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Effects of blood-pressure-lowering treatment on outcome incidence. 12. Effects in individuals with high-normal and normal blood pressure: overview and meta-analyses of randomized trials

Thomopoulos, Costasa; Parati, Gianfrancob,c; Zanchetti, Albertod,e

doi: 10.1097/HJH.0000000000001547

Background: It is currently unknown whether individuals with SBP/DBP values in the ranges 120–139/80–89 mmHg, usually defined as with prehypertension or high-normal and normal blood pressure (BP), benefit from BP-lowering treatment and whether benefits in these individuals depend on the level of their cardiovascular risk.

Objectives: Meta-analyzing all available data from randomized controlled trials (RCTs) about the effects on cardiovascular outcomes of BP-lowering treatment in individuals with normal or high-normal BP values in absence of baseline antihypertensive drugs and free from a recent myocardial infarction, left ventricular dysfunction and heart failure.

Methods: From an available database of BP-lowering RCTs updated to end 2016, RCTs were selected only including normotensive individuals or including both hypertensive and normotensive individuals but providing separate information in normotensive individuals. Risk ratios and 95% confidence intervals, and absolute risk reduction of cardiovascular outcomes and all deaths were calculated by a random-effects model.

Results: We identified 24 RCTs providing data on 47 991 high-normal or normal BP individuals. BP-lowering treatment was found to significantly reduce cardiovascular disease risk in these individuals, but risk reduction was limited to stroke. When RCTs were stratified according to total cardiovascular risk, no significant benefits were found in RCTs including individuals at low–moderate risk (13 RCTs, 21 128 individuals), whereas a significant reduction in stroke risk (−60% to a SBP/DBP reduction of 10/5 mmHg) was found in RCTs including individuals at high–very high risk mostly because of symptomatic cardiovascular disease (11 RCTs, 26 863 individuals). In high–very high-risk normotensive individuals, BP-lowering treatment appeared to reduce stroke risk independently of the drug class used.

Conclusion: Individuals with very high cardiovascular risk due to symptomatic cardiovascular disease should consider BP-lowering treatment even when their BP is in the high-normal and normal range.

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aDepartment of Cardiology, Helena Venizelou Hospital, Athens, Greece

bDepartment of Cardiovascular, Neural and Metabolic Sciences, Istituto Auxologico Italiano IRCCS, San Luca Hospital

cDepartment of Medicine and Surgery, University of Milan Bicocca

dScientific Direction, Istituto Auxologico Italiano IRCCS

eCentro Interuniversitario di Fisiologia Clinica e Ipertensione, Università degli Studi di Milano, Milan, Italy

Correspondence to Alberto Zanchetti, Direzione Scientifica, Istituto Auxologico Italiano, Via L. Ariosto, 13, I-20145 Milano, Italy. Tel: +39 02 619112237; fax: +39 02 619112901; e-mail:

Abbreviations: ACE, angiotensin-converting enzyme; BP, blood pressure; CHD, coronary heart disease; CI, confidence interval; LV, left ventricular; MI, myocardial infarction; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses; RAS, renin–angiotensin system; RCT, randomized controlled trial; RR, relative risk

Received 22 June, 2017

Revised 1 August, 2017

Accepted 7 August, 2017

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