The Ideal Blood Pressure Target for Patients With Chronic Kidney Disease—Searching for the Sweet Spot,JAMA Internal Medicine

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The Ideal Blood Pressure Target for Patients With Chronic Kidney Disease—Searching for the Sweet Spot
JAMA Internal Medicine ( IF 22.5 ) Pub Date : 2017-10-01 , DOI: 10.1001/jamainternmed.2017.4467
Csaba P. Kovesdy ₁

Affiliation

Hypertension is the number 1 cardiovascular risk fa ctor, and its treatment prevents major cardiovascular events and lowers mortality. Most patients with chronic kidney disease (CKD) have hypertension, and CKD is characterized by extremely high cardiovascular disease rates. It is thus not surprising that antihypertensive therapy is a universal part of CKD management, and its benefits are broadly accepted. Notwithstanding the general consensus about the pathophysiologic relevance of hypertension, there has been controversy in the medical community regarding the ideal therapeutic blood pressure (BP) target in patients with CKD. Fueling this controversy are concerns about the presence of a J-curve and the paucity of dedicated randomized clinical trials (RCTs) testing the effects of BP lowering to levels that approach physiologic normalcy (ie, <120/80 mm Hg). These uncertainties are further accentuated when assessing the effects of antihypertensive therapy on all-cause mortality, which includes deaths with causes entirely unrelated to hypertension. In this issue of JAMA Internal Medicine, Malhotra et al1 attempt to address the vexing issue of all-cause mortality benefit vs harm associated with intensive vs less intensive BP lowering in hypertensive patients with CKD by performing a meta-analysis of RCTs that included patients with estimated glomerular filtration rates (eGFRs) below 60 mL/min/1.73 m2 and not undergoing renal replacement therapy. The authors analyze published and unpublished data from 18 RCTs on 15 924 patients with CKD exposed to various BP lowering interventions. The mean systolic BP (SBP) achieved in the more intensive vs less intensive BP control arms were 132 vs 140 mm Hg, respectively, with more intensive treatment resulting in a 14% lower risk of all-cause mortality. The results did not show substantial heterogeneity and were consistent in various subgroup analyses. In addition, larger decreases in SBP showed a trend toward more benefit in a meta-regression analysis. This study is a valuable addition to our knowledge about hypertension therapy in CKD, but its interpretation still requires caution, for several reasons. First, the question of whether a normal BP target (as most would define intensive BP control) is beneficial in patients with CKD remains unanswered. The meta-analysis includes RCTs that used various BP targets, and Malhotra et al1 define “intensive” as the lower target in each individual study. The mean overall intensive SBP of 132 mm Hg in the metaanalysis actually falls within the clinical target recommended by most current guidelines (ie, <140 mm Hg) and is also within the range that has been associated with the best outcomes in large observational studies (Figure).2 One could therefore interpret the results of this meta-analysis as solidifying existing evidence about the benefits of lowering BP to a range of 130 to 140 mm Hg but not as proof that truly intensive BP lowering (ie, to a target <120 mm Hg) is beneficial. Another aspect of this question concerns the BP levels achieved in the SPRINT study,3 in which the intensive treatment target was an SBP of lower than 120 mm Hg, but which used a measurement method different from that used in routine clinical practice. When the measurement method is translated to that used in clinical practice, SBP levels might be substantially higher (up to 10-15 mm Hg).4 Using a higher value for the SBP in SPRINT would increase the mean SBP estimated in the metaanalysis and might also affect the result of the subgroup analysis, which implies equally beneficial effects from more intensive BP lowering in RCTs using various target BP levels (including <120 mm Hg). The second question concerns the external validity of RCTs assessing hypertension control in CKD. The observed absolute mortality rate was substantially higher in large cohort studies5 than it was in patients enrolled in the RCTs included in the meta-analysis by Malhotra et al.1 The much higher allcause mortality rate in the general CKD population may be due to causes that are unaffected by BP lowering (eg, infections or malignant conditions). Thus the real-life efficiency of BP lowering may be diluted, and intensive control may even have deleterious effects in some cases. A further concern is that lumping all patients with an eGFR below 60 mL/min/1.73 m2 together under the umbrella of CKD risks mixing different Related article Figure. Mortality Hazard Ratios Associated With Various Baseline Systolic Blood Pressures

中文翻译：

慢性肾病患者的理想血压目标——寻找最佳血压点

高血压是第一大心血管危险因素，其治疗可预防重大心血管事件并降低死亡率。大多数慢性肾病（CKD）患者患有高血压，CKD的特点是心血管疾病发病率极高。因此，抗高血压治疗是 CKD 管理的普遍组成部分，其益处被广泛接受也就不足为奇了。尽管对高血压的病理生理学相关性达成了普遍共识，但医学界对 CKD 患者的理想治疗血压 (BP) 目标存在争议。加剧这一争议的是对 J 曲线的存在的担忧以及缺乏专门的随机临床试验 (RCT) 来测试将血压降低到接近生理正常水平的水平（即 < 120/80 毫米汞柱）。在评估抗高血压治疗对全因死亡率的影响时，这些不确定性进一步加剧，其中包括与高血压完全无关的死因。在本期 JAMA Internal Medicine 中，Malhotra 等人 1 试图通过对 CKD 高血压患者的 RCT 进行荟萃分析，解决全因死亡率获益与危害相关的强化与非强化降压相关的问题。估计肾小球滤过率 (eGFR) 低于 60 mL/min/1.73 m2 且未接受肾脏替代治疗。作者分析了 18 项 RCT 的已发表和未发表数据，这些数据涉及 15 924 名暴露于各种降压干预措施的 CKD 患者。强度较高和强度较低的 BP 控制组实现的平均收缩压 (SBP) 分别为 132 和 140 毫米汞柱，更密集的治疗导致全因死亡风险降低 14%。结果没有显示出显着的异质性，并且在各种亚组分析中是一致的。此外，在荟萃回归分析中，SBP 下降幅度更大，显示出更多获益的趋势。这项研究是我们对 CKD 高血压治疗知识的宝贵补充，但其解释仍然需要谨慎，原因有几个。首先，正常血压目标（大多数情况下，强化血压控制的定义）是否对 CKD 患者有益的问题仍未得到解答。荟萃分析包括使用各种血压目标的随机对照试验，和 Malhotra 等人 1 将“密集”定义为每项研究中的较低目标。荟萃分析中 132 mmHg 的平均总强化 SBP 实际上属于大多数当前指南推荐的临床目标（即 <140 mmHg），并且也在大型观察性研究中与最佳结果相关的范围内。图 2 因此，人们可以将这项荟萃分析的结果解释为巩固了关于将血压降至 130 至 140 毫米汞柱的益处的现有证据，但不能作为真正强化降压的证据（即目标< 120 毫米汞柱）是有益的。这个问题的另一个方面涉及 SPRINT 研究中达到的血压水平，3 其中强化治疗的目标是 SBP 低于 120 毫米汞柱，但所使用的测量方法与常规临床实践中使用的测量方法不同。当测量方法转化为临床实践中使用的测量方法时，SBP 水平可能会高得多（高达 10-15 毫米汞柱）4。4 在 SPRINT 中使用更高的 SBP 值会增加荟萃分析中估计的平均 SBP，并可能也影响亚组分析的结果，这意味着在使用各种目标血压水平（包括 <120 mmHg）的 RCT 中，更强化降压同样有益。第二个问题涉及评估 CKD 高血压控制的 RCT 的外部有效性。在大型队列研究中观察到的绝对死亡率显着高于 Malhotra 等人的荟萃分析中纳入 RCT 的患者。1 一般 CKD 人群中高得多的全因死亡率可能是由于不受血压降低影响的原因（例如，感染或恶性疾病）。因此，降低血压的实际效率可能会被稀释，在某些情况下，强化控制甚至可能产生有害影响。另一个问题是，将 eGFR 低于 60 mL/min/1.73 m2 的所有患者归为 CKD 的风险很大，可能会混淆不同的相关文章图。与各种基线收缩压相关的死亡率风险比另一个问题是，将所有 eGFR 低于 60 mL/min/1.73 m2 的患者归为 CKD 的风险很大，可能会混淆不同的相关文章图。与各种基线收缩压相关的死亡率风险比另一个问题是，将 eGFR 低于 60 mL/min/1.73 m2 的所有患者归为 CKD 的风险很大，可能会混淆不同的相关文章图。与各种基线收缩压相关的死亡率风险比

更新日期：2017-10-01

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