Resistant Hypertension and Susceptible Outcomes: Exploring the Benefits of Aggressive Blood Pressure Control
Resistant Hypertension and Susceptible Outcomes: Exploring the Benefits of Aggressive Blood Pressure Control
复制标题
顽固性高血压和易受影响的结果：探索积极控制血压的好处
DOI：
--
复制
发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Steven M. Smith
中科院分区：
文献类型：
--
作者：
Steven M. Smith
越来越多的证据表明，顽固性高血压-甚至简单地定义为需要四种或更多种抗高血压药物来实现办公室血压（BP）控制-与健康相关的生活质量受损相关，并且相对于非顽固性高血压，心血管不良结局和死亡的风险显著增加。这一证据令人担忧，因为在美国，估计每五名接受治疗的高血压患者中就有一名符合这一顽固性高血压的定义，其中大多数患者的血压不受控制。血压控制，只要它是可以实现的，继续被推荐作为一种手段，以降低心血管风险的顽固性高血压患者。基于一般高血压人群和需要积极治疗的更严重高血压患者的已知和实质性降压获益，这些建议似乎是合理的。另一方面，一些数据表明，更积极的治疗与顽固性高血压患者的预后更差相关。例如，使用更多的抗高血压药物与健康相关生活质量的进行性恶化和不良心血管事件的风险增加有关，因此服用最多抗高血压药物的患者平均结局最差。目前尚不清楚的是，更积极的治疗方案是否会以某种方式导致这些不良结果，或者只是反映了更糟糕的潜在病理学。鉴于这些看似矛盾的数据，临床医生面临着挑战性的问题：在多大程度上（更积极的）治疗，以实现目标血压，受益于特定的顽固性高血压患者？而且，越来越积极的抗高血压治疗是否会带来收益递减甚至危害？在本期杂志中，Fatemi及其同事提供了另一个难题，他们的报告回顾性评估了美国退伍军人顽固性高血压患者的血压控制与全因死亡率之间的关系。这项研究包括628名患有顽固性高血压的退伍军人，定义为在服用三种或三种以上降压药物（包括利尿剂）的同时血压不受控制，他们在华盛顿DC VA医疗中心接受常规高血压治疗。研究者对该队列进行了划分，以便于在3年后续常规护理后实现血压控制的患者（n=234; 37%）和未实现血压控制的患者（n=394; 63%）之间进行比较。两组之间的基线特征基本相似，包括使用每种主要类别降压药的患者比例相似，但b受体阻滞剂除外，在第3年实现血压控制的患者中，b受体阻滞剂的使用频率略高。入选队列时，两组间的门诊血压似乎略有差异，第3年实现血压控制的组可能低约7/2 mmHg，尽管这些数据未明确报告。到第3年随访时（使用BP定义对照组和非对照组的年份），根据设计，BP差异显著更大，控制BP组的平均BP约低22/8 mm Hg。在6年的总随访期间，定义为不受控制的顽固性高血压组的全因死亡发生率明显高于控制的顽固性高血压组。在校正了其他几个已知心血管危险因素的多变量分析中，未控制的血压与全因死亡风险较高之间的这种相关性持续存在（未控制的血压与控制的血压的校正风险比，2.48; 95%置信区间，1.64- 3.76）。作者得出结论，这些数据“强烈表明，在这一高危人群中，血压控制可能会带来稳健的死亡率获益”。在深入研究研究细节之前，值得注意的是，类似的分析之前已经进行过-事实上至少两次-在更大的人群中，得出了不同的结论。使用来自国际维拉帕米-群多普利研究（INVEST）的数据，我们比较了约17，000例冠状动脉疾病和非抵抗性或抵抗性高血压患者的全因死亡率和心血管死亡率风险。毫不奇怪，无论血压控制如何，顽固性高血压患者的全因死亡和心血管死亡风险都高于控制的非顽固性高血压患者。然而，我们观察到控制和不控制的顽固性高血压患者之间的结果没有差异，尽管平均血压差异为通信地址：Smith，PharmD，MPH，University of佛罗里达，PO Box 100486，Gainesville，FL 32610电子邮件：ssmith@cop.ufl.edu
Mounting evidence demonstrates that resistant hypertension––defined even as simply as requiring four or more antihypertensive drugs to achieve office blood pressure (BP) control––is associated with impaired health-related quality of life and a substantially greater risk of adverse cardiovascular outcomes and death relative to nonresistant hypertension. This evidence is concerning given that an estimated one in five treated hypertensive patients in the United States meets this definition of resistant hypertension and, of these, most have uncontrolled BP. BP control, insofar as it is achievable, continues to be recommended as a means to reduce cardiovascular risk in patients with resistant hypertension. Such recommendations certainly seem reasonable based on the known and substantial benefits of BP reduction in the general hypertensive population and in patients with more severe hypertension requiring aggressive therapy. On the other hand, some data suggest that more aggressive therapy is associated with worse outcomes in patients with resistant hypertension. For example, use of more antihypertensive drugs has been linked with a progressive worsening of health-related quality of life and a greater risk of adverse cardiovascular events, such that patients taking the greatest number of antihypertensive agents have the worst outcomes on average. What is not known is whether more aggressive treatment regimens somehow cause these adverse outcomes or simply reflect worse underlying pathology. Given these seemingly conflicting data, clinicians are faced with challenging questions: to what extent does (more aggressive) treatment, to achieve a goal BP, benefit a particular patient with resistant hypertension? And, are there diminishing returns, or even harms, associated with increasingly aggressive antihypertensive therapy? In this issue of the Journal, Fatemi and colleagues provide another piece to this puzzle with their report from a retrospective evaluation of the association between BP control and all-cause mortality among US veterans with resistant hypertension. This study included 628 veterans with resistant hypertension, defined as having uncontrolled office BP while taking three or more antihypertensive drugs (including a diuretic), who were receiving routine hypertension care at the Washington DC VA Medical Center. The investigators divided this cohort to facilitate a comparison between patients who had achieved BP control (n=234; 37%) and patients who had not (n=394; 63%) after 3 years of subsequent routine care. Baseline characteristics were generally similar between the groups, including similar proportions of patients using each of the major classes of antihypertensive agents with the exception of b-blockers, which were employed slightly more frequently in patients who achieved BP control at year 3. Clinic BP at time of inclusion in the cohort appears to have been modestly different between the groups, perhaps ~7/2 mm Hg lower in the group that achieved BP control at year 3, although these data were not explicitly reported. By year 3 of follow-up (the year in which BP was used to define the controlled and uncontrolled comparison groups), BP differences were considerably greater, by design, with mean BP approximately 22/8 mm Hg lower in the controlled BP group. During 6 years of total follow-up, all-cause death occurred significantly more often in the group defined as having uncontrolled resistant hypertension than in the group with controlled resistant hypertension. This association between uncontrolled BP and greater risk of all-cause death persisted in multivariate analyses that adjusted for several other known cardiovascular risk factors (adjusted hazard ratio for uncontrolled vs controlled BP, 2.48; 95% confidence interval, 1.64– 3.76). The authors concluded that these data “strongly suggest a robust mortality benefit probably derived from BP control in this high-risk population.” Before delving into the study details, it’s worth noting that similar analyses have been performed before––at least twice, in fact––in much larger populations and with different conclusions. Using data from the International Verapamil-Trandolapril Study (INVEST), we compared risk of all-cause mortality and cardiovascular mortality among approximately 17,000 patients with coronary artery disease and either nonresistant or resistant hypertension. Not surprisingly, patients with resistant hypertension, regardless of BP control, had a greater risk of all-cause and cardiovascular mortality than patients with controlled nonresistant hypertension. Yet, we observed no difference in outcomes between patients with controlled and uncontrolled resistant hypertension, despite a mean BP difference of Address for correspondence: Steven M. Smith, PharmD, MPH, University of Florida, PO Box 100486, Gainesville, FL 32610 E-mail: ssmith@cop.ufl.edu