DOI: 10.5958/j.2319-5886.2.4.119
International Journal of Medical Research
&
Health Sciences
www.ijmrhs.com Volume 2 Issue 4 Oct-Dec
Coden: IJMRHS Copyright @2013
ISSN: 2319-5886
th
th
Received: 16 July 2013
Revised: 18 Aug 2013
Accepted: 20th Aug 2013
Research article
EFFECT OF TELMISARTAN ON SERUM LIPID PROFILE IN PATIENTS WITH
HYPERTENSION AND DYSLIPIDEMIA
*Vanitha M1, Vijayal K2
1
2
Department of Pharmacology, Osmania Medical College, Hyderabad
Department of Pharmacology, Dr VRK Women’s Medical College & Research Institute, Hyderabad
*Corresponding author email: hayavanitha@yahoo.in
ABSTRACT
Background and Objectives: Hypertension and dyslipidemia are two major risk factors for
cardiovascular disease and they commonly occur together. Management of dyslipidemia in a
hypertensive patient significantly reduces the total cardiovascular risk .Telmisartan is an Angiotensin
receptor blocker with a partial agonistic action on PPAR- . In the present study, the effect of
Telmisartan on serum Lipid Profile was evaluated in hypertensive patients who also have associated
Dyslipidemia and also the efficacy of Telmisartan in reducing systolic and diastolic BP was assessed in
these patients. Materials and Methods: A total of 50 outpatients from the medical outpatient
department of Gandhi Hospital, Secunderabad, were enrolled into the study. These patients had grade І
essential Hypertension and mild dyslipidemia. After the study period of 24 weeks, the efficacy of
Telmisartan in reducing serum lipid profile was evaluated apart from its effect on reducing systolic and
diastolic BP. Results: Telmisartan was very effective in reducing serum triglycerides (27 %↓ , P<0.01),
VLDL-C (27 %↓ , P<0.01), LDL-C (22%↓ , P<0.01). It also decreased serum cholesterol by 16%
(P<0.01). HDL-C increased by 14% (P<0.05). Telmisartan in a dose of 40-80 mg/day, significantly
reduced both systolic BP by 18 %( P<0.01) and diastolic BP by 12 %( P<0.01) Conclusion: In our
study, Telmisartan proved to be effective not only in controlling BP, but had a favorable effect on lipid
profile also So, in conclusion, all the patients with uncomplicated Hypertension and mild dyslipidemia
can be effectively treated with Telmisartan.
Key words: Telmisartan, Hypertension, Dyslipidemia, Serum lipid profile
INTRODUCTION
Coronary heart disease continues to be the
leading cause of morbidity and mortality in the
world1. Several factors increase the risk of CHD
such
as
hypertension,
advancing
age,
dyslipidemia, type 2 diabetes mellitus, family
history of coronary artery disease, cigarette
Vanitha et al.,
smoking, obesity etc,.
Hypertension and
dyslipidemia are the most common risk factors
for cardiovascular disease. It is found that
hypertensive patients have lower levels of HDLcholesterol and higher levels of triglycerides
compared to normal individuals. In patients with
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Int J Med Res Health Sci. 2013;2(4):745-749
hypertension,
dyslipidemia
substantially
increases the cardiovascular risk. So, there is a
need for disciplined diet plan and appropriate
pharmacological therapy in these patients. The
exact pathophysiology by which dyslipidemia
may be involved in the development of
hypertension is not well established. Lipid
disorders cause endothelial dysfunction and this
may become manifest as hypertension
edication therapy for hypertension and
dyslipidemia is becoming more complicated, as
over two-thirds of patients require two or more
anti-hypertensive agents and at least one lipid
lowering agent. The mechanism of action of
majority of anti-hypertensive drugs in use today
is to primarily target the factors which contribute
to development of increased blood pressure.
They do not in any way modify the
pathophysiological
mechanisms
causing
dyslipidemia. Angiotensin II receptor blockers
(ARB) are efficient anti hypertensive agents that
act through inhibition of AT1 receptors. In
experimental models, as well as in some clinical
trials, ARBs have been found to significantly
affect lipid metabolism .More precisely; ARBs
improved the overproduction and accumulation
of TGL in the liver, in experimental models,
through mechanisms independent of their
hypotensive action2. Furthermore, there are
preclinical studies showing that telmisartan
exerts a favourable effect on lipid abnormalities,
due to its partial activation of peroxisome
proliferator-activated receptor-gamma (PPAR- ).
The finding that Telmisartan acts as both an
ARB and a partial agonist of PPAR- has
important implications in the prevention of
atherosclerosis and cardiovascular disease.
Moreover, it has been shown that activation of
PPAR- , downregulates the expression of
angiotensin II type I receptor and modifies the
effects of angiotensin II on intracellular signaling
pathways3.Telmisartan
is
a
potent,
insurmountable and highly selective antagonist
of AT1 receptors, with a long terminal
elimination half-life, Telmisartan is capable of
Vanitha et al.,
activating the nuclear peroxisome proliferatoractivated receptor (PPAR) - also, in addition to
blocking the angiotensin II type I receptor.
PPAR- is a nuclear transcription factor that
exists in the form of a heterodimer complex with
the retinoid X receptor- 4. Activation of PPARcauses the receptor complex to affect the
expression of key target genes that mediate
beneficial effects on glucose and lipid
metabolism. Evidence for the importance of
PPAR- in regulating key features of the
metabolic syndrome comes from the studies of
individuals with mutated forms of the receptor.
Such individuals exhibit multiple features of the
metabolic syndrome, including severe insulin
resistance,
hypertriglyceridemia,
elevated
concentrations of non esterified fatty acids, low
concentrations of HDL cholesterol and
hypertension. Infact PPAR- is an important
target for drugs used in the treatment of insulin
resistance, diabetes mellitus and the metabolic
syndrome4. Thiazolidinedione PPAR- activators,
pioglitazone and rosiglitazone are currently
available, and these agents have been shown to
increase the insulin sensitivity and decrease FA
and triglyceride concentrations in patients with
type 2 diabetes5.
In contrast to other ARBs, relatively low
concentrations of telmisartan were also found to
increase the expression of phosphoenol-pyruvate
carboxykinase (PEPCK) gene in human visceral
adipocytes. PEPCK is a key target gene that
contributes to the ability of PPAR- activators to
reduce the FA levels. Further evidence that
telmisartan activates PPAR- comes from the
findings that telmisartan induces adipocyte
differentiation in vitro and is more effective than
other ARBs in reducing serum concentrations of
glucose, insulin and triglyceride in rats
maintained on a diet rich in fats carbohydrates. In
contrast to glitazones, telmisartan is a selective
PPAR- modulator that activates only a subset of
genes targeted by the full PPAR- agonists and
that’s why it has fewer adverse effects compared
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Int J Med Res Health Sci. 2013;2(4):745-749
to full PPAR- agonists. Telmisartan is highly
lipophilic, and has a high mean volume of
distribution of 460-510 L. This high apparent
volume of distribution and the lipophilic nature
of telmisartan suggest that it may have greater
capacity to enter intracellular compartments and
gain better access to PPAR- than other ARBs
MATERIALS AND METHODS
The present study was conducted in the
Departments of Pharmacology and Medicine,
Gandhi Medical College and Gandhi Hospital,
Secunderabad. 50 newly diagnosed cases of
essential hypertension, having dyslipidemia were
included in the study. The patients were enrolled
from the medical OPD and the study was
conducted in the period from October 2010 to
May 2011. After getting approval from the
Institutional Ethics Committee, newly diagnosed
cases of grade I essential hypertension were first
screened for dyslipidemia by doing serum lipid
profile after overnight fasting for about 10 hrs.
Those patients having both hypertension and
dyslipidemia were included in the study.
Exclusion criteria:
Patients with Diabetes
mellitus, secondary causes for hypertension,
Hepatic or renal insufficiency, coronary artery
disease or cerebrovascular diseases were
excluded from the study. The age of the patients
ranged from 38-65 years with a mean of 52 ± 1.2
years and consisted of 31 males (62%) and 19
females (38%). In each case after the informed
consent was obtained, a detailed clinical history
was taken. All the patients underwent complete
clinical examination including recording of
pulse, B.P, detailed clinical examination of
respiratory system, cardiovascular system and
central nervous system. The biochemical
investigations including Blood sugar, serum
creatinine and serum lipid profile were done.
LFT, TSH, X-ray chest and resting 12 leads
electrocardiogram were done in all the patients.
Serum lipid profile was repeated at the end of 24
weeks. All the patients were started on
Vanitha et al.,
Telmisartan 40 mg orally once daily. They were
followed up with BP recording once in 15 days
and the dose of telmisartan titrated according to
the response.
RESULTS
Initial lipid profile: The initial total serum
cholesterol in the patients ranged between 171281 mg/dl with a mean of 218.86 ± 3.91. The
initial serum triglycerides ranged between 93275 mg/dl with a mean of 170.8 ± 5.25. The
initial LDL-C, ranged between 107-197 mg/dl
with a mean of 144.08 ± 3.65. The initial HDLC, ranged between 32-58 mg/dl with a mean of
40.62 ± 0.76. The initial VLDL-C, ranged
between 19-55 mg/dl with a mean of 34.16 ±
1.04.
All the parameters including total
Cholesterol, LDL-C, Serum Triglycerides, HDLC and VLDL-C, were marginally higher in
female patients, when compared with male
patients.
Lipid profile after 24 weeks: (Table1): After
24 weeks of study period, the mean Total
Cholesterol decreased significantly from 218.86
mg/dl to 185.06 mg/dl (15%↓ ,P<0.01). The mean
Serum Triglycerides decreased significantly from
170.8 mg/dl to 123.86 mg/dl (27%↓ , P<0.01).
The mean LDL-C decreased significantly from
144.08 mg/dl to 112.5 mg/dl (22%↓ , P<0.01).
The mean HDL-C increased from 40.62 mg/dl to
47.5 mg/dl (14%↑ , P<0.05). The mean VLDL-C
decreased from 34.16 mg/dl to 25.06 mg/dl
(27%↓ , P<0.01).
Blood Pressure initial Vs after 24 weeks:
(Table2) The initial systolic BP ranged from 140160 mm Hg with a mean of 149.96 ± 1.0 mm Hg
and the initial diastolic BP ranged from 80-99
mm Hg with a mean of 92.88 ± 0.52 mm Hg.
After 24 weeks of treatment with Telmisartan,
the mean systolic BP in the patients decreased
significantly from 149.96 mm Hg to 122.72 mm
Hg (18%↓ , P<0.01) Similarly, the mean DBP
also decreased from 92.88 mm Hg to 81.92 mm
Hg (12%↓ , P<0.01).
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Int J Med Res Health Sci. 2013;2(4):745-749
Table.1: Lipid profile initial vs after 24 weeks
Lipid parameters (mean Initial
values mg/dl)
Total cholesterol
218.86± 3.91
Serum Triglycerides
170.8±5.25
LDL – Cholesterol
144.08± 3.65
HDL – Cholesterol
40.62± 0.76
34.16± 1.04
VLDL – Cholesterol
After 24 weeks
% of
P value
185.06±5.29
123.86±0.52
112.5±6.11
47.5±3.12
25.06±1.42
15%
27%
22%
- 14%
27%
< 0.01
< 0.01
< 0.01
< 0.05
< 0.01
Table.2: Blood pressure initial vs after 24 weeks
Parameters
Initial
Mean Systolic BP (mm Hg)
Mean Diastolic BP (mm Hg)
149.96± 1.0
92.88 ± 0.52
After
24 % of
weeks
122.72±3.4 18%
81.92±2.33 12%
P value
< 0.01
< 0.01
DISCUSSION
Hypertension is not the only determinant of
cardiovascular damage and the propensity of a
subject to develop atherosclerotic vascular
disease is markedly affected by the presence of
other risk factors such as age, gender, obesity,
smoking, diabetes and dyslipidemia.
There is no doubt that the management of lipid
disorders in hypertensive patients ameliorates
their total cardiovascular risk. Clinical trials
suggest that some antihypertensive agents may
have a beneficial effect on lipid metabolism
through
various
possible
mechanisms.
Telmisartan is an unique angiotensin receptor
blocker (ARB) with an additional PPAR-γ
modulating action6.
It is possible that the lipid lowering effect of
Telmisartan is due to numerous mechanisms. The
ARBs activate PPAR-γ which regulates lipid
metabolism; thereby reduce triglyceride and
LDL-C
levels.
Furthermore,
there
is
experimental evidence suggesting an interaction
between angiotensin system and lipid
metabolism. The ARBs reduce the AT-II
mediated
endothelial
injury and
lipid
7
peroxidation by blocking the AT1 receptor .
Telmisartan is commonly prescribed for grade I
essential hypertension in the medical outpatient
Vanitha et al.,
department. In the present study, the effect of
long term administration of Telmisartan on
serum lipid profile was evaluated. .The patients
who were enrolled into the study had both
hypertension and dyslipidemia. Also, the efficacy
of Telmisartan in reducing both systolic and
diastolic BP was evaluated in this study. In the
present study, there was significant effect on
serum lipid profile in the patients, who were
given Telmisartan 40-80 mg/day, for 6 months.
The total serum cholesterol decreased by 16 %(
P<0.01), LDL-C by 22% (P<0.01), serum
triglycerides decreased by 27 %( P<0.01) and
VLDL-C decreased by 27 %( P<0.01). The
HDL-C increased by 14 %( P<0.05)
This favourable effect on serum lipid profile was
in addition to the proved effect of Telmisartan as
an antihypertensive drug. Telmisartan in a dose
of 40-80 mg/day, significantly reduced both
systolic BP by 18 %( P<0.01) and diastolic BP
by 12 %( P<0.01). In our study, Telmisartan was
well tolerated, except for some minor and
transient side effects like headache, dizziness and
fatigue in a few patients.
The significant effect of Telmisartan on serum
lipid profile in the present study is supported by
preclinical studies conducted on rabbits and also
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Int J Med Res Health Sci. 2013;2(4):745-749
by STAR trial, (Saga Telmisartan Aggressive
Research Study), a single arm, prospective,
multicentric clinical trial conducted in Japan on
197 patients with hypertension and dyslipidemia.
CONCLUSION
In our study, Telmisartan proved to be effective
not only in controlling BP, but had a favorable
effect on lipid profile also. Telmisartan treatment
results in amelioration of cardiovascular risk
factors, not only through arterial pressure
regulation but also through reduction of serum
lipid profile. So, in conclusion, all the patients
with
uncomplicated
hypertension
and
dyslipidemia without other associated risk factors
can be effectively treated with Telmisartan.
5. Diamant M Heine RJ. TZD in type 2
diabetes mellitus (Current clinical evidence).
Drugs.2003; 63:1373 – 05
6. Schupp M, Janke J, Clasen R. Angiotensin
type 1 receptor blockers induce peroxisome
proliferator–activated
receptor
activity.
Circulation, 2004;109: 2054–57.
7. Keidar S, Kaplan M, Hoffman A.
Angiotensin II stimulates macrophagemediated oxidation of low density
lipoproteins. Atherosclerosis 1995; 115: 20115.
ACKNOWLEDGEMENT
The authors are thankful to Management and
staff of Medical Out Patient Department ,Gandhi
Hospital, Secunderabad, Andhra Pradesh , for
providing necessary facilities to carryout the
research work .
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2. Ran J, Hirano T, Adachi M. Angiotensin II
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4. Pershad Singh HA. Peroxisome proliferatoractivated receptor–γ : therapeutic target for
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