Keep Blood Pressure Low, but Not Too Much…
2018; Lippincott Williams & Wilkins; Volume: 123; Issue: 11 Linguagem: Inglês
10.1161/circresaha.118.314017
ISSN1524-4571
AutoresPaolo Verdecchia, Fabio Angeli, Claudio Cavallini, Gianpaolo Reboldi,
Tópico(s)Heart Rate Variability and Autonomic Control
ResumoHomeCirculation ResearchVol. 123, No. 11Keep Blood Pressure Low, but Not Too Much… Free AccessArticle CommentaryPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessArticle CommentaryPDF/EPUBKeep Blood Pressure Low, but Not Too Much…Does Evidence Support the Recommendation of Rigid "Safety Boundaries"? Paolo Verdecchia, Fabio Angeli, Claudio Cavallini and Gianpaolo Reboldi Paolo VerdecchiaPaolo Verdecchia Correspondence to Paolo Verdecchia, FESC, FACC, Fondazione Umbra Cuore e Ipertensione-Organizzazione Non Lucrativa di Utilità Sociale (ONLUS), Ospedale S. Maria della Misericordia, 06129-Perugia, Italy. Email E-mail Address: [email protected] From the Fondazione Umbra Cuore e Ipertensione-ONLUS e Struttura Complessa di Cardiologia (P.V., C.C.), Ospedale S. Maria della Misericordia, Perugia, Italy , Fabio AngeliFabio Angeli Struttura Complessa di Cardiologia e Fisiopatologia Cardiovascolare (F.A.), Ospedale S. Maria della Misericordia, Perugia, Italy , Claudio CavalliniClaudio Cavallini From the Fondazione Umbra Cuore e Ipertensione-ONLUS e Struttura Complessa di Cardiologia (P.V., C.C.), Ospedale S. Maria della Misericordia, Perugia, Italy and Gianpaolo ReboldiGianpaolo Reboldi Dipartimento di Medicina, Università di Perugia, Italy (G.R.). Originally published8 Nov 2018https://doi.org/10.1161/CIRCRESAHA.118.314017Circulation Research. 2018;123:1205–1207If a man will begin with certainties, he shall end in doubts; but if he will be content to begin with doubts, he shall end in certainties.—Francis Bacon, The Advancement of Learning. Holborne. 1605To what extent should blood pressure (BP) be lowered in hypertensive patients? Should ≥1 BP targets be strictly defined? Or should we tailor the goal to individual patients, considering factors such as age, comorbidities, and balancing efficacy and tolerability of treatment?The recently released 2018 European Society of Cardiology/European Society of Hypertension (ESC/ESH) Guidelines state that BP should be lowered to levels <140/90 mm Hg in all patients (class I, level of evidence A recommendation) and to ≤130/80 mm Hg in most patients provided that the treatment is well tolerated (I A recommendation).1Thus, the take-home message of the 2018 ESC/ESH Guidelines is that a BP target <140/90 mm Hg is the first objective of treatment and that a more ambitious BP goal (≤130/80 mm Hg) should be pursued in most patients at condition that the treatment is well tolerated at levels <140/90 mm Hg.1Unfortunately, to quote an aphorism attributed to Voltaire, "the perfect is enemy of the good." Indeed, a few lines below, the European Guidelines1 complicate the message by adding the recommendation (I A) that systolic BP should be lowered to <140 mm Hg, but not to <130 mm Hg, in patients aged ≥65 years, a consistent proportion of hypertensive patients. The 2018 European Guidelines also add that the systolic BP target 130 to <140 mm Hg is recommended at any level of cardiovascular (CV) risk and in patients with and without established CV disease. Therefore, even patients with hypertension complicated by clinical conditions including stable chronic coronary artery disease, prior stroke, congestive heart failure, diabetes mellitus, and kidney failure should not have their systolic BP reduced <130 mm Hg if the age of patient is ≥65 years.Such recommendation contrasts with the 2017 American College of Cardiology/American Heart Association Hypertension Guidelines, approved by other 9 US Scientific Societies, which recommend a systolic BP target <130 mm Hg in almost all hypertensive patients.2In plain words, hypertensive patients aged ≥65 years should not have their systolic BP lowered <130 mm Hg in Europe, whereas it is recommended to lower their systolic BP <130 mm Hg in the United States. Ironically, one could argue that, on one side of the Ocean, someone may have misinterpreted the evidence supporting the Hypertension Guidelines.When looking at younger patients, that is, those aged <65 years, the 2018 European Guidelines state that systolic BP should be lowered to <130 mm Hg in most patients, but not <120 mm Hg (I A recommendation).1Specifically, the guidelines first recommend of being more aggressive with judicio (ie, taking patient's tolerability, as assessed during the clinical visit, into account). Subsequently, however, the guidelines introduce a sort of formal own judicio consisting of precise safety boundaries not to be exceeded (120 mm Hg in patients aged <65 years, 130 mm Hg in patients aged ≥65 years).1 Thus, 31 years after the first report by Cruickshank et al,3 the 2018 ESC/ESH Guidelines seem to fully endorse, with the strength of a I A recommendation, the implication of the J-curve hypothesis. Namely, an excessive reduction in BP should be avoided because it may expose patients to added risk instead of benefit.There are abundant pros and cons reports in the literature on the J-curve hypothesis.3–7 The European Guidelines cite, to support the statement that the risk of harm appears to increase and outweigh the benefits when systolic BP is lowered to <120 mm Hg, a post hoc analysis by Böhm et al8 of the ONTARGET trial (Ongoing Telmisartan Alone and in Combination With Ramipril Global End Point Trial) and TRANSCEND trial (Telmisartan Randomised Assessment Study in ACE Intolerant Participants With Cardiovascular Disease). The ONTARGET and TRANSCEND trials have been conducted in patients aged ≥55 years without symptomatic heart failure at entry and with a history of chronic coronary artery disease, peripheral artery disease, transient ischemic attack, stroke, or diabetes mellitus complicated by organ damage. Patients were recruited in 40 countries and followed up for a median of 56 months. Notably, about 30% of these patients did not have a positive history of hypertension. In analysis by Böhm et al,8 mean achieved systolic BP values <120 mm Hg during treatment were not associated with an increased risk of myocardial infarction or stroke, but were related to a higher risk of all-cause mortality and CV mortality and heart failure, which guided the composite primary outcome of the trial. As a side note, the analysis by Böhm et al8 by no means shows that achieved BP values 65 years expose an increased risk.The discrepancy between the lack of J-curve effect on myocardial infarction and stroke and the effect on mortality raise the possibility of reverse causality as potential contributory to results. Indeed, there is ample evidence that, independent of antihypertensive treatment, low systolic BP values are strongly associated with an excess risk of mortality in the final years of life in patients with heart failure, renal failure, and in the general population with and without frailty.9,10 Thus, nonrandomized epidemiological associations linking low systolic BP with higher mortality should be interpreted cautiously because of the likelihood of reverse causality, especially if the low BP values are recorded a few months or years before death. Correctly, Böhm et al8 concluded that it is not possible to rule out some effect of reverse causality in explaining their results.Interestingly, the study by Böhm et al8 confirms a previous analysis by our group of the same ONTARGET/TRANSCEND database, restricted to patients with coronary artery disease at entry (ie, an ideal population to test the J-curve hypothesis because an excessive reduction in diastolic BP could theoretically lead to coronary hypoperfusion in the presence of significant stenosis). After adjustment for several potential determinants of reverse causality including cancer and heart failure, which entered the analysis as time-varying covariables, a reduction in BP from baseline by 34/21 mm Hg, corresponding to an achieved BP of only 118/68 mm Hg, was associated with a markedly reduced risk of stroke, without any significant increase in the risk of myocardial infarction (Figure).4Download figureDownload PowerPointFigure. Myocardial infarction and stroke. Adjusted hazard ratio for systolic and diastolic blood pressure changes from baseline. Results by multivariable Cox regression with restricted cubic splines and 3 knots for systolic and diastolic blood pressure changes. Reprinted from Verdecchia et al4 with permission. Copyright ©2014, American Heart Association, Inc.The strong (I A) recommendation of ESC/ESH Guidelines1 that systolic BP should not be lowered <130 mm Hg in patients aged ≥65 years, and <120 mm Hg in patients aged <65 years, also contrasts with results of at least 3 well-conducted meta-analyses. In the thorough meta-regression analysis by Ettehad et al,11 a greater reduction in systolic BP, was associated with a greater risk reduction with no evidence of a J-curve effect. In a network meta-analysis by Bundy et al,12 a mean achieved systolic BP 120 to 124 mm Hg was associated with a significant reduction in the risk of CV disease and all-cause mortality even in the comparison with achieved systolic BP levels 125 to 129 mm Hg (hazard ratios of 0.82 (0.67–0.97) and 0.74 (0.57–0.97), respectively). Bangalore et al,13 in a network meta-analysis including trials designed to compare different BP targets, concluded that systolic BP targets <120 and <130 mm Hg ranked number 1 and 2, respectively, as the most efficacious target for prevention of stroke and myocardial infarction, whereas systolic BP targets <140 and <150 mm Hg ranked as number 1 and 2, respectively, as the safest targets. Overall, a systolic BP target <130 mm Hg achieved the best balance between efficacy and safety.13On balance, the evidence accrued to date does not support the 2018 ESC/ESH Guidelines recommendation (I A recommendation) which formally defines safety boundaries that should not be exceeded for the risk of increased harm out-weight the benefits.1Recently, Messerli et al14 remarked a possible rift between those who write the guidelines and those who treat the patients. By applying this concept to the 2018 ESC/ESH Hypertension Guidelines, how should we manage in the daily practice our patients with BP below the safety boundaries and perfect tolerability of treatment? Adherence to guidelines would imply that we should discourage these patients to continue their drug treatment, totally or in part, to bring BP above the safety BP boundaries. If not, there could be a hypothetical risk for a European physician to be indicted, especially in case of ensuing complications, with the charge of noncompliance with the official ESC/ESH Guidelines for enduring a too low BP.To conclude, we think that there is robust evidence from randomized trials and meta-analyses that BP should be lowered to lower levels than thought to date. Having said that, instead of fixing rigid BP targets or safety thresholds, what we should pursue in daily practice is the optimal balance between the magnitude of achieved BP reduction and the tolerability of treatment in each single patient.15 Factors such as age and comorbidities should be carefully considered when assessing this balance.15In our opinion, the 2018 European Guidelines I A recommendation that systolic BP should not be lowered below predefined safety boundaries (120 mm Hg in patients aged <65, 130 mm Hg in patients aged ≥65 years) is unsupported by sound evidence and should be reconsidered.Sources of FundingThis work was funded in part by the Fondazione Umbra Cuore e Ipertensione-ONLUS, Perugia, Italy.DisclosuresNone.FootnotesThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.Correspondence to Paolo Verdecchia, FESC, FACC, Fondazione Umbra Cuore e Ipertensione-Organizzazione Non Lucrativa di Utilità Sociale (ONLUS), Ospedale S. Maria della Misericordia, 06129-Perugia, Italy. Email [email protected]itReferences1. Williams B, Mancia G, Spiering W, et al; ESC Scientific Document Group. 2018 ESC/ESH guidelines for the management of arterial hypertension.Eur Heart J. 2018; 39:3021–3104. doi: 10.1093/eurheartj/ehy339CrossrefMedlineGoogle Scholar2. Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.Hypertension. 2018; 71:e13–e115. doi: 10.1161/HYP.0000000000000065LinkGoogle Scholar3. Cruickshank JM, Thorp JM, Zacharias FJ. Benefits and potential harm of lowering high blood pressure.Lancet. 1987; 1:581–584.CrossrefMedlineGoogle Scholar4. Verdecchia P, Reboldi G, Angeli F, Trimarco B, Mancia G, Pogue J, Gao P, Sleight P, Teo K, Yusuf S. 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Verdecchia P, Reboldi G and Angeli F (2020) The 2020 International Society of Hypertension global hypertension practice guidelines - key messages and clinical considerations, European Journal of Internal Medicine, 10.1016/j.ejim.2020.09.001, 82, (1-6), Online publication date: 1-Dec-2020. Angeli F, Reboldi G and Verdecchia P (2020) Management of hypertension in the very old: an intensive reduction of blood pressure should be achieved in most patients, Journal of Human Hypertension, 10.1038/s41371-020-0345-1, 34:8, (551-556), Online publication date: 1-Aug-2020. Angeli F, Verdecchia P and Reboldi G (2019) Tight Blood Pressure Control Saves Lives in Hypertensive Patients With Chronic Kidney Disease, Hypertension, 73:6, (1172-1173), Online publication date: 1-Jun-2019. Touyz R (2019) Hypertension Guidelines: Effect of Blood Pressure Targets, Canadian Journal of Cardiology, 10.1016/j.cjca.2019.03.014, 35:5, (564-569), Online publication date: 1-May-2019. Saad M, Salehi N, Ding Z and Mehta J (2019) Blood pressure target in diabetics: how low is too low?, European Heart Journal, 10.1093/eurheartj/ehz197, 40:25, (2044-2046), Online publication date: 1-Jul-2019. Angeli F, Reboldi G, Trapasso M, Gentile G, Pinzagli M, Aita A and Verdecchia P (2019) European and US guidelines for arterial hypertension: similarities and differences, European Journal of Internal Medicine, 10.1016/j.ejim.2019.01.016, 63, (3-8), Online publication date: 1-May-2019. Angeli F, Reboldi G, Trapasso M, Aita A and Verdecchia P (2019) Managing hypertension in 2018: which guideline to follow?, Heart Asia, 10.1136/heartasia-2018-011127, 11:1, (e011127), Online publication date: 1-Feb-2019. Verdecchia P, Cavallini C and Angeli F (2022) Advances in the Treatment Strategies in Hypertension: Present and Future, Journal of Cardiovascular Development and Disease, 10.3390/jcdd9030072, 9:3, (72) November 9, 2018Vol 123, Issue 11 Advertisement Article InformationMetrics © 2018 American Heart Association, Inc.https://doi.org/10.1161/CIRCRESAHA.118.314017PMID: 30571468 Originally publishedNovember 8, 2018 Keywordsheart failureblood pressurehypertensiondiabetes mellituscomorbidityPDF download Advertisement
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