Editors Corner
Problems of antihypertensive management: diabetes
mellitus, ethnic differences, organ damage and
resistance to treatment
Alberto Zanchetti
S
everal problematic aspects of hypertension manage-
ment have been investigated in studies published in
the current issue of the Journal of Hypertension.
A group of four studies focus on cardiovascular aspects
of diabetes and their therapeutic management. In indivi-
duals from the Maastricht Study, Veugen et al. (pp. 1052
1060) find that the systolicdiastolic difference in carotid
stiffness is increased in type 2 diabetes, probably a result
from accelerated arterial wall matrix remodeling, but this
increase is not observed in prediabetes. Dasgupta et al.
(pp. 10611069) have studied carotidfemoral pulse wave
velocity, as risk indicator, in a cohort of patients with type 2
diabetes and hypertension and report that physical activity,
quantitatively measured by an accelerometer, has an added
beneficial value on top of good risk control by cardio-
protective medications. Thomopoulos et al. (pp. 922944)
publish the results of a set of comprehensive meta-analyses
comparing the effects of blood pressure (BP)-lowering
treatment in hypertensive patients with and without
diabetes. Contrary to past recommendations, in diabetes
there is little or no further benefit in lowering SBP below
130 mmHg, whereas continuing benefit is seen in the
absence of diabetes also at SBP below 130 mmHg.
Thomopoulos et al. also find that, although all BP-lowering
drugs can beneficially be prescribed in hypertensive
patients with diabetes, there are some additional cardio-
vascular and renal benefits by including a reninangioten-
sin system blocker in the treatment program. Kumarathurai
et al. (pp. 10701078) have investigated whether the
BP-lowering effect of the GLP-1 receptor agonist liraglutide,
as previously shown in clinical trials using office BP
measurements, is also supported by ambulatory BP
measurements, and report no BP-lowering effect of liraglu-
tide could be demonstrated in a small placebo-controlled
trial using 24-h ambulatory BP monitoring. In an editorial,
Nilsson (pp. 953954) comments that the cardiovascular
benefits so far demonstrated by liraglutide and other
GPL-receptor agonists remain enigmatic, and suggests
the effects of these compounds on central hemodynamics
and aortic stiffness should be investigated. Randomized
controlled trials of BP and lipid lowering are also the
objective of a meta-analysis of Hirakawa et al. (pp. 905
913), who have identified 13 BP-lowering and 10 lipid-
lowering trials with a prolonged follow-up after the
termination of the randomized treatment, thus allowing
the evaluation of the long-term effects of these therapeutic
Journal of Hypertension
Copyright 2017 Wolters Kluwer Health, Inc. All rights reserved.
approaches: the authors report that the benefits of both
types of treatment on all-cause and cardiovascular mortality
were persistent, but attenuated after discontinuation of
randomized treatment, indicating the importance of
continuing therapy.
Three studies are focused on ethnic aspects of hyperten-
sion. Mokwatsi et al. (pp. 960967) find that already at age
68 years black boys in South Africa, as compared with
white boys from similar schools, have increased arterial
stiffness in all sections of the arterial tree, along with higher
DBP, carotid intimamedia thickness and advanced glyca-
tion end products. Chiang et al. (pp. 968974) have inves-
tigated the association of 25-hydroxyvitamin D and BP in
young adults with African ancestry in the United States,
South Africa, Ghana, Jamaica, and Seychelles, reporting
that the association is strongest when the vitamin D levels
are lower than 20 ng/ml. Sherwood et al. (pp. 975981)
have tested responsiveness of b-adrenergic and a-adrener-
gic receptors in the early stages of hypertension, and
shown that a blunted b-adrenergic responsiveness and
an enhanced a-adrenergic responsiveness are especially
evident in African Americans.
Hypertension-associated organ damage is the focus of
another group of studies. Van Mil et al. (pp. 10261034)
have studied carotid artery reactivity to a cold pressor test
and reported that lower carotid reactivity is associated with
older age and number of cardiovascular risk factors. As
carotid reactivity is correlated with coronary artery
responses to the cold pressor test, the authors suggest
carotid reactivity may represent a valuable technique to
assess cardiovascular risk. Agabiti Rosei and Rizzoni
(pp. 914921) review the considerable evidence accumu-
lated in recent years, also through their personal work, that
changes in microvascular structure (mostly subcutaneous
small resistance arteries) may have a significant prognostic
relevance, and remark that new techniques for the
Journal of Hypertension 2017, 35:903904
Centro Interuniversitario Fisiologia Clinica e Ipertensione, Universita` degli Studi di
Milano, and Istituto Auxologico Italiano, Milan, Italy
Correspondence to Professor Alberto Zanchetti, Istituto Auxologico Italiano IRCCS
and Centro Interuniversitario di Fisiologia Clinica e Ipertensione, Universita` 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
J Hypertens 35:903904 Copyright 2017 Wolters Kluwer Health, Inc. All rights
reserved.
DOI:10.1097/HJH.0000000000001334
www.jhypertension.com 903
Zanchetti
evaluation of microvascular morphology in the retina may
represent a noninvasive technique allowing a more exten-
sive predictive use of microvascular changes. In an accom-
panying editorial, Heagerty (pp. 945946) suggests that
also confocal microscopy of the nail fold vasculature
may be an alternative noninvasive approach. The cardio-
vascular predictive role of renal microvascular dysfunction
has been investigated by Nemcsik et al. (pp. 11091118) in
patients with nondialyzed chronic kidney disease. They
report that postocclusive reactive hyperemia assessed by
laser Doppler flowmetry has a predictive role, but the
robustness of traditional risk factors outweighs the predic-
tive role of microvascular biomarkers. In commenting these
data, Bruneau (pp. 958959) remarks that, nonetheless,
Nemcsik et al.s findings offer promise for the potential use
of laser Doppler flowmetry as an early assessment tool to
detect subclinical microvascular dysfunction in the kidney.
Alterations in fibrin clot properties are described in hyper-
tensive patients with, but not without, obstructive sleep
apnea by Jozwik-Plebanek et al. (pp. 10351043): the
relationship of these clot alterations with sleep apnea are
supported by their improvement after 3 months with con-
tinuous positive airway pressure treatment. In an accom-
panying editorial, Doumas et al. (pp. 950952) comment
that it would be really important and clinically meaningful
to assess the link of fibrin clot properties with severity of
obstructive sleep apnea. Cognitive decline is another of the
possible complications of hypertension in the elderly, and
Li et al., (pp. 10441051) have explored executive and
memory abilities in a group of elderly hypertensive patients
(and controls) in the context of a functional magnetic
resonance study, finding a relationship between worsening
of cognitive function and altered patterns of activation of
fronto-parietal cortex.
The problem of resistance to treatment is dealt with in
three studies in the current issue. Schneider et al.
(pp. 10861092) have conducted a randomized double-
blind trial in 51 patients with treatment-resistant hyperten-
sion, comparing a similar BP reduction produced either by
adding the mineralocorticoid receptor antagonist eplere-
none or other antihypertensive agents. After a 6-month
follow-up only patients allocated to eplerenone had a
significant reduction of left ventricular mass (precisely
measured by magnetic resonance imaging). These interest-
ing data suggest the mineralocorticoid receptor antagonists
should be used preferentially to achieve an effective
reduction of left ventricular hypertrophy in difficult to treat
hypertensive patients. Rosa et al. (pp. 10931099) publish
the 24-month results of a randomized trial in true resistant
hypertension (elevated BP confirmed by ambulatory
monitoring, treatment with more than five drugs, adher-
ence to treatment verified at baseline), showing that renal
denervation was well tolerated and without any serious
adverse effects, but its BP-lowering effect was not superior
to that of intensified medical treatment including spirono-
lactone. In an accompanying editorial, Hamdidouche and
Boutouyrie (pp. 955957) discuss whether renal denerva-
tion can be considered as an alternative or a complement in
904 www.jhypertension.com
Copyright 2017 Wolters Kluwer Health, Inc. All rights reserved.
the management of resistant hypertension. In another study
on renal denervation, Tsioufis et al. (pp. 11001108) report
that in a group of hypertensive patients with the metabolic
syndrome, this procedure does not only reduce elevated
muscle sympathetic activity at rest, but also restores its
responsiveness to a standard glucose tolerance test, without
significantly changing, however, the HOMA-IR response.
There are other interesting studies in the current issue of
the Journal, touching other aspects of hypertension
research. Scheepers et al. (pp. 982993) have done
cross-sectional analyses in school-age children from the
Dutch KOALA Birth Cohort Study, and found that uric acid
and the ratios of uric acid/xanthine and xanthine/
hypoxanthine were significantly associated with DBP,
suggesting that both uric acid concentration and increased
xanthine oxidase activity are associated with BP. The cur-
rent interest in the relationships between uric acid and BP is
also witnessed by another study on this topic: Saladini et al.
(pp. 9941001), in a cohort of young to middle-aged study
participants prospectively followed up for about 11 years,
report that serum uric acid was a predictor of hypertension,
and suggest that exercise may counteract the mechanisms
involved in the association between hyperuricemia and
future hypertension.
Three studies focus on problems of BP measurement.
Benmira et al. (pp. 10021010), considering that the widely
used oscillometric methods only measure mean BP and
estimate SBP and DBP using various undisclosed algo-
rithms, present a new technique measuring the time interval
from the foot to the apex of the SBP peak of the oscillo-
metric signal, which in their study yielded excellent corre-
lations with SBP values determined by the auscultatory
method. Vinyoles et al. (pp. 10111018), analyzing data
from the large Spanish Ambulatory BP Monitoring Registry,
report that a 24-h ambulatory pulse pressure of 50 mmHg
is the value that best corresponds to an office pulse pressure
60 mmHg. Shaw et al. (pp. 10191025) have tested the
reliability of a sit-to-stand manoeuvre to diagnose ortho-
static hypotension in cases where a supine-to-standing
manoeuvre cannot be performed, and suggest that a SBP
drop at least 15 mmHg or a DBP drop at least 7 mmHg are
useful criteria. These results are discussed in an accompa-
nying commentary by Casiglia and Jordan (pp. 947949),
who remark that the lower BP threshold for diagnosis
mandates particularly careful BP measurements, and
suggest that, whenever possible, the usual supine-to-
upright test should be applied.
Finally, Murata et al. (pp. 10791085) review a large
number of consecutive cases of primary aldosteronism and
conclude that cases with plasma aldosterone within the
normal range are associated with a lower cardio and
cerebrovascular risk than cases with high plasma aldoster-
one concentrations.
ACKNOWLEDGEMENTS
Conflicts of interest
There are no conflicts of interest.
Volume 35  Number 5  May 2017