美国心脏病学会/美国心脏协会（ACC / AHA）公布的高血压诊断和治疗新指南引起了全世界范围内广泛的争论。最近的美国医学学会杂志（JAMA）发表了美国斯坦福大学专家John P. A. Ioannidis 的意见，编录如下：
最近公布的美国心脏病学会/美国心脏协会（ACC / AHA）指南促进了高血压管理方面的根本性改变。 首先，由于高血压定义的变化（血压> 130/80 mm Hg，而非> 140/90 mm Hg），美国成年人被标记为高血压的比例突然从32％上升到46%。其次，新的治疗血压目标也相应降低。 第三，抗高血压药物的使用应以血压，心血管疾病（CVD），糖尿病或10%以上的10年发生心血管疾病的风险为指导。 第四，指南更强调在家里监测血压和基于团队的高血压管理系统。
新指南意味着估计美国现在还有额外的3100万人需要治疗。尽管这个新定义的高血压患者大多数预计可以用非药物治疗，这些新诊断的患者中仍有420万人需要用抗高血压药物。此外，新的目标意味着，在已经服用抗高血压药物的5500万患者中，估计53％的患者需要更严格的血压控制。即2900万患者应该加强目前的抗高血压药物治疗方案。该指导方针强调了廉价药物（例如噻嗪类）是很好的一线药物选择; 然而，为了达到较低的血压目标，许多患者不可避免地需要多种药物的组合，可能包括一些昂贵的药物。随着药物治疗的扩大，药物的不良反应发生率可能也会相应地增加。
将疾病定义的扩大，将更多的人归属于该疾病患者并需要治疗已是很普遍的作法了。许多专业想要通过它来增加患者的数量。工业界也通过新的疾病定义来扩大产品市场。制定指南通常是“专家委员会带来的疾病”和过度治疗的最后一步。但是，这种模式似乎不能充分地解释高血压和2017 ACC / AHA指南的改变的情况。高血压确实是心血管疾病（CVD）和死亡的主要风险因素。收缩压（SBP）从115毫米汞柱的数值开始，血压升高会使CVD事件的风险呈线性地增加。在二十世纪和二十一世纪期间，治疗高血压的大大提高了人类预期寿命。促进健康生活方式的目标值得赞扬，这使得数以百万计的那些生活方式不好的人们获益。 2017年ACA / AHA指南是一个高质量的报告，共有481页，报告对背景证据进行了全面的系统评估。作者小组经验丰富，没有利益冲突。意图非常好，对于拯救生命的前景令人兴奋。但指南的主要问题是这些建议能否在临床实践中得到顺利实施。
2017年ACA / AHA指南中引入的变化的主要驱动因素是SPRINT（收缩压干预试验）。SPRINT由美国国立卫生研究院资助，将9361例SBP大于130 mm Hg的患者随机分为强化血压控制收缩压至小于120毫米汞柱 vs. 小于140毫米汞柱 （对照组）。强化控制干预里平均使用2.8个降压药，对照组为1.8个降压药。在平均随访时间为3.26年里，这个额外的药物导致了综合主要终点（Composite Primary End Point, 即心肌梗塞，其他急性冠状动脉综合征，中风，心力衰竭和心血管死亡）下降了0.54％，在统计学上有显著意义，总体死亡率显着降低，导致试验提前终止。
虽然SPRINT是一项完善的研究，但是在将其结果转化为指南，然后转化为临床实践时，确实有一些重要的事项需要注意。早期终止的临床试验通常会夸大试验结论。无论如何，通过推动降低血压目标毫无疑问存在一些好处。问题是如何去获得这些好处。
SPRINT中的血压是在理想的研究条件下测量的，病人安静地休息，5分钟内没有做任何事情。尽管扩大家庭测量的使用来诊断和监测是一个好主意，但血压测量的质量可能得不到保证。要培训数以亿计的普通人在家里进行可靠的，高质量的血压测量是需要有资源的。对于在繁忙的临床医生来说，要复制SPRINT的理想测量条件是困难的。对于高血压的错误标记可能更常见于130/80 mm Hg阈值下限。美国的医疗保健系统已经负担过重，估计额外的3100万高血压患者，加上可能数以百万计的人被错误地诊断为高血压将会给美国的医疗保健系统造成相当大的压力。鉴于高血压需要终身管理（治疗），这种压力可能是激烈和持续的。
强化血压的控制带来好处的同时，也会伴随着副作用的增加（SPRINT中，如低血压，晕厥，电解质异常，每年急性肾损伤衰竭发生在治疗组1.21％vs 对照组0.35％）。所以随着治疗重点转向降低血压范围，实际上在临床实践中的益处可能会变小。而且如果药物被滥用，副作用可能会会更高。 SPRINT数据的预测风险模型显示，更高强度的血压控制的益处主要来自心血管事件预测风险上三分之一人群中，不良事件主要集中在一部分人群中。强化血压的控制带来明显有益的，利害关系比例占优的患者可能还只是少数。
也许最重要的是，SPRINT试验中，都是已经确定的高血压患者，按照老的定义（> 140/90 mm Hg），已经接受过降压药物治疗，年龄超过50岁（平均年龄68岁）的患者。尚不清楚这些结果与数百万根据新指南，新近被标记为高血压的年轻成年人相关性有多大。在45岁以下的人群中，新的定义估计使男性的高血压患病率增加了三倍，女性的患病率增加了一倍。大多数新诊断的非老年患者按以前的标准并没有高血压。因此，是否药物治疗在很大程度上取决于这些个体是否有估计10年心血管疾病风险超过10％存在。在这里，选择ACC / AHA汇总队列方程（ooled cohort equation）来估计心血管疾病风险会带来更多的困难。不过其优点是ACC / AHA胆固醇指南使用相同的风险评估。然而，风险评估者也缺乏适当的校准和高估风险，特别是在年轻人中。这可能导致更多的低风险人群也会进行强化的药物治疗，所以这种治疗的利-害比存在疑问。
指南推荐的最大好处可能是强调年轻人最可能的治疗是生活方式干预，包括减肥，健康饮食，体育锻炼，减少钠摄入量，增加钾摄入量，减少饮酒。原则上，将医疗保健系统更多地转向生活方式措施进行预防，这是一个值得欢迎的举措。从长远来看，生活方式干预这一重点可能会增加预防，特别是一级预防的卫生保健系统的价值（目前是低估了的）。然而，患者和临床医师是否准备好进行这种改变还不清楚，这些数千万人是否能够得到适当的健康咨询，并认可有效的，可持续的生活方式改变也是个问题。资源，支持人员和基础设施在大多数地方还没能适应这个长期的变化。如果一级预防措施失败，那么可能的选择是使用药物治疗，即使对于改善了生活方式的患者也是如此。因此，强调以生活方式为基础的预防可能自相矛盾地促使美国社会进一步过度医疗化。
我们欢迎希望从血压控制中获得一切好处，即使对于风险相对较低的患者也是如此。 然而，临床医生不应该忘记，即使血压很高，许多高危患者仍然未被诊断出来。 即使根据更为保守的高血压定义，许多其他人也得不到最理想的治疗。 新指南推动了基于团队的系统方法，以更好地诊断和管理高血压，实际上，有证据表明基于团队的系统可以在这些方面提供实质性的收益。在临床实践中将这些收益推广到不同环境的能力，明智地使用有限的资源仍然是一个公开的挑战。
John P. A. Ioannidis, MD, DSc1 JAMA. Published online December 14, 2017. doi:10.1001/jama.2017.19672
Stanford Prevention Research Center, 1265 Welch Rd, Medical School Office Bldg, Room X306, Stanford, CA 94305 (jioannid@stanford.edu).
December 14, 2017
Diagnosis and Treatment of Hypertension in the 2017 ACC/AHA Guidelines and in the Real World
John P. A. Ioannidis, MD, DSc1
Author Affiliations Article Information
JAMA. Published online December 14, 2017. doi:10.1001/jama.2017.19672
The recently released American College of Cardiology/American Heart Association (ACC/AHA) guidelines1promote radical changes in the management of hypertension. First, given the change in the definition of the condition (blood pressure >130/80 mm Hg instead of >140/90 mm Hg), the proportion of adults in the United States labeled as having hypertension has suddenly increased from 32% to 46%.2 Second, the new blood pressure target of treatment is also accordingly lower. Third, use of antihypertensive drugs is to be guided by blood pressure as well as by the presence of cardiovascular disease (CVD), diabetes, or a more than 10% 10-year risk of developing CVD. Fourth, the guidelines put more emphasis on monitoring blood pressure at home and on team-based systems for managing hypertension.
The new guidelines mean that an estimated additional 31 million individuals in the United States now need treatment.2 Most of this newly defined population of individuals with hypertension is expected to be manageable with nonpharmacological interventions, although 4.2 million of these newly diagnosed patients will require antihypertensive medication. Furthermore, with the new goals, an estimated 53% of the 55 million patients already taking antihypertensive drugs will need better blood pressure control.2 This means that 29 million currently treated patients should intensify their current antihypertensive medication regimens. The guidelines reinforce the message that inexpensive drugs (eg, thiazides) are excellent first-line choices; however, to attain the lower blood pressure target, unavoidably, many patients will require combinations of multiple drugs, potentially including some expensive ones. The incidence of adverse events will likely increase with expanded treatment.
Expanding the definition of disease to label more people as having medical conditions and in need of treatment has become more common. Many specialties want to increase their volume of patients. Industry also cherishes larger markets for its products through expansive definitions of illness.3 Guidelines are typically the final step to justify illness-by-committee and treatment overuse. However, this pattern does not seem to sufficiently explain the case of hypertension and the 2017 ACC/AHA guidelines. Hypertension is indeed a major risk factor for CVD and death. Starting at values as low as 115 mm Hg for systolic blood pressure (SBP), higher blood pressure linearly increases the risk of CVD events. Treatment of hypertension has substantially contributed toward increasing life expectancy in the 20th and 21st centuries. The goal of promoting a healthy lifestyle in millions of additional people who might be otherwise outside the scope of appropriate lifestyle modification is laudable. The 2017 ACA/AHA guidelines are a stellar report running at 481 pages, with full systematic review of the background evidence. The panel of authors is highly experienced and has no conflicts of interest. The intentions are superb and the prospects of saving lives are exciting. The main question is whether the recommendations are feasible in clinical practice.
A major driver for the changes introduced in the 2017 ACA/AHA guidelines was SPRINT (Systolic Blood Pressure Intervention Trial).4,5 Funded by the National Institutes of Health, SPRINT randomized 9361 patients with SBP greater than 130 mm Hg to intensive blood pressure control of SBP to less than 120 mm Hg vs less than 140 mm Hg. The intensive control intervention used on average 2.8 antihypertensive drugs vs 1.8 in the control group. This one extra drug resulted in a statistically significant 0.54% reduction in the composite primary end point (myocardial infarction, other acute coronary syndromes, stroke, heart failure, and cardiovascular death) over a median follow-up of 3.26 years as well as a statistically significant reduction in overall mortality, leading to the early trial termination.
SPRINT was a well-done study, but it does have some caveats that become important when trying to translate its results to guidelines and then to actual clinical practice. Trials that are stopped early typically provide exaggerated estimates of benefits.6 Regardless, some benefits do exist unquestionably by pushing for a lower blood pressure target. The issue is how to reap those benefits.
Blood pressure in SPRINT was measured under idealized research conditions in the participating clinical sites, with the patient resting quietly and not doing anything for 5 minutes.4 Although expanding the use of home measurements for diagnosis and monitoring is a good idea, the quality of these measurements in the expanded population of labeled hypertensive patients may be uneven. Training hundreds of millions of people to perform reliable, good-quality blood pressure measurements requires committed resources. For management done in busy clinical settings, reproducing the ideal measurement conditions of SPRINT is difficult. Mislabeling of hypertension may be more common with the lower 130/80 mm Hg threshold. Flooding an already overburdened health care system with an estimated extra 31 million patients with hypertension plus probably several more millions of individuals falsely diagnosed as having hypertension will pose a considerable strain. Given that hypertension requires lifelong management, this strain may be both intense and sustained.
The benefits of intensive blood pressure control come with an accompanying increase in adverse effects (eg, hypotension, syncope, electrolyte abnormalities, and 1.21% per year vs 0.35% per year in the control group of acute kidney injury or failure in SPRINT).4 As the treatment focus shifts to lower blood pressure ranges, benefits in actual clinical practice may become smaller. Conversely, adverse effects may remain equally high, or even become higher if medications are misused. Predictive risk modeling of the SPRINT data7 showed that the benefit of more intensive blood pressure control was driven largely from the upper third of predicted risk of CVD events and that the adverse events were mostly in a subset of the population. Patients who have a clearly favorable, major benefit-to-harm ratio may be the minority.
Perhaps most important, SPRINT included patients with already established hypertension according to the old definition (>140/90 mm Hg), who were already treated with antihypertensive drugs and were older than 50 years (mean age, 68 years).4 It is unclear how relevant these results are to the millions of younger adults who have been newly labeled with hypertension based on the new guidelines. In the group younger than 45 years, the new definition is estimated to triple hypertension prevalence among men and double the prevalence among women. Most of the newly diagnosed, nonelderly patients would have no previous disease. Therefore, the decision to treat with medications would depend largely on whether these individuals are estimated to be at more than 10% 10-year CVD risk. Here, the choice of ACC/AHA pooled cohort equations8 to estimate CVD risk creates additional difficulties. The advantage is that the respective ACC/AHA cholesterol guidelines use the same risk estimator. However, the risk estimator has also been criticized for lacking proper calibration and for overestimating risk, particularly in young individuals. This may lead more low-risk people to aggressive drug treatment with questionable benefit-to-harm ratios.
The greatest benefit of the guideline recommendations may be that they emphasize, most likely for young adults, lifestyle interventions, including weight loss, healthy diet, physical exercise, reduced sodium intake, increased potassium intake, and curtailed alcohol consumption. In principle, shifting the health care system more toward prevention with lifestyle measures is a welcome move.9 In the long-term, this emphasis may add value for the current health care system that undervalues prevention, and primary prevention in particular. However, it is unclear whether patients and clinicians are ready for such a change and whether these tens of millions of individuals will be able to obtain appropriate counseling and endorse effective, sustainable lifestyle modifications. Resources, supporting personnel, and infrastructure are still lacking in most places to achieve this long-due change. If primary prevention efforts fail, the likely option will be to resort to medications even for patients who would have done well with lifestyle modification. Thus, an emphasis on lifestyle-based prevention may paradoxically promote further overmedicalization of US society.
The wish to reap every benefit possible from blood pressure control, even for relatively low-risk patients, is welcome. However, clinicians should not forget that many high-risk patients remain undiagnosed even with very high blood pressure. Many others receive suboptimal treatment, even according to more conservative definitions of hypertension. The new guidelines promote team-based system approaches for better diagnosis and management of hypertension and, indeed, there is evidence that team-based systems can offer substantial gains on these fronts.10 The ability to generalize these gains across diverse settings in clinical practice and to use limited resources wisely remains an open challenge.
Article Information
Corresponding Author: John P. A. Ioannidis, MD, DSc, Stanford Prevention Research Center, 1265 Welch Rd, Medical School Office Bldg, Room X306, Stanford, CA 94305 (jioannid@stanford.edu).
Published Online: December 14, 2017. doi:10.1001/jama.2017.19672
Conflict of Interest Disclosures: The author has completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.
Funding/Support: The work of Dr Ioannidis is supported by an unrestricted gift from Sue and Bob O’Donnell. METRICS is supported with funding from the John and Laura Arnold Foundation.
Role of the Funder/Sponsor: The funders had no role in the preparation, review, or approval of the manuscript, or the decision to submit the manuscript for publication.
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