Abstract: Background　Currently，the landscape of cancer treatment has undergone significant transformations，with numerous cancer patients now surviving in a chronic disease paradigm over extended periods. Research indicates that a substantial number of cancer survivors succumb to non-tumor factors，with cardiovascular disease（CVD） being a prominent cause among them. Nevertheless，the potential CVD risks associated with cancer treatment are frequently overlooked，resulting in inadequate early intervention and protective measures.The estimated pulse wave velocity（ePWV） can reflect the degree of arterial stiffness and is an independent predictor of cardiovascular events. The simple calculation method provides feasibility for cardiovascular risk stratification in cancer patients. Objective　To assess the influencing factors of ePWV for all-cause mortality and cardiovascular disease mortality in a cohort of cancer patients. Methods　A retrospective cohort design was used. The cohort included 4 632 cancer patients who attended the National Health and Nutrition Examination Survey（NHANES） database from 1999 to 2018. Baseline data were collected，including age，gender，race，body mass index（BMI），chest circumference， baseline heart rate，total cholesterol（TC），high-density lipoprotein cholesterol（HDL-C），systolic blood pressure（SBP）， diastolic blood pressure（DBP），diabetes status，history of cardiovascular disease，smoking and drinking status. Follow-up to July 2023. With ePWV as the variable，the quartile method was used for grouping. All the subjects were divided into 4 groups，which were recorded as Q1，Q2，Q3 and Q4 groups. The baseline levels of the 4 groups were compared，and the Kaplan-Meier survival curves related to all-cause mortality and cardiovascular disease mortality of the patients were plotted. Cox proportional hazard regression model were used to explore the relationship of ePWV and mortality in cancer patients. The receiver operating characteristic（ROC） curve of the predictive value of ePWV for death in cancer patients was drawn，and the area under the ROC curve（AUC） was calculated. Results　A total of 4 632 patients，with an average age of（60.7±1.01） years，were enrolled，comprising 2 426 females（52.37%） and 2 206 males（47.63%）. There were 1 158 cases（25.0 %） in Q1-Q4 groups. Significant differences were observed among the four groups in terms of age，gender，race，BMI，chest circumference，baseline heart rate，TC，HDL-C，SBP，DBP，diabetes history，cardiovascular disease history，smoking status，and alcohol consumption status（P<0.05）. During the follow-up period，830（17.9 %） of 4632 cancer patients died of all-cause and 376（8.1 %） died of cardiovascular disease.There were significant differences in all-cause mortality and cardiovascular disease mortality among the four groups（P<0.001）. Kaplan-Meier survival analysis revealed statistically significant differences in the survival curves related to all-cause mortality and CVD mortality among 4 groups（χ2 =587.11，P<0.001；χ2 =322.97，P<0.001）. The results of multivariate Cox regression analysis indicated that，compared with patients in Q1，those in Q2，Q3，and Q4 had an increased risk of all-cause mortality（Q2：HR=1.30，95%CI=1.23-1.38，P=0.045；Q3：HR=1.46，95%CI=1.01-2.13，P=0.047；Q4：HR=1.24，95%CI=1.04-1.49，P=0.017）. Additionally，patients in Q3 and Q4 exhibited an elevated risk of CVD mortality（Q3：HR=1.28，95%CI=1.05~1.56，P=0.013；Q4：HR=2.73，95%CI=1.67-4.48，P=0.026）；ROC curve showed that the AUC values of Q1，Q2，Q3 and Q4 quartile groups were 0.514，0.624，0.598 and 0.772，respectively. Conclusion　For the first time，it was verified that elevated ePWV was positively correlated with the risk of all-cause and cardiovascular disease mortality in cancer patients. ePWV may be a predictor of the risk of death in this population.

Key words: Cancer, Arterial stiffness, Cardiovascular disease, Mortality rate, Cohort studies, Retrospective study, Root cause analysis

摘要： 背景　目前癌症治疗发生了巨大的变革，许多癌症患者以一种慢性病的模式长期生存。研究显示，众多癌症幸存者死于非肿瘤因素，而心血管疾病（CVD）则是主要原因之一。然而癌症治疗潜在的CVD常被忽视，进而导致早期干预与保护不足。估算的脉搏波传导速度（ePWV）可以反应动脉僵硬度的程度，是心血管事件的独立预测指标，其简单的计算方法为癌症患者的心血管风险分层提供了可行性。目的　通过队列研究分析ePWV与癌症患者全因死亡和心血管疾病死亡的关系。方法　本研究为回顾性队列研究，选取1999—2018年国家健康和营养检查调查（NHANES）数据库中的4 632例癌症患者为研究对象。收集患者基线资料，包括年龄、性别、种族，体质指数、胸围、基础心率、总胆固醇、高密度脂蛋白胆固醇、收缩压、舒张压、糖尿病疾病史、心血管疾病史、吸烟、饮酒状态，随访至2023年7月，记录患者全因死亡率和心血管疾病死亡率。根据动脉僵硬度协作组推导公式计算ePWV值，并根据ePWV数值大小将患者分为Q1~Q4组；比较4组患者基线水平，绘制患者全因死亡和心血管疾病死亡相关Kaplan-Meier生存曲线；采用多因素Cox比例风险模型分析患者全因死亡和心血管病死亡影响因素；绘制ePWV预测癌症心血管疾病死亡的受试者工作特征（ROC）曲线，计算ROC曲线下面积（AUC）；结果　共纳入4 632例患者，平均年龄为（60.7±1.01）岁，女性2 426例（52.37%），男性2 206例（47.63%）。Q1~Q4组各1 158例（25.0%）。4组年龄、性别、种族、BMI、胸围、RHR、TC、HDL-C、SBP、DBP、糖尿病病史、心血管病史、吸烟、饮酒状态比较，差异均有统计学意义（P<0.05）。随访11.8年，4 632例癌症患者中全因死亡者830例，全因死亡发生率为17.9%；心血管疾病相关死亡376例，心血管疾病相关死亡发生率为8.1%。4组组患者全因死亡率和心血管疾病死亡率比较，差异均有统计学意义（P<0.001）。Kaplan-Meier生存分析结果显示，四组患者全因死亡和心血管疾病死亡相关生存曲线比较，差异均有统计学意义（χ2=587.11，P<0.001；χ2=322.97，P<0.001）。多因素Cox回归分析结果显示，相比于Q1组，Q2、Q3、Q4组患者发生全因死亡的危险增加（Q2：HR=1.30，95%CI=1.23~1.38，P=0.045；Q3：HR=1.46，95%CI=1.01~2.13，P=0.047；Q4：HR=1.24，95%CI=1.04~1.49，P=0.017）；Q3、Q4组患者发生心血管疾病死亡的危险增加（Q3：HR=1.28，95%CI=1.05~1.56，P=0.013；Q4：HR=2.73，95%CI=1.67~4.48，P=0.026）。ROC曲线显示，Q1、Q2、Q3和Q4组对应的AUC值分别为0.514、0.624、0.598、0.772。结论　首次在癌症患者中验证了ePWV升高与全因死亡风险和心血管疾病死亡风险呈正相关。ePWV或可成为预测癌症患者死亡风险的预测因子。

关键词: 癌症, 动脉僵硬度, 心血管疾病, 死亡率, 队列研究, 回顾性性研究, 影响因素分析