Abstract
Despite the effectiveness of low-density lipoprotein (LDL)-lowering strategies for
the treatment of diabetic dyslipidemia, significant residual risk of atherosclerotic
cardiovascular disease remains. Residual risk might in part be explained by lipid
abnormalities that go beyond LDL cholesterol elevation, collectively termed the “atherogenic
dyslipidemia complex (ADC),” consisting of hypertriglyceridemia, elevated small dense
LDL particles, reduced high-density lipoprotein cholesterol, and high-density lipoprotein
particle numbers, increased remnant lipoproteins, and postprandial hyperlipidemia.
In this review, we briefly discuss the pathophysiology of the typical dyslipidemia
that occurs in insulin-resistant states including obesity, the metabolic syndrome,
and type 2 diabetes. Lipid-modifying strategies including lifestyle modification,
ezetimibe, statins, fibrates, niacin, and cholesteryl ester transfer protein inhibitors
in treating ADC are discussed. With the advent of novel therapies involving antisense
oligonucleotides and monoclonal antibodies, new targets can be specifically downregulated
to potentially promote lipoprotein clearance or suppress production. We review novel
approaches currently undergoing clinical testing and we speculate on their suitability
for use in treating ADC for the prevention of atherosclerotic cardiovascular disease.
In addition, future targets that might be considered for therapeutic development are
discussed.
Résumé
Malgré l’efficacité des stratégies de réduction du taux de lipoprotéines de faible
densité (LDL) dans le traitement de la dyslipidémie du diabétique, un important risque
résiduel de maladie cardiovasculaire athéroscléreuse demeure. Ce risque résiduel pourrait
être en partie expliqué par des anomalies lipidiques autres que la hausse du cholestérol
LDL, collectivement appelées dyslipidémies athérogènes et comprenant l’hypertriglycéridémie,
le taux élevé de petites particules LDL denses, la diminution du cholestérol à lipoprotéines
de haute densité et de particules de lipoprotéines de haute densité, l’augmentation
de lipoprotéines reliquats et l’hyperlipidémie postprandiale. Dans cette analyse,
nous abordons brièvement la physiopathologie de la dyslipidémie type qui survient
en cas d’insulinorésistance, observée en présence d’obésité, de syndrome métabolique
et de diabète de type 2. Nous abordons les stratégies visant à corriger la lipidémie,
comme la modification du mode de vie, l’ézétimibe, les statines, les fibrates, la
niacine et les inhibiteurs de la protéine de transfert de l’ester de cholestéryle,
pour traiter les dyslipidémies athérogènes. Avec la venue de nouveaux traitements
comportant des oligonucléotides antisens et des anticorps monoclonaux, les nouvelles
cibles peuvent être particulièrement abaissées pour potentiellement favoriser la clairance
des lipoprotéines ou en supprimer la production. Nous étudions des méthodes novatrices
impliquant des épreuves cliniques existantes et nous spéculons sur la possibilité
de leur utilisation dans le traitement des dyslipidémies athérogènes pour prévenir
la maladie cardiovasculaire athéroscléreuse. De plus, nous abordons de futures cibles
qui pourraient être considérées dans la mise au point de traitements.
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Article info
Publication history
Published online: December 14, 2017
Accepted:
December 7,
2017
Received:
November 2,
2017
Footnotes
See page 602 for disclosure information.
Identification
Copyright
© 2017 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
