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COMMENTARIES
POSTED IN MARCH 2009
Dyslipidemia and
Cardiovascular Risk: Focus on the Role of Low HDL-Cholesterol
Concentrations
in Developing Atherosclerotic
Disease and in Accelerating
Its Progression from Subclinical Lesions to Clinical Events. Evidence and
Therapeutic Implications
Authors: S. Novo, P. Carità, E. Corrado, G.
Coppola, and G. Novo
In estimating the global cardiovascular risk
(GCVR), awareness of the role that dyslipidemia plays, has
greatly influenced the management of patients, both in primary
and in secondary prevention of CV diseases.
There is ample evidence supporting the pathogenic role of
LDL cholesterol (LDL-C), as well as the benefits arising from
drugs used for reducing plasma levels. The AHA guidelines state
that this treatment has, in general, a crucial role in reducing
the risk of heart attacks and CV events in patients with coronary
artery disease (CAD). The majority of scientific evidence deals
with the issue of statins. One of the first analyses carried
out to test its effectiveness was the 4S, a Scandinavian trial
of secondary prevention conducted with simvastatin on patients
with chronic ischemic heart disease with hypercholesterolemia.
It showed a significant reduction in LDL-C (about 35%) and
in the relative risk of fatal and non-fatal myocardial infarction
(about 34%) [1].
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The Accelerated Atherosclerosis in Patients with Systemic Lupus
Erythematosus
Authors: Barbara Maria Colombo, M.D., Ph.D. and Prof. Francesco
Puppo
Systemic lupus erythematosus (SLE) is a prototypic
autoimmune disease characterized by multisystem involvement
in association with a diverse array of autoantibodies. Similar
to other autoimmune diseases, SLE appears to arise from a combination
of genetic and environmental factors that interact to cause
a state of immune hyperactivity. SLE is a disease of unknown
etiology characterized by inflammation in many different organ
systems associated with the production of antibodies reactive
with nuclear, cytoplasmic, and cell membrane antigens.
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Carbohydrate Response Element Binding Protein (Chrebp) Is a Glucose-Activated
Transcription Factor Involved in the Development of Metabolic Syndrome
Authors: BaKatsumi Iizuka and Yukio Horikawa
Excess carbohydrate is converted to triglyceride
in the liver and excess fat accumulation in the body leads
to insulin resistance [1]. Glucose and insulin are potent factors
in regulating de novo lipogenesis from glucose in the liver.
Insulin signaling activates several transcription factors such
as SREBP1c and LXR, while those activated by glucose remain
unknown [2].
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Genotypes and Haplotypes of beta2-adrenergic
Receptor and Parameters of the Metabolic Syndrome in Korean
Adolescents
Authors: Hye Soon Park, Eun Soon Shin, and Jong Eun Lee
The metabolic syndrome is associated with an increased risk
of total and cardiovascular mortality [1,2]. As juvenile obesity
has increased, the metabolic syndrome in adolescents has become
an emerging health problem throughout the world. The metabolic
syndrome is present in 3.3% of Korean adolescents [3], a proportion
similar to that reported in adolescents in the United States
[4]. Worryingly, the prevalence of this condition among children
and adolescents has been increasing in Asian countries. As
in other chronic diseases, genetic and environmental influences
have been implicated in the metabolic syndrome, and it was
recently suggested that the metabolic syndrome may originate
in utero [5].
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Inflammation and Atherosclerosis in Rheumatoid Arthritis
(RA) and Systemic Lupus Erythematosus (SLE)
Author: Ian Bruce
Rheumatoid arthritis (RA) and systemic lupus erythematosus
(SLE) are chronic autoimmune inflammatory diseases. RA has
a peak incidence in the sixth decade and affects approximately
1% of the adult population. The primary lesion is inflammatory
synovitis which causes progressive erosion and destruction
of joints. SLE is a multi-system autoimmune disease which
frequently affects women in their child-bearing years and
can cause a range of clinical manifestations including rashes,
arthritis, renal disease, central nervous system disorders,
etc. It has a prevalence of approximately 25-50 per 100,000
and has a higher prevalence in Afro-Caribbeans, African-Americans,
and Chinese populations. Both conditions significantly increase
the risk of future cardiovascular disease (CVD).
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Cerebral Perfusion Patterns in Patients with Carotid Stenosis
and the Effect of Carotid Revascularization
Authors: Giorgos S. Sfyroeras,1 M.D., Ph.D., Christos D. Karkos,2
M.D., FRCS, Ph.D., and Thomas S. Gerassimidis,2 M.D., Ph.D.
Patients with extracranial carotid artery stenosis, symptomatic
or asymptomatic, demonstrate altered cerebral perfusion. Carotid
revascularization procedures such as carotid endarterectomy
(CEA) and carotid artery stenting (CAS), aim mainly at stroke
prevention from thromboembolic events; their impact on cerebral
perfusion has not been extensively examined.
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Conjugated Linoleic Acid (CLA)-Mediated Gene Expression
and Implications for Atherosclerosis
Authors: Yukiko K. Nakamura and Stanley T. Omaye
Kritchevsky et al. [1] was first to report the inhibition
of atherosclerosis (34%) as well as the regression (30%) of
established atherosclerosis in rabbits fed mixtures of conjugated
linoleic acid (CLA) isomers (0.1-1.0% of diet) for 90 days.
CLAs are geometric and positional isomers of linoleic acid
(18:2 ?-6) found in food products derived from ruminants,
such as beef, milk, and cheese. CLAs are synthesized in ruminant
rumen by gram-negative bacteria, Butyrivibrio fibrisolvens
[2].
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Prevalence of Diabetes Mellitus and Metabolic Syndrome
in Slovakia
Author: Prof. Marián Mokán, M.D., D.Sc.
Slovakia and other countries of Central
and Eastern Europe are regions with a high prevalence of
coronary hearth disease
(CHD) [1]. However, the west-east prevalence gradient in Europe
is not quite clear [2]. Besides the expected social and economical
factors, different factors including diabetes mellitus (DM)
and single metabolic syndrome (MS) components involving glucose
metabolism disorders associated with insulin resistance (IR),
central obesity, dyslipidemia connected with increased triglyceride
(TG) levels, low HDL cholesterol, and arterial hypertension
(HT) may appear.
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Cytochrome P450 and Gene Activation - Cholesterol Elimination and Regression
of Atherosclerosis
Author: Pauli V. Luoma
Investigations in the 1970s revealed that plasma
levels of apolipoprotein AI (apo AI) and HDL cholesterol (HDL-C)
vary in proportion to the extent of drug-caused microsomal
P450-induction in the liver [1,2]. Subsequently, LDL cholesterol
(LDL-C) levels were found to decrease with increasing hepatic
P450-activity [2,3]. These studies on P450 and gene-activating
agents with anti-atherogenic effects presented a novel approach
to atherosclerosis – i.e. activation of P450 and other
genes coding proteins which regulate cholesterol balance in
the body – and pointed to new avenues of research [1-3].
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Dose-Dependent Effect of Rosuvastatin on Very-Low Density Lipoprotein- Apolipoprotein
C-III Kinetics in the Metabolic Syndrome
Authors: Esther M.M. Ooi, Gerald F. Watts, Dick C. Chan, Meifania M. Chen,
Paul J. Nestel, Dmitri Sviridov, and P. Hugh R. Barrett
The concurrence of visceral obesity, insulin
resistance, and dyslipidemia comprises the concept of the
metabolic syndrome. The metabolic syndrome is an escalating
problem in developed and developing societies that tracks
with the obesity epidemic. Dyslipidemia in the metabolic syndrome
is a risk factor for cardiovascular disease (CVD). It is characterized
by hypertriglyceridemia and low plasma HDL cholesterol. Apolipoprotein
C-III (apoC-III) is an 8.8 kD glycoprotein synthesized by
the liver and intestines. ApoC-III is associated with hypertriglyceridemia
and is a powerful independent predictor of CVD risk. ApoC-III
impairs the lipolysis of triglyceride-rich lipoproteins (TRL)
by inhibiting lipoprotein lipase (LPL) and the hepatic uptake
of TRL by remnant receptors. In the circulation, apoC-III
is associated with TRL and HDL, and freely exchanges among
these lipoprotein particle systems. In addition, experimental
evidence shows that apoC-III may also have a direct role in
atherosclerosis. Hence, interventions that target apoC-III
metabolism are clinically important.
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The Problem of Metabolic Syndrome in
Patients with Bipolar Disorder
Authors: Virginio Salvi and Giuseppe Maina
In recent years several studies have reported that mortality
for cardiovascular disease is higher in psychiatric patients
than in the general population. This increase in mortality
seems due to the high prevalence of cardiovascular disease
in psychiatric populations. Besides schizophrenia, the latest
reports have observed that patients with bipolar disorder
display similar risks of premature death from natural causes
[1-3].
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