Narrative review
Why is functional capacity decreased in hypertensive
patients? From mechanisms to clinical studies
Marijana Tadica and Branislava Ivanovicb,c
The influence of arterial hypertension on functional capacity
is poorly understood. Studies have shown that peak oxygen
consumption has been reduced in hypertensive patients,
but the mechanisms are unclear. Left ventricular systolic
and diastolic dysfunction, as well as left ventricular
hypertrophy, are associated with lower functional capacity
in patients with arterial hypertension. Furthermore, some
investigations found a significant relationship between right
ventricular systolic function and functional capacity in the
general population. The aim of this review was to
summarize current knowledge about the mechanisms of
reduced functional capacity in hypertensive patients,
including the impact of systemic and pulmonary
circulations, as well as the influence of the left and right
ventricle on oxygen consumption. Additionally, we reviewed
Introduction
The influence of arterial hypertension on target organ
damage has been widely investigated. Studies also
showed that exercise capacity is significantly decreased
in patients with arterial hypertension,1–6 and even in
individuals with high-normal blood pressure.7,8 Further-
more, Faselis et al.9 found an inverse relationship
between exercise capacity and the rate of progression
from prehypertension to hypertension in middle-aged
male veterans. However, the mechanisms of the relation-
ship between blood pressure and functional capacity are
still unknown.
The purpose of this review is to summarize current
knowledge about the mechanisms of decreased exercise
capacity in hypertensive patients, as well as clinical
studies that concern this topic.
Physiological models of maximal oxygen
consumption limitations
Maximal oxygen consumption depends on several physio-
logical parameters: ventilation, oxygen diffusion at the
lung level, oxygen transport by the circulation, peripheral
perfusion and diffusion, and mitochondrial function. Di
Prampero et al.10,11 classified these parameters into three
types of resistances to maximal oxygen flow, which are
physiologically important: convective oxygen transport by
the circulation of blood, peripheral oxygen transfer from
the capillaries to the mitochondria, and oxygen consump-
tion in the mitochondria. Among these resistances, the
most significant limiting factor to peak oxygen uptake
(about 70%) is the convective oxygen transport.10 The
1558-2027 ß 2014 Italian Federation of Cardiology
Copyright © Italian Federation of Cardiology. Unauthorized reproduction of this article is prohibited.
all clinical studies regarding functional capacity in the
population with arterial hypertension.
J Cardiovasc Med 2014, 15:447–455
Keywords: arterial hypertension, functional capacity, left ventricle,
peak oxygen uptake, pulmonary circulation, right ventricle, systemic
circulation
a
University Clinical Hospital Center ‘Dr Dragisa Misovic’, bClinical Centre of
Serbia, Clinic for Cardiology and cMedical School of Belgrade, University of
Belgrade, Belgrade, Serbia
Correspondence to Marijana Tadic, MD, PhD, University Clinical Hospital Center
‘Dr Dragisa Misovic’, Heroja Milana Tepica 1, 11000 Belgrade, Serbia
E-mail: marijana_tadic@hotmail.com
Received 28 June 2013 Revised 7 August 2013
Accepted 6 September 2013
structural and functional modifications in the respiratory
system, following different physiological and pathophy-
siological conditions, do not change the percentage on
which these three resistances are combined in limiting
peak oxygen uptake.10
There are two different methods that could be used for
the analysis of peak oxygen uptake limitation. First
method was proposed by Wagner12 who studied a two-
site system (perfusion vs. diffusion), and investigated the
importance of peripheral oxygen diffusion as a factor
limiting oxygen uptake. An algebraic model of this sys-
tem was also proposed by the same author by applying
the diffusive–convective interaction equations.13 Both
methods disregarded the lungs as a specified possible
source that could limit peak oxygen uptake.12,13
Ferretti and di Prampero14 confirmed previous results
that cardiovascular oxygen transport represents a great
portion in the limitation of peak oxygen uptake in the
condition of a normal oxygen level, and revealed that
with a decrease in partial pressure of inspired oxygen, the
role of the lungs in limiting peak oxygen uptake becomes
greater and the importance of the cardiovascular system
becomes smaller.
The endothelial dysfunction in patients with arterial
hypertension leads to significant impairments in blood
oxygen transport indices,15 which could impact hemo-
globin-oxygen affinity and tissue oxygen supply. Alter-
nation of hemoglobin-oxygen supply may be the cause of
decreased oxygen uptake in arterial hypertension
patients. The confirmation of this research is found in
DOI:10.2459/JCM.0000000000000050
 448 Journal of Cardiovascular Medicine 2014, Vol 15 No 6
another investigation, which revealed that antihyper-
tensive treatment with nebivolol that stimulates nitric
oxide production, improves endothelium-dependent
dilatation and finally improves blood oxygen transport
in hypertensive patients.16 Additionally, mitochondrial
function in arterial hypertension is impaired, which
contributes to lower oxygen consumption and induces
oxidative stress,17 which also could be the reason for
lower peak oxygen uptake in the arterial hypertension
population.
Systemic circulation and exercise in arterial
hypertension
The adequate response of the systemic circulation to
exercise is increased cardiac and stroke volume index and
decreased systemic vascular resistance. This also happens
in hypertensive patients, but to a lesser extent than in
normotensive individuals. The possible reasons could be
endothelial dysfunction,3,18 increased circulating levels
of catecholamines and angiotensin II,19 myocardial
hypertrophy,8 or increased diastolic filling pressure.3,20
Another explanation for increased peripheral vascular
resistance in arterial hypertension could be an increase
in sodium gradient across the sarcolemma, which induces
increase in Ca2þ,21 and causes vasoconstriction, which
further significantly increases blood pressure during exer-
cise in arterial hypertension patients in comparison with
normotensive individuals. In contrast, hypertrophic
remodeling of small arteries and arterioles, as well as
reduction of precapillary arterioles, increases resistance
and mean blood pressure. This further increases arterial
stiffness and pulse pressure, which induces great
elevation of blood pressure during exercise in arterial
hypertension patients.22 The arteriolar remodeling in
arterial hypertension, consequent changes in wall/lumen
ratio,23,24 and capillary rarefaction25 could also decrease
vasodilatation during exercise, which contributes to lower
exercise capacity.
There is still no agreement about the impact of arterial
hypertension on endothelial function. Namely, Bruning
et al.26 and Cockcroft et al.27 found no difference in
endothelium-dependent vasodilator microvasculature
responses between arterial hypertensive patients and
normotensive individuals, whereas other studies revealed
impaired endothelium-dependent relaxation in microcir-
culation in arterial hypertensive patients due to oxidative
stress.3,4,18,28 The impairment of endothelium-depen-
dent relaxation in arterial hypertensive patients could
be the reason of increased peripheral resistance and the
cause of significantly greater exercise-induced blood
pressure elevation in arterial hypertensive patients.
Furthermore, increased systemic resistance leads to a
reduction in cardiac output, which could be an additional
cause of decreased oxygen uptake and reduced functional
capacity in the hypertensive population.29 Cornelissen
and Fagard30 in a meta-analysis found that endurance
Copyright © Italian Federation of Cardiology. Unauthorized reproduction of this article is prohibited.
training (
4 weeks) in arterial hypertensive patients
results in decreased systemic vascular resistance by
7.1%, plasma norepinephrine by 29%, and plasma renin
activity by 20%. Moreover, the authors showed that this
regimen, regardless of drug usage, significantly decreased
insulin resistance. These hemodynamic and biohumoral
changes resulted in a significant decrease in resting blood
pressure (6.9/4.9 mmHg) compared with the others
(1.9/1.6 mmHg).30 Lifestyle modifications, including
exercise and weight reduction, significantly improved
large and small vascular remodeling.22 These are the
reasons why exercise is considered to be an efficient
additional therapy for arterial hypertension.31
Impact of left ventricle on exercise capacity in
arterial hypertension
Studies have shown that the peak oxygen consumption
correlates with the volumes of the left ventricular
mass,8,19,32–34 systolic function,33,35 and diastolic dys-
function.3,4,20,33,36 The cornerstone of the relationship
between the left ventricle and functional capacity is
myocardial perfusion reserve, which is significantly
reduced in arterial hypertension patients.29 On the other
hand, some authors have claimed that myocardial oxygen
consumption is even increased in arterial hypertension
patients without left ventricular hypertrophy, but normal
in arterial hypertension patients with hypertrophy.37
This normalization of oxygen consumption through
hypertrophy happens at the expense of efficiency, which
is reduced in arterial hypertension patients with left
ventricular hypertrophy.37
The second reason that could explain impaired functional
capacity in arterial hypertension patients is certainly
increased peripheral resistance, which initiates a cascade:
it increases SBP, prolongs myocardial relaxation,
increases left ventricular stiffness and filling pressure,
induces left ventricular diastolic dysfunction, increases
left ventricular volumes, causes left ventricular hypertro-
phy, and finally decreases cardiac output. Interestingly,
Pierson et al.32 showed that different left ventricular
geometry patterns have a different influence on func-
tional capacity. Thus, untreated arterial hypertensive
patients with concentric left ventricular hypertrophy
had significantly lower peak oxygen consumption than
arterial hypertensive participants with concentric remo-
deling or normal left ventricular geometry.32
Biohumural systems such as catecholamines, renin–
angiotensin–aldosterone system, and brain natriuretic
peptide, are also responsible for impaired functional
capacity in arterial hypertensive patients. Grassi et al.38
revealed that the sympathetic activity was significantly
greater in arterial hypertensive patients who had left
ventricular diastolic dysfunction as opposed to those
without it, whereas previous researchers found that angio-
tensin II, aldosterone, catecholamines, and endothelin
could induce fibroblast-mediated collagen synthesis,
 Arterial hypertension and functional capacity Tadic and Ivanovic 449
which further promotes left ventricular hypertrophy.39
Recent studies showed that myocardial fibrosis could also
be the result of insufficient collagen degradation by
interstitial collagenase, especially, the metalloproteinase
1, whose activity is downregulated by angiotensin II,
aldosterone, and catecholamines.40,41 Additionally, Lim
et al.42 found that the brain natriuretic peptide, which is
released in response to activation of ventricular mechan-
oreceptors sensitive to pressure and stretch, was signifi-
cantly and inversely associated with peak oxygen uptake
in arterial hypertensive patients regardless of left
ventricular hypertrophy. Other researchers revealed a sig-
nificant correlation between left ventricular mass index
and the brain natriuretic peptide in arterial hypertensive
patients.43,44 These results show that the brain natriuretic
peptide could be one of the homeostatic regulators of
exercise capacity in arterial hypertensive patients.
Impact of left atrium on exercise capacity in
arterial hypertension
Investigations demonstrated that left atrial diameter and
function correlates significantly with exercise capacity in
patients with recent myocardial infarction, hypertension,
dilated and hypertrophic cardiomyopathy, and chronic
congestive heart failure.45–49 Increased left ventricular
filling pressure, often present in arterial hypertensive
patient, contributes to left atrial dysfunction and dilata-
tion, which further deteriorates left ventricular diastolic
filling and decreases cardiac output during exercise.46
Considering the previous findings that a mitral filling
pattern significantly correlates with exercise capacity in
arterial hypertensive patients,3,4,20,33,36 it is reasonable to
hypothesize that exercise capacity in arterial hyper-
tension is affected long before left atrial dysfunction
becomes apparent.
Pulmonary circulation and exercise in arterial
hypertension
The pulmonary circulation is characterized by low pres-
sure and high flow.50 Considering the fact that cardiac
output during exercise is six times greater than that in
resting condition, and that oxygen uptake is up to 20
times beyond resting values, it is clear why pulmonary
circulation is under significant stress while trying to
maintain the normal function of the right ventricle and
trying to avoid pulmonary edema. High blood flow during
exercise could be associated with high pulmonary blood
pressure (40–50 mmHg), as well as high capillary pres-
sure (20–25 mmHg). Adaptation of pulmonary circulation
in these circumstances is achieved through the distension
of the capillaries.50
The pulmonary circulation and right ventricular hemo-
dynamic in arterial hypertension have not been suffi-
ciently investigated, and the available results are
conflicting. Some authors reported that arterial hyperten-
sion was associated with increased pulmonary arterial
Copyright © Italian Federation of Cardiology. Unauthorized reproduction of this article is prohibited.
pressure and pulmonary arteriolar resistance, which
was not a consequence of impaired left ventricular func-
tion.51,52 Olivari et al.51 performed hemodynamic evalu-
ation of 33 hypertensive patients with blood pressure
more than 180/100 mmHg and 14 normotensive controls,
and found that pulmonary systolic, diastolic, and pulmon-
ary wedge pressure were significantly increased in the
hypertensive patients. However, other authors who per-
formed noninvasive measurements of pulmonary blood
pressure did not find any difference between the arterial
hypertension and the controls.53,54
Guazzi et al.55 reported that increased pulmonary arter-
iolar resistance was not associated with pulmonary blood
flow and volume, left ventricular filling pressure or func-
tion. The authors also claimed that systemic vascular
resistance significantly correlated with pulmonary resist-
ance; and that a calcium-channel blockade reduced
systemic and pulmonary arterial resistance, which again
emphasized the importance of Ca2þ for vasoconstriction
in both circulations. Furthermore, the same authors
found that catecholamines induced vasoconstriction in
pulmonary circulation as a consequence of vascular over-
reactivity.56 Namely, pulmonary arteriolar resistance in
the normotensive group was reduced by 13% and
increased by 7% of baseline, respectively. On the other
hand, in the hypertensive group, pulmonary resistance
increased by 31%.56 The opposite changes in pulmonary
resistance between normotensive and hypertensive
patients induced by epinephrine advocates that pulmon-
ary circulation becomes hypersensitive in a condition
of arterial hypertension.56,57 These results could be
explained by abnormalities in the number of adrenergic
receptors in pulmonary circulation, or their quality.58 The
other explanation could lie in the interconnections
between Naþ, Ca2þ, and natriuretic peptides, biohumoral
systems involved in the smooth muscle excitation and
contraction.55,59
Additional factors that contribute to impaired pulmonary
resistance are certainly oxidative stress products, which
cause endothelial damage and induce vasoconstriction, as
well as vasoconstrictors endothelin-1 and angiotensin II,
and vasodilators such as prostacyclin and nitric oxide,
which are normally released by pulmonary endothelium.
All these humoral markers could contribute to reduced
functional capacity in pulmonary circulation in arterial
hypertension; however, future studies will reveal the
exact mechanisms.
Impact of right ventricle on exercise capacity
in arterial hypertension
The right ventricle has been considered as a dispensable
heart chamber for overall cardiac function for a very long
time. After the Multi-Ethnic Study of Atherosclerosis
(MESA) study and findings that undoubtedly confirmed
the importance of right ventricular remodeling as an
important predictor of heart failure and mortality in a
 450 Journal of Cardiovascular Medicine 2014, Vol 15 No 6
population free of cardiovascular risk factors,60,61 the right
ventricle was brought into focus in the domain of cardio-
vascular investigations.
In 1980, Ferlinz62 reported that arterial hypertensive
patients had increased right-sided pressures and mark-
edly decreased right ventricular ejection fraction in
comparison with the controls, whereas left ventricular
function and cardiac index were similar between the
observed groups. Considering the fact that the author
included patients with severe arterial hypertension and
developed target organ damage, especially left ventricu-
lar hypertrophy, these results could be the consequence
of backward transmission of increased diastolic ventricu-
lar pressure in the noncompliant and stiffened left
ventricle, and not isolated increased pulmonary resist-
ance. In contrast, other authors did not find depression of
right ventricular systolic function in arterial hypertensive
patients.63–65 However, the introduction of new tech-
niques such as tissue Doppler and speckle tracking
imaging, which could recognize minimal changes in right
ventricular systolic and diastolic function, as well as
ventricular mechanics, has significantly changed our per-
ception of right ventricular damage in the early stage of
hypertension, even in prehypertension.54,66 Previous
studies that investigated patients with heart failure,67,68
the general population,68,69 or athletes70,71 showed that
different parameters of right ventricular systolic function
are associated with peak oxygen uptake. Thus, it is
reasonable to assume that a similar relationship exists
also among arterial hypertensive patients, which could
partly explain the decreased functional capacity in these
patients.
Right ventricular diastolic function in arterial hypertension
was reported more than two decades ago. Cuspidi et al.72
reported right ventricular diastolic dysfunction only in
arterial hypertensive patients with left ventricular hyper-
trophy. After this research, many other investigations
confirmed these results in hypertensive patients with
or without left ventricular hypertrophy.53,54,63,65,73–75
Considering the fact that some studies demonstrated a
relationship between right ventricular diastolic function
and peak oxygen uptake,71 impaired right ventricular
diastolic function could also contribute to decreased func-
tional capacity in arterial hypertensive patients.
The right ventricular hypertrophy in arterial hyper-
tensive patients probably represents the cornerstone of
reduced right ventricular systolic and impaired diastolic
function. Gottdiener et al.76 were the first who reported
right ventricular hypertrophy in arterial hypertensive
patients. This was confirmed by many other authors
who subsequently studied that topic.54,64,72,75–80 The
mechanisms that lead to right ventricular hypertrophy
are as follows: biohumoral mechanisms of myocardial
interstitial fibrosis induced by catecholamines, renin–
angiotensin–aldosterone system, growth factors (insulin),
Copyright © Italian Federation of Cardiology. Unauthorized reproduction of this article is prohibited.
or inactivated inhibitors of metalloproteinase 1; hemo-
dynamic mechanisms that involve increased pulmonary
vascular resistance and increased right-sided press-
ures;80,81 and interventricular dependence, which pro-
bably has the most important role in right ventricular
remodeling in arterial hypertensive patients.80,82 There
is no evidence that right ventricular hypertrophy directly
impacts exercise capacity in arterial hypertensive patients.
An additional reason for reduced exercise capacity in
arterial hypertensive patients could lie in the physiology
of right coronary circulation. Namely, resting right cor-
onary blood flow is lower than left coronary blood flow,
because of the lesser work of the right ventricle. Also the
left ventricle uses 75% of the delivered oxygen, whereas
the right ventricle extracts only 50%.83 Endogenous nitric
oxide increases the right coronary blood flow during
exercise and provides adequate balance between oxygen
demand and supply.84 However, the autoregulation of
right coronary circulation is poor, and much worse than
left coronary circulation. During exercise, the left ven-
tricle achieves the six-fold increase in oxygen demands
primarily by increasing coronary blood flow (about five-
fold), whereas oxygen extraction increases only dis-
creetly.84,85 On the contrary, in the right ventricle, oxy-
gen extraction significantly increases during exercise,
suggesting essential differences in blood flow regulation
between these two cardiac chambers.84,85 Furthermore,
right coronary vasodilation during exercise occurs signifi-
cantly later than left coronary vasodilatation, which dis-
ables adequate increase in coronary blood flow and results
in moderate hypoperfusion of the right ventricle and
decreased right ventricular contractility.83,85 These phys-
iological differences between right and left coronary cir-
culation during exercise in arterial hypertensive patients
with already impaired endothelium-dependent vasodila-
tation, possibly could explain the decreased right ventri-
cular function and exercise capacity in this population.
Clinical studies about exercise capacity in
arterial hypertension
In the last decade, several large studies have investigated
the relationship between exercise capacity and increased
blood pressure, but there is a lack of homogeneity in
methodology, which is used for estimating exercise
capacity (Tables 1 and 2). The vast majority of studies
with a large number of arterial hypertensive participants
used standard exercise testing, which could provide only
approximate results of exercise capacity,1,6–9,33,35,86–90
whereas cardiopulmonary exercise testing was used in
a significantly lower number of investigations.2–5,29,32,36
Because of the inconsistency in methodology, it is far
more complicated to analyze the relationship between
exercise capacity and arterial hypertension, and make a
final conclusion.
Kokkinos et al.7,8,86 were mostly involved in this field by
including and following thousands of individuals, of both
 Arterial hypertension and functional capacity Tadic and Ivanovic 451
Table 1 Studies that investigated the relationship between functional capacity and mortality in patients with high-normal or high blood
pressure
Reference Sample size and participants included in the study
1
Kokkinos et al. 4631 hypertensive male veterans
Kokkinos et al.88 6749 Afro-Americans and 8911 white hypertensive
male veterans
Kokkinos et al.90 5314 male veterans, aged 65–92 years
Kokkinos et al.86 1727 male veterans with high-normal blood pressure
Kokkinos et al.7 4478 male veteran with high-normal blood pressure
Kokkinos et al.89 407 men and 243 women with high-normal blood
pressure
Faselis et al.9 2303 male veterans with high-normal blood pressure
Faselis et al.6 4183 hypertensive male veterans
METs, metabolic equivalents.
sexes, with prehypertension and hypertension, and thus
they found a strong, inverse, graded, and independent
association between exercise capacity and all-cause
mortality in individuals with high-normal blood pressure
and high blood pressure, regardless of race and age1,6,88,90
(Table 1). The authors also revealed that moderate
physical activity promotes lower 24-h blood pressure in
prehypertensive men and women,89 and also decreases
the possibility of progression from prehypertension to
hypertension.9 The same investigators identified SBP
more than 150 mmHg at the exercise levels of 5 metabolic
equivalents (METs) as the threshold for left ventricular
hypertrophy in prehypertensive individuals.8 They
estimated that the risk of left ventricular hypertrophy
was a four-fold increase for each 10 mmHg increment in
SBP beyond this threshold (odds ratio: 1.15; 95% confi-
dence interval: 1.12–1.18).8 These findings showed that
improvement in exercise capacity reached by moderate
physical activity could significantly improve hemody-
namics and cardiac performance in prehypertensive
individuals, and decrease the left ventricle load, which
finally results in the reduction of left ventricular mass.
The same study group revealed that increased exercise
capacity was related to decreased mortality risk in hyper-
tensive men regardless of BMI.6 Interestingly, the risk of
Copyright © Italian Federation of Cardiology. Unauthorized reproduction of this article is prohibited.
Type of testing Main findings
Treadmill test Exercise capacity was the strongest predictor
of all-cause mortality in hypertensive men.
The relationship was inverse and graded.
Treadmill test Exercise capacity was a strong predictor of
all-cause mortality in Afro-Americans and
whites. Authors found a similar impact on
mortality outcomes for both Afro-Americans
and whites.
Treadmill test Exercise capacity is an independent predictor of
all-cause mortality in older men. Most survival
benefits were found in individuals with
an exercise capacity >5 METs.
Treadmill test Authors reported a strong, inverse, graded, and
independent association between exercise
capacity and all-cause mortality in individuals
with high-normal blood pressure.
Treadmill test A strong relationship between exercise capacity
and all-cause mortality was detected in
prehypertensive patients. The protective
effects of increased fitness were more
pronounced in younger individuals.
Treadmill test Moderate physical activity promotes lower
blood pressure during a 24-h period in
prehypertensive men and women.
Treadmill test Researchers found an inverse, S-shaped
association was shown between exercise
capacity and the rate of progression
from prehypertension to hypertension in
middle-aged and older male veterans.
Treadmill test Increased exercise capacity is related with
lower mortality risk in hypertensive men
independently of BMI. The risk for overweight
and obese, but fit individuals was significantly
lower when compared with normal weight, but
unfit patients.
overweight and obese individuals with higher exercise
capacity was significantly lower than that in normal
weight individuals with decreased exercise capacity.
These findings suggest that in arterial hypertension, it
might be better to be fit irrespective of body weight, than
unfit and normal weight.6 This controversial theory was
also confirmed by other authors who did not find the
relationship between conventional parameters of body
weight (BMI) and peak oxygen consumption.31 However,
these authors concluded that diminished functional
capacity in arterial hypertensive patients with left ven-
tricular hypertrophy was associated with the impairment
in myocardial perfusion reserve and left ventricular
diastolic function.
The investigations that studied the relationship between
different left ventricular parameters (hypertrophy, systo-
lic and diastolic function) and functional capacity are
presented in Table 2. Kim et al.35 found that left ven-
tricular contractile reserve and relaxation are significant
cardiac parameters that determine exercise capacity in
arterial hypertensive individuals. Pierson et al.32 included
obese untreated hypertensive patients and revealed
that the left ventricular geometric pattern, especially
concentric hypertrophy, was related with decreased
 452 Journal of Cardiovascular Medicine 2014, Vol 15 No 6
Table 2 Studies that investigated the relationship between left ventricular parameters and functional capacity in patients with high-normal or
high blood pressure
Reference Sample size and participants included in the study
8
Kokkinos et al. 790 participants with high-normal blood pressure
Zheng et al.2 50 hypertensive patients who received a 6-month
exercise program in addition to pharmacological
treatment
Dekleva et al.3 60 hypertensive patients
Dekleva et al.4 42 hypertensive patients and with mild left ventricular
diastolic dysfunction and 30 controls
Danciu et al.5 25 hypertensive patients
35
Kim et al. 48 hypertensive patients with normal left ventricular
ejection fraction
Pierson et al.32 89 overweight women and men with untreated mild
hypertension
Ogunyemi et al.33 50 hypertensive patients and 50 controls
Sekiguchi et al.36 26 men with hypertension, cardiomyopathy and
controls
Gerdts et al.91 60 patients with hypertension and
electrocardiographic left ventricular hypertrophy
Janiszewski et al.92 53 patients with metabolic syndrome (100%
participants had hypertension) and 33 controls
Kusunose et al.93 486 patients with preserved left ventricular
ejection fraction
a, late diastolic mitral flow (pulse Doppler); á, peak late diastolic relaxation velocity of the septal/lateral segment of mitral annulus (tissue Doppler); CPET, cardiopulmonary
exercise testing; E, early diastolic mitral flow (pulse Doppler); é, peak early diastolic relaxation velocity of the septal/lateral segment of mitral annulus (tissue Doppler); IVRT,
isovolumic relaxation time; s, systolic velocity of the septal/lateral segment of mitral annulus; VO2max, peak oxygen uptake.
exercise capacity in these individuals. Nevertheless, the
authors did not take into consideration BMI, which was
significantly higher in patients with left ventricular
concentric hypertrophy. On the other hand, Ogunyemi
et al.33 detected significantly reduced exercise capacity in
arterial hypertensive patients with and without left
ventricular hypertrophy in comparison with normotensive
individuals. Lim et al.42 also showed that exercise capacity
was decreased in arterial hypertensive individuals inde-
pendently of left ventricular mass, but they also revealed
that the brain natriuretic peptide was strongly and inver-
sely associated with peak oxygen uptake (Table 3).
Guirado et al.87 demonstrated that continuous training of
the elderly (mean age was 68  8) with arterial hyper-
tension increased functional capacity without changing
left ventricular diastolic function. This small study that
included only 15 patients challenged investigations that
demonstrated that left ventricular diastolic dysfunction
is one of the major predictors of lower exercise
capacity.3,4,36,91 There is also no consensus about left
Copyright © Italian Federation of Cardiology. Unauthorized reproduction of this article is prohibited.
Type of testing Main findings
Treadmill test Moderate improvements in exercise capacity
achieved by physical activity can improve
hemodynamics and decreased left ventricular
mass.
CPET Continuous exercise improved left ventricular
diastolic function. The change of transmitral E/A
and é/á ratio were predictors of VO2max.
CPET Hypertensive patients had decreased VO2max in
comparison with controls. Left ventricular
relaxation and oxidative stress were associated
with VO2max.
CPET Asymptomatic hypertensive patients with mild left
ventricular diastolic dysfunction had reduced
VO2max. Transmitral E/A ratio correlated with
VO2max.
CPET Resting mitral e’ and peak stress e’/a’ correlated
with VO2max in hypertensive patients.
Treadmill test Mitral ś, e’, a’ and percentage increase of s’ velocity
after exercise correlated with exercise time.
CPET The left ventricular geometric pattern, especially
concentric hypertrophy, was associated with
exercise capacity in untreated hypertensive
patients.
Treadmill test The study showed significant impairment of exercise
capacity in hypertensive patients with or without
left ventricular hypertrophy compared with
normotensive controls. Left ventricular EF
correlated with VO2max.
CPET Authors showed that resting éand change of é
correlated with VO2max in whole study group.
CPET Resting transmitral E/A ratio and greater reduction in
IVRT during exercise correlated with VO2max, but
blunted reduction in IVRT was a stronger predictor
of lower VO2max.
CPET VO2max was significantly decreased in patients with
metabolic syndrome. Mitral E/A ratio was
associated with VO2max.
Exercise echocardiography Mitral E/ératio, left atrial strain, and BMI correlated
with VO2max.
ventricular diastolic parameters that are responsible for
impaired functional capacity. Some authors revealed
impaired left ventricular relaxation,3,4,35 others detected
early diastolic transmitral velocity obtained by tissue
Doppler,5,36 whereas some investigators found isovolu-
mic relaxation time and transmitral early to atrial filling
velocity as main predictors of lower oxygen uptake,2,91,92
or the ratio between early diastolic transmitral velocity
obtained by pulsed and tissue Doppler (E/é),93 or even
the ratio between early and late transmitral velocity
assessed by tissue Doppler2,5 as predictors of peak
oxygen uptake. Additionally, Kusunose et al.93 revealed
a negative influence of reduced left atrial function
on impaired exercise capacity in individuals with pre-
served left ventricular ejection fraction, which empha-
sized the role of ventriculoatrial coupling to left
ventricular dysfunction and possibly decreased func-
tional capacity.
There are only few clinical studies that concerned the
relationship between the right ventricle and functional
 Arterial hypertension and functional capacity Tadic and Ivanovic 453
Table 3 The possible mechanisms involved in the reduction of exercise capacity in patients with arterial hypertension
Systemic circulation Left ventricle Left atrium
Increased peripheral vascular Hypertrophy Dilatation
resistance
Endothelial dysfunction Systolic dysfunction Dysfunction
Increased circulating levels of Diastolic dysfunction Increased left
catecholamines ventricular filling
pressure
Increased circulating levels of
angiotensin II
Arteriolar remodeling
(changes in wall/
lumen ratio)
Capillary rarefaction
capacity in patients without pulmonary hypertension or
congenital heart diseases. In these investigations, mainly
systolic right ventricular parameters (ejection fraction,
tricuspid annular plane systolic excursion, myocardial
performance index, ventricular strain rate, systolic
velocity across lateral segment of tricuspid annulus
obtained by tissue Doppler) are found to be predictors
of depressed functional capacity.68,71 However, these
findings are not sufficient, and further studies in this
field are necessary to provide answers to many questions
about the influence of arterial hypertension on functional
capacity.
Antihypertensive treatment and functional
capacity
The data about the influence of different antihyperten-
sive drugs on peak oxygen uptake in patients with arterial
hypertension are rather limited. Considering the fact that
renin–angiotensin system, catecholamines, and Ca2þ
have an important role in the relationship between arter-
ial hypertension and functional capacity, it would be
reasonable to assume that renin–angiotensin system
inhibitors, b-blockers, and calcium channel blockers
are the drugs most commonly chosen. This hypothesis
is confirmed by Faselis et al.6 who found that the usage
of calcium channel blockers, angiotensin-converting
enzyme inhibitors, and angiotensin receptor blockers,
as well as diuretics and statins is gradually higher from
the lowest to the highest fit category of hypertensive
patients. In this study, however, blood pressure progress-
ively decreased in the same way that could also explain
better exercise capacity.
Carreira et al.94 compared the effect of two angiotensin-
converting enzyme inhibitors in arterial hypertensive
patients, and found that there was no difference in
functional capacity between these two drug regimens,
although trandolapril was slightly more effective than
captopril in blood pressure control during exercise in
arterial hypertensive patients. Other authors compared
treatment with nebivolol to placebo during a 6-month
Copyright © Italian Federation of Cardiology. Unauthorized reproduction of this article is prohibited.
Pulmonary circulation Right ventricle
Increased pulmonary vascular Hypertrophy
resistance
Increased pulmonary systolic, Systolic dysfunction
diastolic, and wedge pressure
Vascular overreactivity Diastolic dysfunction
Endothelial dysfunction Interventricular dependence
Increased circulating levels of Poor autoregulation of
catecholamines right coronary circulation
Increased circulating levels
angiotensin II
period and failed to demonstrate the improvement of
exercise capacity in patients with diastolic dysfunction.95
They tried to explain these results with a negative
chronotropic effect of nebivolol. To our knowledge,
the effects of calcium channel blockers on functional
capacity in arterial hypertension have not been studied
yet.
Conclusion
The impact of arterial hypertension on functional
capacity has not been sufficiently examined so far.
Studies have shown that peak oxygen uptake is signifi-
cantly lower in hypertensive patients, but the mechan-
isms of this influence are still unknown. On the other
hand, continuous exercise causes significant improve-
ment of large and small vessel remodeling, which further
considerably decreases blood pressure in arterial hyper-
tensive patients, and could be used as an important
nonpharmacological therapy in these patients. In the
future, we need prospective studies that would include
arterial hypertensive individuals, and use regular cardi-
opulmonary testing instead of ordinary exercise testing in
order to obtain exact values of peak oxygen uptake, and
detailed echocardiographic examination (two-dimen-
sional and three-dimensional), an effective noninvasive
method that provides important hemodynamic
parameters instead of invasive cardiac catheterization,
which is inappropriate and ethically unacceptable in
asymptomatic hypertensive patients.
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