Current
Hypertension Reviews
ISSN: 1573-4021
Current Hypertension Reviews
Volume 3, Number 3, August 2007
Contents
Functional Genomics of the Oxidative Stress Pathway
Pp. 156-165
Christian Delles, María U. Moreno, Sandosh Padmanabhan,
Delyth Graham, Martin W. McBride and Anna F. Dominiczak
[Abstract]
Hypertension, Cognitive Impairment and Dementia:
An Epidemiological Perspective Pp. 166-176
Christiane Reitz and José A. Luchsinger
[Abstract]
Postmenopausal Hypertension: Insights from Rat
Models Pp. 177-181
Licy L. Yanes, Lourdes A. Fortepiani, Julio C. Sartori-Valinotti,
Radu Iliescu and Jane F. Reckelhoff
[Abstract]
Prevention and Management of Hypertension Without
Drugs Pp. 182-195
Saverio Stranges and Francesco P. Cappuccio
[Abstract]
Evaluation of Intermediate Endpoints: Clinical Implications
in the Management of Arterial Hypertension Pp. 196-202
Massimo Volpe and Giuliano Tocci
[Abstract]
The Relevance of Long-Term Adherence to Non Pharmacological
and Pharmacological Treatment of Hypertension Pp.
203-207
Bernard Waeber and François Feihl
[Abstract]
The Role of Adipokines in Hypertension and Cardiovascular
Disease Pp. 208-215
Andrew M. Wilson and Marno C. Ryan
[Abstract]
Arterial Stiffness and Hypertension: A Review of Mechanism
and Clinical Relevance Pp. 216-222
Julia Wong
[Abstract]
Hemolysis-Associated Pulmonary Hypertension in Sickle
Cell Disease: Global Disruption of the Arginine-Nitric Oxide
Pathway Pp. 223-230
Claudia R. Morris
[Abstract]
Abstracts
[Back to top]
Functional Genomics of the Oxidative Stress
Pathway
Christian Delles, María U. Moreno, Sandosh Padmanabhan,
Delyth Graham, Martin W. McBride and Anna F. Dominiczak
Oxidative stress plays an important role in the pathogenesis
of a variety of disorders including cardiovascular disease.
Understanding the genetic background of increased oxidative
stress will facilitate targeted prevention and therapy of
these diseases. Strategies to analyse genomics of oxidative
stress include genome scans in rodent models, construction
of congenic animals and candidate gene approaches. A new family
of candidate genes for human cardiovascular disease, glutathione
S-transferases (GSTMs), have been derived from experiments
in congenic rats. Knowledge of the physiology of superoxide
production led to analysis of genetic variants of the CYBA
gene encoding the p22phox unit of NADPH oxidase. Against the
background of rapidly evolving genotyping technology we are
currently facing challenges in accurate phenotyping and biomarker
development to measure oxidative stress, together with the
need to develop new statistical paradigms to encompass gene-gene
and gene-environment interactions.
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Hypertension, Cognitive Impairment and Dementia:
An Epidemiological Perspective
Christiane Reitz and José A. Luchsinger
There is increasing interest in the relation of blood pressure
with cognitive function and dementia. While some cross-sectional
studies have shown an inverse association between blood pressure
levels and cognitive impairment or dementia, longitudinal
studies have yielded controversial results. Most studies relating
blood pressure levels in mid-life with late-life risk of cognitive
decline or dementia have reported a harmful effect of hypertension
on cognitive function. Studies assessing the effect of late-life
blood pressure levels have reported that low diastolic and
very high systolic levels may increase the risk. Observational
studies and randomized clinical trials provide some evidence
for a protective effect of antihypertensive therapy. However,
it is possible that in some susceptible older persons lower
blood pressure increases the risk of cognitive impairment
and dementia. Because hypertension is the main risk factor
for cerebrovascular disease, it seems reasonable to expect
that vascular cognitive impairment, characterized by executive
cognitive impairment, is most affected and this is supported
by existing evidence. The impact of hypertension of Alzheimer’s
disease is controversial and remains to be clarified.
[Back to top]
Postmenopausal Hypertension: Insights from Rat
Models
Licy L. Yanes, Lourdes A. Fortepiani, Julio C. Sartori-Valinotti,
Radu Iliescu and Jane F. Reckelhoff
The increase in blood pressure following menopause sets women
up for increased risk of negative cardiovascular outcomes.
The increase in blood pressure occurs 5-10 years following
cessation of menses which suggests that mechanisms other than
loss of female sex hormones may play roles in mediating the
hypertension. Recent studies using rat models of aging have
begun to shed light on some of possible mechanisms responsible
for postmenopausal hypertension. This review outlines the
most recent studies and addresses questions remaining to be
addressed.
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Prevention and Management of Hypertension Without
Drugs
Saverio Stranges and Francesco P. Cappuccio
Lifestyle modifications and non-drug therapies are a vast
group of measures essential to the prevention and management
of hypertension. International experts unanimously recommend
some of them. However, not all measures are equally valuable
or have the same evidence base. The first step in the management
of patients at any age who have hypertension should be a reduction
in salt intake, either alone or in combination with drug therapy,
to which is often additive. A high potassium diet achieved
with an increase in the consumption of fruit and vegetables
is also recommended. Weight reduction, regular dynamic exercise
and reduction of alcohol consumption should be included in
management plans for the prevention and non-pharmacological
treatment of hypertension. The qualitative composition of
diet is also an important factor to consider for the prevention
and management of hypertension. Beyond the benefits associated
with specific nutrients, adherence to a dietary pattern based
on the DASH (Dietary Approaches to Stop Hypertension) diet,
as part of a comprehensive lifestyle intervention, is a suitable,
cost-effective approach to prevent high blood pressure in
normotensive individuals; moreover, if combined with reduced
sodium intake, it may represent an alternative to drug therapy
for individuals with mild hypertension willing to comply with
long-term dietary changes.
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Evaluation of Intermediate Endpoints: Clinical Implications
in the Management of Arterial Hypertension
Massimo Volpe and Giuliano Tocci
Arterial hypertension heavily contributes to the global cardiovascular
burden of morbidity and mortality, as well as to increase
individual absolute cardiovascular risk. In addition, the
clustering of cardiovascular risk factors and target organ
damage in hypertensive patients is indeed an extremely frequent
observation in both the epidemiological studies and in the
clinical practice. In this view, a systematic research of
intermediate endpoints or disease markers may represent an
useful strategy in order to evaluate the presence of target
organ damage as well as to predict cardiovascular events in
essential hypertension. In fact, when considering the long
natural history of hypertension, it appears very useful to
postulate that modifications in measurable intermediate endpoints
may permit a better evaluation of the efficacy of a given
treatment in preventing or modifying the course of target
organ damage, rather than variation in the future risk for
development of hard endpoints. This represents a valuable
approach in the clinical practice and can be easily undertaken
by physicians to evaluate the status of a patient, the prognosis
and the effectiveness of a treatment through a better stratification
of absolute cardiovascular risk in individual patients, resulting
in a more strict and cost-effective control of high blood
pressure levels.
[Back to top]
The Relevance of Long-Term Adherence to Non Pharmacological
and Pharmacological Treatment of Hypertension
Bernard Waeber and François Feihl
Current hypertension guidelines point to the necessity of
achieving sustained and strict blood pressure control in every
hypertensive patient. To reach this goal the patient should
comply both with hygienic measures and pharmacologic treatment.
This remains a difficult task, particularly since hypertension
is generally asymptomatic and since any therapeutic intervention
might adversely alter the patient’s quality of life.
Long-term persistence with antihypertensive therapy is facilated
when the treatment is initiated with well tolerated antihypertensive
agents, especially blockers of the renin-angiotensin system.
Having a normal blood pressure during treatment is also an
important determinant of persistence. This explains the growing
interest for fixed-dose combinations, which have the main
advantage to be at the same time efficient and well tolerated.
These simple to use preparations have even gained acceptance
as first-line drug regimen.
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The Role of Adipokines in Hypertension and Cardiovascular
Disease
Andrew M. Wilson and Marno C. Ryan
The prevalence of overweight (currently defined as body mass
index (BMI) >25 kg/m2) and obesity (BMI >30 kg/m2) is
rapidly increasing and has been associated with increased
morbidity and mortality. Obesity is associated strongly with
insulin resistance and type 2 diabetes, which are major risk
factors for hypertension and cardiovascular disease. Recent
evidence has emerged that adipocytes function as highly active
endocrine cells and secrete a wide range of inflammatory and
vaso-active agents. These include leptin and adiponectin which
appear to display a range of effects on the cardiovascular
system, particularly in vitro. A better understanding
of the roles for these and other adiopcyte derived agents
in cardiovascular disease pathogenesis may lead to the development
of better prevention strategies and novel therapies.
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Arterial Stiffness and Hypertension: A Review of Mechanism
and Clinical Relevance
Julia Wong
Purpose of review: This review is intended to provide the
background for a broad view of the influence of large-artery
stiffness on the development of hypertension in aging, diabetes
and end-stage renal disease.
Recent findings: Arterial stiffness, particularly in aorta,
is a major determinant of isolated systolic hypertension in
the elderly. Studies have consistently shown that large-artery
stiffness results in augmented amplitude of reflected pressure
waves and their early return. This disturbed physiological
phenomenon can alter the heart-vessel coupling and lead to
increased cardiovascular risk. This review describes the structural,
functional, environmental and genetic factors that influence
arterial stiffness, wave reflection, and blood pressure. It
also discusses non-invasive techniques to measure arterial
stiffness and analyze arterial waveforms. The effects of various
antihypertensive agents with respect to arterial stiffness
and blood pressure reduction are examined. In addition, studies
on non-pharmacologic interventions to modify large artery
behavior are reviewed.
Summary: Optimal clinical management of hypertension depends
on better understanding of the contribution of vascular stiffness
to hypertension. This information has significant implications
for therapeutic decisions.
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Hemolysis-Associated Pulmonary Hypertension in Sickle
Cell Disease: Global Disruption of the Arginine-Nitric Oxide
Pathway
Claudia R. Morris
Nitric oxide is inactivated in sickle cell disease (SCD),
while bioavailability of L-arginine, the substrate for nitric
oxide synthesis is diminished. Impaired nitric oxide bioavailability
represents the central feature of endothelial dysfunction,
and is a major factor in the pathophysiology of SCD. Inactivation
of nitric oxide correlates with hemolytic rate and is associated
with erythrocyte release of cell-free hemoglobin and arginase
during intravascular hemolysis. Accelerated consumption of
nitric oxide is enhanced further by the inflammatory environment
of oxidative stress that exists in SCD. Based upon its critical
role in mediating vasodilation and inhibiting cell growth,
decreased nitric oxide reactivity has also been implicated
in the pathogenesis of pulmonary hypertension (PHT). Secondary
PHT, a common life-threatening complication of SCD, also occurs
in thalassemia and most hereditary and chronic hemolytic disorders.
Aberrant arginine metabolism contributes to endothelial dysfunction
and PHT in SCD, and is therefore strongly associated with
prospective patient mortality. The central mechanism responsible
for this metabolic disorder is enhanced arginine turnover,
occurring secondary to enhanced plasma arginase activity.
This is consistent with a growing appreciation of the role
of excessive arginase activity in human diseases, including
asthma and pulmonary artery hypertension. Decompartmentalization
of hemoglobin into plasma consumes endothelial nitric oxide
and thus drives a metabolic requirement for arginine, whose
bioavailability is further limited by arginase activity. New
treatments aimed at maximizing both arginine and nitric oxide
bioavailability through arginase inhibition, suppression of
hemolytic rate, or oral arginine supplementation may represent
novel therapeutic strategies for this common pulmonary complication
of hemolytic disorders.
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