Download Isolated Systolic Hypertension in the Elderly

Hypertension
Isolated Systolic Hypertension in the Elderly
Sheldon Tobe, MD, FRCP(C), Assistant Professor of Medicine, Nephrology,
University of Toronto; Division Director Nephrology, Sunnybrook & Women’s
College Health Sciences Centre,Toronto, ON.
Sudha Cherukuri, MD, DNB(Nephrology), Clinical Fellow, University of Toronto,
Toronto, ON.
Isolated systolic hypertension (ISH) is a common disorder in the elderly. Several studies
have shown a constant positive and graded association between the level of systolic blood
pressure and subsequent mortality from cardiovascular disease and stroke. ISH is defined
as an elevated systolic pressure above 160mmHg and a diastolic pressure below 90mmHg.
Arterial stiffening is the main cause of increasing systolic pressure in the elderly.The finding of high systolic blood pressure with diastolic below 90mmHg is a marker of higher cardiovascular risk and an indication to follow this patient more closely.The placebo-controlled
SHEP and Syst-Eur trials have demonstrated that the treatment of ISH with diuretics or
long-acting calcium channel blockers results in a marked reduction in cardiovascular events
and stroke.
Key words: hypertension, isolated systolic hypertension, clinical trials, drug therapy, elderly.
Introduction
Incidence
Hypertension is an established risk factor for cardiovascular disease morbidity and mortality. Results of
prospective epidemiological studies in
different population groups indicate a
constant positive and graded association between the level of systolic blood
pressure and subsequent mortality
from cardiovascular disease and
stroke—especially with advancing
age—irrespective of the level of diastolic blood pressure.
This disorder is primarily seen in older
patients. Data from the Framingham
Heart Study have shown that the systolic
pressure rises and the diastolic pressure
falls after the age of 60 years in both the
normotensive and untreated hypertensive subjects (Figure 1).4 ISH rises in
prevalence from 8% in individuals aged
70 and older to 25% in those 80 and
older.5 The elevation in pulse pressure in
this setting is primarily due to diminished arterial compliance. In the group 50
years and older with either untreated or
inadequately treated hypertension, 80%
have isolated systolic hypertension.6
Definition
Isolated systolic hypertension (ISH) is
defined as an elevated systolic pressure
above 160mmHg and a diastolic pressure that is below 90mmHg (Table 1).1
The MRFIT study demonstrated that
as well as a graded, increased risk with
higher systolic blood pressure, there
was a particularly high risk for those
with the highest systolic blood pressure and the lowest diastolic blood
pressure.2 This was recently confirmed
by a prospective study of over 9,000
people with hypertension 65 years and
older followed for an average of 10.6
years.3
Importance
ISH is associated with a two- to four-fold
increase in the risk of myocardial infarction, left ventricular hypertrophy, stroke
and cardiovascular mortality.7 The peak
systolic pressure promotes the development of heart failure and atherosclerosis
by increasing cardiac work and predisposing to vascular endothelial injury.
related aortic stiffening.8 The ascending
and descending aorta dilate with age,
with the aortic diameter increasing by
15–35% from age 20–80. Histological
changes occurring with normal aging
include distorted normal orientation of
the laminar unit, fracturing and fragmentation of the elastin fibres and
increased collagen content of the vessel
wall. These changes influence the aortic
pulse, systemic pressure and ventricular performance.
In addition, age-related changes
occur in the arterial pulse. Left ventricular ejection creates a pressure wave
that travels the length of the aorta to the
periphery at a faster rate than blood
flow. The velocity of the pressure wave
is termed the pulse wave velocity.9 The
pulse wave velocity is measured by
recording the pulse wave at two sites,
usually the carotid and femoral arteries.
It is calculated as the distance from the
carotid to the femoral artery divided by
the time required for the pulse wave to
travel this distance. With normal aging,
the speed with which the pulse moves
along the aorta markedly increases (Figure 2). In older subjects, the faster pulse
wave velocity and wave reflection
result in the reflected wave traveling
back to the heart to reach the ascending
aorta in late systole rather than early
diastole. This causes an elevation in the
systolic blood pressure and a fall in the
diastolic blood pressure (wider pulse
pressure). Normally, the reflected wave
arriving back in early diastole results in
Table 1
Classification of
Hypertension According to
WHO/ISH
Category
Systolic Diastolic
(mmHg) (mmHg)
Pathogenesis
Isolated systolic
hypertension
≥140
One factor which may play a pivotal
role in the pathogenesis of ISH is age-
Subgroup: borderline 140–149 <90
<90
www.geriatricsandaging.ca 27
Isolated Systolic Hypertension
pressure for coronary perfusion much
like the effect of intra-aortic balloon
counterpulsation, and its loss due to
increased arterial stiffness will lead to
reduced diastolic coronary perfusion
and increased systolic work. Therefore,
age-related aortic stiffening contributes
to the prevalence of isolated systolic
hypertension in the elderly and to a
greater risk of cardiac ischemia.
Age-related changes leading to ISH
have important physiologic associations.
In multiple studies, the systolic blood
pressure and pulse pressure are stronger
risk factors for cardiovascular disease in
older subjects than the mean arterial pressure or the diastolic pressure.10 Treatment
that lowers blood pressure in patients
with isolated systolic hypertension is
associated with significant reduction in
cardiac and cerebrovascular events.11
Treatment
The SHEP (Systolic Hypertension in the
Elderly) trial was the first to demonstrate that people with ISH could not
only benefit from therapy, but were also
a much higher risk group than previously thought.12 Although 15 years later
it is hard to believe that it used to be ethical to treat elderly ISH patients with a
placebo, the state of knowledge at the
time was such that this was reasonable.
In this study, 4,736 patients with ISH
were randomized to either active antihypertensive therapy with diuretic or
placebo, with the aim to reduce systolic
blood pressure by at least 20mmHg or
to a level below 160mmHg. Achieved
blood pressures were 143/68mmHg in
the treatment group compared to
155/72mmHg in the placebo arm. At
four to five years, the incidence of
stroke was reduced from 8.2% in the
placebo group to 5.2% in the treated
group (a 36% relative risk reduction and
a 3% absolute risk reduction, with a
number needed to treat of only 33 for
the outcome stroke). A similar reduction
was noted in cardiac events as well. The
Syst-Eur trial, which randomized 4,695
patients with ISH to placebo or
nitrendipine—a dihydroperidine calcium channel blocker—also demonstrated a risk reduction equivalent to that
found in the SHEP trial for both stroke
and cardiovascular mortality.11,13
One issue that is frequently raised
in the treatment of ISH is what happens
if the diastolic blood pressure falls too
low. However, we know from placebocontrolled trials such as SHEP and Syst-
Figure 1
Patterns of Age-related Changes in Blood Pressure
Group 1 (SBP < 120)
Group 2 (SBP 120–139)
Systolic
140
80
120
70
100
60
30
30
Age (years)
Franklin SS et al. Circulation 1997;96:308-315.
28 GERIATRICS & AGING • February 2003 • Vol 6, Num 2
Choice of Therapy
Based on the results of the SHEP and
Syst-Eur trials, low-dose thiazide therapy is the preferred initial therapy for ISH.
Hydrochlorothiazide at 12.5 or 25mg has
the advantage of low cost, efficacy and
proven benefit. The Syst-Eur trial demonstrated the safety and efficacy of long-acting dihydropyridine calcium antagonists
for the treatment of ISH (Figure 3).
It is recommended that all people
older than 65 years have their blood
pressure taken at least annually if they
are normotensive, and every three to six
months if their high blood pressure has
been controlled. The finding of high
systolic blood pressure with diastolic
below 90mmHg is a marker of higher
cardiovascular risk, and this patient
must be followed more closely. Recently ambulatory blood pressure monitoring has been found to be a better
predictor of adverse outcomes in older
patients with widened pulse pressure
and ISH. Home monitoring with an
approved device may be a better way to
monitor therapy and eliminate a white
coat effect.
Prevention
Prevention of age-related aortic changes
is possible with both lifestyle changes
and drug therapy. Modifying lifestyle factors to lower blood pressure—such as
weight loss, regular aerobic exercise, diet
with low sodium content, cessation of
smoking, moderation of alcohol intake
and management of dyslipidemia and
blood sugar control—will help to protect
the vascular tree.
Future
–3
35 4
–3
40 9
–
45 44
–4
50 9
–5
55 4
–5
60 9
–
65 64
–6
70 9
–7
75 4
–7
80 9
–8
4
90
Age (years)
Diastolic
100
160
–3
35 4
–3
40 9
–
45 44
–4
50 9
–5
55 4
–5
60 9
–
65 64
–6
70 9
–7
75 4
–7
80 9
–8
4
Blood Pressure (mmHg)
180
Group 3 (SBP 140–159)
Group 4 (SBP 160+)
Eur that treatment of these patients is
better than no treatment at all. In a
meta-analysis of clinical trials with a
total of 15,693 people with ISH, active
treatment reduced total mortality by
13%, all stroke by 30% and all coronary
events by 23%.11
The clinical utility of measuring parameters of arterial stiffness beyond the
pulse pressure have not yet been determined. However, in the future serial
Isolated Systolic Hypertension
Left ventricular ejection
creates pressure wave
through aorta to periphery
Pressure (mmHg)
Pressure wave
reflected back in
early diastole
Normal Diastole
Faster pulse wave
velocity causes
reflected wave to
travel back to heart
in late systole rather
than early diastole
Ventricles
contract
Normal Systole
Figure 2:
The Pathogenesis
of Isolated Systolic
Hypertension
Pressure (mmHg)
Increased
systolic pressure
To counteract reflected pressure wave,
cardiac muscle must contract harder
in systole, thereby increasing systolic
blood pressure
With Aging
www.geriatricsandaging.ca 29
Isolated Systolic Hypertension
Figure 3
Treatment Algorithm for Isolated Systolic Hypertension:
Target < 140mmHg
Lifestyle modifications
Low-dose thiazide
Long-acting dihydropyridine
calcium channel blocker
Neither alpha- nor beta-blockers
are indicated as first-line
monotherapy for ISH due to the
results of ALLHAT and other trials
Combination
Effective two-drug
combination
CONSIDER
– Nonadherence?
– Secondary hypertension?
– Interfering drugs or lifestyle?
– White coat effect?
}
(Add ACE-I or beta-blocker)
Combination
Triple or quadruple
therapy
measurements of arterial tonometry
and pulse wave velocity to assess the
effects of therapeutic interventions will
provide more specific, clinically important information unavailable from the
measurement of blood pressure alone.
The focus of ISH treatment is to bring
down the systolic blood pressure. In the
future, ISH may no longer remain a separate entity in clinical practice guidelines, as treatment of high blood
pressure will be initiated if blood pressure in the uncomplicated patient is
greater than 140 systolic and/or 90 diastolic. Therefore, having a separate category for those with systolic pressure
greater than 160 and diastolic less than
90 will be redundant. Today, however,
there are a large number of treatment
trials involving patients with ISH that
help guide treatment in this higher risk
group of hypertensives.
Conclusion
In summary, ISH is associated with a
higher risk of cardiovascular disease
and mortality. Wider pulse pressure in
ISH is a marker of loss of vascular elasticity associated with hardening of the
arteries. Treatment of ISH has been
proven to be beneficial. The goal should
be to bring the systolic blood pressure
down to 140mmHg, or at least by
20mmHg. Multiple medications may be
30 GERIATRICS & AGING • February 2003 • Vol 6, Num 2
required. Because patients with ISH are
at high risk, they should be assessed for
multiple cardiovascular risk reduction
strategies.
◆
No competing financial interests declared.
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