Editor’s Corner
Highlights of the January issue
Giuseppe Mancia
T
he January issue of the Journal of Hypertension
opens with two meta-analyses on blood pressure
(BP) regression to the mean, as calculated from
randomized controlled trials. Salam et al. (pp. 16–23)
confirm, on a total of 86 trials in about 350 000 patients,
that, due to regression to the mean, office BP shows a
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reduction when initial values are higher and an increase
when they are lower. They further show that this phenom-
enon is quantitatively so large as to make, in patients with a
higher initial office BP, the BP-lowering effect greater than
that due to antihypertensive treatment. As often mentioned
in the past, regression to the mean makes the BP range of a
given study group much smaller in the follow-up than in the
screening or pretreatment phase, increasing the steepness
of the relationship between BP and outcomes and thus
upgrading the importance of BP as a risk factor for cardio-
vascular events. Significantly, in the other meta-analysis
(Moore et al., pp. 24–29) regression to the mean is also
reported for ambulatory BP whose day and night follow-up
mean values were found to be lower and higher in patients
with initially higher and lower values, respectively, similarly
to office BP. To several investigators this will appear sur-
prising because ambulatory mean BP values have often
been reported to be similar with measurements performed
at shorter or longer time intervals from the initial measure-
ments, with in addition little or no BP-lowering effect also of
prolonged periods under placebo. Indeed, this has been
traditionally listed as an advantage of ambulatory over
office BP measurements for the study of antihypertensive
drugs. The meta-analysis of Moore et al. challenges this
concept and calls for further investigation of this issue,
hopefully by a database larger than that available in the
present meta-analysis. The two papers are commented by
the interesting Editorial of Messerli and Rexhaj (pp. 4–5)
who provide information on the origin and the develop-
ment of the concept as well as on its implications for the
interpretation (and misinterpretation) of the results of clini-
cal trials.
The following three articles provide new data on BP and
haemodynamic measurements in hypertension. Stabouli
et al. (pp. 30–36) tested the new oscillometric Sphygmocor
XCEL device (AtCor Medical Pty Ltd, West Ryde, NSW,
Australia) in individuals aged 6–20 years and found its
ability to measure pulse wave velocity and central BP
similar to that provided by the gold standard tonometric
measurements. Central BP and pulse wave velocity are
more and more frequently part of the clinical examination
of adults and children with hypertension, making simplifi-
cation of data collection by newer vs. classical methods, a
relevant advantage. Palatini et al. (pp. 37–41) show that in
Journal of Hypertension
Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
very obese individuals cuffs that reflect the troncoconical
shape of their arms provide lower BP values (5/
3 mmHg) than cylindric cuffs, thereby reducing the well
known overestimation of BP in overweight patients. This is
not of marginal clinical relevance because overestimation
of BP values in obese individuals may lead to unnecessary
drug treatment. Finally, Seo et al. (pp. 42–49) show, in
more than 1200 patients, that unobserved (or unattended)
office and daytime mean BP measurements exhibited large
discrepancies, the differences being particularly evident in
patients with a high cardiovascular risk. This implies that
unattended office BP measurements do not provide, as
often claimed, BP values that are superimposable to the
daily life ones, thereby sharing with them a superior prog-
nostic significance. Unattended BP measurements my pro-
vide values that are closer to daily life BP because they are
immune from the white-coat effect that characterizes clas-
sical attended office BP measurements. However, daily life
BP is modulated by countless other factors that make
discrepancies with office BP, no matter whether attended
or unattended, by no means surprising. The issue is dis-
cussed by the editorial commentary of Kjeldsen and Mancia
(pp. 6–8) also in relationship to the SPRINT trial, in which
unattended office BP measurements were, at least as
reported in the protocol, the BP measurement of choice.
The following series of articles focus on heart and
vessels. Tadic et al. (pp. 50–56) show that hypertensive
patients have lower left ventricular (LV) global longitudinal
and circumferential strains than their normotensive coun-
terparts, this being the case more in men than in women.
Sex differences in the adaptation to hypertension are more
and more frequently discovered, also with clinical and
therapeutic implications. Milan et al. (pp. 57–64) describe
the results of a study (ARGO-SIIA project) designed to
determine the prevalence of ascending aorta dilatation in
untreated hypertension. Compared with normotensive con-
trols aortic dilatation was quite frequent (13%) in hyperten-
sive individuals, its detection being frequently associated
with an increase of LV mass. Aortic dilatation not rarely goes
unreported by the echocardiographic examination of
patients with an increased BP, whereas it deserves attention
Journal of Hypertension 2019, 37:1–3
Università Milano-Bicocca, Milan, Italy
Correspondence to Prof Giuseppe Mancia, Università Milano-Bicocca, Piazza dei
Daini, 4, 20126 Milano, Italy. Tel: +39 3474327142;
e-mail: giuseppe.mancia@unimib.it
J Hypertens 37:1– 3 Copyright ß 2018 Wolters Kluwer Health, Inc. All rights
reserved.
DOI:10.1097/HJH.0000000000001999
www.jhypertension.com 1
Mancia
both because, as shown by Milan et al., is not rare and
because the possibility that the combination of LV hyper-
trophy and aortic dilatation increases cardiovascular risk
more than LV hypertrophy alone cannot be excluded. Pan
et al. (pp. 65–72) describe the relationship between a large
number of plasma biomarkers, including those related to
inflammation, and expansion of extracellular volume or
increased LV mass as assessed by cardiac magnetic reso-
nance. Several biomarkers correlated with one or both
abnormalities, scoring in favour of the possibility to predict
in the future the development of hypertension-related
abnormalities by plasma variables of simple collection.
Izawa-Ishizawa et al. (pp. 73–83) describe a model of
aortic dissection obtained in mice by inducing endothelial
dysfunction via administration of L-NAME. Aortic dissection
and aneurysmal rupture were much more frequent in mice
administered L-NAME than in control mice, which supports
a causal role of endothelial damage in the pathogenesis of
this clinically dramatic condition. Significantly, administra-
tion of pitavastatin had protective effects, which suggests
that statins may be a therapeutic coadjuvant, possibly
because of their anti-inflammatory effect. Yang et al.
(pp. 84–91) provide further data on the relationship
between long-term (i.e. visit-to-visit) SBP variability and
all-cause death, using a real life cohort from China. The
interesting aspects of the study are that also long-term heart
rate (HR) variability showed a relationship with fatal events;
BP variability was prognostically more detrimental in
patients with a higher HR variability, suggesting an interac-
tion between these two phoenomena. Finally, Alves-Cab-
rato et al. (pp. 92–98) describe the results obtained by
studying the prognostic value of ankle–brachial index
(ABI) in an impressively large number of hypertensive
patients with no previous cardiovascular events
(n ¼ 9126 out of a database of more than 44 000 patients).
Compared with what is regarded as the normal value (<0.9)
an increased ABI was associated, over a 6-year follow-up,
with an increased cardiovascular risk, which was maximally
evident for heart failure and reached 44% for values greater
than 1.3. This strengthens the evidence in favour of includ-
ing ABI among the measures of asymptomatic vascular
damage in the screening of patients with high BP, as already
recommended by several guidelines. The challenge is to
conclusively prove that treatment-induced changes in ABI
are predictive of patients’ protection, a goal still elusive for
this as well as for other markers of vascular damage.
Several articles of the January issue deal with the patho-
genetic, diagnostic and treatment aspects of renal damage
or on the determinants of cardiovascular risk. Zhang et al.
(pp. 99–108) examined the validity of five published equa-
tions that estimate 24-h urinary sodium excretion via time
spot urine specimen, measuring spot and 24-h urinary
sodium excretion in 99 healthy volunteers. No equation
was particularly accurate and indeed with all equations an
up to 60% misclassification of the true individual salt intake
was observed. This confirms the limitations of spot urine as
well as the need of more accurate measurements, keeping
in mind, however, that complex measurements are incom-
patible with the size of epidemiological and intervention
studies that need to be performed to give the long-term
relationship among sodium intake and cardiovascular risk a
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reliable answer. Underwood et al. (pp. 109–115) provide
evidence that in mice with Lewis polycystic kidney disease
vasopressin as well as activation of the hypothalamic para-
ventricular nucleus (obtained by the inactivating effect of
muscimol) contribute to the accompanying BP elevation.
The obvious implication is that studying the effect of
interventions against these mechanisms may have a thera-
peutic rationale. Khatir et al. (pp. 116–124) describe that, in
patients with advanced chronic kidney disease, randomi-
zation to an additional vasodilating medical therapy (cal-
cium channel and a renin–angiotensin system blocker)
reduced BP and renal vascular resistance more effectively
than randomization to a nonvasodilating therapy (a beta-
blocker) which had a renal vasoconstrictor effect. Over a
period of 18 months, however, this did not translate into a
difference in cortical or medullary oxygenation values, the
decline of glomerular filtration rate being also similar in the
two groups. This adds to the evidence of trials and meta-
analyses, that aggressive BP reductions may not carry any
advantage to the kidney, even when, as suggested by the
results of Khatir et al., drugs elicit a powerful renal vasodi-
lation, thus in theory protecting organ perfusion in the face
of the reduction in perfusion pressure. Lin et al. (pp. 125–
134) report the results of a retrospective analysis of more
than 7000 patients with acute kidney disease in which
treatment made or did not make use of a mineralocorticoid
receptor antagonist. Use of a mineralocorticoid receptor
antagonist did not lower the rate of major cardiovascular
events and death compared with nonmineralocorticoid-
based treatments. However, although increasing the risk
of hyperkalaemia, mineralocorticoid antagonist therapy
was associated with a 17% significant reduction in the risk
of dialysis, suggesting a favourable effect of this therapeutic
approach in the transition from acute to chronic kidney
disease. An insight into the pathogenetic role of aldosterone
for chronic kidney disease as well as into the renal effects of
mineralocorticoid receptor antagonists is provided by the
editorial commentary of Maiolino and Calò (pp. 9–10).
The articles on determinants of cardiovascular risk focus
on BP and other risk factors. Using an animal model of
hypertension Cardoso et al. (pp. 135–143) report a favour-
able effect of chronic exercise (swimming) on hyperten-
sion-mediated memory dysfunction, possibly via
modulation of the purinergic system in the brain. He
et al. (pp. 144–153) show that euthyroid individuals with
increased thyroid-stimulating hormone levels have a
greater risk of developing hypertension. Kerr et al.
(pp. 154–166) provide evidence that nicotine-containing
electronic cigarettes did not increase BP but increased HR
and reduced peak expiratory flow, indicating that some of
the acute adverse effects of smoking are not completely
avoided. Of note, both electronic cigarettes and tobacco
smoking did not have a pressor effect, at variance from old
studies in which smoking a cigarette was associated with a
marked and prolonged pressor response. Kuwabara et al.
(pp. 167–174) provide data from a Japanese nondiabetic
population that higher baseline glucose levels are associ-
ated with an increased risk of incident hypertension, this
being the case both in men and women. This adds to the
already large body of evidence that blood glucose and BP
are related by a sort of a positive interaction, the basis of
Volume 37  Number 1  January 2019

which may be the stimulating effect of sympathetic activ-
ity on insulin resistance and secretion, and the sympa-
thetic activation caused by the increased insulin levels.
The epidemiological link of hyperglycaemia and BP is
emphasized by the Editorial of Nilsson (pp. 11–12).
Finally, Rosenbaum et al. (pp. 175–181) report on the
central BP and vascular alterations of patients with con-
genital adrenal hyperplasia. Compared with well matched
controls, 26 individuals with congenital adrenal hyper-
plasia exhibited an early increase of central BP. Some-
what surprisingly this was not accompanied by an
increase of pulse wave velocity and carotid intima–media
thickness, leading the authors to advance the hypothesis
that in congenital adrenal hyperplasia vascular damage
depends on and thus follows a BP elevation.
The following four articles deal with preeclampsia. In the
article by Salazar et al. (pp. 182–186) evidence is presented
that in high risk midpregnancy nocturnal hypertension is
frequent and represents a strong predictor of preeclampsia
or eclampsia. As discussed in the accompanying editorial of
Webster (pp. 13–15), this provides further evidence on the
importance of the information offered by ambulatory BP in
pregnancy, strengthening the case for use of this approach
on a routine basis. Further supporting data are shown in the
second article in which Lv et al. (pp. 187–196) document a
relationship of nocturnal hypertension and preeclampsia
with an excessive coiling of the umbilical cord, probably via
mechanical interference with fetoplacental vascular resis-
tance. In this setting, a considerable interest has also the
third article (Shao et al., pp. 197–205) which shows that
early preeclampsia is associated with an imbalance of the
levels of plasma testosterone and oestradiol, which corre-
lates with the levels of procoagulation factors. Information
on biomarkers that may predict preeclampsia is making
considerable progress, and the hope of future clinical
Journal of Hypertension
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Highlights of the January issue
applications is by no means chimeric. Finally, Iwama
et al. (pp. 206–215) provide a large descriptive evidence
that in monochorionic and dichorionic twin pregnancies
early, mid and late SBP or DBP values are somewhat greater
than in the singleton pregnancy. The implications of these
differences for gestational and perinatal problems remain to
be studied.
Last but not least, Lind et al. (pp. 216–222) report the
results of a genetic research that has a special element of
interest because it links proteomic patterns with functional
cardiovascular derangement, a genetic–mechanistic
approach that is not yet common in genetic research. Lind
et al. examined proteins known to be associated with
cardiovascular risk for their relationship with endothelial
dependent forearm vasodilation, elicited by intra-arterial
acetylcholine infusion. Endothelial dependent vasodilation
was selected because endothelial dysfunction is the first
step in the cascade of events that leads to atherosclerosis.
Out of the 84 proteins found to have a cardiovascular link in
two related population studies, 15 showed an association
with endothelial dysfunction, a replication being obtained
in seven of them. Eventually, after adjustment for con-
founders, the plasma levels of cathepsin-D showed a sig-
nificant inverse relationship with the endothelial-mediated
vascular effect, a result that supports the validity of this
research approach, which will hopefully become more and
more common in the future. It is obvious that, once the
genes are involved in hypertension and cardiovascular
disease are identified, we need to know through which
mechanisms they operate.
ACKNOWLEDGEMENTS
Conflicts of interest
There are no conflicts of interest.
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