The Journal of International Medical Research
2005; 33 (Suppl 1): 3A – 11A
Left Ventricular Hypertrophy – the
Problem and Possible Solutions
P GOSSE
Cardiology Service – Arterial Hypertension, Hospital Saint-André, Bordeaux, France
Left ventricular hypertrophy (LVH), which
describes pathological changes in cardiac
structure, is a powerful and reversible
predictor of cardiovascular risk. There is
a continuous relationship between left
ventricular mass (LVM) and the likelihood
of cardiovascular events, with no cut-off
between the absence of such events and
heightened risk. A correlation between LVH
and blood pressure is well established.
There is a paradox, however, that the
structural changes to the heart as a result
of increased workload due to high blood
pressure appear to promote cardio-
vascular disease. This may be partially
explained by the fact that ambulatory
blood pressure measurements correlate
more closely with LVH than resting
blood pressure. Blood pressure variation
throughout the day is also emerging as an
important correlate of LVH, and a strong
association has been identified between an
KEY WORDS: LEFT VENTRICULAR HYPERTROPHY; LEFT VENTRICULAR MASS; PATHOPHYSIOLOGY;
HYPERTENSION; TREATMENT; ANGIOTENSIN II RECEPTOR BLOCKERS
Introduction
Left ventricular hypertrophy (LVH) is, in
simple terms, an adaptive response to
chronic exposure of the heart to an increased
workload, a common cause being systemic
hypertension. At the cellular level, the
cardiomyocytes expand in thickness and
3A
early morning rise in blood pressure and
increased LVM. Use of anti-hypertensive
agents not only lowers blood pressure, but
can also bring about LVH regression. The
pathological role of angiotensin II in
LVH and target-organ damage within
the cardiovascular continuum suggest
that agents targeting the renin –
angiotensin – aldosterone system (RAAS),
such as the angiotensin-converting enzyme
inhibitors and angiotensin II receptor
blockers, may prove particularly effective
and may confer beneficial effects in
addition to the lowering of blood pressure.
The angiotensin II receptor blockers may
be very appropriate treatment options
because of their placebo-like tolerability
and the possibility of more complete
blockade of the RAAS. Within this class of
anti-hypertensive agents, pharmacological
differences may mean that some agents
afford greater cardioprotection than others.
length, but with little or no increase in the
number of cells, to compensate for the
increased haemodynamic stress on the ven-
tricular wall.1 In addition, as distinct from
the hypertrophy seen in growth and as a
result of exercise and physical training, fibro-
blasts proliferate with abnormal accumulation
of collagen, leading to fibrosis.1 The overall
 P Gosse
LVH problem and solutions

effect of these histological changes is an Left ventricular hypertrophy is widely

increase in left ventricular mass (LVM).
In LVH, normal cardiac function becomes
compromised.2 The accumulation of fibrillar
collagen within the adventitia of the intra-
myocardial coronary arteries and interstitial
spaces brings about ventricular stiffness and
decreases coronary flow reserve. Increased
ventricular stiffness can lead to abnormal
diastolic function and heart failure, with
preserved systolic function.3 The decreased
coronary flow reserve increases the risk of
cardiac ischaemia, potentially lethal cardiac
arrhythmias and myocardial infarction.4 In
addition, the fibrosis disrupts the electrical
and mechanical behaviour of the hypertro-
phied myocardium. Reduced cardiac contrac-
tility may finally occur as a result of increased
workload and myocardial ischaemia.
recognized as a powerful, but reversible, risk
factor for cardiovascular morbidity and
mortality. Indeed, after age, LVH is the single
strongest predictor of cardiovascular events,
cardiovascular death and total mortality.5
Epidemiological studies have shown that
LVH is an independent risk factor for
cardiovascular morbidity and mortality and
for all-cause mortality in the general pop-
ulation,6 as well as in individuals already at
higher risk, such as those with hypertension7
or coronary artery disease.8 The risk is mag-
nified even in hypertensive individuals with
increases in echocardiographically detected
LVM too small to be defined as LVH.9,10
Findings from the Bordeaux cohort who were
initially untreated reinforce this correlation
(Fig. 1) and confirm that very small increases

LVM/h2.7 quintiles
5th = 77
4th = 60
3rd = 52
2nd = 44
1st = 35
1.0

0.9
Event-free survival ratio

0.8

0.7

0.6

0.5
0 100 200
Follow-up (months)

FIGURE 1: Age-, sex-, and blood pressure-adjusted event-free survival curves for left
ventricular mass (LVM) indexed to height to the power 2.7 in 520 patients of the
Bordeaux cohort followed up over 102 ± 42 months with 56 cardiovascular events
recorded

4A
 P Gosse
LVH problem and solutions
in LVM still impact on cardiovascular risk,
independently of other variables.11
Screening for LVH
Diagnosis of LVH is not a simple matter. LVH
is undetectable on physical examination.3
Using voltage criteria and QRS duration,
electrocardiograms can identify LVH with
high specificity, but poor sensitivity.12
Repolarization abnormalities (ST changes)
are frequent, but can be regarded as a
witness of reduced perfusion of the internal
layers of the myocardial wall rather than
being a specific marker of LVH.13 Echo-
cardiography, which is about eight-fold more
sensitive,14 has become the reference method
to detect LVH. It provides a safe and non-
invasive method for evaluating cardiac
anatomy and function, and has been
extensively used in clinical trials. More
recently, magnetic resonance imaging has
been developed that allows high-resolution
visualization of the entire heart and gives an
accurate measurement of LVM, in a manner
that is independent of shape or perfusion.15
The technique, which provides interstudy
reproducibility in normal, dilated and
hypertrophic hearts and is superior to two-
dimensional echocardiography,16 is now
accepted as the method of choice for LVM
determination in clinical investigations and
for serial evaluation of selected patients. As
yet, it is not routinely used for diagnosis.
The definition of LVH depends on the
method by which the LVM is indexed (i.e.
height, body surface area or height to the
power 2.7, which appears to be particularly
sensitive).17 The cut-off proposed in the
literature displays important differences
between one study and another,17 and the
definition of the cut-off from the analysis of
‘normal’ populations may not provide the
most useful criterion. In the light of large
variability in LVM measurements provided
5A
by echocardiography even in normal
subjects, the calculation of the 95th
percentile usually leads to a high cut-off
value. Consequently, LVH is better defined in
terms of risk prediction, there being a strong
link between increased LVM and increased
incidence of cardiovascular complications.6
LVH and hypertension
Numerous studies have demonstrated a
correlation between LVM and blood pressure.
This is logical as increased LVM can be
regarded as a response to greater workload
associated with high blood pressure, and
could be considered a useful adaptation to a
chronic increase in myocardial strain. There
is, however, a paradox that LVH appears
to promote cardiovascular disease. Three
possible explanations have been proposed.18
One possibility is that, as a marker of
cardiovascular risk, LVH integrates the effect
of various factors – the main one being blood
pressure – with these effects being integrated
over time. Two arguments support this
hypothesis: first, LVH is a risk factor for not
only cardiac disease but also for other cardio-
vascular events, such as stroke;19 secondly,
ambulatory blood pressure measurements
correlate more closely with LVH than resting
blood pressure, as discussed later.
The second hypothesis is that, although
LVH is an adaptive process, it is limited. The
initial advantages of lowering parietal stress
may be gradually overridden by the stim-
ulated myocyte growth and the consequent
remodelling of the left ventricular chamber.1
This hypothesis, however, is not supported by
the observation that the correlation between
LVM and cardiovascular risk is continuous,
with no obvious threshold.11
The third hypothesis is that there is a clear
distinction between physiological and
pathological LVH from the outset. The
proliferation of interstitial tissue and
 P Gosse
LVH problem and solutions
accumulation of collagen is possibly
stimulated by different mechanisms to those
causing myocyte hypertrophy.16
Systolic blood pressure is more closely
related to LVM than diastolic blood pressure.
Other haemodynamic factors that can
contribute to LVH include increased arterial
stiffness of the aorta20 and increased blood
viscosity,21 both of which increase the
workload of the heart, and thus stimulate
hypertrophic changes. Other factors may
contribute to LVH; for example, the
prevalence of LVH correlates strongly and
independently with alcohol consumption,
obesity and age.18
Increased LVM correlates even more closely
with 24-h mean ambulatory blood pressure
than with isolated clinic measurements
(Table 1).22 – 26 As a result, 24-h mean values
of ambulatory blood pressure are now
regarded as more sensitive predictors of LVH.27
Furthermore, treatment-induced reductions
in LVM are reflected in corresponding
reductions in 24-h mean blood pressure,
but correlation between 24-h mean blood
pressure and LVM is still relatively weak.26
Other parameters, such as blood pressure
recorded during activity, the difference
between daytime and night-time values, and
TABLE 1:
Studies examining the relationship between clinic and ambulatory systolic blood pressures
(SBP) in hypertensive subjects and left ventricular mass
Number Clinic
studied SBP
Rowlands et al.22 46 0.48
Devereux and Pickering23 100a 0.24
White et al.24 30 0.13
Verdecchia et al.25 137 0.33
Gosse et al.26 355 0.35
aHypertensive plus normal subjects.
6A
blood pressure recorded when the subject
arises in the morning, have been proposed
as being of greater prognostic value.28 Most
people, including those with hypertension,
display a circadian variation in blood
pressure, with levels being highest during the
day and lowest in the middle of the night.28
At the time of awakening, there is a surge in
blood pressure.29 This rapid elevation in
blood pressure is accompanied by an
acceleration in cardiac rhythm, with no
significant correlation between the two
parameters. The increase in blood pressure
on rising has been linked to the overall
variability in blood pressure, but appears
independent of the mean blood pressure over
24 h.29 In previously untreated patients with
hypertension, both LVM and left ventricular
wall thickness correlate with systolic blood
pressure on arising. Two other studies have
found that in treated and untreated
hypertensive patients with a morning surge
in blood pressure, LVM indexes are
significantly higher.30,31 It is interesting to
note that the time of the early morning surge
in blood pressure coincides with the peak
incidence of acute cardiovascular events,32
thus providing further evidence for the link
between early morning blood pressure surge
Correlation coefficients
Daytime Night-time 24-h mean
SBP SBP SBP
0.52 0.47 0.54
0.50 0.10 0.38
0.39 0.42 0.54
0.38 0.51 0.51
0.41 0.41 0.45
 P Gosse
LVH problem and solutions
and LVH. More recently, it has been
demonstrated that, in elderly Japanese
subjects, those with the greatest morning
blood pressure experience a significantly
higher incidence of silent and overt
cerebrovascular events.33
Other aspects of blood pressure variability
may impact on LVH. In patients with similar
24-h mean blood pressures, those who do not
exhibit the normal circadian variation and
display little or no night-time fall in blood
pressure (i.e. ‘non-dippers’) have higher LVM
values compared with normal ‘dippers’.34 It
has been proposed that blunted reduction in
nocturnal blood pressure, if it persists over a
period of time, may play a pivotal role in the
development of some expressions of target-
organ damage, such as LVH and intima-
media thickening, during the early phase
of essential hypertension.34 Whatever the
mechanisms, LVH appears more and more
as a surrogate endpoint for morbid events in
hypertension and thus deserves special
attention. It fulfils most of the conditions of a
substitute criterion,35 with lower LVM during
anti-hypertensive treatment being associated
with lower incidences of clinical endpoints.36
LVH and the role of the
renin – angiotensin –
aldosterone system
The Framingham Heart Study has shown
that LVH is reversible and responds well to
the lowering of blood pressure.37 Increasing
use of anti-hypertensive therapy over the
period 1950 – 1989 was associated with a
reduced prevalence of high blood pressure
and a concomitant decline in LVH in the
general population. In part, this is thought
to explain the considerable decline in
mortality from cardiovascular disease
observed since the late 1960s. However, this
is not cause for complacency.
7A
The renin – angiotensin – aldosterone
system (RAAS) orchestrates many of the
cellular, biochemical and pathological
changes that initiate and perpetuate LVH,
with angiotensin II playing a key role
(Fig. 2).38 Elevated levels of circulating
angiotensin II and aldosterone have been
shown to correlate positively with increased
LVM and reduced left ventricular function.39,40
Thus, pharmacological interruption of the
RAAS offers a potent method of preventing
hypertension and regressing LVH, as well as
protecting other target organs from
angiotensin-II-induced damage.
Recently, a meta-analysis was conducted
on data from double-blind, randomized,
controlled trials performed up until
September 2002 that evaluated the effects
of diuretics, β-blockers, calcium channel
blockers, angiotensin-converting enzyme
(ACE) inhibitors and angiotensin II receptor
blockers (ARBs) on echocardiographically
evaluated LVM in essential hypertension.41
The meta-analysis revealed that treatments
targeting the RAAS resulted in the most
substantial reductions in LVM. Clinical
studies have consistently shown that
treatment of mildly hypertensive patients
with ACE inhibitors42,43 or ARBs3,44 brings
about LVH regression through mechanisms
that seem partially independent of their
ability to reduce blood pressure.
Angiotensin-converting
enzyme inhibitors versus
angiotensin II receptor
blockers
The mechanisms of action of ACE inhibitors
and ARBs differ. Formation of angiotensin II
from angiotensin I is prevented by ACE inhib-
itors; however, angiotensin II can be gener-
ated by alternative enzymatic pathways,
such as chymase present in the heart, that
 P Gosse
LVH problem and solutions

Local Circulating
Angiotensin

Vasoconstriction

Fibrosis
Hypertension
Myocardial remodelling

Myocyte hypertrophy

Left ventricular hypertrophy

Increased ventricular Reduced cardiac Decreased coronary

stiffness contractility flow reserve

Abnormal diastolic function and

congestive heart failure

FIGURE 2: The role of angiotensin II in left ventricular hypertrophy and cardiac

pathophysiology38

are not susceptible to ACE inhibition.45,46 In Conclusions

contrast, the ARBs prevent the binding of
angiotensin II to the type 1 receptors present
in various tissue; thus, the deleterious effects
of angiotensin II are overcome irrespective of
whether it is produced systemically or locally
and by whatever mechanism.47
Extensive data have shown that ARBs
have an important role in LVH manage-
ment.48 In clinical studies, ARBs have been
shown to bring about regression of LVM.49 – 52
The Losartan Intervention For Endpoint
reduction in hypertension (LIFE) study, for
example, has demonstrated that treatment
with losartan, plus hydrochlorothiazide and
other medications when needed for blood
pressure control, resulted in greater LVH
regression in patients than did conventional
atenolol-based treatment.53
If allowed to advance, LVH is a considerable
cause of cardiovascular disease and death.
LVH regression by aggressive control of blood
pressure may make a valuable contribution
to improving prognosis. In the light of the
important role that angiotensin II plays
within the cardiovascular continuum,
pharmacological targeting of the RAAS may
confer additional benefits in terms of LVH
reversal and improved prognosis to that
provided by effective blood pressure alone
using other anti-hypertensive agents.
The ARBs, a class of anti-hypertensive
agents with well-established efficacy and a
placebo-like safety profile,54 may prove
especially valuable, by providing more
complete blockade of angiotensin II than

8A
 P Gosse
LVH problem and solutions
ACE inhibitors. Evidence is amassing that
use of ARBs may be a superior therapeutic
option for LVH management. Pharmaco-
logical differences within the class, such
as duration of action, may differentiate
between the cardioprotective properties of
the commercially available ARBs. In the
future, well-designed, sufficiently powered,
long-term outcome studies using accurate
Copyright © 2005 Cambridge Medical Publications
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Address for correspondence

Dr P Gosse
Cardiology Service – Arterial Hypertension, Hospital Saint-André,
1 rue Jean Burguet, 33075 Bordeaux Cedex, France.
E-mail: philippe.gosse@chu-bordeaux.fr

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