Editor’s Corner
Factors and consequences of hypertension
Alberto Zanchetti
T
he articles published in the current issue of the
Journal of Hypertension focus on risk factors for
the development of hypertension and on the
relationship of hypertension with cardiovascular disease.
Two articles illustrate the role of early-life exposure to risk
factors for development of hypertension and vascular
disease in adulthood. Yu et al. (pp. 63–68) report data
from the Dongfeng–Tongji cohort of participants born or
having spent their childhood during the Chinese famine of
1959–1961, the largest in recent human history, showing that
exposure to famine in early life increased the risk of hyper-
tension prevalence in adulthood. In an accompanying
editorial, Banegas (pp. 29–32) carefully reviews all studies
reporting the late health consequences of the Chinese famine
and concludes that, despite inconsistencies among studies,
practically all studies show that early-life environment is
critical for the role of hypertension in adult life. This suggests
that, to control the major diseases of adult life, it may be
necessary to improve not only the nutrition and environment
of adults but also the nutrition and environment of pregnant
mothers and small babies. Another study from China, how-
ever, reminds us that not only starvation but also overweight
in childhood influences blood pressure (BP) and vascular
damage in adulthood: investigating the Beijing Blood
Pressure Cohort, Yan et al. (pp. 47–54) found that BMI
and SBP in childhood predicted carotid intima–media thick-
ness in adulthood, and childhood BP predicted adulthood
pulse wave velocity. Another article from Brazil (Silva et al.,
pp. 39–46) shows that the obnoxious effects of excessive
BMI and waist circumference are maintained during
adulthood: in a longitudinal study in south Brazil, being
overweight, maintaining an elevated waist circumference
or having an annual rise of these measurements above
expected values increased the incidence of high BP.
Another major risk factor for hypertension, excessive salt
consumption, is the topic of a systematic review and meta-
analysis of studies on dietary salt intake in Indian adults:
Johnson et al. (pp. 3–9) have calculated an overall
mean salt intake of almost 11 g/day. Although the available
data leave some uncertainty, there is little doubt that popu-
lation salt consumption far exceeds the recommended
maximum of 5 g/person/day.
The impacts of hypertension and diabetes on mortality
have been investigated by Oh et al. (pp. 55–62) in the
community-dwelling older adults of the Rancho Bernardo
study in California: they report the novel finding that
hypertension is more strongly associated with all-cause
and cardiovascular mortality than diabetes. However,
having both risk factors confers some increase in the hazard
particularly of cardiovascular death.
Journal of Hypertension
Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.
BP variability has recently emerged as a relevant risk
factor for cardiovascular diseases. In the current issue,
Wang et al. (pp. 10–17) publish a meta-analysis of 23
publications reporting a significant, albeit moderate, associ-
ation of visit-to-visit SBP variability with all-cause mortality,
cardiovascular mortality, cardiovascular disease, coronary
disease and stroke. In another article, McDonald et al.
(pp. 140–147) have explored the role of 24-h ambulatory
BP variability on cognitive function changes over a 5-year
follow-up in community-dwelling people aged over
65 years, finding increased daytime BP variability to be
associated with poorer performance in various cognitive
functional indices. A third article focused on BP measure-
ments has assessed the accuracy of the SphygmoCor XCEL
device (Atcor Medical, Sydney, Australia) in measuring
central BP (Shoji et al., pp. 69–75).
A considerable number of articles are devoted to path-
ophysiological and clinical aspects of hypertension-related
vascular disease. Suvorava et al. (pp. 76–88), working on
mice, find that oxidative stress generated by endothelial-
specific expression of genetically destabilized C101A-endo-
thelial nitric oxide synthase (eNOS) selectively prevents
the BP-reducing activity of vascular eNOS, while having
no effect on aortic endothelium-dependent relaxation.
In a cohort of hypertensive women, treated with hydro-
chlorothiazide, and randomized either to magnesium
supplementation or placebo for 6 months, Cunha et al.
(pp. 89–97) found that magnesium supplementation was
associated with better BP control, improved endothelial
function and amelioration of subclinical atherosclerosis. In
an elegant technical study, Spronck et al. (pp. 98–104)
show that, although the arterial stiffness index ß and the
cardio-ankle vascular index (CAVI) are often considered to
be pressure-independent indices of arterial stiffness, they
are inherently BP-dependent, instead. In an accompanying
editorial commentary, Segers (pp. 33–35) remarks that this
dependency had gone unnoticed until now, despite its
obviousness. The good news, according to Segers, is that
Spronck et al. propose a very simple way to correct index ß
and CAVI for their pressure dependency. By no means, in
Segers’ opinion, the study by Spronck et al. is a reason to
Journal of Hypertension 2017, 35:1–2
Istituto Auxologico Italiano and Centro Interuniversitario Fisiologia Clinica e Iperten-
sione, Università degli Studi di Milano, Milan, Italy
Correspondence to Alberto Zanchetti, Istituto Auxologico Italiano and Centro Inter-
universitario Fisiologia Clinica e Ipertensione, Università di Milano, Milano, Milan, Italy.
E-mail: alberto.zanchetti@unimi.it
J Hypertens 35:1–2 Copyright ß 2016 Wolters Kluwer Health, Inc. All rights reserved.
DOI:10.1097/HJH.0000000000001186
www.jhypertension.com 1
Zanchetti
discourage the use of the ß stiffness index or derived
indices, once adequately corrected. In another article
(Maloberti et al., pp. 154–161), arterial stiffness (pulse wave
velocity) in treated hypertensive patients was found to be
significantly associated with annexin A5 plasma levels. In a
study of 125 families in the southeast of Brazil, carotid–
femoral pulse wave velocity was found to have intermedi-
ate heritability (Alvim et al., pp. 105–110). Another genetic
study (Thomsen et al., pp. pp. 132–139) has identified the
antihypertensive methylenetetrahydrofolate reductase gene
polymorphism rs17367504-G as a possible novel protective
locus for preeclampsia in a Norwegian cohort, although this
association did not replicate in an Australian preeclampsia
case–control cohort.
In a longitudinal study in a multiethnic cohort of
middle-aged men in United States of America, Guo et al.
(pp. 111–117) report that progression of brachial–ankle
pulse wave velocity is positively associated with the annual
change in SBP, but not its baseline level. In the authors’
opinion, this implies that, regardless of initial BP, effective
control of BP may be important to slow arterial wall
stiffening and hence reduce cardiovascular risk.
A few studies focus on sleep disturbances in hyperten-
sion. Janssen et al. (pp. 118–124) have used the endothelin
antagonist, bosentan, in a randomized, crossover, double-
blinded, placebo-controlled study to show that endothelin
contributes to the rise in systolic pressure, but not to the
increased muscle sympathetic nerve activity, in response to
acute hypoxia in patients with severe obstructive sleep
apnea. Tagetti et al. (pp. 125–131) have also investigated
endothelial function and arterial stiffness in obese children
with sleep-disordered breathing and found a significant
relationship between the apnea–hypopnea index and car-
otid distensibility, but not flow-mediated vasodilatation.
Obesity has also been the focus of the Moli-sani study,
investigating ECG criteria for defining left ventricular hyper-
trophy in obesity (Muiesan et al., pp. 162–169). Another
study in patients with treatment-resistant hypertension
associated with obstructive sleep apnea reports significant
BP reductions at 6 months from renal denervation in the
Global Symplicity registry (Linz et al., pp. 148–153).
Finally, four articles focus on important therapeutic
problems. Zhou et al. (pp. 18–26) have made a meta-
analysis of all randomized controlled trials assessing
the BP effects of metformin in nondiabetic patients. They
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Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.
report a significant, but quantitatively small, SBP decrease
(about 2 mmHg) compared with placebo, but a larger effect
(5/3 mmHg SBP/DBP) in patients with impaired glucose
tolerance and obesity. In their accompanying editorial,
Thomopoulos et al. (pp. 27–28) underline that, although
the number of selected studies was large (26 studies), the
total number of individuals was rather small (n ¼ 4113), and
BP assessment was not the primary purpose of the inves-
tigators in most of the studies. Because of these and other
limitations of available evidence, Thomopoulos et al. point
out that additional and appropriately designed clinical trials
are required before the antihypertensive effect of metfor-
min in individuals without diabetes is clearly established.
Chuang et al. (pp. 170–177), analyzing the National
Health Insurance Research Database in Taiwan, report that
spironolactone is associated with a significant lower risk of
prostate cancer in male patients and of bladder cancer in
women. In his editorial, Teo (pp. 36–38) comments that
the androgen receptor blocking properties of spironolac-
tone may be involved in cancer suppression, as suggested
by the demonstration of antiandrogenic therapy benefits in
the treatment of prostate cancers. However, in Teo’s
opinion, whether or not spironolactone can actually reduce
urinary tract cancers needs further confirmation, preferably
by randomized controlled trials.
Bokrantz et al. (pp. 188–197) have analyzed data of
57 822 hypertensive individuals in the Swedish Primary
Care Cardiovascular Database and confirmed that thiazide
therapy is associated with a reduced risk of osteoporotic
fractures. The effect was more pronounced in men and
increased with longer treatment, but treatment discontinu-
ation increased the risk of fractures.
Finally, Kulchaitanaroaj et al. (pp. 178–187) have made
an estimation of long-term costs and outcomes attributable
to a physician–pharmacist collaborative intervention for
treating hypertension in community-based medical offices
in the Midwest United States of America (compared
with physician management alone) and conclude that
team-based care appears to be a cost-effective strategy
for treating hypertension, particularly in high-risk patients.
ACKNOWLEDGEMENTS
Conflicts of interest
There are no conflicts of interest.
Volume 35  Number 1  January 2017