Editor’s Corner
Mechanisms, diagnosis and therapy of hypertension
Alberto Zanchetti
T
he articles in the current issue of the Journal of
Hypertension approach mechanistic, diagnostic
and therapeutic aspects of hypertension.
Mechanisms of hypertension and hypertension-related
organ damage have been explored by a large body of
studies. Four articles focus on the role of several blood
pressure (BP) parameters on cardiovascular risk and
organ damage. Kollias et al. (pp. 243–249) report that a
two-night home BP schedule (six readings) appears to
provide reasonable agreement with ambulatory BP and to
be associated with asymptomatic organ damage, and
Sherwood et al. (pp. 250–258) find that blunted night-
time dipping is associated with impairment of the systemic
vasodilatation occurring during the night-time sleep
period, impairment that is especially prominent among
African Americans. According to the authors, these find-
ings suggest that nondipping may be a manifestation, or
marker, of more advanced vascular disease. In the
Maastricht Study database, Zhou et al. (pp. 259–267) have
calculated short-to-mid-term BP variability in individuals
with normal glucose metabolism, prediabetes and type-2
diabetes and found that both diabetes and prediabetes are
associated with a slightly greater variability that may
explain a small part of the increased cardiovascular
risk seen in prediabetes. Another cross-sectional study
(Dore et al., pp. 268–276) has investigated the possible
role of intraindividual BP variability in cognitive decline in
community dwelling participants in the Maine-Syracuse
Longitudinal Study and report that, in individuals aged
over 60 years, intraindividual BP variability was inversely
correlated with a number of indices of cognitive function.
Three articles focus on the mechanisms and consequen-
ces of arterial stiffness. Han et al. (pp. 299–305) have used
computed tomography to measure abdominal and subcu-
taneous fat in a group of Japanese Americans followed up
for 5 years and report the accumulation of abdominal fat
(but not of subcutaneous fat) over time independently
predicted future pulse pressure, taken as a marker of arterial
stiffness. Rasmussen et al. (pp. 277–285) have investigated
the cardiovascular effects of abuse of anabolic androgenic
steroids in a group of current and former abusers: current
abusers displayed increased 24-h SBP and higher
aortic stiffness, together with a decreased plasma concen-
tration of vasodilating natriuretic peptides. Sadekova et al.
(pp. 286–298) have used a mouse model of increased
arterial stiffness (application of CaCl2 to the adventitia of
the right carotid artery) and investigated its consequences
in the brain: increased cerebral gliosis was found, mediated
by oxidative stress and attenuated by Tempol treatment.
The authors conclude that correcting arterial stiffness may
Journal of Hypertension
Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
offer a novel paradigm to protect the brain in populations in
which stiffness is prominent.
Two other mechanistic articles concern the kidney.
Cervantes-Perez et al. (pp. 361–366) find that angioten-
sin-II-induced hypertension in mice requires, at least in
part, activation of the renal NaCl cotransporter via the
WNK/SPAK signaling pathway, whereas aldosterone-
induced hypertension depends on epithelial sodium chan-
nel activation in a WNK/SPAK-independent manner. Mar-
tı́nez-Martı́nez et al. (pp. 368–376) show that galactin-3
inhibition attenuates early renal damage in the spontane-
ously hypertensive rat, as indicated by reduced albumin-
uria, improved renal function and decreased renal fibrosis,
epithelial–mesenchymal transition and inflammation, inde-
pendently of BP levels.
Two articles investigate problems related to preeclamp-
sia. Wang et al. (pp. 306–318) report that in preeclamptic
placenta, a lowered level of miR-195 may be induced by
chorionic oxidative stress and may subsequently form a
compensation mechanism to defend the disturbed energy
production and cell apoptosis upon oxidative stress.
Brussé et al. (pp. 319–325) show neurophysiological
adaptation to pregnancy of the visual cortex in normo-
tensive pregnant women, which is apparently lost in
women with severe preeclampsia. A final mechanistic
article reports left ventricular subclinical systolic dysfunc-
tion in patients with primary aldosteronism (Chen et al.,
pp. 353–360).
Three articles focus on the diagnosis of primary aldoste-
ronism. Yamashita et al. (pp. 326–334) have developed and
validated a scoring system for screening newly diagnosed
hypertensive patients who should proceed to endocrino-
logic examinations for primary aldosteronism. On the basis
of a series of 130 consecutive patients, 24 of whom were
diagnosed with primary aldosteronism by an elevated
plasma aldosterone concentration-to-plasma renin activity
ratio, Yamashita et al. conclude that a score based on urine
pH at least 7.0 (P), female sex (F) and hypokalemia (K)
(PFK score) may be a better parameter than hypokalemia
Journal of Hypertension 2018, 36:205–207
Istituto Auxologico Italiano and Centro Interuniversitario Fisiologia Clinica e Iperten-
sione, Università degli Studi di Milano, Milano, Italy
Correspondence to Prof Alberto Zanchetti, Istituto Auxologico Italiano IRCCS and
Centro Interuniversitario di Fisiologia Clinica e Ipertensione, Università degli Studi di
Milano, Via F. Sforza, 35, 20122 Milano, Italy. Tel: +39 02 50320484;
e-mail: alberto.zanchetti@unimi.it, alberto.zanchetti@auxologico.it
Received 7 November 2017 Accepted 7 November 2017
J Hypertens 36:205–207 Copyright ß 2018 Wolters Kluwer Health, Inc. All rights
reserved.
DOI:10.1097/HJH.0000000000001638
www.jhypertension.com 205
Zanchetti
alone for screening patients with a high probability of
having primary aldosteronism. Rossitto et al. (pp. 335–
343) have investigated the hypothesis that sequential blood
sampling from the adrenal veins on both sides may
decrease the diagnostic accuracy of the lateralization index
for identification of an aldosterone-secreting adenoma and
found it generates factitious between-side gradients, which
lower its diagnostic accuracy, likely because of the stress
reaction arising upon starting adrenal vein catheterization.
Genovesi et al. (pp. 344–352) have measured plasma
aldosterone and plasma renin concentrations and aldoste-
rone-to-renin ratios in a cohort of 287 children attending a
specialized clinic and found the aldosterone-to-renin ratio
is lower than in adults and diverges with increasing age
between sexes.
A large body of articles focus on different aspects of
antihypertensive treatment. A position article of the
Latin American Society of Hypertension (Coca et al.,
pp. 208–220) discusses the best antihypertensive strategies
to improve BP control in that part of the world and, more
generally, how to overcome barriers to achieve good BP
control in low-income countries. The document underlines
randomized trials have shown there are little substantial
differences between the benefits of major classes of BP-
lowering drugs and prevention of major cardiovascular
events depends on BP lowering independently of the drugs
used. Within each drug class, although some compounds
have been tested in trials more widely than others, there is
no evidence of major differences between molecules, and
the suggestion is given to prescribe those that can be
purchased by health providers or by the patients at the
lowest price, provided that good manufacturing quality is
guaranteed. In the current issue of the journal, an article by
Macquart de Terline et al. (pp. 395–401) raises the problem
of the quality of antihypertensive generic medication in
low-income countries: the authors report that nearly one-
quarter of the generic antihypertensive drugs available in
the sub-Saharian countries were found to be of poor
quality, although poor quality was not necessarily associ-
ated with the purchase price of the drug. In a thoughtful
accompanying editorial, Alcocer (pp. 230–233) under-
lines the importance of assuring quality of generic drugs,
particularly in low-to-middle income countries, in which
purchasing costly medications can lead a family toward
poverty, and points out the responsibility for ensuring
that the drug prescribed under a generic name is inter-
changeable with the original medication rests with
government health authorities.
Some of the difficult problems associated with so-called
treatment-resistant hypertension are approached by two
articles. Analyzing data from the Swedish Primary Care
Cardiovascular Database from 2006 to 2012, including over
4300 patients who could be defined as resistant to anti-
hypertensive treatment, Holmqvist et al. (pp. 402–409)
found they had a poor prognosis beyond BP level,
with a particularly high risk for heart failure. Renal dener-
vation is being recently considered as a possible therapeutic
approach in these patients, and Persu et al. (pp. 221–229)
have carried out a patient-level meta-analysis of 24-h BP
recordings in 167 patients with treatment-resistant
hypertension receiving renal denervation treatment: they
206 www.jhypertension.com
Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
report that renal denervation was associated with a
decrease in BP variability independent of BP level, suggest-
ing that responders may derive benefit from the BP vari-
ability reduction.
The SPRINT trial data have been reanalyzed by Ferreira
et al. (pp. 428–435) to relate absolute benefit and absolute
harm of more intense BP-lowering treatment: antihyper-
tensive treatment intensification was associated with lower
cardiovascular event rates, but increased the risk of adverse
events. However, mortality within 1 year of an efficacy
outcome was nearly three-fold higher than following a
safety (adverse) outcome. The authors conclude that hav-
ing adverse events has less weight when it comes to
therapeutic decisions. On the other hand, the risk of exces-
sive lowering of DBP was analyzed by Wokhlu et al.
(pp. 419–427) in data from the INVEST trial in hypertensive
patients with coronary heart disease: in these patients, the
mortality risk related to an achieved DBP lower than
69 mmHg was accentuated when SBP also achieved values
lower than 120 mmHg. Although being post-hoc and with
lost randomization, these analyses raise concern about
intense BP lowering in coronary patients.
The recommendation by the Eighth Joint National
Committee (JNC-8) to raise the BP target of antihyperten-
sive treatment in the elderly to values below 150/
90 mmHg has generated two studies published in the
current issue of the Journal of Hypertension. Asayama
et al. (pp. 410–418) publish an analysis of cardiovascular
mortality in young-old and old-old participants from
seven Japanese general populations, reporting that, irre-
spective of antihypertensive medication, the risk increase
of total cardiovascular and stroke mortality with elevation
of BP was significant among young-old, but did not reach
significance among old-old participants. Nayor et al.
(pp. 436–443) have calculated the incidence of cardio-
vascular disease in individuals whose BP manage-
ment strategy would change with adoption of the JNC-8
guidelines in two large, community-based cohorts, the
Framingham and Jackson Heart Studies and conclude
that adoption of the JNC-8 recommendation to treat BP
levels less aggressively in the elderly may be associated
with substantial residual cardiovascular disease risk. In
commenting these data in an accompanying editorial,
Currie and Delles (pp. 234–236) try to put them into
the current precision medicine landscape and suggest
that, to enter the precision medicine age also for the
diagnosis and treatment of hypertension, we have to
generate deeper phenotypic data by which to answer
questions about BP targets and several other current
controversies.
Three additional articles in this issue of the Journal
may have therapeutic implications. Dolmatova et al.
(pp. 237–242), examining data from the National Health
and Nutrition Examination Survey (1999–2012), find that
sodium intake has increased over the last two decades
among US individuals with hypertension, especially His-
panics and African Americans, and call for more effective
strategies and aggressive approaches to reduce the sodium
consumption among hypertensive adults. Mali et al.
(pp. 377–386) provide new evidence in mice that smooth
muscle cell stromal interacting molecule-1 disruption
Volume 36  Number 2  February 2018

protects the heart from myocardial infarction through
reduction of endoplasmic reticulum stress, oxidative stress,
mitogen-activated protein-kinase, apoptosis and inflamma-
tion. Azegami et al. (pp. 387–394) have developed an
intranasal vaccine that simultaneously targets hypertension
and pneumonia, consisting of nanogel incorporating angio-
tensin II type 1 receptor partial peptide conjugated with
pneumococcal surface protein A. Given intranasally to
Journal of Hypertension
Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
Mechanisms, diagnosis and therapy of hypertension
spontaneously hypertensive rats, the vaccine attenuated
the development of hypertension and protected the rats
from lethal pneumococcal infection.
ACKNOWLEDGEMENTS
Conflicts of interest
There are no conflicts of interest.
www.jhypertension.com 207