中国高血压人群心脑肾靶器官保护的最佳降压靶值探索

Essential hypertension affects 260 million Chinese, and is a major contributor to the leading causes of morbidity and mortality in China, including stroke, myocardial infarction, and renal failure. Despite past 20 year intervention effort, hypertension induced end organ morbidity and mortality such as stroke continue to rise rapidly in China. This proposal aims to fill a critical data gap on what are the optimal thresholds and goals of treating hypertension in order to best prevent end-organ complications in Chinese? The available guideline is primarily based on the data from the U.S. / European populations. There is a particular lack of evidence-based guideline that is well-suited for Chinese hypertensive adults, taking into account unique characteristics of Chinese population, including (1) disease pattern: the stroke/MI ratio is 6-13:1 in Chinese vs. 1:1 in western population; (2) clinical feature: hypertension is commonly accompanied by elevated homocystein (H-Hypertension, 50-75%) in Chinese vs. high cholesterol in Western population; (3) genetic susceptibility: the MTHFR C677T mutation is much more common in Chinese than in Western population (20% vs. <5%); and (4) environmental difference: dietary intake (e.g., no folic acid fortification), life style (high rate of cigarette smoking in Chinese males). This proposal will leverage the existing data and resources of our recently completed, double blind, randomize, clinical trial on primary prevention of stroke among hypertensive Chinese (N=20702) drawn from different geographic regions, urban and rural settings and followed for a total of 5 years. We will conduct systematic analyses on blood pressure control (baseline BP, degree of BP lowering and longitudinal patterns) in relation to the development of specific end organ damage (brain, heart, kidney, retina) and overall and cause-specific mortality. We will further examine if optimal thresholds and goals vary by age groups; gender; pre-existing conditions (e.g. diabetes); and other risk factors (e.g. MTHFR variant, hyperhomocysteinemia, cigarette smoking, central obesity). We expect that this study will identify optimal thresholds and goals of hypertension management for the primary prevention of hypertension induced end organ complications. Findings from this project will lay an important foundation for developing evidence-based, cost-effective strategies for the management of hypertension and its end organ complications in Chinese populations.

心、脑、肾血管并发症是高血压患者最常见的致死、致残原因。靶器官损伤与高血压控制与否密切相关，然而血压降至何种程度能最有效地降低血管并发症风险？各种靶器官保护是否需要不同的降压靶目标值？目前国内外尚无循证医学证据。本项目拟利用已建立的大样本(n=20,702)、长程随访（平均5年）、双盲、随机对照的社区高血压人群队列（CSPPT队列），通过确定靶器官功能和器官功能障碍相关事件以及CSPPT全数据库分析，研究降压干预达到的不同血压水平与死亡、脑卒中、心肌梗死、肾功能快速减退等终点事件的相关关系；比较降低不同靶器官风险事件所需的最佳血压控制值；研究基线血压、降压速度和时间平均血压对高血压预后（死亡和靶器官损伤）的影响。从而探索中国高血压人群心脑肾靶器官保护的最佳降压靶值，为制定符合我国高血压人群特点的最佳降压治疗方案提供科学证据。

背景：高血压是威胁全世界及我国人民的重大公共卫生问题。据估计，全球有大约10亿高血压患者，其中我国就有大约3亿成人高血压患者。高血压是死亡及心脑血管疾病的最主要的危险因素。大量研究已经证实控制血压可以降低高血压相关并发症及死亡风险。然而，研究同时也发现，血压控制在同等水平时，我国人群脑卒中风险显著高于其他人群，提示我国高血压具有与西方人群显著不同的人群特征，我国人群可能需要不同于西方国家人群的降压标准。然而目前大多数降压指南的推荐血压靶值主要来源于西方人群的研究结果，缺乏我国人群的研究结果。因此迫切需要来自于我国人群的关于降压靶值的相关证据，以指导我国人群的降压，从而有效地降低我国高血压人群死亡率及相关心脑肾并发症的发生，减少医疗费用支出，提高国民健康水平。. 主要研究内容：探讨降压干预达到的不同血压水平与死亡、脑卒中、心肌梗死、肾功能快速减退等终点事件的相关关系；比较降低不同靶器官风险事件所需的最佳血压控制值；研究基线血压、降压速度和时间平均血压对高血压预后（死亡和靶器官损伤）的影响。. 重要结果及关键数据：本项目拟利用已建立的大样本(n=20,702)、长程随访（平均5年）、双盲、随机对照的社区高血压人群队列（CSPPT队列），结果表明，治疗后过程平均SBP和脑卒中的发生风险呈现“U”型关系。过程平均SBP高于或低于 120-130 mmHg发生脑卒中风险均显著增加。与过程平均SBP120-130mmHg的患者相比，过程平均SBP130-135 mmHg的受试者发生脑卒中的风险比（HR）为1.63（95%可信区间：1.01-2.63），过程平均SBP135-140mmHg受试者HR为1.85（1.17-2.93），而过程平均SBP<120 mmHg的受试者发生脑卒中HR为4.37（2.10-9.07）；在复合心血管事件中也观察到相似的结果。主要结果发表在Hypertension杂志。. 科学意义：本项目通过精准的试验设计和结果解析，确定了中国高血压人群心脑肾靶器官保护的最佳降压靶值，为制定符合我国高血压人群特点的最佳降压治疗方案提供科学证据。