Current
Hypertension Reviews
ISSN: 1573-4021
Current Hypertension Reviews
Volume 3, Number 2, May 2007
Contents
Silent Cerebral Damage in Hypertension Pp.
83-88
Cristina Sierra and Antonio Coca
[Abstract]
Reliability of Blood Pressure Patterns Defined by
a Single 24-Hour Ambulatory Blood Pressure Monitoring: The
Case of the Dipping/Non Dipping and Isolated Clinic Hypertension
Pp. 89-92
Cesare Cuspidi, Carla Sala, Alberto Zanchetti and Giuseppe
Mancia
[Abstract]
Hypothyroidism and Atherosclerosis-Possible Implication
of the Renin-Angiotensin System Pp. 93-96
Toshihiro Ichiki
[Abstract]
Interplay Between ACE2 and Angiotensin-(1-7) in the
Regulation of Blood Pressure Pp. 97-104
Carlos M. Ferrario and Jewell A. Jessup
[Abstract]
Brain Angiotensin and Cardiovascular Reactivity to
Negative and Positive Emotional Stress Pp. 105-117
Dmitry N. Mayorov
[Abstract]
Detection and Treatment of Alcohol-Induced Hypertension
Pp. 119-127
Scott H. Stewart and Peter M. Miller
[Abstract]
Potential Contribution of Action of Renin Angiotensin
System to Bone Metabolism Pp. 129-132
Hironori Nakagami, Mariana Kiomy Osako, Hideo Shimizu,
Rie Hanayama and Ryuichi Morishita
[Abstract]
Early Vascular Ageing and Hypertension – A New
Model for Understanding Cardiovascular Risk Pp. 133-136
Peter M. Nilsson
[Abstract]
Hypertensive Heart Disease and the Role of Aldosterone
Antagonists Pp. 137-142
Chanwit Roongsritong, Ashwani Kumar and Leigh Ann Jenkins
[Abstract]
Aldosterone and Resistant Hypertension Pp.
143-147
Andrea Semplicini, Michelangelo Sartori and Lorenzo A.
Calò
[Abstract]
Anti-Vascular Endothelial Growth Factor (VEGF) Therapy:
A New Cause of Hypertension Pp. 149-155
Xiaolei Zhu and Mark A. Perazell
[Abstract]
Abstracts
[Back to top]
Silent Cerebral Damage in Hypertension
Cristina Sierra and Antonio Coca
Stroke is the third most-frequent cause of death after cancer
and heart disease in developed countries, and is one of the
most common reasons for developing cognitive impairment and
vascular dementia. Hypertension is known to be the most important
factor for developing stroke and vascular dementia. In addition,
the presence of cerebral white matter lesions (WML) is an
important prognostic factor for the development of stroke,
cognitive impairment and dementia. Older age and hypertension
are constantly reported to be the main risk factors for cerebral
WML. Hypertensive patients have a higher rate and extent of
areas of cerebral WML compared with normotensives and, among
hypertensive patients, treated uncontrolled patients have
higher rates of WML than those who are controlled. Recent
evidence strongly supports the idea that the presence of cerebral
WML in hypertensive patients should be considered a silent
early marker of brain damage.
[Back to top]
Reliability of Blood Pressure Patterns Defined by
a Single 24-Hour Ambulatory Blood Pressure Monitoring: The
Case of the Dipping/Non Dipping and Isolated Clinic Hypertension
Cesare Cuspidi, Carla Sala, Alberto Zanchetti and Giuseppe
Mancia
Classification of hypertensive subjects according to different
blood pressure patterns : i.e sustained vs isolated clinic
hypertension (ICH) , dipping vs non dipping is now regarded
as a useful mean for a more precise individual risk stratification
and therapeutic making decisions. However, this subdivision
is routinely based on a single ambulatory blood pressure monitoring
(ABPM), despite the well-known day-to-day variability in blood
pressure due to variations in mental, physical and environmental
stimuli.
In this short review we have tried to answer the following
question : how reliable is the classification of non-dipping
and ICH pattern based on single 24-h ABPM recording?
Data from the recent literature clearly indicate that these
categorizations in non diabetic mild to moderate hypertensive
patients on the basis of a single ABPM are highly unreliable
, as a large fraction of subjects (20-50%) classified in these
categories at the first ABPM, do not confirm the same BP pattern
during a second ABPM.
Thus, these findings support the idea that a more reliable
classification of patients according to dipping/nondipping
status or ICH vs sustained hypertension should be performed
by repeating a second ABPM within a short-term period.
[Back to top]
Hypothyroidism and Atherosclerosis-Possible Implication
of the Renin-Angiotensin System
Toshihiro Ichiki
Clinical and autopsy studies have suggested that patients
with hypothyroidism have more advanced coronary atherosclerosis.
The accelerated atherosclerosis has been explained by increases
in low density lipoprotein cholesterol, blood pressure and
newer risk factors such as homocysteine, C-reactive protein
and plasminogen activator inhibitor-1 in hypothyroid state.
In addition, recent studies have suggested that thyroid hormone
has a direct effect on blood vessel, which may attenuate the
progression of atherosclerosis. In addition to a direct relaxation
of blood vessel through non-genomic effect, thyroid hormone
has been reported to induce production of adrenomedullin and
adenosine in vascular smooth muscle cells, which may be involved
in vasodilation. Thyroid hormone also inhibits angiotensin
II type1 receptor expression and signal transduction, and
attenuates neointimal formation after balloon injury. These
data suggest that thyroid hormone inhibits atherogenesis through
direct effects on the vasculature as well as modifying risk
factors.
[Back to top]
Interplay Between ACE2 and Angiotensin-(1-7) in the
Regulation of Blood Pressure
Carlos M. Ferrario and Jewell A. Jessup
The primacy of angiotensin II (Ang II) as the critical component
mediating the multiple biological actions of the renin angiotensin
system is undergoing a critical revision given the growth
of the biochemical and physiological evidence demonstrating
the existence of other proteins that, within the system, lead
to the formation of alternate forms of angiotensin peptides.
The persistent notion that Ang II is at the center of the
mechanisms of action by which the renin angiotensin system
exerts complex and pleiotropic effects on cellular growth,
metabolism, and contraction has been challenged by the emerging
understanding of the biochemical pathways entailing expression
and function of the vasodilator/anti-growth properties of
angiotensin-(1-7) [Ang-(1-7)], the role of the mas
receptor as its ligand, and the cloning of a homologue of
angiotensin converting enzyme (ACE2), which may limit the
actions of Ang II by converting the peptide into Ang-(1-7).
We analyze in this article the biochemical processing pathways
leading to the formation of Ang-(1-7) from both angiotensin
I and Ang II within the context of a functional paradigm that
suggests that a deficit in the functional activity of the
arm of the renin angiotensin system [ACE2/Ang-(1-7)/mas receptor]
may play a critical role in the pathogenesis of hypertension.
[Back to top]
Brain Angiotensin and Cardiovascular Reactivity to
Negative and Positive Emotional Stress
Dmitry N. Mayorov
Cardiovascular reactivity, an abrupt increase in blood pressure
and heart rate in response to negative emotional stress is
a risk factor for hypertension and heart disease. Brain angiotensin
II (Ang II) has been recognized as an important regulator
of cardiovascular reactivity. Apart from threatening events,
exposure to appetitive stimuli is capable of inducing a distinct,
sympathetically mediated rise in blood pressure in both animals
and humans. Recent animal studies employing microinjection
of AT1 receptor antagonists
directly into hypothalamic and brainstem nuclei indicate that
locally released AngII acts to facilitate, through a superoxide-dependent
mechanism, the pressor response to negative stress. Conversely,
animal studies demonstrated that brain Ang II is less important
in the regulation of cardiovascular arousal associated with
positively motivated behavior, such as anticipation and consumption
of palatable food. Thus, endogenous AngII in the brain appears
to control the activation of central pathways primarily associated
with the defense response, rather than non-specifically modulating
cardiovascular reactivity regardless of emotional valence
(attraction or aversion) of stimuli. These findings may be
of clinical importance as they suggest that targeted inhibition
of Ang II -superoxide signaling in the brain may selectively
reduce blood pressure reactivity to negative emotional stress,
without affecting cardiovascular arousal associated with normal
daily activities.
[Back to top]
Detection and Treatment of Alcohol-Induced Hypertension
Scott H. Stewart and Peter M. Miller
Heavy alcohol use causes or exacerbates a number of medical
conditions. In particular, hypertension (HTN), the most common
primary diagnosis in primary care, is particularly alcohol-sensitive.
In patients with HTN, excessive alcohol use (3 or more drinks
a day) can interfere with successful blood pressure control
and facilitate disease complications. Excessive alcohol use
is one of 6 major causes of treatment-resistant HTN. This
article summarizes the literature on the relationship between
excessive drinking and HTN as well as findings supporting
a beneficial BP-lowering impact of routine alcohol screening
and intervention with hypertensive adults. Screening specifically
for alcohol-induced hypertension rather than an alcohol use
disorder per se is emphasized. Recent health services investigations
have also addressed the problem of practical implementation
of HTN alcohol screening in busy medical settings. These findings
have important implications for the successful management
of HTN patients in general and treatment-resistant HTN patients
in particular.
[Back to top]
Potential Contribution of Action of Renin Angiotensin
System to Bone Metabolism
Hironori Nakagami, Mariana Kiomy Osako, Hideo Shimizu,
Rie Hanayama and Ryuichi Morishita
Bone metabolism is closely regulated by hormones and cytokines,
which have effects on both bone resorption and deposition.
Since renin-angiotensin system (RAS) has been known to play
an important role to regulate remodeling in several tissues,
we focused on the potential role of RAS in bone metabolism.
It is known that the receptors of angiotensin II are expressed
in culture osteoclasts and osteoblasts, and angiotensin II
is postulated to be able to act upon the cells involved in
bone metabolism: osteoblasts and osteoclasts; and to regulate
blood flow in bone marrow capillaries. In in vitro
system, angiotensin II induced the differentiation and activation
of osteoclasts responsible for bone resorption and the pro-liferation
of osteoblast-rich populations of cells. As it has been known
that osteoclast differentiation is regulated by a variety
of hormones, local factors and inflammatory cytokines, such
as IL-1 and TNF-α,
RAS might also be involved in this autocrine system. In another
aspect of RAS, angiotensin II can also regulate blood flow
in bone marrow capillaries. Since recent evidence suggests
that blood flow can be important to the development of matured
bone, the blockade of renin-angiotensin system may improve
blood flow in bone marrow capillaries, which consequently
enhances bone formation.
Of importance, sub-analysis of recent clinical study demonstrated
that the usage of angiotensin-converting enzyme inhibitors
significantly reduced the fracture risk. RAS might be a novel
target to treat the subgroups of hypertensive patients with
osteoporosis.
[Back to top]
Early Vascular Ageing and Hypertension – A New
Model for Understanding Cardiovascular Risk
Peter M. Nilsson
Many individuals do not appear to have matching chronological
and biological age, as evaluated by their general outlook,
physical examination, or clinical investigations. One aspect
of this is the concept of early vascular ageing. This could
be useful both in research and clinical practice to understand
and treat the increased cardiovascular risk in many patients,
e.g. with hypertension in poor control. New ways of measuring
biological ageing have been introduced, for example telomere
length (“mitotic senescence”) that has now been
explored in observational studies, and is promising to use
also to evaluate biological effects in intervention studies.
If the process of vascular ageing could be better understood,
as well as its genetic and environmental correlates, new and
better ways of offering preventive strategies to risk individu-als
could be formed. Smoking cessation is one of the classical
ways to counteract biological and vascular ageing, but a variety
of drugs could also be of potential importance in this respect,
e.g. statins, blockers of the renin-angiotensin system, metformin
and glitazones. This has to be evaluated in prospective studies,
but pravastatin has already been shown to attenuate the associate
between short telomere length and risk of coronary heart disease
in the WOSCOP study in high-risk Scottish men.
[Back to top]
Hypertensive Heart Disease and the Role of Aldosterone
Antagonists
Chanwit Roongsritong, Ashwani Kumar and Leigh Ann Jenkins
Hypertensive heart disease (HHD) encompasses a spectrum of
abnormalities resulting from structural and functional adaptations
to chronic pressure overload. The clinical manifestations
of HHD range from asymptomatic left ventricular hypertrophy
(LVH) to symptomatic heart failure. HHD has been associated
with increased risk of cardiovascular morbidity and all cause
mortality. However, regression of LVH by antihypertensive
therapy has been associated with improved outcome.
The pathogenesis of HHD involves various hemodynamic and nonhemodynamic
factors including neurohormone, aldosterone. Aldosterone enhances
myocardial fibrosis through its direct effect on mineralocorticoid
and angiotensin II receptors leading to excessive collagen
deposition within the myocardium. Increased myocardial fibrosis
is a major determinant of hypertensive remodeling and the
transition to heart failure.
Aldosterone antagonists are effective antihypertensive agents.
Additionally, they have been shown to improve LV structural
remodeling, systolic and diastolic function in patients with
HHD independent of its effect on blood pressure. Data on long-term
benefit of these agents have thus far been limited to patients
with advanced systolic heart failure and post-acute myocardial
infarction LV systolic dysfunction. The potential benefit
of aldosterone antagonists in patients with heart failure
and preserved LV systolic function is currently being investigated
in large scale clinical trials.
[Back to top]
Aldosterone and Resistant Hypertension
Andrea Semplicini, Michelangelo Sartori and Lorenzo A.
Calò
Refractory or resistant hypertension, defined as the failure
to control systolic (<140 mmHg) and/or diastolic blood
pressure (< 90 mmHg) despite the use of three or more different
classes of antihypertensive agents, is a common problem in
clinical practice. Several factors induce treatment resistance,
especially secondary hypertension, such as primary aldosteronism.
Some authors have argued for a direct role of aldosterone
autonomy as a mechanism for drug resistance and have recommended
the search for primary aldosteronism in cases of severe or
resistant hypertension. This proposal is further supported
by the demonstration of antihypertensive efficacy of aldosterone
antagonists in patients with refractory hypertension. Recently,
we have demonstrated a direct role of aldosterone excess as
a mechanism for drug resistance, since patients with elevated
aldosterone plasma levels develop resistant hypertension,
even in the absence of clinically diagnosed primary aldosteronism.
The mechanism of resistance may be ascribed to increased plasma
volume, regardless of renal function, and cardiovascular remodeling.
The present review highlights the role of aldosterone excess
as a cause of treatment resistance beyond true primary aldosteronism
and provides a conceptual framework for the use of aldosterone
antagonists in patients with resistant hypertension.
[Back to top]
Anti-Vascular Endothelial Growth Factor (VEGF) Therapy:
A New Cause of Hypertension
Xiaolei Zhu and Mark A. Perazell
Vascular endothelial growth factor (VEGF) is a potent angiogenic
factor that has multiple effects on the vascular endothelium
and many other cells. Many cancers utilize VEGF for proliferation,
progression and metastasis, making it a logical target of
anti-tumor therapy. Numerous clinical oncology trials have
employed this therapeutic approach to effectively treat various
malignancies. Hypertension has emerged as one of the most
important adverse effects of anti-VEGF therapy. This is supported
by multiple clinical trials, using either anti-VEGF antibody,
or small molecules targeting VEGF receptor tyrosine kinases.
The incidence of hypertension associated with anti-VEGF antibody
therapy ranges from 11 to 32% in most phase III clinical trials,
while the incidence is about 16 to 43% with therapy targeted
at VEGF receptors. The mechanisms underlying anti-VEGF associated
hypertension are not understood. Several potential mechanisms
have been proposed including vascular rarefaction, endothelial
dysfunction, altered nitric oxide metabolism and aberrant
neurohormones. More importantly, anti-VEGF related hypertension
may have significant clinical implications. Poorly controlled
hypertension may be associated with worsening cardiac and
renal function, and reversible posterior encephalopathy syndrome.
Further studies should focus on uncovering the mechanisms
of anti-VEGF induced hypertension, as well as guiding therapy
for this adverse effect.
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