風城黑鷹
善待自己的身體
美國心髒病學會/美國心髒協會（ACC / AHA）公布的高血壓診斷和治療新指南引起了全世界範圍內廣泛的爭論。最近的美國醫學學會雜誌（JAMA）發表了美國斯坦福大學專家John P. A. Ioannidis 的意見，編錄如下：
最近公布的美國心髒病學會/美國心髒協會（ACC / AHA）指南促進了高血壓管理方麵的根本性改變。 首先，由於高血壓定義的變化（血壓> 130/80 mm Hg，而非> 140/90 mm Hg），美國成年人被標記為高血壓的比例突然從32％上升到46%。其次，新的治療血壓目標也相應降低。 第三，抗高血壓藥物的使用應以血壓，心血管疾病（CVD），糖尿病或10%以上的10年發生心血管疾病的風險為指導。 第四，指南更強調在家裏監測血壓和基於團隊的高血壓管理係統。
新指南意味著估計美國現在還有額外的3100萬人需要治療。盡管這個新定義的高血壓患者大多數預計可以用非藥物治療，這些新診斷的患者中仍有420萬人需要用抗高血壓藥物。此外，新的目標意味著，在已經服用抗高血壓藥物的5500萬患者中，估計53％的患者需要更嚴格的血壓控製。即2900萬患者應該加強目前的抗高血壓藥物治療方案。該指導方針強調了廉價藥物（例如噻嗪類）是很好的一線藥物選擇; 然而，為了達到較低的血壓目標，許多患者不可避免地需要多種藥物的組合，可能包括一些昂貴的藥物。隨著藥物治療的擴大，藥物的不良反應發生率可能也會相應地增加。
將疾病定義的擴大，將更多的人歸屬於該疾病患者並需要治療已是很普遍的作法了。許多專業想要通過它來增加患者的數量。工業界也通過新的疾病定義來擴大產品市場。製定指南通常是“專家委員會帶來的疾病”和過度治療的最後一步。但是，這種模式似乎不能充分地解釋高血壓和2017 ACC / AHA指南的改變的情況。高血壓確實是心血管疾病（CVD）和死亡的主要風險因素。收縮壓（SBP）從115毫米汞柱的數值開始，血壓升高會使CVD事件的風險呈線性地增加。在二十世紀和二十一世紀期間，治療高血壓的大大提高了人類預期壽命。促進健康生活方式的目標值得讚揚，這使得數以百萬計的那些生活方式不好的人們獲益。 2017年ACA / AHA指南是一個高質量的報告，共有481頁，報告對背景證據進行了全麵的係統評估。作者小組經驗豐富，沒有利益衝突。意圖非常好，對於拯救生命的前景令人興奮。但指南的主要問題是這些建議能否在臨床實踐中得到順利實施。
2017年ACA / AHA指南中引入的變化的主要驅動因素是SPRINT（收縮壓幹預試驗）。SPRINT由美國國立衛生研究院資助，將9361例SBP大於130 mm Hg的患者隨機分為強化血壓控製收縮壓至小於120毫米汞柱 vs. 小於140毫米汞柱 （對照組）。強化控製幹預裏平均使用2.8個降壓藥，對照組為1.8個降壓藥。在平均隨訪時間為3.26年裏，這個額外的藥物導致了綜合主要終點（Composite Primary End Point, 即心肌梗塞，其他急性冠狀動脈綜合征，中風，心力衰竭和心血管死亡）下降了0.54％，在統計學上有顯著意義，總體死亡率顯著降低，導致試驗提前終止。
雖然SPRINT是一項完善的研究，但是在將其結果轉化為指南，然後轉化為臨床實踐時，確實有一些重要的事項需要注意。早期終止的臨床試驗通常會誇大試驗結論。無論如何，通過推動降低血壓目標毫無疑問存在一些好處。問題是如何去獲得這些好處。
SPRINT中的血壓是在理想的研究條件下測量的，病人安靜地休息，5分鍾內沒有做任何事情。盡管擴大家庭測量的使用來診斷和監測是一個好主意，但血壓測量的質量可能得不到保證。要培訓數以億計的普通人在家裏進行可靠的，高質量的血壓測量是需要有資源的。對於在繁忙的臨床醫生來說，要複製SPRINT的理想測量條件是困難的。對於高血壓的錯誤標記可能更常見於130/80 mm Hg閾值下限。美國的醫療保健係統已經負擔過重，估計額外的3100萬高血壓患者，加上可能數以百萬計的人被錯誤地診斷為高血壓將會給美國的醫療保健係統造成相當大的壓力。鑒於高血壓需要終身管理（治療），這種壓力可能是激烈和持續的。
強化血壓的控製帶來好處的同時，也會伴隨著副作用的增加（SPRINT中，如低血壓，暈厥，電解質異常，每年急性腎損傷衰竭發生在治療組1.21％vs 對照組0.35％）。所以隨著治療重點轉向降低血壓範圍，實際上在臨床實踐中的益處可能會變小。而且如果藥物被濫用，副作用可能會會更高。 SPRINT數據的預測風險模型顯示，更高強度的血壓控製的益處主要來自心血管事件預測風險上三分之一人群中，不良事件主要集中在一部分人群中。強化血壓的控製帶來明顯有益的，利害關係比例占優的患者可能還隻是少數。
也許最重要的是，SPRINT試驗中，都是已經確定的高血壓患者，按照老的定義（> 140/90 mm Hg），已經接受過降壓藥物治療，年齡超過50歲（平均年齡68歲）的患者。尚不清楚這些結果與數百萬根據新指南，新近被標記為高血壓的年輕成年人相關性有多大。在45歲以下的人群中，新的定義估計使男性的高血壓患病率增加了三倍，女性的患病率增加了一倍。大多數新診斷的非老年患者按以前的標準並沒有高血壓。因此，是否藥物治療在很大程度上取決於這些個體是否有估計10年心血管疾病風險超過10％存在。在這裏，選擇ACC / AHA匯總隊列方程（ooled cohort equation）來估計心血管疾病風險會帶來更多的困難。不過其優點是ACC / AHA膽固醇指南使用相同的風險評估。然而，風險評估者也缺乏適當的校準和高估風險，特別是在年輕人中。這可能導致更多的低風險人群也會進行強化的藥物治療，所以這種治療的利-害比存在疑問。
指南推薦的最大好處可能是強調年輕人最可能的治療是生活方式幹預，包括減肥，健康飲食，體育鍛煉，減少鈉攝入量，增加鉀攝入量，減少飲酒。原則上，將醫療保健係統更多地轉向生活方式措施進行預防，這是一個值得歡迎的舉措。從長遠來看，生活方式幹預這一重點可能會增加預防，特別是一級預防的衛生保健係統的價值（目前是低估了的）。然而，患者和臨床醫師是否準備好進行這種改變還不清楚，這些數千萬人是否能夠得到適當的健康谘詢，並認可有效的，可持續的生活方式改變也是個問題。資源，支持人員和基礎設施在大多數地方還沒能適應這個長期的變化。如果一級預防措施失敗，那麽可能的選擇是使用藥物治療，即使對於改善了生活方式的患者也是如此。因此，強調以生活方式為基礎的預防可能自相矛盾地促使美國社會進一步過度醫療化。
我們歡迎希望從血壓控製中獲得一切好處，即使對於風險相對較低的患者也是如此。 然而，臨床醫生不應該忘記，即使血壓很高，許多高危患者仍然未被診斷出來。 即使根據更為保守的高血壓定義，許多其他人也得不到最理想的治療。 新指南推動了基於團隊的係統方法，以更好地診斷和管理高血壓，實際上，有證據表明基於團隊的係統可以在這些方麵提供實質性的收益。在臨床實踐中將這些收益推廣到不同環境的能力，明智地使用有限的資源仍然是一個公開的挑戰。
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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