Correspondence come Paolo Verdecchia, FESC, FACC, Fondazione Umbra Cuore e Ipertensione-Organizzazione no Lucrativa di Utilità Sociale (ONLUS), Ospedale S. Maria della Misericordia, 06129-Perugia, Italy. Email E-mail Address:

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 Angeli

Struttura Complessa di Cardiologia e Fisiopatologia Cardiovascolare (F.A.), Ospedale S. Maria della Misericordia, Perugia, Italy


Claudio 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


Originally published8 Nov 2018https://doi.org/10.1161/CIRCRESAHA.118.314017Circulation Research. 2018;123:1205–1207

If a guy will begin with certainties, that shall end in doubts; however if he will certainly be content to start with doubts, the shall end in certainties.

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—Francis Bacon, The development of Learning. Holborne. 1605


To what level should blood pressure (BP) be lowered in hypertensive patients? should ≥1 BP targets be strictly defined? Or must we keep going the score to separation, personal, instance patients, considering factors such as age, comorbidities, and balancing efficacy and also tolerability the treatment?

The recently released 2018 European culture of Cardiology/European culture of Hypertension (ESC/ESH) accuse state the BP must be lowered to levels 1

Thus, the take-home post of the 2018 ESC/ESH guidelines is that a BP target 1

Unfortunately, to quote one aphorism attributed come Voltaire, “the perfect is adversary of the good.” Indeed, a couple of lines below, the europe Guidelines1 complicated the message by adding the recommendation (I A) that systolic BP need to be lower to 2

In plain words, hypertensive patients aged ≥65 years have to not have actually their systolic BP lower 1

Specifically, the guidelines first recommend of being much more aggressive with judicio (ie, taking patient’s tolerability, as assessed throughout the clinical visit, into account). Subsequently, however, the guidelines introduce a type of formal very own judicio consisting of an exact safety boundaries not to be surpassed (120 mm Hg in patients age 1 Thus, 31 year after the very first report by Cruickshank et al,3 the 2018 ESC/ESH Guidelines seem to totally endorse, v the toughness of a i A recommendation, the implication of the J-curve hypothesis. Namely, an too much reduction in BP need to be avoided due to the fact that it may expose patients to added risk instead of benefit.

There are abundant pros and also cons reports in the literature on the J-curve hypothesis.3–7 The european Guidelines cite, to support the statement the the risk of harm shows up to increase and outweigh the benefits once systolic BP is lower to 8 the the ONTARGET attempt (Ongoing Telmisartan Alone and also in combination With Ramipril worldwide End allude Trial) and TRANSCEND psychological (Telmisartan Randomised Assessment research in ACE Intolerant Participants v Cardiovascular Disease). The ONTARGET and TRANSCEND trials have been carried out 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 to be recruited in 40 countries and followed up because that a median of 56 months. Notably, around 30% of these patients go not have a positive history of hypertension. In analysis by Böhm et al,8 mean achieved systolic BP values 8 through no method shows that achieved BP worths 65 years disclose an raised risk.

The discrepancy in between the absence of J-curve impact on myocardial infarction and also stroke and the impact on mortality progressive the opportunity of reverse origin as potential contributory to results. Indeed, there is ample proof that, elevation of antihypertensive treatment, short systolic BP values room strongly connected with an excess danger of mortality in the final years of life in patients v heart failure, renal failure, and in the general population with and also without frailty.9,10 Thus, nonrandomized epidemiological associations linking low systolic BP with greater mortality need to be taken cautiously due to the fact that of the likelihood of turning back causality, specifically if the short BP values are taped a couple of months or years before death. Correctly, Böhm et al8 concluded that it is not feasible to dominion out some effect of reverse causality in explaining your results.

Interestingly, the study by Böhm et al8 confirms a previous evaluation by our team of the exact same ONTARGET/TRANSCEND database, minimal to patients v coronary artery condition at entry (ie, one ideal population to test the J-curve hypothesis due to the fact that an too much reduction in diastolic BP can theoretically cause coronary hypoperfusion in the existence of significant stenosis). After adjustment for several potential components of reverse causality including cancer and heart failure, which entered the evaluation as time-varying covariables, a reduction in BP indigenous baseline by 34/21 mm Hg, equivalent to an achieved BP of just 118/68 mm Hg, was connected with a markedly diminished risk that stroke, there is no any far-reaching increase in the risk of myocardial infarction (Figure).4

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The solid (I A) reference of ESC/ESH Guidelines1 that systolic BP should not be lowered 11 a greater reduction in systolic BP, was associated with a greater risk reduction with no proof of a J-curve effect. In a network meta-analysis by Bundy et al,12 a mean accomplished systolic BP 120 come 124 mm Hg was linked with a significant reduction in the danger of CV an illness and all-cause mortality even in the comparison with completed systolic BP levels 125 come 129 mm Hg (hazard ratios that 0.82 (0.67–0.97) and also 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 the systolic BP targets 13

On balance, the proof accrued to day does not support the 2018 ESC/ESH Guidelines recommendation (I A recommendation) which formally defines safety borders that must not be exceeded for the risk of increased harm out-weight the benefits.1

Recently, Messerli et al14 remarked a possible rift between those that write the guidelines and also those that treat the patients. By applying this principle to the 2018 ESC/ESH Hypertension Guidelines, how should we regulate in the everyday practice our patients through BP listed below the security boundaries and perfect tolerability the treatment? follow to guidelines would suggest that we need to discourage this patients to proceed their medicine treatment, totally or in part, to bring BP above the safety BP boundaries. If not, there might be a theoretical risk for a European doctor to it is in indicted, specifically in case of occurring complications, v the fee of noncompliance with the main ESC/ESH Guidelines because that enduring a also low BP.

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To conclude, we think the there is robust proof from randomized trials and meta-analyses the BP need to be lower to reduced levels than thought to date. Having actually said that, rather of resolving rigid BP targets or security thresholds, what we have to pursue in daily practice is the optimal balance between the magnitude of accomplished BP reduction and the tolerability of treatment in each single patient.15 factors such as age and comorbidities need to be very closely considered when assessing this balance.15

In our opinion, the 2018 european Guidelines ns A referral that systolic BP must not be lowered below predefined safety borders (120 mm Hg in patients age

The opinions expressed in this write-up are not necessarily those that the editors or the the American love Association.