Review
Hypertension in aortic stenosis: a focused review and
recommendations for clinical practice
Sahrai Saeed a, Filippo Scalise b, John B. Chambers c, and Giuseppe Mancia d
In patients with aortic stenosis, the presence of
hypertension negatively affects the hemodynamic severity
of the stenosis, and worsens adverse left ventricular
remodeling. It accelerates the progression of the stenosis
and is associated with worse prognosis. Proper
management of hypertension is thus crucial but there are
concerns about the safety and efficacy of
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antihypertensive medications as well as uncertainty
about optimal blood pressure (BP) targets and their
impact on left ventricular mass regression and survival
benefits. In the present review, we discuss these issues
based on the evidence available in the current literature.
Focus is first directed on the consequences of a
persistently elevated BP before and after surgical aortic
valve replacement or transcatheter valve implantation,
and the clinical significance of an abnormal BP response
during exercise in patients with significant aortic stenosis.
Available data on use of antihypertensive drugs are then
critically addressed, the conclusion being that calcium
channel blockers may be associated with lower survival,
and that diuretics may have disadvantages in patients
with left ventricular hypertrophy and smaller left
ventricular cavity dimensions, b-blockers may be well
tolerated and a better choice for patients with
concomitant coronary artery disease and arrhythmias.
Renin–angiotensin system blockers improve survival
given either before or after valve intervention.
Emphasis is placed on the fact that evidence is not
derived from randomized trials but only from
observational studies. Finally, we discuss the optimal SBP
level to reach in patients with aortic stenosis. Again,
randomized trials are not available but observational
evidence suggests that values between 130 and
139 mmHg systolic and 70 – 90 mmHg diastolic might
represent the best option, and lower BP targets should
probably be avoided.
Keywords: antihypertensive treatment, aortic stenosis,
aortic valve replacement, hypertension, left ventricular
hypertrophy, prognosis, renin–angiotensin system blockers
Abbreviations: ACE, angiotensin-converting enzyme;
ARBs, angiotensin-receptor blockers; AVR, aortic valve
replacement; BP, blood pressure; CCB, calcium channel
blockers; LV, left ventricle/ventricular; LVH, left ventricular
hypertrophy; RAS, renin–angiotensin system; TAVI,
transcutaneous aortic valve implantation
Journal of Hypertension
Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.
INTRODUCTION
T
he most common cause of aortic valve stenosis is the
calcification of the aortic valve, which is closely
related to the conventional cardiovascular risk fac-
tors. These include hypertension, diabetes, obesity, smok-
ing, hypercholesterolemia, and chronic renal failure [1].
Hypertension is frequently associated with degenerative
aortic stenosis and portends worse prognosis [1]. The
prevalence varies from 61 to 92% [2–5], and elderly women
with aortic stenosis, in particular, have a significantly higher
burden of hypertensive heart disease [6]. Traditionally,
hypertension in patients with aortic stenosis is defined
by an office blood pressure (BP) at least 140/90 mmHg,
a history of hypertension or treatment with antihyperten-
sive drugs [2–6]. Ambulatory and home BP measurements
are not routinely performed. This means that the preva-
lence and clinical significance of phenotypes, such as white
coat hypertension (elevated office but normal out-of-office
BP), or masked hypertension (normal office but elevated
out-of-office BP) in aortic stenosis is not clear. The preva-
lence and prognostic effect of the magnitude of the noc-
turnal BP decline is similarly unknown, despite its,
importance in the general hypertensive population [7].
In aortic stenosis, the left ventricle (LV) is exposed to at
least three types of challenges: valve stenosis; hypertension;
large artery stiffness (Fig. 1). The severity of aortic stenosis
has an obvious predominant impact on the structural and
functional LV alterations but the other two factors also play
a role in the LV modifications and in the determination of
the hemodynamic severity of aortic stenosis. Arterial stiff-
ness correlates poorly with the severity of aortic stenosis [8],
but increases markedly with age and contributes to total LV
outflow impedance independent of hypertension [8–10].
Hypertension has been more widely studied in aortic
stenosis. It may accelerate the progression of aortic stenosis,
but importantly may reduce the transaortic pressure
Journal of Hypertension 2020, 38:1211–1219
a
Department of Heart Disease, Haukeland University Hospital, Bergen, Norway,
b
Department of Interventional Cardiology, Policlinico di Monza, Monza, Italy, cCar-
Cardiothoracic Centre, Guy’s & St Thomas’ Hospital, London, United Kingdom and
d
University of Milano-Bicocca, Milano and Policlinico di Monza, Monza, Italy
Correspondence to Giuseppe Mancia, University of Milano-Bicocca, Milano and
Policlinico di Monza, Monza, Italy. E-mail: giuseppe.mancia@unimib.it
Received 27 December 2019 Revised 30 January 2020 Accepted 17 February 2020
J Hypertens 38:1211–1219 Copyright ß 2020 Wolters Kluwer Health, Inc. All rights
reserved.
DOI:10.1097/HJH.0000000000002426
www.jhypertension.com 1211
Saeed et al.

FIGURE 1 The interaction between age, hypertension, and large artery stiffening and their shared impact on aortic valve and left ventricular myocardium. In aortic stenosis,
LV is exposed to at least three types of afterload increase: aortic valve stenosis; hypertension; larger artery stiffening. The latter may have a bilateral relationship with
hypertension. The grade of valve stenosis severity has poor correlation with arterial stiffness. This may be explained by the fact that increased arterial stiffness is a product
of age and hypertension. LVH, left ventricular hypertrophy; AS, aortic stenosis.

differences leading to underestimation of the aortic stenosis
grade [11], especially when mean pressure gradient is in the
moderate range (<40 mmHg) but effective orifice area is in
the severe range (<1.0 cm2). To minimize this inconve-
nience, current international guidelines recommend to
carefully measure BP at every echocardiographic assess-
ment, and, if severely elevated, the hemodynamic severity
of aortic stenosis should be reassessed when the BP is
normalized [11]. However, in the echocardiographic assess-
ment of aortic stenosis, BP is not always measured, partic-
ularly during follow-up. In a SEAS (Simvastatin Ezetimibe in
Aortic Stenosis) study, BP was available in 100% patients
(n ¼ 1767) at baseline but was missing in 10% of the patients
(n ¼ 177) at a 2-year and 16% (n ¼ 283) at a 4-year follow-
up [12]. SEAS study was a prospective study of patients with
initially asymptomatic mild-to-moderate aortic stenosis ran-
domized to placebo or combined treatment with ezetimibe
10 mg and simvastatin 40 mg daily with a 4.3 years’ follow-
up. The study population was highly selected and did not
include patients with coronary heart disease, heart failure,
diabetes mellitus, previous stroke, or peripheral vascular
disease. However, hypertension was common.
Currently, there are no dedicated guidelines on the
management of hypertension in valvular heart disease,
and thus the general guidelines on the management of
hypertension in adult patients are followed [9]. The most
recent European guidelines on hypertension [9], recom-
mend in patients with a bicuspid aortic valve, a congenital
type of aortic stenosis that more often affects men and is
associated with aortopathy, aortic root dilatation, and
acute aortic syndromes [13], BP-lowering treatment at
BP values at least 140/90 mmHg and have as a therapeutic
target 130/80 mmHg or less (<140/80 mmHg in the
elderly), like the more general hypertensive population.
However, a bicuspid aortic valve may function normally
and there is no mention of the hemodynamic significance
and prognostic value of treating hypertension in degener-
ative aortic stenosis [9]. By contrast, the most recent
American guidelines, include a brief section on the man-
agement of hypertension in aortic valve disease [14]. The
section highlights that careful use of antihypertensive
medications in aortic stenosis is well tolerated and that
use of the renin–angiotensin system (RAS) blockers may be
advantageous because of their beneficial effects on myo-
cardial fibrosis (regression), symptoms, and functional
capacity [14]. Beta-blockers, by contrast, are mainly
reserved for patients with prior myocardial infarction,
arrhythmias, LV dysfunction or angina pectoris, whereas
diuretics should be used sparingly in patients with small LV
chamber dimensions [14].
In this clinical review, we will address the following
important considerations in the routine clinical care of
patients with aortic stenosis: how low should BP be
reduced with treatment, that is, what is the best BP target
for survival and other clinical benefits in patients with aortic
stenosis before and after valve intervention; which antihy-
pertensive drugs are best; what is the clinical significance of
a persistently elevated BP after surgical aortic valve replace-
ment (AVR) or transcatheter aortic valve implantation
(TAVI); what is the clinical significance of an abnormal

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BP response during exercise in patients with moderate or
severe aortic stenosis.
OPTIMAL BLOOD PRESSURE LEVELS IN
AORTIC STENOSIS
This issue has never been properly addressed by random-
ized trials, and available data are derived only from pro-
spective or retrospective observational studies. In the SEAS
study of 1767 asymptomatic patients with mild-to-moderate
aortic stenosis, Nielsen et al. [12] showed that a SBP from
130 to 139 mmHg was associated with the best survival
whereas a SBP at least 160, 120–129 mmHg, or less than
120 mmHg was associated with higher mortality (hazard
ratio 1.7, P ¼ 0.033, hazard ratio 1.6, P ¼ 0.039 and 1.6;
P ¼ 0.047, respectively) after adjusting for age and DBP.
Similarly, in a multivariable analysis, all-cause mortality was
greater with a DBP at least 90 mmHg or pulse pressure less
than 50 mmHg. The authors concluded that in aortic steno-
sis, the optimal BP level seemed to range between 130 and
139 mmHg systolic and 70–90 mmHg diastolic, and sug-
gested that a SBP less than 120/70 mmHg may indicate
the need for down-titration of antihypertensive medication
[12]. This is considerably closer to the general recommen-
dations of the European rather than the American guide-
lines as the latter indicate values less than 130/80 mmHg as
the optimal BP target in virtually all individuals whereas the
former state that in younger patients reducing BP less than
140/80 mmHg should represent the initial target, a further
reduction of SBP to 130 mmHg or below being pursued
only if tolerated; a SBP less than 140 mmHg but higher than
130 mmHg should be the goal in elderly patients, and a BP
less than 120/70 mmHg should never be pursued. This finds
support in a recent study showing that, compared with a BP
range of 120–149/60–79 mmHg, a range of 90–119/30–
59 mmHg 1 month after TAVI or surgical AVR was associ-
ated with a significant increase in cardiovascular and all-
cause mortality [15]. A SBP of 150–179 mmHg and DBP of
80–99 mmHg were not associated with increased mortality
[15], which the same group of investigators had previously
found to increase if, after TAVI, SBP was 100–129 mmHg
[5]. These observations are largely in line with what has
been observed in aortic stenosis patients before valve
intervention [12]. Thus, although in aortic stenosis, infor-
mation on the BP values associated with the best outcome
before and after valve intervention suffers from absence of
randomized trials, aggressive BP targets for antihyperten-
sive treatment should probably be avoided, in favour of a
more conservative approach both before and after aortic
stenosis correction. Starting with high doses and rapid up-
titration of the antihypertensive agents should also be
avoided as these patients may be sensitive to a rapid
reduction in preload and the related immediate and marked
baroreflex-mediated inotropic and vasomotor excitatory
response to relative hypotension. Finally, it is important
to underline that in the natural history of severe aortic
stenosis, a gradual decrease in stroke volume and resultant
pseudonormalization of SBP can be observed [16]. There-
fore, during the progression of aortic stenosis, the intensity
of antihypertensive treatment should be continuously eval-
uated and adjusted as necessary.
Journal of Hypertension
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Hypertension in aortic stenosis
WHICH ANTIHYPERTENSIVE DRUG
SHOULD BE PREFERRED?
Evidence on which antihypertensive drugs are well toler-
ated and effective, and have clinical long-term advantages is
also scarce. Historically, in patients with aortic stenosis, use
of all antihypertensive drugs has been associated with
adverse events especially at high doses and/or in multiple
combinations. Adverse events include hypotension, syn-
cope, and worsening of renal function [6,17]. Table 1
presents an overview on safety, functional recovery, and
the prognostic impact of antihypertensive and cardiopro-
tective medications in major aortic stenosis studies.
Beta-blockers
Beta-blockers have been considered harmful in patients
with aortic stenosis, especially in the presence of LV dys-
function [6]. More recently, however, some favorable data
have emerged, although not consistently in all studies. In a
large propensity-matched study of mild-to-moderate
asymptomatic aortic stenosis with preserved LV ejection
fraction, Bang et al. showed that use of beta-blockers (in
50% of the patients) was well tolerated and associated with
a lower risk of cardiovascular and all-cause mortality [18],
although major cardiovascular events showed some
increase, which was interpreted as because of the risk of
cardiac surgery [18]. No reduction in mortality with beta-
blockers was reported in the EXTAS (EXercise Testing in
Aortic Stenosis) cohort study [19]. EXTAS study was a
retrospective study of 316 apparently asymptomatic
patients with moderate or severe aortic stenosis who under-
went serial echocardiography and exercise treadmill tests. It
was initially designed to assess the safety and tolerability of
exercise treadmill test, determine the incidence of revealed
symptoms, and to explore the impact of revealed symptoms
and abnormal BP response on survival [3]. This study also
showed no adverse effects, and patients on antihyperten-
sive treatment were less likely to develop symptoms during
exercise treadmill testing [10,19]. Taken together, these data
suggest that beta-blockers are well tolerated and may be
suitable for patients with aortic stenosis, particularly if they
have concomitant coronary artery disease, arrhythmias, or
LV dysfunction. This recommendation is supported by the
current American hypertension guidelines [14].
Calcium channel blockers
Approximately 20–36% of aortic stenosis patients receive a
calcium channel blocker (CCB), prescribed as an antihy-
pertensive agent, antianginal agent or both [1,18–21]. In a
study of 1704 patients with severe aortic stenosis and
preserved LV ejection fraction (>50%), CCB was used by
36.5% of the entire study population, and more often in
patients with aortic stenosis of the low-flow (stroke volume
index <35 ml/m2) low-gradient (mean pressure gradient
<40 mmHg) subtype (n ¼ 25; 47%) in which mortality was
higher (n ¼ 24; 45%) compared with other flow-gradient
subtypes. The association of antihypertensive treatment
with all-cause mortality was not reported but hypertension
per se was a significant predictor of all-cause mortality in a
multivariable analysis [21]. In the EXTAS study, use of CCB
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Saeed et al.

TABLE 1. Studies showing the effects of antihypertensive and cardioprotective medications in patients with aortic stenosis
First author, Mean age Drug class Safety and
year (years) N Design evaluated Follow-up efficacy Major findings
a
Bang et al., 2017 67 1873 Prospective Beta-blockers 4.3  0.9 years Safe Lower risk of mortality independent
of in-treatment BP, time-
dependent AVR, and CABG.
Saeed et al., 2019 65 314 Retrospective Calcium-channel 2.9  2.9 years Adverse event during Seven-fold increased risk of all-
blockers exercise test cause mortality independent of
age, hypertension, diabetes,
LVEF, and aortic valve area.
Chockalingam 45 52 Prospective, ACE inhibitors 3 months Safe, well tolerated Improved exercise tolerance (NYHA
et al., 2004 randomized, class, Borg index and 6-min walk
double-blinded distance).
O’Brien et al., 2005 68 123 Retrospective ACE inhibitors 2.6  1.8 years Safe, well tolerated Lower rates of aortic valve
calcification assessed by CT.
Rosenhek et al., 2004 70 211 Retrospective ACE inhibitors 2.0  1.5 years No event reported Had no effect on AS progression.
Capoulade et al., 2013 69 338 Retrospective RAS blockers 6.2  2.4 years No event reported ARBs but not ACE inhibitors were
associated with slower AS
progression rate and better
survival.
Bull et al., 2015 69 96 Prospective, ACE inhibitors 1 year Safe and well tolerated Improved LV systolic function and
randomized, reduction in LV mass.
double-blind
Nadir et al., 2011 73 2117 Retrospectivea RAS blockers 4.2 years Safe, well tolerated Lower rates of all-cause mortality
and CV events both in patients
with severe and mild-to-
moderate AS.
Bang et al., 2014 67 1873 Prospectivea RAS blockers 4.3  0.9 years Safe, well tolerated RAS blocker were not associated
with mortality, and showed
greater reduction in SBP and a
slower progression of LV mass
Rodriguez-Gabella 81 2785 Retrospectivea RAS blockers 3 years Safe, well tolerated Reduced CV mortality at 1- and 3-
et al., 2019 year after TAVI. Greater
reduction of LV volumes and
hypertrophy and lower rates of
atrial fibrillation and
cerebrovascular events.
Magne et al., 2018 74 508 Retrospectivea RAS blockers 4.8  2.7 years Safe, well tolerated Better long-term survival after
isolated surgical AVR for severe
AS.
Inohara et al., 2018 82 21 312 Retrospectivea RAS blockers 1 year Safe, well tolerated Receipt of a prescription for a RAS
blocker at hospital discharge was
associated with lower risk of
mortality and re-hospitalizations
at 1-year after TAVI.
Goel et al., 2014 72 1752 Retrospectivea RAS blockers Median 5.8 years Safe, well tolerated Better long-term survival after
surgical AVR for severe AS. This
was not explained by changes in
LV mass, LVEF or left atrial size.
Ochiai et al., 2018 84 1215 Retrospective RAS blockers Median 1.1 year Safe, well tolerated RAS blockers after TAVI were
associated with greater LV mass
regression at 6-months and
lower all-cause mortality at 2-
years.

ACE, angiotensin-converting enzyme; ARBs, angiotensin-receptor blockers; AVR, aortic valve replacement; BP, blood pressure; CABG, coronary artery bypass grafting; CT, computed
tomographic; CV, cardiovascular; LV, left ventricular; LVEF, left ventricular ejection fraction; RAS, renin angiotensin system; TAVI, transcatheter aortic valve implantation.
a
Propensity score-matched.

(25% of the patients) was associated with a seven-fold
increased risk of all-cause mortality (hazard ratio 7.09;
95% CI 2.15–23.38, P ¼ 0.001) independent of age, hyper-
tension, diabetes, LV ejection fraction, and aortic valve area
[19]. Patients using CCB were more likely to experience an
adverse event during the exercise test, primarily a blunted
BP response. Although the number of patients included in
the EXTAS study was too low to provide information on
events or permit a propensity-matched comparison, these
data speak against the use of CCB in aortic stenosis patients
with hypertension and perhaps also angina pectoris and/or
arrhythmias. Whether this applies to both CCB categories
(dihydropyridines versus nondihydropyridines) has not
been investigated. Of note, American hypertension
guidelines in the general adult population contraindicated
intravenous dihydropyridines (Nicardipine and Clevidi-
pine) for hypertensive emergencies in patients with
advanced aortic stenosis [14].
Renin–angiotensin system blockers
Safety, tolerability, and impact on progression of
aortic stenosis
The most common evidence-based indications for angio-
tensin-converting enzyme (ACE) inhibitors or angiotensin-
receptor blockers (ARBs) are hypertension, impaired LV
function, diabetic and nondiabetic nephropathy, and the
postmyocardial infarction state. The cardioprotective

1214 www.jhypertension.com Volume 38  Number 7  July 2020

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effects and prognostic benefits of these drugs are well
documented, in particular, in patients with heart failure
[22,23] and hypertension [24,25]. Favorable data are also
available on the safety of RAS blockers in aortic stenosis
[26,27]. In the Symptomatic Cardiac Obstruction-Pilot study
of the Enalapril in Aortic Stenosis (SCOPE-AS) study, a total
of 52 patients with severe symptomatic aortic stenosis were
randomized to enalapril 10 mg twice daily versus placebo
[27]. Enalapril was generally well tolerated. However, it
needed to be discontinued for hypotension in three patients
in all of whom the SBP was less than 100 mmHg before the
initiation of enalapril. In patients who tolerated the drug,
there was a significant improvement in functional capacity.
Similar data on the safety and tolerability of RAS blockers in
native aortic stenosis or after intervention has been
reported [26,28–36]. The effect of RAS blockers on other
clinical variables has been less consistent. O’ Brien et al. [28]
showed that use of an ACE inhibitor was associated with a
significantly lower rate of aortic valve calcification whereas
other studies [29,30], showed no such association. Capou-
lade et al. [1] showed that ARBs but not ACE inhibitors were
associated with a slower progression rate of aortic stenosis
compared with treatments that did not involve RAS block-
ers. A further study of 208 patients showed that ARBs were
associated with a lower degree of inflammation and a lower
weight of the valve explanted at the time of AVR [37]. These
findings support the use of RAS blockers to decrease
disease activity in aortic stenosis, although there is so far
no medical treatment proven to cause regression of valve
calcification and fibrosis.
Reverse left ventricular remodeling and functional
recovery
In the natural course of aortic stenosis and/or hypertension,
LV hypertrophy (LVH) is a geometric adaptive response to
normalize wall stress and maintain LV systolic function.
However, the accompanying myocardial fibrosis means
that LVH is also maladaptive and is a powerful independent
determinant of cardiovascular morbidity and mortality
[6,24–25]. The effect of ACE inhibitors on LV mass reduction
has been previously documented in a small prospective,
double-blind, randomized placebo-controlled trial of
asymptomatic patients with moderate or severe aortic ste-
nosis over a 1-year follow-up [31]. ACE inhibitors also
improved systolic LV function as assessed by tissue Doppler
systolic velocity. Interestingly, the LV function recovery and
reverse cardiac remodeling was not explained by a reduc-
tion in BP, which was minimal and not significantly differ-
ent in the control and active treatment arms [31]. Similar
conclusions were reached by other studies. In a study of
Nadir et al. [26], on a large retrospective, propensity-score
matched population, it was shown that LVH regression was
greater with RAS blockers than with other drugs in absence
of a BP difference between the treatment arms. Further-
more, in a recent propensity score-matched large retrospec-
tive study, use of RAS blockers following TAVI was
associated with a greater reduction of LV volumes and
hypertrophy [32]. Finally, in the SEAS study [30], patients
exhibited, overall, an increase of LV mass index, which was
smaller, however, in those receiving RAS blockers. Thus,
RAS blockers appear to be more effective than other
Journal of Hypertension
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Hypertension in aortic stenosis
antihypertensive drugs in promoting regression of LVH
in patients with aortic stenosis. This is in line with the effect
of these drugs in the general hypertension population in
which both ACE inhibitors and ARBs have been found to be
associated with a greater regression of LVH than other drug
classes [24–25,38]. This effect is at least partly independent
of a reduction in BP and the afterload to the heart, and
rather accounted for by blocking the direct action of angio-
tensin II to promote cardiac muscle growth [39–41]. There
may also be an antifibrotic effect, as angiotensin II and
aldosterone (whose secretion is also reduced by RAS block-
ers), also stimulate cardiac fibrosis [32]. Similar cardiac
effects have been reported for sympathetic influences,
which are amplified at peripheral levels by angiotensin II
[42].
Survival benefits
With few exceptions, the available studies indicate that RAS
blockers do not adversely affect, and probably improve
survival in patients with aortic stenosis either untreated or
undergoing surgical AVR [33,34] or TAVI [32,35,36]. In the
small EXTAS cohort of patients with moderate-to-severe
aortic stenosis, no increase in all-cause mortality was found
with the use of ACE inhibitors or ARBs [19], a finding similar
to other studies [26,30,32,33]. Furthermore Capoulade et al.
[1] showed that survival was better in patients treated with
RAS blockers, although the effect was limited to ARBs and
did not extend to ACE inhibitors. Finally, in a review of five
studies of patients undergoing AVR either surgical or TAVI,
use of RAS blockers was consistently associated with a
reduction of all-cause mortality, varying from 17 to 69%
[43]. Most importantly, favourable results have been
recently reported by comparing propensity score-matched
groups of patients. In a large propensity score-matched
retrospective study, use of RAS blockers following TAVI
was associated with lower cardiovascular mortality at 1 (3.5
versus 5.8%; P ¼ 0.003) and 3-year (5.6 versus 9.3%;
P < 0.001) follow-up, an effect, which was associated also
with a lower rate of atrial fibrillation and cerebrovascular
events [32]. Similarly, in another propensity score-matched
study [33], patients previously treated with RAS blockers
had a better survival after surgical AVR than those who had
not had RAS blockers. There was a significant, albeit small,
difference in 8-year survival in favour of ARBs versus ACE
inhibitors (87  3% for ARBs and 79  4% for ACE inhibitors,
P ¼ 0.028 compared with 52  5% in the absence of RAS
blockers). It is important to highlight that the survival
benefits of RAS blockers in aortic stenosis patients are
evident whether these drugs were used before valve inter-
vention [33], or prescribed at hospital discharge after valve
intervention [35]. In a large registry-based study of 7948
propensity score-matched equal pairs of aortic stenosis
patients undergoing TAVI, Inohara et al. [35] showed that
patients receiving a prescription for a RAS blocker at
discharge had significantly lower mortality rates (12.5 vs.
14.9%, P ¼ 0.002) and heart failure readmissions (12 vs.
13.8%, P ¼ 0.004) over 1 year compared with those who
did not receive a prescription of a RAS blocker. This effect
was observed only in patients with preserved LV ejection
fraction, which according to the authors, might have origi-
nated by the different effects of RAS blockers on LV
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Saeed et al.
remodeling and the lower frequencies of postintervention
aortic regurgitation in the two groups of patients. However,
follow-up BP measurements were not available, which
represents a serious limitation to the interpretation of the
factors involved.
ELEVATED BLOOD PRESSURE
FOLLOWING AORTIC VALVE
INTERVENTION
After the relief of aortic valve stenosis by surgical AVR or
TAVI, the LV is entirely or partly unloaded, leading to
regression of the increased LV mass, and, to a certain extent,
of cardiac fibrosis (Fig. 2). In this context, however, the role
of a persistently elevated cardiac afterload (arterial hyper-
tension) has been poorly studied. In aortic stenosis patients,
the restricted aortic valve lumen dampens the projectile
forces of the contracting heart. Theoretically, it is possible
that, after the relief of valve stenosis, restoration of the
effects of the cardiac contractile forces leads to an increase
of SBP. This increase may be enhanced if stiffer large
arteries (as a result of aging, hypertension, and atheroscle-
rosis) are no longer able to effectively buffer the repetitive
high energy pressure waves generated by the heart. There
will also be early return of the reflected pressure waves
from the peripheral circulation to merge with the central
forward–backward wave, which may disturb the blood
flow pattern in aortic sinuses [44,45]. This will lead to an
increased systolic, a reduced diastolic (and an increase in
differential pressure), with adverse consequences, such as
persistently higher LV load, a decreased coronary perfusion
(which depends mainly on diastolic pressure) and trans-
mission of pulsatile pressure as well as damage to the
microcirculation [44]. In addition, systolic hypertension
FIGURE 2 The impact of transcutaneous aortic valve implantation and surgical aortic valve replacement, and antihypertensive treatment on left ventricular remodeling,
functional recovery, and survival benefits. Blood pressure control may be achieved but its prognostic value in AS patients is poorly understood. AVR, aortic valve
replacement; TAVI, transcatheter aortic valve implantation.
1216 www.jhypertension.com
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may increase the mechanical stress on the valve cusps
during systole. In view of these considerations, close obser-
vations of BP patterns and optimal treatment of hyperten-
sion after relief of valve stenosis is clinically crucial [5]. Some
patients, particularly elderly women, may show an exag-
gerated BP rise immediately after TAVI which has rarely
been addressed [46,47] but is believed to be caused by
abrupt changes in LV hemodynamics, with a rise in stroke
volume. Perlman et al. [46] demonstrated that a significant
rise in BP after TAVI was associated with better clinical
outcome even in the presence of LV dysfunction at baseline.
By contrast, another study of 23 patients showed that a
hypertensive response after TAVI might have unfavorable
effects on the arterial tree [47].
EXERCISE PHYSIOLOGY IN AORTIC
STENOSIS
Abnormal blood pressure response during
exercise test
Current European and American guidelines on the man-
agement of valvular heart disease recommend exercise
testing for patients with severe aortic stenosis who are
asymptomatic on the history [48,49]. Exercise-induced
symptoms are a class I indication for AVR and a blunted
BP response (a sustained fall in SBP 20 mmHg below the
baseline level a class IIa indication [48,49]. Interestingly,
some patients show an exaggerated BP response during
exercise, a phenotype which is associated with a higher risk
of incident hypertension [50–52] in the general population
but whose clinical significance and prognostic value is
poorly understood in aortic stenosis. In the EXTAS study
of asymptomatic patients with moderate or severe aortic
stenosis, an exaggerated BP response (peak SBP
Volume 38  Number 7  July 2020

>190 mmHg) during treadmill exercise was found in 21%
patients, and was associated with higher resting BP,
increased LV mass, and increased arterial stiffness. How-
ever, it did not predict mortality [53]. There is no consensus
on the definition of an exaggerated BP response during
exercise, in part because peak SBP during exercise is
affected by several factors including age, baseline BP level,
and the protocol of the exercise test [53]. In the general
population and hypertensive patients, an exaggerated BP
rise has been defined as a peak SBP of approximately 190–
210 mmHg [54].
The impact of hypertension and peak SBP on
symptoms and functional capacity
The EXTAS study has recently addressed the impact of
history of or actual hypertension and peak SBP on symp-
toms and functional capacity in patients with asymptomatic
moderate or severe aortic stenosis [10]. Hypertension was
associated with a higher cardiovascular disease burden but
did not interact with symptoms or functional capacity
during treadmill exercise [10]. In a multivariate logistic
regression analysis, antihypertensive treatment was associ-
ated with a lower risk of symptoms, whereas a lower peak
SBP and an early rapid rise in heart rate (within the first
6 min of exercise) were associated with a higher risk of
symptoms. This effect was independent of age, obesity, LV
ejection fraction, and aortic valve area. Hypertensive
patients walked on average 2.5 min less and achieved lower
metabolic equivalents (METs) compared with normoten-
sive patients. This difference was not explained by the
incidence of symptoms, which occurred in equal frequen-
cies in both hypertensive and normotensive patients [10].
Patients who remained asymptomatic during the exercise
treadmill test, achieved significantly higher peak SBP and
METs, and walked longer on the treadmill compared with
those who developed symptoms. Women were more likely
to walk for a shorter time on the treadmill and to achieve
lower METs than men but they achieved similar peak heart
rates and BP. The frequency of symptoms during exercise
test was comparable in both sexes [55].
CONCLUSION
Patients with aortic stenosis are exposed to a high risk of
adverse cardiovascular events and, in the hope of mitigating
this, optimal BP control is advised both before and after
valve intervention. Evidence on the use of CCBs in aortic
stenosis is scarce but suggests the avoidance of these drugs.
Diuretics may have short-term benefits in terms of symptom
reduction but attention should be paid when treating
patients with LVH and smaller LV cavity dimensions. Fur-
thermore, the impact of the long-term use of diuretics on
prognosis in patients with aortic stenosis should be investi-
gated. Beta-blockers are by and large well tolerated and
may be an appropriate treatment option, especially for
patients with concomitant CAD and arrhythmias. A wide
number of studies, though all observational, show that RAS
blockers are well tolerated and may improve clinical out-
come whether used prior to or after valve intervention.
Patients following valve interventions should be carefully
monitored for their BP status, values within the 130–139/
Journal of Hypertension
Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.
Hypertension in aortic stenosis
70–90 mmHg range (systolic/diastolic) being probably the
wisest option. Marked reductions of BP should be avoided.
Currently, there are no special recommendations for use of
RAS blockers in patients with aortic stenosis. However, in
view of the available data, their use for the treatment of
hypertension in aortic stenosis may be probably the
first choice.
Future directions
The safety and efficacy in terms of LV mass regression and
survival benefit of antihypertensive drugs in patients with
aortic stenosis should be investigated in larger randomized
trials, as most of the data presented in this review are
derived from prospective or retrospective observational
studies. Furthermore, the safety, tolerability, and efficacy
in terms of BP reduction and end-points of diuretics and
mineralocorticoid receptor antagonists in aortic stenosis
should be explored in future studies.
Data on ambulatory and home BP monitoring in the risk
stratification of aortic stenosis patients are scarce, and are
thus also desirable because of their superior prognostic
impact versus office BP in the general hypertensive popu-
lation. The 24-h awake and asleep DBP has been signifi-
cantly associated with advanced aortic valve calcification
[56]. However, its prognostic significance has not been
explored in aortic stenosis patients. Utilization of ambula-
tory BP may give a better picture of the true hemodynamic
load, identify hypertension subtypes at different cardiovas-
cular risk, quantify the night-time BP decline, and detect
daily life hypotensive episodes, thereby being important for
all aortic stenosis patients with a history of hypertension,
those with an actual BP elevation and even patients under
antihypertensive drugs in whom office BP may seem under
control. Ambulatory BP monitoring may offer clinically
useful information even in normotensive aortic stenosis
patients.
Isolated systolic hypertension (SBP 140 mmHg without
DBP elevation) is the most common form of hypertension
in patients with degenerative aortic stenosis. It is associated
with faster progression of aortic valve calcification and has a
major impact on outcome [57]. Thus, a SBP elevation should
not be considered simply an acceptable product of age but
should be treated actively with antihypertensive medication
suited for every individual patient.
After the relief of valve stenosis with TAVI or surgical
AVR, the LV is partially unloaded. The normalization of
mean pressure gradient is usually used as a marker of short-
term therapeutic success. However, a reduction in ZVa or
global LV impedance (SBP þ mean aortic pressure gradi-
ent)/stroke volume index) incorporates both valve and
arterial load and may be a better marker of long-term
therapeutic success. To reduce ZVa optimally may require
the treatment of hypertension in addition to surgical AVR
or TAVI.
Finally, the earlier TAVI populations were typically
elderly with a high risk from conventional surgery. The
outcome of interest was a short-term survival benefit. In
recent years, however, TAVI has been increasingly offered
to intermediate and lower cardiovascular risk patients who
are often younger and expected to have improved long-
term survival. This will only be possible if concomitant
www.jhypertension.com 1217
Saeed et al.
comorbidities, such as hypertension and atherosclerotic
cardiovascular risk factors are optimally treated.
ACKNOWLEDGEMENTS
Conflicts of interest
There are no conflicts of interest.
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