Currie, Gemma

Delles, Christian

English

Gemma Currie

Christian Delles

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Journal of Hypertension

Blood pressure targets in the elderly

Enlighten

Editorial CommentBlood pressure targets in the elderlyGemma Currie and Christian DellesSee original paper on page 436Several factors surrounding the treatment of hyperten-sion have continually caused controversy over thelast decades and remain unresolved. Key examples ofthese issues include choice of first-line antihypertensivetherapy, the role of combination therapy, blood pressure(BP) in the context of other cardiovascular risk factors andthe role of assessment of subclinical and overt organdamage in defining treatment strategies. Nothing, however,has stimulated debate to the extent seen over BP targets.Contemporary guidelines generally advocate lower BPtargets compared with earlier recommendations whenhypertension was first recognized as an important yetmodifiable cardiovascular risk factor. The issue is furtherillustrated by more sophisticated classification of BP notonly in the hypertensive range but also within normoten-sive values; concepts such as ‘prehypertension’ and ‘highnormal blood pressure’ illustrate that there could be anoptimal BP range that is lower than the current diagnosticthreshold of 140/90mmHg. Discussions about J-shaped andU-shaped curves that describe the relationship between BPand cardiovascular risk are important in this context andhave been revisitedmany times over the years. It has indeedbeen recognized that comorbidities such as diabetes andrenal failure may mandate different and often lower BPtargets compared with the general population as a result ofaltered relationships between BP and cardiovascular risk inthese high-risk patients [1]. Studies that specifically addressthe question of optimal BP targets such as HypertensionOptimal Treatment [2] and more recently SPRINT [3] havetherefore attracted widespread attention but also critique[4]. It is probably fair to say that there is still debate onoptimal BP targets but that a ‘the lower the better’ concept isgenerally accepted for most patients.It therefore came as a surprise to the hypertensioncommunity when the Eighth Joint National CommitteeJournal of Hypertension 2018, 36:234–236Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UKCorrespondence to Prof Christian Delles, MD, BHF Glasgow Cardiovascular ResearchCentre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, 126University Place, Glasgow G12 8TA, UK. Tel: +44 141 330 2749;fax: +44 141 330 3360; e-mail: Christian.Delles@glasgow.ac.ukJ Hypertens 36:234–236 Copyright  2018 The Author(s). Published by WoltersKluwer Health, Inc. This is an open access article distributed under the terms of theCreative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it ispermissible to download, share, remix, transform, and buildup the work provided it isproperly cited. The work cannot be used commercially without permission from thejournal.DOI:10.1097/HJH.0000000000001576234 www.jhypertension.com(JNC 8) defined a higher BP target for people above theage of 60 years [5]. Of course the decision to recommend atarget of 150/90mmHg was well justified by the committeeand based on the existing literature, applying a new andrigorous pipeline to examine the existing evidence, inkeeping with Institute of Medicine recommendations.However, the 150/90-mmHg target in the elderly was stilla decision against the general ‘the lower the better’ trend.And it was not accepted by all committee members; oppo-nents of this target published a ‘minority report’ outliningtheir views and interpretation of the evidence in more detailcompared with the statements in the JNC 8 report [6].There are good reasons to define different BP targetsdepending on comorbidities, organ damage, sex and age totake specific pathophysiological mechanisms and cardio-vascular risk in different groups of patients into account. Inthe elderly, it has repeatedly been argued that low BP couldlead to dizziness and orthostatic reactions, thereby increas-ing the risk of falls and fractures [7]. It has also been arguedthat increased vascular stiffness in the elderly which resultsin lower diastolic pressure and higher pulse pressure wouldrequire different BP-lowering strategies compared withyounger patients [8]. In addition, one of the largest BP trialsavailable at the time of the JNC 8 process, the Hypertensionin the Very Elderly Trial, specifically looked into a 150/80-mmHg target [9]. Nevertheless, there have been concernsthat a more relaxed BP target in the elderly would lead toundertreatment of those who may benefit most from anti-hypertensive therapy and that JNC 8 has sent out a ‘wrong’message to the clinical community [6].The current discussion about 10mmHg in the elderly isof course only a continuation of the general debate on BPtargets that we havewitnessed for many years. There will beno absolute ‘right’ or ‘wrong’ and it is well possible that thisrecommendation, not unlike other recommendations, willbe updated and modified in future editions of the JNCguidelines. In fact, to some extent the discussion in 2014does not fully apply to the situation in 2017 in whichSPRINT has shown benefits of more intensive BP treatmentalso in the elderly [3]. One should also bear in mind thatguidelines indeed provide general guidance but that treat-ment decisions in individual patients will always be drivenby person-specific factors based on the clinical picture andexperience of the physician. There is a fine balancebetween an abstract population benefit of tight BP control(that can of course also translate to individual benefits) andthe concrete adverse effects in individual patients includingVolume 36  Number 2  February 2018Blood pressure targets in the elderlydizziness, falls risk, risk of renal failure and electrolytedisturbance and generally polypharmacy – particularly inthe elderly. However, this concept is not specific to theelderly, and treatment decisions will always be tailored tothe individual with guidelines providing, indeed, onlyguidance.In this issue of the Journal of Hypertension, we findfurther data on BP targets in the elderly in an article byNayor et al. [10]. The authors have modelled in two largegeneral population cohorts, the Framingham (FHS) andJackson Heart Studies (JHS), the incidence of cardiovascularevents in people above the age of 60 years with BP (treatedor untreated) in the rangeof 140–149mmHg systolic and lessthan 90mmHg diastolic. Compared with people withouthypertension, their risk was consistently higher, and this riskextended to those aged 60 years and older. The authorsconclude that treatment to JNC 8 recommendations in theelderly, aiming at BP below 150mmHg systolic, is associatedwith substantial residual risk of cardiovascular events.Such epidemiological data have been available for manyyears. For example, the Prospective Studies Collaborationshowed direct relationships between BP and cardiovascularrisk across all ages and levels of BP [11], and there are otherlarge-scale population studies that have fuelled the discus-sions on BP targets in recent years. In fact, an analysis byBavishi et al. [12] along the same lines as the data providedby Nayor et al. arrived at very similar conclusions. Such datawill always have to be interpreted with caution as they donot derive from randomized controlled trials, but they caninform the discussion. In this sense, the data by Nayor et al.[10] are important albeit probably not surprising. They have,however, been derived from contemporary US Americanpopulation cohorts and should have particular relevance tothe JNC that in the first instance addresses the situation inthe United States of America.We recommend the reader to critically assess the evi-dence provided in the article by Nayor et al. [10]. There arestrengths and weaknesses but in the light of decades ofdiscussions on BP targets it cannot be the task of thiseditorial to add further arguments. The data in the articleby Nayor et al. are clear and well presented and appear tosupport the notion that 150/90mmHg is too high a thresh-old for initiation of antihypertensive therapy and too high atreatment target in the elderly.A few issues in the article by Nayor et al. [10], however,deserve special attention. First, the data derive from twocohorts with different BP measurement protocols. We haveseen in the post-SPRINT discussions how important theexact measurement protocols can be, depending on themethod used the actual measured BP can differ by several,maybe up to 10mmHg. Even tiny BP differences onlyoccurring during certain phases of a trial can result indifferences in cardiovascular outcomes as the ValsartanAntihypertensive Long-term Use Evaluation trial has pain-fully demonstrated [13]. We do not know if the FHS and JHSdata can be meaningfully combined, even if the meta-analysis approach and the provided sensitivity analysesoffer some reassurance. Second, not much is known aboutthe details of antihypertensive therapy in the FHS and JHSparticipants – when was the therapy initiated, why was itinitiated, what targets were defined for individual patientsJournal of Hypertensionby their physician, what (e.g. adverse effects) has driven achange in therapy? It should also be noted that BP targetswill have generally changed over decades in parallel toupdated guidelines. All this information would be impor-tant beyond the simple numerical BP values that have beenused for the present analysis by Nayor et al. [10]. In addition,third, this analysis has been performed with the benefit ofhindsight but not as a prospective clinical trial. It is some-what easier to explore existing datasets than to set up aprospective clinical trial to more robustly answer a clinicalquestion, and as with every secondary or not predefinedanalysis, there is a risk of both false positive and falsenegative findings.We would like to leave the exact interpretation of thedata by Nayor et al. [10] to the clinical community and tofuture guideline committees. Instead we would like to putthis article into the current precision medicine landscapeand see it as a wake-up call for the hypertension communityto generate better andmore detailed data [14,15]. As valid asthe analysis of a relationship between BP level and outcomemay be on the population level or in the context of largeclinical trials, the treatment of individual patients oftenrequires information beyond such simple data. We havealready mentioned such factors including duration ofhypertension, adverse effects, degree of organ damageand comorbidities above, and they can be supplementedby biomarkers, genetic and genomic information and otherfactors that stratify patients into specific groups with regardto risk and treatment options. In fact, this information hasthe potential to define individual subtypes of hypertensionand characterize the phenotype far better than the numbersthat we read on a sphygmomanometer.Such information is not available in the present analysisof FHS and JHS data by Nayor et al. [10] and in all fairness, isnot available in any of the larger population based andclinical trial datasets. The best we can currently do is indeedwhat Nayor et al. have done: to analyse BP figures againstdefined outcomes, adjusted for the available relevant clini-cal data. We thereby reduce a complex phenotype to areadout and miss opportunities to define tailored treat-ments for individual patients or patient groups. In the caseof the elderly, this is not only a question of missing molec-ular (biomarker, genetics) data but very much also a ques-tion of stratification by sex in which one would expectdifferences in the pathophysiological make-up of hyper-tension in postmenopausal women who ‘catch up’ withtheir cardiovascular risk compared with men who havedifferent onset and development of high BP. By simplyadjusting for sex, we cannot answer such fundamentalquestions in existing datasets.In summary, the article by Nayor et al. [10] provides datathat inform the discussion on BP targets, but even moreimportantly, it provides food for thought for the design offuture clinical trials and general population cohorts. Theexperienced team of Nayor et al. has carefully analysed theavailable datasets using sophisticated statistical methodsand are still limited by the missing phenotypic depth ofthese datasets. If we really want to enter the precisionmedicine age also for the diagnosis and treatment of hyper-tension, we have to generate deeper phenotypic data andwill then, hopefully, be able to answer questions about BPwww.jhypertension.com 235Currie and Dellestargets and all the other controversies that the hypertensioncommunity has struggled to answer for so many years.ACKNOWLEDGEMENTSOur work is supported by grants from the European Com-mission [Cooperative Research Projects ‘sysVASC’ (603288),‘HOMAGE’ (305507) and ‘PRIORITY’ (101813)] and theBritish Heart Foundation (Centre of Research ExcellenceAward RE/13/5/30177).Conflicts of interestThere are no conflicts of interest.REFERENCES1. Mancia G, Fagard R, Narkiewicz K, Redo´n J, Zanchetti A, Bo¨hmM, et al.2013 ESH/ESCGuidelines for themanagement of arterial hypertension:the Task Force for the management of arterial hypertension of theEuropean Society of Hypertension (ESH) and of the European Societyof Cardiology (ESC). J Hypertens 2013; 31:1281–1357.2. Hansson L, Zanchetti A, Carruthers SG, Dahlo¨f B, Elmfeldt D, Julius S,et al. Effects of intensive blood-pressure lowering and low-dose aspirinin patients with hypertension: principal results of the HypertensionOptimal Treatment (HOT) randomised trial. HOT Study Group. Lancet1998; 351:1755–1762.3. Wright JT Jr, Williamson JD, Whelton PK, Snyder JK, Sink KM, RoccoMV, et al., SPRINT Research Group. A randomized trial of intensiveversus standard blood-pressure control. N Engl J Med 2015; 373:2103–2116.4. Kjeldsen SE, Narkiewicz K, Hedner T, Mancia G. The SPRINT study:outcome may be driven by difference in diuretic treatment demaskingheart failure and study design may support systolic blood pressuretarget below 140 mmHg rather than below 120mmHg. Blood Press2016; 25:63–66.236 www.jhypertension.com5. James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C,Handler J, et al. 2014 Evidence-based guideline for the management ofhigh blood pressure in adults: report from the panel membersappointed to the Eighth Joint National Committee (JNC 8). JAMA2014; 311:507–520; Erratum in: JAMA 2014; 311: 1809.6. Wright JT Jr, Fine LJ, Lackland DT, Ogedegbe G, Dennison HimmelfarbCR. Evidence supporting a systolic blood pressure goal of less than150mm Hg in patients aged 60 years or older: the minority view. AnnIntern Med 2014; 160:499–503.7. Butt DA,MamdaniM, Austin PC, Tu K, Gomes T, Glazier RH. The risk ofhip fracture after initiating antihypertensive drugs in the elderly. ArchIntern Med 2012; 172:1739–1744.8. Smulyan H, Mookherjee S, Safar ME. The two faces of hypertension:role of aortic stiffness. J Am Soc Hypertens 2016; 10:175–183.9. Beckett NS, Peters R, Fletcher AE, Staessen JA, Liu L, Dumitrascu D,et al. Treatment of hypertension in patients 80 years of age or older. NEngl J Med 2008; 358:1887–1898.10. Nayor M, Duncan MS, Musani SK, Xanthakis V, LaValley MP, LarsonMG, et al. Incidence of cardiovascular disease in individuals affected byrecent changes to US blood pressure treatment guidelines. J Hypertens2018; 36:436–443.11. Lewington S, Clarke R, Qizilbash N, Peto R, Collins R, ProspectiveStudies Collaboration. Age-specific relevance of usual blood pressureto vascular mortality: a meta-analysis of individual data for one millionadults in 61 prospective studies. Lancet 2002; 360:1903–1913; Erratumin: Lancet 2003; 361: 1060.12. Bavishi C, Bangalore S, Messerli FH. Outcomes of intensive bloodpressure lowering in older hypertensive patients. J Am Coll Cardiol2017; 69:486–493.13. Julius S, Kjeldsen SE, Weber M, Brunner HR, Ekman S, Hansson L, et al.Outcomes in hypertensive patients at high cardiovascular risk treatedwith regimens based on valsartan or amlodipine: the VALUE random-ised trial. Lancet 2004; 363:2022–2031.14. Dominiczak A, Delles C, Padmanabhan S. Genomics and precisionmedicine for clinicians and scientists in hypertension. Hypertension2017; 69:e10–e13.15. Currie G, Delles C. The future of ‘omics’ in hypertension. Can J Cardiol2017; 33:601–610.Volume 36  Number 2  February 2018

Enlighten: Publications

Editorial CommentBlood pressure targets in the elderly
Gemma Currie and Christian DellesSee original paper on page 436S
everal factors surrounding the treatment of hyperten-
sion have continually caused controversy over the
last decades and remain unresolved. Key examples of
these issues include choice of first-line antihypertensive
therapy, the role of combination therapy, blood pressure
(BP) in the context of other cardiovascular risk factors and
the role of assessment of subclinical and overt organ
damage in defining treatment strategies. Nothing, however,
has stimulated debate to the extent seen over BP targets.
Contemporary guidelines generally advocate lower BP
targets compared with earlier recommendations when
hypertension was first recognized as an important yet
modifiable cardiovascular risk factor. The issue is further
illustrated by more sophisticated classification of BP not
only in the hypertensive range but also within normoten-
sive values; concepts such as ‘prehypertension’ and ‘high
normal blood pressure’ illustrate that there could be an
optimal BP range that is lower than the current diagnostic
threshold of 140/90mmHg. Discussions about J-shaped and
U-shaped curves that describe the relationship between BP
and cardiovascular risk are important in this context and
have been revisitedmany times over the years. It has indeed
been recognized that comorbidities such as diabetes and
renal failure may mandate different and often lower BP
targets compared with the general population as a result of
altered relationships between BP and cardiovascular risk in
these high-risk patients [1]. Studies that specifically address
the question of optimal BP targets such as Hypertension
Optimal Treatment [2] and more recently SPRINT [3] have
therefore attracted widespread attention but also critique
[4]. It is probably fair to say that there is still debate on
optimal BP targets but that a ‘the lower the better’ concept is
generally accepted for most patients.
It therefore came as a surprise to the hypertension
community when the Eighth Joint National CommitteeJournal of Hypertension 2018, 36:234–236
Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
Correspondence to Prof Christian Delles, MD, BHF Glasgow Cardiovascular Research
Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, 126
University Place, Glasgow G12 8TA, UK. Tel: +44 141 330 2749;
fax: +44 141 330 3360; e-mail: Christian.Delles@glasgow.ac.uk
J Hypertens 36:234–236 Copyright  2018 The Author(s). Published by Wolters
Kluwer Health, Inc. This is an open access article distributed under the terms of the
Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is
permissible to download, share, remix, transform, and buildup the work provided it is
properly cited. The work cannot be used commercially without permission from the
journal.
DOI:10.1097/HJH.0000000000001576
234 www.jhypertension.com(JNC 8) defined a higher BP target for people above the
age of 60 years [5]. Of course the decision to recommend a
target of 150/90mmHg was well justified by the committee
and based on the existing literature, applying a new and
rigorous pipeline to examine the existing evidence, in
keeping with Institute of Medicine recommendations.
However, the 150/90-mmHg target in the elderly was still
a decision against the general ‘the lower the better’ trend.
And it was not accepted by all committee members; oppo-
nents of this target published a ‘minority report’ outlining
their views and interpretation of the evidence in more detail
compared with the statements in the JNC 8 report [6].
There are good reasons to define different BP targets
depending on comorbidities, organ damage, sex and age to
take specific pathophysiological mechanisms and cardio-
vascular risk in different groups of patients into account. In
the elderly, it has repeatedly been argued that low BP could
lead to dizziness and orthostatic reactions, thereby increas-
ing the risk of falls and fractures [7]. It has also been argued
that increased vascular stiffness in the elderly which results
in lower diastolic pressure and higher pulse pressure would
require different BP-lowering strategies compared with
younger patients [8]. In addition, one of the largest BP trials
available at the time of the JNC 8 process, the Hypertension
in the Very Elderly Trial, specifically looked into a 150/80-
mmHg target [9]. Nevertheless, there have been concerns
that a more relaxed BP target in the elderly would lead to
undertreatment of those who may benefit most from anti-
hypertensive therapy and that JNC 8 has sent out a ‘wrong’
message to the clinical community [6].
The current discussion about 10mmHg in the elderly is
of course only a continuation of the general debate on BP
targets that we havewitnessed for many years. There will be
no absolute ‘right’ or ‘wrong’ and it is well possible that this
recommendation, not unlike other recommendations, will
be updated and modified in future editions of the JNC
guidelines. In fact, to some extent the discussion in 2014
does not fully apply to the situation in 2017 in which
SPRINT has shown benefits of more intensive BP treatment
also in the elderly [3]. One should also bear in mind that
guidelines indeed provide general guidance but that treat-
ment decisions in individual patients will always be driven
by person-specific factors based on the clinical picture and
experience of the physician. There is a fine balance
between an abstract population benefit of tight BP control
(that can of course also translate to individual benefits) and
the concrete adverse effects in individual patients includingVolume 36  Number 2  February 2018
Blood pressure targets in the elderlydizziness, falls risk, risk of renal failure and electrolyte
disturbance and generally polypharmacy – particularly in
the elderly. However, this concept is not specific to the
elderly, and treatment decisions will always be tailored to
the individual with guidelines providing, indeed, only
guidance.
In this issue of the Journal of Hypertension, we find
further data on BP targets in the elderly in an article by
Nayor et al. [10]. The authors have modelled in two large
general population cohorts, the Framingham (FHS) and
Jackson Heart Studies (JHS), the incidence of cardiovascular
events in people above the age of 60 years with BP (treated
or untreated) in the rangeof 140–149mmHg systolic and less
than 90mmHg diastolic. Compared with people without
hypertension, their risk was consistently higher, and this risk
extended to those aged 60 years and older. The authors
conclude that treatment to JNC 8 recommendations in the
elderly, aiming at BP below 150mmHg systolic, is associated
with substantial residual risk of cardiovascular events.
Such epidemiological data have been available for many
years. For example, the Prospective Studies Collaboration
showed direct relationships between BP and cardiovascular
risk across all ages and levels of BP [11], and there are other
large-scale population studies that have fuelled the discus-
sions on BP targets in recent years. In fact, an analysis by
Bavishi et al. [12] along the same lines as the data provided
by Nayor et al. arrived at very similar conclusions. Such data
will always have to be interpreted with caution as they do
not derive from randomized controlled trials, but they can
inform the discussion. In this sense, the data by Nayor et al.
[10] are important albeit probably not surprising. They have,
however, been derived from contemporary US American
population cohorts and should have particular relevance to
the JNC that in the first instance addresses the situation in
the United States of America.
We recommend the reader to critically assess the evi-
dence provided in the article by Nayor et al. [10]. There are
strengths and weaknesses but in the light of decades of
discussions on BP targets it cannot be the task of this
editorial to add further arguments. The data in the article
by Nayor et al. are clear and well presented and appear to
support the notion that 150/90mmHg is too high a thresh-
old for initiation of antihypertensive therapy and too high a
treatment target in the elderly.
A few issues in the article by Nayor et al. [10], however,
deserve special attention. First, the data derive from two
cohorts with different BP measurement protocols. We have
seen in the post-SPRINT discussions how important the
exact measurement protocols can be, depending on the
method used the actual measured BP can differ by several,
maybe up to 10mmHg. Even tiny BP differences only
occurring during certain phases of a trial can result in
differences in cardiovascular outcomes as the Valsartan
Antihypertensive Long-term Use Evaluation trial has pain-
fully demonstrated [13]. We do not know if the FHS and JHS
data can be meaningfully combined, even if the meta-
analysis approach and the provided sensitivity analyses
offer some reassurance. Second, not much is known about
the details of antihypertensive therapy in the FHS and JHS
participants – when was the therapy initiated, why was it
initiated, what targets were defined for individual patientsJournal of Hypertensionby their physician, what (e.g. adverse effects) has driven a
change in therapy? It should also be noted that BP targets
will have generally changed over decades in parallel to
updated guidelines. All this information would be impor-
tant beyond the simple numerical BP values that have been
used for the present analysis by Nayor et al. [10]. In addition,
third, this analysis has been performed with the benefit of
hindsight but not as a prospective clinical trial. It is some-
what easier to explore existing datasets than to set up a
prospective clinical trial to more robustly answer a clinical
question, and as with every secondary or not predefined
analysis, there is a risk of both false positive and false
negative findings.
We would like to leave the exact interpretation of the
data by Nayor et al. [10] to the clinical community and to
future guideline committees. Instead we would like to put
this article into the current precision medicine landscape
and see it as a wake-up call for the hypertension community
to generate better andmore detailed data [14,15]. As valid as
the analysis of a relationship between BP level and outcome
may be on the population level or in the context of large
clinical trials, the treatment of individual patients often
requires information beyond such simple data. We have
already mentioned such factors including duration of
hypertension, adverse effects, degree of organ damage
and comorbidities above, and they can be supplemented
by biomarkers, genetic and genomic information and other
factors that stratify patients into specific groups with regard
to risk and treatment options. In fact, this information has
the potential to define individual subtypes of hypertension
and characterize the phenotype far better than the numbers
that we read on a sphygmomanometer.
Such information is not available in the present analysis
of FHS and JHS data by Nayor et al. [10] and in all fairness, is
not available in any of the larger population based and
clinical trial datasets. The best we can currently do is indeed
what Nayor et al. have done: to analyse BP figures against
defined outcomes, adjusted for the available relevant clini-
cal data. We thereby reduce a complex phenotype to a
readout and miss opportunities to define tailored treat-
ments for individual patients or patient groups. In the case
of the elderly, this is not only a question of missing molec-
ular (biomarker, genetics) data but very much also a ques-
tion of stratification by sex in which one would expect
differences in the pathophysiological make-up of hyper-
tension in postmenopausal women who ‘catch up’ with
their cardiovascular risk compared with men who have
different onset and development of high BP. By simply
adjusting for sex, we cannot answer such fundamental
questions in existing datasets.
In summary, the article by Nayor et al. [10] provides data
that inform the discussion on BP targets, but even more
importantly, it provides food for thought for the design of
future clinical trials and general population cohorts. The
experienced team of Nayor et al. has carefully analysed the
available datasets using sophisticated statistical methods
and are still limited by the missing phenotypic depth of
these datasets. If we really want to enter the precision
medicine age also for the diagnosis and treatment of hyper-
tension, we have to generate deeper phenotypic data and
will then, hopefully, be able to answer questions about BPwww.jhypertension.com 235
Currie and Dellestargets and all the other controversies that the hypertension
community has struggled to answer for so many years.
ACKNOWLEDGEMENTS
Our work is supported by grants from the European Com-
mission [Cooperative Research Projects ‘sysVASC’ (603288),
‘HOMAGE’ (305507) and ‘PRIORITY’ (101813)] and the
British Heart Foundation (Centre of Research Excellence
Award RE/13/5/30177).
Conflicts of interest
There are no conflicts of interest.REFERENCES
1. Mancia G, Fagard R, Narkiewicz K, Redo´n J, Zanchetti A, Bo¨hmM, et al.
2013 ESH/ESCGuidelines for themanagement of arterial hypertension:
the Task Force for the management of arterial hypertension of the
European Society of Hypertension (ESH) and of the European Society
of Cardiology (ESC). J Hypertens 2013; 31:1281–1357.
2. Hansson L, Zanchetti A, Carruthers SG, Dahlo¨f B, Elmfeldt D, Julius S,
et al. Effects of intensive blood-pressure lowering and low-dose aspirin
in patients with hypertension: principal results of the Hypertension
Optimal Treatment (HOT) randomised trial. HOT Study Group. Lancet
1998; 351:1755–1762.
3. Wright JT Jr, Williamson JD, Whelton PK, Snyder JK, Sink KM, Rocco
MV, et al., SPRINT Research Group. A randomized trial of intensive
versus standard blood-pressure control. N Engl J Med 2015; 373:
2103–2116.
4. Kjeldsen SE, Narkiewicz K, Hedner T, Mancia G. The SPRINT study:
outcome may be driven by difference in diuretic treatment demasking
heart failure and study design may support systolic blood pressure
target below 140 mmHg rather than below 120mmHg. Blood Press
2016; 25:63–66.236 www.jhypertension.com5. James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C,
Handler J, et al. 2014 Evidence-based guideline for the management of
high blood pressure in adults: report from the panel members
appointed to the Eighth Joint National Committee (JNC 8). JAMA
2014; 311:507–520; Erratum in: JAMA 2014; 311: 1809.
6. Wright JT Jr, Fine LJ, Lackland DT, Ogedegbe G, Dennison Himmelfarb
CR. Evidence supporting a systolic blood pressure goal of less than
150mm Hg in patients aged 60 years or older: the minority view. Ann
Intern Med 2014; 160:499–503.
7. Butt DA,MamdaniM, Austin PC, Tu K, Gomes T, Glazier RH. The risk of
hip fracture after initiating antihypertensive drugs in the elderly. Arch
Intern Med 2012; 172:1739–1744.
8. Smulyan H, Mookherjee S, Safar ME. The two faces of hypertension:
role of aortic stiffness. J Am Soc Hypertens 2016; 10:175–183.
9. Beckett NS, Peters R, Fletcher AE, Staessen JA, Liu L, Dumitrascu D,
et al. Treatment of hypertension in patients 80 years of age or older. N
Engl J Med 2008; 358:1887–1898.
10. Nayor M, Duncan MS, Musani SK, Xanthakis V, LaValley MP, Larson
MG, et al. Incidence of cardiovascular disease in individuals affected by
recent changes to US blood pressure treatment guidelines. J Hypertens
2018; 36:436–443.
11. Lewington S, Clarke R, Qizilbash N, Peto R, Collins R, Prospective
Studies Collaboration. Age-specific relevance of usual blood pressure
to vascular mortality: a meta-analysis of individual data for one million
adults in 61 prospective studies. Lancet 2002; 360:1903–1913; Erratum
in: Lancet 2003; 361: 1060.
12. Bavishi C, Bangalore S, Messerli FH. Outcomes of intensive blood
pressure lowering in older hypertensive patients. J Am Coll Cardiol
2017; 69:486–493.
13. Julius S, Kjeldsen SE, Weber M, Brunner HR, Ekman S, Hansson L, et al.
Outcomes in hypertensive patients at high cardiovascular risk treated
with regimens based on valsartan or amlodipine: the VALUE random-
ised trial. Lancet 2004; 363:2022–2031.
14. Dominiczak A, Delles C, Padmanabhan S. Genomics and precision
medicine for clinicians and scientists in hypertension. Hypertension
2017; 69:e10–e13.
15. Currie G, Delles C. The future of ‘omics’ in hypertension. Can J Cardiol
2017; 33:601–610.Volume 36  Number 2  February 2018


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