Effects of thyroid replacement therapy on arterial

blood pressure in patients with hypertension and

hypothyroidism
John Dernellis, MD, and Maria Panaretou, MD Mytilini, Greece

Background Hypothyroidism is frequently accompanied by cardiac dysfunction, increased vascular resistance, and a
greater prevalence of hypertension. Treatment of hypothyroidism may lead to normalization of blood pressure, although
some patients may exhibit sustained hypertension. The mechanism of this condition may be the alterations in aortic stiffness.
Methods Aortic stiffness was studied in 30 patients who never received treatment for hypertension or hypothyroidism, 15
patients with normal blood pressure and hypothyroidism, and 15 patients with hypertension and normal thyroid function. Thirty
healthy age- and sex-matched subjects with normal thyroid function served as control subjects. Aortic diameter evaluated by M-
mode echocardiography and blood pressure measured by a sphygmomanometer were used to calculate aortic stiffness index.
Results Patients with high blood pressure and hypothyroidism, those with normal blood pressure and hypothyroidism,
and those with hypertension and normal thyroid function showed increased aortic stiffness index (18.8 ± 6.4, 11.7 ± 3.5,
and 19.2 ± 5.3 vs 9.5 ± 2.7; P < .001) compared with control subjects. In 15 patients with hypertension and hypothy-
roidism, levothyroxine therapy showed only a small decrease in blood pressure (151/105 ± 9/9 mm Hg, group A). The
remaining 15 patients showed complete normalization of blood pressure (118/83 ± 8/3 mm Hg, group B). Aortic stiffness
index was increased in group A compared with group B both before and after treatment (before, 24.0 ± 4.1 vs 13.7 ± 3.2;
and after, 22.3 ± 4.2 vs 11.1 ± 2.9; P < .001 for both comparisons). Felodipine was given to patients in group A after
levothyroxine was administered, resulting in normalization of blood pressure and a significant decrease of aortic stiffness
index (P < .001). Aortic stiffness index was decreased in patients with hypothyroidism and hypertension after administration
of levothyroxine (9.5 ± 2.2; P < .001) and felodipine (14.5 ± 7.5; P < .001) therapy, respectively. Percent changes in sys-
tolic blood pressure showed a significant correlation with percent changes in aortic stiffness index in all patients (r = 0.65, P
< .001). After multivariate adjustment, aortic stiffness index (odds ratio = 1.9932; confidence interval = 1.1481 to 3.4605)
was significantly associated with incomplete normalization of blood pressure.
Conclusions Patients with hypertension and hypothyroidism have increased aortic stiffness. Aortic stiffness is
decreased in all patients, whereas hypertension is completely reversible in 50% of patients by hormone replacement ther-
apy. Sustained hypertension may be due to increased aortic stiffness. (Am Heart J 2002;143:718-24.)

The heart is a major target organ for thyroid hormone
action, and marked changes occur in cardiovascular
function in patients with hypothyroidism.1 In patients
with hypothyroidism, a true enhanced incidence of
hypertension (increased peripheral vascular resistance)
has been found.2,3 The reported prevalence of hyper-
tension in hypothyroidism varies between 0% and 50%.
Hypothyroidism has been identified as a cause of hyper-
tension in 3% of patients with high blood pressure.
Patients with hypothyroidism have a 3-fold increased
prevalence of hypertension, usually diastolic.2-4 In addi-
From the Department of Cardiology, Vostanion Hospital, Mytilini.
Submitted December 21, 2000; accepted September 27, 2001.
Reprint requests: John Dernellis, MD, 1 Kathigitou Karakatsani St, 811 00 Mytilini,
Greece.
Copyright 2002, Mosby, Inc. All rights reserved.
0002-8703/2002/$35.00 + 0 4/1/120766
doi:10.1067/mhj.2002.120766
tion, hypercholesterolemia and impairment of fatty acid
mobilization are associated with myxedema and present
additional risk factors for the development of athero-
sclerotic cardiovascular disease.5,6
Thyroid hormone replacement therapy in patients
with high blood pressure and hypothyroidism do not
always successfully decrease the blood pressure.7 The
pathogenesis and the exact mechanism of sustained
hypertension in spite of pharmaceutical normal thyroid
function have not been delineated. Impairment of the
aortic elastic properties may be the cause for the incom-
plete normalization of blood pressure in patients with
hypothyroidism and hypertension.8 But no study has
examined the elastic properties of the aorta before and
after hormone replacement therapy in patients with
hypothyroidism and high blood pressure.
The aim of this study was to investigate the reversibil-
ity of arterial hypertension and of the impairment in
American Heart Journal
Volume 143, Number 4 Dernellis and Panaretou 719

aortic stiffness as measured by echocardiography after Figure 1

restoration of normal thyroid function in patients with
hypertension and hypothyroidism. Furthermore, we
examined any possible relation between aortic stiff-
ness and the response of blood pressure to levothy-
roxine.

Methods
Study population
Thirty patients (27 women, age 44 ± 12 years) who were
referred for arterial hypertension and hypothyroidism were
studied. These patients were selected after 1004 patients with
hypertension were screened. Patients included in the study ful-
filled the following criteria: (1) resting blood pressure > 140/90
mm Hg at repeated sphygmomanometric measurements, (2) a
diagnosis of primary hypothyroidism, (3) low serum levels of
thyroid hormone and elevated serum thyroid-stimulating hor-
mone (TSH) levels, (4) no evidence of coronary artery disease at
routine medical examinations (standard and effort electrocar-
diography, and echocardiography), and (5) no other major dis-
ease and no current treatment with cardiovascular or noncar-
diovascular drugs. Fifteen age- and sex-matched patients with
hypothyroidism and normal blood pressure who met the above
criteria but with resting blood pressure < 140/90 mm Hg, as
well as 15 age- and sex-matched patients with normal thyroid
function and hypertension who had no evidence of coronary
artery disease at routine medical examinations and no other
major disease and no current treatment with cardiovascular or
noncardiovascular drugs were also studied. Thirty age- and sex-
matched control subjects with normal thyroid function and nor-
mal blood pressure were also selected.
Study protocol
TSH, free-triiodothyronine, free-thyroxin, and total choles-
terol levels were measured before the study from a blood
sample taken from an antecubital vein. In patients with
hypothyroidism TSH, free-triiodothyronine, and free-thy-
roxin were measured at various times during hormone
replacement therapy. The initial dosage of levothyroxine is
based on body weight (1.6 µg/kg/d) and was lower than 50
µg/d. The dosage was increased every 2 weeks by 25
µg/kg/d until the target dosage is achieved. When the val-
ues showed that an euthyroid condition had been reached,
a second study was performed. The euthyroid state was
achieved 9.0 ± 2.5 months later. A calcium channel antago-
nist (felodipine) was added to the hormone replacement
therapy in all patients of group A, who showed only a small
decrease in blood pressure (>140/90 mm Hg) after levothy-
roxine. These patients were studied again after levothyrox-
ine and felodipine were given for an additional 6 months.
Patients with normal thyroid function and hypertension
were also studied at baseline and 6 months after felodipine
treatment.
Aortic stiffness measurement
The transverse displacement of the aortic wall was meas-
ured with commercially available equipment (Image Point;
Hewlett Packard, Andover, Mass) with a 2.5-MHz transducer.
Measurement of aortic diameters from 2-dimensional guided
M-mode tracings. M-mode cursor on long axis parasternal 2-
dimensional echocardiogram is directed approximately 3 cm
above aortic valve. Electrocardiogram (ECG) is also shown.
After routine conventional echocardiographic examination,
patients were placed in a left mild recumbent position, and
the ascending aorta was recorded in the 2-dimensional guided
M-mode tracings. The protocol was similar to that used in pre-
vious studies.9-11 The aortic diameter was recorded by M-
mode echocardiography at a level of 3 cm above the aortic
valve. Internal aortic diameters were measured by means of a
caliper in systole and diastole as the distance between the
trailing edge of the anterior aortic wall and the leading edge of
the posterior aortic wall (Figure 1).
Aortic systolic (AoS) diameter was measured at the time of
full opening of the aortic valve, and diastolic (AoD) diameter
was measured at the peak of QRS. Ten consecutive beats were
measured routinely and averaged. The percentage change of
the aortic root was calculated as %∆Ao = 100 × (AoS –
AoD)/AoD to obtain the aortic strain.9-11
All patients had blood pressure measured manually in the
left arm while they were in the supine position by use of a
mercury sphygmomanometer. Korotkoff phases I and V were
used to determine the systolic and diastolic pressures, respec-
tively, and the average of 3 readings was regarded as the clini-
cal blood pressure. The aortic stiffness index (β) was calcu-
lated:9,12-14 β = 1n (SBP/DBP)/(AoS – AoD)/AoD (pure
number), where SBP is systolic arterial pressure and DBP is
diastolic arterial pressure.
Left ventricular ejection fraction was measured by 2-dimen-
sional echocardiography by use of the area-length method.
Baseline measurements were obtained after diagnosis and
before administration of any treatment and after hormone
replacement therapy resulting in alleviation of symptoms and
normalization of serum hormones.
Systemic vascular resistance measurements
Systemic vascular resistance (SVR) was calculated by the
equation SVR = Mean arterial blood pressure/Cardiac output.
Both parameters were measured noninvasively. Mean arterial
blood pressure was calculated by the formula [(Systolic – Dia-
 American Heart Journal
720 Dernellis and Panaretou April 2002

Table I. Data of control subjects and patients with hypothyroidism and normal blood pressure, patients with normal thyroid function
and hypertension, and patients with hypothyroidism and hypertension at baseline
Patients with
Patients with Patients with hypothyroidism P
Control subjects hypothyroidism hypertension and hypertension value

No. 30 15 15 30
Age (y) 43.7 ± 11.8 40.0 ± 13.6 44.8 ± 12.5 43.5 ± 11.9 NS
Sex (female) 27 13 13 27 NS
Heart rate (beats/min) 70.1 ± 10 61.5 ± 5.0* 70.6 ± 3.8 62.6 ± 9.2* .01
Systolic blood pressure (mm Hg) 125.2 ± 8.3 121.2 ± 11.7 154.8 ± 9.3† 160.0 ± 10.7† .001
Diastolic blood pressure (mm Hg) 77.6 ± 12.1 86.4 ± 10.5‡ 107.5 ± 16.2† 108.6 ± 10.2† .001
Systolic AD (mm) 32.6 ± 2.2 33.6 ± 4.1 37.1 ± 3.5† 36.1 ± 2.7† .001
Diastolic AD (mm) 30.8 ± 2 32.6 ± 4.0‡ 36.4 ± 3.4† 35.3 ± 2.8† .001
Strain (%) 5.56 ± 2.43 2.95 ± 0.55† 1.97 ± 0.44† 2.32 ± 0.91† .001
β 9.53 ± 2.69 11.65 ± 3.54‡ 19.16 ± 5.29† 18.82 ± 6.36† .001
SVR (dynes/sec/cm–5) 1520 ± 211 2557 ± 254† 2335 ± 257† 2927 ± 462† .001
Ejection fraction (%) 64.4 ± 5.9 63.6 ± 5.3 64.2 ± 8.7 64.3 ± 5.9 NS
Cholesterol (mg/dL) 200.6 ± 21.6 320.6 ± 21.4† 204.1 ± 16.9 321.2 ± 25.3† .001
TSH (µU/mL) 1.9 ± 0.16 81.22 ± 7.88† 2.06 ± 0.46 81.10 ± 8.92† .001
Free-triiodothyronine (pg/mL) 3.37 ± 0.61 1.95 ± 0.49† 3.49 ± 0.25 1.90 ± 0.18† .001
Free-thyroxin (pg/mL) 10.82 ± 2.08 3.85 ± 0.45† 10.05 ± 1.12 3.99 ± 0.65† .001

AD, Aortic diameter; β, aortic stiffness index.

*P < .01.
†P < .001.
‡P < .05.

stolic)/3 + Diastolic] blood pressure. Cardiac output is calcu- Results

lated by multiplying the stroke volume with the heart rate.
This principle is applied to the left ventricular outflow tract,
by means of echocardiography. The diameter of the left ven-
tricular outflow tract immediately below the aortic valve is
measured in a parasternal long-axis view, and a circular cross-
section of the outflow tract is assumed, which is calculated as
π × r2, with r one half of the diameter. An apical long-axis
view is used to acquire the pulsed-wave Doppler recording,
with the sample volume positioned in the outflow tract
directly below the aortic valve.15
Statistical analyses
Data are presented as mean ± SD. For comparisons of char-
acteristics between patients and control subjects, the 1-way
analysis of variance was used. Least significant difference, as a
post hoc operation, was used to determine which means dif-
fered (Table I). Qualitative data were compared with the χ2
test. Changes during the study within each group were evalu-
ated by use of the paired t test or the repeated measure analy-
sis of variance (Table II). Correlations were evaluated by use
of standard linear regression analysis. The following independ-
ent variables for explanation of the response of blood pres-
sure to hormone replacement therapy (dichotomous variable)
were entered in a forward logistic regression analysis: age,
sex, systolic and diastolic blood pressures and aortic diame-
ters, left ventricular ejection fraction, heart rate, total choles-
terol, TSH, free-triiodothyronine and free-thyroxin levels. All
variables except sex were entered as continuous ones. The
results of the logistic regression model were expressed as
odds ratio and the 95% confidence interval. The level of signif-
icance was P < .05.
Compared with control subjects, patients with hyper-
tension and hypothyroidism, as well as patients with
normal blood pressure and hypothyroidism, had lower
free-triiodothyronine and free-thyroxin, higher TSH and
higher plasma cholesterol values (P < .001, Table I).
Systolic and diastolic blood pressure (P < .001) was
increased whereas heart rate was decreased in patients
with hypertension and hypothyroidism compared with
control subjects (P < .001; Table I). Similarly, systolic
and diastolic diameters were increased in these patients
compared with control subjects (P < .001; Table I). Fur-
thermore, patients showed a significant increase in aor-
tic stiffness index and SVR compared with control sub-
jects (P < .001; Table I).
Patients with hypertension and normal thyroid function
showed a significant increase in systolic and diastolic aor-
tic pressures and diameters (P < .001), whereas patients
with normal blood pressure and hypothyroidism showed
a significant increase only in diastolic aortic pressure and
diameter (P < .05). Both groups showed significant
decrease in aortic strain and increase in aortic stiffness
and SVR compared with control subjects (Table I).
In the patients with hypertension and hypothy-
roidism and in patients with normal blood pressure and
hypothyroidism, hormone replacement therapy was
accompanied by a marked increase in free-triiodothyro-
nine and free-thyroxin, and a striking reduction in TSH
(P < .001; Tables II and III). Furthermore, the plasma
cholesterol level was significantly reduced (P < .001).
American Heart Journal
Volume 143, Number 4 Dernellis and Panaretou 721

Table II. Data at baseline and after treatment in patients who showed only a small decrease in blood pressure (group A) and in
patients who showed complete normalization of blood pressure (group B)
Group A Group B

Baseline L-T4 Rx CCA Rx P value* Baseline L-T4 Rx P value†

Heart rate (beats/min) 61.5 ± 10.7 67.6 ± 12 68.5 ± 7.4 NS 63.7 ± 7.6 70.5 ± 10.2 .01
Systolic blood pressure 164.1 ± 10.1 151.2 ± 9 114.3 ± 10.1 .001 155.9 ± 10 118.4 ± 8.1 .001
(mm Hg)
Diastolic blood pressure 112.8 ± 10.8 104.8 ± 8.9 83.1 ± 4.2 .001 104.3 ± 7.6 82.9 ± 3.4 .001
(mm Hg)
Systolic AD (mm) 37.7 ± 2 36.5 ± 2.5 36.2 ± 3.2 NS 34.6 ± 2.5 33.3 ± 3.1 NS
Diastolic AD (mm) 37.1 ± 2 35.9 ± 2.5 35.6 ± 3.3 NS 33.6 ± 2.3 32.3 ± 3 NS
Strain (%) 1.61 ± 0.37 1.69 ± 0.39 1.82 ± 0.62 .001 3.03 ± 0.7 3.33 ± 0.77 .001
β 23.95 ± 4.12 22.32 ± 4.21 19.86 ± 9.55 .001 13.69 ± 3.2 11.08 ± 2.92 .001
SVR (dynes/sec/cm–5) 3319 ± 241 3121 ± 246 2839 ± 389 .001 2534 ± 234 2123 ± 177 .001
Ejection fraction (%) 65.4 ± 5.7 63.3 ± 5.3 64.9 ± 6.4 NS 63.2 ± 6.2 65.4 ± 5.7 NS
Cholesterol (mg/dL) 329.9 ± 25.7 239.7 ± 20.4 236.4 ± 24.5 .001 312.6 ± 22.5 238.1 ± 19.9 .001
TSH (µU/mL) 85.62 ± 8.32 2.12 ± 0.63 1.87 ± 0.42 .001 76.58 ± 7.19 2.33 ± 0.63 .001
Free-triiodothyronine 1.9 ± 0.17 3.22 ± 0.25 3.20 ± 0.44 .001 1.90 ± 0.19 3.47 ± 0.31 .001
(pg/mL)
Free-thyroxin (pg/mL) 4.13 ± 0.8 10.07 ± 1.24 10.91 ± 1.82 .001 3.86 ± 0.45 9.93 ± 0.99 .001

L-T4 Rx, Levothyroxine therapy; CCA Rx, calcium channel antagonist (felodipine) therapy.
*Comparisons before and after treatment with L-T4 Rx and after CCA Rx in group A, (repeated measures analysis of variance).
†Pairwise comparisons before and after treatment in group B, (paired t test).

Table III. Data before and after treatment in patients with normal blood pressure and hypothyroidism (who received levothyroxine)
and patients with hypertension and normal thyroid function (who received calcium channel antagonist-felodipine)
Patients with hypothyroidism Patients with hypertension

Baseline L-T4 Rx P value* Baseline CCA Rx P value*

Heart rate (beats/min) 61.5 ± 5 67.0 ± 4.7 .01 70.6 ± 3.8 69.2 ± 3.7 NS
Systolic blood pressure (mm Hg) 121.2 ± 11.7 113.0 ± 9.2 .05 154.8 ± 9.3 113.3 ± 11.3 .001
Diastolic blood pressure (mm Hg) 86.4 ± 10.5 84.2 ± 3.7 NS 107.5 ± 16.2 84.9 ± 3.5 .001
Systolic AD (mm) 33.6 ± 4.1 32.8 ± 4.0 NS 37.1 ± 3.5 36.0 ± 3.5 NS
Diastolic AD (mm) 32.6 ± 4.0 31.8 ± 4.0 NS 36.4 ± 3.4 35.3 ± 3.5 NS
Strain (%) 2.95 ± 0.55 3.12 ± 0.56 .001 1.97 ± 0.44 2.14 ± 0.44 .001
β 11.65 ± 3.54 9.49 ± 2.18 .001 19.16 ± 5.29 14.47 ± 7.47 .001
SVR (dynes/sec/cm–5) 2557 ± 254 2020 ± 289 .001 2335 ± 257 1836 ± 321 .001
Ejection fraction (%) 63.6 ± 5.3 65.7 ± 3.6 NS 64.2 ± 8.7 64.7 ± 5.7 NS
Cholesterol (mg/dL) 320.6 ± 21.4 242.0 ± 17.9 .001 204.1 ± 16.9 196.6 ± 24.7 NS
TSH (µU/mL) 81.22 ± 7.88 2.07 ± 0.39 .001 2.06 ± 0.46 1.76 ± 0.48 NS
Free-triiodothyronine (pg/mL) 1.95 ± 0.49 3.43 ± 0.40 .001 3.49 ± 0.25 3.62 ± 0.55 NS
Free-thyroxin (pg/mL) 3.85 ± 0.45 10.17 ± 0.94 .001 10.05 ± 1.12 10.16 ± 2.16 NS
*Pairwise comparisons before and after treatment in patients with hypothyroidism and hypertension, respectively (paired t test).

In 15 patients levothyroxine therapy showed only a
small decrease in blood pressure (151/105 ± 9/9 mm
Hg, group A; Table II). The remaining 15 patients
showed complete normalization of blood pressure
(118/83 ± 8/3 mm Hg, group B). Aortic stiffness index
and SVR significantly decreased in both groups (P <
.001; Figures 2 and 3, Table II). After 6 months of
felodipine therapy, blood pressure was completely nor-
malized in group A. This was accompanied with a fur-
ther decrease of aortic stiffness index and SVR (P <
.001; Table II).
Furthermore, aortic stiffness index and SVR signifi-
cantly decreased in patients with normal blood pres-
sure and hypothyroidism and in patients with hyperten-
sion and normal thyroid function after levothyroxine
and felodipine therapy, respectively (P < .001; Figures
2 and 3 and Table III). There were no changes in global
systolic function (ejection fraction) (P = NS for all com-

722 Dernellis and Panaretou
Figure 2
Aortic stiffness index (β) at baseline and after treatment with
levothyroxine (L-T4 Rx) and calcium channel antagonist (CCA
Rx) felodipine, in patients with hypertension and hypothy-
roidism who showed small decrease in blood pressure (group
A) and in patients with hypertension and hypothyroidism who
showed complete normalization of blood pressure (group B).
Aortic stiffness index in patients with normal blood pressure
and hypothyroidism and patients with hypertension and normal
thyroid function at baseline and after treatment, as well as in
control subjects at baseline are also shown. Data are
expressed as means ± SD.
Figure 3
SVR at baseline and after treatment with levothyroxine (L-T4
Rx) and calcium channel antagonist (CCA Rx) felodipine, in
patients with hypertension and hypothyroidism who showed
small decrease in blood pressure (group A) and in patients
with hypertension and hypothyroidism who showed complete
normalization of blood pressure (group B). SVR in patients
with normal blood pressure and hypothyroidism and patients
with hypertension and normal thyroid function at baseline and
after treatment, as well as in control subjects at baseline are
also shown. Data are expressed as means ± SD.
American Heart Journal
April 2002
Figure 4
Linear regression analysis for aortic stiffness index changes
and systolic blood pressure changes in whole population.
parisons; Tables II and III). No patient showed an
increase in cholesterol, peripheral systolic and diastolic
pressures, aortic stiffness index β, and SVR.
Percent changes in systolic blood pressure showed a
significant correlation with percent changes in aortic
stiffness index (r2 = 0.70, P < .001; Figure 4). This find-
ing shows that 70% of the percent systolic blood pres-
sure changes resulted from the changes in aortic stiff-
ness. After multivariate adjustment aortic stiffness
index (odds ratio = 1.9932, confidence interval =
1.1481 to 3.4605; P < .01) was significantly associated
with incomplete normalization of blood pressure.
Discussion
The main findings of this study are that the patients
with hypertension and hypothyroidism have predomi-
nantly diastolic hypertension. Hypothyroidism leads to
increased aortic stiffness and SVR. Thyroid hormone
replacement therapy decreases both aortic stiffness and
SVR. Complete normalization of blood pressure is less
likely in patients with increased aortic stiffness. Antihy-
pertensive treatment improves aortic elastic properties
in patients with hypertension and hypothyroidism with
sustained hypertension similar to patients with hyper-
tension and normal thyroid function.
Effects of hypothyroidism on aortic stiffness—
mechanism of aortic stiffness and hypertension
in hypothyroidism
It is known that hypothyroidism leads to increased
vascular resistance, greater arterial wall thickness, and
endothelial dysfunction.3,8,16 Increased vascular resist-
ance was also found in this study in patients with hy-
pothyroidism and hypertension, as well as in patients
American Heart Journal
Volume 143, Number 4
with hypothyroidism and normal blood pressure. Aortic
stiffness has never been directly assessed in patients
with hypothyroidism, in spite of its importance for car-
diac function and its role in the development of athero-
sclerosis. We found that patients with hypertension and
hypothyroidism have increased aortic stiffness com-
pared with control subjects. Blood pressure was
increased, therefore these alterations are associated
with and dependent on blood pressure increase. Hyper-
cholesterolemia is associated with a reduction in aortic
compliance.9 Thus the increase in aortic stiffness char-
acterizing hypothyroidism also depends on the accom-
panying hypercholesterolemia. Furthermore, elevated
plasma homocysteine levels were described in hypothy-
roidism and may be an independent risk factor for the
accelerated atherosclerosis seen in primary hypothy-
roidism.17
Mechanisms responsible for the increased aortic stiff-
ness and hypertension in hypothyroidism may be the
following. Thyroid hormones interact with the sympa-
thetic nervous system.16,18,19 Hypothyroidism alters
responsiveness to sympathetic stimulation presumably
by modulating adrenergic receptor function and den-
sity.20 Patients with hypothyroidism display a decreased
response to β-adrenergic stimulation, which occurs in
spite of elevated, normal, or even decreased plasma
norepinephrine levels. Sympathetic nerve activity in
the smooth muscles of the vessels in patients with
hypothyroidism also seems to be increased. The num-
ber of β-adrenergic receptors is decreased, leading to
increased α-adrenergic responses, which may explain
the increase in peripheral vascular resistance and
hypertension of hypothyroidism.21 These changes may
be reversible after hormone substitution.19-22 In this
study we found that half of the patients with hypothy-
roidism and hypertension had complete normalization
of their blood pressure, whereas the remaining half had
shown a small decrease in blood pressure. Further-
more, patients with normal blood pressure and
hypothyroidism have shown a decrease in aortic stiff-
ness after hormone replacement therapy. These find-
ings support the hypothesis that hypothyroidism per se
results in increased aortic stiffness. Thus hypothy-
roidism may be a treatable cause of atherosclerosis.
Mechanism of no response in treatment with
levothyroxine
The blood pressure was normalized in half of the
patients, largely as a result of changes seen in aortic
stiffness. In our study it was shown that patients with
sustained hypertension after levothyroxine therapy
have aortic stiffness significantly increased compared
with those patients who have complete normalization
of blood pressure. Our findings indicate that the
response in the treatment of hypertension in hypothy-
roidism was blunted in some patients because of the
Dernellis and Panaretou 723
detrimental effects of hypothyroidism on aortic stiff-
ness. We showed that aortic elastic properties in
patients with hypertension and hypothyroidism are
impaired before, as well as after, hormone replacement
therapy because aortic remodeling alterations may exist
for an unknown period of time.
Increased aortic stiffness and systemic vascular resist-
ance were also found in patients with normal blood
pressure and hypothyroidism at baseline. Furthermore,
in these patients aortic stiffness and SVR were
decreased after levothyroxine therapy. These findings
also show the deleterious effects of hypothyroidism on
the vessels. In addition, antihypertensive therapy
reduces blood pressure and SVR in the patients with
hypertension and hypothyroidism who did not respond
to levothyroxine treatment. This effect was similar to
that observed in patients with hypertension and normal
thyroid function who showed a significant decrease in
blood pressure after felodipine therapy. Our findings
are in accordance with those of previous studies.23,24 It
can be assumed that part of the aortic stiffness in
patients with hypertension and hypothyroidism is due
to hypothyroidism and part to hypertension. The first
part is decreased after levothyroxine, whereas the sec-
ond decreased after felodipine therapy. Hypothy-
roidism causes atherosclerosis by means of increased
aortic stiffness and SVR, which in turn increase blood
pressure and concomitantly aggravate aortic stiffness.
Aortic stiffness predicts sustained hypertension after
hormone replacement therapy. Furthermore, the
changes in systolic blood pressure were correlated with
the changes in aortic stiffness index. This correlation
reveals that a possible explanation of sustained hyper-
tension in patients who received treatment for hyper-
tension and hypothyroidism is the increased aortic stiff-
ness that occurred after loss of adequate thyroid
hormone secretion. Aortic alterations accompanying
hypothyroidism did not return to normal state in all
patients. Hypothyroidism-related aorta alterations are
reversible in 50% of patients. This is the case at least
when hypothyroidism is therapeutically corrected soon
after its appearance.
Clinical implications
Hypothyroidism is a potentially important but over-
looked cause of hypertension, and restoration of nor-
mal thyroid function with levothyroxine therapy usu-
ally results in a substantial reduction in both systolic
and diastolic blood pressure.25 In addition to levothy-
roxine therapy, an antihypertensive drug may be
required in patients with hypertension and hypothy-
roidism with long-standing elevated blood pressure.
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