EDITORIAL COMMENT
Dyslipidemia and cardiovascular diseases
Homa Mahdavi, Juyong Brian Kim, Scheila Safarpour, Duc A. Tien and
Mohamad Navab
David Geffen School of Medicine, University of California, Los Angeles,
California, USA
Correspondence to Mohamad Navab, BH-307 CHS, Cardiology-Medicine,
10833 Le Conte Avenue, Los Angeles, CA, USA
Tel: +1 310 206 2678; e-mail: mnavab@mednet.ucla.edu
Current Opinion in Lipidology 2009, 20:157–158
Introduction
Despite the progress made in the management of hyperch-
olesterolemia with statins, events are reduced by only 30%
[1]. Protecting the other 70% requires, additionally,
interventions including adjunctive use of anti-inflamma-
tory or immunologic treatments. The results of the statin
trials seriously underestimate the ultimate potential of
cholesterol-lowering therapy. Experts suggest continuing
and more extensive use of lipid-improving regimens and
intervention at an earlier stage [1].
HDL therapy
HDL, which is a major target for therapy in CAD, is
highly heterogeneous, has a variety of functions that may
contribute to its cardiovascular protective effects,
including promotion of reverse cholesterol transport
(RCT), anti-inflammatory and nitric oxide-promoting
effects [2]. Under the inflammatory pressure, however,
HDL can become dysfunctional [3]. Normal HDL has
high levels of antioxidants and active antioxidant
proteins/enzymes and is anti-inflammatory (aiHDL).
Proinflammatory HDL (piHDL) has high levels of
prooxidant molecules, which interfere with HDL
removal of cellular toxic waste and HDL delivery of this
metabolic waste for elimination.
HDL from individuals with coronary artery disease
(CAD) was not able to prevent LDL lipid oxidation
[4] and HDL from obese individuals was unable to
maintain vascular relaxation [5]. In renal patients, the
survival rate for those with aiHDL was four-fold than for
those with piHDL [6]. Women with systemic lupus
erythematosus (SLE) have increased risk of coronary
artery disease (CAD). McMahon et al. [7] showed that
SLE patients had high levels of piHDL, which correlated
with the levels of oxidized LDL. SLE patients with CAD
had higher piHDL scores than those without CAD.
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Patients with Crohn’s disease had piHDL, which
improved upon standard therapy [8].
Among other factors, the failure of torcetrapib has fuelled
speculation that in addition to raising HDL-cholesterol,
the quality and function of HDL needs to be improved
[9]. Statins were shown to improve HDL quality and
function in patients with CAD [10]. Patients with
rheumatoid arthritis (RA) have increased risk of myo-
cardial infarction. Charles-Schoeman et al. [11] showed
that in a group of patients with active RA, unlike HDL
from healthy individuals, HDL from patients with RA
was proinflammatory. This piHDL was rendered anti-
inflammatory by high-dose atorvastatin [11].
Novel compounds and approaches
Several compounds are being tested in clinical trials
including an extended-release niacin, which does not
produce flushing and increases HDL–apoA1 and
decreases triglycerides and VLDL/LDL [12]; a PPAR-a
agonist LY518674, affecting the production and clearance
of apoA-I and HDL [13]; the apoA-I mimetic peptide 4F,
which was shown to be safe and well tolerated and
improved the HDL anti-inflammatory index [4]; and a
microsomal triglyceride transfer protein inhibitor (AEGR-
733) [14]. In addition, it is recommended [15,16] that
efforts be directed toward promotion of RCT and its
robust measures.
As obesity and metabolic syndrome have become a
serious global health issue [17], therapeutic strategies
are needed that directly target adipose tissue to optimally
reduce cardiometabolic risk.
Conclusion
Certain lipoproteins and the renin–angiotensin–
aldosterone system are important in the pathogenesis
of atherosclerotic cardiovascular disease.
Understanding how risk factors such as high blood pres-
sure, dysregulated blood lipids and diabetes contribute to
atherosclerotic disease, as well as elucidation of the
molecular pathogenesis of atherosclerotic plaques, are
leading to new targets for therapy [18].
DOI:10.1097/MOL.0b013e32832956ed
 158 Bimonthly update Dyslipidemia and cardiovascular diseases
References and recommended reading
Papers of particular interest, published within the annual period of review, have
been highlighted as:
 of special interest
 of outstanding interest
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Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
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This review skillfully analyzes the role of dyslipidemia, hypertension and diabetes in
the molecular pathogenesis of atherosclerotic plaques and discusses approaches
towards understanding targets for therapy.