0.69，95%CI 0.49～0.94，p = 0.020）、身体质量指数升高（OR = 0.93，95%CI 0.90～0.97，p < 0.001）与baPWV降低相关。

结论：在冠心病患者中，增龄、高血压史、糖尿病史、收缩压升高、心率及血沉增快是导致baPWV不同程度升高的独立影响因素。

第二部分：脉搏波传导速度在冠心病预后评估及卒中风险预测中的临床价值

内容一：臂踝脉搏波传导速度（baPWV）与估算的脉搏波传导速度（ePWV）在冠心病预后评估中的比较研究

背景：臂踝脉搏波传导速度（brachial-ankle pulse wave velocity，baPWV）和基于年龄与血压的估算的脉搏波传导速度（estimated pulse wave velocity，ePWV）作为评估动脉僵硬度的便捷无创方法，已被证实是评估冠心病患者预后的重要指标。然而，两种方法的关联及其在预后评估中的差异尚未得到充分研究。

方法：采用回顾性队列研究，纳入2014年1月至2022年11月因冠心病入院的患者，同步测量baPWV并计算ePWV。主要研究终点为主要不良心血管事件（major adverse cardiovascular events，MACE），即由全因死亡、非致死性心肌梗死、非致死性卒中及计划外血运重建组成的复合终点；次要终点为全因死亡。使用Spearman相关系数分析baPWV与ePWV之间的相关性，结合Cox比例风险回归模型和受试者工作特征（receiver operating characteristic，ROC）曲线下面积（area under curve，AUC）评估二者对不同研究终点的预测效能。

结果：最终纳入3126例患者（平均年龄58.54 ± 10.25岁，男性84.2%），中位随访57个月，期间共发生646例（20.7%）MACE和127例（4.1%）全因死亡。baPWV与ePWV之间呈中度正相关（r = 0.569，p < 0.001）。单变量Cox回归分析表明，baPWV和ePWV每增加1 m/s，MACE的风险比分别为1.05（95%CI 1.03～1.07）和1.09（95%CI 1.04～1.14），全因死亡的风险比分别为1.13（95%CI 1.11～1.16）和1.60（95%CI 1.48～1.74），多变量调整后仍具统计学显著性。ROC曲线分析显示，baPWV和ePWV对MACE的预测性能相似（baPWV：AUC = 0.55，ePWV：AUC = 0.53，p = 0.241），而ePWV在预测全因死亡方面优于baPWV（baPWV：AUC = 0.67，ePWV：AUC = 0.73，p = 0.001）。

结论：在冠心病患者中，baPWV与ePWV在评价动脉硬化方面具有中度相关性，二者均为主要不良心血管事件和全因死亡的独立预测因子，基于临床常规参数的ePWV在预测全因死亡方面显示出更优的临床价值。

内容二：baPWV联合标准可改变心血管危险因素（SMuRFs）分层对冠心病患者的预后价值评价

目的：动脉硬化与传统心血管危险因素密切相关，而这些因素可能影响动脉硬化对冠心病患者预后的评估价值。本研究基于不同标准可改变心血管危险因素（standard modifiable cardiovascular risk factors，SMuRFs）（即高血压、糖尿病、高脂血症及抽烟）分层，旨在探讨臂踝脉搏波传导速度（brachial-ankle pulse wave velocity，baPWV）水平对冠心病患者预后的预测价值差异。

方法：采用回顾性队列研究设计，纳入2014年1月至2022年11月收治的冠心病患者3126例。基于SMuRFs累积数量进行危险分层：0~1、2、3~4个危险因素组。研究终点为主要不良心血管事件（major adverse cardiovascular events，MACE），即由全因死亡、非致死性心肌梗死、非致死性卒中及计划外血运重建组成的复合终点。通过受试者工作特征曲线确定不同分组里baPWV的最佳截断值，建立Cox比例风险回归模型评估分类变量（高/低baPWV组）和连续变量baPWV的预后价值，并采用限制性立方样条分析其剂量-反应关系。

结果：患者平均年龄58.5 ± 10.3岁，其中男性占84.2%，中位随访57个月，累计发生MACE 646例（20.7%）。作为分类变量时，与低baPWV组相比，高baPWV组的MACE风险显著更高（0~1 SMuRF：HR 1.59，95%CI 1.02～2.49；2 SMuRFs：HR 1.41，95%CI 1.04～1.91；3~4 SMuRFs：HR 1.32，95%CI 1.01～1.72）。作为连续变量时，仅在3~4 SMuRFs组中，baPWV每增加1m/s，MACE风险显著增加（HR 1.05，95%CI 1.01～1.09），而在其余两组中，baPWV对MACE风险预测无统计学意义。限制性立方样条分析进一步表明，在3~4 SMuRFs组中，baPWV与MACE风险呈线性正相关（总p = 0.039，非线性p = 0.232）。

结论：baPWV作为分类变量时，高baPWV组在所有SMuRFs分组中MACE风险均显著增加，而其作为连续变量的预测效能呈现危险分层依赖性，仅在SMuRFs高负担（≥ 3个）人群中表现出显著的量效关系。

内容三：估算的脉搏波传导速度（ePWV）对中老年人群卒中风险的预测价值：来自三项前瞻性队列研究

目的：动脉硬化已被证实是卒中的重要危险因素之一。然而，估算的脉搏波传导速度（estimated pulse wave velocity，ePWV）作为动脉僵硬度评估的新兴指标，其与中老年人群卒中风险的关联尚未完全明确。本研究旨在探讨中老年人群中ePWV与卒中风险之间的关系，为卒中的一级预防提供新的依据。

方法：本研究基于美国健康与退休研究（Health and Retirement Study，HRS）、英国老龄化纵向研究（English Longitudinal Study of Ageing，ELSA）和中国健康与养老追踪调查（China Health and Retirement Longitudinal Study，CHARLS）三项前瞻性队列研究数据，通过年龄和平均动脉压计算ePWV，采用Cox比例风险模型分析ePWV与卒中风险之间的关联，结果以风险比（hazard ratios，HR）及其95%置信区间（confidence intervals，CI）表示。采用限制性立方样条（restrictive cubic spline，RCS）分析ePWV与卒中风险的非线性关联。

结果：最终纳入HRS队列6458人（平均年龄66.99岁，男性40.4%）、ELSA队列6458人（平均年龄66.32岁，男性44.4%）以及CHARLS队列12415人（平均年龄58.60岁，男性46.2%）。分别经过10.28年、9.95年及6.30年的随访，HRS、ELSA和CHARLS队列新发卒中分别为624例（9.7%）、374例（5.8%）和656例（5.3%）。经多因素校正后，ePWV每增加1 m/s，卒中风险显著升高（HRS：HR 1.29，95% CI 1.24～1.35；ELSA：HR 1.37，95% CI 1.28～1.46；CHARLS：HR 1.20，95% CI 1.15～1.25）。RCS模型显示，HRS和ELSA队列中ePWV与卒中风险呈线性正相关（HRS：总p < 0.001，非线性p = 0.186；ELSA：总p < 0.001，非线性p = 0.652），而在CHARLS队列中ePWV与卒中风险呈非线性关联（总p < 0.001，非线性p = 0.002）

结论：本研究显示，ePWV升高与中老年人群卒中风险增加显著相关，在HRS和ELSA队列中ePWV与卒中风险之间呈现线性正相关关系，而在CHARLS队列中则表现出非线性关联。

Part I: Risk Factors of Arterial Stiffness in Patients with Coronary Artery Disease

Objective: The brachial-ankle pulse wave velocity (baPWV), a crucial clinical indicator for assessing arterial stiffness, has demonstrated significant predictive value in the occurrence and progression of coronary artery disease (CAD). This study aimed to investigate the independent risk factors influencing arterial stiffness in patients with CAD, providing potential insights for clinical prevention and treatment.

Methods: This retrospective study enrolled 3703 patients hospitalized for CAD between January 2014 and November 2022. All patients underwent baPWV measurements. Based on predefined baPWV cutoff values, patients were divided into two groups: baPWV ≤ 14 m/s vs. baPWV > 14 m/s, and baPWV ≤ 18 m/s vs. baPWV > 18 m/s. Multivariate logistic regression models were used to identify independent factors associated with baPWV > 14 m/s and baPWV > 18 m/s. Odds ratios (OR) and 95% confidence intervals (CI) were used to represent the results.

Results: In this study, the patients had a mean age of 58.46 ± 10.26 years, with 3111 males (84%). 2377 (64.2%) patients were in the baPWV > 14 m/s group, and 660 (17.8%) were in the baPWV > 18 m/s group. The analysis revealed that increased age (OR = 1.09, 95%CI 1.08～1.10, p < 0.001), history of hypertension (OR = 1.32, 95%CI 1.08～1.61, p = 0.006), history of diabetes (OR = 1.36, 95%CI 1.07～1.73, p = 0.012), elevated systolic blood pressure (OR = 1.04, 95%CI 1.03～1.05, p < 0.001), increased heart rate (OR = 1.01, 95%CI 1.01～1.02, p = 0.002), and elevated erythrocyte sedimentation rate (ESR) (OR = 1.02, 95%CI 1.01～1.03, p < 0.001) were independent influencing factors for mild increase in baPWV ( baPWV> 14 m/s), while an increase in body mass index (BMI) (OR = 0.95, 95%CI 0.92～0.98, p = 0.001) was associated with a decrease in baPWV. For a significant increase in baPWV (baPWV > 18 m/s), independent influencing factors included increased age (OR = 1.10, 95%CI 1.09～1.12, p < 0.001), history of hypertension (OR = 1.79, 95%CI 1.36～2.37, p < 0.001),history of diabetes (OR = 1.48, 95%CI 1.12～1.96, p = 0.006), elevated systolic blood pressure (OR = 1.02, 95%CI 1.02～1.03, p < 0.001), increased heart rate (OR = 1.03, 95%CI 1.02～1.04, p < 0.001), and elevated fasting glucose (OR = 1.06，95%CI 1.00～1.12，p = 0.036) and ESR (OR = 1.01, 95%CI 1.00～1.02, p = 0.014). Male gender (OR = 0.69, 95% CI 0.49～0.94, p = 0.020) and increased BMI (OR = 0.93, 95% CI 0.90～0.97, p < 0.001) were associated with decreased baPWV.

Conclusions: In patients with CAD, increased age, history of hypertension, history of diabetes, elevated systolic blood pressure, increased heart rate, and accelerated ESR were associated with different levels of baPWV elevation.

Part II: Clinical Value of Pulse Wave Velocity in Prognostic Evaluation of Coronary Artery Disease and Prediction of Stroke Risk

Content I: A Comparative Study of Brachial-Ankle Pulse Wave Velocity (baPWV) and Estimated Pulse Wave Velocity (ePWV) in Prognostic Evaluation of Coronary Artery Disease

Background: Brachial-ankle pulse wave velocity (baPWV) and estimated pulse wave velocity (ePWV), derived from age and blood pressure parameters, serve as non-invasive and easily accessible methods for assessing arterial stiffness. Both parameters have been established as significant prognostic markers in patients with coronary artery disease (CAD). However, the relationship between these two measures and their differences in prognostic evaluation have not been fully explored.

Methods: This study adopted a retrospective cohort design, enrolling CAD patients hospitalized from January 2014 to November 2022, who underwent simultaneous measurement of baPWV and calculation of ePWV. The primary endpoint, major adverse cardiovascular event (MACE), was defined as a composite of all-cause mortality, non-fatal myocardial infarction, non-fatal stroke, and unplanned revascularization. The secondary endpoint was all-cause mortality. Spearman's correlation coefficient was utilized to analyze the relationship between baPWV and ePWV. Cox proportional hazards regression models, receiver operating characteristic (ROC) curves, and area under the curve (AUC) were used to evaluate the predictive performance of both measures for different study endpoints.

Results: Among the 3126 enrolled patients (mean age 58.54 ± 10.25 years, 84.2% male) with a median 57-month follow-up, 646 MACEs (20.7%) and 127 (4.1%) all-cause deaths occurred. A significantly positive correlation was observed between baPWV and ePWV (r = 0.569, p < 0.001). Univariate Cox regression analysis showed that each 1 m/s increase in baPWV and ePWV was associated with an increased risk of MACE (baPWV: HR 1.05, 95%CI 1.03～1.07; ePWV: HR 1.09, 95%CI 1.04～1.14) and all-cause mortality (baPWV: HR 1.13, 95%CI 1.11～1.16; ePWV: HR 1.60, 95%CI 1.48～1.74), which remained statistically significant after multivariate adjustment. ROC analysis revealed comparable predictive performance for MACE (baPWV: AUC = 0.55, ePWV: AUC = 0.53, p = 0.241), while ePWV demonstrated superior predictive accuracy for all-cause mortality (baPWV: AUC = 0.67, ePWV: AUC = 0.73, p = 0.001).

Conclusions: This study demonstrated that baPWV and ePWV are moderately correlated in patients with CAD, and both were independent predictors of MACE and all-cause mortality. Notably, ePWV, based on routine clinical parameters, exhibited superior predictive value for all-cause mortality compared to baPWV. 

Content II: Combined Effect of Brachial-Ankle Pulse Wave Velocity (baPWV) and Standard Modifiable Cardiovascular Risk Factors (SMuRFs) on Prognosis in Patients with Coronary Artery Disease

Objective: Arterial stiffness is closely correlated with traditional cardiovascular risk factors, which might confound the prognostic value of artery stiffness assessment in patients with coronary artery disease (CAD). This study aims to investigate the predictive value of brachial-ankle pulse wave velocity (baPWV) for cardiovascular outcomes in CAD patients with varying burdens of standard modifiable cardiovascular risk factors (SMuRFs), which included hypertension, diabetes, hyperlipidemia, and smoking.

Methods: This study adopted a retrospective cohort design, enrolling 3126 CAD patients hospitalized between January 2014 and November 2022. Participants were stratified by SMuRF burden: 0~1, 2, and 3~4 risk factor groups. The primary endpoint was major adverse cardiovascular events (MACE), a composite of all-cause mortality, non-fatal myocardial infarction, non-fatal stroke, and unplanned revascularization. Optimal baPWV cutoffs were determined using receiver operating characteristic curves. Cox proportional hazards regression models were used to assess the prognostic value of both categorical (high/low baPWV groups) and continuous baPWV measurements, with restricted cubic splines (RCS) employed to analyze dose-response relationships.

Results: The mean age of the patients was 58.5 ± 10.3 years, and 84.2% were male. During a median follow-up of 57 months, 646 MACE cases (20.7%) occurred. When analyzed as a categorical variable, the high baPWV group demonstrated significantly higher MACE risk compared to the low baPWV group across all strata (0~1 SMuRFs: HR 1.59, 95%CI 1.02～2.49; 2 SMuRFs: HR 1.41, 1.04～1.91; 3~4 SMuRFs: HR 1.32, 1.01～1.72). As a continuous variable, each 1 m/s increase in baPWV was significantly associated with elevated MACE risk only in the 3~4 SMuRFs group (HR 1.05, 95% CI 1.01～1.09), with no statistically significant association observed in the other groups. RCS analysis further confirmed a linear positive correlation between baPWV and MACE risk in the 3~4 SMuRFs group (p for overall = 0.039, p for non-linearity = 0.232).

Conclusions: When baPWV was used as a categorical variable, the high baPWV group showed a significantly increased risk of MACE in all SMuRFs groups. However, as a continuous variable, its predictive effectiveness depended on risk stratification, showing a significant dose-response relationship only in the population with a high burden of SMuRFs (≥ 3 factors).

Content III: Estimated Pulse Wave Velocity and Stroke among Middle-aged and Older Population: Insights from Three Prospective Cohorts

Objective: Arterial stiffness is recognized as a new risk factor for stroke. However, the association between estimated pulse wave velocity (ePWV), a well-established indirect measure of arterial stiffness, and stroke remains incompletely investigated. This study aims to investigate the relationship between ePWV and stroke risk in middle-aged and older adults, providing new evidence for the primary prevention of stroke.

Methods: This study utilized data from three prospective, nationally representative cohorts: the Health and Retirement Study (HRS) in the United States, the English Longitudinal Study of Ageing (ELSA) in the United Kingdom, and the China Health and Retirement Longitudinal Study (CHARLS) in China. ePWV was calculated based on age and mean arterial pressure. The Cox proportional hazards model was employed to analyze the association between ePWV and stroke risk, with results expressed as hazard ratios (HRs) and their 95% confidence intervals (CIs). A restrictive cubic spline (RCS) was used to analyze the non-linear relationship between ePWV and stroke risk.

Results: The final analysis included 6458 participants from the HRS (mean age: 66.99 years, 40.4% men), 6458 from the ELSA (mean age: 66.32, 44.4% men), and 12415 from the CHARLS (mean age: 58.60, 46.2% men). Over follow-up periods of 10.28 years in the HRS, 9.95 years in the ELSA, and 6.30 years in the CHARLS, 624 (9.7%), 374 (5.8%), and 656 (5.3%) participants developed stroke, respectively. After multivariate adjustment, per 1 m/s increase in ePWV was associated with a significant increase in stroke risk (HRS: HR 1.29, 95% CI 1.24～1.35; ELSA: HR 1.37, 95% CI 1.28～1.46; CHARLS: HR 1.20, 95% CI 1.15～1.25). The RCS model showed a linear positive association between ePWV and stroke risk in the HRS and ELSA cohorts (p for non-linearity = 0.186 and 0.652, respectively), while a non-linear association was observed in the CHARLS cohort (p for non-linearity = 0.002).

Conclusions: This study showed that higher levels of ePWV were associated with increased risks of incident stroke among middle-aged and older populations. A linear positive relationship was observed between ePWV and stroke risk in the HRS and ELSA cohorts, while a non-linear association was found in the CHARLS cohort.