难治性高血压的流行及诊治进展

doi:10.16150/j.1671-2870.2025.05.002

摘要/Abstract

摘要：

难治性高血压（resistant hypertension， RH）是指患者尽管使用最佳联合方案，但血压仍不达标的临床治疗瓶颈，其背后是多机制交织的复杂病理生理网络，核心涉及肾素-血管紧张素-醛固酮系统（renin angiotensin aldosterone system，RAAS）过度激活、交感神经系统（sympathetic nervous system， SNS）兴奋性增高、遗传因素、血管内皮功能障碍及炎症反应等多系统交互作用，并与显著升高的心血管风险密切相关。RH占高血压人群的1.9%~18.0%，多数研究提示RH占高血压人群的10%。RH评估需规范血压测量（推荐结合诊室与家庭血压测量），并客观评估患者的服药依从性（约50%依从性差）。高血压的继发性病因筛查至关重要，如原发性醛固酮增多症在RH中患病率达17%~23%（筛查率仅2.1%）；睡眠呼吸暂停综合征患者中>50%伴高血压；肾动脉狭窄性高血压在RH患者中约占24%。全面识别高血压病因可显著改善患者的血压控制及预后。RH的治疗强调生活方式干预[如DASH（dietary approaches to stop hypertensio）饮食可降压约6.97 mmHg]、药物及器械治疗。螺内酯作为首选第四联药物，可降低收缩压约8.70 mmHg。新型药物中，醛固酮合酶抑制剂lorundrostat、baxdrostat与安慰剂相比，2组收缩压分别降低约9.1 mmHg、9.8 mmHg；aprocitentan与安慰剂相比，收缩压降低约3.7 mmHg。肾交感神经消融术（renal denervation， RDN）可持久降低动态收缩压约13.6 mmHg，安全性良好。展望未来，在循证医学与创新疗法（新型药物与器械）的双重驱动下，RH的治疗领域正迎来一场以精准与个体化为核心的范式转移，这将为患者预后的提升带来革命性影响。

关键词: 高血压, 难治性高血压, 诊断, 治疗

Abstract:

Resistant hypertension (RH), defined as uncontrolled blood pressure despite the use of optimal combination therapy, represents a major clinical treatment challenge. Its underlying mechanism is a complex pathophysiological network involving multiple interacting systems, primarily including excessive activation of the renin-angiotensin-aldosterone system (RAAS), increased excitability of the sympathetic nervous system (SNS), genetic predisposition, vascular endothelial dysfunction, and inflammatory responses. These are closely associated with significantly increased cardiovascular risk. RH accounts for 1.9%-18.0% of the hypertensive population, with most studies indicating about 10% of hypertensive patients have RH. Evaluation of RH requires standardized blood pressure measurement (with a combination of office and home blood pressure recommended), and objective evaluation of patient medication adherence (with poor adherence observed in nearly 50% of patients). Screening for secondary causes of hypertension is crucial. For example, the prevalence of primary aldosteronism among RH patients reaches 17%-23% (with a screening rate of only 2.1%). Over 50% of patients with sleep apnea syndrome have hypertension, and renal artery stenosis hypertension accounts for about 24% of RH patients. Comprehensive identification of the underlying causes of hypertension can significantly improve blood pressure control and prognosis. RH treatment emphasizes lifestyle interventions [such as DASH (dietary approaches to stop hypertension) diet, which can reduce blood pressure by about 6.97 mmHg], as well as drug and device-based therapies. Spironolactone, as the preferred fourth-line agent, can reduce systolic blood pressure by about 8.70 mmHg. Among novel agents, the aldosterone synthase inhibitors lorundrostat and baxdrostat reduced systolic blood pressure by approximately 9.1 mmHg and 9.8 mmHg compared with placebo, respectively, while aprocitentan lowered systolic blood pressure by about 3.7 mmHg compared with placebo. Renal sympathetic denervation (RDN) can persistently reduce ambulatory systolic blood pressure by about 13.6 mmHg, with good safety. Looking ahead, driven by both evidence-based medicine and innovative therapies (new drugs and devices), RH treatment is undergoing a paradigm shift centered on precision and individualized care, which is expected to bring revolutionary impact on the improvement of patient prognosis.

Key words: Hypertension, Resistant hypertension, Diagnosis, Treatment

中图分类号:

R544.1

马志强, 林子昕, 吴昊, 王再佳, 张象涛, 董一飞. 难治性高血压的流行及诊治进展[J]. 诊断学理论与实践, 2025, 24(05): 471-484.

MA Zhiqiang, LIN Zixin, WU Hao, WANG Zaijia, ZHANG Xiangtao, DONG Yifei. Prevalence， diagnosis， and treatment progress of resistant hypertension[J]. Journal of Diagnostics Concepts & Practice, 2025, 24(05): 471-484.

图/表 2

图1

表1

最新的降压药物治疗临床研究汇总

治疗方式	研究	年份	研究设计	样本量(例)	研究人群	主要终点	主要结果
lorundrostat	Target-HTN^[84]	2023	随机、安慰剂对照试验	200	正在接受≥2种降压药物治疗但血压仍未控制的高血压患者	基线至研究第8周诊室收缩压的变化	50 mg组与安慰剂组间收缩压变化差异为-9.6 mmHg（90% CI：-15.8 ~ -3.4；P=0.01）；类似的，100 mg组为-7.8 mmHg[90% CI：(-14.1)~(-1.5)；P=0.04]
lorundrostat	Advance-HTN^[85]	2025	多中心、双盲、随机、安慰剂对照试验	285	正在接受2~5种降压药治疗但血压仍未控制的高血压患者	基线至第12周24小时平均收缩压的变化	固定剂量组与安慰剂组间24 h平均收缩压变化差异为-7.9 mmHg[97.5% CI：(-13.3)~(-2.6)；P=0.001]；剂量调整组为-6.5 mmHg [97.5% CI：(-11.8)~(-1.2)；P=0.006]
lorundrostat	Launch-HTN^[86]	2025	12周的随机双盲治疗期后开放标签试验	1083	正在接受2~5种降压药治疗但血压仍未控制的高血压患者	第6周时收缩压较基线的变化	治疗组与安慰剂组间收缩压变化差异为-9.1 mmHg [95% CI：(-13.3)~(-4.9)；P<0.001]
baxdrostat	BrigHTN^[87]	2023	多中心、双盲、随机、安慰剂对照试验	248	至少应用3种最大耐受剂量的降压药物仍未控制的高血压患者	治疗12周后患者的收缩压较基线的变化	2 mg组与安慰剂组间变化差异为-11.0 mmHg [95% CI：(-16.4)~(-5.5)； P<0.001]；1 mg组差异为-8.1 mmHg[95% CI：(-13.5)~(-2.8)；P=0.003]
aprocitentan	PRECISION^[88]	2022	随机、双盲、安慰剂对照试验	730	至少应用3种最大耐受剂量的降压药物仍未控制的高血压患者	从基线至第4周的诊室收缩压变化	与安慰剂组相比，治组疗可使收缩压持续降低约3 mmHg；24小时动态血压变化类似
RDN	Symplicity HTN-1^[89]	2009	前瞻性、多中心、开放标签试验	50	至少应用3种降压药物仍未控制的高血压患者	RDN术后1、3、6、9和12个月的诊室血压	术后诊室血压下降幅度分别为：1个月-14/-10 mmHg、3个月-21/-10 mmHg、6个月-22/-11 mmHg、9个月-24/-11 mmHg、12个月-27/-17 mmHg
RDN	Symplicity HTN-2^[90]	2010	多中心、前瞻性、随机对照试验	190	至少应用3种降压药物仍未控制的高血压患者	6 个月时坐位诊室收缩压的变化	RDN组诊室收缩压平均下降32 mmHg，而对照组血压较基线无变化；2组间血压差异为 33/11 mmHg（P<0.0001）
RDN	Symplicity HTN-3^[91]	2014	前瞻性、多中心、随机、单盲、假手术对照	535	至少应用3种降压药物仍未控制的高血压患者	6 个月时诊室收缩压的变化	肾去神经术组收缩压平均下降-14.13± 23.93 mmHg，对照组下降-11.74 ± 25.94 mmHg，2组间差异为-2.39 mmHg[95% CI：(-6.89)~(2.12)，P=0.26]
RDN	Iberis-HTN^[92]	2024	随机、单盲、假手术对照试验	217	至少应用3种降压治疗后血压仍控制不佳的患者	基线至第6个月24 h平均收缩压的变化	与假手术组相比，RDN组下降幅度更大，基线调整后2组间差异为-9.4 mmHg[95% CI：(-12.8)~(-5.9)，P<0.001]

表1

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