Send Orders for Reprints to reprints@benthamscience.ae
Current Hypertension Reviews, 2017, 13, 000-000 1
REVIEW ARTICLE
1573-4021/17 $58.00+.00 © 2017 Bentham Science Publishers
Early Vascular Ageing (EVA): Definitions and Clinical Applicability
Pedro G. Cunha
a,b,c,*
, Pierre Boutouyrie
d
, Peter M. Nilsson
e
and Stéphane Laurent
d
a
Center for the Research and Treatment of Arterial Hypertension and Cardiovascular Risk, Internal Medicine
Department, Hospital Senhora da Oliveira, Guimarães / Minho University. Portugal;
b
Life and Health Science Research
Institute (ICVS) and School of Medicine, University of Minho;
c
ICVS/3B’s - PT Government Associate Laboratory,
Braga/Guimarães, Portugal;
d
Department of Pharmacology and INSERM U970, Assistance Publique Hôpitaux de
Paris, Université Paris Descartes, Paris, France;
e
Department of Clinical Sciences, Lund University, Skane University
Hospital, Malmö, Sweden
Abstract: Arterial stiffness has been accumulating evidence as an intermediate cardiovascular
endpoint. It has been established as an independent risk marker for cardiovascular disease, and
reflects the dissociation between chronologic and biologic age of large arteries-attributing earlier
the risk that a normal vascular ageing process had installed to occur several years later. The
concept of Early Vascular Ageing (EVA) is developed to establish primordial prevention, identify-
ing individuals whose ageing path has been accelerated either by inherent features, interaction
with the environment or arterial exposure to several types of insults that evolve to medial layer
morphological changes. Understanding the pathophysiology of vascular ageing, its consequences
and therapeutic opportunities is therefore an advantage that could be translated in time of prevention
and survival free of cardiovascular disease. As the EVA construct is advancing, new features appear
as interesting to better translate it into clinical practice.
Keywords: Arterial stiffness, cardiovascular risk, early vascular ageing, epidemiology, large artery, pulse wave velocity.
1. INTRODUCTION
Early Vascular Ageing (EVA) is an evolving concept [1-
3] that has been growing around the accumulating evidence
surrounding arterial stiffness as an intermediate end-point
and an independent predictor of cardiovascular disease and
cardiovascular as well as total mortality [4]. This construct
(EVA) is elaborating on the core idea that it is possible to
identify at an early stage subjects with signs of an unsuccess-
ful vascular ageing. This unsuccessful ageing (accelerated
ageing), if undetected otherwise, would lead those subjects
into earlier development of cardiovascular disease (CVD)
and irrecoverable residual risk in spite of therapeutic primary
or secondary prevention measures undertaken, later in time.
The purpose of this overview is to: 1) briefly review key
pathophysiologic concepts concerning vascular ageing and
associated risk of development of cardiovascular disease, as
*Address correspondence to Pedro Guimarães Cunha, MD, PhD, at the
Center for the Research and Treatment of Arterial Hypertension and Car-
diovascular Risk. Serviço de Medicina Interna do Hospital de Guimarães,
Centro Hospitalar do Alto Ave; Life and Health Science Research Institute
(ICVS), Minho University. Rua dos Cutileiros, Creixomil, 4810, Guimarães,
Portugal; Tel: +351-253540330 (extension 41952);
E-mail: pedrocunha@ecsaude.uminho.pt
well as the established value of pulse wave velocity (PWV),
a direct measurement of arterial stiffness, as a valuable bio-
marker of cardiovascular risk; 2) discuss existing definitions
of EVA and its premises; 3) propose the clinical applicability
of the concept to specific target groups; 4) review existing
records of the prevalence of EVA in order to gauge future
directions concerning therapeutic intervention and research;
and to finally 5) debate therapeutic implications for subjects
with EVA.
2. CHANGES IN THE ARTERIAL TREE IN HYPER-
TENSION CONDITIONING PROGRESSION TO
ARTERIAL STIFFNESS AND ITS COMPLICATIONS
The process of arterial ageing begins during the human
intra-uterine life. During this period, not only the uterine
environment, but also the development of the fetus and its
cardiovascular system are under the influence of maternal
hormonal, socio-economical and health characteristics [5, 6].
The extent of the success of ageing could intuitively be
measured as the accumulated number of chronologic years
that a subject survives without disease or disease induced
limitations. Still, one must be aware that the process of nor-
mal vascular ageing can be accelerated by a combination of
the exposure to different factors that insult the arterial wall
and the time of exposure to these insulting factors [7]. Thus,
A R T I C L E H I S T O R Y
Received: February 20, 2017
Revised: March 30, 2017
Accepted: April 03, 2017
DOI:
10.2174/1573402113666170413094319
2 Current Hypertension Reviews, 2017, Vol. 13, No. 0 Cunha et al.
biologically speaking, the arterial wall can in fact appear
older than its chronological age, reflecting adaptive changes
to repeated insults and exposing earlier the subjects to the
risk of development of cardiovascular disease that they
would be subjected only years later [8].
With advancing age, and especially after 30 years of life,
large arteries progressively lose their elastic properties [9,
10]. The process of arterial stiffening is mainly due to
changes in the medial layer of the arterial wall, altogether
referred to as arteriosclerosis. The normal media is com-
posed of elastin, collagen, vascular smooth muscle cells
(VSMC) and a mucopolysaccharide matrix [11]. These
components are distributed in different proportions as we
move from central (elastic) to peripheral (muscular) arteries;
with age, large arteries are characterized by: 1) a reduction of
the elastin component and changes in the interaction of
elastin lamellae; 2) an increase in collagen and mucopoly-
saccharide matrix; 3) a reduction of VSMC and an increase
in VSMC stiffness; and 4) a decreased activity in proteolytic
enzymes, reducing the vessel’s remodeling process as in-
tended [11, 12].
Changes in the medial layer occur normally with ageing,
and are the result of an equilibrium established between
3 key mechanisms: 1) cyclic stress (reflecting the cardiac
cycle and subsequent repeated changes in the arterial struc-
ture promoted by the incident and the retrograde flow and
pressure waves); 2) the arterial wall’s repair mechanisms that
correct the injuries promoted by this mechanical/elastic
stress (9), but also, the insults to the arterial wall provoked
by different aggressors (excessive blood pressure, dyslipi-
demia, diabetes and its advanced glycation end (AGE) prod-
ucts, smoking, inflammation, oxidative-stress, endothelial
dysfunction and so many others) [13-18]; at the extreme of
the possibilities leading to stiffer arteries, are the acquired or
inherited lack of effective repairing mechanisms of the arte-
rial wall or hereditary conditions promoting vascular ageing
[6, 19]. All these conditions can lead to an acceleration of
medial changes naturally observed with age, and hence, in-
creased cardiovascular risk.
As the central arteries become stiffer, they maintain their
conduit function, but progressively lose their buffering prop-
erty, transmitting high energy pulsatility into the vascular
bed of organs highly vascularized but prepared only to deal
with a continuous flow of blood, like the brain and the kid-
ney – promoting target organ damage through pulsatility
energy transmission, especially when the proximal/distal
large arteries mismatch is lost, in response to the premature
ageing, thus stiffening, of large arteries [9, 11, 20-23].
Finally, and concurring to the pathophysiology of cardio-
vascular disease promoted by changes in the arterial wall,
stiffer arteries transmit not only the forward, but also the
reflected pressure waves with higher velocity, and eventually
with greater magnitude [24]. This earlier reflection will su-
perimpose on the cardiac after-load and increase central and
peripheral blood pressures, increasing the pulsatile energy
transmitted to target organ damage and reducing coronary
perfusion (as the coronary flow should be assured by the
reflecting wave later in the diastole) [12, 24].
2.1. The Blood Pressure Paradox in its Relationship with
Arterial Stiffness
The main determinants of pulse wave velocity (PWV) are
age and blood pressure [25-27]. In a paradoxical sense, and
as demonstrated by preceding arguments, increasing arterial
stiffness will promote augmented pulse wave reflection and
concurrent blood pressure increase. Until recently, this
would appear a cyclic event, with higher blood pressure in-
creasing arterial stiffness, and the later promoting higher
levels of blood pressure. New evidence has surfaced in lon-
gitudinal studies, showing that not only is arterial stiffness a
predictor of future development of hypertension [28, 29],
but also that PWV and peripheral blood pressure have
divergent evolutions in time [27, 30] and according to
gender, obviating a partial independence of these players,
who must have other variables explaining their variance.
This is an argument in favor of directly measuring arterial
stiffness, instead of estimating it through blood pressure and
age algorithms.
On one hand, one can find a link between arterial
stiffness and other blood pressure characteristics that have an
impact in cardiovascular mortality: blood pressure variabil-
ity, heart rate variability and impaired baroreceptor function
(causing orthostatic hypotension) [31]; on the other hand,
several mechanisms have been associated to the accelerated
development of arterial stiffness and (indirectly) of increased
blood pressure: the metabolic syndrome, inflammation and
neurohormonal disorders, all inducing endothelial dysfunc-
tion [32].
3. Arterial Stiffness and its Evolution as an Independent
Predictor of Cardiovascular Risk
The degree of arterial stiffness provoked by arteriosclero-
sis generates a faster pressure wave through a more rigid
conduit. Thus, the degree of stiffness (or disease of the me-
dia, or arteriosclerosis) can be measured using pulse wave
velocity, considered as the gold standard measure [33]. PWV
has been accumulating evidence as an intermediate cardio-
vascular risk marker, after initial observations by Avolio et
al. in China [34, 35].
Its independent power to predict cardiovascular disease
was first determined in high-risk groups (chronic kidney
disease, hypertension, diabetes) [36-39] and finally in
the general population or in apparently healthy individuals
[40-42].
For each increase in PWV of 1m/s the risk of cardiovas-
cular events or all-cause mortality increases by 14 to 15%
[43]; or if one prefers, by each increase in 1 standard devia-
tion (SD) of PWV, the risk of cardiovascular events in-
creased by 30% [4] – this most recent meta-analysis had yet
another particular detail: it associated PWV with an in-
creased risk of stroke, especially in younger age classes.
In a recent consensus document endorsed by the Euro-
pean Society of Cardiology and the Artery Society [44], ca-
rotid-femoral PWV has been established as a biomarker that
is highly sensitive for identification of subjects with different
phenotypes and with clinical relevance for therapy guidance,
Early Vascular Ageing (EVA): Definitions and Clinical Applicability Current Hypertension Reviews, 2017, Vol. 13, No. 0 3
as well as bearing risk prediction improvement; nowadays it
fulfills 8 of the 9 criteria established by the two societies to
be considered a valuable biomarker (by use of an upgraded
classification from Hlatky and colleagues [45]), and it gathers
a “IIa” recommendation (with an “A” level of evidence) for
use in risk stratification [44] – one of the three new biomark-
ers that achieve this classification. It is important to remem-
ber that the 2013 ESH-ESC Guidelines for the management
of arterial hypertension, graded this recommendation as “IIa”
(PWV should be considered to detect arterial stiffening) with
a “B” level of evidence [46].
The definition of reference values for pulse wave veloc-
ity, according to age groups (in the “healthy population”)
and according to age and blood pressure class (in the
“reference population” – corresponding to subjects that
either smoke, have high-normal blood pressure or untreated
hypertension or dyslipidemia) [25], has established a
grid against which one can now compare the dimension of
arterial damage expected for a given age in predetermined
circumstances, identifying subjects that are off the grid as
evidencing an abnormal vascular ageing process.
4. THE CONCEPT AND PROPOSED DEFINITIONS
OF EARLY VASCULAR AGEING
The EVA concept is a tool for early identification of sub-
jects that could benefit the most from early primary preven-
tion measures. It embraces the knowledge of all the
physiopathology of arterial ageing described summarily in
previous sections of this overview, as well as all the singular
capability of risk prediction concerning CVD by PWV
measurements (as a proxy of arterial stiffness or arterioscle-
rosis) to answer the following questions: do the large arteries
of an individual exhibit signs of accelerated or unsuccessful
ageing? Does this abnormal rate of arterial ageing place this
individual at a risk level for cardiovascular event that would
imply early clinical intervention?
4.1. Current Methods Used to Identify EVA Subjects
The palpable definition of a subject exhibiting EVA is a
work in development. For the time being it has relied mainly
on three different methods: 1) to use the normal distribution
of PWV values in a population, and define as EVA subjects
those who place themselves 2 standard deviations above the
mean PWV value [47]; 2) to transform all PWV values of
the population into z-scores and classify as EVA those sub-
jects who present z-score above the 95
th
percentile [47]; or 3)
the last method is similar in concept to the previous two pre-
sented, but it uses as reference for normality those values
published in the European Reference Values Collaboration
[25]: EVA subjects are those who have a PWV value 2 SD
above the “normal” PWV expected for age (according to the
European Reference Values Collaboration) or whose z-score
is above the 97.5
th
percentile (using the age attributed “nor-
mal” PWV value as comparator) [48].
These are still probably incomplete and rough methods to
establish those who have EVA. Will subjects having PWV
within the 90
th
percentile of the distribution be free of con-
cern regarding their future cardiovascular health? Are there
any other biomarkers that can be added to these definitions
or that can complement them? For this matter, much data has
been published concerning carotid Intima Media Thickness
(cIMT), and it makes sense that we add a direct observation
of the arterial wall to also identify those whose medial di-
mension has enlarged. Several studies and meta-analysis
have supported this premise, evidencing that cIMT increases
cardiovascular risk prediction beyond established risk algo-
rithms, as well as it presents a modest risk reclassification
power [49-51]; in one other meta-analysis however, the
added value of measuring cIMT above the Framingham risk
score was minor and precluded its clinical use [52]. However,
the inclusion of this biomarker in the identification of EVA
subjects has already spurred interest in the scientific com-
munity [53], and the fact that recent European reference val-
ues of cIMT, obtained with high resolution echo-tracking,
have been published is obviously a facilitator of its transition
to clinical use [54]. Results from the CARDIA, the Amster-
dam Growth and Health Longitudinal and the Bogalusa stud-
ies are seriously encouraging in this domain as they evidence
a correlation of early exposure to cardiovascular risk factors
and concurrent changes in cIMT [55, 56], as well as devel-
opment of cognitive dysfunction [57].
Should EVA subjects be considered as such if one of the
characteristics (PWV or cIMT) present higher than expected
(above the 97.5
th
percentile) values for healthy individuals of
the same age group, using the European Reference Values
Collaboration as comparators? Or should they present both
characteristics simultaneously? These are questions to be
answered in the future.
5. WHO, HOW AND WHEN TO SCREEN? THE EVA-
HAS CONSTELLATION
5.1. Who
Even if the measurement devices of PWV are easy to use,
their availability is not yet disseminated in clinical practice.
The European Society of Hypertension / European Society of
Cardiology guidelines already include PWV as a part of tar-
get organ damage evaluation recommended for all hyperten-
sive subjects [46], which constitutes a clear opportunity to
evaluate EVA, whether target organ damage is absent (i.e., if
PWV < 10 m/sec), or not. Still, many other individuals with
cardiovascular risk factors, or chronic inflammatory diseases
should be screened for EVA [16]; as such, individuals with a
positive familial history of premature cardiovascular disease,
obstructive sleep apnea, chronic obstructive pulmonary dis-
ease, chronic inflammatory rheumatologic and immunologic
conditions [58, 59], diabetes mellitus, dyslipidemia (espe-
cially familial hereditary forms), smoking, or chronic kidney
disease, amongst others, should have their arterial stiffness
evaluated.
5.2. The EVA-HAS Constellation
Attention has also been devoted to hemodynamic signs
that appear as a consequence of arterial stiffness, and that
could be incorporated in what one could denominate as an
early vascular ageing – hemodynamic ageing syndrome
(EVA – HAS) [31]; postural hypotension, elevated blood
pressure variability [60], and isolated systolic hypertension
could, thus, be also signals that when detected could lead the
4 Current Hypertension Reviews, 2017, Vol. 13, No. 0 Cunha et al.
clinician to evaluate arterial stiffness and evidence of EVA.
It can be suggested that morphological changes in the arterial
wall constitute the fundament for EVA, but that the hemody-
namic changes that occur as a consequence of the morpho-
logical changes can be regarded as HAS.
5.3. When
Scheduling an arterial stiffness evaluation should be
prompt during the first evaluation of every hypertensive in-
dividual, or during the first evaluation of any of the indi-
viduals showing the above mentioned conditions or signs. A
special attention should still be addressed to subjects that,
during their first clinical evaluation, are classified by risk
algorithms as having moderate added risk, as these are the
ones most benefiting from reclassification into higher risk
classes and concurrent treatment intensification [61].
5.4. How
The conditions of correct measurement of PWV have
been extensively reviewed in several documents [33] and
recently in a consensus document [62]. Three sets of recom-
mendations are particularly noteworthy: 1) the pre-
measurement conditions to observe – fasting (including no
caffeinated beverages), no smoking, a 10 minute rest before
examination in a quiet room and in the supine position; 2)
the direct carotid – femoral distance should be measured in a
straight line, and the obtained PWV with this distance should
be multiplied by 0.8 to obtain the final PWV value; 3) at
least two measurements that do not differ more than 0.5 m/s
should be taken for each individual. Conditions precluding
the inability to use the technique should be taken into con-
sideration [62]. Another aspect to consider pertains to the
standardization of PWV obtained with different devices and
using different peripheral blood pressure measurements to
calibrate the pulse wave form (systolic blood pressure + dia-
stolic blood pressure vs. mean blood pressure). This issue
has been fully addressed elsewhere [25].
6. PREVALENCE OF EARLY VASCULAR AGEING
IN THE GENERAL POPULATION
Till recently, no estimate of the prevalence of EVA had
been published. In a cohort study, including a randomly se-
lected representative sample of two adjacent cities in the
north of Portugal (Guimarães and Vizela), a thorough pheno-
typic evaluation of subjects concerning cardiovascular risk
was performed. In a two-visit screening study, collection of
data regarding clinical history, extensive biochemical
workup of blood and urine, measurement of central hemody-
namic parameters and cognitive function was performed in
three thousand and thirty eight subjects. A full description
of the followed methodology has been reported elsewhere
[63].
Of the 2542 subjects who completed the observation
plan, we registered a mean age of 45.5 years and a 55%
prevalence of females. After transforming PWV values into
z-scores we compared the PWV values of our subjects with
what would be the expected PWV value for someone his/her
age in the normal (“healthy”) population of the European
Reference Values Collaboration. Using this method we ob-
served that 12.5% of the population showed signs of EVA.
The prevalence of EVA was mainly occurring in the age
classes below 50 years, and the most striking observation
was that 26.1% of individuals under 30 years of age pre-
sented its features, according to this definition, with a sig-
nificantly increased prevalence in young males [48]. As we
previously discussed, a cut-off value is always arbitrary and
the fact is that cardiovascular risk has an increasing continu-
ous relationship with the increase of PWV values. Thus, also
worrisome was the finding, in this same study, that approxi-
mately 35% of individuals aged less than 40 years present a
PWV value that is above the 90
th
percentile of PWV ex-
pected for his/her age according to the European Reference
Values Collaboration [25]. These data are of importance
when we consider that the two studied adjacent cities are
located in the region of Western Europe with the highest
stroke rate incidence [64, 65].
Shortcomings of this observational study should be ac-
knowledged, mainly due to the fact that only one PWV
measurement was performed in each subject, and that a his-
torical bias can have been introduced in the interpretation of
results, as some of the studied cohorts that are included in
the European Reference Values Collaboration have been
examined 20 years ago [48].
Even if, so far, no other study has determined the preva-
lence of EVA, it is noteworthy to analyze two different as-
pects that could offer partial explanation for these results: a)
following a political revolution approximately 40 years ago,
Portugal has experienced a significant change in both living /
nutritional habits and social behavior; the truth to the matter
is that nowadays, statistics show high levels of childhood
and teenager overweight and obesity as well as physical in-
activity and elevated blood pressure levels [66, 67] – for
subjects below 40 years of age, for instance, blood pressure
levels are significantly above the minimum theoretical expo-
sure risk values for the development of cardiovascular dis-
ease [68]; b) in several studies looking into another vascular
biomarker (cIMT), an inverse relationship has been found
between the maintenance of ideal cardiovascular health be-
haviors in childhood and measured values of cIMT [69-71].
On a totally different (but related) topic, one must con-
sider the use of EVA in different fields of clinical cardiovas-
cular disease prevention. For example, in a case– control
study involving 223 catheter laboratory workers, a signifi-
cant association was found between high risk exposure to
radiation, increased cIMT and shorter telomere length [72].
Thus, radiation exposure is another factor that could to be
involved in accelerated biological ageing. This opens new
population targets to evaluate for EVA, i.e. occupationally,
circumstantially or warfare exposed to radiation.
7. THERAPEUTIC IMPLICATIONS: DE-STIFFENING
THE ARTERIAL WALL
The role of arterial stiffness as a surrogate marker for
cardiovascular disease, with significant implications for the
risk of its development has been well established and dem-
onstrated both herein and in the extensive research work
presented by different research teams around the world. The
issue of treatment of arterial stiffness as a therapeutic target
Early Vascular Ageing (EVA): Definitions and Clinical Applicability Current Hypertension Reviews, 2017, Vol. 13, No. 0 5
is still subject to debate, with clear ramifications to the ra-
tional of clinical approach of the patient with EVA.
The pharmacologic treatment options for subjects with
EVA, according to the existing evidence, are mainly depend-
ent of the fact that the same individual has hypertension or
not. In fact, using anti-hypertensive drug therapy will, in
parallel, reduce arterial stiffness by decreasing the stiffness
proportion corresponding to the pressure load of collagen
fibers in the arterial wall, by increased blood pressure. With
current existing evidence, (and due to the lack of trials show-
ing that PWV can itself be a therapeutic target with proven
cardiovascular benefit) these drugs can only be used in hy-
pertensive subjects.
Still, no mistake should be made that, in the EVA sub-
jects with no clinical indication to use anti-hypertensive
treatment, other ways of reducing blood pressure (and thus
obtain stiffness reduction through the above mentioned
mechanism) should be recommended in so far as this blood
pressure reduction would not harm the individual, taking into
account his/her particular clinical features (Tables 1 & 2);
these non-pharmacological blood pressure reductions should
be achieved through reduction of salt consumption [73], ap-
propriate regular physical activity, weight loss and reduction
of alcohol consumption [74, 75].
Other therapeutic interventions for the subject with EVA
include pragmatic and strict attitudes on: a) smoking cessa-
tion; b) detection and control of traditional and non-
traditional cardiovascular risk factors (diabetes, dyslipide-
mia, abdominal obesity); c) detection and reversion of the
metabolic syndrome [17]; d) appropriate primary prevention
measures and treatment targets, in accordance with the
global cardiovascular risk class [74]; and e) control of in-
flammatory disease states, reduction of oxidative stress and
improvement of endothelial dysfunction. One capital issue in
these subjects is close follow-up and constant reassessment
of interventions.
7.1. Arterial Stiffness and EVA in Hypertensive Patients
For the EVA subject with hypertension, other pharma-
cologic therapeutic options can be included in the treatment
strategy of the patient, in accordance with the existing evi-
dence. Two particular aspects should be considered: 1) all
the above mentioned treatment strategies, which are appro-
priate for the non-hypertensive EVA subject, are still indi-
cated in the EVA hypertensive patient; 2) The fundamental
cornerstone of treatment is blood pressure control – even if
one must not put aside the role in arterial remodeling (and
arterial stiffness reduction) achieved by a long term use of
Table 1. Therapeutic interventions in subjects with Early Vascular Aging.
Obtain non-pharmacologic and clinically sustainable reductions of BP by reducing salt consumption, appropriate regular physical
activity, weight loss and reduction of alcohol consumption
Smoking cessation
Control of traditional and non-traditional cardiovascular risk factors (hyperglycemia/diabetes, dyslipidemia, abdominal obesity)
Reversion of the metabolic syndrome
Non-
Hypertensive
Subjects
Control of chronic inflammatory disease states
Institute equally all the non-pharmacologic / healthy lifesytle measures proposed for non-hypertensive subjects
Control Blood Pressure (independently of drug class used)
Hypertensive
Subjects
If possible, use preferentially ACE inhibitors, ARB’s, aldosterone antagonists, calcium channel blockers and/or vasodilating beta-
blockers. Inhibitors of the renin – angiotensin system and calcium channel blockers (either alone or in combination, should be preferred)
Table 2. Summary about EVA.
1.
EVA is an evolving concept aiming at earlier identification of subjects at increased risk of CVD
2.
The BP/Arterial Stiffness paradox: BP is a main determinant of Arterial stiffness; still evidence shows that these variables have a divergent
evolution with age, according to gender, making it clear that they bear different prognostic information in terms of CVD risk
3.
Arterial Stiffness is an independent predictor of CVD, both in high-risk CV subjects and at the general population level
4.
Screening for EVA should be done in; hypertensive patients (with no TOD); individuals with CVRF or chronic inflammatory diseases; subjects
with moderate risk for the development of CVD
5.
In one population based study, the prevalence of EVA was 12.5%; one out of every for subjects bellow
30 years of age presented with this characteristic
6.
Therapeutic implications – there are two distinct sets of recommendations for therapeutic attitudes in subjects with EVA,
considering their hypertension status (please see Table 1)
