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Current Hypertension
Reviews
ISSN: 1573-4021
Current Hypertension Reviews
Volume 4, Number 4, November 2008
Contents
Aldosterone to Renin Ratio (ARR) in Clinical use,
with Reference to the Primary Care Setting: ARR to Whom, When,
How, What for? Pp. 227-233
Oliviero Olivieri, Francesca Pizzolo and Roberto Corrocher
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Hypertension and Cardiovascular Risk: The Importance
of a Global Approach to Risk Management in the Light of Current
Hypertension Guidelines Pp. 234-240
Sebastiano Sciarretta, Francesca Palano, Francesco Paneni,
Valentina Valenti, Giuliano Tocci, Andrea Ferrucci and Massimo
Volpe
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Article]
Hypertension in China: Past, Present, and Future
Pp. 241-244
Tak W. Kwan, Christine Yu, Yixiu Zheng, Joanne Kwan, Richard
A. Stein, Shaoliang Chen and Dayi Hu
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Role of Reactive Oxygen Species in Tumor Necrosis
Factor-alpha Induced Endothelial Dysfunction Pp.
245-255
Xiuping Chen, Bradley T. Andresen, Michael Hill, Jing
Zhang, Frank Booth and Cuihua Zhang
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Article]
Thiazide Diuretics: 50 Years and Beyond
Pp. 256-265
Michael E. Ernst and Richard H. Grimm, Jr
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Article]
Lifestyle Modifications in the Treatment of Hypertension
Pp. 266-274
Matthew T. Bennett, Andrew Ignaszewski and Scott A. Lear
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Article]
Hypertensive Left Ventricular Hypertrophy Regression:
Does It Matter? Pp. 275-288
Wadih Nadour and Robert W.W. Biederman
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Article]
Pharmacokinetic-Pharmacodynamic Modeling of Antihypertensive
Drugs: From Basic Research to Clinical Practice Pp.
289-302
Christian Höcht, Marcos A. Mayer, Javier A. W. Opezzo,
Facundo M. Bertera and Carlos A. Taira
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Article]
Endothelial Dysfunction in the Hypertensive State:
Mechanisms of Hypertensive Cardiovascular Complications
Pp. 303-312
Allison B. Reiss, Arup K. Nath, Bipasha Nath and Kamran
Anwar
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Article]
Abstracts
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Aldosterone to Renin Ratio (ARR) in Clinical use,
with Reference to the Primary Care Setting: ARR to Whom, When,
How, What for?
Oliviero Olivieri, Francesca Pizzolo and Roberto Corrocher
Compelling evidence indicates that primary aldosteronism
(PA) is the most frequent cause of secondary hypertension,
with an estimated prevalence ranging from 10 to 15% in the
population referred to specialist hypertension units. In clinical
practice, the aldosterone to renin ratio (ARR) is the cornerstone
of population screening, although difficulties in methodology
and thus in defining precise cut-off values still represent
an area of uncertainty.
In hypertensive subjects, the elevated ARR is a marker of
inappropriately high aldosterone secretion for the degree
of renin-angiotensin system activation, and often is the only
index capable of distinguish normokalemic PA from essential
hypertension. On the basis of such a high prevalence, it is
unclear whether ARR measurement should be reserved for selected
subgroups of patients, or extended to all hypertensive subjects
in the population as a whole. In unselected, nor-motensive
populations elevated aldosterone levels and elevated ARR have
recently been reported as predisposing factors to the subsequent
development of hypertension, raising the question of the optimal
timing for ARR measurement, especially in those with a family
history of hypertension in primary care.
In a large proportion of patients presenting elevated ARR
the diagnosis of PA is formally ruled out by confirmatory/exclusion
testing, although the clinical relevance of “inappropriate
aldosterone secretion” in these patients remains unclear.
May it serve as a predictor of the usefulness of mineralocorticoid
receptor antagonist treatment? These and related questions
will be examined in this review, particularly given clearly
unsatisfactory levels of BP control even in the populations
of Western countries.
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Hypertension and Cardiovascular Risk: The Importance of a
Global Approach to Risk Management in the Light of Current
Hypertension Guidelines
Sebastiano Sciarretta, Francesca Palano, Francesco Paneni,
Valentina Valenti, Giuliano Tocci, Andrea Ferrucci and Massimo
Volpe
Arterial hypertension is an hard cardiovascular risk
factor, being responsible for an high occurrence of cardiovascular
adverse events such as myocardial infarction, stroke and congestive
heart failure. However, hypertension rarely is the only contributor
to such events since in most of cases the presence of elevated
blood pressure values is associated with other conditions,
particularly obesity, hypercholesterolemia, atherogenic dyslipidemia
and diabetes mellitus. The presence of these conditions sensibly
increases the level of risk, thus leading to an high morbidity
and mortality. Indeed, most of adverse events related to hypertension
are observed in patients with a mild increase of blood pressure
levels suggesting that the concomitant presence of other risk
factors significantly contributes to the overall risk. Moreover,
it has been shown that untreated hypertension produces preclinical
damages on cardiovascular system (heart, kidneys, vessels),
further increasing the global risk. Indeed, left ventricular
hypertrophy, microalbuminuria and vascular alterations are
all in-dependent predictors of cardiovascular morbidity and
mortality. Based on these considerations, the current European
hypertension guidelines are now drawing the attention to the
concept of a global approach to cardiovascular risk in the
management of hypertension. In fact, this strategy can lead
to a better risk stratification of hypertensives based on
the integrated evaluation of their risk factors, thus guiding
the physicians to the choice of the most suitable therapeutic
strategy to reduce the global cardiovascular risk of these
patients.
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Hypertension in China: Past, Present, and Future
Tak W. Kwan, Christine Yu, Yixiu Zheng, Joanne Kwan, Richard
A. Stein, Shaoliang Chen and Dayi Hu
Since 1958 multiple national surveys have been carried
out to estimate the prevalence of hypertension in China. With
each passing decade the prevalence of hypertension rose significantly
(5-11%, 7.7%, 11%, and 24-27%, respectively for 1958, 1979-1980,
1991 and 2000). An obvious trend emerged in the 1980s that
prevalence increases from southern (23%) to northern (33%)
parts of China. A then popular concept that prevalence of
hypertension is lower in rural area of China due to poor living
conditions no longer held true. Urbanization and industrialization
are rapidly catching up in the rural areas as well. Interestingly,
the northern Liaoning province (considered to be rural China)
has a hypertension awareness of 27%. It is significantly lower
than the Chinese national rates of 43% and U.S. national rate
of 73%. The combination of low education along with sedentary
lifestyle and prevalence of a diet rich in salt and fat predispose
the rural population to a high risk for hypertension. Furthermore,
there is a significantly higher relative risk for stroke in
Chinese hypertensive patients than Caucasian. A 5mmHg increase
in blood pressure increases the risk of coronary heart disease
by 27% and stroke by 46% in Chinese and Japanese populations.
By treating 1000 hypertensive patients for 5 years, one could
prevent 39 strokes, 59 major cardiovascular complications
and 55 deaths. Promoting public awareness of hypertension
and healthy life style choices (especially in rural areas
of China) should be on the top of China’s public health
agenda.
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Role of Reactive Oxygen Species in Tumor Necrosis Factor-alpha
Induced Endothelial Dysfunction
Xiuping Chen, Bradley T. Andresen, Michael Hill, Jing
Zhang, Frank Booth and Cuihua Zhang
Endothelial cell injury and dysfunction are the major
triggers of pathophysiological processes leading to cardiovascular
disease. Endothelial dysfunction (ED) has been implicated
in atherosclerosis, hypertension, coronary artery disease,
vascular complications of diabetes, chronic renal failure,
insulin resistance and hypercholesterolemia. Although now
recognized as a class of physiological second messengers,
reactive oxygen species (ROS) are important mediators in cellular
injury, specifically, as a factor in endothelial cell damage.
Uncontrolled ROS production and/or decreased anti-oxidant
activity results in a deleterious state referred to as ‘oxidative
stress’. A candidate factor in causing ROS produc-tion
in endothelial cells is tumor necrosis factor alpha (TNF-α),
a pleiotropic inflammatory cytokine. TNF-α
has been shown to both be secreted by endothelial
cells and to induce intracellular ROS formation. These observations
provide a potential mechanism by which TNF-α
may activate and injure endothelial cells resulting
in ED. In this review, we focus on the relationship between
intracellular ROS formation and ED in endothelial cells or
blood vessels exposed to TNF-α
to provide insight into the role of this important
cytokine in cardiovascular disease.
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Thiazide Diuretics: 50 Years and Beyond
Michael E. Ernst and Richard H. Grimm, Jr
Since the introduction of chlorothiazide into clinical
practice in 1958, thiazide-type diuretics have weathered decades
of criticism and controversy. Fifty years later, they remain
the single most important class of antihypertensives available.
Numerous clinical trials across broad populations consistently
demonstrate superior reductions in cardiovascular outcomes
with thiazide-based regimens and most notably using the thiazide-like
diuretic, chlorthalidone. Recent evidence suggests there may
be important differences among thiazides that favor chlorthalidone
due to its longer half-life and duration of action. Despite
their proven record, thiazide diuretics continue to be scrutinized
for their well-known adverse metabolic profile, especially
hypokalemia. Glucose intolerance and incident diabetes with
diuretic therapy has received significant attention; however,
evidence from the ALLHAT study and others indicate the reductions
in cardiovascular outcomes with thiazides are also observed
in diabetics. Potassium depletion may be associated with diuretic
dysglycemia. To minimize the adverse metabolic profile of
thiazides, clinicians should preferentially use low doses.
Combinations with potassium-sparing agents, or with renin-angiotensin
system drugs such as angiotensin-converting enzyme inhibitors
or angiotensin receptor blockers should also be considered.
The last fifty years has seen remarkable advances in our understanding
and treatment of hypertension and thiazides remain the most
important pharmacologic advancement in our therapy of hypertension.
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Lifestyle Modifications in the Treatment of Hypertension
Matthew T. Bennett, Andrew Ignaszewski and Scott A. Lear
Having elevated blood pressure or hypertension increases
one's risk for renal failure, stroke, cardiovascular disease
and mortality. Therefore, timely and effective treatment of
hypertension can have dramatic implications on patient outcomes
and quality of life. Today, health care providers have a number
of treatment modalities at their disposal, one of which consists
of 'lifestyle therapy'. These therapies attempt to reduce
blood pressure by altering patient behaviour. Over the last
few decades, a number of key studies have highlighted the
benefit of lifestyle therapy for the treatment and reduction
of hypertension, so much so that all major hypertension associations
espouse the use of lifestyle therapy as a first line therapy
or in combination with pharmacological therapy. These lifestyle
therapies, which include alterations in diet (in-creasing
the amount of fruits and vegetables, reducing the amount of
dietary fat and simple carbohydrates), reducing dietary sodium,
participating in regular physical activity, reducing weight,
and psychosocial interventions, have been shown to dramatically
reduce blood pressure. Understanding the benefits and challenges
of implementing lifestyle therapies for the treatment of hypertension
can lead to better uptake of these practices and improve patient
outcomes.
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Hypertensive Left Ventricular Hypertrophy Regression: Does
It Matter?
Wadih Nadour and Robert W.W. Biederman
Hypertensive left ventricular hypertrophy (LVH) has a
devastating pathologic, clinical and socioeconomic impact.
The recognition of the consequences of hypertension, the incidence
of LVH and its subsequent long-term manifestations on our
population continues to increase. Escalating amounts of medical
resources are devoted towards the understanding of hypertension
and its treatment, all aimed in some part at decreasing, either
directly or indirectly, LVH. LVH is further complicated by
relatively inexpensive and inexact clinical tools to detect
its presence, namely EKG. While echo-cardiography has improved
the recognition of LVH, more recent data demonstrate that
cardiovascular MRI (CMR) is the ‘gold standard’
for its quantitation.
In this review article, we aim to delineate the pathology
of hypertrophy at the level of the myocyte and interstitium,
incor-porating new data that suggests the interstitium plays
a heretofore unknown, but increasing role in the pathogenesis
of LVH. We will review the pathophysiology of LVH as it relates
to morbidity and mortality while reviewing the current tools
for detecting LVH. Most importantly, we will review the studies
that answer the question of whether LVH does matter. Specifically,
we will review classical studies that, while demonstrating
LVH’s importance, failed to show that LVH regression
led to substantial improvement in clinical outcome, while
such recent studies, such as the LIFE study, have pointed
to the primacy of LVH, not only as a surrogate marker for
cardiovascular morbidity and mortality, but suggesting that
its regression offers major impact into cardiovascular disease
with potential long-term socioeconomic benefits. Herein, the
impact of myocardial performance using advanced technologies
such as CMR is illustrated as an ideal tool for understanding
more complex pathophysiologic perturbations. Finally, and
most intriguing, is a threshold of LVH in g/m² that we
suggest as a potential pharmacologic goal in order to institute
a clinically meaningful impact of LVH regression.
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Pharmacokinetic-Pharmacodynamic Modeling of Antihypertensive
Drugs: From Basic Research to Clinical Practice
Christian Höcht, Marcos A. Mayer, Javier A. W. Opezzo,
Facundo M. Bertera and Carlos A. Taira
Knowledge of pharmacokinetic-pharmacodynamic (PK/PD)
properties of antihypertensive drugs may optimize drug therapy
of hypertension. PK/PD modeling of antihypertensive drugs
in both basic and clinical research could contribute to drug
development and clinical practice in several aspects, including
a profound evaluation of the efficacy and safety of investigational
antihypertensive agents, enhancement of preclinical information
during the development process, identification of factors
that contribute to drug response variability, by allowing
a rapid identification of poor or non-responders and by helping
to determine optimal antihypertensive drug and dose requirements
in each hypertensive patient. Although a concentration-response
relationship for antihypertensive agents was found in normotensive
and hypertensive patients, there are some limitations in PK/PD
modeling of antihypertensive drugs in the clinical setting,
including application of inadequate pharmacodynamic models
and the inability to study large doses of antihypertensive
drugs in order to determine the complete pharmacodynamic range
of their antihypertensive effect. Most limitations in the
clinical study of PK/PD models of antihypertensive drugs are
not present in basic research, and therefore study of PK/PD
models in laboratory animals could be of interest. The aim
of the present review is to describe the current knowledge
of PK/PD modeling of antihypertensive drugs in basic and clinical
research and its future applications.
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Article]
Endothelial Dysfunction in the Hypertensive State: Mechanisms
of Hypertensive Cardiovascular Complications
Allison B. Reiss, Arup K. Nath, Bipasha Nath and Kamran
Anwar
Hypertension is a common public health concern that leads
to significant cardiovascular morbidity and mortality worldwide.
Blood pressure control is very important in clinical practice
to reduce end organ complications such as stroke, myocardial
infarction, heart failure, and kidney disease. Untreated hypertension
leads to endothelial dysfunction by triggering oxidative stress
and a proinflammatory state. Under these conditions, there
is increased production of vasocon-strictor prostanoids and
reactive oxygen species that cause inactivation of nitric
oxide. The reduced nitric oxide bioavailability that characterizes
endothelial dysfunction may incite important steps in the
appearance and progression of atherosclerotic lesions, including
monocyte and leukocyte adhesion, vascular smooth muscle proliferation,
and platelet activa-tion. This article will review mechanisms
by which persistent endothelial dysfunction directly relates
to the development of clinically relevant cardiovascular events.
The presence of endothelial dysfunction as indicated by an
impaired vasodilatory response to acetylcholine may serve
as a marker of future cardiovascular events in patients with
essential hypertension. We will also discuss some of the evidence,
both experimental and clinical, that available pharmacologic
treatment may reverse hypertension-associated endothelial
dysfunction. This may represent a new target for therapeutic
intervention in essential hypertension.
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