| Introduction
Recent
reports have indicated that hypertension, a silent disease,
affects a significant percentage of the adult Egyptian
population (1). Various antihypertensive agents
are already on the market in this country, with varying
prices and side effects. Not all have been effective in
lowering blood pressure in the Egyptian population. The
explanation may lie in racial differences, as many studies
have shown a different drug response between Afro-american
and white populations (2,3).
Recently angiotensin receptor
blockers have been added to the list of antihypretensive
drug choices. They have been proposed as an alternative
to ACE inhibitors because they do not interfere with the
degradation of biologically active peptides in the kallekrein
kinin prostaglandin system, thus theoretically they are
devoid of the side effects described with ACE inhibitor
use (4,5,6 ).
These drugs act directly
on the angiotensin II AT1 receptors and are thus more
specific than ACE inhibitors. While proven to be effective
in Europe and the U.S., there have been no reports as
to their efficacy in other populations, where high renin
hypertension may not be as common. This study represents
the first one using Valsartan to treat Egyptians suffering
from mild to moderate hypertension
Methods and Patient
Population
The study was conducted
on two stages.
In the first stage, angiotensin
II levels were measured in 132 hypertensives and 20 normotensives
after a two week washout period to determine whether angiotensin
II levels differed in Egyptian hypertensives from Egyptian
normotensives.
In the second stage, the
hypertensive population was divided into two subgroups:
- Sixty seven patients
receiving placebo (GpI);
- and sixty five patients
receiving valsartan daily (GpII).
Supine and standing blood
pressure and angiotensin II levels were measured after
the washout period and after 8 weeks of placebo/valsartan
administration.
Routine echocardiographic
measurements were taken including left ventricular end-systolic
and end-diastolic dimensions, septal and posterior wall
thickness, left atrial and Aortic root dimensions. Derived
measurements included fractional shortening and left ventricular
mass.
The biochemical work up
angiotensin II levels, included serum sodium, potassium
and creatinine.
Results
Baseline values of angiotensin
II after the washout period were significantly higher
in hypertensives than in normotensive controls (40.13
± 8.88 pmol/l versus 31.55 ± 10.18 pmol/l, with a p value
less than 0.001).
After 8 weeks, both groups
showed reduction in supine and standing blood pressure,
but his reduction was significantly higher in Gp II. The
plasma level of angiotensin II was significantly higher
in group II (37.9±
13.4 Pmol/l vs. 53.5±
11.7r mol/l, p < 0.01) There
was virtually no change in serum sodium or potassium levels,
no significant change in serum creatinine. Left ventricular
mass did not change significantly either.
Discussion
Valsartan is one of the
angiontensin receptor blockers. Because of their direct
effect on the angiotensin receptors, these drugs potentially
offer several advantages over the conventionally used
ACE inhibitors. These drugs act by inhibiting the converting
enzyme that changes angiotensin I into angiotensin II,
thus preventing its action on both AT1 and AT2 receptors.
They also inhibit the kininase responsible for the breakdown
of bradykinin and neurokinin. While ACE inhibitors have
been proven to be safe and effective blood pressure lowering
agents with cardio and renoprotective effects, they may
not be effective as a monotherapy |
|
in blacks, they
may produce irritative cough, can cause a marked drop
of blood pressure in patients with hyponatremia and rarely,
may cause angioedema. Angiotensin receptor blockers on
the other hand specifically act on AT1 receptors, with
no effect on AT2 receptors nor the brady and neurokinin
levels, thus eliminating the side effects produced by
elevated levels of these substances such as irritative
cough and angioedema. They are theoretically the drugs
with no typical side effect. Their efficacy in the Egyptian
population however has not been established.
This study was conducted
in two stages, stage I, in which angiotensin II levels
were compared in normotensive and hypertensive Egyptians,
and stage II, in which the effects of valsartan were compared
to those of a placebo. Stage I has shown that Egyptian
hypertensives have higher angiotensin II levels than normotensives,
a previously unproven fact, which indicated that an angiotensin
II receptor blocker would probably be effective as an
antihypertensive agent in this population. In stage II,
it was shown that Valsartan was more effective in lowering
blood pressure than placebo, while not affecting serum
sodium, potassium or creatinine levels. This is in accordance
with other international studies (5-11). The
echocardiographic parameters showed no change, and this
is explained by two facts, the 8 weeks duration of follow
up was too short to record any significant change, and
the baseline figures were all within the normal range
to begin with.
Conclusion
This study has shown that
valsartan is an effective and safe agent in lowering blood
pressure in Egyptians, however, longer term studies are
needed to demonstrate any cardio- or reno- protective
effects.
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