REVIEWS

Management of hypertension in the elderly

Eduardo Pimenta and Suzanne Oparil
Abstract | Hypertension is the most-prevalent modifiable risk factor for cardiovascular morbidity and mortality
worldwide. Hypertension is highly prevalent among older adults (≥65 years), and aging of the population will
substantially increase the prevalence of this condition. Age-related endothelial dysfunction and increased
arterial stiffness contribute to the increased prevalence of hypertension, particularly systolic hypertension,
among the elderly. The incidence of some forms of secondary hypertension also increases with age, mainly
owing to the use of drugs (especially NSAIDs that have pressor effects) and the presence of chronic kidney
disease, obstructive sleep apnea, and renal artery stenosis. Guidelines differ in thresholds and goals for
antihypertensive drug therapy in the elderly because of a paucity of high-level evidence from randomized
controlled trials and inconsistencies in the definition of ‘elderly’. Medical treatment of hypertension reduces
cardiovascular morbidity and mortality in the elderly, and all guidelines recommend lifestyle modifications and
medical treatment for elderly patients whose blood pressure exceeds prescribed thresholds and who are at
moderate or high cardiovascular disease risk. In the absence of comorbidities, which constitute ‘compelling
indications’ for the use of specific antihypertensive drugs or drug classes, no clear evidence exists to support
recommendations for the use of particular antihypertensive-drug classes in older adults.

Pimenta, E. & Oparil, S. Nat. Rev. Cardiol. 9, 286–296 (2012); published online 13 March 2012; doi:10.1038/nrcardio.2012.27

Introduction
Cardiovascular disease (CVD) is the leading cause of 2036.7 In the UK, 16.6% of the population were aged
mortality and the third-largest cause of disability in ≥65 years in 2010, and the elderly population is expected
developed and developing countries.1–5 Hypertension, to increase to 22% by 2030.8 Most babies born since 2000
defined as blood pressure (BP) above 140/90 mmHg, is in developed countries such as France, Germany, Italy,
the most-prevalent modifiable risk factor for CVD; in the UK, the USA, Canada, and Japan are likely to cele­
2001, 7.6 million premature deaths worldwide, includ- brate their 100th birthday if life expectancy continues
ing 54% of fatal strokes and 47% of deaths from ischemic to increase.9
heart disease, were attributed to high BP.3 In 2000, 26.4% The prevalence of hypertension increases markedly with
of the adult population of the world had hypertension advancing age.2,4,10 In a 2005 report from the Framingham
and by 2025, this figure is projected to rise to 29.2%, the Heart Study, the prevalence of hypertension was 27.3% in
equivalent of 1.5 billion people.1 In the first quarter of those aged <60 years, 63.0% in those aged 60–79 years, and
Endocrine Hypertension
Research Centre and the 21st century, the worldwide prevalence of hypertension 74.0% in those aged ≥80 years.4 Data from the US National
Clinical Centre of is expected to increase by 9% in men and 13% in women Health and Nutrition Examination Surveys (NHANES)
Research Excellence in
Cardiovascular Disease owing to projected changes in age distribution.1 of 2003–2004 showed that the prevalence of hyper­tension
and Metabolic Aging of the population means that the proportion increased from 7.3% to 32.6% to 66.3% among indivi­duals
Disorders, University
of Queensland School
of ‘elderly’ (≥65 years) individuals is growing rapidly. In aged 18–39, 40–59, and ≥60 years, respectively (Figure 1).10
of Medicine, Princess the USA, approximately 39 million people (13% of the The data on the prevalence of hypertension in the elderly
Alexandra Hospital, population) were aged ≥65 years in 2008; this number is in other countries are sparse, and comparisons cannot
5th Floor, Ipswich Road,
Woolloongabba, expected to increase to 72 million (20% of the popula- easily be drawn owing to variations in date of publication
Brisbane, QLD 4102, tion) by 2030.5 In Japan, the proportion of elderly people and the definition of ‘elderly’. The age-adjusted and sex-
Australia (E. Pimenta).
Vascular Biology and
was expected to reach 23.4% of the total population by adjusted prevalence of hypertension in North America and
Hypertension Program, January 2012.6 In Canada, the number of elderly people six European countries were reported by Wolf-Maier and
Division of increased from 2.4 million to 4.2 million between 1981 colleagues in 2003.11
Cardiovascular
Disease, Department and 2005 and the eldery are projected to account for Elderly persons, particularly elderly women, tend to
of Medicine, University more than a quarter of the Canadian population by have more-severe hypertension and lower rates of BP
of Alabama at
Birmingham, 703 19th
control than middle-aged and young adults.4 For example,
Street South, Competing interests in the Framingham Heart Study, only 23% of women aged
ZRB 1034, >80 years (compared with 38% of men) had BP controlled
S. Oparil declares associations with the following companies/
Birmingham, AL 35294,
USA (S. Oparil).
organizations: Bayer, Daiichi Sankyo, Joint National Committee to <140/90 mmHg. Whether the age-related decline in BP
on Prevention, Detection, Evaluation, and Treatment of High
control among women is related to true treatment resis-
Correspondence to: Blood Pressure, Medtronic, Merck and Co., Novartis, Pfizer, and
E. Pimenta Takeda. See the article online for full details of the relationships. tance owing to biological factors, inadequate intensity
e.pimenta@uq.edu.au E. Pimenta declares no competing interests. of, or adherence to, treatment, or to inappropriate drug

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© 2012 Macmillan Publishers Limited. All rights reserved

70
Prevalence of hypertension (%)
60
50
40
30
20
10
0
18–39 40–59 ≥ 60
Age (years)
Figure 1 | Prevalence of hypertension according to age
among adults in the USA between 1999 and 2004.10
choices, is unknown.12 In this article, we review the patho-
physiology of hypertension in the elderly and how best to
assess and treat these individuals.
Pathophysiology
With each ejection of blood from the left ventricle, a
pressure (pulse) wave is generated and travels from the
heart to the periphery at a speed (known as the pulse
wave velocity; PWV) that depends on the elastic proper-
ties of the conduit arteries. The pulse wave is reflected at
any point of discontinuity in the arterial tree and returns
to the aorta and left ventricle. The elastic properties and
length of the conduit arteries determine the timing of the
wave reflection. Increased arterial stiffness (reduction of
elasticity), with the resultant increase in PWV and altera-
tion in wave reflection, is largely responsible for the age-
related rise in the prevalence of hypertension.13 Changes
in the load-bearing media of elastic arteries, including loss
of the orderly arrangement of elastic fibers and laminae,
thinning, splitting, fraying, and fragmentation of elastin
fibers with replacement by more-rigid collagen fibers, and
calcification all contribute to the stiffening process.14,15 In
young individuals (Figure 2a), the PWV is sufficiently slow
(~5 m/s) that the reflected pulse wave reaches the aortic
valve after closure, elevating the diastolic BP and enhanc-
ing coronary perfusion by providing a ‘boosting’ effect. In
older adults, particularly if they are hyper­tensive, PWV is
greatly increased (~20 m/s) owing to central arterial stiff-
ening.16 Thus, the reflected wave reaches the aortic valve
before closure, which augments systolic BP, pulse pres-
sure, and afterload and reduces diastolic BP (Figure 2b).
This phenomenon accounts for the increase in systolic BP
and pulse pressure, and the fall in diastolic BP (isolated
systolic hypertension; ISH) that are commonly seen in
the elderly compared with younger persons.13,16–18 ISH can
develop de novo in normotensive individuals or in persons
with antecedent diastolic hypertension. In a community
survey of 3,243 individuals that included rescreening after
an average of 8 years, 16% of those who developed ISH had
previous diastolic hypertension.19 Those with ‘burned-
out’ diastolic hypertension (a decrease in diastolic BP that
contributes to the development of isolated systolic hyper­
tension) were more likely to be smokers and to have lost
more weight than those who developed ISH de novo.19
The rise in systolic BP increases cardiac metabolic
NATURE REVIEWS | CARDIOLOGY VOLUME 9  |  MAY 2012  |  287
© 2012 Macmillan Publishers Limited. All rights reserved
FOCUS ON HYPERTENSION
Key points
■■ Hypertension is highly prevalent among older adults (≥65 years), and aging
of the population will substantially increase the prevalence of this condition
worldwide
■■ Increased arterial stiffness, which is commonly found in elderly individuals,
contributes to systolic hypertension and wide pulse pressure, in part by
increasing pulse wave velocity
■■ Medical treatment of hypertension in older adults reduces cardiovascular
morbidity and mortality
■■ No clear evidence exists to support recommendations for the use of particular
drug classes in older adults
requirements and predisposes the individual to the
develop­ment of left ventricular hypertrophy and heart
failure. Pulse pressure is closely related to systolic BP and
is linked to cardiovascular events, including myocardial
infarction and stroke. Aortic stiffness has been shown
to be an independent predictor of all-cause and cardio­
vascular mortality, fatal and nonfatal coronary events, and
fatal stroke in patients with essential hypertension, type 2
diabetes mellitus, and end-stage renal disease.20
Endothelial dysfunction, characterized by an unfa-
vorable balance between vasodilators, such as nitric
oxide (NO), and vasoconstrictors, such as endothelin,
is another important contributor to BP elevation in the
elderly. Endothelial dysfunction and decreased NO avail-
ability related to mechanical and inflammatory injury of
aging arteries have been associated with increased arte-
rial stiffness and development of ISH.21 Furthermore, a
decline in flow-mediated vasodilator capacity owing to
decreased endothelium-derived NO has been related
to aging.22.23 Interestingly, the age-related decline in endo-
thelial function occurs much later in women than in men,
perhaps because of the stimulatory effects of endogenous
estrogen on NO synthesis.23 The functional relevance of
impaired endothelium-mediated vasodilatation in the
elderly is particularly evident during exercise and causes
the exaggerated exercise-induced increases in BP seen in
this age group.24
Secondary causes of hypertension
Polypharmacy
Polypharmacy, the concomitant use of a variety of pre-
scription and over-the-counter drugs, is common among
the elderly. On average, elderly individuals take more than
six different prescription medications.25 Comorbidities
such as osteoarthritis, chronic kidney disease (CKD),
chronic pain, and depression are prevalent among elderly
persons, and medications commonly taken for these con-
ditions, such as NSAIDs and corticosteroids, can increase
BP.26 Psychotropic medications have diverse effects on BP;
the most-widely used are listed in Table 1.27–31
Assessment of comorbidities and use of medications,
including nonprescription drugs, is essential in the evalu-
ation of elderly patients with hypertension. In particular,
asking patients whether they have pain and, if so, what
type of pain medication they use is important, because
these drugs are the most-commonly used medications
that increase BP. Elderly patients and those with dia­betes
are particularly susceptible to these adverse effects. In
REVIEWS
a tension in the pharyngeal airway, arousal threshold, and
b ute to BP elevation in these patients. OSA is a strong and
Figure 2 | Distensibility and pulse wave velocity. Simple tubular models of the arterial
system, connecting the heart (left) to the peripheral circulation (right). a | Normal
distensibility and normal pulse wave velocity in a young individual. b | Decreased
distensibility and increased pulse wave velocity in an older individual. The distal end
of the tube constitutes a reflection site where the pressure wave travelling down the
tube is reflected back to the heart. The wave travels slowly in the young distensible
tube (a) so that the reflected wave boosts pressure in diastole when it returns to the
proximal end. The wave travels faster in the old stiffer tube (b), returns earlier, and
boosts pressure in late systole. Flow input from the heart is intermittent in both
young and old subjects. In the young subject (a), pulsations (first, thicker arrow) are
absorbed (second, thinner arrow) in the distensible tube so that outflow is steady or
almost so. In the old subject (b), pulsations cannot be absorbed (arrows remain the
same), by the stiff tube and so output into peripheral microvessels is pulsatile.
Reprinted from J. Am. Coll. Cardiol. 50, O’Rourke, M. F. & Hashimoto, J. Mechanical
factors in arterial aging: a clinical perspective, 1–13, © (2007), with permission from
Elsevier and the American College of Cardiology.
the Nurses’ Health Study,32 the BP effect of non-narcotic
analgesics was prospectively analyzed in 51,630 normo-
tensive women aged 44–69 years over an 8‑year period.
Compared with nonusers, women who used aspirin, acet-
aminophen, or NSAIDs on a regular basis had 21%, 20%,
and 35% increased risk of hypertension, respectively. All
NSAIDs, including the selective cyclooxygenase (COX)‑2
inhibitors, seem to elevate mean BP and antagonize the
BP-lowering effects of antihypertensive drugs.32 A meta-
analysis of 45,451 patients enrolled in 19 randomized
controlled trials showed that COX‑2 inhibitors elevate
BP by an average of ~4/1 mmHg compared with placebo,
and by ~3/1 mmHg compared with NSAIDs.33 If patients
require NSAIDs or COX‑2 inhibitors, these drugs should
be prescribed at the lowest effective doses for the shortest
time possible. If analgesics are necessary in patients with
hypertension, medications such as paracetamol, tramadol,
or hydrocodone and nerve block, which are not generally
associated with BP elevations, can be used.
Medications that can potentially interfere with BP
control should be stopped to allow accurate assessment of
BP, as well as to improve the response to antihyper­tensive
therapy. However, clinical judgment and liaison with
other health-care providers, including pain-management
experts, are essential to optimize management of both BP
and common comorbidities.
Obstructive sleep apnea
Obstructive sleep apnea (OSA) is characterized by
increased and sustained respiratory effort despite partial
or complete occlusion of the upper airway. Volume over-
load, cephalic fluid shifts, loss of lung volume during sleep,
instability of ventilator control system, variable surface
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© 2012 Macmillan Publishers Limited. All rights reserved
asynchronous timing of activation of upper airway versus
pump muscles are proposed mechanisms of OSA.34 Some
of these mechanisms, including volume overload and
fluid shifts, as well as increases in sympathetic activation,
oxidative stress, inflammation, and release of vasoactive
substances secondary to intermittent hypoxemia, contrib-
indepen­dent risk factor for development and progression
of hypertension, especially treatment-resistant hyper­
tension and its cardiovascular and renal complications.34–41
The prevalence of OSA in the elderly is three-times higher
than in middle-aged individuals, with estimates ranging
from 32% to 81%.42–48
Diagnosis of OSA requires formal, overnight poly­
somno­graphy. Obesity is the single most-important cause
of OSA, and a cornerstone of treatment is weight loss,
which improves sleep efficiency and oxygenation and
lowers BP.34 For patients who are unable to lose weight,
have persistent OSA despite weight loss, or both, indefi-
nite treatment with continuous positive airway pressure
is recommended to reduce the number of hypoxemic
events.34,49 In the absence of dramatic reductions in etio-
logic factors for OSA, these patients generally require life-
time treatment with continuous positive airway pressure.
Addition of the mineralocorticoid-receptor antagonist
spironolactone to conventional antihypertensive-drug
regimens has been shown to reduce the severity of OSA,
and to lower BP, in patients with OSA and resistant hyper-
tension.50 Similarly, radiofrequency-induced renal-nerve
ablation has been shown in one small study to reduce
both BP and the severity of OSA in patients with OSA
and resistant hypertension.51
Chronic kidney disease
CKD, defined as decreased kidney function (estimated
glomerular filtration rate <60 ml/min/1.73 m2) or kidney
damage (albuminuria) that persists for 3 months or more,
is common in elderly people; the risk of this condition is
more than doubled in those aged ≥75 years compared
with younger individuals.52–54 Between the ages of 30 and
85 years, renal mass, and particularly cortical mass, is esti-
mated to decline by 20–25%.53 CKD can be either a cause
or a consequence of hypertension. Hypertension can
develop secondary to structural and functional abnor-
malities of the kidney, including glomerular, vascular,
tubulointerstitial, and cystic disease, whereas long-term
exposure to high BP can lead to glomerulosclerosis and
impaired renal function.54,55 Rising systolic BP is indepen-
dently associated with a decline in kidney function among
elderly patients with ISH.56 Fluid retention, activation of
the renin–angiotensin–aldosterone system, increased
sympathetic-nervous-system activity, and concomitant
use of medications, such as NSAIDs that impair renal
salt and water handling, contribute to the development
and maintenance of hypertension in elderly patients
with CKD.25 In addition to low glomerular filtration rate
and CVD risk factors, the presence of albuminuria acceler-
ates the development of cardiovascular and renal outcomes
in patients with CKD.54

Angiotensin-converting-enzyme (ACE) inhibitors or
angiotensin-receptor blockers (ARBs) are indicated for
the management of elderly patients with hypertension
and CKD only if proteinuria is present.25 In the absence
of proteinuria, the presence of CKD in an elderly patient
with hypertension is not a compelling indication for
any particular antihypertensive regimen or intensity
of treatment. The effects of intensive (systolic BP goal
<120 mmHg) compared with standard (systolic BP goal
<140 mmHg) antihypertensive treatment on progres-
sion of CKD, as well as cardiovascular outcomes and
mortality, is currently being examined in the ongoing
Systolic Blood Pressure Intervention Trial (SPRINT),57
which is discussed in greater detail later. Patients with
CKD constitute a very important subgroup of the hyper­
tensive population, and the presence of CKD has been an
exclusion criterion in many previous outcome trials of
antihypertensive treatment; therefore, the SPRINT study
population of 9,250 people will include 4,300 participants
with CKD (estimated glomerular filtration rate 20–59 ml/
min/1.73 m2) to allow assessment of the treatment effect
on both CVD and progression of renal disease in this
under-investigated population.
Atherosclerotic renal artery stenosis
The prevalence of atherosclerotic renal artery stenosis
(ARAS) increases with age and was shown in one autopsy
study to approach 90% among persons aged ≥75 years.58
Hemodynamically important ARAS can contribute to BP
elevation by limiting renal blood flow, leading to sodium
and water retention, as well as by stimulating renin syn-
thesis and release, with consequent activation of the
renin–angiotensin system.59 ARAS is important because
of its strong association with widespread atherosclerotic
vascular disease and cardiovascular events.25 However, the
evaluation and treatment of patients with suspected ARAS
are problematic for several reasons. Firstly, many, if not
most, anatomic lesions in the renal arteries are found inci-
dentally (for example, on coronary angiography) and are
unrelated to renal ischemia or the pathogenesis of hyper-
tension.60,61 Secondly, indications and choice of treatment
(medical therapy versus revascularization) for ARAS are
controversial owing to a paucity of data from randomized
controlled trials. Data from observational and cohort
studies indicate that ARAS generally progresses slowly and
seldom leads to severe uncontrolled hypertension or major
loss of renal function.61,62 Further, cohort studies and the
few randomized controlled trials in which the effects
of medical treatment with statins and antihypertensive
drugs (usually including ACE inhibitors or ARBs) have
been compared with revascularization (usually stenting)
in patients with ARAS, many of whom were elderly, have
found no major between-group differences in renal or
cardiovascular outcomes, mortality, or BP control.62,63 In
the absence of benefit, and in the presence of harm (lower-
extremity amputations, acute kidney injury, and cardiac
death) related to renal angiography and revascularization,
the widespread practice of screening elderly patients with
resistant hypertension for ARAS and performing renal
revascularization has been questioned.63
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© 2012 Macmillan Publishers Limited. All rights reserved
FOCUS ON HYPERTENSION
Table 1 | Psychotropic medications that can affect BP
Drug Effect(s) on BP
Tricyclic antidepressants
Amitriptyline, clomipramine, doxepin, Postural hypotension
imipramine
Desipramine, notriptyline Hypertension
Amoxapine Increased BP or postural hypotension
Third-generation antidepressants
Nefazodone, trazodone Hypotension
Bupropion Mild hypertension
Serotonin–norepinephrine reuptake inhibitors (SNRIs)
Venfalaxine Severe hypertension possible at high doses
Duloxetine Mild hypertension possible
Monoamine-oxidase inhibitors
Isocarboxazid, phenelzine Hypotension; hypertension with dietary
interactions
Tranylcypromine Hypotension and hypertension
Neuroleptics
Chlorpromazine, clozapine, fluphenazine, Hypotension
olanzapine, risperidone, thioridazine
Stimulants
Dextroamphetamine, methylphenidate Hypertension
Benzodiazepines
Clonazepam, diazepam Can lower BP; withdrawal can elevate BP
Abbreviation: BP, blood pressure.
The aim of the ongoing Cardiovascular Outcomes
in Renal Atherosclerotic Lesions (CORAL) trial 64 is to
determine whether optimal revascularization of patients
with ARAS and hypertension prevents cardiovascular
and renal events when added to optimal medical therapy.
Pending the results of this trial (final collection of data
is planned for 2012),65 renal revascularization should be
performed only in the subset of patients with ARAS and
resistant hypertension, evidence of rapidly progressive
deterioration in renal function, acute kidney injury,66 or
‘flash’ pulmo­nary edema.67
Patient evaluation
The evaluation of elderly individuals for hypertension
is generally similar to that recommended for younger
adults, with some exceptions 25,68 because increased
arterial stiffness in the elderly can lead to erroneous
diagnoses. The phenomenon of ‘pseudohypertension’ is
defined as a falsely increased systolic BP that results from
failure of stiff arteries to collapse during BP cuff infla-
tion. Pseudohypertension should be suspected in elderly
individuals with resistant hypertension, no organ damage,
symptoms of overmedication, or all three.69 Diagnosis of
pseudohypertension is necessary to avoid overtreating
BP in elderly patients with hypertension. Definitive diag­
nosis of pseudohypertension requires direct intra-arterial
measurement of BP, an invasive procedure that adds cost
and risk to patient evaluation.70 The Osler maneuver,
which involves occlusion of the radial or brachial artery
manually or by cuff pressure, followed by palpation of the
REVIEWS
pulseless artery distal to the occlusion, is a bedside proce-
dure that can be used in an attempt to diagnose pseudo­
hypertension.71 A positive Osler sign might suggest that
systolic BP is overestimated by cuff BP measurement.
However, this bedside maneuver cannot quantify the
extent of the overestimation, and thus cannot determine
the true BP of the patient.
Other anomalies in BP that are common among the
elderly, and of which the physician should be aware,
include postural and postprandial hypotension. Postural
hypotension, defined as a decrease in systolic BP of
≥20 mmHg or a decrease in diastolic BP of ≥10 mmHg
within 3 min of standing, is common in the elderly and
can result from blunting of the carotid baroreflex owing
to increased stiffness of the carotid arteries. Treatment-
induced symptomatic postural hypotension can limit
therapeutic options for elderly patients with hyper­tension,
as well as reduce quality of life and cause life-threatening
events, such as falls.25 BP should be measured with the
patient standing for 1–3 min to determine whether pos-
tural hypotension is present. Postprandial hypo­tension,
defined as a decrease in systolic BP of ≥20 mmHg or
a decrease to <90 mmHg from a systolic pressure of
≥100 mmHg within 2 h after a meal, is a common and
often unrecognized cause of hypotension among the
elderly.72–74 Postprandial hypotension should be sus-
pected in any elderly patient presenting with syncope or
falls and clinicians should inquire whether the patient
experiences symptoms of hypotension after meals, espe-
cially in patients with Parkinson disease, diabetes, or end-
stage renal disease.72 The principal cause of postprandial
hypotension is inadequate compensation for the normal
physiological decrease in BP after meals (that is, a blunted
sympathetic response to hypotension).72 Diagnosis is
made by ambulatory BP monitoring (ABPM) timed to
include at least one meal that the patient considers most
symptomatic. Treatment includes both nonpharmaco­
logical and pharmacological options. Medications
known to cause hypovolemia, such as diuretics, should
be avoided or used with extreme caution, as they can
exacerbate postprandial hypotension. Pharmacological
agents used to treat postprandial hypotension, such as
α‑glucosidase inhibitors, have common adverse effects
and are poorly tolerated by many patients. Further
research is needed to identify more-effective therapies
with acceptable adverse effect profiles.
Because most elderly patients with hypertension are
already in the health-care system, a vigorous attempt to
obtain old medical records, including laboratory tests
and evidence of previous treatment, should be made.
This information can minimize costs and burden to the
patients by reducing unnecessary and repetitive diag­
nostic tests and reintroduction of therapies that had been
previously tried without benefit, with adverse effects, or
both, that might not be recalled by the patient. History
taking and laboratory evaluation should be directed
towards identifying evidence of target organ damage,
concomitant CVD risk factors, and secondary causes
of hyper­tension, all of which are more common in the
elderly than in younger patients.
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© 2012 Macmillan Publishers Limited. All rights reserved
As in the general population, diagnosis of hyper­tension
in elderly patients is made on the basis of office BP mea-
surements.25,68 However, guidelines generally advocate
the additional use of home BP monitoring and ABPM.
In 2011, the UK National Institute for Health and Clinical
Excellence (NICE) guidelines mandated that diagnosis of
hypertension be confirmed by 24 h ABPM, which should
be performed, if tolerated, in all patients with elevated
office BP.75 ABPM is useful in diagnosing white-coat
hypertension, in which BP is persistently elevated in the
office setting, but controlled at home or in other out-
of-office environments, as well as masked hypertension,
in which BP is controlled in the office setting, but elevated in
out-of-office environments.76–78 Home BP monitoring and
ABPM are particularly useful in diagnosing excessive BP
reduction in the ambulatory setting resulting from over-
zealous treatment, a frequent occurrence in the elderly
because the white-coat effect (difference between elevated
office systolic BP and lower home BP) increases progres-
sively with age.76 These excessive home BP reductions can
be particularly dangerous in the fragile elderly.
Treatment
General considerations
Guidelines differ in thresholds and goals for anti­
hypertensive therapy in the elderly because of a paucity
of high-level evidence from randomized controlled
trials and inconsistencies in the definition of ‘elderly’.
Guideline groups and expert consensus panels have,
therefore, used data from systematic reviews and meta-
analyses, subgroup analyses from trials in which both
elderly and younger patients were enrolled, and expert
opinion to recommend thresholds and goals for BP
treatment in the elderly. The NICE guidelines for clini-
cal management of primary hypertension in adults75
recommend anti­hypertensive-drug treatment for indivi­
duals aged <80 years with stage 1 hypertension (BP
140–159/90–99 mmHg) only in the presence of target
organ damage, antecedent CVD, CKD, diabetes, or a
10‑year CVD risk ≥20%. These guidelines recommend
drug treatment for people of any age with stage 2 hyper-
tension (BP >160/100 mmHg).75 The ACC Foundation/
AHA guidelines propose a threshold of 140/90 mmHg
for individuals aged 65–79 years and a systolic BP thresh-
old of 150 mmHg for those aged >80 years, regardless
of comorbidities and level of cardio­vascular risk.25 The
NICE guidelines propose target BPs of <140/90 mmHg
for those aged <80 years, and <150/90 mmHg for those
aged ≥80 years,75 whereas the ACC Foundation/AHA
proposes a systolic BP target of <140/90 mmHg for
those aged 65–80 years and a target of 140–145 mmHg
with an upper limit of 150 mmHg, if tolerated, as “rea-
sonable” for those aged >80 years.25 The paucity of data
from clinical trials to support the latter recommendation
was, however, acknowledged in the ACC Foundation/
AHA report.25
The benefits and risks of antihypertensive therapy
compared with placebo in persons aged ≥80 years have
been specifically tested in only one randomized con-
trolled trial. In the Hypertension in the Very Elderly

Trial (HYVET),79 3,845 patients in this age group with
systolic BP ≥160 mmHg were randomly assigned to the
thiazide diuretic indapamide with or without the ACE
inhibitor perindopril or to placebo to achieve a target
BP of <150/80 mmHg. The trial was stopped early (after
2 years) because of benefit in the active-treatment group.
Antihypertensive treatment was associated with signifi-
cant reductions in all-cause mortality (21%), heart failure
(64%), fatal stroke (39%), and mean BP (15.0/6.1 mmHg)
compared with placebo. Nonsignificant reductions in
fatal or nonfatal stroke (30%) and cardiovascular death
(23%) were also observed. Interestingly, the incidence
of dementia or cognitive dysfunction was not reduced,
perhaps because of the brief duration of follow-up.80
In early 2012, outcomes for short-term and long-term
follow up were analyzed in a subgroup of 1,712 HYVET
participants who enrolled in a 1 year, open-label, active-
treatment extension of the trial.81 Participants randomly
assigned to receive active BP-lowering treatment contin-
ued taking the active drug, and those originally assigned
to placebo received the medications used in the main
trial, indapamide (sustained release) 1.5 mg (plus per-
indopril 2–4 mg if required), with the same target BP
(<150/80 mmHg). After 6 months, BP was similar in both
groups and no significant differences were seen for stroke
or cardiovascular events. However, the between-group
differences in total mortality and cardiovascular mortal­
ity seen in the main trial remained significant during
the extension, suggesting that medical treatment of very
elderly patients with hypertension provides benefits in
both the short-term and the long-term.81
Despite these impressive treatment benefits, HYVET
has been criticized on a number of grounds. First, the
results cannot easily be generalized to the entire elderly
population, since frail and medically comprised indivi­
duals were excluded from the trial. Second, the vast
majority of participants were enrolled from Eastern
Europe and China, where patient characteristics and
health-care systems differ from those in the USA and
Western Europe. Third, individuals with stage 1 hyper-
tension were excluded from the study. Finally, the investi­
gators did not attempt to define the optimal BP goal for
reducing cardiovascular events and mortality.25
Several randomized controlled trials designed to assess
whether treatment to more-aggressive systolic BP targets
in populations of elderly participants, or including a sub-
group of elderly patients, yielded conflicting results.82–84
Cardio‑Sis82 was an open-label randomized trial in which
the effects of tight BP control (systolic BP <130 mmHg)
were compared with those of usual BP control (sys-
tolic BP <140 mmHg) on an intermediate end point—
electrocardiographic left ventricular hypertrophy—and
on cardiovascular events in 1,111 adults aged ≥55 years
who had at least one additional cardiovascular risk factor
other than diabetes or CKD. After 2 years of follow-up,
a significant reduction in left ventricular hypertrophy
(P = 0.013) was observed, but no difference was seen in
any cardio­vascular outcome other than coronary revas-
cularization procedures, which were significantly reduced
(P = 0.032) in the tight control group.82
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© 2012 Macmillan Publishers Limited. All rights reserved
FOCUS ON HYPERTENSION
The Japanese Trial to Assess Optimal Systolic Blood
Pressure in Elderly Hypertensive Patients (JATOS)83 was a
randomized study in which the effects of strict BP control
(systolic BP <140 mmHg) were compared with mild BP
control (systolic BP ≥140 mmHg to <160 mmHg) on
cardio­vascular events in 4,418 Japanese adults with hyper-
tension and aged 65–85 years. After 104 weeks of follow-
up, no differences were recorded between groups in any
cardiovascular outcome.83
In the Action to Control Cardiovascular Risk in
Diabetes (ACCORD) blood-pressure trial,84 the effect of
a target systolic BP <120 mmHg was compared with the
standard target of <140 mmHg on major cardiovascular
events among high-risk persons aged 40–79 years (mean
age 62 years) with diabetes. Except for stroke, which was
significantly reduced (P = 0.01) in the intensive-­treatment
group, no significant differences in fatal and nonfatal
major cardiovascular events were reported between
groups. However, significantly more serious adverse
events occurred in the intensive-treatment than the stan-
dard-treatment group (P <0.001).84 Thus, published studies
have not produced convincing evidence of the benefits of
aggressive BP lowering in the older, high-risk population.
The investigators of the ongoing SPRINT trial57 are
enrolling an enriched population of 3,250 patients aged
≥75 years with hypertension to test the hypothesis that
aggressive BP treatment (systolic BP goal <120 mmHg)
will reduce cardiovascular and renal outcomes and delay
the progression of cognitive decline and the develop-
ment of dementia and small vessel ischemic disease of
the brain in the elderly population. Pending the results
of SPRINT, which are expected to be available in 2018,
little enthusiasm currently exists for attempting to lower
BP to <120 mmHg with pharmacological antihypertensive
therapy in elderly patients. In all guidelines, the recom-
mendation is to lower BP with a combination of medi-
cations and lifestyle modification in elderly patients with
hypertension. Specific thresholds and goals for treatment
differ among guidelines, as discussed above.
Nonpharmacological treatment
Nonpharmacological treatment, including lifestyle
modification, has been shown to benefit all patients
with hypertension, including the elderly, by lowering
BP, modifying other CVD risk factors, and reducing the
number and doses of antihypertensive drugs needed for
BP control.25,85–93 Some interventions, such as dietary salt
reduction, are more effective for lowering BP in the elderly
than in younger adult patients with hyper­tension.94 In the
Trial of Nonpharmacologic Interventions in the Elderly
(TONE),94 carried out in 681 patients aged 60–80 years
with hypertension, reduction of dietary sodium to
80 mmol (2 g) per day reduced BP over 30 months
compared with a control group. Approximately 40% of
patients on the low-salt diet were able to discontinue their
antihypertensive medications.94 Older persons should also
be encouraged to avoid excessive alcohol intake.95 Despite
these benefits, nutrition and exercise counseling is less-
often provided to elderly patients with hypertension than
to their younger counter­parts.96 This difference could
REVIEWS

Table 2 | Antihypertensive drugs commonly used in the elderly*

Drug class/drug Differences from pharmacokinetics in younger Dosage adjustment
patients
Aldosterone-receptor blockers
Eplerenone, spironolactone Unknown No initial adjustment needed
Angiotensin-II-receptor blockers
Candesartan, eprosartan, Eprosartan clearance reduced; no relevant No adjustment needed
irbesartan, losartan, olmesartan, differences in irbesartan half-life; valsartan half-life
telmisartan, valsartan increased
Angiotensin-converting-enzyme inhibitors
Benazepril Half-life increased, clearance reduced No adjustment needed
Captopril, enalapril No relevant difference in half life; clearance reduced Initiate at lowest dose; titrate to response
Fosinopril, quinapril, trandolapril Unknown No adjustment needed
Lisinopril Half-life increased, clearance reduced Initiate at lowest dose; titrate to response
Perindopril Clearance reduced Initiate at lowest dose; titrate to response
Ramipril Unknown Initiate at lowest dose; titrate to response
Centrally acting α-adrenergic agonists
Guanfacine Half-life increased, clearance reduced Initiate at lowest dose; titrate to response
Peripherally acting α1-selective adrenergic antagonists
Doxazosin Half-life increased, volume of distribution increased Initiate at lowest dose; titrate to response
Prazosin, terazosin Half-life increased Initiate at lowest dose; titrate to response
Nonselective β-adrenergic blockers, without ISA
Nadolol No relevant difference in half life Initiate at lowest dose; titrate to response
Propranolol Half-life increased, clearance reduced Initiate at lowest dose; titrate to response
Selective β1-adrenergic blockers, without ISA
Atenolol Half-life increased, no relevant difference in volume Initiate at lowest dose; titrate to response
of distribution, clearance reduced
Metoprolol No relevant differences Initiate at lowest dose; titrate to response
Selective β1-adrenergic blockers, with ISA
Acebutolol Half-life increased, volume of distribution decreased Initiate at lowest dose; titrate to response
Dual-acting agents
Carvedilol Unknown Initiate at lowest dose; titrate to response
Labetalol No relevant difference in clearance Initiate at lowest dose; titrate to response
Nebivolol Unknown No adjustment needed
Calcium antagonists
Amlodipine Half-life increased, clearance reduced Initiate at lowest dose; titrate to response
Diltiazem, nifedipine, verapamil Half-life increased, no relevant difference in volume Initiate at lowest dose; titrate to response
of distribution, clearance reduced
Felodipine No relevant difference in volume of distribution, Initiate at lowest dose; titrate to response
clearance reduced
Nicardipine No relevant difference in half-life No initial adjustment needed
Loop diuretics
Bumetanide No relevant difference in volume of distribution No initial adjustment needed
Furosemide Half-life increased, no relevant difference in volume No initial adjustment needed
of distribution
Torsemide Unknown No initial adjustment needed
Potassium-sparing diuretics
Amiloride, triamterene Half-life increased Initiate at lowest dose; titrate to response
Thiazide diuretics
Chlorthalidone, hydrochlorothiazide Half-life increased, clearance reduced Initiate at lowest dose; titrate to response
Indapamide No relevant differences No adjustment needed
Abbreviation: ISA, intrinsic sympathomimetic activity

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© 2012 Macmillan Publishers Limited. All rights reserved

be related to a higher percentage of debili­tated persons
among the elderly population, or it could reflect failure of
practitioners to recognize the benefits of modifying diet
and activity in older patients.97
Pharmacological treatment
Special considerations in the choice of antihyperten-
sive treatment in elderly patients include age-related
physio­logical characteristics that influence the absorp-
tion, distribution, metabolism, and excretion of drugs
(Table 2),25,98,99 as well as the presence of comorbidities,
such as diabetes, heart failure with both preserved and
reduced left ventricular function, atrial fibrillation, and
CKD, which are highly prevalent in the elderly. Such
comorbidities dictate the need for vigilance to avoid
treatment-related adverse effects, such as electrolyte dis-
turbances, deterioration in renal function, and excessive
orthostatic BP decline.25 Because of these concerns, the
general recommendation is to initiate antihypertensive
drugs in the elderly at low doses, with gradual up-titra-
tion to the maximum tolerated dose depending on the BP
response.25,68 A second agent from a different class should
be added if the BP response to the initial medication is
inadequate after reaching the full dose (not necessarily
the maximum recommended dose). If no therapeutic
response occurs, or in the presence of substantial adverse
effects, a medication from another class should be sub-
stituted. Nonadherence to BP medications, drug inter-
actions, secondary hypertension, and pseudoresistance
to antihypertensive drugs (that is, the apparent lack of
BP control caused by inaccurate measurement of BP,
inappropriate drug choices or doses, nonadherence to
prescribed therapy, or the white-coat effect) need to be
considered before adding another agent.
Numerous randomized controlled trials have shown
substantial reductions in cardiovascular outcomes with
antihypertensive-drug therapy in cohorts of patients aged
60–79 years.100,101 Although elderly patients with hyper­
tension are at higher absolute risk and derive greater
absolute risk reduction from antihypertensive treatment
than younger individuals, data from randomized con-
trolled trials indicate that elderly and younger patients
with hypertension derive similar relative benefit from BP
reduction.101 The Blood Pressure Lowering Treatment
Trialists’ Collaboration compared the relative reductions
in BP and CVD risk achieved with various BP-lowering
regimens in younger (<65 years) and older (≥65 years)
adults in a meta-analysis that included 31 trials with a
total of 190,606 partici­pants.101 Comparisons included
active treatments versus placebo, more-intensive versus
less-intensive BP-lowering regimens, and comparisons
between different drug classes and combinations in
the older and younger age groups. No significant age-
dependent differences between the effects of the drug
classes on BP reduction or major cardio­vascular events
were observed. Moreover, no significant interaction
between age and the effects of treatment were seen when
age was considered as a continuous variable and overall
effects were estimated across trials. The risk reduction
and the unit reduction in BP for the primary outcome
NATURE REVIEWS | CARDIOLOGY VOLUME 9  |  MAY 2012  |  293
© 2012 Macmillan Publishers Limited. All rights reserved
FOCUS ON HYPERTENSION
Age <80 years Age ≥80 years
Office BP ≥140/90 mmHg Office BP ≥160/100 mmHg
and ABPM ≥135/85 mmHg and ABPM ≥150/95 mmHg
and ≥1 of the following: target organ
damage, established cardiovascular
disease, renal disease, diabetes mellitus,
a 10-year cardiovascular risk ≥20%
BP goals
Office BP<140/90 mmHg in people aged <80 years with treated hypertension
Office BP<150/90 mmHg in people aged ≥80 years with treated hypertension
Step 1
Treatment with a CCB in people aged >55 years and black people of African or Caribbean
origin of any age*
Step 2
Treatment with a CCB* in combination with either an ACEI or an ARB‡
Step 3
Review medication to ensure step 2 treatment is at optimal or best-tolerated doses
If treatment with three drugs is required, the combination of ACEI
or ARB + CCB + thiazide-like diuretic should be used
Step 4
Consider adding a fourth antihypertensive drug and/or seeking expert advice
Consider further diuretic therapy with low-dose spironolactone if K+ ≤4.5 mmol/l
Consider higher-dose thiazide-like diuretic treatment if K+ >4.5 mmol/l
If further diuretic therapy is not tolerated, or is contraindicated or ineffective,
consider an α-blocker or β-blocker
Figure 3 | Algorithm for treatment of hypertension in the elderly according to the
2011 NICE guideline recommendations.75 *If a CCB is not suitable for treatment, for
example because of edema or intolerance, or if evidence or a high risk of heart
failure exists, offer a thiazide-like diuretic (preference for chlortalidone or
indapamide). ‡For people of African or Caribbean family origin, consider an ARB in
preference to an ACEI, in combination with a CCB. Abbreviations: ABPM, ambulatory
blood pressure monitoring; ACEI, angiotensin-converting-enzyme inhibitor;
ARB, angiotensin-receptor blocker; BP, blood pressure; CCB, calcium-channel
blocker; NICE, National Institute for Health and Clinical Excellence.
of major cardiovascular events, or for any secondary
outcome, was similar in the two age groups. The Trialists
concluded that BP reduction is beneficial in both younger
and older adults, with no evidence that protection against
major cardiovascular events afforded by various drug
classes varies substantially with age.
Current recommendations of the European Society
of Hypertension (ESH)/European Society of Cardiology
(ESC),102,103 the Seventh Report of the Joint National
Committee on prevention, detection, evaluation, and
treatment of high blood pressure (JNC 7),68 and the ACC
Foundation/AHA 25 are consistent with the Trialists’
analy­sis. These guidelines recommend initiating anti­
hypertensive treatment in both elderly and younger
patients with either a calcium-channel blocker (CCB),
a thiazide-type diuretic, an ACE inhibitor or ARB, or a
β‑blocker. This approach embraces the concept that the
benefits of antihypertensive treatment are largely attribu­
table to BP lowering per se and that all classes of anti-
hypertensive drugs that have been shown to lower BP
REVIEWS

effectively and to reduce cardiovascular outcomes are
suitable for the initi­ation and maintenance of antihyper-
tensive therapy.100,101 The choice of agent for each indi-
vidual patient is dictated by efficacy, tolerability, presence
of specific comorbidities, and cost.
By contrast, the NICE guidelines recommend that drug
choices be made on the basis of patient age, with CCBs
or (for those intolerant of CCBs) thiazide-like diuretics
preferred as initial therapy for patients aged >55 years,
whereas ACE inhibitors (or ARBs for those who are ACE-
inhibitor intolerant) are preferred for younger patients
(Figure 3).75 These guidelines recommend specifically
that more-potent and longer-acting thiazide-like diuretics
(chlorthalidone 12.5–25.0 mg daily or indapamide 2.5 mg,
or 1.5 mg modified release, daily) be used in preference to
conventional thiazide diuretics (such as hydrochlorothia-
zide or bendroflumethiazide), on the basis of data from
randomized controlled trials, and that β‑blockers not be
used as first-line treatment in older patients. The NICE
guidelines refer to evidence from randomized controlled
trials that traditional β‑blockers, particularly atenolol,
are ineffective in lowering BP and preventing cardio­
vascular outcomes in the elderly.104–108 The NICE guide-
lines recommend that β‑blockers be reserved as fifth-line
therapy for patients who fail to achieve BP control on a
quadruple combination of an ACE inhibitor or ARB, a
CCB, a thiazide-­like diuretic, and spironolactone.75 Newer
β‑blockers, such as carvedilol and nebivolol, that promote
vasodilatation by improving endothelial function could
provide outcome benefits not seen with traditional
β‑blockers, although they have not yet been tested in
outcome trials in elderly patients with hypertension.
Conclusions
Hypertension is highly prevalent among older adults and
aging of the population will further increase the preva-
lence of this condition worldwide. Assessment of the
concomitant use of medications that interfere with BP
control, especially NSAIDs, as well as secondary causes of
hypertension, such as CKD, OSA, and ARAS, is essential
in the evaluation of elderly patients with hypertension.
Medical treatment of hypertension in the elderly popula-
tion reduces cardiovascular morbidity and mortality, and
all guidelines recommend treating elderly people with
hypertension with lifestyle modifications in addition to
antihypertensive medications. However, guidelines differ
in thresholds and goals for antihypertensive therapy in
the elderly because of inconsistencies in the definition
of ‘elderly’ and a paucity of high-level evidence from
randomized controlled trials, both of which should be
addressed in future research.
Review criteria
We searched the PubMed database using the terms
“hypertension”, “blood pressure”, “elderly”, and
“ageing”. Only full-text papers published in English since
1934 were considered.

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Author contributions
Both authors researched data for the article,
contributed to the discussion of the content, wrote the
article, and reviewed/edited the manuscript before
submission.