Current Pharmaceutical Design, Volume 9, No. 29, 2003
Contents
Anti-Hypertensive
Agents in Relation to Modifying Coronary Risk Factors
Control of Blood Pressure in the Community:
An Unsolved Problem
Pp.2375-2384
Antonio
Salvetti and Daniele Versari
Mechanisms of Endothelial Dysfunction: Clinical
Significance and Preventive Non-Pharmacological Therapeutic Strategies Pp.2385-2402
S.
Taddei, L. Ghiadoni, A. Virdis, D. Versari, A. Salvetti
New Technological Developments in the
Clinical Imaging of Atherosclerotic Plaque Pp.2403-2415
Luigi
Landini, Maria Filomena Santarelli, Alessandro Pingitore and Vincenzo Positano
Relationship Between Cigarette Smoking and Other
Coronary Risk Factors in Atherosclerosis: Risk of Cardiovascular Disease and
Preventive Measures
Pp.2417-2423
Aurelio Leone
The Effects of Lipid-Regulating Therapy on
Haemostatic Parameters
Pp.2425-2443
Haralampos J. Milionis, Moses S. Elisaf and Dimitri P. Mikhailidis
The Effects of Antihypertensive Therapy on
Haemostatic Parameters
Pp.2445-2464
E.S.
Ganotakis, J.A. Papadakis, G.E. Vrentzos
and D.P. Mikhailidis
Coronary Risk Factors in the Elderly: Their
Interactions and Treatment
Pp.2465-2478
Pierugo Carbonin, Giuseppe Zuccala, Emanuele Marzetti, and Maria Rita Lo Monaco
Abstracts
[Back to top] Control of Blood Pressure in the Community:
An Unsolved Problem
Antonio
Salvetti and Daniele Versari
Available data indicate that blood pressure (BP) is reduced below
140-90 mmHg in less than 30% of hypertensive patients. This poor control of BP
derives from lack of diagnosis (unawareness of hypertension), lack of treatment
of aware hypertensive patients and lack of efficacy of treatment. Systolic BP
(SBP) is now considered as the most important parameter for diagnosis and
stadiation of hypertension, above all in elderly patients, and the most
frequent cause of unsatisfactory control of BP in the population. Lack of SBP
control is caused both by physicians' attitude and difficulty in reducing SBP.
Physicians are more prone to consider diastolic BP as the most important
parameter for diagnosis and stadiation of hypertension, decision to treat and
intensification of treatment and therefore SBP is often forgotten and-or
misinterpreted in this decision making process. On the other hand, since
current antihypertensive drugs are equally effective in lowering SBP and DBP
and-or less effective in lowering SBP more than DBP, SBP is often uncontrolled
in treated patients with isolated systolic hypertension or prevalent increase
in SBP. The possibility of obtaining
better control of SBP in the future is linked to better education of
physicians, who need to pay greater attention to SBP as a parameter for
diagnosing, treating and intensifying treatment, and to the development of new
drugs more active in reducing SBP.
[Back to top] Mechanisms of Endothelial Dysfunction:
Clinical Significance and Preventive Non-Pharmacological Therapeutic Strategies
S.
Taddei, L. Ghiadoni, A. Virdis, D. Versari, A. Salvetti
Endothelium-derived NO is not only a potent vasodilator but also
inhibits platelet aggregation, vascular smooth muscle cell migration and
proliferation, monocyte adhesion and adhesion molecule expression, thus
protecting the vessel wall against the development of atherosclerosis.
Cardiovascular risk factors are associated with an imbalance of the redox
equilibrium towards oxidative stress and, therefore, impair the integrity of
the endothelium, leading to endothelial activation which involves blunted
endothelium-dependent vasodilation (vasodilator dysfunction) as well as
inflammatory processes extending to the milieu within the whole vasculature,
making plaques prone to rupture. In prospective studies endothelial dysfunction
is associated with increased incidence of cardiovascular events. Thus, the
prevention of endothelial dysfunction can determine a strong advantage in the
clinical outcome of patients with cardiovascular risk factors.
Several non-pharmacological interventions can prevent endothelial
dysfunction or improve impaired endothelium-dependent vasodilation. Probably
the most effective non-pharmacological measure is represented by aerobic
physical activity, which can reduce production of oxidative stress associated
to increasing age. Moreover, physical activity can improve endothelial
dysfunction even in patients with cardiovascular risk factors such as essential
hypertension.
In addition several other approaches, including vitamin and fish oil
supplementation, or tea and red wine consumption, can lead to an improvement of
endothelium-dependent vasodilation, possibly by a restoration of NO
availability. It is worth noting that most of non-pharmacological measures act
by preventing or reducing oxidative stress.
[Back to top] New Technological Developments in the
Clinical Imaging of Atherosclerotic Plaque
Luigi
Landini, Maria Filomena Santarelli, Alessandro Pingitore and Vincenzo Positano
Direct visualization of the composition of the atherosclerotic plaque
during its natural history and after therapeutic intervention may be helpful in
detecting lesions with high risk of acute events and in understanding
progression and regression of the disease. A wide variety of invasive and
non-invasive imaging techniques is available to detect clue aspects of
atherosclerosis from the early stage to the clinical evidence appearance. We
will firstly review the ongoing technological and clinical research on both
invasive and non-invasive techniques. Afterward, we will discuss in detail the
use of high-resolution, multi-contrast magnetic resonance imaging for
non-invasive imaging of the plaque and its characterization in terms of its
various components (i.e., thickness, lipid, fibrous, calcium, or thrombus).
Finally, we will describe the potential of quantitative analysis in describing
of plaque constituents with improved reproducibility.
[Back to top] Relationship Between Cigarette Smoking and
Other Coronary Risk Factors in Atherosclerosis: Risk of Cardiovascular Disease
and Preventive Measures
Aurelio Leone
Among the major Coronary Risk Factors (CRF) cigarette smoking has shown
undoubtedly harmful effects on the heart and blood vessels either as active
smoking (smoking a cigarette) or passive smoking (exposure to environmental
tobacco smoke -ETS). The strong relationship between cigarette smoking and
cardiovascular disease has been seen independent of the other CRF in a number
of well-designated epidemiologic studies. However, a strong increase in the
excess of cardiovascular risk has been defined along with the interaction of
cigarette smoking and other major CRF.
Thousands of pharmacologically active substances are present in tobacco
smoke, and a large number of direct and indirect effects have been
demonstrated. Different responses are also related to these types of exposure:
active exposure or passive exposure. The cardiovascular risk increases with
increasing levels of blood pressure and/or serum cholesterol and diabetes
mellitus, and at each level of these three risk factors, distributed with
different rates according to age and gender in individuals, the risk in active
smokers or passive smokers is greater than the risk in nonsmokers.
Further analytical and methodological observations are needed for
better understanding of the chemical and biological synergism. Nevertheless,
evidence is clear that cigarette smoking greatly increases the risk of
cardiovascular diseases in individuals already at increased risk because of
other CRF.
Preventive measures must be absolutely conducted to prevent the CRF
interaction. These are the changes in lifestyle (i.e. to give up smoking and
make physical activity), drug administration, diet supplementation especially
by those substances with antioxidant effects.
[Back to top] The Effects of Lipid-Regulating Therapy on
Haemostatic Parameters
Haralampos J. Milionis, Moses S. Elisaf and Dimitri P. Mikhailidis
There is growing evidence that the components of the haemostatic system
play a significant role in the development and progression of atherosclerosis
and its complications. Lipid-lowering interventions have been associated with a
significant reduction of morbidity and mortality. However, the improvement in
cardiovascular risk seen in several clinical trials is incompletely explained
by cholesterol reduction. Therefore, the benefit from lipid lowering drugs may involve
non-lipid mechanisms. These include beneficial effects on the arterial wall,
improved endothelial function and a favourable influence on blood rheology and
thrombogenesis.
In this review, we consider the influence of lipid-lowering
interventions on rheological and haemostatic parameters as well as the
potential clinical relevance of these effects.
[Back to top] The Effects of Antihypertensive Therapy on
Haemostatic Parameters
E.S. Ganotakis, J.A. Papadakis, G.E. Vrentzos and D.P. Mikhailidis
There is extensive trial-based evidence showing that antihypertensive
drugs reduce the risk of vascular events (e.g. stroke and myocardial
infarction) as well as target organ damage (e.g. left ventricular hypertrophy
and microalbuminuria). However, some of these benefits appear to be, at least
partially, independent of the extent of blood pressure (BP) lowering. It is
also evident that in certain clinical situations some antihypertensive drugs
are more effective than others. In this review we discuss the effects of
antihypertensive drugs on the endothelium, platelets, fibrinolysis and
coagulation. These properties may account for the observed BP-independent
actions.
Antihypertensive drugs exert multiple effects on the vascular endothelium.
These include effects on nitric oxide (NO) and angiotensin II-mediated actions.
Many BP lowering drugs can inhibit platelet activity, although the relevance of
this property is unknown, especially if patients are also taking platelet
inhibitors (e.g. aspirin). Antihypertensive drugs also influence fibrinolysis
and coagulation. These effects may be mediated by a variety of mechanisms,
including altering insulin sensitivity.
The haemostatic actions of antihypertensive drugs deserve greater recognition
and further investigation.
[Back to top] Coronary Risk Factors in the Elderly: Their
Interactions and Treatment
Pierugo Carbonin, Giuseppe Zuccala, Emanuele Marzetti,
and Maria Rita Lo Monaco
Coronary disease is currently a major cause of disability and mortality
in older populations. Due to several factors - including increased
noncardiovascular mortality, atypical presentation of coronary events,
selective survival, and, possibly, clustering of protective genetic traits -
the relative risk associated with almost all risk factors decreases with
advancing age. Nonetheless, all available evidences from both observational
studies and randomized trials indicate that, due to the higher event rates, the
absolute risk reduction yielded by preventive interventions is much greater in
the older age segments of populations. Another implication of the complex
relationships between risk factors and comorbid conditions in the pathogenesis
of coronary-related events and mortality, typical of the elderly subjects, is
represented by the multiple effects of treatment for single risk factors, such
as the decrease in LDL-cholesterol levels and inflammation markers yielded by
statins. Taken together, these factors account for the more favorable
cost-effectiveness ratios of preventive interventions in the older, as compared
with the middle-aged subjects. On the other hand, the high level of interaction
between coexistent risk factors and comorbidity renders a global approach to
the prevention of coronary events in older subjects mandatory for physicians,
as well as for decision-makers. In fact, a multidimensional assessment -
including the evaluation of cognitive, affective and social disturbances-
driving a multidisciplinary treatment of risk factors -encompassing behavioral
counseling and social support - is essential to improve patients’ compliance
and to effectively reduce the burden of coronary-related morbidity and
mortality in older populations.