Abstract: Background　Either arterial stiffness or essential hypertension has been sufficiently proved to be a major risk for cardio-cerebrovascular disease，but combined association of them with cardio-cerebrovascular disease has been rarely reported. Objective　To further explore the relationship of arterial stiffness or essential hypertension with cardio-cerebrovascular disease in Chinese population in a large prospective community-based cohort study，and examine whether the former two have a combined association with the latter. Methods　Participants（n=33 820）were selected from individuals attending the four annual follow-up visits（2010—2011，2012—2013，2014—2015，2016—2017）of Kailuan study and had brachial-ankle pulse wave velocity（baPWV）measurement（without any cardio-cerebral vascular events prior to the measurement）and ABI<0.9. Age，gender，systolic blood pressure（SBP），diastolic blood pressure（DBP），baPWV，heart rate，body mass index（BMI），fasting blood glucose（FBG），total cholesterol（TC），triglyceride（TG），low-density lipoprotein cholesterol（LDL-C），high-density lipoprotein cholesterol（HDL-C），uric acid（UA），smoking，drinking，physical exercise，education level，diabetes，and the use of antihypertensive drugs and hypoglycemic drugs were collected. The study was completed until December 31，2017，with the occurrence of a cardiovascular or cerebrovascular event as the endpoint event. Arterial stiffness was defined as baPWV > 1 400 cm/s. By the prevalence of arterial stiffness and essential hypertension during the follow-up period，participants were categorized into group 1（having no essential hypertension and arterial stiffness），group 2（having no essential hypertension but arterial stiffness），group 3（having essential hypertension and arterial stiffness），and group 4（having essential hypertension but no arterial stiffness）. Multivariate Cox regression analysis was used to further investigate the association of arterial stiffness or essential hypertension with cardio-cerebrovascular disease，and the strength of combined association of the former two with the latter. Results　The average follow-up years was（3.34±2.38）. The incidence density of cardio-cerebrovascular disease was 51.67 per 10 000 person-year. The cumulative incidence of cardio-cerebrovascular disease in groups 1-4 was 0.28%，1.94%，1.75%，4.70%，respectively. Four groups had statistically significant differences in male proportion，mean age，baPWV，BMI，FBG，TC，TG，LDL-C，HDL-C，SBP，DBP，heart rate，BMI，FBG，TC，TG，LDL-C，UA，smoking，drinking，physical exercise，diabetes，prevalence of taking antihypertensive drugs，prevalence of taking hypoglycemic drugs，and cumulative incidence of cardio-cerebrovascular disease（P<0.05）. Multivariate Cox regression analysis showed that prevalence of arterial stiffness 〔HR=2.60，95%CI（1.88，3.61）〕，baPWV-SD〔HR=1.22，95%CI（1.12，1.33）〕，prevalence of essential hypertension〔HR=2.05，95%CI（1.59，2.64）〕 and SBP-SD〔HR=1.26，95%CI（1.14，1.38）〕 were the associated with cardio-cerebrovascular disease（P<0.05）. Compared with group G1，the HR of cardio-cerebral vascular events in groups 2-4 was 3.33〔95%CI（2.08，5.33）〕，2.81〔95%CI（1.57，5.03）〕and 5.98〔95%CI（3.79，9.43）〕，respectively. The results suggested there was no interact effect between arterial stiffness and essential hypertension on cardio-cerebrovascular disease（P=0.789）. No result was changed after repeating the above analysis after excluding the population taking antihypertensive medications. Conclusion　Our study found that both arterial stiffness and essential hypertension increased the risk of cardio-cerebrovascular disease，and they had a combined association with cardio-cerebrovascular disease.

Key words: Arterial stiffness, Essential hypertension, Cardiovascular disease, Cerebrovascular disorders, Combined effect, Root cause analysis, Follow-up studies

摘要： 背景　动脉硬化与原发性高血压均是心脑血管疾病（CVD）的重要危险因素，目前单一因素对CVD发病的影响已得到充分阐明，但关于动脉硬化与原发性高血压二者联合对CVD影响的研究鲜有报道。目的　通过一项以社区人群为基础的大型前瞻性队列研究，分析动脉硬化及原发性高血压在中国人群中对CVD发病的影响，并探讨两者间是否存在联合作用。方法　选取参加开滦研究2010—2011、2012—2013、2014—2015、2016—2017年度随访且同时完成臂踝脉搏博传导速度（baPWV）测量者为观察对象，排除baPWV测量前发生心脑血管事件者和踝肱指数（ABI）<0.9者，最终共有33 820例观察对象纳入统计分析，收集其年龄、性别、收缩压（SBP）、舒张压（DBP）、baPWV、心率、体质指数（BMI）、空腹血糖（FBG）、总胆固醇（TC）、三酰甘油（TG）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）、尿酸（UA）、吸烟、饮酒、体育锻炼、教育程度、糖尿病、服用降压药物及降糖药物情况等资料。研究随访至2017-12-31，以发生心脑血管事件为终点事件。根据baPWV是否>1 400 cm/s以及同期观察对象是否患有原发性高血压，将观察对象分为非原发性高血压及非动脉硬化组（G1组）、非原发性高血压及动脉硬化组（G2组）、原发性高血压及动脉硬化组（G3组）和原发性高血压及非动脉硬化组（G4组）。采用多因素Cox比例风险回归模型分析进一步探究动脉硬化及原发性高血压对CVD发病的影响，并分析动脉硬化与原发性高血压对CVD的联合作用。结果　平均随访时间（3.34±2.38）年，CVD的发病密度为51.67/万人年，各组CVD累积发病率分别为0.28%、1.94%、1.75%、4.70%。4组年龄、男性占比、baPWV、BMI、FBG、TC、TG、LDL-C、HDL-C、SBP、DBP、baPWV、心率、BMI、FBG、TC、TG、LDL-C、UA、吸烟、饮酒、体育锻炼、糖尿病、服用降压药物比例、服用降糖药物比例、CVD累积发病率比较，差异均有统计学意义（P<0.05）。多因素Cox比例风险回归模型结果显示，动脉硬化情况〔HR=2.60，95%CI（1.88，3.61）〕、baPWV/baPWV的标准差（baPWV-SD）〔HR=1.22，95%CI（1.12，1.33）〕、原发性高血压情况〔HR=2.05，95%CI（1.59，2.64）〕、SBP/SBP的标准差（SBP-SD）〔HR=1.26，95%CI（1.14，1.38）〕均为CVD发病的影响因素（P<0.05）；与G1组相比，各组发生CVD的HR分别为3.33〔95%CI（2.08，5.33）〕、2.81〔95%CI（1.57，5.03）〕、5.98〔95%CI（3.79，9.43）〕，且动脉硬化与原发性高血压对CVD发病无交互作用（P=0.789），在删除服用降压药物人群后重复上述分析结果未发生改变。结论　动脉硬化及原发性高血压均是CVD发病的危险因素，并且两者间存在联合作用。

关键词: 动脉硬化, 原发性高血压, 心血管疾病, 脑血管障碍, 联合作用, 影响因素分析, 随访研究