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Current
Pharmaceutical Design
ISSN: 1381-6128
Current Pharmaceutical Design
Volume 15, Number 10, 2009
Contents
Modifying Cardiovascular Risk Factors: Newer Insights and
Preventive Measures
Executive Editor: Aurelio Leone
Editorial: Pp. 1034-1037
Molecular and Biochemical Changes of the Cardiovascular System
due to Smoking Exposure Pp. 1038-1053
C. Armani, L. Landini Jr. and A. Leone
[Abstract] [Purchase
Articles] [PMID: 19355946 PubMed - indexed for MEDLINE]
The Role of Statins for the Primary and
Secondary Prevention of Coronary Heart Disease in Women
Pp. 1054-1062
K. Tziomalos, A.I. Kakafika, V.G. Athyros,
A. Karagiannis and D.P. Mikhailidis
[Abstract] [Purchase
Articles] [PMID: 19355947 PubMed - indexed for MEDLINE]
Obesity in the Childhood: A Link to Adult
Hypertension Pp. 1063-1071
A. Virdis, L. Ghiadoni, S. Masi, D. Versari,
E. Daghini, C. Giannarelli, A. Salvetti and S. Taddei
[Abstract] [Purchase
Articles] [PMID: 19355948 PubMed - indexed for MEDLINE]
Flavonoids, Vascular Function and Cardiovascular
Protection Pp. 1072-1084
D. Grassi, G. Desideri, G. Croce, S. Tiberti,
A. Aggio and C. Ferri
[Abstract] [Purchase
Articles] [PMID: 19355949 PubMed - indexed for MEDLINE]
Aspirin Resistance in Cardiovascular
Disease: Pathogenesis, Diagnosis and Clinical Impact Pp.
1085-1094
A. Papathanasiou, J. Goudevenos and
A.D. Tselepis
[Abstract] [Purchase
Articles] [PMID: 19355950 PubMed - indexed for MEDLINE]
Angiogenesis as Risk Factor for Plaque
Vulnerability Pp. 1095-1106
R. Di Stefano, Francesca Felice and
Alberto Balbarini
[Abstract] [Purchase
Articles] [PMID: 19355951 PubMed - indexed for MEDLINE]
Role of Endothelial Progenitor Cell Mobilization
After Percutaneous Angioplasty Procedure Pp.
1107-1122
M.C. Barsotti, R. Di Stefano, P. Spontoni,
D. Chimenti and A. Balbarini
[Abstract] [Purchase
Articles] [PMID: 19355952 PubMed - indexed for MEDLINE]
The Biological Effects of Diagnostic
Cardiac Imaging Pp. 1123-1130
L. Landini, A. Ripoli, M.F. Santarelli,
L. Landini Jr. and V. Positano
[Abstract] [Purchase
Articles] [PMID: 19355953 PubMed - indexed for MEDLINE]
Imaging and Laboratory Biomarkers in
Cardiovascular Disease Pp. 1131-1141
M.G. Andreassi, A. Gastaldelli, A. Clerico,
P.A. Salvadori, R. Sicari and E. Picano
[Abstract] [Purchase
Articles] [PMID: 19355954 PubMed - indexed for MEDLINE]
Cardiovascular Disease: An Economical
Perspective Pp. 1142-1156
A. Lazzini and S. Lazzini
[Abstract] [Purchase
Articles] [PMID: 19355955 PubMed - indexed for MEDLINE]
Abstracts
[Back to top]
Editorial: Modifying Cardiovascular Risk Factors:
Newer Insights and Preventive Measures
Nowadays, there is no doubt that cardiovascular risk
factors, how ever they may be identified – and there
is considerable evidence that permits to assess their role
to cause, maintain and potentiate cardiovascular events –
are continuously increasing in number and new pathogenetic
mechanisms of damage are continuously recognised.
The degree of cardiovascular damage caused by risk factors
depends on isolated or combined action of how these factors
determine clinical, biochemical, metabolic and pharmacologic
alterations which could be strongly related with cardiovascular
pathology.
The reviews in this issue set a goal to analyse newer insights
that link some features of the main cardiovascular risk factors
with cardiac and vascular pathology.
Among the major cardiovascular risk factors, there is always
more and more evidence that genetic mechanisms adversely influence
heart and blood vessels of active smokers or individuals exposed
passively to cigarette smoke.
Armani et al. [1] analyse molecular and biochemical
changes of cardiac myocytes as well as the mechanisms involved
in cigarette smoking-related cardiovascular dysfunction.
Recent experimental and clinical data support the hypothesis
that cigarette smoke exposure increases oxidative stress as
a potential mechanism of damage.
Cardiac myocytes, as well as and other long-lived postmitotic
cells show dramatic smoke-related alterations that mainly
affect the mitochondria and lysosomal compartment. Mitochondria
are primary sites of reactive oxygen species formation that
causes progressive damage to mitochondrial DNA and proteins
in parallel to intralysosomal lipofuscin accumulation. There
is amassing evidence that various mechanisms may contribute
to accumulation of damaged mitochondria following initial
oxidative injury. Such mechanisms may include clonal expansion
of defective mitochondria, decreased propensity of altered
mitochondria to become autophagocytosed, suppressed autophagy
because of heavy lipofuscin loading of lysosomes and decreased
efficiency of specific proteases involved in mitochondrial
degradation
Newer insights involve lipid metabolism with regard either
to gender of individuals affected by lipid alterations or
treatment.
Tziomalos et al. [2] review describes coronary heart
disease (CHD) as the leading cause of death in the developed
world in both men and women. Elevated low-density lipoprotein
cholesterol (LDL-C) levels are strong and independent vascular
risk factors in both genders. Statins effectively decrease
LDL-C levels, reduce vascular morbidity and mortality and
are an essential component of CHD preventive strategies. However,
women are less likely to be prescribed statins than men in
both primary and secondary prevention settings. It was argued
that there is no conclusive evidence showing that statins
are beneficial for the prevention of vascular disease in women,
particularly in those without established CHD. Accumulating
data, however, suggest that statins are equally effective
in both men and women. The lack of significant effects in
some studies appears to be primarily due to the under-representation
of women and the ensuing lack of statistical power. Current
guidelines for the prevention of vascular disease also recommend
a similar management of dyslipidemia in both men and women.
Therefore, statin treatment should be implemented with the
same criteria and goals in both genders.
The rapid increasing prevalence of obesity worldwide represents
a serious health hazard. Obesity predisposes to increased
risk for diabetes, hypertension, renal failure. Direct mechanisms
link visceral adiposity and atherosclerosis through the action
of adipose-derived proinflammatory cytokines.
The review of Virdis et al. [3] underlines that hypertension
can be considered the most important cardiovascular risk factor
linking obesity to the development of cardiovascular disease.
Obesity among children and adolescents is reaching epidemic
proportions in the industrialized world. Childhood obesity
strongly predisposes to cardiovascular adult mortality. The
main strategies for prevention and treatment of overweight
and obesity in childhood, which need to involve community,
school and family, are the promotion of lifestyle interventions,
including a correct dietary approach, with fish and vegetables,
and physical activity.
The review of Grassi et al. [4] contributes to further
clarify those preventive measures capable to reduce vascular
damage. The dietary intake of polyphenols - particularly of
flavonoids and the specific class of flavonoids named flavanols
- might be able to exert some beneficial vascular effects
reducing the risk for cardiovascular morbidity and mortality.
The flavonoids are a heterogeneous group of natural molecules
differently represented in fruit and vegetables. However,
definitive data that demonstrate protection of the vascular
system by these foods is lacking.
Pharmacological effects of aspirin resistance are the subject
of the Papathanasiou et al. review [5].
Aspirin is the cornerstone of treatment in patients with coronary
artery disease. However, several studies investigating the
in vitro response of platelets to the administration
of aspirin showed this response to be variable, with some
patients exhibiting non-responsiveness or resistance.
Aspirin resistance may be categorised as either ‘laboratory’
or ‘clinical’. Laboratory aspirin resistance is
defined as the failure of aspirin to inhibit the production
of thromboxane A2 (TxA2)
by platelets or to inhibit platelet activation that depends
on TxA2 production. Clinical
aspirin resistance is defined as the failure to prevent the
occurrence of atherothrombotic ischaemic episodes in patients
to whom it is administered. So far, there is no generally
accepted method for the ex vivo evaluation of platelet
activation or for assessing the degree of platelet activation
following aspirin administration and data concerning the clinical
impact of aspirin resistance are conflicting. For these reasons
it is not possible to suggest specific guidelines for the
treatment of patients who show high levels of platelet activation
or a low level of platelet inhibition after treatment with
aspirin.
A strong relationship links some biological responses to the
cardiovascular system and cardiovascular risk factors. Biological
response may positively or adversely influence cardiac outcomes
according to several combined actions whose power would seem
to be a determining factor.
The review of Di Stefano et al. [6] identifies atherosclerosis
as an inflammatory disease, characterized by degenerative
changes and extracellular accumulation of lipid and cholesterol.
The evolving inflammatory reaction plays an important role
in the initiation of atherosclerotic plaques and their destabilization,
converting a chronic process into an acute disorder with an
ensuing thrombo-embolism. Neovascularization has also been
recognized as an important process for the progression of
atherosclerotic plaques. In fact, vulnerable atherosclerotic
plaques prone to rupture are characterized by an enlarged
necrotic core containing an increased number of vasa vasorum,
apoptotic macrophages, and more frequent intraplaque haemorrhage.
This network of immature blood vessels is a viable source
of intraplaque haemorrhage providing erythrocyte-derived phospholipids
and free cholesterol. However, the relationship between the
process of angiogenesis and its causal association with the
progression and complication of atherosclerosis is still challenging
and controversial.
In the review of Barsotti et al. [7] the role of
endothelial progenitor cell mobilization after percutaneous
angioplasty procedure is widely debated.
Circulating endothelial progenitor cells (EPCs) are bone marrow-derived
cells, contributing to endothelial cell regeneration of injured
vessels as well as neovascularization of ischemic lesions.
EPC levels and function are inversely correlated with cardiovascular
risk factors, can predict the occurrence of adverse events
and atherosclerotic disease progression. Ischemia and inflammation
are the primary triggers for EPC mobilization and homing,
however, vascular trauma, as occurs during surgical procedures,
has been demonstrated to stimulate EPC mobilization even in
absence of tissue ischemia. The effect of angioplasty on EPCs
is not yet well defined, mainly because of the different and
sometimes contrasting clinical results, due to low numbers
of patients enrolled and to lack of standardization in evaluating
EPCs.
The effect on EPCs of different kinds of stents and the potential
use of new stents able to attract EPCs reach different results
in patients who undergo angioplasty in different vascular
districts (coronary, peripheral and carotid).
Also current diagnostic procedures reach more and more advanced
goal in identifying cardiac pathology as well as the role
of coronary risk factors.
The review by Landini et al. [8] focuses on the merits
of some cardiovascular diagnostic techniques. Cardiovascular
imaging can be used for diagnosis and/or assessing prognostic
outcome of patients affected by cardiovascular disease. These
techniques are constantly in progress and their diagnostic
power is expanding with increased knowledge of the possible
adverse effects of contrast media. Sensitivity and specificity
of diagnostic tests should be carefully established to obtain
a favourable ratio between cost and benefit.
The relationship between imaging techniques and laboratory
biomarkers is widely discussed in the review of Andreassi
et al. [9]. Imaging and laboratory biomarkers are
an essential support to modern practice of medicine, allowing
a better identification, severity titration, staging and follow-up
of atherosclerosis and heart failure disease. This review
provides an overview of imaging, biochemical and genetic biomarkers
used in order to evaluate the 4 different aspect of patient
vulnerability to cardiovascular disease: arterial; blood;
myocardial; metabolic vulnerability.
Yet, no single perfect biomarker exists and there is wide
room for optimization and integration between clinical evaluation
and biomarker evaluation. In general, a targeted approach
tailored on the individual patient should be preferred to
a carpet diagnostic bombing, which will lead to an exorbitant
multiplier of costs, risks and inappropriate testing.
Finally, a noteworthy revision conducted by Lazzini and Lazzini
[10] on the economical points of view that are associated
with the balance existing between costs of cardiovascular
disease and costs of its prevention. The authors underline
how there are different procedures to establish economic measures
that permit to assess cardiovascular costs around the world
and, moreover, observations on the economic characteristics
of the subject are conducted up till now more preferably on
the cardiac disease than on its prevention. This trend should
be changed.
Some points that are beyond the content of these papers should
be stressed. Firstly, there is recent evidence [11, 12] according
to the results of GISSI –HF and CORONA trials that statins
are not beneficial in treating heart failure. Results of that
have been demonstrated particularly in older individuals [12].
Heart failure is often the end stage of cardiovascular disease.
So, a drug may prevent the progression of cardiovascular disease
but be ineffective when the heart failure is established.
Evidence is also mounting showing that stopping statins suddenly
in high risk patients may be very dangerous [13-15]
Some points should be stressed on the role of EPCs. In the
past, restoration of injured endothelium was attributed to
migration of EPCs and consequent replacement and regeneration
of the damaged cells. Other studies [16] have decreased the
importance of EPCs identifying additional factors, particularly
biochemical and cellular components, which contribute to repair
the injured endothelium.
There is evidence [17] that during atherosclerotic plaque
evolution, changes in fibrous cap thickness that make the
plaque vulnerable are mediated by inflammatory phenomena at
the site of an atheroma under the effects of major cardiovascular
risk factors. Plaque instability is one of the major determinants
of ischaemic acute events. Continuous plaque remodelling is
strongly associated with changes in coronary risk factors
that may occur spontaneously or following preventive measures.
It is therefore of interest that a recent primary prevention
trial has shown that elevated levels of high sensitivity C-reactive
protein predicts significant clinically relevant benefits
from treatment with a statins (JUPITER trial [18]) in apparently
healthy individuals without hyperlipidemia even when all subgroups
of study were analysed.
Usually, thrombi formation follows plaque instability since
vulnerable plaque easily undergoes rupture which occurs more
frequently as plaque volume is bigger and macrophage content
elevated [19]. However, the relationship between incidence
of coronary events and lipid metabolism changes, particularly
changes in cholesterol concentrations, is yet far to be fully
clarified as well as the role of the statins in those individuals
with other major coronary risk factors associated and, at
the same time, treated by specific therapy. A recent metanalysis
[20] conducted to assess the quantitative relationship between
triglyceride concentrations in blood and cardiovascular risk
reached interesting results to be discussed. Data concerning
2 perspective large-scale trials together with other smaller
studies including 262,525 individuals with a mean of 4% of
nonfatal and fatal coronary events showed that there was a
correlation between cardiovascular risk and level of triglycerides.
Risk further increased when HDL-Cholesterol had lower values.
Increasing evidence describes additional cellular alterations
of cardiocytes as a result of the toxic effects of cigarette
smoking [21]. Coronary heart disease is a complex condition
resulting from numerous gene-gene and gene environment interactions
[22], including cigarette smoking.
An increasing number of observations are identifying different
and new mechanisms by which vascular risk factors lead to
cardiovascular pathology. This is an evolving chapter that
requires continuous updating.
Moreover, analysing the preventive measures conducted to control
the adverse effects of major cardiovascular risk factors,there
is evidence that not only changes in lifestyle but also therapeutic
lifestyle changes have an important beneficial effect on cardiovascular
morbidity and mortality and should be an integral component
of any prevention program [23, 24]. Both dietary modification
and drug therapy should be used to achieve the goal of a significant
reduction in cardiovascular nonfatal and fatal events. Drug
therapy should not be postponed if the target for LDL-cholesterol
lowering is unlikely to be achieved in the near term by therapeutic
lifestyle changes.
Large-scale trials have been and are always more frequently
used to assess the role and significance of the major cardiovascular
risk factors. That has occurred replacing some mathematical
models of study that were, in a recent past, a simplified
description of a system permitting to establish calculations
and predictions of how risk factors, particularly some of
them [25], could adversely influence heart and blood vessel
responses as well as provide results to be reproduced experimentally
in several other findings. In our opinion, mathematical models
should be yet widely used in association with large-scale
studies since the observations obtained by the first methods
give reproducible results that may be valuably completed by
the epidemiologic data of large-scale trials.
Taken together, the articles in this issue provide a current
approach to a better understanding of how cardiovascular risk
may damage heart and blood vessels and, consequently, how
their adverse action could be avoided. Therefore, this issue
further contribute to update researchers, physicians and also
students on a subject that is continuously expanding.
Finally, I thank very much Professor L. Landini and Professor
D.P. Mikhailidis who, as co-executive editors of this issue,
have contributed actively to editorial drafting with valuable
suggestions and experience.
References
[1] Armani C, Landini L Jr, Leone A. Molecular and biochemical
changes of the cardiovascular system due to smoking exposure.
Curr Pharm Des 2009; 15(10): 1038-53.
[2] Tziomalos K, Kakafika AI, Athyros VG, Karagiannis A, Mikhailidis
DP. The role of statins for the primary and secondary prevention
of coronary heart disease in women. Curr Pharm Des 2009; 15(10):
1054-62.
[3] Virdis A, Ghiadoni L, Masi S, Versari D, Daghini E, Giannarelli
C, et al. Obesità in the childhood. A link to adult
hypertension. Curr Pharm Des 2009; 15(10): 1063-71.
[4] Grassi D, Desideri G, Croce G, Tiberti S, Aggio A, Ferri
C.Flavonoids, vascular function and cardiovascular protection.
Curr Pharm Des 2009; 15(10): 1072-84.
[5] Papathanasiou A, Goudevenos J, Tselepis AD. Aspirin resistance
in cardiovascular disease: pathogenesis, diagnosis and clinical
impact. Curr Pharm Des 2009; 15(10): 1085-94.
[6] Di Stefano R, Felice F, Balbarini A. Angiogenesis as risk
factor for plaque vulnerability. Curr Pharm Des 2009; 15(10):
1095-106.
[7] Barsotti MC, Di Stefano R, Spontoni P, Chimenti D, Balbarini
A. Role of endothelial progenitor cell mobilization after
percutaneous angioplasty procedure. Curr Pharm Des 2009; 15(10):
1107-22.
[8] Landini L, Ripoli A, Santarelli MF, Landini L Jr., Positano
V. The biological effects of diagnostic cardiac imaging. Curr
Pharm Des 2009; 15(10): 1123-30.
[9] Andreassi MG, Gastaldelli A, Clerico A, Salvatori P, Sicari
R, Picano E. Imaging and laboratory biomarkers in cardiovascular
disease. Curr Pharm Des 2009; 15(10): 1131-41.
[10] Lazzini A, Lazzini S. Cardiovascular disease: an economical
perspective. Curr Pharm Des 2009; 15(10): 1142-56.
[11] GISSI-HF Investigators. Effect of rosuvastatin in patients
with chronic heart failure (the GISSI-HF trial) a randomised,
double-blind, placebo-controlled trial. Lancet 2008; 372:
1231-39.
[12] Kjekshus J, Apetrei E, Barrios V, Bohm M, Cleland JGF,
Cornel JH, et al. Rosuvastatin in older patients
with systolic heart failure. N Engl J Med 2007; 357: 2248-61.
[13] Daskalopoulou SS, Delaney JA, Filion KB, Brophy JM, Mayo
NE, Suissa S. Discontinuation of statin therapy following
an acute myocardial infarction: a population-based study.
Eur Heart J 2008; [Epub ahead of print].
[14] Liberopoulos EN, Florentin M, Mikhailidis DP, Elisaf
MS. Compliance with lipid-lowering therapy and its impact
on cardiovascular morbidity and mortality. Expert Opin Drug
Saf 2008; 7(6): 717-25.
[15] Tziomalos K, Athyros VG, Mikhailidis DP. Statin discontinuation:
an underestimated risk? Curr Med Res Opin 2008. [Epub ahead
of print].
[16] Werner N, Junk S, Laufs U, Link A, Walenta B, Bohm M,
Nickering G. Intravenous transfusion of endothelial progenitor
cells reduces neointima formation after vascular injury. Circ
Res 2003; 93: E 17-24.
[17] Libby P. Inflammation in atherosclerosis. Nature 2002;
420: 868-74.
[18] Ridker PM, Danielson E, Fonseca FAH, Genest J, Gotto
AM Jr., Kastelein JJP, et al. Rosuvastatin to prevent
vascular events in men and women with elevated C-reactive
protein. N Engl J Med 2008; 359: 2195-207.
[19] Mann JM, Davies MJ. Vulnerable plaque: Relation of characteristics
to degree of stenosis in human coronary arteries. Circulation
1996; 94: 928-31.
[20] Sarwar N, Danesh J, Eiriksdottir G, Sigurdsson G, Wareham
N, Bingham S, et al. Triglycerides and the risk of
coronary heart disease. 10,158 incident cases among 262,525
partecipants in 29 Western Prospective Study. Circulation
2007; 115: 450-8.
[21] Leone A, Landini L Jr., Biadi O, Balbarini A. Smoking
and cardiovascular system: cellular features of the damage.
Curr Pharm Des 2008; 14: 1771-77.
[22] Stephens JW, Humphries SE. The molecular genetics of
cardiovascular disease: clinical implications. J Inter Med
2003; 253: 120-27.
[23] Leone A. Relationship between cigarette smoking and other
coronary risk factors in atherosclerosis: Risk of cardiovascular
disease and preventive measures. Curr Pharm Des 2003; 9: 2417-23.
[24] Iestra JA, Kromhout D, van der Schouw YT, Grobbee DE,
Boshuizen HC, van Staveren WA. Effect size estimates of lifestyle
and dietary changes on all-cause mortality in coronary artery
disease patients. A systematic review. Circulation 2005; 112:
924-34.
[25] Leone A. Passive smoking exposure and cardiovascular
health. In: Jeorgensen NA Ed. Passive Smoking and Health Research,
Nova Publishers, Inc.: New York 2007; 65-94.
Co-Executive Editors:
Luigi Landini
Professor of Biomedical Engineering
University of Pisa, Italy
Executive Editor:
Dr. Aurelio Leone
Via Provinciale 27
19030 Castelnuovo Magra (SP)
Italy
Tel/Fax: +390187 676346
E-mail: reliol@libero.it
Dimitri P Mikhailidis
Dept. of Clinical Biochemistry
(Vascular Disease Prevention Clinics)
Royal Free Hospital Campus University College London
UK
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[Purchase
Articles] [PMID: 19355946 PubMed - indexed for MEDLINE]
Molecular and Biochemical Changes of the Cardiovascular System
due to Smoking Exposure
C. Armani, L. Landini Jr. and A. Leone
Cigarette smoking (CS) is a major health hazard particularly
for the cardiovascular system and cancer. The mechanisms involved
in CS-related cardiovascular dysfunction have been largely
debated. CS increases inflammation, thrombosis, and oxidation
of low-density lipoproteins. Recent experimental and clinical
data support the hypothesis that cigarette smoke exposure
increases oxidative stress as a potential mechanism for initiating
cardiovascular dysfunction.
Cardiac myocytes, as well as and other long-lived postmitotic
cells show dramatic smoke-related alterations that mainly
affect the mitochondria and lysosomal compartment. Mitochondria
are primary sites of reactive oxygen species formation that
cause progressive damage to mitochondrial DNA and proteins
in parallel to intralysosomal lipofuscin accumulation. There
is amassing evidence that various mechanisms may contribute
to accumulation of damaged mitochondria following initial
oxidative injury. Such mechanisms may include clonal expansion
of defective mitochondria, decreased propensity of altered
mitochondria to become autophagocytosed, suppressed autophagy
because of heavy lipofuscin loading of ly-sosomes and decreased
efficiency of specific proteases involved into mitochondrial
degradation.
A possible interplay between microtubule plasticity and oxidative
stress also exists in cardiomyocytes, so this could represent
another potential mechanism by which smoking induces/accelerates
atherosclerosis.
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[Purchase
Articles] [PMID: 19355947 PubMed - indexed for MEDLINE]
The Role of Statins for the Primary and Secondary Prevention
of Coronary Heart Disease in Women
K. Tziomalos, A.I. Kakafika, V.G. Athyros,
A. Karagiannis and D.P. Mikhailidis
Coronary heart disease (CHD) is the leading cause of
death in the developed world in both men and women. Elevated
low-density lipoprotein cholesterol (LDL-C) levels are strong
and independent vascular risk factors in both genders. Statins
effectively decrease LDL-C levels, reduce vascular morbidity
and mortality and are an essential component of CHD preventive
strategies. However, women are less likely to be prescribed
statins than men in both primary and secondary prevention
settings. It was argued that there is no conclusive evidence
showing that statins are beneficial for the prevention of
vascular disease in women, particularly in those without established
CHD. This review summarizes the evidence regarding the effects
of statins in the prevention of CHD in women. Accumulating
data suggest that statins are equally effective in both men
and women. The lack of significant effects in some studies
appears to be primarily due to the under-representation of
women and the ensuing lack of statistical power. Current guidelines
for the prevention of vascular disease also recommend a similar
management of dyslipidemia in both men and women. Therefore,
statin treatment should be implemented with the same criteria
and with the same goals in both genders.
[Back to top]
[Purchase
Articles] [PMID: 19355948 PubMed - indexed for MEDLINE]
Obesity in the Childhood: A Link to Adult Hypertension
A. Virdis, L. Ghiadoni, S. Masi, D. Versari,
E. Daghini, C. Giannarelli, A. Salvetti and S. Taddei
The rapid increasing prevalence of obesity worldwide
represents a serious health hazard. Obesity predisposes to
increased risk for diabetes, hypertension, renal failure.
Direct mechanisms link visceral adiposity and the atherosclerosis
process through the action of adipose-derived proinflammatory
cytokines.
In particular, hypertension can be considered the most important
cardiovascular risk factor linking obesity to the development
of cardiovascular disease. Obesity among children and adolescents
has also reaching epidemic proportions in the industrialized
world. Childhood obesity strongly predisposes to cardiovascular
adult mortality. Recent reports documented a tracking of blood
pressure from childhood to adulthood and obesity occurring
in young age plays a crucial pathogenic role. Indeed, fighting
overweight and obesity in the pediatric and adolescent age
may prevent the occurrence of adults with hypertension and
cardiovascular disease. The main strategies for prevention
and treatment of overweight and obesity in childhood, which
need to involve community, school and family, are the promotion
of lifestyle interventions, including as a correct dietary
approach, rich in fruit and vegetables and low-fat dairy products,
and physical activity.
[Back to top]
[Purchase
Articles] [PMID: 19355949 PubMed - indexed for MEDLINE]
Flavonoids, Vascular Function and Cardiovascular Protection
D. Grassi, G. Desideri, G. Croce, S. Tiberti,
A. Aggio and C. Ferri
A large body of evidence supports that the dietary intake
of polyphenols - particularly of flavonoids and the specific
class of flavonoids named flavanols - might be able to exert
some beneficial vascular effects and reduce the risk for cardiovascular
morbidity and mortality. The review of epidemiological and
mechanistic studies supports the role of flavonoids, particularly
cocoa and tea flavanols, in protecting the cardiovascular
system against cardiovascular disease. Nevertheless, flavonoids
are an heterogeneous group of natural molecules differently
represented in fruit and vegetables and definitive data on
cardiovascular benefits are lacking. The weakness of the available
data include few and very small studies, no crossover designed
studies and a wide range of dose and type of flavonoids tested.
Thus, although flavonoid-rich foods and beverages are likely
to protect cardiovascular system, further research is needed
to characterize the mechanism of action on flavanol-rich foods.
Long-term clinical trials are also needed to definitively
clarify the benefits deriving from long-term consumption of
flavanol-rich foods, particularly focussing on the lowest
effective levels as well as synergism or antagonistic actions
between different classes of flavonoids commonly found in
foods.
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[Purchase
Articles] [PMID: 19355950 PubMed - indexed for MEDLINE]
Aspirin Resistance in Cardiovascular Disease: Pathogenesis,
Diagnosis and Clinical Impact
A. Papathanasiou, J. Goudevenos and
A.D. Tselepis
Aspirin is the cornerstone of treatment in patients with
coronary artery disease. However, several studies investigating
the in vitro response of platelets to the administration
of aspirin showed this response to be variable, with some
patients exhibiting non-responsiveness or resistance.
Aspirin resistance may be categorised as either ‘laboratory’
or ‘clinical’. Laboratory aspirin resistance is
defined as the failure of aspirin to inhibit the production
of thromboxane A2 (TxA2)
by platelets or to inhibit platelet activation that depends
on TxA2 production. Clinical
aspirin resistance is defined as the failure to prevent the
occurrence of atherothrombotic ischaemic episodes in patients
to whom it is administered. So far, there is no generally
accepted method for the ex vivo evaluation of platelet
activation or for assessing the degree of platelet activation
following aspirin administration and data concerning the clinical
impact of aspirin resistance are conflicting. For these reasons
it is not possible to suggest specific guidelines for the
treatment of patients who show high levels of platelet activation
or a low level of platelet inhibition after treatment with
aspirin.
The aim of this review is to present data from laboratory
and clinical studies that are related to resistance to aspirin,
and to discuss the possible causes, the clinical significance,
and the ways of managing such resistance at a clinical level.
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[Purchase
Articles] [PMID: 19355951 PubMed - indexed for MEDLINE]
Angiogenesis as Risk Factor for Plaque Vulnerability
R. Di Stefano, Francesca Felice and
Alberto Balbarini
Atherosclerosis is now generally accepted as an inflammatory
disease, characterized by degenerative changes and extracellular
accumulation of lipid and cholesterol. The evolving inflammatory
reaction plays an important role in the initiation of atherosclerotic
plaques and their destabilization, converting a chronic process
into an acute disorder with an ensuing thrombo-embolism. Neovascularization
has been, also, recognized as an important process for the
progression of atherosclerotic plaques. In fact, vulnerable
atherosclerotic plaque prone to rupture are characterized
by an enlarged necrotic core containing an increased number
of vasa vasorum, apoptotic macrophages, and more frequent
intraplaque haemorrhage. Various functional roles have been
assigned to intimal microvessels. This network of immature
blood vessels is a viable source of intraplaque haemorrhage
providing erythrocyte-derived phospholipids and free cholesterol.
However, it is still challenging and controversial the relationship
between the very process of angiogenesis and its causal association
with the progression and complication of atherosclerosis.
The selective targeting of neoangiogenesis poses a possible
approach for the elimination of pre-existing and new growth
of microvessels. The identification of target lesions is a
critical issue, because current technologies have yet to achieve
the goal of characterizing plaque morphology to the degree
necessary to correctly identify rupture-prone lesions according
to pathologic criteria. However, few imaging techniques can
be used to detect the neovascularization within the atherosclerotic
plaque in vivo.
This review discusses the potential role of intraplaque
angiogenesis as risk factor for plaque vulnerability.
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Role of Endothelial Progenitor Cell Mobilization After Percutaneous
Angioplasty Procedure
M.C. Barsotti, R. Di Stefano, P. Spontoni,
D. Chimenti and A. Balbarini
Circulating endothelial progenitor cells (EPCs) are bone
marrow-derived cells, contributing to endothelial cell regeneration
of injured vessels as well as neovascularization of ischemic
lesions. EPC levels and function are inversely correlated
with cardiovascular risk factors, can predict the occurrence
of adverse events and atherosclerotic disease progression.
Ischemia and inflammation are the primary triggers for EPC
mobilization and homing, however, vascular trauma, as it occurs
during surgical procedures, has been demonstrated to stimulate
EPC mobilization even in absence of tissue ischemia. The effect
of angioplasty on EPCs is not well defined, mainly because
of the different and sometimes contrasting clinical results,
due to low numbers of patients enrolled and to lack of standardization
in evaluating EPCs.
Aim of this review is to report recent results on the effect
of EPC mobilization and homing after angioplasty, attempting
to summarize them in a comprehensive model. The effect on
EPCs of different kind of stents and the potential use of
new stents able to attract EPCs will be also described. Results
obtained in patients undergoing angioplasty in different vascular
districts (coronary, peripheral and carotid) will be shown,
together with the correlation between circulating progenitor
cells and restenosis.
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The Biological Effects of Diagnostic Cardiac Imaging
L. Landini, A. Ripoli, M.F. Santarelli,
L. Landini Jr. and V. Positano
In this paper the authors deal with the main imaging
techniques available to clinical cardiologists, with a brief
overview of biophysical and biological aspects which are of
relevance for the assessment of health effects related to
the exposure of patients to both ionizing and non ionizing
radiation. A main contribute is the reviewing published evidence
on biological effects of radiation, trying to compose a balanced
issue in order to increase awareness and knowledge about radiation
exposure from cardiac imaging and implications for health
risk.
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Imaging and Laboratory Biomarkers in Cardiovascular Disease
M.G. Andreassi, A. Gastaldelli, A. Clerico,
P.A. Salvadori, R. Sicari and E. Picano
Imaging and laboratory biomarkers are an essential support
to modern practice of medicine, allowing a better identification,
severity titration, staging and follow-up of atherosclerosis
and heart failure disease. This review provides an overview
of imaging, biochemical and genetic biomarkers used in clinical
practice and for research purposes in order to evaluate the
4 different aspect of patient vulnerability to cardiovascular
disease: arterial; blood; myocardial; metabolic vulnerability.
Yet, no single perfect biomarker exists and there is wide
room for optimization and integration between clinical evaluation
and biomarker evaluation. In general, a targeted approach
tailored on the individual patient should be preferred to
a carpet diagnostic bombing, which will lead to an exorbitant
multiplier of costs, risks and inappropriate testing.
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Cardiovascular Disease: An Economical Perspective
A. Lazzini and S. Lazzini
Cardiovascular diseases represent a relevant problem
worldwide. Data from World Health Organization (W.H.O.) demonstrate
that they are one of the principle causes of death: 30% of
all losses of human life throughout the world are due to heart
diseases. Such data buries a substantial economic cost considering
both the direct component, first of all the national health
expense, and the indirect part, such as absenteeism rate,
productivity loss, quality of life and, more generally, social
costs. The future scenario pictured by the W.H.O. reveals
a negative trend due to an increasing in the rate of morbidity
and mortality especially in Emerging Countries. One of the
solution to stem the costs – economic and not –
connected to cardiovascular diseases is to empower the prevention
activities overall the actions of primary prevention. This
require a change in the traditional patient-physician relationship
management model to get to an organizational model centred
on patient and based on a proactive approach. In this perspective
in the paper will be analysed the principal changes that occurred
in the Italian national healthcare system and in particular
the strategic plans and actions in theme of cardiovascular
prevention.
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