Download Management of Hypertension in the Elderly

Journals of Gerontology: MEDICAL SCIENCES
Cite journal as: J Gerontol A Biol Sci Med Sci. 2012 December;67(12):1343–1351
doi:10.1093/gerona/gls148
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Advance Access publication August 22, 2012
Translational Article
Special Issue on the Aging Kidney
Management of Hypertension in the Elderly Population
Raymond V. Oliva1 and George L. Bakris2
1
Section of Hypertension, Department of Medicine, Philippine General Hospital, Manila, Philippines.
ASH Comprehensive Hypertension Center, Department of Medicine, The University of Chicago Medicine, Illinois.
2
Address correspondence to George L. Bakris, MD, FASN, FASH, The University of Chicago Medicine, 5841 S. Maryland, MC 1027 Rm P-328,
Chicago, Illinois 60637. Email: [email protected]
Hypertension is common in people aged 65 and older. African Americans and women have a higher prevalence of
hypertension than white individuals, and in those aged 70 and older, the hypertension was more poorly controlled than
in those aged 60–69. The number of trials available in the elderly population compared with the general population
are limited; hence, the database for strong recommendations as to goal blood pressure (BP) are limited. The American
College of Cardiology with the American Heart Association has recently published a consensus report of management
of hypertension in the elderly population. This review presents an overview of this consensus report and reviews specific
studies that provide some novel findings regarding goal BP and progression of nephropathy. In general, the evidence
strongly supports a BP goal of less than 150/80 mmHg. The evidence review for the consensus report supports a goal of
<150/80 mmHg for the elderly with scant data in those over age 80. However, it was decided to set the goal to less than
140/90 mmHg unless the patient cannot tolerate it and then try for 140–145 mmHg. The data are scant at best for those
over age 80 mmHg but some evidence exists for <150/80 mmHg. Diuretics and calcium antagonists are the most efficacious single agents for treatment; however, most patients will require two or more drugs to achieve such goals.
Key words: Elderly adults—Hypertension—Management.
Received February 27, 2012; Accepted May 17, 2012
Decision Editor: Luigi Ferrucci, MD, PhD
T
he elderly population represents several medical challenges, particularly in the management of hypertension,
affecting the success or failure in the treatment of our elderly patients. These individuals have more organ damage or
clinical cardiovascular (CV) disease, and they may respond
differently to treatment goals of “normal” aged populations.
According to the latest National Health and Examination
Survey (1), 67% of adults aged 60 and older were found to
be hypertensive, and with increasing age, not only it is more
likely that someone will develop hypertension, but their
risk of dying from CV disease is increased, even during the
prehypertensive range (2–4), Figure 1. Despite the relative
high incidence of hypertension, the elderly population are
not represented in clinical trials as they have upper age limits or do not present age-specific results. The release of the
Hypertension in the Very Elderly Trial (HYVET) (5), and
the subsequent publication in 2011 of the American College
of Cardiology Foundation/American Heart Association
Consensus Document on Hypertension in the Elderly (6),
changed the management of hypertension particularly in
patients older than 80 years. It is but appropriate that issues
in this specific population subgroup be put into perspective,
particularly in the management of hypertension in the elderly population. However, each patient responds to different
treatment, thus, there is a need to individualize hypertension management in the elderly population.
Pathophysiology of Hypertension in the
Elderly Population
Age-related blood pressure (BP) elevations derive from
changes in the arterial structure and function accompanying
aging. The elasticity of the large vessels decreases due to
the alteration of the various collagen components in the
vessel wall (7). These changes cause increases in the pulse
wave velocity, leading to late systolic BP augmentation
and increasing myocardial oxygen demand. Reduction of
forward flow also occurs, limiting organ perfusion. The
arterial stiffness is manifested clinically by the widening
of pulse pressure, which is seen commonly in the elderly
patients (8,9). Data from the Framingham Heart Study
suggest that after age 50, systolic BP continues to increase,
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OLIVA and BAKRIS
Figure 1. Coronary heart disease risk in the context of age and level of
blood pressure (BP) (4).
whereas diastolic BP decreases, resulting in the widened
pulse pressure (10).
Elderly patients are relatively more salt sensitive due to
their reduced ability to excrete a sodium load. This is partly
due to the decline in kidney function with age and secondarily due to the reduced generation of the natriuretic substances, such as prostaglandin E2 (PGE2) and dopamine.
Progressive renal dysfunction because of glomerulosclerosis and interstitial fibrosis with a reduction of glomerular filtration rate and other renal homeostatic mechanism
leading to increased intracellular sodium, reduced Na–Ca
exchange, and volume expansion may also contribute to the
pathophysiology of hypertension in the elderly population
(11–14).
Secondary causes of hypertension should also be considered in this age group, such as renal artery stenosis (15),
sleep apnea (16), primary hyperaldosteronism (17), and
thyroid disorders (18). Excess in lifestyle such as overeating
or high alcohol consumption as well as medications such as
nonsteroidal anti-inflammatory medications can also contribute to the elevation of BP in the elderly patients (4).
Definition of Hypertension in the Elderly
Population
Hypertension is age dependent, and the usual definition
of hypertension and target BP levels might not be applicable to the elderly hypertensive population. According to
the 2011 consensus of American College of Cardiology
Foundation/American Heart Association (6), a clinical
diagnosis of hypertension is established by demonstrating
a systolic BP of greater than or equal to 140 mmHg, and/or
diastolic BP of greater than or equal to 90 mmHg on at least
three different BP measurements, taken on two or more than
two separate office visits to account for natural variability
of BP. BP should also be measured standing for 1–3 minutes to evaluate postural hypotension. In addition, in certain
conditions such as chronic kidney disease with proteinuria,
a systolic BP of greater than or equal to 130 mmHg may be
considered hypertensive.
Isolated systolic hypertension is very common in the
elderly and is defined as the presence of systolic BP of
greater than or equal to 160 mmHg with a diastolic BP
below 90 mmHg (19,20). This condition is associated with
a two-to-fourfold increase in the risk of myocardial infarction, left ventricular hypertrophy, renal dysfunction, stroke,
and CV mortality.
Criteria to define what an ELDERLY is may also vary.
The American College of Cardiology Foundation/American
Heart Association decided to define elderly patients in the
traditional demographic definition of greater than or equal
to 65 years of age, however, recognizing that there are relevant physiological changes among the “young–old” (65–
74 years), the “older old” (75–84 years), and the “oldest old”
(≥85 years old). Aging is a continuous process for both sexes
and vascular aging rates may considerably change among
individuals as a result of genetic, cultural, environmental,
behavioral, and disease-related factors (6). In this article,
we decided to follow the traditional definition of more than
65 years old for elderly patients keeping in mind the different pathological changes surrounding this age group.
Although a specific BP level may be used to classify a
person as hypertensive, a finite BP level is only a biomarker
that is somewhat removed from the complex CV disorder
called hypertension (6). Improved descriptors may evolve
in the future to define who has the disorder, predict those at
risk for adverse outcomes, and better target treatment.
Blood Pressure Goal in the Elderly Population
The current evidence supports a BP goal of less than
150/80 mmHg in the elderly population. However, present
guidelines are based mostly on expert opinion rather than
results of clinical trials due to lack of sufficient data from
clinical trials involving this age group. The consensus report
by the American College of Cardiology/American Heart
Association (ACC/AHA) suggests a goal BP of less than
140/90 mmHg in all elderly patients, and for those who cannot tolerate this pressure, 140–145 mmHg. For those older
than 80 years, a systolic BP of 140–145 mmHg, if tolerated,
is acceptable, but there is no compelling evidence for this
level of BP other than the HYVET.
A concern in patients with isolated systolic hypertension
is the reduction of diastolic BP after initiation of antihypertensive therapy. Too low a diastolic BP may interfere with
coronary perfusion and possibly increase CV risk. The relationship between diastolic BP and CV death, particularly
myocardial infarction is like a J-shaped curve, thus excessive reduction in diastolic pressures should be avoided in
patients with coronary artery disease who are being treated
Hypertension in the Elderly Population
for hypertension. A BP of 119/84 mmHg was identified as
a nadir when treating patients with coronary artery disease
(21). When treating patients with isolated systolic hypertension, the 7th Joint National Committee on Prevention,
Detection, Evaluation and Treatment of High Blood Pressure
(22) suggests a minimum posttreatment diastolic BP of
60 mmHg overall or perhaps 65 mmHg in patients with
known coronary artery disease, unless symptoms that could
be attainable to hypoperfusion occur at higher pressures.
This was seen in the findings of the Systolic Hypertension
in the Elderly Program (SHEP) trial (23), where elderly
patients with lower diastolic BP have higher CV event rates.
Like most BP guidelines, the ACC/AHA used achieved
end BP targets from the clinical trials instead of using
data from intention-to-treat analyses of the various clinical
trials, which unfortunately, may lead to differences in the
interpretation of results. In an analysis of different clinical
trials, results based on achieved BP lead to markedly
different inferences than traditional intention-to-treat
analyses, attributed in part to confounding of achieved BP
with comorbidities, disease severity, and adherence (24).
A potential limitation to the goals of BP control is that
lowering the BP may impair mental function, leading to
manifestations such as confusion or sleepiness. If this happens, antihypertensive therapy should be reduced and the
systolic BP allowed to increase to levels at which symptoms
resolve. Thus, it is very important that individualization of
treatment be employed in the management of elderly hypertensives (6).
Clinical Trials Involving the Elderly
Population
Hypertension clinical trials involving the elderly populations are summarized in Table 1, and the achieved systolic BP is shown in Figure 3. Most patients recruited in
these trials prior to HYVET were older than 80 years,
limiting information about octogenarians. Results in
these trials showed reduction in the incidence of both
stroke and CV morbidity, but a trend toward an increase
in all-cause mortality. Previous clinical trials showed that
lowering BP in the elderly have no effect on overall mortality or on the incidence of fatal or nonfatal myocardial
infarction (25,26). However, there was a benefit in stroke
outcomes. Thus, clinical practice guidelines prior to
HYVET and subsequently the ACC/AHA recommended
that in participants aged 80 years and above, “evidence
for benefits of anti-hypertensive treatment is as yet inconclusive (22).”
The HYVET in 2008 changed how hypertension in the
elderly patient is managed. It randomly assigned to almost
4,000 patients who were 80 years old and above and have
systolic BP of more than 160 mmHg to either indapamide
or placebo. Results of the HYVET provided clear evidence
1345
that BP lowering with treatment using antihypertensive
medications is associated with definite CV benefits. The use
of indapamide supplemented by perindopril showed reductions in the incidence of stroke, congestive heart failure, and
CV fatal events (5).
Stricter BP goals showed no benefit in the CV morbidity and mortality in the elderly populations. The Japanese
Trial to Assess Optimal Systolic Blood Pressure in Elderly
Hypertensive Patients (JATOS) study showed that the systolic BP goals of less than 140 mmHg did not have any statistically significance in the CV mortality of patients older
than 65 years (27).
Treatment Plans in the Management of
Hypertension in the Elderly Population
Nonpharmacological Intervention
Lifestyle changes may be the appropriate treatment for
mild hypertensive elderly patients (28,29). Interventions
include smoking cessation, weight reduction, decrease in
mental stress, sodium and alcohol restriction, and increased
physical activity. These changes may even reduce the doses
of antihypertensive medications (30–32). Weight reduction
combined with salt restriction result in greater benefit in elderly
patients. In the Trial of Non-pharmacologic Interventions in
the Elderly (TONE) (33), the combination of weight loss and
sodium restriction showed a drop of 5.3 ± 1.2 mmHg in the
systolic BP and 3.4 ± 0.8 mmHg diastolic BP in obese, elderly
hypertensive patients. The goal of sodium restriction was
1.8 g/24 h and the goal for weight reduction was 10 pounds.
Other lifestyle changes recommended in the elderly
patient include increasing potassium intake, either by
fruits and vegetables or pills. Intake of nonsteroidal
anti-inflammatory drugs should also be decreased to a minimum, as these patients are more likely to take nonsteroidal
anti-inflammatory medications for arthritis and pain. These
drugs are known to cause hypertension by inhibiting the
production of vasodilatory prostaglandins and may increase
BP by as much as 6 mmHg (34,35).
Pharmacological Intervention
According to the 2011 American College of Cardiology
Foundation/American Heart Association consensus guidelines, the initial antihypertensive drug should be started at
the lowest dose and gradually be increased depending on
the BP response up to the maximum tolerated dose. If the
response to initial therapy is inadequate after reaching full
dose (not necessarily the maximum recommended dose), a
second drug from another class should be added. The full
dose of the drug is the highest pharmacological dose of
drug available, whereas the maximum dose is the highest
dose that the person can tolerate without side effects. If the
Clonidine, nifedipine and atenolol 181/97
+ chlorthalidone
Nifedipine
155/87
Nitrendipine ± enalapril or HCTZ ~161/94
Nitrendipine ± captopril or HCTZ 178/93
4,736
1,627
3,496
665
1,632
4,695
2,394
3,845
4,418
3,079
72 (70–84 y)
70 (65–74 y)
83 (65–89 y)
67 (60–79 y)
70 (≥60 years)
67 (≥ 60 y)
84 (80–105 y)
75 (65–85 y)
76 (70–84 y)
Valsartan
Efonidipine hydrochloride
Indapamide ± perindopril
HCTZ ± amiloride vs atenolol
142/76.1
145.6/78.1
158.5/84
~169/79
161/97
155/72
180/89
157/73
72 (≥60 y)
Atenolol ± bendrofluazide
Chlorthalidone ± hydralazine/
reserpine/methyldopa
Chlorthalidone ± atenolol or
reserpine
Atenolol ± HCTZ or amiloride
884
552
159/85
68 (60–79 y)
72 (≥60 y)
Hydrochlorothiazide (HCTZ) +
triamterene, ± methyldopa
840
Drugs Used
72 (≥60 y)
Number
of Patients
Mean
Achieved BP;
Control/Placebo
(mmHg)
136.6/74.8
135.9/74.8
143/78
151/76
151/79
147/85
165.2/85.6
~150/80
159/81
143/68
178/87
141/68
155/84
Mean Achieved BP;
Treatment (mmHg)
BP targets <140 mmHg are safely achievable in relatively healthy
subjects of >70 y of age, but the study was underpowered to
definitely determine whether strict control was superior to less
stringent BP targets
Significant reduction in stroke and fatal and nonfatal cardiac end
points
Significant reductions in total strokes, all-cause mortality, and all
fatal and nonfatal cardiac end points
Reduction in the rate of fatal and nonfatal strokes, all-cause
mortality, death from CV events, and heart failure
The incidence of strictly lowering BP in the elderly patients
showed no statistically significance in CV mortality and renal
disease when compared with the mildly treated group
Reduction in the incidence of stroke and a trend in the reduction
of cardiac events
Significant reduction in the frequency of fatal and nonfatal stroke
and myocardial infarction
Use of diuretics reduce the risk of stroke, coronary, and all CV
events
Fixed-dose combination of beta blocker and diuretic reduced
mortality
Significant reduction in stroke and total CV events
Significant reduction in stroke
Twofold difference in stroke rates from treatment with a diuretic
Reduction in cardiovascular (CV) mortality
Results
Note: ALLHAT = Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial; Australia HTN = HTN-hypertension; CA = calcium antagonist; CONVINCE = Controlled Onset Verapamil Investigation
of Cardiovascular End Points Trial; EWPHE = European Working Party on Hypertension in the Elderly; INVEST = International Verapamil SR-Trandolapril study; LVD = left ventricular dysfunction.
European Working Party in High Blood
Pressure in the Elderly (EWHPE),
1985 (59)
Coope and Warrender Trial, 1986 (60)
Systolic Hypertension in the Elderly
Pilot Program (SHEP-P), 1989 (61)
Systolic Hypertension in the Elderly
(SHEP) 1991 (62)
Swedish Trial in Old Patients with
Hypertension (STOP) 1991(63)
Medical Research Council Trial in the
Elderly (MRC) 1992 (64)
Cardiovascular Study in the Elderly
(CASTEL), 1994 (65)
Shanghai Trial of Nifedipine in the
Elderly (STONE), 1996 (66)
Systolic Hypertension in Europe
(Syst-Eur) 1997 (19)
Systolic Hypertension in China
(Syst-China) 2000 (67)
Hypertension in the Very Elderly Trial
(HYVET) 2008(5)
Japanese Trial to Assess Optimal
Systolic Blood Pressure in Elderly
Hypertensive Patients (JATOS) study
group 2008 (27)
Valsartan in Elderly Isolated Systolic
Hypertension (VALISH) study 2010
(68)
Clinical Trials
Mean Age of
Participants (Age
Range)
Table 1. Summary of Antihypertensive Clinical Trials in the Elderly Patients
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OLIVA and BAKRIS
Hypertension in the Elderly Population
1347
Figure 2. Proposed algorithm in the treatment of hypertension in the elderly population. ACE-I = angiotensin-converting enzyme inhibitors; ARB = angiotensin
receptor blockers; BP = blood pressure; CKD = chronic kidney disease; MI = myocardial infarction; SBP = systolic blood pressure; RAAS = renin–angiotensin–
aldosterone system.
person is having no therapeutic response or had significant
side effects, a drug from another class should be substituted.
In fact, most elderly patients require two or more drugs to
achieve the recommended goals in clinical trials. Either a
diuretic or calcium antagonist may be an initial drug or a
diuretic should be one of the first two agents when starting
combination drugs. When BP is more than 20/10 mmHg
above goal, the recommendation is to initiate with two antihypertensive medications, with one of the choices is a diuretic. Single-pill combinations that incorporate logical doses
of two agents may enhance convenience and compliance
in elderly patients (6). A proposed algorithm is seen in
Figure 2 in the management of hypertension in this age
group. However, there is still a need for individualization of
treatment, thus treatment options should be carefully considered in the elderly population. The benefits of lowering
BP must be weighed with the risks of side effects and the
concomitant morbidity of the patient.
Thiazide diuretics such as hydrochlorothiazide, chlorthalidone, and bendrofluazide are recommended for initiating
therapy (22). Diuretics cause an initial reduction of intravascular volume, peripheral vascular resistance, BP in more
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OLIVA and BAKRIS
Figure 3. Achieved systolic blood pressure (Sbp) in hypertension clinical trials involving elderly population. ACCOMPLISH = Avoiding Cardiovascular Events
through Combination Therapy in Patients Living with Systolic Hypertension trial; HYVET = Hypertension in the Very Elderly Trial; LIFE = Losartan Intervention For
Endpoint study;MRC-elderly = Medical Research Council Trial in the Elderly; SHEP = Systolic Hypertension in the Elderly study; STOP-2 = Swedish Trial in Old
Patients with Hypertension; STONE = Shanghai Trial of Nifedipine in the Elderly; Syst-China = Systolic Hypertension in China; Syst-Eur = Systolic Hypertension
in Europe.
than 50% of patients, and are basically well-tolerated and
inexpensive (36,37). However, they can cause hypokalemia,
hypomagnesemia, and hyponatremia and are therefore not
recommended in patients with baseline electrolyte abnormalities. Serum potassium should be monitored and supplementation should be given if needed (6). Indapamide, a
nonthiazide sulfonamide diuretic, may also be used in the
elderly population (5).
Calcium antagonists are well suited for elderly patients
whose hypertensive profile is based on increasing arterial
dysfunction secondary to decreased atrial and ventricular compliance. This class of drugs dilates coronary and
peripheral arteries in doses that do not severely affect myocardial contractility (38–41). They hold promise in the treatment in the elderly population. Most adverse effects relate
to consequences of vasodilation including ankle edema,
headache, and postural hypotension. First-generation
drugs, such as nifedipine, verapamil, and diltiazem should
be avoided in patients with left ventricular dysfunction.
Nondihydropyridines can precipitate heart blocks in the
elderly with underlying conduction defects (42).
Renin–angiotensin–aldosterone system blockers, such as
angiotensin-converting enzyme inhibitors (ACE-Is), angiotensin receptor blockers, and direct renin inhibitors, may
be used in the elderly population (43–45). Theoretically as
aging occurs, there is a reduction in the angiotensin levels,
thus ACE-Is may not be an effective medication for hypertension in the elderly population; however, several clinical
trials have shown otherwise. The use of ACE-Is is beneficial
in the reduction of morbidity and mortality in patients with
myocardial infarction, reduced systolic function, heart failure, and reduction in the progression of diabetic renal disease
and hypertensive nephrosclerosis (46–49). In elderly patients
with hypertension and diabetes, angiotensin receptor blockers are considered first-line treatment and as an alternative to
ACE-I in patients who cannot tolerate the latter (50). Finally,
it appears that use of a blocker of the renin–angiotensin system may provide greater benefit on CV and renal risk reduction than use of a diuretic based on data from the Avoiding
Cardiovascular Events through Combination Therapy in
Patients Living with Systolic Hypertension (ACCOMPLISH)
trial, a large outcome trial of 11,506 people with a mean age
of 68 years. Although there are very few data on kidney disease in the elderly population, ACCOMPLISH trial (51) did
provide some evidence worthy of being tested in a prospective trial, that is, that a calcium antagonist/ACE-I combination led to fewer people going on dialysis than a diuretic/
ACE-I combination; an effect that could not be explained by
differences in BP (Figure 4). It must be noted that those older
than 70 years tend to drink small amounts of fluid and hence,
this makes them more vulnerable to decline in kidney function by renin–angiotensin–aldosterone system blockade;
Hypertension in the Elderly Population
1349
Figure 4. Improvement of kidney function when using combination of amlodipine/benazepril as compared with benazepril/hydrochlorothiazide (hctz) in elderly
hypertensive patients (ACCOMPLISH trial). ACCOMPLISH = Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic
Hypertension trial).
thus, it is recommended that they increase their fluid intake
to prevent dehydration.
The clinical benefits of beta blockers as monotherapy
in uncomplicated elderly patients are poorly documented.
They may have a role in combination therapy, especially
with diuretics. Beta blockers have established roles in
hypertensive patients complicated by certain arrhythmias,
migraine headaches, senile tremors, coronary artery disease, or heart failure (52,53). Nebivolol, a selective beta-1
blocker with nitric oxide properties, does not show any
associated symptoms of depression, sexual dysfunction,
dyslipidemia, and hyperglycemia in the elderly population,
unlike earlier generation of beta blockers (54,55).
Potassium-sparing diuretics are useful when combined with other agents. Aldosterone-blocking agents like
spironolactone and eplerenone reduce vascular stiffness
and systolic BP (56–58). They are also useful for hypertensive patients with heart failure or primary hyperaldosteronism. Gynecomastia and sexual dysfunction are the limiting
adverse events or reactions in men using spironolactone but
are less frequent with eplerenone. The epithelial sodium
transport antagonists (amiloride, triamterene) are most useful when combined with another diuretic.
Other agents, such as alpha blockers, centrally acting
drugs (eg, clonidine), and nonspecific vasodilators (eg,
minoxidil) should not be used as first-line treatment in the
elderly hypertensive patient. Instead, they are reserved as
part of a combination regimen to maximize BP control after
other agents have been deployed (6).
Conclusion
The elderly population is increasing, and the dilemma
in treatment is aggravated by the changes in their physiology and arterial structure brought about by aging. Thus,
there is a need to give extra care in this age group of
patients. The advent of the 2011 consensus guidelines
delineates for doctors the management of hypertension in
this age group, but it is the prerogative of the physician
to individualize treatment, as every elderly hypertensive
patient may react differently to the treatment. It is our
goal to not just decrease the risk of CV diseases brought
about by elevated BPs but to prolong their lives as well.
Funding
This article had no funding support from any federal or private agency
or group and is solely the work of the authors.
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