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目的:探讨不同类型难治性高血压患者的患病情况及心脑血管预后。方法:本研究为多中心前瞻性队列研究。研究对象来自中国动态和家庭血压监测登记研究，入选2009年8月至2017年10月在全国19个省份共42家医院高血压门诊就诊且接受降压药物治疗的高血压患者。根据诊室血压控制情况诊断表观难治性高血压，表观难治性高血压定义为使用≥3种降压药物治疗诊室血压仍未控制（≥140/90 mmHg，1 mmHg=0.133 kPa），或使用≥4种降压药物治疗诊室血压控制（<140/90 mmHg）。其中诊室血压未控制者进一步根据24 h动态血压监测结果分为假性难治性高血压和真性难治性高血压。主要终点为致死性和非致死性心脑血管事件，即由心脑血管死亡、缺血性和出血性卒中、心肌梗死、冠状动脉血运重建、不稳定心绞痛、心力衰竭以及通过冠状动脉造影证实的冠状动脉狭窄≥50%组成的复合终点。次要终点为致死性和非致死性卒中，致死性和非致死性心脏事件。以仅服用1或2种类型降压药物后诊室血压控制的患者作为参照，采用Kaplan-Meier曲线、对数秩检验和Cox比例风险模型评价表观难治性高血压对心脑血管预后的影响。结果:共纳入2 782例高血压患者，年龄（58.1±12.3）岁，其中男性1 403例（50.4%）。在所有接受降压药物治疗的患者中，表观难治性高血压的患病率为15.1%（420/2 782），真性难治性高血压占比10.5%（293/2 782）。中位随访时间为5年，表观难治性高血压患者中，58例发生致死性和非致死性心脑血管事件（28.2例/1 000人年），24例发生致死性和非致死性卒中（11.2例/1 000人年），40例发生致死性和非致死性心脏事件（19.1例/1 000人年）。Kaplan-Meier曲线及对数秩检验结果显示，表观难治性高血压患者尤其是真性难治性高血压患者的致死性和非致死性心脑血管事件、卒中以及心脏事件的累积发生率较高（ P均<0.05）。多因素Cox回归分析显示，真性难治性高血压与致死性和非致死性心脑血管事件（ HR=1.73，95% CI 1.17~2.56， P=0.006）以及卒中（ HR=2.81，95% CI 1.53~5.17， P=0.001）的发生风险增加相关。 结论:表观难治性高血压尤其是真性难治性高血压与较高的致死性和非致死性心脑血管事件风险相关。

Objective:To investigate the prevalence and associated risk of cardiovascular event of resistant hypertension in treated outpatients.Methods:This study was a nationwide multi-center prospective cohort study. The participants were treated outpatients enrolled in the China Nationwide Ambulatory and Home Blood Pressure Registry study of 42 hospitals in 19 provinces across the country from August 2009 to October 2017. Apparent resistant hypertension was defined as uncontrolled office blood pressure (≥140/90 mmHg, 1 mmHg=0.133 kPa) in spite of the use of three antihypertensive drugs or controlled office blood pressure (<140/90 mmHg) with four antihypertensive drugs or more. Subjects diagnosed with uncontrolled office blood pressure were further subdivided as pseudo-resistant hypertension and true resistant hypertension based on 24 h ambulatory blood pressure monitoring. The primary endpoint was fatal and non-fatal cardiovascular and cerebrovascular events, which was a composite endpoint consisting of cardiovascular and cerebrovascular death, ischemic and hemorrhagic stroke, myocardial infarction, coronary artery revascularization, unstable angina, heart failure, and coronary artery stenosis≥50% confirmed by coronary angiography. Secondary outcomes included fatal and non-fatal stroke or cardiac events. Patients with controlled office blood pressure after taking only 1 or 2 antihypertensive drugs were included as control. Kaplan-Meier survival curves, log-rank test, and Cox proportional risk model were used to evaluate the risk of apparent refractory hypertension in relation to cardiovascular and cerebrovascular prognosis.Results:A total of 2 782 treated hypertensive patients, aged (58.1±12.3) years were enrolled, including 1 403 (50.4%) men. The prevalence of apparent and true resistant hypertension was 15.1% (420/2 782) and 10.5% (293/2 782), respectively. Among patients with apparent resistant hypertension, during a median of 5 years follow-up, the cumulative incidence rate was 28.2, 11.2 and 19.1 per 1 000 person-years for fatal and non-fatal cardiovascular events ( n=58), stroke ( n=24) and cardiac events ( n=40), respectively. The Kaplan-Meier curve and log-rank test showed that those patients with true resistant hypertension, had the highest cumulative incidence rate of fatal and non-fatal cardiovascular events, stroke, and cardiac events. Multivariable Cox regression analyses showed that true resistant hypertension was associated with a significantly higher risk of fatal and non-fatal cardiovascular events ( HR=1.73, 95% CI 1.17-2.56, P=0.006) and stroke ( HR=2.81, 95% CI 1.53-5.17, P=0.001). Conclusion:Resistant hypertension, especially true resistant hypertension, is associated with a higher risk of fatal and non-fatal cardiac and cerebrovascular events.