Abstract: Background　Hypertension is a risk factor for new-onset cardio-cerebrovascular diseases in the general population. At present，most studies focus on whether attaining the target blood pressure level has an influence on the morbidity of newly developed cardio-cerebrovascular diseases in hypertensive patients. There is no research on the association of times of attaining the target blood pressure level and cardio-cerebrovascular disease incidence in patients with hypertension. Objective　To evaluate the association of times of attaining the target blood pressure level with cardio-cerebrovascular disease morbidity in hypertensive patients. Methods　A prospective cohort study design was applied. A total of 16 131 hypertensive participants who participated in four annual health examinations（2006，2008，2010，2012） conducted by Kailuan（Group） Limited Liability Corporation and had no history of cardio-cerebrovascular diseases and cancer were enrolled. The follow-up started from the completion of the 2012 annual health examination，and ended till the onset of newly diagnosed cardio-cerebrovascular disease，death or the last day of follow-up period（2017-12-31）. For ease of estimating the association of times of attaining the target blood pressure level with cardio-cerebrovascular disease incidence，those who were found with attaining the target blood pressure level for 0，1，2，and 3 times in 2008，2010，and 2012 annual examinations were assigned to zero-time（n=5 850），one-time（n=4 838），two-time （n=3 276），and three-time（n=2 167） groups，respectively，and baseline data and incidence of cardio-cerebrovascular disease were compared between the groups. The cumulative incidence was estimated by Kaplan-Meier approach，and was compared by Log-Rank test. Multivariate Cox regression model was used to analyze the effect of the times of attaining the target blood pressure level on the incidence of cardio-cerebrovascular diseases. After excluding those with diabetes，hyperlipidemia and smoking habit，the Cox regression model was analyzed for sensitivity analysis. Results　There were significant differences in average age，male proportion，SBP，DBP，FBG，TC，and hs-CRP，proportion of smokers，proportion of drinkers，proportion of physical exercisers，detection rate of diabetes，detection rate of hyperlipidemia，and proportions of people taking antihypertensive drugs and hypoglycemic drugs among the groups（P<0.05）. The average follow-up period was （4.61±0.80） years. The incidence rate of CVD was 102.40/10 000 years. The cumulative incidence of cardio-cerebrovascular disease for zero-time，one-time，two-time，and three-time groups was 7.5%，6.9%，3.4% and 1.9%，respectively. And Log-Rank test showed that the difference in cumulative incidence of cardio-cerebrovascular disease among the groups was significant（χ2=128.33，P<0.01）. The Cox regression analysis presented that after adjusting for age，gender，BMI，hs-CRP，hyperlipidemia，diabetes，history of taking antihypertensive drugs，smoking，drinking，and physical exercise，compared with zero-time group，the HR（95%CI） for cardio-cerebrovascular disease incidence in one-time，two-time，and three-time groups was 0.90（0.76，1.06），0.53（0.42，0.68）and 0.37（0.26，0.53），respectively. The above results were not changed after excluding the diabetic，smoking and hyperlipidemia participants in the sensitivity analysis. Conclusion　 More times of attaining the target blood pressure level may be a protective factor for cardio-cerebrovascular disease，and continuous attaining the target may be associated with decreased risk of cardio-cerebrovascular disease.

Key words: Hypertension, Disease management, Cardiovascular diseases, Prospective studies

摘要： 背景　高血压是一般人群新发心脑血管疾病（CVD）的危险因素。目前研究大多集中于高血压患者血压水平是否达标对新发CVD的影响，国内外尚缺乏高血压患者血压达标次数对新发CVD影响的研究。目的　探讨高血压患者血压达标次数对CVD发病的影响。方法　采用前瞻性队列研究方法，选取连续参加开滦集团2006、2008、2010、2012年度体检且无CVD病史、肿瘤病史的高血压患者为观察对象，共16 131例观察对象纳入统计分析。以观察对象完成2012年度健康体检时点为随访起点，以新发CVD、死亡或随访结束（2017-12-31）为随访终点。根据在2008、2010、2012年度健康体检中血压值是否达标将观察对象分为达标0次组（5 850例）、达标1次组（4 838例）、达标2次组（3 276例）和达标3次组（2 167例）。观察各组人群基线资料和新发脑卒中发病率。经Kaplan-Meier法计算累积发病率，以Log-Rank法进行检验，采用多因素Cox回归模型分析高血压患者血压达标次数对心脑血管疾病发病的影响，分别删除糖尿病人群、吸烟人群和高脂血症人群后，进行敏感性分析。结果　不同血压达标次数组间年龄、男性占比、收缩压（SBP）、舒张压（DBP）、空腹血糖（FBG）、总胆固醇（TC）、超敏C反应蛋白（hs-CRP）、吸烟者占比、饮酒者占比、体育锻炼者占比、糖尿病检出率、高脂血症检出率、服降压药者占比及服降糖药者占比比较，差异有统计学意义（P<0.05）。平均随访（4.61±0.80）年，CVD的发病密度为102.40/万人年，血压达标0、1、2、3次组CVD累积发病率分别为7.5%、6.9%、3.4%和1.9%，经Log-Rank检验后，各组间CVD累积发病率比较，差异有统计学意义（χ2=128.33，P<0.01）。Cox回归分析结果显示，校正年龄、性别、BMI水平、hs-CRP水平、高脂血症、糖尿病、服用降压药史、吸烟、饮酒、体育锻炼后，与血压达标0次组比较，血压达标1次组、血压达标2次组和血压达标3次组发生CVD的HR（95%CI）分别为0.90（0.76，1.06）、0.53（0.42，0.68）和0.37（0.26，0.53）。在敏感性分析中，分别删除糖尿病人群、吸烟人群和高脂血症人群后上述结果未发生改变。结论　高血压患者血压达标次数多是CVD的保护因素，持续血压达标可以降低CVD发病风险。

关键词: 高血压, 疾病管理, 心脑血管疾病, 前瞻性研究