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Left ventricular hypertrophy (LVH), which early morning rise in blood pressure and
describes pathological changes in cardiac increased LVM. Use of anti-hypertensive
structure, is a powerful and reversible agents not only lowers blood pressure, but
predictor of cardiovascular risk. There is can also bring about LVH regression. The
a continuous relationship between left pathological role of angiotensin II in
ventricular mass (LVM) and the likelihood LVH and target-organ damage within
of cardiovascular events, with no cut-off the cardiovascular continuum suggest
between the absence of such events and that agents targeting the renin –
heightened risk. A correlation between LVH angiotensin – aldosterone system (RAAS),
and blood pressure is well established. such as the angiotensin-converting enzyme
There is a paradox, however, that the inhibitors and angiotensin II receptor
structural changes to the heart as a result blockers, may prove particularly effective
of increased workload due to high blood and may confer beneficial effects in
pressure appear to promote cardio- addition to the lowering of blood pressure.
vascular disease. This may be partially The angiotensin II receptor blockers may
explained by the fact that ambulatory be very appropriate treatment options
blood pressure measurements correlate because of their placebo-like tolerability
more closely with LVH than resting and the possibility of more complete
blood pressure. Blood pressure variation blockade of the RAAS. Within this class of
throughout the day is also emerging as an anti-hypertensive agents, pharmacological
important correlate of LVH, and a strong differences may mean that some agents
association has been identified between an afford greater cardioprotection than others.
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LVH problem and solutions
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
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LVH problem and solutions
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LVH problem and solutions
TABLE 1:
Studies examining the relationship between clinic and ambulatory systolic blood pressures
(SBP) in hypertensive subjects and left ventricular mass
Correlation coefficients
Number Clinic Daytime Night-time 24-h mean
studied SBP SBP SBP SBP
Rowlands et al.22 46 0.48 0.52 0.47 0.54
Devereux and Pickering23 100a 0.24 0.50 0.10 0.38
White et al.24 30 0.13 0.39 0.42 0.54
Verdecchia et al.25 137 0.33 0.38 0.51 0.51
Gosse et al.26 355 0.35 0.41 0.41 0.45
aHypertensive plus normal subjects.
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LVH problem and solutions
and LVH. More recently, it has been The renin – angiotensin – aldosterone
demonstrated that, in elderly Japanese system (RAAS) orchestrates many of the
subjects, those with the greatest morning cellular, biochemical and pathological
blood pressure experience a significantly changes that initiate and perpetuate LVH,
higher incidence of silent and overt with angiotensin II playing a key role
cerebrovascular events.33 (Fig. 2).38 Elevated levels of circulating
Other aspects of blood pressure variability angiotensin II and aldosterone have been
may impact on LVH. In patients with similar shown to correlate positively with increased
24-h mean blood pressures, those who do not LVM and reduced left ventricular function.39,40
exhibit the normal circadian variation and Thus, pharmacological interruption of the
display little or no night-time fall in blood RAAS offers a potent method of preventing
pressure (i.e. ‘non-dippers’) have higher LVM hypertension and regressing LVH, as well as
values compared with normal ‘dippers’.34 It protecting other target organs from
has been proposed that blunted reduction in angiotensin-II-induced damage.
nocturnal blood pressure, if it persists over a Recently, a meta-analysis was conducted
period of time, may play a pivotal role in the on data from double-blind, randomized,
development of some expressions of target- controlled trials performed up until
organ damage, such as LVH and intima- September 2002 that evaluated the effects
media thickening, during the early phase of diuretics, β-blockers, calcium channel
of essential hypertension.34 Whatever the blockers, angiotensin-converting enzyme
mechanisms, LVH appears more and more (ACE) inhibitors and angiotensin II receptor
as a surrogate endpoint for morbid events in blockers (ARBs) on echocardiographically
hypertension and thus deserves special evaluated LVM in essential hypertension.41
attention. It fulfils most of the conditions of a The meta-analysis revealed that treatments
substitute criterion,35 with lower LVM during targeting the RAAS resulted in the most
anti-hypertensive treatment being associated substantial reductions in LVM. Clinical
with lower incidences of clinical endpoints.36 studies have consistently shown that
treatment of mildly hypertensive patients
LVH and the role of the with ACE inhibitors42,43 or ARBs3,44 brings
renin – angiotensin – about LVH regression through mechanisms
that seem partially independent of their
aldosterone system ability to reduce blood pressure.
The Framingham Heart Study has shown
that LVH is reversible and responds well to Angiotensin-converting
the lowering of blood pressure.37 Increasing enzyme inhibitors versus
use of anti-hypertensive therapy over the
period 1950 – 1989 was associated with a
angiotensin II receptor
reduced prevalence of high blood pressure blockers
and a concomitant decline in LVH in the The mechanisms of action of ACE inhibitors
general population. In part, this is thought and ARBs differ. Formation of angiotensin II
to explain the considerable decline in from angiotensin I is prevented by ACE inhib-
mortality from cardiovascular disease itors; however, angiotensin II can be gener-
observed since the late 1960s. However, this ated by alternative enzymatic pathways,
is not cause for complacency. such as chymase present in the heart, that
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LVH problem and solutions
Local Circulating
Angiotensin
Vasoconstriction
Fibrosis
Hypertension
Myocardial remodelling
Myocyte hypertrophy
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LVH problem and solutions
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LVH problem and solutions
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LVH problem and solutions
Gross V, Bader M, et al: Blood pressure- A, Lind L, et al: Regression of left ventricular
independent effects in rats with human renin hypertrophy in human hypertension with
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35: 587 – 594. 52 Thurmann PA: Angiotensin II antagonism and
47 McConnaughey MM, McConnaughey JS, the heart: valsartan in left ventricular hyper-
Ingenito AJ: Practical considerations of the trophy. Cardiology 1999; 91 (Suppl 1): 3 – 7.
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48 Dahlof B: Left ventricular hypertrophy and Regression of hypertensive left ventricular
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2001; 14: 174 – 182. atenolol: the Losartan Intervention for
49 Cuspidi C, Muiesan ML, Valagussa L, Salvetti Endpoint Reduction in Hypertension (LIFE)
M, Di Biagio C, Agabiti-Rosei E, et al: trial. Circulation 2004; 110: 1456 – 1462.
Comparative effects of candesartan and 54 Siragy HM: Angiotensin receptor blockers: how
enalapril on left ventricular hypertrophy in important is selectivity? Am J Hypertens 2002;
patients with essential hypertension: the 15: 1006 – 1014.
candesartan assessment in the treatment of 55 Gosse P, Dubourg O, Gueret P: Regression of left
cardiac hypertrophy (CATCH) study. J Hypertens ventricular hypertrophy with echocardio-
2002; 20: 2293 – 2300. graphy: some lessons from the LIVE study.
50 Dahlof B, Zanchetti A, Diez J, Nicholls MG, Yu J Hypertens 2003; 21: 217 – 221.
CM, Barrios V, et al: Effects of losartan and 56 Verdecchia P, Angeli F, Borgioni C, Gattobigio
atenolol on left ventricular mass and R, de Simone G, Devereux RB, et al: Changes
neurohormonal profile in patients with in cardiovascular risk by reduction of
essential hypertension and left ventricular left ventricular mass in hypertension: a meta-
hypertrophy. J Hypertens 2002; 20: 1855 – 1864. analysis. Am J Hypertens 2003; 16: 895 – 899.
51 Malmqvist K, Kahan T, Edner M, Held C, Hagg
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