Angiology
Volume 60 Number 2
Effect of Antihypertensive Therapy
on Serum Lipids in Newly Diagnosed
Essential Hypertensive Men
Hanumanthappa Nandeesha, MD, Purushothaman Pavithran, MSc,
and T Madanmohan, MD
The effect of antihypertensives on serum lipids in newly
diagnosed male essential hypertensive patients was stud-
ied. The participants (n = 99) were randomly allocated to
receive amlodipine, atenolol, enalapril, hydrochloroth-
iazide, and a combination of amlodipine and atenolol.
Lipid parameters were estimated before and after 8 weeks
of therapy. The atenolol and thiazide group showed a
significant increase in triglycerides (TGs) and very-
low-density lipoprotein cholesterol (VLDL-C). High-
density lipoprotein cholesterol (HDL-C) and HDL-C to
low-density lipoprotein cholesterol (LDL-C) ratio were
Introduction
Hypertension is a major modifiable risk factor for
cardiovascular disorders and is accompanied by a
widespread metabolic disarray, including dyslipi-
demia.1 Recent studies have demonstrated that dys-
lipidemia antedates and predicts the risk for
cardiovascular disease2 and reported that high
triglyceride (TG) and low-density lipoprotein choles-
terol (LDL-C) concentrations are strong risk factors
for the development of cardiovascular disorders.3,4
Clustering of these multiple risk factors may hinder
the improvement in coronary heart disease mortality
provided by simple blood pressure (BP) reduction
From the Department of Biochemistry (HN) and the Department
of Physiology (PP, TM), Jawaharlal Institute of Postgraduate
Medical Education and Research, Pondicherry 605006, India.
The present study was funded by the Indian Council of Medical
Research (ICMR) in the form of a senior research fellowship to
Mr Purushothaman Pavithran. Hanumanthappa Nandeesha
and Purushothaman Pavithran contributed equally to the study.
Address correspondence to: P. Pavithran, Senior Research Fellow,
Autonomic Laboratory, Department of Physiology, Jawaharlal
Institute of Postgraduate Medical Education and Research,
Pondicherry, 605006, India; e-mail: pavithranpp@gmail.com.
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April/May 2009 217-220
© 2009 The Author(s)
10.1177/0003319708316167
http://ang.sagepub.com
significantly increased and TC to HDL-C ratio was sig-
nificantly decreased in the amlodipine and amlodipine–
atenolol combination groups. In the enalapril group, we
found a significant reduction in TC, TGs, VLDL-C, non-
HDL-C, and TG to HDL-C ratio after treatment. It can
be concluded from the present study that some drugs
have beneficial effects on the lipid status, whereas others
adversely affect the lipid status in hypertension.
Keywords: essential hypertension; antihypertensives;
dyslipidemia
alone. Recent guidelines have emphasized the
importance of correcting dyslipidemia along with
lowering arterial pressure to reduce cardiovascular
risk in these patients.5
Antihypertensive agents are reported to exhibit a
wide range of effects on lipid metabolism. Some
drugs adversely affect the serum lipids, whereas oth-
ers have a favorable effect. Previous studies have
reported that diuretics and β-blockers negatively
affect serum lipid levels.6,7 Hernandez et al8 have
reported calcium antagonists, especially the highly
lipophilic amlodipine to possess antioxidant proper-
ties, reducing the oxidation of LDL and its influx
into the arterial wall, their by reducing atheroscle-
rotic lesions in animals. Pinilla et al9 as well as
Libretti and Catalano10 have reported that the
angiotensin-converting enzyme (ACE) inhibitor
enalapril reduces total cholesterol (TC), TGs, and LDL-
C. Youssef et al11 reported that enalapril increased high-
density lipoprotein cholesterol (HDL-C), whereas
Libretti and Catalano10 did not find any change
in HDL-C after enalapril treatment. Other stud-
ies have reported ACE inhibitors and calcium
channel blockers to have neutral effects on lipid
metabolism.12,13
217
218 Angiology / Vol. 60, No. 2, April/May 2009
Even though the association between antihyper-
tensive drugs and lipid parameters is well established,
there are only limited reports regarding the same in
Indian patients. The present study was designed to
evaluate the effect of the antihypertensive agents
amlodipine, atenolol, enalapril, hydrochlorothiazide,
and amlodipine–atenolol combination on serum
lipids in nondiabetic, nonobese newly diagnosed male
hypertensive patients.
Materials and Methods
The present study was done in the departments of
Physiology and Biochemistry of the Jawaharlal
Institute of Postgraduate Medical Education and
Research (JIPMER), Pondicherry, India. We enrolled
150 newly diagnosed male hypertensive patients
and 40 controls in the study. Newly diagnosed
hypertensive patients were defined as those who
were diagnosed with hypertension during the
period of the study and were not on any antihyper-
tensive medication. The patients were asked to sit
in a chair with their back supported for 5 minutes
after which the BP was recorded using a mercury
sphygmomanometer (Diamond, India). Patients
with evidence of target organ damage from high
BP, secondary hypertension, diabetes, smoking,
and alcoholism and those who were receiving any
kind of medications were excluded. Hypertensive
patients were randomly allocated to receive amlodip-
ine (5 mg), atenolol (25 mg), amlodipine–atenolol
combination (5 + 50 mg), enalapril (5 mg), and
hydrochlorothiazide (25 mg) for 8 weeks. None of
the patients was on cholesterol-lowering drugs. All
participants gave written informed consent. The
research and ethics committees of JIPMER
approved the study protocol. Out of 150 hyperten-
sive patients, only 99 patients came for follow-up
after 8 weeks, and data from these patients were
included for the final study. Among these 99
patients, 20 belonged to the amlodipine group, 20
to the atenolol group, 29 to the enalapril group, and
15 each to the hydrochlorothiazide and amlodipine–
atenolol groups.
Anthropometric Measurements
Body weight and height of the participants were
measured. Body mass index was calculated as weight
in kilograms divided by squared height in meter
squared.
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Blood Sample Collection and
Analysis of Parameters
After the patients had fasted overnight for at least 8
hours, blood was drawn and collected in bottles.
Serum was collected by allowing the blood to clot and
centrifuging it at 5000 rpm for 5 minutes. Serum lipid
parameters were estimated immediately and after 8
weeks of antihypertensive therapy. TC was estimated
by the cholesterol oxidase method, TGs by glycerol oxi-
dase method, and HDL-C by the phosphotungstate
magnesium chloride method using a reagent kit from
Agappe Diagnostics (Maharashtra, India) adapted to
550 express plus a random-access autoanalyzer (Ciba
Corning, Oberlin, OH). LDL-C was calculated by
Friedwald’s formula.14 Non-HDL-C was calculated as
TC minus HDL-C. The atherogenic indices as indi-
cated by various risk ratios were calculated as
TC/HDL-C, HDL-C/LDL-C, and TG/HDL-C.
Statistical Analysis
All data are expressed as mean ± standard deviation.
SPSS (Version 13, SPSS Inc, Chicago, IL) was used
for statistical analysis. The unpaired t test or the
Mann-Whitney U test was used as appropriate for sta-
tistical comparisons between the groups. The paired t
test or the Wilcoxon signed rank test was used in the
analysis of within-group changes. A 2-tailed P value <
.05 was considered statistically significant.
Results
Baseline characteristics of hypertensive patients and nor-
motensive controls are shown in Table 1. TC, TGs, LDL-
C, non-HDL-C, TC/HDL-C, and TG/HDL-C were
significantly increased, and HDL-C and HDL-C/ LDL-C
were significantly decreased in hypertensive patients.
The effect of 8 weeks of antihypertensive therapy
on lipid parameters is shown in Table 2. Systolic as well
as diastolic BPs were significantly decreased after treat-
ment in all the groups. The atenolol (P < .05) and thi-
azide groups (P < .01) showed significant increases in
TGs and very-low-density lipoprotein cholesterol
(VLDL-C). HDL-C and HDL-C/LDL-C were signifi-
cantly increased, and TC/HDL-C was significantly
decreased in the amlodipine (P < .05) and amlodipine–
atenolol groups (P < .05). In the enalapril group, we
found a significant reduction in TC (P < .05), TGs
(P < .01), VLDL-C (P < .01), non-HDL-C (P < .05),
and TG/HDL-C (P < .01) after treatment.
 Effect of Antihypertensive Therapy on Serum Lipids / Nandeesha et al 219

Table 1. Baseline Blood Pressure and Lipid Profile in It is clearly evident that newly diagnosed hyper-
Normotensive Controls and Hypertensive Patients tensive patients in the present study have an altered
Controls Hypertensive lipid profile. Data from the present study also con-
Parameters (n = 40) Patients (n = 99) firm and extend the results of previous studies that
examined the effects of various antihypertensive
Age (years) 43 ± 10 45 ± 8
agents on serum lipid parameters. In the current
BMI (kg/m2) 24 ± 5 25 ± 6
SP (mm Hg) 113 ± 9 160 ± 17a study, both atenolol and hydrochlorothiazide signifi-
DP (mm Hg) 74 ± 7 99 ± 9a cantly increased TG and VLDL-C levels confirming
TC (mmol/L) 4.26 ± 0.60 4.72 ± 0.94a previous reports of negative effects on plasma lipid
TG(mmol/L) 0.95 ± 0.27 1.32 ± 0.60a parameters with both β-blockers and diuretics,6,12,16
HDL-C (mmol/L) 1.28 ± 0.25 1.03 ± 0.14a but in contrast to these reports we didn’t find any
LDL-C (mmol/L) 2.54 ± 0.61 3.09 ± 0.90a
VLDL-C (mmol/L) 0.43 ± 0.12 0.60 ± 0.27a
significant alteration in HDL-C and LDL-C levels
TC/HDL-C 3.44 ± 0.86 4.70 ± 1.32a after treatment in both the groups. Although the
TG/HDL-C 0.77 ± 0.29 1.32 ± 0.70a mechanisms behind the drug-induced dyslipidemia
HDL-C/LDL-C 0.54 ± 0.20 0.36 ± 0.13a remain uncertain, it has been suggested that both
Non-HDL-C 2.97 ± 0.63 3.69 ± 0.96a atenolol and hydrochlorothiazide are associated with
NOTE: SP = systolic pressure; DP = diastolic pressure; TC = total reduced insulin sensitivity and hyperinsulinemia,
cholesterol; TG = triglyceride; HDL-C = high-density lipopro- which in turn may cause dyslipidemia characterized
tein cholesterol; LDL-C = low-density lipoprotein cholesterol; by high TG levels.17-19
VLDL-C = verylow-density lipoprotein cholesterol. The effect of calcium antagonists and ACE
a
P < .01 compared with controls (data are expressed as mean ± inhibitors on plasma lipid levels remains controversial.
standard deviation).
Several studies report that these drugs are metabolically
neutral and cause few lipoprotein alterations.12,13 In the
Discussion present study, we noted significant increases in HDL-C
and HDL-C/LDL-C and decrease in TC/HDL-C in the
Hypertensive patients who are at risk for cardiovas- amlodipine and amlodipine–atenolol groups. These
cular events often present with an abnormal serum findings were in accordance with a previous report that
lipid profile. In contrast to previous approaches that demonstrated an increase in HDL-C on treatment with
focused solely on the reduction of elevated BP, the calcium antagonists.20 In patients treated with enalapril
management of hypertension has focused on the we found significant reductions in TC, TGs, VLDL-C,
need for an integrated approach to reduce overall non-HDL-C, and TG/HDL-C, which were similar to
cardiovascular risk.15 those reported in a previous population-based study.21

Table 2. Blood Pressure and Lipid Profile in Patients Before and After 8 Weeks of Antihypertensive Therapy
Atenolol Amlodipine Enalapril Thiazide Amlodipine+
(n = 20) (n = 20) (n = 29) (n = 15) Atenolol (n = 15)

Before After Before After Before After Before After Before After

SP (mm Hg) 166 ± 9 129 ± 6b 155 ± 18 128 ± 5b 160 ± 17 117 ± 13b 151 ± 10 126 ± 7b 168 ± 14 127 ± 8b
DP (mm Hg) 99 ± 9 79 ± 6b 100 ± 11 79 ± 7b 98 ± 6 74 ± 7b 95 ± 8 78 ± 6b 104 ± 9 78 ± 6b
TC (mmol/L) 4.73 ± 0.91 4.96 ± 0.82 4.94 ± 0.78 4.71 ± 0.63 4.92 ± 0.99 4.60 ± 0.68a 4.28 ± 0.91 4.51 ± 0.53 4.49 ± 1.02 4.27 ± 0.85
TG(mmol/L) 1.30 ± 0.44 1.66 ± 0.72a 1.55 ± 0.74 1.42 ± 0.69 1.44 ± 0.50 1.26 ± 0.45b 0.89 ± 0.35 1.20 ± 0.45b 1.22 ± 0.77 1.24 ± 0.65
HDL-C 1.02 ± 0.14 1.03 ± 0.12 1.03 ± 0.14 1.14 ± 0.15a 1.02 ± 0.12 1.06 ± 0.12 1.02 ± 0.17 1.08 ± 0.18 1.02 ± 0.16 1.15 ± 0.15a
(mmol/L)
LDL-C 3.11 ± 1.06 3.17 ± 0.80 3.20 ± 0.74 2.92 ± 0.68 3.23 ± 0.98 2.95 ± 0.73 2.85 ± 0.77 2.87 ± 0.44 2.90 ± 0.85 2.56 ± 0.82a
(mmol/L)
VLDL-C 0.59 ± 0.20 0.75 ± 0.33a 0.70 ± 0.34 0.64 ± 0.31 0.65 ± 0.22 0.57 ± 0.20b 0.40 ± 0.16 0.54 ± 0.20b 0.55 ± 0.35 0.56 ± 0.29
(mmol/L)
TC/HDL-C 4.77 ± 1.62 4.80 ± 0.59 4.83 ± 0.95 4.17 ± 0.76a 4.92 ± 1.54 4.39 ± 0.88 4.23 ± 0.77 4.24 ± 0.69 4.47 ± 1.31 3.80 ± 1.02b
TG/HDL-C 1.27 ± 0.39 1.66 ± 0.90 1.57 ± 0.94 1.30 ± 0.77 1.43 ± 0.60 1.19 ± 0.42b 0.91 ± 0.41 1.12 ± 0.42 1.24 ± 0.93 1.17 ± 0.85
HDL-C/LDL-C 0.36 ± 0.14 0.33 ± 0.06 0.33 ± 0.07 0.41 ± 0.10a 0.36 ± 0.18 0.41 ± 0.26 0.37 ± 0.07 0.38 ± 0.09 0.38 ± 0.12 0.49 ± 0.17a
Non HDL-C 3.70 ± 0.99 3.92 ± 0.74 3.91 ± 0.75 3.56 ± 0.61 3.89 ± 1.05 3.53 ± 0.74a 3.26 ± 0.83 3.42 ± 0.51 3.46 ± 1.04 3.12 ± 0.88

NOTE: SP = systolic pressure; DP = diastolic pressure; TC = total cholesterol; TG = triglyceride; HDL-C = high-density lipoprotein cholesterol;
LDL-C = lowdensity lipoprotein cholesterol; VLDL-C = very-low-density lipoprotein cholesterol.
a
P < .05, bP < .01 compared with before treatment (data are expressed as mean ± standard deviation).

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220 Angiology / Vol. 60, No. 2, April/May 2009
To conclude, it is clear from the present study that
different antihypertensives have different effects on
serum lipids in newly diagnosed hypertension.
Atenolol and the thiazide diuretic had deleterious
effects on serum lipids, whereas amlodipine, enalapril,
and the combination of amlodipine and atenolol
brought about an improvement in the lipid status.
These factors are to be taken into consideration while
prescribing antihypertensive drugs in patients with
clear evidence of dyslipidemia.
The novelty of the study lies in the fact that we
studied untreated hypertensive patients and tested 4
different classes of antihypertensive drugs plus a com-
bination therapy at the same time. The main limitation
of our study is the small sample size and short dura-
tion of therapy (8 weeks) because of which we are
unable to assess the type of antihypertensive drug that
is potentially beneficial with regard to lipid metabo-
lism in those with essential hypertension.
References
1. Reaven GM, Lithell H, Landsberg L. Hypertension and
associated metabolic abnormalities—the role of insulin
resistance and the sympathoadrenal system. N Engl J
Med. 1996;334:374-381.
2. Halperin RO, Sesso HD, Buring JE, et al. Dyslipidemia and
the risk of incident hypertension in men. Hypertension.
2006;47:45-50.
3. Lowe GDO. Blood viscosity and cardiovascular risk.
Curr Opin Lipidol. 1993;4:283.
4. Hokanson JE, Austin MA. Plasma triglyceride level is a risk
factor for cardiovascular disease independent of high-density
lipoprotein cholesterol: a meta-analysis of population based
prospective studies. J Cardiovasc Risk. 1996;3:213-219.
5. Keane WF, Eknoyan G. Proteinuria, albuminuria, risk,
assessment, detection, elimination (PARADE): a posi-
tion paper of the National Kidney Foundation. Am J
Kidney Dis. 1999;33:1004-1010.
6. Dimmitt SB, Williams PD, Croft KD, Beilin LJ. Effects
of beta-blockers on the concentration and oxidizability
of plasma lipids. Clin Sci. 1998;94:573-578.
7. Neutel JM. Metabolic manifestations of low-dose
diuretics. Am J Med. 1996;101:71S-82S.
8. Hernandez RH, Armas-Hernandez MJ, Velasco M,
Israili ZH, Armas-Padilla MC. Calcium antagonists and
For reprints and permissions queries, please visit SAGE’s Web site at http://www.sagepub.com/journalsPermissions.nav.
Downloaded from ang.sagepub.com at PENNSYLVANIA STATE UNIV on September 18, 2016
atherosclerosis protection in hypertension. Am J Ther.
2003;10:409-414.
9. Pinilla FC, Otero LM, Claros MN, Osa AJM, Rodicio Diàz
JL, Urioste RLM. Treatment of essential arterial hyper-
tension with hypercholesterolemia. Effects of an alpha-
adrenergic blocker and an inhibitor of the angiotensin
converting enzyme. Med Clin (Barc). 1993;101:168-171.
10. Libretti A, Catalano M. Lipid profile during antihyperten-
sive treatment. The SLIP Study Group. Study on Lipids
with Isoptin Press. Drugs. 1993;46(suppl 2):16-23.
11. Youssef S, Osman L, Sabbour MS. Serum lipoprotein
profile under different antihypertensive therapy. Int J
Clin Pharmacol Res. 1992;12:109-116.
12. Kasiske BL, Ma JZ, Kalil RSN, Louis TA. Effects of anti-
hypertensive therapy on serum lipids. Ann Intern Med.
1995;122:133-141.
13. Brook RD. Mechanism of differential effects of antihy-
pertensive agents on serum lipids. Curr Hypertens Rep.
2000;2:370-377.
14. Friedewald WT, Levy RI, Fredrickson DS. Estimation of
the concentration of low density lipoprotein cholesterol
in plasma without use of the preparative ultracentrifuge.
Clin Chem. 1972;18:499-502.
15. Bakris GL, Williams M, Dworkin L, et al. Preserving
renal function in adults with hypertension and diabetes:
a consensus approach. National Kidney Foundation
Hypertension and Diabetes Executive Committees
Working Group. Am J Kidney Dis. 2000;36:646-661.
16. Moser M. Why are physicians not prescribing diuretics
more frequently in the management of hypertension?
JAMA. 1998;279:1813-1816.
17. Lithell H. Hypertension and hyperlipidemia. Am J
Hypertens. 1993;6:303S-308S.
18. Weidmann P, de Courten M, Ferrari P. Effect of diuretics on
the plasma serum lipids. Eur Heart J. 1992;13:61-67.
19. Jeppesen J, Hein HO, Suadicani P, Gyntelberg F.
Relation of high TG–low HDL cholesterol and LDL
cholesterol to the incidence of ischemic heart disease.
An 8 year follow-up in the Copenhagen Male study.
Arterioscler Thromb Vasc Biol. 1997;17:1114-1120.
20. Leonetti G. Effects of nilvadipine and amlodipine in
patients with mild to moderate essential hypertension: a
double blind, prospective, randomized clinical trial.
Curr Med Res Opin. 2005;21:951-958.
21. Marques-Vidal P, Montaye M, Haas B, et al. Association
of hypertensive status and its drug treatment with lipid
and haemostatic factors in middle-aged men: the
PRIME study. J Hum Hypertens. 2000;14:511-518.