Curr Hypertens Rep (2013) 15:582–589
DOI 10.1007/s11906-013-0384-x
HYPERTENSION AND THE BRAIN (M BANACH AND A ZANCHETTI, SECTION EDITORS)
Hypertension-Related Stroke Prevention in the Elderly
Wilbert S. Aronow
Published online: 16 August 2013
# Springer Science+Business Media New York 2013
Abstract Hypertension is a major risk factor for cardiovascu-
lar events, including ischemic stroke and hemorrhagic stroke.
Reduction of blood pressure by lifestyle measures and antihy-
pertensive drug therapy reduces stroke in elderly men and
women. The use of diuretics, beta blockers, calcium channel
blockers, angiotensin-converting enzyme inhibitors, or angio-
tensin receptor blockers causes a similar reduction in reducing
coronary events and stroke for a given reduction in blood
pressure. The American College of Cardiology Foundation/
American Heart Association 2011 expert consensus document
on hypertension in the elderly recommended that the blood
pressure should be reduced to less than 140/90 mm Hg in adults
younger than 80 years at high risk for cardiovascular events.
On the basis of data from the Hypertension in the Very Elderly
trial, these guidelines recommended that the systolic blood
pressure should be reduced to 140 to 145 mm Hg if tolerated
in adults aged 80 years and older. The 2013 European Society
of Hypertension guidelines recommended that reducing blood
pressure to less than 130/80 mm Hg in adults at high risk for
cardiovascular events was unsupported by prospective trial
data. The systolic blood pressure should be reduced to less
than 140 mm Hg in these adults and to between 140 to 150 mm
Hg in adults aged 80 years and older.
Keywords Hypertension . Stroke . Elderly . Diuretics .
Antihypertensive drug therapy Cardiovascular events
Introduction
Numerous studies have demonstrated that hypertension is a
major risk factor for stroke in elderly persons [1–4, 5••, 6–16].
W. S. Aronow (*)
Cardiology Division, New York Medical College, Macy Pavilion,
Room 138, Valhalla, NY 10595, USA
e-mail: wsaronow@aol.com
Hypertension is present in 77 % of patients with a first stroke
[17]. A higher the systolic or diastolic blood pressure is
associated with a higher the incidence of stroke [1]. In the
Framingham Heart Study, hypertension was the risk factor
most strongly related with stroke incidence in elderly men and
women and increased the risk ratio of stroke 1.9 times in
elderly men and 2.3 times in elderly women [1]. At 42-
month follow-up of 664 men, mean age 80 years, and at 48-
month follow-up of 1,488 women, mean age 82 years, hyper-
tension increased the relative risk of new stroke 2.2 times in
elderly men and 2.4 times in elderly women [3]. In elderly
blacks and whites with hypertension, the incidence of new
stroke at 42-month follow-up was increased by prior stroke
(odds ratio=2.6), echocardiographic left ventricular hypertro-
phy (LVH) (odds ratio=4.2), and electrocardiographic LVH
(odds ratio=2.1) [4]. This review presents the most current
knowledge on the therapy and prevention of stroke in hyper-
tensive elderly patients.
Search Strategy
The electronic databases - MEDLINE (1966 – July 2013), and
SCOPUS (1965 – July 2013), as well as abstracts from na-
tional and international cardiovascular meetings, were
searched. Where necessary, the relevant authors were
contacted to obtain further data. The main data search terms
were: hypertension, stroke, elderly, diuretics, antihypertensive
drug therapy, cardiovascular events, and therapy.
Lifestyle Measures
Lifestyle modification should be used in older persons to
retard development of hypertension and to reduce the dose
levels of drugs needed to control hypertension. Weight reduc-
tion, consuming a diet rich in fruits, vegetables, and low-fat
Curr Hypertens Rep (2013) 15:582–589
dairy products with a reduced amount of saturated fat and total
fat, sodium reduction, smoking cessation, regular aerobic
physical activity, avoidance of excessive caffeine, avoidance
of excessive alcohol intake, and avoidance of drugs that can
increase blood pressure, including sympathomimetics, non-
steroidal anti-inflammatory drugs, and glucocorticoids, are
recommended [5••, 18–20]. Implementing a national salt-
reduction program is likely a simple and cost-effective way
of improving public health [20–22]. Current guidelines sug-
gest no more than 2,300 mg of sodium daily in the general
population and no more than 1,500 mg of sodium daily in
persons with hypertension, in blacks, in elderly persons, and
in persons with chronic kidney disease, heart failure, or dia-
betes mellitus [20, 23].
Effect of Antihypertensive Drug Therapy on Stroke
in Elderly Persons
In the European Working Party on High Blood Pressure in the
Elderly Trial, 840 patients (70 % women), mean age
71.5 years, with a blood pressure of 182/101 mm Hg were
randomized in a double-blind study to placebo or hydrochlo-
rothiazide plus triamterene (Table 1) [6]. If the blood pressure
remained raised, methyldopa was added to the drug therapy
group and matching placebo to the placebo group. At last
follow-up, the blood pressure was 167/90 mm Hg in the
placebo group and 148/85 mm Hg in the drug therapy group.
Table 1 Studies of effect of antihypertensive drug therapy on stroke in elderly persons
Study Mean Age
European Working Party on High Blood 71.5 years
Pressure in the Elderly Trial [6]
Randomized trial of treatment of hypertension 68.8 years
in elderly in primary care [7]
Systolic Hypertension in the Elderly 71.6 years
Program [8, 9]
Swedish Trial in Old Patients with 75.7 years
Hypertension [10]
Medical Research Council trial [11] 70.3 years
Systolic Hypertension in Europe trial [12, 13] 70.3 years
Systolic Hypertension in China trial [14] 66.5 years
Hypertension in the Very Elderly Trial [15] 83.6 years
583
Follow-up was 3.0 years for placebo and 3.4 years for drug
therapy. Compared to placebo, drug therapy reduced cerebro-
vascular mortality by 43 % (p =0.15) and non-terminating
cerebrovascular events by 52 % (p =0.026) [6].
A total of 884 patients (69 % women), mean age 68.8 years,
followed in a primary care practice with a blood pressure of
196/99 mm Hg were randomized to a control group or a drug
treatment group (Table 1) [7]. The principal antihypertensive
drugs administered were atenolol and bendrofluazide. Blood
pressure decreased by 16/10 mm Hg in the control group.
Blood pressure decreased by 18/11 mm Hg more in the drug
treatment group than in the control group. Mean follow-up
was 4.4 years. Compared to the control group, the drug
treatment group had a 30 % reduction in fatal stroke (p <
0.025) and a 58 % reduction in fatal plus nonfatal strokes
(p <0.03) [7].
The Systolic Hypertension in the Elderly Program (SHEP)
randomized 4,736 persons (57 % women) living in the com-
munity, mean age 71.6 years, with isolated systolic hyperten-
sion and a baseline blood pressure of 170/77 mm Hg to
double-blind placebo or to drug therapy with chlorthalidone
and if needed to atenolol or to reserpine if atenolol was
contraindicated (Table 1) [8, 9]. The 5-year average blood
pressure was 155/72 mm Hg in the placebo group and 143/
68 mm Hg in the drug treatment group. Mean follow-up was
4.5 years. The 5-year incidence of total stroke was 8.2 per 100
persons treated with placebo and 5.2 per 100 persons treated
with drug therapy [8]. Compared to placebo, drug therapy
Follow-Up Results
3.2 years Compared to placebo, drug therapy reduced cerebrovascular mortality
43 % (p =0.15) and non-terminating cerebrovascular events 52 %
(p =0.026)
4.4 years Compared to control, drug therapy fatal stroke 30 % (p <0.025) and all
strokes 58 % (p <0.03)
4.5 years Compared to placebo, drug therapy reduced total strokes 36 %
(p =0.0003) with a 5-year absolute reduction of 30 strokes per 1,000
persons; Compared to placebo, drug therapy reduced ischemic strokes
by 37 % (95 % CI, 0.48–0.82) and hemorrhagic strokes by 54 %
(95 % CI, 0.21–1.02)
25 months Compared to placebo, drug therapy reduced all strokes by 47 %
(95 % CI, 0.33–0.86) and fatal strokes by 76 % (95 % CI,
0.04–0.91)
5.8 years Compared to placebo, drug therapy reduced all strokes by 25 %
(p =0.04), diuretic therapy reduced all strokes by 31 % (p =0.04),
and atenolol insignificantly reduced all strokes by 18 %
2 years Compared to placebo, drug therapy reduced all strokes by 42 %
(p =0.003) and nonfatal stroke by 44 % (p =0.007)
3 years Compared to placebo, drug therapy reduced all strokes by 38 %
(p =0.01) and fatal strokes by 58 % (p =0.02)
1.8 years Compared to placebo, drug therapy reduced all strokes by 30 %
(p =0.06) and fatal strokes by 39 % (p =0.05)
584
reduced total stroke by 36 % (p =0.0003) with a 5-year
absolute reduction of 30 strokes per 1,000 persons [8].
In SHEP, ischemic strokes occurred in 132 persons treated
with placebo and in 85 persons treated with drug therapy
(adjusted relative risk=0.63; 95 % CI, 0.48–0.82) [9]. In
SHEP, hemorrhagic strokes occurred in 19 persons treated
with placebo and in 9 persons treated with drug therapy
(adjusted relative risk=0.46; 95 % CI, 0.21–1.02) [9]. Treat-
ment effect was observed within 1 year for hemorrhagic
strokes but was not seen until the second year for ischemic
strokes [9]. Total stroke was reduced 33 % if the systolic blood
pressure was reduced to <160 mm Hg (95 % CI, 0.51–0.89),
38 % if the systolic blood pressure was reduced to <150 mm
Hg (95 % CI, 0.47–0.82), and 22 % if the systolic blood
pressure was reduced to <140 mm Hg (95 % CI, 0.51–1.07)
[9]. If the SHEP goal of reducing systolic blood pressure at
least 20 mm Hg to <160 mm Hg was reached, there was a
33 % reduction in total stroke (95 % CI, 0.51-0.84) [9].
The Swedish Trial in Old Patients With Hypertension
(STOP-Hypertension) randomized 1,627 persons (63 % wom-
en), mean age 75.7 years, with a baseline blood pressure of
195/102 mm Hg to double-blind placebo or to drug therapy
with either atenolol, hydrochlorothiazide plus amiloride, met-
oprolol, or pindolol (Table 1) [10]. At the last follow-up, the
blood pressure was 186/96 mm Hg in the placebo group and
167/87 mm Hg in the drug treatment group. Mean follow-up
was 25 months. Compared with placebo, drug therapy re-
duced total stroke by 47 % (95 % CI, 0.33–0.86) and fatal
stroke by 76 % (95 % CI, 0.04–0.91) [10].
The Medical Research Council trial randomized 4,396
persons (58 % women), mean age 70.3 years, with a baseline
blood pressure of 185/91 mm Hg to placebo or to drug therapy
with atenolol or hydrochlorothiazide plus amiloride (Table 1)
[11]. After 2 years, the reduction in systolic and diastolic
blood pressure compared to placebo was similar in persons
randomized to atenolol or diuretic therapy. Mean follow-up
was 5.8 years. Compared with placebo, drug therapy reduced
stroke by 25 % (p =0.04), diuretic therapy reduced stroke by
31 % (p =0.04), and atenolol insignificantly reduced stroke by
18 % [11].
The Systolic Hypertension in Europe (Syst-Eur) trial
randomized 4,695 persons (67 % women), mean age
70.3 years, with isolated systolic hypertension with a
baseline blood pressure of 174/86 mm Hg to placebo or
to drug therapy with nitrendipine with the addition of
enalapril and hydrochlorothiazide if needed (Table 1)
[12, 13]. At 2-year follow-up, blood pressure was reduced
13/2 mm Hg by placebo and 23/7 mm Hg by drug ther-
apy. Median follow-up was 2 years. Compared with pla-
cebo, drug therapy reduced fatal and nonfatal stroke by
42 % (p =0.003) and nonfatal stroke by 44 % (p =0.007).
Treatment of 1,000 patients for 5 years with drug therapy
would prevent 29 strokes [12, 13].
Curr Hypertens Rep (2013) 15:582–589
The Systolic Hypertension in China (Syst-China) trial of
2,394 persons (36 % women), mean age 66.5 years, with
isolated systolic hypertension with a baseline blood pressure
of 171/86 mm Hg assigned alternate patients to placebo or to
drug therapy with nitrendipine with the addition of captopril
or hydrochlorothiazide or both if needed (Table 1) [14]. After
2 years, the blood pressure was reduced 10.9/1.9 mm Hg in
the placebo group and 20.0/5.0 mm Hg in the drug treatment
group. Mean follow-up was 3.0 years. Compared to placebo,
drug therapy reduced all strokes by 38 % (p =0.01) and fatal
stroke by 58 % (p =0.02). Treatment of 1,000 patients for
5 years with drug therapy would prevent 39 strokes [14].
A meta-analysis of seven randomized, controlled antihy-
pertensive drug trials included 20,802 women and 19, 975
men [24]. Antihypertensive drug therapy reduced all strokes
by 38 % in women (p <0.001) and by 34 % in men (p <0.001)
(p not significant between women and men) [24]. Antihyper-
tensive drug therapy reduced fatal strokes by 29 % in women
(p =0.03) and by 43 % in men (p <0.001) (p not significant
between women and men) [24]. The overall data suggest that
reduction in stroke in persons with hypertension is related
more to a reduction in blood pressure than to the type of
antihypertensive drugs used [25].
The Hypertension in the Very Elderly Trial (HYVET) is the
only randomized, double-blind, placebo-controlled trial inves-
tigating the effects of antihypertensive drug treatment in pa-
tients aged 80 years and older [15]. In this study, 3,845
patients (61 % women), mean age 83.6 years, with a baseline
blood pressure of 173/90.8 mm Hg were randomized to
double-blind placebo or to drug therapy with indapamide
and if needed to perindopril to achieve a target blood pressure
of 150/90 mm Hg. At 2 years, the blood pressure was reduced
14.5/6.8 mm Hg in the placebo group and 29.5/12.9 mm Hg in
the drug treatment group. The lowest systolic blood pressure
reached was 143 mm Hg. Median follow-up was 1.8 years.
Drug therapy caused a 30 % reduction in fatal or nonfatal
stroke (p =0.06) and a 39 % reduction in fatal stroke (p =
0.05). Treatment of 1,000 patients for 2 years would prevent
11 strokes. The study was terminated prematurely for ethical
reasons because drug therapy caused a 21 % reduction in all-
cause mortality (p =0.02) [15].
Antihypertensive Drugs and Strokes
Of 6,105 patients with a prior stroke or transient ischemic
attack in the perindopril protection against recurrent stroke
study (PROGRESS), 948 patients with hypertension were
randomized to combination therapy with perindopril plus
indapamide and 955 patients with hypertension were random-
ized to placebo [26]. Follow-up was 4 years. Drug therapy
reduced stroke risk by 44 % (95 % CI, 28–57) in hypertensive
patients with prior stroke or transient ischemic attack [26].
Curr Hypertens Rep (2013) 15:582–589
In the Swedish Trial in Old Patients with Hypertension-2
study, 6,614 patients, mean age 76 years, with hypertension
were randomized to drug treatment with conventional antihy-
pertensive drug therapy (atenolol, metoprolol, pindolol, or
hydrochlorothiazide plus amiloride) or to drug treatment with
newer drugs (enalapril, lisinopril, felodipine, or isradapine)
[27]. Old and new antihypertensive drugs were similar in
reducing strokes [28].
The overall data suggest that reduction in stroke in persons
with hypertension is related more to a reduction in blood
pressure than to the type of antihypertensive drugs used [5••,
25]. A meta-analysis of 147 randomized trials in 464,000
persons treated for hypertension showed that with the excep-
tion of the extra protective effect of beta blockers given shortly
after a myocardial infarction and the minor additional effect of
calcium channel blockers in preventing stroke, use of beta
blockers, angiotensin-converting enzyme inhibitors, angioten-
sin receptor blockers, diuretics, and calcium channel blockers
cause a similar reduction in reducing coronary events and
stroke for a given decrease in blood pressure [28, 29].
The American College of Cardiology Foundation/
American Heart Association 2011 expert consensus document
on hypertension in the elderly recommended that diuretics,
angiotensin-converting enzyme inhibitors, angiotensin recep-
tor blockers, beta blockers, and calcium channel blockers have
all demonstrated benefit in reducing cardiovascular events in
randomized trials [5••]. The choice of specific antihyperten-
sive drugs depends on efficacy, tolerability, presence of spe-
cific comorbidities, and cost [5••].
Optimal Blood Pressure Goal in Treatment
of Hypertension
In the absence of randomized control data, the seventh report
of the Joint National Committee on Prevention, Detection,
Evaluation, and Treatment of High Blood Pressure recom-
mended that patients with diabetes mellitus or with chronic
kidney disease should have their blood pressure reduced to
less than 130/80 mm Hg [18, 30]. In the absence of random-
ized control data, the American Diabetes Association recom-
mended that patients with diabetes mellitus and hypertension
should have their blood pressure reduced to less than 130/
80 mm Hg [30, 31]. In the absence of randomized control
data, the National Kidney Foundation Kidney Disease Out-
come Quality Initiative guidelines recommended that pa-
tients with chronic kidney disease and hypertension should
have their blood pressure lowered to less than 130/80 mm
Hg [30, 32].
In the absence of randomized control data, the American
Heart Association 2007 guidelines recommended that patients
with hypertension at high risk for coronary events such as
those with coronary artery disease, a coronary artery risk
585
equivalent , diabetes mellitus, chronic kidney disease, or a
10-year Framingham risk score ≥10 % should have their blood
pressure reduced to less than 130/80 mm Hg [31]. These
guidelines also recommended that patients with hypertension
and left ventricular dysfunction should have their blood pres-
sure reduced to <120/80 mm Hg [30, 33].
The European Society of Hypertension Task Force that
reassessed the 2007 European Society of Hypertension-
European Society of Cardiology guidelines recommended that
reducing the blood pressure to less than 130/80 mm Hg
in patients at high risk for cardiovascular events was
unsupported by prospective trial data, and that the systolic
blood pressure should be reduced to less than 140 mm Hg in
these patients [29, 34, 35] The American College of Cardiol-
ogy Foundation/American Heart Association 2011 expert
consensus document on hypertension in the elderly recom-
mended that the blood pressure should be reduced to less than
140/90 mm Hg in adults younger than 80 years at high risk for
cardiovascular events [5••, 34]. On the basis of data from the
Hypertension in the Very Elderly trial [15], these guidelines
recommended that the systolic blood pressure should be re-
duced to 140 to 145 mm Hg if tolerated in adults aged 80 years
and older. The 2013 European Society of Hypertension guide-
lines recommended that reducing blood pressure to less than
130/80 mm Hg in adults at high risk for cardiovascular events
was unsupported by prospective trial data [36••]. The systolic
blood pressure should be reduced to less than 140 mm Hg in
these adults and to between 140 to 150 mm Hg in adults aged
80 years and older [36••]. I concur with these guidelines [5••,
34, 36••, 37–43]. The below studies discuss the reasons for my
recommendations.
The Pravastatin or Atorvastatin Evaluation and Infection
Therapy-Thrombolysis in Myocardial Infarction (PROVE IT-
TIMI) 22 trial enrolled 4,162 patients with an acute coronary
syndrome (acute myocardial infarction with or without ST-
segment elevation or high-risk unstable angina pectoris) [44].
At 24-month mean follow-up, the lowest cardiovascular
events rates occurred with a systolic blood pressure between
130 to 140 mm Hg and a diastolic blood pressure between 80
to 90 mm Hg with a nadir of 136/85 mm Hg. The event rate
for stroke was too small to derive a relationship between blood
pressure and stroke. The investigators suggested that a blood
pressure less than 110/70 mm Hg may be dangerous for
patients with an acute coronary syndrome [44].
An observational subgroup analysis was performed in the
6,400 patients enrolled in the International Verapamil SR-
Trandolapril Study (INVEST) who had diabetes mellitus and
coronary artery disease[45]. Patients were categorized as hav-
ing tight control of their blood pressure if they could maintain
their blood pressure below 130/85 mm Hg, usual control if
they could maintain their systolic blood pressure between 130
to 139 mm Hg, and uncontrolled if their systolic blood pres-
sure was 140 mm Hg or higher. The total stroke event rate per
586
100 patient-years was 0.59 in patients with tight control of
hypertension, 0.61 in patients with usual control of hyperten-
sion, and 1.19 with uncontrolled hypertension, p <0.001.
When extended follow-up to 5 years following the close of
INVEST was included, the all-cause mortality rate was 22.8 %
with tight control of blood pressure versus 21.8 % with
usual control of blood pressure (adjusted hazard ratio=1.15,
p =0.04) [45].
The Action to Control Cardiovascular Risk in Diabetes
(ACCORD ) blood pressure trial randomized 4,733 patients
with type 2 diabetes mellitus to intensive blood pressure
control with a target systolic blood pressure of less than
120 mm Hg or to standard blood pressure control with a target
systolic blood pressure less than 140 mm Hg [34, 46]. The
primary composite outcome was nonfatal myocardial infarc-
tion, nonfatal stroke, or death from cardiovascular causes.
Mean follow-up was 4.7 years. After 1 year, the mean systolic
blood pressure was 119.3 mm Hg in the intensive blood
pressure control group versus 133.5 mm Hg in the standard
blood pressure control group. The annual rates of the primary
outcome, of death from any cause, and of cardiovascular death
were not significantly different between intensive and stan-
dard blood pressure control. The annual stroke rate, a
prespecified secondary outcome, was 0.32 % in the intensive
blood pressure control group versus 0.53 % in the standard
blood pressure control group, p =0.01 (number needed to treat
by intensive blood pressure control to reduce 1 stroke=476
patients). Serious adverse events attributed to antihypertensive
treatment occurred in 3.3 % of the intensive blood pressure
control group versus 1.27 % of the standard blood pressure
control group (p <0.001) (number needed to treat by intensive
blood pressure control to increase 1 serious adverse event=49
patients) [34, 46].
The ongoing Telmisartan Alone and in combination with
Ramipril Global Endpoint Trial (ONTARGET) included pa-
tients, mean age 67 years, with hypertension at high risk for
cardiovascular events in which 12,273 patients had their blood
pressure reduced to <140/90 mm Hg and 16,743 patients had
their blood pressure reduced to <130/80 mm Hg and were
evaluated for stroke [47]. Mean follow-up was 4.6 years.
Stroke was reduced 19 % in patients who had their blood
pressure reduced to <140/90 mm Hg (p =0.017). Stroke was
insignificantly reduced 11 % in patients who had their blood
pressure reduced to <130/80 mm Hg [47].
In both diabetics and nondiabetics in ONTARGET, antihy-
pertensive drug treatment reduced the primary outcome of
cardiovascular death, nonfatal myocardial infarction, nonfatal
stroke, or hospitalization for heart failure if the baseline sys-
tolic blood pressure was between 143 to 155 mm Hg [34, 48].
Except for stroke, there was no benefit in reducing fatal or
nonfatal cardiovascular outcomes by lowering the systolic
blood pressure below 130 mm Hg in diabetics and in nondi-
abetics. The lowest incidence of death from cardiovascular
Curr Hypertens Rep (2013) 15:582–589
causes in diabetics occurred with a systolic blood pressure of
135.6 mm Hg (range 130.6 to 140.5 mm Hg). The lowest
incidence of death from cardiovascular causes in nondiabetics
occurred with a systolic blood pressure of 133.1 mm Hg
(range 128.8 to 137.4 mm Hg). For the primary outcome,
the highest risk in both diabetics and in nondiabetics
occurred in patients with the lowest or highest in-trial
diastolic blood pressure (67.2 mm Hg and 86.7 mm Hg,
respectively) [34, 48].
A meta-analysis of 2,272 patients with hypertensive chron-
ic kidney disease without diabetes demonstrated that a blood
pressure of less than 125/75 to 130/80 mm Hg did not improve
clinical outcomes more than a target blood pressure of less
than 140/90 mm Hg [49]. Whether a blood pressure of less
than 130/80 mm Hg benefits patients with proteinuria greater
than 300 to 1,000 mg per day requires further study [49]. In
7,785 patients with mild to moderate chronic systolic and
diastolic congestive heart failure in the Digitalis Investigation
Group trial, a baseline systolic blood pressure greater than
120 mm Hg was associated with better clinical outcomes than
a systolic blood pressure of ≤120 mm [50].
The Prevention Regimen for Effectively Avoiding Second
Strokes (PROFESS) trial included 20,330 patients, mean age
66 years, with a recent non-cardioembolic ischemic stroke
[51••]. Mean follow-up was 2.5 years. The primary outcome
was first recurrence of stroke of any type. The secondary
outcome was a composite of stroke, myocardial infarction,
or death from vascular causes.
The recurrent stroke rates were 8.0 % for patients with a
systolic blood pressure <120 mm Hg, 7.2 % for patients with a
systolic blood pressure of 120 to 129 mm Hg, 6.8 % for
patients with a systolic blood pressure of 130 to 139 mm
Hg, 8.7 % for patients with a systolic blood pressure of 140
to 149 mm Hg, and 14.1 % for patients with a systolic blood
pressure of ≥150 mm Hg [51••]. Compared with patients with
a systolic blood pressure of 130–139 mm Hg, the risk of the
primary outcome was increased in patients with a systolic
blood pressure <120 mm Hg (adjusted hazard ratio=1.29;
95 % CI, 1.07 to 1.56), increased in patients with a systolic
blood pressure of 140 to 149 mm Hg (adjusted hazard ratio=
1.23; 95 % CI, 1.07 to 1.41), and increased in patients with a
systolic blood pressure ≥150 mm Hg (adjusted hazard ratio=
2.08; 95 % CI, 1.83 to 2.37). Compared with patients with a
systolic blood pressure of 130–139 mm Hg, the risk of the
secondary outcome was increased in patients with a systolic
blood pressure<120 mm Hg (adjusted hazard ratio=1.31;
95 % CI, 1.13 to 1.52), increased in patients with a systolic
blood pressure of 120 to 129 mm Hg (adjusted hazard ratio=
1.16; 95 % CI, 1.03 to 1.31), increased in patients increased in
patients with a systolic blood pressure of 140 to 149 mm Hg
(adjusted hazard ratio=1.24; 95 % CI, 1.11 to 1.39), and
increased in patients with a systolic blood pressure ≥150 mm
Hg (adjusted hazard ratio=1.94; 95 % CI, 1.74 to 2.16) [51••].
Curr Hypertens Rep (2013) 15:582–589
After the extensive review of the studies relating achieved
blood pressure with cardiovascular events and strokes, one
must be cautious about the limitations of this approach.
Ogihara et al. [52] demonstrated that cardiovascular events
showed a J-curve relationship with systolic blood pressure in
patients aged 75 years and older with a higher incidence of
cardiovascular events with a systolic blood pressure less than
120 mm Hg compared with a systolic blood pressure of 120 to
139 mm Hg. The analyses from the Felodipine Event Reduc-
tion (FEVER) trial provide strong support to guidelines
recommending a goal systolic blood pressure of less than
140 mm Hg in uncomplicated hypertensives, adults with
moderately elevated blood pressure, and elderly hypertensives
[53]. In the Japanese trial to assess optimal systolic blood
pressure in elderly hypertensive patients (JATOS), the final
blood pressures were lower in patients aged 65 to 85 years in
the strict treatment group (135.9/74.8 mm Hg ) than in the
mild treatment group (145.6/78.1 mm Hg) [54]. At 2-year
follow-up, the incidence of the primary endpoint of cardio-
vascular disease and renal failure was similar in both
groups [54].
Until additional data from randomized controlled trials
(including the Systolic Blood Pressure Intervention Trial
[SPRINT]) comparing various blood pressure targets in older
and younger patients as well as data from the Stroke in
Hypertension Optimal treatment (SHOT) trial [55] become
available, existing epidemiologic and clinical trial data sug-
gest that the blood pressure in patients with hypertension at
high risk for cardiovascular events because of coronary artery
disease, diabetes mellitus, chronic kidney disease, stroke, or
heart failure should be reduced to <140/90 mm Hg in patients
younger than 80 years and the systolic blood pressure reduced
to 140 to 145 mm Hg if tolerated in patients aged 80 years and
older [5••]. Hyperlipidemia and renal function must also be
considered in the treatment of hypertension in the elderly [56,
57]. The results of the Reasons for Geographic And Racial
Differences in Stroke (REGARDS) cohort study (which will
be presented in detail during 2013 European Society of
Cardiology Annual Congress) generate a hypothesis that
for all patients >55 years the recommended level of SBP
should be <140 mmHg with optimal values possibly between
120–139 mmHg, and intensive hypertension treatment
(BP <120 mmHg) should be a matter of further investigations.
The authors also emphasized that all future trials addressing
the optimal SBP goal should also take into account an
individual’s frailty status [58].
Conclusions
In conclusion, lifestyle measures and antihypertensive drug
therapy should be used to prevent stroke and other cardiovas-
cular events in elderly men and women with hypertension.
587
Other modifiable risk factors for stroke, especially smoking
and dyslipidemia, should be treated. Clinical trial data are
needed to determine the efficacy of lifestyle measures, differ-
ent types of antihypertensive drugs, and other interventional
approaches to control hypertension in the elderly, especially in
octogenarians [59]. Finally, there is no evidence in elderly
persons to support the use of lower blood pressure targets in
elderly patients at high risk for stroke and other cardiovascular
events. However, some observational studies also suggest for
this group of patients that a systolic blood pressure level less
than 140 mm Hg should be considered.
Compliance with ethics Guidelines
Conflict of Interest Wilbert S. Aronow declares that he has no conflict
of interest.
Human and Animal Rights and Informed Consent This article does
not contain any studies with human or animal subjects performed by the
author.
References
Recently published papers of particular interest have been
highlighted as:
•• Of major importance
1. Kannel WB. Hypertension in the elderly: Epidemiologic appraisal
from the Framingham study. Cardiol in Elderly. 1993;1:359–63.
2. Garland C, Barrett-Connor E, Suarez L, Criqui MH. Isolated systolic
hypertension and mortality after age 60 years. Am J Epidemiol.
1983;118:365–76.
3. Aronow WS, Ahn C, Gutstein H. Risk factors for new
atherothrombotic brain infarction in 664 older men and 1,488 older
women. Am J Cardiol. 1996;77:1381–3.
4. Aronow WS, Ahn C, Kronzon I, Koenigsberg M. Congestive heart
failure, coronary events and atherothrombotic brain infarction in
elderly blacks and whites with systemic hypertension and with and
without echocardiographic and electrocardiographic evidence of left
ventricular hypertrophy. Am J Cardiol. 1991;67:295–9.
5. •• Aronow WS, Fleg JL, Pepine CJ, et al. ACCF/AHA 2011 expert
consensus document on hypertension in the elderly: A report of the
american college of cardiology foundation task force on clinical
expert consensus documents. Developed in collaboration with the
American Academy of Neurology, American Geriatrics Society,
American Society for Preventive Cardiology, American Society of
Hypertension, American Society of Nephrology, Association of
Black Cardiologists, and European Society of Hypertension. J Am
Coll Cardiol. 2011;57:2037–114. This paper is the American College
of Cardiology Foundation/American Heart Association consensus
document on hypertension in the elderly.
6. Amery A, Birkenhager W, Brixko P, et al. Mortality and morbidity
results from the European working party on high blood pressure in
the elderly trial. Lancet. 1985;1:1349–54.
7. Coope J, Warrender TS. Randomised trial of treatment of hyperten-
sion in elderly patients in primary care. BMJ. 1986;293:1145–51.
8. SHEP Cooperative Research Group. Prevention of stroke by antihy-
pertensive drug treatment in older persons with isolated systolic
588
hypertension. Final results of the systolic hypertension in the elderly
program (SHEP). JAMA. 1991;265:3255–64.
9. Perry Jr HM, Davis BR, Price TR, et al. Effect of treating isolated
systolic hypertension on the risk of developing various types and
subtypes of stroke. The systolic hypertension in the elderly program
(SHEP). JAMA. 2000;284:465–71.
10. Dahlof B, Lindholm LH, Hansson L, et al. Morbidity and mortality in
the Swedish trial in Old patients with hypertension (STOP hyperten-
sion). Lancet. 1991;338:1281–5.
11. MRC Working Party. Medical research council trial of treatment of
hypertension in older adults: Principal results. BMJ. 1992;304:
405–12.
12. Staessen JA, Fagard R, Thijs L, et al. Randomised double-blind
comparison of placebo and active treatment for older patients with
isolated systolic hypertension. Lancet. 1997;350:757–64.
13. Staessen JA, Thijs L, Gasowski J, et al. Treatment of isolated systolic
hypertension in the elderly: Further evidence from the systolic
hypertension in Europe (syst-Eur) trial. Am J Cardiol. 1998;82:
20R–2R.
14. 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;16:1823–9.
15. Beckett NS, Peters R, Fletcher AE, et al. Treatment of hypertension in
patients 80 years of age or older. N Engl J Med. 2008;358:1887–98.
16. Miura K, Nakagawa H, Ohashi Y, et al. Four blood pressure indexes
and the risk of stroke and myocardial infarction in Japanese men and
women. A meta-analysis of 16 cohort studies. Circulation.
2009;119:1892–8.
17. Lloyd-Jones D, Adams R, Carnethon M, et al. Heart disease and
stroke statistics-2009 update: A report from the American heart
association statistics committee and stroke statistics subcommittee.
Circulation. 2009;119:e21–e181.
18. Chobanian AV, Bakris GL, Black HR, et al. The seventh report of the
joint national committee on prevention, detection, evaluation, and
treatment of high blood pressure. The JNC 7 report. JAMA.
2003;289:2560–72.
19. Spence JD. Nutritional and metabolic aspects of stroke prevention.
Adv Neurol. 2003;92:173–8.
20. Aronow WS. Treatment of systemic hypertension. Am J Cadiovasc
Dis. 2012;2:160–70.
21. Webster JL, Dunford EK, Hawkes C, Neal BC. Salt reduction initia-
tives around the world. J Hypertens. 2011;29:1043–50.
22. Frohlich ED, Susic D. Sodium and its multiorgan targets. Circulation.
2011;124:1882–5.
23. Whelton PK. Urinary sodium and cardiovascular disease risk:
Informing guidelines for sodium consumption. JAMA. 2011;
306:2262–4.
24. Gueyffier F, Boutitie, Boissel J-P. Effect of antihypertensive drug
treatment on cardiovascular outcomes in women and men. A meta-
analysis of individual patient data from randomized, controlled trials.
Ann Intern Med. 1997;126:761–7.
25. Aronow WS, Frishman WH. Treatment of hypertension and preven-
tion of ischemic stroke. Curr Cardiol reports. 2004;6:124–9.
26. Progress Collaborative Group. Randomised trial of a perindopril-
based blood-pressure-lowering regimen among 6105 individuals
with previous stroke or transient ischaemic attack. Lancet.
2001;358:1033–41.
27. 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:
1751–6.
28. Law MR, Morris JK, Wald NJ. Use of BP lowering drugs in the
prevention of cardiovascular disease: Meta-analysis of 147
randomised trials in the context of expectations from prospective
Curr Hypertens Rep (2013) 15:582–589
epidemiological studies. BMJ. 2009;338:b1665. doi:10.1136/bmj.
b1665.
29. Mancia G, Laurent S, Agabiti-Rosei E, et al. Reappraisal of European
guidelines on hypertension management: A European society of
hypertension task force document. Blood Press. 2009;18:308–47.
30. Aronow WS. What should the optimal blood pressure goal be in
patients with diabetes mellitus or chronic kidney disease? Arch Med
Sci. 2012;8:399–402.
31. American Diabetes Association. Standards of medical care for pa-
tients with diabetes mellitus. Diabetes Care. 2003;26(1):S33–50.
32. National Kidney Foundation. K/DOQI clinical practice guidelines for
chronic kidney disease: Evaluation, classification, and stratification.
Am J Kidney Dis. 2002;39(1):S1–266.
33. Rosendorff C, Black HR, Cannon CP, et al. Treatment of hyperten-
sion 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;115:2761–88.
34. Aronow WS. Treatment of hypercholesterolemia and hypertension in
diabetics with coronary artery disease. Clinical Lipidology.
2012;7:689–95.
35. Zanchetti A, Grassi G, Mancia G. When should antihypertensive
drug treatment be initiated and to what levels should systolic blood
pressure be lowered? a critical appraisal. J Hypertens. 2009;27:923–
34.
36. •• Mancia G, Fagard R, Narkiewicz K, et al. 2013 ESH/ESC guide-
lines for the management of hypertension 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). Eur Heart J. 2013;34:2159–219. This paper is
the European Society of Hypertension/European Society of Cardiol-
ogy 2013 guidelines document on management of hypertension.
37. Aronow WS. Hypertension guidelines. Hypertension. 2011;58:347–
8.
38. Banach M, Michalska M, Kjeldsen SE, et al. What should be the
optimal levels of blood pressure: Does the J-curve phenomenon
really exist? Expert Opin Pharmacother. 2011;12:1835–44.
39. Banach M, Aronow WS. Should we have any doubts about hyper-
tension therapy in elderly patients. ACCF/AHA 2011 expert consen-
sus document on hypertension in the elderly. Pol Arch Med Wewn.
2011;121:253–8.
40. Aronow WS, Banach M. Ten most important things to learn from the
ACCF/AHA 2011 expert consensus document on hypertension in the
elderly. Blood Pressure. 2012;21:3–5.
41. Aronow WS. Ten key points from the American College of Cardiol-
ogy Foundation/American Heart Association 2011 expert consensus
document on hypertension in the elderly. Am J Therap. In press
42. Banach M, Aronow WS. Hypertension therapy in the elderly-do we
know the answers to all the questions? The status after publication of
the ACCF/AHA 2011 Expert Consensus Document on Hypertension
in the Elderly. J Hum Hypertens. 2012;26:641–3.
43. Banach M, Aronow WS. Blood pressure J-curve: Current concepts.
Curr Hypertens Rep. 2012;14:556–66.
44. Bangalore S, Qin J, Sloan S, et al. What is the optimal blood pressure
in patients after acute coronary syndromes? Relationship of
blood pressure and cardiovascular events in the Pravastatin or
Atorvastatin Evaluation and Infection Therapy-Thrombolysis
in Myocardial Infarction (PROVE IT-TIMI) 22 trial. Circulation.
2010;122:2142–51.
45. Cooper-DeHoff RM, Gong Y, Handberg EM, et al. Tight blood
pressure control and cardiovascular outcomes among hypertensive
patients with diabetes and coronary artery disease. JAMA.
2010;304:61–8.
46. The ACCORD Study Group. Effects of intensive blood-pressure
control in type 2 diabetes mellitus. N Engl J Med. 2010;362:
1575–85.
Curr Hypertens Rep (2013) 15:582–589
47. Mancia G, Schumacher H, Redon J, et al. Blood pressure targets
recommended by guidelines and incidence of cardiovascular and
renal events in the ongoing telmisartan alone and in combination
with ramipril global endpoint trial (ONTARGET). Circulation.
2011;124:1727–36.
48. Redon J, Mancia G, Sleight P, et al. Safety and efficacy of
low blood pressures among patients with diabetes. Subgroup
analyses from the ONTARGET (ONgoing telmisartan alone and in
combination with ramipril global endpoint trial). J Am Coll Cardiol.
2012;59:74–83.
49. Upadhyay A, Earley A, Haynes SM, Uhlig K. Systematic review:
Blood pressure target in chronic kidney disease and proteinuria as an
effect modifier. Ann Intern Med. 2011;154:541–8.
50. Banach M, Bhatia V, Feller MA, et al. Relation of baseline
systolic blood pressure and long-term outcomes in ambulatory
patients with chronic mild to moderate heart failure. Am J
Cardiol. 2011;107:1208–14.
51. •• Ovbiagele B, Diener H-C, Yusuf S, et al. Level of systolic
blood pressure within the normal range and risk of recurrent
stroke. JAMA. 2011;306:2137–44. This paper discusses in
20 ,330 patients with a recent non -cardioembolic ischemic
stroke the recurrent stroke rates for different blood pressure
levels .
52. Ogihara T, Matsuoka H, Rakugi H. Practitioner's trial on the efficacy
of antihypertensive treatment in elderly patients with hypertension II
589
(PATE-hypertension II study) in Japan. Geriatr Gerontol Int.
2011;11:414–21.
53. Zhang Y, Zhang X, Liu L, et al. Is a systolic blood pressure target
<140 mm Hg indicated in all hypertensives? Subgroup analyses of
findings from the randomized FEVER trial. Eur Heart J.
2011;32:1500–8.
54. JATOS Study Group. Principal results of the Japanese trial to assess
optimal systolic blood pressure in elderly hypertensive patients
(JATOS). Hypertens Res. 2008;31:2115–27.
55. Zanchetti A, Liu L, Mancia G, et al. Stroke in hypertension optimal
treatment (SHOT) trial: Protocol and organization (abstract). J
Hypertens. 2013;31(A):e255.
56. Barylski M, Malyszko J, Rysz J, et al. Lipids, blood pressure, kidney-
what was new in 2011? Arch Med Sci. 2011;7:1055–66.
57. Malyszko J, Bachorzewska-Gajewska H, Malyszko J, et al. Markers
of kidney function in the elderly in relation to the new CKD-EPI
formula for estimation of glomerular filtration rate. Arch Med Sci.
2011;7:658–64.
58. Banach M. Optimal blood pressure levels in elderly persons in the
reasons for geographic and racial differences in stroke (REGARDS)
cohort study. Clinical Trial Update Hot Line III session. European
Society of Cardiology Annual Congress, Amsterdam 31st August-
4th September, 2013.
59. Aronow WS. Editorial commentary on dilemmas in treating hyper-
tension in octogenarians. J Clin Hypertens. 2012;14:665–7.