Treatment of hypertension in older adults,

particularly isolated systolic hypertension

Author: Brent M Egan, MD
Section Editors: George L Bakris, MD, Kenneth E Schmader, MD, William B White, MD
Deputy Editors: John P Forman, MD, MSc, Lisa Kunins, MD

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is
complete.

Literature review current through: Aug 2019. | This topic last updated: Jul 01, 2019.

INTRODUCTION

Hypertension is a common problem in older adults (age greater than 60 to 65

years), reaching a prevalence as high as 70 to more than 80 percent [1-3]. In the
United States, for example, hypertension, defined as systolic blood pressure ≥130
mmHg and/or diastolic blood pressure ≥80 mmHg was observed in 76 percent of
adults aged 65 to 74 years and 82 percent of adults aged 75 years or older who
were participants in the National Health and Nutrition Examination Survey
(NHANES) [1].

Hypertension control rates are lower among older patients. In the same study
mentioned above, control of blood pressure to <130/<80 mmHg among those
taking antihypertensive drug therapy was achieved by 54, 50, 46, and 33 percent of
individuals aged 20 to 54 years, 55 to 64 years, 65 to 74 years, and 75 or more
years, respectively [1].

A related issue is the risk of developing hypertension over time in an older adult
who is normotensive. This issue was addressed in two reports from the
Framingham Heart Study that defined hypertension as a systolic pressure ≥140
and/or a diastolic pressure ≥80 mmHg:

● One study examined the incidence of hypertension (defined as blood pressure

greater than 140/90 mmHg or use of antihypertensive drug) over a four-year
period among individuals who initially had optimal (less than 120/80 mmHg),
normal (120 to 129/80 to 84 mmHg), or high-normal (130 to 139/85 to 89
mmHg) blood pressure [4]. There was a progressive increase in the frequency
of development of hypertension in patients over age 65 years (16, 26, and 50
percent in the optimal, normal, and high-normal groups, respectively). Similar
findings were noted in younger individuals, but the rates of progression were
lower.

● The second report estimated that individuals aged 55 to 65 years who do not
have hypertension have a 90 percent lifetime risk of developing mild
hypertension (blood pressure 140 to 159/90 to 99 mmHg) and a 40 percent
lifetime risk of developing more severe hypertension (blood pressure ≥160/
≥100 mmHg) [5].

Isolated systolic hypertension and the efficacy of antihypertensive drug therapy in

older adults are presented in this topic. The diagnosis and evaluation of
hypertension and our recommendations about goal blood pressure are discussed
elsewhere. (See "Overview of hypertension in adults" and "Initial evaluation of the
hypertensive adult" and "Goal blood pressure in adults with hypertension".)

ISOLATED SYSTOLIC HYPERTENSION

Isolated systolic hypertension (ISH) has often been defined as a systolic blood
pressure above 160 mmHg, with a diastolic blood pressure below 90 mmHg [6-8].
However, using definitions from the 2017 American College of
Cardiology/American Heart Association Blood Pressure Guideline [2], a systolic
pressure of 130 mmHg is the upper limit of normal at all ages.

ISH mostly occurs in older patients. Data from the Framingham Heart Study and
the National Health and Nutrition Examination Survey (NHANES) have shown that
the systolic pressure rises and the diastolic pressure falls after age 60 years in
both normotensive and untreated hypertensive subjects [9] and that ISH accounts
for 60 to 80 percent of cases of hypertension in older adults [10,11]. Furthermore,
the systolic and pulse pressures appear to be the major predictors of coronary
disease in older adults; in contrast, diastolic pressure is the major predictor under
age 50 years, and all three indices were equal predictors between the ages of 50
and 59 years [12].

The elevation in pulse pressure in patients with ISH is primarily due to diminished
arterial compliance. ISH may also result from an increase in cardiac output due to
anemia, hyperthyroidism, aortic insufficiency, arteriovenous fistula, or Paget
disease of bone [13].

ISH (when defined as a systolic pressure ≥140 mmHg) is associated with a two- to
fourfold increase in the risk of myocardial infarction, left ventricular hypertrophy,
renal dysfunction, stroke, and cardiovascular mortality [14,15]. Even in patients
who also have diastolic hypertension, the cardiovascular risk correlates more
closely with the systolic than the diastolic blood pressure [16].

Importance of diastolic pressure — Among older adults, coronary heart disease

risk varies directly with the systolic and pulse pressures and inversely with the
diastolic pressure (ie, lower diastolic pressures are associated with increased risk)
[6,12,17,18]. (See "Goal blood pressure in adults with hypertension".)

The relative importance of the systolic, diastolic, and pulse pressures is different
in younger patients [12,17]. (See "Increased pulse pressure".)
However, the observations concerning worse outcomes in older adult patients with
lower diastolic pressures primarily came from population studies or from baseline
blood pressures in clinical trials, not after treatment in clinical trials. In the SHEP
trial, for example, the mean baseline blood pressure was 170/77 mmHg and the
attained blood pressure was 143/68 mmHg in the treated group and 155/72 in the
placebo group; the mean age was 72 years [19]. Despite the low attained diastolic
pressure, the treated group had significantly better outcomes, including fewer
coronary heart disease events. A similar mean systolic blood pressure and higher
diastolic blood pressure (143/78 mmHg) were attained in the treated group in the
HYVET trial of the very old (mean age 84 years) [20]. (See 'SHEP trial' below and
'HYVET trial' below.)

When treating older adult patients with isolated systolic hypertension, there are no
clear data that provide guidance related to the minimum diastolic blood pressure
that can be tolerated. An analysis from the SHEP trial found significant increases
in cardiovascular events in the active treatment group when the diastolic blood
pressure was ≤60 mmHg [21]. In other reports of treated patients, an increase in
risk of stroke began at diastolic pressures below 65 mmHg in a report from the
observational Rotterdam study [22] and, in the INVEST trial of hypertensive
patients with coronary artery disease who were randomly assigned to a verapamil-
or atenolol-based strategy, an increased risk of myocardial infarction that began at
diastolic pressures between 61 and 70 mmHg and increased approximately 2.5-
fold further at diastolic pressures ≤60 mmHg [23].

These observations do not prove a cause-and-effect relationship between lower

diastolic pressures and adverse outcomes. In a meta-analysis that included two
trials of isolated systolic hypertension, a J-shaped curve for mortality was noted
with both systolic pressure (figure 1) and diastolic pressure (figure 2) [24].
However, a J-curve was seen in treated and untreated patients and was not
specific for cardiovascular mortality. The authors concluded that the J-curve is
probably explained by poor health associated with lower blood pressures, not an
adverse effect of antihypertensive therapy.

In summary, although adverse outcomes that can be ascribed only to excessive

blood pressure lowering with antihypertensive drugs are probably not common in
patients with isolated systolic hypertension, cardiovascular events can occur if the
diastolic pressure is reduced below the level needed to maintain perfusion to vital
organs, particularly the heart. We suggest a minimum posttreatment diastolic
pressure, when using typical office-based measurements, of 60 mmHg overall.
(See 'Goal blood pressure' below.)

EVIDENCE FOR EFFICACY OF BLOOD PRESSURE LOWERING

Treatment of hypertension in all patients, independent of age, consists of lifestyle

modifications and antihypertensive therapy.

Lifestyle modifications — As in younger patients, lifestyle modifications (eg,

dietary salt restriction, weight loss in obese patients) can lower the blood pressure
in older adult patients with hypertension. In particular, dietary sodium intake
should be moderately restricted to 100 to 120 mEq/day (2300 to 2800 mg/day)
since the pressor effect of sodium excess and the antihypertensive efficacy of
sodium restriction progressively increase with age [25]. (See "Overview of
hypertension in adults", section on 'Nonpharmacologic therapy' and "Diet in the
treatment and prevention of hypertension".)

The efficacy of salt restriction and weight loss in hypertensive older adult patients
was demonstrated in the TONE trial of 975 older persons (aged 60 to 80) who had
a blood pressure <145/<85 mmHg on one antihypertensive drug; 585 were obese
[26]. The patients were randomly assigned to usual care or to salt restriction,
weight loss (in obese patients), or both. Those assigned to salt restriction had a
40 mEq/day decrease in sodium excretion while, in obese patients, a regimen of
diminished caloric intake and increased physical activity was associated with a
persistent weight loss of 4.7 kg; these parameters were unchanged in the usual
care group. After three months of intervention, withdrawal of the antihypertensive
drug was attempted.

The primary endpoint was a diagnosis of high blood pressure at one or more
follow-up visits, treatment with antihypertensive drugs, or a cardiovascular event.
The reduction in blood pressure compared with usual care were 2.6/1.1 mmHg
with salt restriction, 3.2/0.3 mmHg with weight loss, and 4.5/2.6 mmHg with
combined therapy. The primary endpoint at 30 months occurred significantly less
often with salt restriction (62 versus 76 percent with usual care), weight reduction
in obese subjects (61 versus 74 percent), and combined salt restriction and weight
reduction in obese subjects (56 versus 84 percent).

Older patients may have difficulty complying with dietary salt restriction for two
reasons:

● They may ingest more salt to compensate for a decrease in taste sensitivity.

● They may depend more upon processed, prepackaged foods that are high in
sodium rather than fresh foods that are low in sodium.

Antihypertensive therapy — Randomized trials have provided clear evidence of

benefit from treating hypertension in older adult patients, including those over the
age of 80 years (table 1) [6,19,20,27-30]. Most of these trials involved patients with
isolated systolic hypertension, but some had diastolic hypertension. In addition,
trials of patients with diastolic hypertension included some older adult patients.

Meta-analysis — A 2000 meta-analysis included eight outcome trials of 15,693

patients ≥60 years of age with isolated systolic hypertension (including SHEP,
Syst-Eur, and MRC described below) [6]. At a median follow-up of 3.8 years, the
number of patients who needed to be treated for five years to prevent one major
cardiovascular event was 26. The number needed to be treated was lower in men
(18 versus 38 in women [percent of patients benefitting 5.6 and 2.6 percent,
respectively]), patients aged 70 or more years (19 versus 39 in patients under age
70 years [percent of patients benefitting 5.3 and 2.6 percent, respectively]), and
those with previous cardiovascular events (16 versus 37 without such a history
[percent of patients benefitting 6.3 and 2.6 percent, respectively]).

Total mortality correlated directly with systolic blood pressure at study entry, but
inversely with diastolic blood pressure. However, the diastolic blood pressure was
not significantly associated with outcome for combined fatal and nonfatal events.

These results underestimate the true benefit of effectively treating versus not
treating isolated systolic hypertension, as illustrated by findings in the SHEP trial
described in the next section [19]. Only approximately 70 percent of treated
patients reached goal blood pressure during the study, yet the outcomes of the
nonresponders were included in the analysis. In addition, increases in blood
pressure necessitated the institution of antihypertensive medications in 13
percent of placebo-treated patients at one year and 44 percent at five years.

The trials in the meta-analysis all had baseline mean systolic pressures of 160
mmHg or more [6]. In addition, these trials failed to achieve a systolic pressure
less than 140 mmHg, although two trials with favorable outcomes attained a
mean systolic pressure between 140 and 145 mmHg. No trials have been
performed in patients with isolated systolic hypertension with baseline systolic
pressures of 140 to 159 mmHg [31]. This evidence gap led the majority of
committee members appointed to the eighth Joint National Committee (JNC-8) to
recommend a treatment goal of less than 150/90 mmHg in adults aged 60 years
and older who do not have diabetes or chronic kidney disease (the goal was less
than 140/90 mmHg among patients with diabetes or chronic kidney disease) [32].

SHEP trial — The Systolic Hypertension in the Elderly Program (SHEP) trial

included 4376 older adult patients (mean age 72 years) with a mean blood
pressure of 170/77 mmHg at baseline [19]. The patients were randomly assigned
to antihypertensive therapy or placebo; the aim of therapy was at least a 20 mmHg
reduction in systolic pressure to a level below 160 mmHg. Treatment began with
12.5 mg/day of chlorthalidone, which was then increased to 25 mg/day if
necessary. Almost one-half of patients reached goal pressure solely with low-dose
chlorthalidone. Atenolol or reserpine was added if a further antihypertensive
response was required.

The attained blood pressures were 143/68 mmHg with active therapy and 155/72
mmHg with placebo. Despite the potential risk of the relatively low diastolic
pressures, the incidence of stroke at four to five years was significantly lower in
treated patients (5.5 versus 8.2 percent with placebo) (figure 3). A similar one-third
to one-quarter reduction was noted in the incidence of cardiac events, although
this trend was not quite statistically significant [33]. These benefits were noted in
both men and women and in all age groups, including patients over the age of 80
years, who were the focus of the HYVET trial. (See 'HYVET trial' below.)

Further analyses demonstrated that active therapy was associated with a

reduction in left ventricular mass index (-13 versus +6 percent with placebo) [34]
and that the reduction in cardiovascular events was not seen in the 7.2 percent of
patients who developed hypokalemia (serum potassium less than 3.5 mEq/L) [35].

Syst-Eur trial — The Syst-Eur trial randomly assigned 4695 patients over age 59
years (mean age 70 years) with isolated systolic hypertension (mean initial sitting
blood pressure of 174/86 mmHg) to therapy with placebo or nitrendipine plus, if
necessary, enalapril and hydrochlorothiazide [28]. The fall in blood pressure was
greater with active therapy (23/7 versus 13/2 mmHg).

At four years, significant reductions were noted in stroke (7.9 versus 13.7 total
endpoints per 1000 patient-years), and fatal and nonfatal cardiac endpoints. It was
estimated that treatment of 1000 patients for five years would prevent 53
cardiovascular endpoints and 29 strokes. Subgroup analysis found that the
mortality benefit increased significantly with a higher systolic blood pressure at
study entry, fell with increasing age [36], and was more pronounced in patients
with diabetes mellitus [37]. (See "Treatment of hypertension in patients with
diabetes mellitus".)

In a subset of Syst-Eur, the vascular dementia project of over 2400 patients,

antihypertensive therapy significantly lower the incidence of dementia compared
to placebo (3.8 versus 7.7 cases per 1000 patient-years) [38]. It was estimated
that treatment of 1000 patients for five years would prevent 19 cases of dementia.

MRC trial — A Medical Research Council (MRC) trial included 3496 older adult
patients (age 65 to 74 years) with systolic hypertension with or without diastolic
hypertension (mean blood pressure 185/91 mmHg) who were randomly assigned
to one of three regimens: hydrochlorothiazide (25 to 50 mg/day) plus amiloride;
atenolol; or placebo [39]. The patients were followed for a mean of 5.8 years.
Compared to placebo, both treatment groups had a similar reduction in diastolic
pressure. The reduction in systolic pressure was less in the atenolol group for the
first two years, but not thereafter due at least in part to a higher rate of receiving
supplemental antihypertensive drugs.

Hydrochlorothiazide plus amiloride significantly reduced the incidence of stroke,

coronary events, and all cardiovascular events by 31, 44, and 35 percent,
respectively. In contrast, atenolol did not produce significant reductions in these
endpoints. Similar findings have been noted in other trials in which beta blockers
were associated with worse cardiovascular outcomes than other antihypertensive
drugs, an effect that was primarily limited to patients over age 60 years [40,41].

HYVET trial — The benefit of treating hypertension in very old patients was

directly addressed in the HYVET trial [20]. In HYVET, 3845 patients who were at
least 80 years of age (mean age 84 years) and had a sustained systolic blood
pressure of at least 160 mmHg (mean 173/91 mmHg) were randomly assigned to
placebo or the thiazide diuretic indapamide. The angiotensin-converting enzyme
(ACE) inhibitor, perindopril, or matching placebo was added in individuals who
failed to meet the target blood pressure of 150/80 mmHg. At two years, the mean
blood pressure was 15.0/6.1 mmHg lower with active therapy (approximately
143/78 versus 158/84 mmHg).

The primary endpoint was fatal or nonfatal stroke. At two years, active therapy
was associated with a significant reduction in fatal stroke (6.5 versus 10.7
percent) and an almost significant reduction in all strokes (12.4 versus 17.7
percent, p<0.06). Death from all causes was reduced from 59.6 per 1000 persons
per year in the placebo group to 47.2 per 1000 persons per year in the active
treatment group.

The authors suggested that the results of HYVET support a target blood pressure
of less than 150/80 mmHg in treated patients over age 80 years and that the
efficacy of further reductions in blood pressure need to be established.

More versus less intensive blood pressure lowering — Goal blood pressure in

older adults was studied in the Systolic Pressure Intervention Trial (SPRINT). A
detailed discussion of SPRINT is presented in another topic. (See "Goal blood
pressure in adults with hypertension".)

The results from SPRINT in the subgroup of individuals aged 75 years or older are
discussed below. (See 'Goal blood pressure' below.)

DRUG THERAPY

Drug therapy should be started in older adult hypertensive patients if lifestyle

changes are not sufficient.

General principles — A number of issues need to be considered before initiating

antihypertensive drug therapy in older adults (see 'Problem of orthostatic
hypotension' below and 'Problem of frailty' below):
 ● Lower initial doses (approximately one-half that in younger patients) should
be used to minimize the risk of side effects.

● Older adult patients may have sluggish baroreceptor and sympathetic neural
responses, as well as impaired cerebral autoregulation. Thus, in the absence
of a hypertensive emergency or urgency, blood pressure should be lowered to
goal gradually over a period of three to six months rather than hours to days in
order to minimize the risk of ischemic symptoms, particularly in patients with
orthostatic hypotension. This approach is consistent with recommendations
made by the European Society of Hypertension/European Society of
Cardiology [42]. Even more caution is advised in the very old, although the
benefits from careful therapy probably outweigh the risks in these patients
[18,20].

● Many trials showing benefit from the treatment of hypertension in older adults
were performed in relatively fit patients. However, the Systolic Pressure
Intervention Trial (SPRINT) included a large number of community-dwelling
hypertensive older adults (aged 75 years or older) who were less fit or frail at
the time of enrollment. As noted below, the benefits from more intensive
blood pressure lowering were present in fit, less fit, and frail older adult
patients. Thus, while it is important to be cautious and avoid overtreating frail
older adults, this group also appears to benefit from better control of systolic
blood pressure. (See 'Goal blood pressure' below.)

When treating older adults and especially frail older adults hypertensive, extra
caution is appropriate in the setting of significant orthostatic hypotension, as
described in the next section.

Problem of orthostatic hypotension — A potential limiting factor to the use of

antihypertensive drugs is that orthostatic (postural) and/or postprandial
hypotension are found in as many as 20 percent of older adult patients with
isolated systolic hypertension [43,44]. Hypertensive older adults with orthostatic
hypotension are significantly more likely to fall than those without orthostatic
hypotension [45,46]. In addition, antihypertensive treatment in older adult patients
is associated with an increased risk of hip fracture during the first one to two
months following initiation of therapy [47].

As a result, supine and standing pressures should be measured in older adult

patients prior to the initiation of antihypertensive therapy (whether blood
pressures are measured in the office or at home). Orthostatic hypotension is
diagnosed when, within two minutes of quiet standing, one or more of the
following is present:

● At least a 20 mmHg fall in systolic blood pressure

● At least a 10 mmHg fall in diastolic blood pressure

● Symptoms of cerebral hypoperfusion, such as dizziness

Weakness, fatigue, or dizziness following meals may signal postprandial

hypotension, which can be verified by timely measurement of blood pressure. This
is discussed in detail separately. (See "Mechanisms, causes, and evaluation of
orthostatic hypotension".)

Problem of frailty — The randomized trials that showed benefit from the

treatment of hypertension in older adults included relatively fit patients since frail
patients often have difficulty with participation in such trials. Some observational
studies suggest that older adults who are frail may not benefit from
antihypertensive therapy. The following studies illustrate a range of findings:

● In a cohort of 1127 frail nursing home residents from France and Italy (aged
80 years and older), two-year mortality rates were highest among those who
were treated with two or more antihypertensive drugs and had a systolic
pressure less than 130 mmHg (32 percent) [48]. In comparison, mortality was
lower among individuals who had higher blood pressure despite taking two or
 more antihypertensive drugs (20 percent) and among those taking fewer
medications who had systolic pressures above and below 130 mmHg (20 and
18 percent, respectively). The adjusted hazard ratio for death was greater for
those who had a systolic pressure less than 130 mmHg while being treated
with two or more drugs compared with the other three groups (HR 1.78, 95%
CI 1.34-2.37). This association may have been due to a higher prevalence of
heart failure and coronary heart disease among those who had lower systolic
pressure treated with dual therapy (35 versus 14 percent, and 35 versus 18
percent, respectively).

● In an observational study of 2340 adults older than 65 years, the association

between blood pressure and mortality was examined according to whether or
not individuals were frail (defined as an inability to walk 6 meters in less than
8 seconds) [49]. Among frail adults, there was no association between blood
pressure and mortality. In addition, a higher blood pressure was associated
with a lower risk of death among the most frail (ie, those who could not walk
the distance at all). The expected association of a higher blood pressure with
a greater mortality risk was observed among the fit individuals.

However, the Systolic Pressure Intervention Trial (SPRINT) found a similar benefit
from more as compared with less intensive blood pressure lowering in both fit and
frail older adults (aged 75 years or older). These results are presented below. (See
'Goal blood pressure' below.)

Choice of antihypertensive drugs — The 2015 American Heart Association

statement on the treatment of blood pressure in ischemic heart disease, the 2013
European Society of Hypertension/European Society of Cardiology guidelines on
the management of hypertension, and meta-analyses from 2008 and 2009
concluded that the amount of blood pressure reduction is the major determinant
of reduction in cardiovascular risk in both younger and older patients with
hypertension, not the choice of antihypertensive drug [42,50-52]. When differences
in outcomes have been noted, as in the ALLHAT trial, the drug producing better
outcomes had better blood pressure control. (See "Choice of drug therapy in
primary (essential) hypertension", section on 'Importance of attained blood
pressure'.)

This general principle of equivalent efficacy in terms of cardiovascular outcomes

applies to monotherapy but does not appear to apply to combined
antihypertensive therapy. As described below, the combination of an angiotensin
inhibitor and a long-acting dihydropyridine calcium channel blocker appears to
provide a significant reduction in cardiovascular events at the same attained blood
pressure as an angiotensin inhibitor and a thiazide diuretic. (See 'ACCOMPLISH
trial of combination therapy' below.)

ALLHAT trial — The ALLHAT trial of over 41,000 patients with mild hypertension
and at least one other risk factor for coronary heart disease found that low-to-
moderate-dose chlorthalidone (12.5 to 25 mg/day) was associated with fewer
cardiovascular complications than amlodipine and lisinopril [53]. A doxazosin arm
was discontinued early because of a higher rate of adverse outcomes. (See
"Choice of drug therapy in primary (essential) hypertension", section on 'ALLHAT
trial'.)

Approximately 57 percent of the patients were greater than 65 years of age. With
respect to clinical outcomes at follow-up at nearly five years, the following results
were reported in the patients 65 years and older:

● The incidence of fatal coronary heart disease and nonfatal myocardial

infarction (ie, the primary outcome) and all-cause mortality was the same for
all three agents.

● A higher rate of heart failure was observed with amlodipine, compared with
chlorthalidone (RR 1.33, 95% CI 1.18-1.49); the relative risk was similar to that
in the entire ALLHAT population (figure 4).
 ● Compared with chlorthalidone, lisinopril had significantly higher rates of
combined cardiovascular disease outcomes (RR 1.13) (figure 5), combined
coronary heart disease (RR 1.11), and heart failure (RR 1.20) (figure 6). There
was also a nonsignificant trend for a higher rate of stroke with lisinopril (RR
1.13, with a 95% CI 0.98-1.30) (figure 7). Each of these values was similar to
those in the entire ALLHAT population.

Thus, all three antihypertensive agents were associated with the same
cardiovascular and overall mortality and incidence of nonfatal myocardial
infarction, a finding consistent with smaller comparative trials in older adults, such
as STOP-Hypertension-2 [54]. The lower rates of some secondary outcomes with
chlorthalidone in ALLHAT may have reflected at least in part lower attained blood
pressures, rather than a specific drug benefit [53]. In addition, the superiority of
chlorthalidone as compared with lisinopril in preventing certain secondary
endpoints may have been due to the presence a substantial number of black
participants who had inferior antihypertensive responses to lisinopril compared
with chlorthalidone; chlorthalidone and lisinopril produced similar results in whites
[55]. (See "Choice of drug therapy in primary (essential) hypertension", section on
'ALLHAT trial'.)

Long-acting calcium channel blockers — Long-acting calcium channel blockers

have proven efficacy and safety in older adult patients with hypertension,
particularly those with isolated systolic hypertension. This has been demonstrated
in a variety of clinical trials in older adult patients with hypertension, including
ALLHAT [53], Syst-Eur trial [28], STOP Hypertension-2 [54], the Syst-China trial [29],
and the ACCOMPLISH trial [56].

Angiotensin inhibition — In ALLHAT, the angiotensin-converting enzyme (ACE)

inhibitor lisinopril produced, for certain cardiovascular endpoints, inferior
outcomes compared with chlorthalidone at 12.5 to 25 mg daily, an effect that may
have been due at least in part to greater blood pressure reduction with
chlorthalidone [53]. In contrast, ACE inhibitors were associated with a lower rate of
adverse cardiovascular events than thiazide diuretics at the same degree of blood
pressure control in the Second Australian National Blood Pressure (ANBP2) trial of
older adult patients with hypertension [57]. However, there are potentially
important concerns about the design of this trial [58,59]. (See 'ALLHAT trial'
above.)

Many older adult hypertensive patients have a specific indication for an ACE
inhibitor or angiotensin II receptor blocker (ARB), including heart failure, prior
myocardial infarction, and proteinuric chronic kidney disease. (See appropriate
topic reviews.)

Beta blockers — There is evidence that, in the absence of a specific indication

for their use (eg, heart failure, myocardial infarction), beta blockers should not be
considered for primary therapy of hypertension, particularly in older adult patients
[40,60,61]. They may be worse than other agents for the prevention of stroke
(particularly among smokers) and, perhaps with atenolol, death. (See "Choice of
drug therapy in primary (essential) hypertension", section on 'Initial monotherapy'.)

ACCOMPLISH trial of combination therapy — The ACCOMPLISH trial evaluated

the efficacy of initial combination therapy in 11,506 hypertensive patients (mean
age 68 years, mean blood pressure 145/80 mmHg) who were at high risk for
cardiovascular events; almost all of whom were being treated with
antihypertensive drugs [56]. The patients were randomly assigned (without a
washout period) to combination therapy with benazepril (20 mg/day) plus either
amlodipine (5 mg/day) or hydrochlorothiazide (12.5 mg/day); dose escalation was
performed as necessary. The primary endpoint was achieved significantly less
often in the benazepril-amlodipine group (9.6 versus 11.8 percent, hazard ratio
0.80, 95% CI 0.72-0.90). Patients 65 years and older as well as 70 years and older
had the same relative benefit from benazepril-amlodipine as did the overall study
population. Office blood pressure control and 24-hour blood pressure
measurements were similar in the two groups.

The ACCOMPLISH trial is discussed in detail elsewhere. (See "Choice of drug

therapy in primary (essential) hypertension", section on 'ACCOMPLISH trial'.)

Summary of antihypertensive drug choice — For the treatment of hypertension

with monotherapy, there is agreement from a 2008 meta-analysis and major
society guidelines that, in the absence of a specific indication for use of a
particular class of antihypertensive drugs (eg, ACE inhibitors and beta blockers for
heart failure), it is the attained blood pressure, not the particular drug, that is the
primary determinant of outcome with single-agent antihypertensive therapy
[42,51,62]. (See "Choice of drug therapy in primary (essential) hypertension",
section on 'Importance of attained blood pressure'.)

In general, three classes of drugs are considered first-line therapy for the
treatment of hypertension in older adult patients: low-to-moderate-dose thiazide
diuretics (eg, 12.5 to 25 mg/day of chlorthalidone), long-acting calcium channel
blockers (most often dihydropyridines), and ACE inhibitors or ARBs [32]. A long-
acting dihydropyridine or a thiazide diuretic is generally preferred in older adult
patients because of increased efficacy in blood pressure lowering [42].

Among older adult patients in whom there is a reasonable likelihood of requiring a

second drug (eg, more than 10/5 mmHg above goal or failure to attain goal blood
pressure with monotherapy), we and many hypertension experts practice
according to the results of the ACCOMPLISH trial described above in which there
was significant improvement in outcomes at the same attained blood pressure
with benazepril plus amlodipine compared with benazepril plus
hydrochlorothiazide. (See 'ACCOMPLISH trial of combination therapy' above.)

Thus, we prefer initial therapy with a long-acting dihydropyridine calcium channel

blocker. If additional therapy is required, a long-acting ACE inhibitor/ARB can be
added to achieve the desired combination regimen. This suggestion differs slightly
from the American College of Cardiology/American Heart Association (ACC/AHA)
and European Society of Hypertension/European Society of Cardiology (ESH/ESC)
guidelines, which suggest that monotherapy can consist of either an ACE inhibitor
(or ARB), long-acting calcium channel blocker, or a thiazide diuretic and that
combination therapy can consist of any two of these three drugs [2,63]. (See
'Long-acting calcium channel blockers' above and "Choice of drug therapy in
primary (essential) hypertension".)

With all drugs, orthostatic hypotension should be avoided because of the

increased risk of falling in older patients. (See 'Problem of orthostatic hypotension'
above.)

Uncontrolled hypertension — Older hypertensive patients are less likely than

younger patients to attain a systolic blood pressure less than 130 mmHg with
antihypertensive therapy, although older and younger patients achieve a systolic
pressure less than 140 mmHg with equal frequency [64-66]. In the United States,
control of blood pressure to <130/<80 mmHg among those taking
antihypertensive drug therapy was achieved by 54, 50, 46, and 33 percent of
individuals aged 20 to 54 years, 55 to 64 years, 65 to 74 years, and 75 or more
years, respectively [1].

Additional observations come from a report of the National Health and Nutrition
Examination Survey (NHANES) including 13,375 hypertensive adults who had a
mean age of 59 years [67]. Uncontrolled hypertension was defined, at that time, as
a blood pressure ≥140/≥90 mmHg in patients treated with one or two
antihypertensive medications.

The following findings were noted from 2005 to 2008:

● Among all patients on one to two antihypertensive medications, the risk of

being uncontrolled increased by 28 percent with each 10-year increase in age.
 ● Patients who were uncontrolled on one or two antihypertensive drugs were
more likely to be older and to have an estimated 10-year coronary heart
disease risk of >20 percent than those who were controlled.

● These patients accounted for 72 percent of all treated patients with

uncontrolled hypertension; the remaining 28 percent had resistant
hypertension as defined in the following section. (See 'Resistant hypertension'
below.)

These observations suggest that clinicians are reluctant to add a second and third
antihypertensive drug in older patients with uncontrolled hypertension, despite
their high risk for clinical complications from persistent hypertension. However,
older hypertensives are more likely to be frail, to have orthostatic hypotension, and
to have lower diastolic blood pressures than younger hypertensive patients, all of
which may limit antihypertensive therapy. (See 'Problem of orthostatic
hypotension' above.)

Thus, while substantial progress has been made in closing the gap in hypertension
control between all younger and older adults with hypertension [64], it may not be
possible or prudent to fully close the gap. However, the combination of
antihypertensive therapy and lifestyle modifications described above should result
in blood pressure control in a greater proportion of older patients. (See 'Lifestyle
modifications' above.)

Resistant hypertension — In the same NHANES report as in the preceding section,

apparent treatment-resistant hypertension was defined as a blood pressure ≥140/
≥90 mmHg in patients taking three or more antihypertensive medications [67].
These patients accounted for 28 percent of treated patients with uncontrolled
hypertension in 2005 to 2008, which represented an increase from 16 percent in
1988 to 1994. Clinical characteristics associated with resistant hypertension
included older age, obesity, chronic kidney disease, and a Framingham 10-year
coronary risk score of more than 20 percent.
Issues related to resistant hypertension, including the general approach to therapy,
are discussed in detail elsewhere. (See "Definition, risk factors, and evaluation of
resistant hypertension" and "Treatment of resistant hypertension".)

GOAL BLOOD PRESSURE

Goal blood pressure depends in part upon the age of the patient and whether or
not he or she has significant risk factors for cardiovascular and kidney disease.
Goal blood pressure, and specifically our recommended goal blood pressure for
different patient populations, is discussed in detail elsewhere. In general, however,
our recommendation for most hypertensive older adults is to attain a systolic
pressure of 125 to 135 mmHg if standard manual blood pressure measurements
are used, or a systolic pressure of 120 to 125 mmHg if unattended, automated
oscillometric measurements are used. (See "Blood pressure measurement in the
diagnosis and management of hypertension in adults" and "Goal blood pressure in
adults with hypertension" and "Treatment of hypertension in patients with diabetes
mellitus" and "Antihypertensive therapy and progression of nondiabetic chronic
kidney disease in adults" and "Antihypertensive therapy to prevent recurrent stroke
or transient ischemic attack".)

Goal blood pressure in older adults was examined in the Systolic Pressure
Intervention Trial (SPRINT) [68]. SPRINT enrolled a subgroup of more than 2600
ambulatory adults aged 75 years or older with a baseline blood pressure of 142/71
mmHg (consistent with isolated systolic hypertension), including 349 categorized
as being fit, 1456 as less fit, and 815 as frail according to a validated frailty index.
At 3.1 years, rates of both the primary cardiovascular endpoint and all-cause
mortality were significantly lower among those assigned more intensive (mean
achieved unattended, automated systolic blood pressure 123) versus less
intensive (mean achieved automated, unattended systolic blood pressure 135)
blood pressure lowering (2.6 versus 3.8 percent and 1.8 versus 2.6 percent,
respectively). The benefit from more intensive blood pressure control was present
in both fit and frail older adults. Serious adverse events were similar in the two
treatment groups and did not depend upon frailty.

A meta-analysis of 10,857 hypertensive adults aged 65 years or older combined

these results from SPRINT with three other large randomized goal blood pressure
trials [69]. After a mean follow up of 3.1 years, more intensive, versus less
intensive, blood pressure lowering reduced the rates of major adverse
cardiovascular events (3.7 versus 5.2 percent), cardiovascular mortality (1.1
versus 1.7 percent), and heart failure (1.3 versus 2.0 percent). Rates of stroke and
myocardial infarction were also lower, but the results were not statistically
significant.

Blood pressure goals may not be easy to achieve, particularly in older patients with
a baseline systolic pressure greater than 160 mmHg. If attaining goal blood
pressure proves difficult or overly burdensome for the patient, the systolic
pressure that is reached with two or three antihypertensive agents (even if above
target) may be a reasonable interim goal. Once maximally tolerated therapy is
reached and blood pressure control remains suboptimal, then additional efforts to
engage older adults in healthful lifestyle change can facilitate better blood
pressure control.

One potential limitation to achieving goal blood pressure is that lowering the blood
pressure may impair mental function, leading to manifestations such as confusion
or sleepiness. In such patients, antihypertensive therapy should be reduced, and
the systolic pressure should be allowed to rise to a level at which these symptoms
resolve.

Another concern when treating older adult patients with isolated systolic
hypertension is that the low diastolic pressure after therapy may impair tissue
perfusion (particularly coronary perfusion) and possibly increase cardiovascular
risk [6,12,17,18]. However, as noted above, lower diastolic blood pressures are
associated with worse outcomes (both cardiovascular and noncardiovascular) in
both treated and untreated patients (figure 2) [24]. These findings suggest that the
worse outcomes are probably explained by poor health associated with lower
blood pressures, not an adverse effect of antihypertensive therapy. (See
'Importance of diastolic pressure' above.)

Despite these observations, there may be a threshold diastolic blood pressure

below which adverse cardiovascular outcomes might increase in older adult
patients. When treating patients with isolated systolic hypertension, we and others
(including JNC-7) suggest a minimum posttreatment diastolic pressure of 60
mmHg (using office-based blood pressure) [21,23].

SOCIETY GUIDELINE LINKS

Links to society and government-sponsored guidelines from selected countries

and regions around the world are provided separately. (See "Society guideline
links: Hypertension in adults".)

INFORMATION FOR PATIENTS

UpToDate offers two types of patient education materials, "The Basics" and
"Beyond the Basics." The Basics patient education pieces are written in plain
language, at the 5th to 6th grade reading level, and they answer the four or five key
questions a patient might have about a given condition. These articles are best for
patients who want a general overview and who prefer short, easy-to-read
materials. Beyond the Basics patient education pieces are longer, more
sophisticated, and more detailed. These articles are written at the 10th to 12th
grade reading level and are best for patients who want in-depth information and
are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We
encourage you to print or e-mail these topics to your patients. (You can also locate
patient education articles on a variety of subjects by searching on "patient info"
and the keyword(s) of interest.)

● Beyond the Basics topics (see "Patient education: High blood pressure in
adults (Beyond the Basics)" and "Patient education: High blood pressure
treatment in adults (Beyond the Basics)" and "Patient education: High blood
pressure, diet, and weight (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

● The prevalence of hypertension among older adults (age greater than 60 to 65
years) is reportedly as high as 70 to more than 80 percent. (See 'Introduction'
above.)

● Isolated systolic hypertension (ISH), which is common in older adults, has

been often defined as a systolic blood pressure equal to or above 160 mmHg,
with a diastolic blood pressure below 90 mmHg. Some expert panels,
however, have defined 130 mmHg as the upper limit of normal at all ages.
(See 'Isolated systolic hypertension' above.)

● Older hypertensive patients should attempt lifestyle modification to lower the

blood pressure. If goal blood pressure is not attained with lifestyle
modification, antihypertensive therapy should be initiated. (See 'Lifestyle
modifications' above.)

● In the absence of a hypertensive emergency or urgency, blood pressure

reduction should always be gradual in older adults, aiming for control within
three to six months. All patients should receive nonpharmacologic therapy,
particularly dietary salt restriction and weight loss in obese patients. Drug
therapy should be started if lifestyle changes are not sufficient. A potential
limiting factor to the use of antihypertensive drugs is that orthostatic
(postural) and/or postprandial hypotension is common among older
 hypertensive patients. (See 'Lifestyle modifications' above and 'Drug therapy'
above.)

● Among older hypertensive patients who require antihypertensive medication

and who do not have an indication for a specific drug, we recommend initial
monotherapy with a low-dose thiazide-type diuretic, a long-acting calcium
channel blocker, or an angiotensin-converting enzyme (ACE)
inhibitor/angiotensin II receptor blocker (ARB) (Grade 1B). A long-acting
dihydropyridine or a thiazide diuretic is generally preferred because of
increased blood pressure-lowering efficacy in this population. Among older
adult patients in whom there is a reasonable likelihood of requiring a second
drug (eg, systolic pressure more than 10/5 mmHg above goal), we suggest
initial therapy with a long-acting dihydropyridine calcium channel blocker
(Grade 2C). This is because, if additional therapy is required, a long-acting
ACE inhibitor/ARB can be added to achieve the desired combination regimen
of a long-acting ACE inhibitor/ARB plus a long-acting dihydropyridine calcium
channel blocker. (See 'Summary of antihypertensive drug choice' above.)

● Goal blood pressure is presented in detail separately. In general, however, our

recommendation for most hypertensive older adults is to attain a systolic
pressure of 125 to 135 mmHg if standard manual office blood pressure
measurements are used, or a systolic pressure of 120 to 125 mmHg if
automated oscillometric measurements are used. If attaining goal blood
pressure proves difficult or overly burdensome for the patient, the systolic
pressure that is reached with two or three antihypertensive agents (even if
above target) may be a reasonable interim goal. (See "Goal blood pressure in
adults with hypertension" and "Treatment of hypertension in patients with
diabetes mellitus", section on 'Goal blood pressure' and "Antihypertensive
therapy and progression of nondiabetic chronic kidney disease in adults",
section on 'Blood pressure goal' and "Antihypertensive therapy to prevent
 recurrent stroke or transient ischemic attack" and "Treatment of hypertension
in patients with diabetes mellitus".)

REFERENCES

1. Muntner P, Carey RM, Gidding S, et al. Potential US Population Impact of the

2017 ACC/AHA High Blood Pressure Guideline. Circulation 2018; 137:109.

2. Whelton PK, Carey RM, Aronow WS, et al. 2017

ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline
for the Prevention, Detection, Evaluation, and Management of High Blood
Pressure in Adults: A Report of the American College of Cardiology/American
Heart Association Task Force on Clinical Practice Guidelines. Hypertension
2018; 71:e13.

3. Bundy JD, Mills KT, Chen J, et al. Estimating the Association of the 2017 and
2014 Hypertension Guidelines With Cardiovascular Events and Deaths in US
Adults: An Analysis of National Data. JAMA Cardiol 2018; 3:572.

4. Vasan RS, Larson MG, Leip EP, et al. Assessment of frequency of progression
to hypertension in non-hypertensive participants in the Framingham Heart
Study: a cohort study. Lancet 2001; 358:1682.

5. Vasan RS, Beiser A, Seshadri S, et al. Residual lifetime risk for developing
hypertension in middle-aged women and men: The Framingham Heart Study.
JAMA 2002; 287:1003.

6. Staessen JA, Gasowski J, Wang JG, et al. Risks of untreated and treated
isolated systolic hypertension in the elderly: meta-analysis of outcome trials.
Lancet 2000; 355:865.

7. National High Blood Pressure Education Program Working Group Report on

Hypertension in the Elderly. National High Blood Pressure Education Program
 Working Group. Hypertension 1994; 23:275.

8. National Institute for Health and Clinical Excellence. Hypertension: managem

ent of hypertension in adults in primary care (NICE clinical guideline update).
http://www.nice.org.uk (Accessed on January 21, 2009).

9. Franklin SS, Gustin W 4th, Wong ND, et al. Hemodynamic patterns of age-
related changes in blood pressure. The Framingham Heart Study. Circulation
1997; 96:308.

10. Franklin SS, Jacobs MJ, Wong ND, et al. Predominance of isolated systolic
hypertension among middle-aged and elderly US hypertensives: analysis
based on National Health and Nutrition Examination Survey (NHANES) III.
Hypertension 2001; 37:869.

11. Kannel WB. Blood pressure as a cardiovascular risk factor: prevention and
treatment. JAMA 1996; 275:1571.

12. Franklin SS, Larson MG, Khan SA, et al. Does the relation of blood pressure to
coronary heart disease risk change with aging? The Framingham Heart Study.
Circulation 2001; 103:1245.

13. Chobanian AV. Clinical practice. Isolated systolic hypertension in the elderly. N
Engl J Med 2007; 357:789.

14. Izzo JL Jr, Levy D, Black HR. Clinical Advisory Statement. Importance of
systolic blood pressure in older Americans. Hypertension 2000; 35:1021.

15. Young JH, Klag MJ, Muntner P, et al. Blood pressure and decline in kidney
function: findings from the Systolic Hypertension in the Elderly Program
(SHEP). J Am Soc Nephrol 2002; 13:2776.

16. Neaton JD, Wentworth D. Serum cholesterol, blood pressure, cigarette

smoking, and death from coronary heart disease. Overall findings and
 differences by age for 316,099 white men. Multiple Risk Factor Intervention
Trial Research Group. Arch Intern Med 1992; 152:56.

17. Pastor-Barriuso R, Banegas JR, Damián J, et al. Systolic blood pressure,

diastolic blood pressure, and pulse pressure: an evaluation of their joint effect
on mortality. Ann Intern Med 2003; 139:731.

18. Protogerou AD, Safar ME, Iaria P, et al. Diastolic blood pressure and mortality
in the elderly with cardiovascular disease. Hypertension 2007; 50:172.

19. Prevention of stroke by antihypertensive drug treatment in older persons with

isolated systolic hypertension. Final results of the Systolic Hypertension in the
Elderly Program (SHEP). SHEP Cooperative Research Group. JAMA 1991;
265:3255.

20. Beckett NS, Peters R, Fletcher AE, et al. Treatment of hypertension in patients
80 years of age or older. N Engl J Med 2008; 358:1887.

21. Somes GW, Pahor M, Shorr RI, et al. The role of diastolic blood pressure when
treating isolated systolic hypertension. Arch Intern Med 1999; 159:2004.

22. Vokó Z, Bots ML, Hofman A, et al. J-shaped relation between blood pressure
and stroke in treated hypertensives. Hypertension 1999; 34:1181.

23. Messerli FH, Mancia G, Conti CR, et al. Dogma disputed: can aggressively
lowering blood pressure in hypertensive patients with coronary artery disease
be dangerous? Ann Intern Med 2006; 144:884.

24. Boutitie F, Gueyffier F, Pocock S, et al. J-shaped relationship between blood

pressure and mortality in hypertensive patients: new insights from a meta-
analysis of individual-patient data. Ann Intern Med 2002; 136:438.

25. Appel LJ, Espeland MA, Easter L, et al. Effects of reduced sodium intake on
hypertension control in older individuals: results from the Trial of
 Nonpharmacologic Interventions in the Elderly (TONE). Arch Intern Med 2001;
161:685.

26. Whelton PK, Appel LJ, Espeland MA, et al. Sodium reduction and weight loss
in the treatment of hypertension in older persons: a randomized controlled
trial of nonpharmacologic interventions in the elderly (TONE). TONE
Collaborative Research Group. JAMA 1998; 279:839.

27. Staessen JA, Richart T, Verdecchia P. Reducing blood pressure in people of

different ages. BMJ 2008; 336:1080.

28. Staessen JA, Fagard R, Thijs L, et al. Randomised double-blind comparison of

placebo and active treatment for older patients with isolated systolic
hypertension. The Systolic Hypertension in Europe (Syst-Eur) Trial
Investigators. Lancet 1997; 350:757.

29. Liu L, Wang JG, Gong L, et al. Comparison of active treatment and placebo in
older Chinese patients with isolated systolic hypertension. Systolic
Hypertension in China (Syst-China) Collaborative Group. J Hypertens 1998;
16:1823.

30. Staessen JA, Richart T, Birkenhäger WH. Less atherosclerosis and lower
blood pressure for a meaningful life perspective with more brain.
Hypertension 2007; 49:389.

31. Chaudhry SI, Krumholz HM, Foody JM. Systolic hypertension in older persons.
JAMA 2004; 292:1074.

32. James PA, Oparil S, Carter BL, 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.
33. Kostis JB, Davis BR, Cutler J, et al. Prevention of heart failure by
antihypertensive drug treatment in older persons with isolated systolic
hypertension. SHEP Cooperative Research Group. JAMA 1997; 278:212.

34. Ofili EO, Cohen JD, St Vrain JA, et al. Effect of treatment of isolated systolic
hypertension on left ventricular mass. JAMA 1998; 279:778.

35. Franse LV, Pahor M, Di Bari M, et al. Hypokalemia associated with diuretic use
and cardiovascular events in the Systolic Hypertension in the Elderly Program.
Hypertension 2000; 35:1025.

36. Staessen JA, Fagard R, Thijs L, et al. Subgroup and per-protocol analysis of
the randomized European Trial on Isolated Systolic Hypertension in the
Elderly. Arch Intern Med 1998; 158:1681.

37. Tuomilehto J, Rastenyte D, Birkenhäger WH, et al. Effects of calcium-channel

blockade in older patients with diabetes and systolic hypertension. Systolic
Hypertension in Europe Trial Investigators. N Engl J Med 1999; 340:677.

38. Forette F, Seux ML, Staessen JA, et al. Prevention of dementia in randomised
double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur)
trial. Lancet 1998; 352:1347.

39. Medical Research Council trial of treatment of hypertension in older adults:

principal results. MRC Working Party. BMJ 1992; 304:405.

40. Khan N, McAlister FA. Re-examining the efficacy of beta-blockers for the
treatment of hypertension: a meta-analysis. CMAJ 2006; 174:1737.

41. Messerli FH, Grossman E, Goldbourt U. Are beta-blockers efficacious as first-

line therapy for hypertension in the elderly? A systematic review. JAMA 1998;
279:1903.

42. Mancia G, Fagard R, Narkiewicz K, et al. 2013 ESH/ESC Guidelines for the
management 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.

43. Vanhanen H, Thijs L, Birkenhäger W, et al. Associations of orthostatic blood

pressure fall in older patients with isolated systolic hypertension. Syst-Eur
Investigators. J Hypertens 1996; 14:943.

44. Applegate WB, Davis BR, Black HR, et al. Prevalence of postural hypotension
at baseline in the Systolic Hypertension in the Elderly Program (SHEP) cohort.
J Am Geriatr Soc 1991; 39:1057.

45. Gangavati A, Hajjar I, Quach L, et al. Hypertension, orthostatic hypotension,

and the risk of falls in a community-dwelling elderly population: the
maintenance of balance, independent living, intellect, and zest in the elderly of
Boston study. J Am Geriatr Soc 2011; 59:383.

46. Tinetti ME, Han L, Lee DS, et al. Antihypertensive medications and serious fall
injuries in a nationally representative sample of older adults. JAMA Intern
Med 2014; 174:588.

47. Butt DA, Mamdani M, Austin PC, et al. The risk of hip fracture after initiating
antihypertensive drugs in the elderly. Arch Intern Med 2012; 172:1739.

48. Benetos A, Labat C, Rossignol P, et al. Treatment With Multiple Blood Pressure
Medications, Achieved Blood Pressure, and Mortality in Older Nursing Home
Residents: The PARTAGE Study. JAMA Intern Med 2015; 175:989.

49. Odden MC, Peralta CA, Haan MN, Covinsky KE. Rethinking the association of
high blood pressure with mortality in elderly adults: the impact of frailty. Arch
Intern Med 2012; 172:1162.

50. Rosendorff C, Lackland DT, Allison M, et al. Treatment of hypertension in

patients with coronary artery disease: a scientific statement from the
 American Heart Association, American College of Cardiology, and American
Society of Hypertension. Circulation 2015; 131:e435.

51. Blood Pressure Lowering Treatment Trialists' Collaboration, Turnbull F, Neal B,

et al. Effects of different regimens to lower blood pressure on major
cardiovascular events in older and younger adults: meta-analysis of
randomised trials. BMJ 2008; 336:1121.

52. Law MR, Morris JK, Wald NJ. Use of blood pressure lowering drugs in the
prevention of cardiovascular disease: meta-analysis of 147 randomised trials
in the context of expectations from prospective epidemiological studies. BMJ
2009; 338:b1665.

53. ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research
Group. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart
Attack Trial. Major outcomes in high-risk hypertensive patients randomized to
angiotensin-converting enzyme inhibitor or calcium channel blocker vs
diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart
Attack Trial (ALLHAT). JAMA 2002; 288:2981.

54. Hansson L, Lindholm LH, Ekbom T, et al. Randomised trial of old and new
antihypertensive drugs in elderly patients: cardiovascular mortality and
morbidity the Swedish Trial in Old Patients with Hypertension-2 study. Lancet
1999; 354:1751.

55. Wright JT Jr, Probstfield JL, Cushman WC, et al. ALLHAT findings revisited in
the context of subsequent analyses, other trials, and meta-analyses. Arch
Intern Med 2009; 169:832.

56. Jamerson K, Weber MA, Bakris GL, et al. Benazepril plus amlodipine or
hydrochlorothiazide for hypertension in high-risk patients. N Engl J Med 2008;
359:2417.
57. Wing LM, Reid CM, Ryan P, et al. A comparison of outcomes with angiotensin-
converting--enzyme inhibitors and diuretics for hypertension in the elderly. N
Engl J Med 2003; 348:583.

58. Davis BR, Furberg CD, Wright JT Jr, et al. ALLHAT: setting the record straight.
Ann Intern Med 2004; 141:39.

59. Frohlich ED. Treating hypertension - what are we to believe? N Engl J Med
2003; 348:639.

60. Lindholm LH, Carlberg B, Samuelsson O. Should beta blockers remain first
choice in the treatment of primary hypertension? A meta-analysis. Lancet
2005; 366:1545.

61. Bradley HA, Wiysonge CS, Volmink JA, et al. How strong is the evidence for
use of beta-blockers as first-line therapy for hypertension? Systematic review
and meta-analysis. J Hypertens 2006; 24:2131.

62. Rosendorff C, Black HR, Cannon CP, et al. Treatment of hypertension in the
prevention and management of ischemic heart disease: a scientific statement
from the American Heart Association Council for High Blood Pressure
Research and the Councils on Clinical Cardiology and Epidemiology and
Prevention. Circulation 2007; 115:2761.

63. Williams B, Mancia G, Spiering W, et al. 2018 Practice Guidelines for the
management of arterial hypertension of the European Society of Cardiology
and the European Society of Hypertension. Blood Press 2018; 27:314.

64. Egan BM, Li J, Shatat IF, et al. Closing the gap in hypertension control between
younger and older adults: National Health and Nutrition Examination Survey
(NHANES) 1988 to 2010. Circulation 2014; 129:2052.

65. Egan BM, Bland VJ, Brown AL, et al. Hypertension in african americans aged
60 to 79 years: statement from the international society of hypertension in
 blacks. J Clin Hypertens (Greenwich) 2015; 17:252.

66. Egan BM, Li J, Wagner CS. Systolic Blood Pressure Intervention Trial (SPRINT)
and Target Systolic Blood Pressure in Future Hypertension Guidelines.
Hypertension 2016; 68:318.

67. Egan BM, Zhao Y, Axon RN, et al. Uncontrolled and apparent treatment
resistant hypertension in the United States, 1988 to 2008. Circulation 2011;
124:1046.

68. Williamson JD, Supiano MA, Applegate WB, et al. Intensive vs Standard Blood
Pressure Control and Cardiovascular Disease Outcomes in Adults Aged ≥75
Years: A Randomized Clinical Trial. JAMA 2016; 315:2673.

69. Bavishi C, Bangalore S, Messerli FH. Outcomes of Intensive Blood Pressure

Lowering in Older Hypertensive Patients. J Am Coll Cardiol 2017; 69:486.

Topic 3863 Version 34.0

© 2019 UpToDate, Inc. All rights reserved.