Resistant and refractory hypertension: two sides of the same disease?

Abstract Refractory hypertension (RfH) is an extreme phenotype of resistant hypertension (RH), being considered an uncontrolled blood pressure besides the use of 5 or more antihypertensive medications, including a long-acting thiazide diuretic and a mineralocorticoid antagonist. RH is common, with 10-20% of the general hypertensives, and its associated with renin angiotensin aldosterone system hyperactivity and excess fluid retention. RfH comprises 5-8% of the RH and seems to be influenced by increased sympathetic activity. RH patients are older and more obese than general hypertensives. It is strongly associated with diabetes, obstructive sleep apnea, and hyperaldosteronism status. RfH is more frequent in women, younger patients and Afro-americans compared to RFs. Both are associated with increased albuminuria, left ventricular hypertrophy, chronic kidney diseases, stroke, and cardiovascular diseases. The magnitude of the white-coat effect seems to be higher among RH patients. Intensification of diuretic therapy is indicated in RH, while in RfH, therapy failure imposes new treatment alternatives such as the use of sympatholytic therapies. In conclusion, both RH and RfH constitute challenges in clinical practice and should be addressed as distinct clinical entities by trained professionals who are capable to identify comorbidities and provide specific, diversified, and individualized treatment.

摘要 难治性高血压（Refractory hypertension, RfH）是抵抗性高血压（Resistant hypertension, RH）的极端表型，指在联用包括长效噻嗪类利尿剂（long-acting thiazide diuretic）与盐皮质激素拮抗剂（mineralocorticoid antagonist）在内的5种及以上降压药物后，血压仍未得到有效控制的临床状态。
抵抗性高血压较为常见，约占总体高血压人群的10%~20%，其发病与肾素-血管紧张素-醛固酮系统（renin angiotensin aldosterone system）过度激活及体液潴留过多密切相关。难治性高血压占抵抗性高血压的5%~8%，其发生似乎与交感神经活动增强有关。
抵抗性高血压患者较普通高血压人群年龄更大、肥胖比例更高，且与糖尿病、阻塞性睡眠呼吸暂停（obstructive sleep apnea）及醛固酮增多症（hyperaldosteronism）显著相关。
与抵抗性高血压患者相比，难治性高血压在女性、年轻群体及非裔美国人中更为多见。两类高血压亚型均与白蛋白尿（albuminuria）、左心室肥厚（left ventricular hypertrophy）、慢性肾脏病（chronic kidney diseases）、脑卒中及心血管疾病风险升高相关。
抵抗性高血压患者的白大衣效应（white-coat effect）程度似乎更为显著。
临床对于抵抗性高血压推荐强化利尿剂治疗方案；而针对难治性高血压，若现有治疗失败，则需采用交感神经溶解疗法（sympatholytic therapies）等新型治疗手段。
综上，抵抗性高血压与难治性高血压均为临床实践中的诊疗难题，应将二者视为独立的临床疾病实体，由能够识别合并症并提供针对性、多元化及个体化治疗方案的专业医护人员进行规范处置。