Editorial Commentary

Hypertension Guidelines
Is It Time to Reappraise Blood Pressure Thresholds and Targets?
Rhian M. Touyz, Anna F. Dominiczak

H eart disease, stroke, and renal failure are leading causes of

death with hypertension being the predominant risk fac-
tor.1,2 Extensive evidence from randomized controlled trials has
benefit when blood pressure is treated more intensively to a
goal lower than 140/90 mmHg.
Exactly how low blood pressure should be targeted
clearly demonstrated benefit of antihypertensive treatment and remains a matter of intense discussion. This is highlighted by
blood pressure reduction in reducing cardiovascular events in the many studies that have demonstrated that below a certain
individuals with hypertension.35 Accordingly effective blood level of blood pressure, more aggressive reductions may not
pressure control is essential to prevent the adverse sequelae be associated with benefit and actually increase the risk of
of hypertension. Although modern drugs have the capacity to harm. The notion of the J curve, defined as the occurrence of
reduce blood pressure in almost every patient with hyperten- additional cardiovascular events when the blood pressure is
sion,6,7 the actual blood pressure thresholds at which treatment lowered beyond the level required to maintain tissue perfu-
should be initiated and the target levels at which blood pressure sion, refers primarily to diastolic blood pressure.16,17 Exactly
what the critical diastolic blood pressure is, particularly in the
should be maintained still remain a topic of much discussion
population at large, still unclear, but treatment to a level <65
and debate.
mmHg has been suggested to be associated with additional
To inform healthcare providers and to provide pragmatic
harm.1618 Current guidelines suggest treatment targets for
clinical suggestions and recommendations, international,
diastolic blood pressure <90 mmHg, which seems safe in the
regional, and national hypertension guidelines have been J-curve phenomenon.
developed by expert groups globally. Most major hyper- But what about systolic blood pressure? Is there a J-curve
tension treatment guidelines currently suggest that clini- for systolic blood pressure and is 140 mmHg truly the level
cians should strive to treat adults to a blood pressure target associated with maximum benefit? Despite guidelines sug-
of 140/90 mmHg.814 About goals of older individuals, a gesting this, until recently, there was little evidence that lower
2014 report from panel members of the Eighth Joint National systolic blood pressure targets may have greater cardiovascular
Committee (JNC8) suggested that in patients aged 60 years, protection. However, 3 recent important studies, the Systolic
blood pressure should be targeted to <150/90 mmHg.12 The Blood Pressure Intervention Trial (SPRINT)19 and 2 large
French guidelines recommend that individuals aged 80 years meta-analyses clearly showed that lower systolic blood pres-
should be treated to a target of 150/90 mmHg,15 whereas the sures may indeed be better.20,21 The main finding in SPRINT
Canadian guidelines suggest that in the very elderly (80 was that a primary composite outcome of cardiovascular dis-
years), the threshold for initiating drug treatment should be ease and death was reduced by 25% and all-cause mortality by
160 mmHg.14 27% in patients treated intensively to a systolic blood pressure
Hypertension guidelines, in large part, are evidence based target of <120 mmHg.19 However, it should be stressed that
and are usually dictated by randomized controlled trial data SPRINT was restricted to hypertensive adults, including the
and observational studies. Although there is general consen- elderly (>75 years), at above-average risk of cardiovascular
sus between major guidelines that treatment should aim at disease and that diabetic patients and those who had already
lowering blood pressure in adults to 140/90 mmHg,814 what had a stroke, were excluded.12 Xie et al,20 in a meta-analysis of
has been less clear is whether there is further cardiovascular >44000 patients, showed that intensive blood pressurelower-
ing <140 mmHg was associated with improved cardiovascular
and renal outcomes. Ettehad et al21 reported in a systematic
The opinions expressed in this article are not necessarily those of the review and meta-analysis of >613000 participants that lower-
American Heart Association. ing blood pressure to a systolic blood pressure of <130 mmHg
From the Institute of Cardiovascular and Medical Sciences, British significantly reduced cardiovascular events and mortality.
Heart Foundation (BHF) Glasgow Cardiovascular Research Centre,
University of Glasgow, Glasgow, United Kingdom. Although these recent meta-analyses, together with the
This article was sent to Robert M. Carey, Consulting Editor, for review SPRINT findings, are highly suggestive that there is increased
by expert referees, editorial decision, and final disposition. benefit when patients with hypertension are treated to systolic
Correspondence to Rhian M. Touyz, Institute of Cardiovascular and
blood pressures below the currently suggested target of 140
Medical Sciences, BHF Glasgow Cardiovascular Research Centre,
College of Medical, Veterinary and Life Sciences, University of Glasgow, mmHg, there are some important aspects of these studies that
126 University Pl, Glasgow G12 8TA, United Kingdom. E-mail Rhian. should be highlighted. In particular, the meta-analyses com-
[email protected] prised trials with heterogeneous cohorts and thus identifying
(Hypertension. 2016;67:00-00.
DOI: 10.1161/HYPERTENSIONAHA.116.07090.) those individuals who would benefit most from intensive treat-
2016 American Heart Association, Inc. ment to lower blood pressure targets is difficult. In addition,
Hypertension is available at http://hyper.ahajournals.org in all 3 studies, the focus of intensive therapy was on systolic
DOI: 10.1161/HYPERTENSIONAHA.116.07090 blood pressure and it remains unclear whether a concomitant
1
2Hypertension April 2016

reduction in diastolic blood pressure (which is likely with inten- 5. SHEP Cooperative Research Group. Prevention of stroke by antihyperten-
sive drug treatment in older persons with isolated systolic hypertension:
sive antihypertensive treatment) would also result in a reduced
final results of the Systolic Hypertension in the Elderly Program (SHEP).
rate of cardiovascular events. Notwithstanding some of these JAMA. 1991;265:32553264.
issues, the potential impact of SPRINT and the recent meta- 6. Chobanian AV. Shattuck Lecture. The hypertension paradoxmore uncon-
analyses, on diagnosing, treating, and managing patients with trolled disease despite improved therapy. N Engl J Med. 2009;361:878
887. doi: 10.1056/NEJMsa0903829.
hypertension, is immense, not only from the healthcare and 7. Chobanian AV. Time to Reassess Blood-Pressure Goals. N Engl J Med.
patients well-being point of view but also from the societal and 2015;373:20932095. doi: 10.1056/NEJMp1513290.
health economic position. It is likely that these studies will lead 8. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr,
to changes in clinical practice. Accordingly, it is now timely Jones DW, Materson BJ, Oparil S, Wright JT Jr, Roccella EJ; Joint National
Committee on Prevention, Detection, Evaluation, and Treatment of High
to rethink blood pressure thresholds and targets. As hyperten- Blood Pressure. National Heart, Lung, and Blood Institute; National
sion experts we have the responsibility to re-evaluate current High Blood Pressure Education Program Coordinating Committee.
evidence and reappraise guidelines for diagnosis and manage- Seventh report of the Joint National Committee on Prevention, Detection,
Evaluation, and Treatment of High Blood Pressure. Hypertension.
ment. Exactly what the future recommendations will be remain 2003;42:12061252. doi: 10.1161/01.HYP.0000107251.49515.c2.
uncertain because the data from the recent studies1921 still need 9. Mancia G, Fagard R, Narkiewicz K, et al; Task Force Members. 2013
to be digested and further analyzed in the context of current ESH/ESC Guidelines for the management of arterial hypertension:
evidence-based studies, but it is very likely that there will be a the Task Force for the management of arterial hypertension of the
European Society of Hypertension (ESH) and of the European Society
strong move toward more aggressive control of hypertension to of Cardiology (ESC). J Hypertens. 2013;31:12811357. doi: 10.1097/01.
lower blood pressure targets. With the awaited new American hjh.0000431740.32696.cc.
College of Cardiology/American Heart Association guidelines 10. Weber MA, Schiffrin EL, White WB, et al. Clinical practice guide-
lines for the management of hypertension in the community a state-
soon to be finalized, reassessment of existing guidelines and ment by the American Society of Hypertension and the International
more SPRINT substudies to be published, the landscape of Society of Hypertension. J Hypertens. 2014;32:315. doi: 10.1097/
diagnosing and treating hypertension may change significantly HJH.0000000000000065.
in the near future. 11. McManus RJ, Caulfield M, Williams B; National Institute for Health and
Clinical Excellence. NICE hypertension guideline 2011: evidence based
Over the next few months, we will seek opinions and evolution. BMJ. 2012;344:e181.
comments from key leaders involved in regional and inter- 12. James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for
national hypertension guidelines. As such we will provide the management of high blood pressure in adults: report from the panel
members appointed to the Eighth Joint National Committee (JNC 8).
views from across the world on the potential impact of the
JAMA. 2014;311:507520. doi: 10.1001/jama.2013.284427.
new findings of lower systolic blood pressure targets and 13. Stephan D, Gaertner S, Cordeanu EM. A critical appraisal of the guide-
future guidelines. Through this platform, Hypertension, as lines from France, the UK, Europe and the USA for the management of
the premier journal in the field, will serve the hypertension hypertension in adults. Arch Cardiovasc Dis. 2015;108:453459. doi:
10.1016/j.acvd.2015.05.006.
community by keeping readers abreast of how the new land- 14. Daskalopoulou SS, Rabi DM, Zarnke KB, et al. The 2015 Canadian
mark studies will influence major guidelines and decision Hypertension Education Program recommendations for blood pres-
making for best practice. sure measurement, diagnosis, assessment of risk, prevention, and treat-
ment of hypertension. Can J Cardiol. 2015;31:549568. doi: 10.1016/j.
cjca.2015.02.016.
Sources of Funding 15. Blacher J, Halimi JM, Hanon O, Mourad JJ, Pathak A, Schnebert B,
Dr Touyz was supported through a British Heart Foundation Chair Girerd X; French Society of Hypertension. Management of hypertension
award (CH/12/4/29762). in adults: the 2013 French Society of Hypertension guidelines. Fundam
Clin Pharmacol. 2014;28:19. doi: 10.1111/fcp.12044.
Disclosures 16. Kaplan NM. The diastolic J curve: alive and threatening. Hypertension.
2011;58:751753. doi: 10.1161/HYPERTENSIONAHA.111.177741.
None. 17. Williams B. Hypertension and the J-curve. J Am Coll Cardiol.
2009;54:18351836. doi: 10.1016/j.jacc.2009.06.043.
References 18. Boutitie F, Gueyffier F, Pocock S, Fagard R, Boissel JP; INDANA Project
1. Mozaffarian D, Benjamin EJ, Go AS, et al. Heart disease and stroke Steering Committee. INdividual Data ANalysis of Antihypertensive inter-
statistics2016 update: a report from the American Heart Association vention. J-shaped relationship between blood pressure and mortality in
[published online ahead of print December 16, 2015]. Circulation. hypertensive patients: new insights from a meta-analysis of individual-
doi: 10.1161/CIR.0000000000000350. http://circ.ahajournals.org/content/ patient data. Ann Intern Med. 2002;136:438448.
early/2015/12/16/CIR.0000000000000350.long. Accessed January 21, 2016. 19. Wright JT Jr, Williamson JD, Whelton PK, et al; SPRINT Research Group.
2. Huang Y, Su L, Cai X, Mai W, Wang S, Hu Y, Wu Y, Tang H, Xu D. A Randomized Trial of Intensive versus Standard Blood-Pressure Control.
Association of all-cause and cardiovascular mortality with prehyperten- N Engl J Med. 2015;373:21032116. doi: 10.1056/NEJMoa1511939.
sion: a meta-analysis. Am Heart J. 2014;167:160168.e1. doi: 10.1016/j. 20. Xie X, Atkins E, Lv J, et al. Effects of intensive blood pressure lowering on
ahj.2013.10.023. cardiovascular and renal outcomes: updated systematic review and meta-
3. Staessen JA, Fagard R, Thijs L, et al. Randomised double-blind compari- analysis [published online ahead of print November 7, 2015]. Lancet. doi:
son of placebo and active treatment for older patients with isolated sys- 10.1016/S0140-6736(15)00805-3. http://www.thelancet.com/journals/lancet/
tolic hypertension. The Systolic Hypertension in Europe (Syst-Eur) Trial article/PIIS0140-6736(15)00805-3/fulltext. Accessed January 21, 2016.
Investigators. Lancet. 1997;350:757764. 21. Ettehad D, Emdin CA, Kiran A, Anderson SG, Callender T, Emberson J,
4. Beckett NS, Peters R, Fletcher AE, et al; HYVET Study Group. Treatment Chalmers J, Rodgers J, Rahimi K. Blood pressure lowering for preven-
of hypertension in patients 80 years of age or older. N Engl J Med. tion of cardiovascular disease and death: a systematic review and meta-
2008;358:18871898. doi: 10.1056/NEJMoa0801369. analysis. Lancet 2015. doi: 10.1016/S0140-6736(15)01225-01228.