轻度高血压患者存在系统性微血管稀疏，个体化运动方案可降低血压水平｜ACC 2019
微血管稀疏（MVR）是高血压的重要的病理生理改变，通过增加血管阻力及改善微环境，促进靶器官损害的发生发展。已有证据表明中等强度运动能一定程度降低血压、改善内皮功能，而且，内皮祖细胞（EPCs）对维持血管内皮稳态具有重要作用，然而，运动是否能通过改善EPCs功能来改善高血压MVR缺乏相关研究。
在ACC 2019年会上，中山大学附属第八医院梁建文博士等提交的一项研究结果显示，轻度高血压患者存在系统性微血管稀疏且能通过OCTA联合指襞显微镜发现，个体化中等强度运动方案可显著降低轻度高血压患者的血压水平。
研究简介
本研究通过入组年轻（25-40岁）1级高血压且未经药物治疗的患者35例和年龄匹配的健康志愿者35例，两组均行指襞显微镜检查指襞微血管密度（SCD）及眼底OCT检测视网膜微血管密度（RCD）和无灌注面积（R-NPA）评估系统微循环灌注情况；高血压患者经心肺运动测试（CPET）后，行中等强度运动（功率自行车阻力平台模式，运动强度为最大运动耐量METs的70%，5次/周，每次运动的时间分配为3分钟热身，45分钟阻力运动及10分钟恢复，约3000 Kcal/周）干预12周。运动前后检测EPCs的功能并分析与NOTCH-eNOS信号通路间的关系。
研究结果提示，高血压患者的SCD及RCD均较健康志愿者降低（P<0.05），R-NPA较健康人群明显增加（P<0.01），存在微血管稀疏现象，且OCT检查方法较传统的指襞显微镜方法的检测效能要高[(RCD AUC 0.81 >0.64 of SCD, P<0.001; R-NPA AUC 0.78 >0.64 of SCD, P<0.001)]；EPCs的迁移、粘附及血管新生能力较健康组下降，细胞的NOTCH1受体表达水平升高，eNOS表达水平下降。
经中等强度运动干预后，高血压患者的收缩压及舒张压均较运动前明显下降（SBP: 133.11±6.65 mmHg vs. 142.86±8.36 mmHg, P<0.01；DBP: 80.4±5.46 mmHg vs. 86.84±5.83 mmHg, P<0.01），RCD较运动前明显增加，R-NPA明显减少，高血压患者的运动耐量、氧摄入量及左心舒张功能均较前明显改善，EPCs的迁移粘附能力改善且血管新生能力明显增加，NOTCH1表达水平下降，eNOS表达水平显著增加，且NOTCH是eNOS-NO信号的上游信号。
本研究首次揭示轻度高血压患者存在系统性微血管稀疏且能通过OCTA联合指襞显微镜发现，OCTA的检测效能有优于传统指襞显微镜的趋势，个体化中等强度运动方案可显著降低轻度高血压患者的血压水平，改善微血管稀疏与NOTCH-eNOS信号通路介导的EPCs功能改善相关。
梁建文博士作为伍贵富教授团队一员，目前主持的“增强型体外反搏对冠心病合并糖尿病患者心肌微循环障碍的影响”项目为一项前瞻性、对照、开放标签的单中心临床研究，计划入组冠心病合并糖尿病患者200例，通过压力导丝测定的微循环阻力指数（IMR）评估心肌微循环障碍，研究在规范的冠心病二级预防基础上，完整疗程的体外反搏治疗对心肌微循环障碍的疗效，该研究现已完成注册及预试验，期待研究结果对冠心病合并糖尿病患者心肌微循环障碍的诊疗提供临床证据。
研究摘要
Topic 1: Effect of Exercise on Improving Microvascular Rarefaction in Patients with Hypertension: Primary Results of EXCAVATION-CHN1 (1277-447)
Authors: Jianwen Liang, Wenbin Wei, Wenhao Xia, Jun Tao, The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen,Guangdong, People's Republic of China, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China
Background: Microvascular rarefaction (MVR), a loss of terminal arterioles and capillaries, is generally regarded as a pivotal pathophysiology process of hypertension. Exercise is recommended as a non-drug treatment in hypertension management. However, the effect of exercise on hypertensive MVR has not been reported yet.
Methods: This is a prospective, control and open label study, the registration number is NCT02817204. Fifty consecutive outpatients with newly diagnosed grade 1 hypertension (age: 25-40 years old) without any medical treatment were enrolled. All subjects were assigned to 12-week moderate active exercise training (5 days a week, about 3000Kcal/week). Retina optical coherence tomography was performed to identify the retina capillary density (RCD) and non-perfused area (NPA) before and after intervention in all subjects. In addition, the ambulatory blood pressure monitoring, exercise tolerance by cardiopulmonary exercise test (CPET), echocardiography and flow mediated vasodilatation function (FMD) were examined.
Results: Exercise increased RCD [(54.51±2.35) % vs. (52.85±2.9)%, P<0.05] and decreased R-NPA [(0.09±0.07) mm2 vs. (0.12±0.07) mm2, P<0.05)] in patients with hypertensive MVR. Exercise reduced both systolic and diastolic blood pressures [SBP: (133.11±6.65) mmHg vs. (142.86±8.36) mmHg, P<0.01]; DBP: [(80.4±5.46) mmHg vs. (86.84±5.83) mmHg, P<0.01] and increased exercise tolerance level [Time duration: (19.2±1.58)min vs. (15.99±2.54)min, P<0.01; maximum metabolic equivalent (METs): (9.35±0.78) vs. (7.46±0.92), P<0.01; Oxygen consumption per kilogram: (30.14±2.53) L vs. (25.26±3.43) L, P<0.01]. Moderate intensity exercise tended to improve left ventricular diastolic function [IVRT: (85.11±15.11)] ms vs. (89.74±15.68) ms, P<0.05] and endothelial mediated vasodilatation function in hypertension [(8.99±1.74)] % vs. (7.27±2.19) %, P<0.05].
Conclusion: MVR presents in hypertension and can be early, effectively detected by retina OCTA. Exercise could improve hypertensive MVR, decreases blood pressure, increases exercise tolerance level, improve left ventricular diastolic function and endothelial mediated vasodilatation function.
Topic 2: Moderate Intensity Exercise Attenuates Hypertensive Microvascular Rarefaction through Enhancing the Function of Endothelial Progenitor Cells (1235-453)
Authors: Jianwen Liang, Wenhao Xia, Xinzhu Tong, Jun Tao, The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen,Guangdong, People's Republic of China, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China
Background: Microvascular Rarefaction (MVR) is the landmark of hypertensive pathophysiological change and exercise is recommended as a non-drug treatment in hypertension management. Endothelial progenitor cells (EPCs) dysfunction which is pivotal to endothelial repair and tube formation has been reported in hypertension. However, the effect of exercise on MVR and the mechanism related to EPCs in hypertension remains unknown.
Methods: This study was designed to compare skin capillary density by intravital capillaroscopy in hypertensive patients (n=35) and healthy volunteers (n=35), then hypertensive patients were assigned to moderate intensity exercise for 12 weeks, peripheral blood was draw for EPCs cultivation, furthermore, EPCs functions and in vitro experiments were launched.
Results: Our results showed lower skin capillary density, declined EPCs functions and higher expression of NOTCH1 receptor level of EPCs in hypertension, moderate intensity exercise decreased blood pressure [SBP: (128±10.3) mmHg vs. (139.2±8.5) mmHg, P<0.05; DBP: (94.5±5.9) mmHg vs. (87.4±6.3) mmHg, P<0.05] and restore EPCs functions,moreover, improvement of EPCs activities by exercise was correlated to inhibition of NOTCH1 receptor expression.
Conclusion: The present study for the first time elucidates that moderate intensity exercise attenuates hypertensive MVR through enhancing EPCs function which relates to inhibition of NOTCH signaling pathway.
作者简介
梁建文，男，中山大学附属第八医院心血管内科主治医师，博士，临床主要从事冠心病介入治疗，研究方向为冠脉微循环和高血压微循环障碍的机制及干预，是广东省医师协会心血管分会临床研究学组组员，广东省病理生理学会心血管分会委员，广东省医师协会心血管分会国际交流学组组员，主持广东省自然科学基金、广东省科技计划项目、中山大学5010培育项目等，发表SCI论文及中文核心论文共10余篇。
医脉通-ACC 2019专题