Lipid metabolism and emerging targets for lipid-lowering therapy

Abstract Cardiovascular disease (CVD) is one of the leading causes of morbidity and mortality worldwide, and dyslipidemia constitutes a major risk factor for CVD and premature atherosclerosis. Therapies reducing the plasma levels of atherogenic lipoproteins are well-established interventions that de...

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Bibliographic Details
Published in:Canadian journal of cardiology 2017-07, Vol.33 (7), p.872-882
Main Authors: Gaudet, Daniel, MD, PhD, Drouin-Chartier, Jean-Philippe, MSc, Couture, Patrick, MD, FRCP(C), PhD
Format: Article
Language:English
Subjects:
Cardiovascular
Cardiovascular Diseases - epidemiology
Cardiovascular Diseases - etiology
Cardiovascular Diseases - prevention & control
Dyslipidemias - blood
Dyslipidemias - complications
Dyslipidemias - drug therapy
Global Health
Humans
Hypolipidemic Agents - therapeutic use
Lipid Metabolism - drug effects
Lipids - blood
Morbidity
Precision Medicine - methods
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Summary:Abstract Cardiovascular disease (CVD) is one of the leading causes of morbidity and mortality worldwide, and dyslipidemia constitutes a major risk factor for CVD and premature atherosclerosis. Therapies reducing the plasma levels of atherogenic lipoproteins are well-established interventions that decrease CVD risk. However, treatment of dyslipidemia with the most widely used lipid-lowering drugs (i.e., statins and ezetimibe) often fails to protect a significant proportion of patients from cardiovascular risk. The development of several novel therapies to treat lipid-related disorders and their associated risks is ongoing and includes the following: (a) reducing plasma levels of atherogenic lipoproteins using proprotein convertase subtilisin/kexin type 9 inhibitors, antisense inhibitors of apo(a), microsomal triglyceride transfer protein inhibitors, antisense oligonucleotides of apoB for inhibiting VLDL production, and inhibitors of angiopoietin-like protein 3 or apoC-III for triglyceride-rich lipoprotein (TRL) management upstream of LDL production as well as gene replacement therapy to improve LDL and TRL clearance; (b) emerging therapies that target HDL and reverse cholesterol transport using cholesteryl ester transfer protein inhibitors, HDL peptide mimetics, and autologous infusion of pre-beta HDLs. Clinical trials of several of these emerging therapies are currently being conducted. Despite the potential efficacy of these new therapies in CVD prevention, their costs may limit their use due to limited reimbursement funds. Therefore, the real challenge facing the next generation of lipid-lowering agents will most likely be accessibility, reflecting a new paradigm that applies to almost all emerging therapies for any disease in the era of precision medicine.
ISSN:0828-282X
1916-7075
DOI:10.1016/j.cjca.2016.12.019