Dataset Information

Regulatory effects of fenofibrate and atorvastatin on lipoprotein A-I and lipoprotein A-I:A-II kinetics in the metabolic syndrome.

ABSTRACT: Subjects with the metabolic syndrome have reduced HDL cholesterol concentration and altered metabolism of high-density lipoprotein (Lp)A-I and LpA-I:A-II particles. In the metabolic syndrome, fenofibrate and atorvastatin may have differential effects on HDL particle kinetics.Eleven men with metabolic syndrome were studied in a randomized, double-blind, crossover trial of 5-week intervention periods with placebo, fenofibrate (200 mg/day), and atorvastatin (40 mg/day). LpA-I and LpA-I:A-II kinetics were examined using stable isotopic techniques and compartmental modeling.Compared with placebo, fenofibrate significantly increased the production of both LpA-I:A-II (30% increase; P < 0.001) and apoA-II (43% increase; P < 0.001), accounting for significant increases of their corresponding plasma concentrations (10 and 23% increases, respectively), but it did not alter LpA-I kinetics or concentration. Atorvastatin did not significantly alter HDL concentration or the kinetics of HDL particles.In the metabolic syndrome, fenofibrate, but not atorvastatin, influences HDL metabolism by increasing the transport of LpA-I:A-II particles.

SUBMITTER: Chan DC

PROVIDER: S-EPMC2768190 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature

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Regulatory effects of fenofibrate and atorvastatin on lipoprotein A-I and lipoprotein A-I:A-II kinetics in the metabolic syndrome.

Chan Dick C DC Watts Gerald F GF Ooi Esther M M EM Rye Kerry-Anne KA Ji Juying J Johnson Anthony G AG Barrett P Hugh R PH

Diabetes care 20090803 11

<h4>Objective</h4>Subjects with the metabolic syndrome have reduced HDL cholesterol concentration and altered metabolism of high-density lipoprotein (Lp)A-I and LpA-I:A-II particles. In the metabolic syndrome, fenofibrate and atorvastatin may have differential effects on HDL particle kinetics.<h4>Research design and methods</h4>Eleven men with metabolic syndrome were studied in a randomized, double-blind, crossover trial of 5-week intervention periods with placebo, fenofibrate (200 mg/day), and ...[more]

PMID: 19651918

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Project description:The fibric acid derivative, fenofibrate (FF) has been used in the US since 1998 to manage patients with dyslipidemia. Typical changes in serum lipids as result a of FF treatment include clinically important mean reductions of serum triglycerides (TG) by a mean change of -93.7 mg/dL (-39.3%), increases of high density lipoprotein cholesterol (HDLC) by +5.5 mg/dL (+12.4%), and reductions in low density lipoprotein cholesterol (LDLC) by -17.9 mg/dL (-12.3%). The greatest reductions in serum TG are usually observed in subjects with elevated baseline TGs including those with the metabolic syndrome (MetS). Although statins remain the mainstay of therapy for most dyslipidemic patients, their combined use with FF would be expected to address residual risk resulting from less than optimal TG and HDLC levels in such patients. Clinical trials examining the cardiovascular benefits of FF alone or combined with statins have produced mixed results. These observations underscore our lack of understanding of which patients may benefit from FF therapy and which do not. Although FF's basic mechanism of action is known to involve PPAR-alpha agonist activity resulting in altered transcription of several genes, the actual genetic bases for variability in lipid response is poorly understood. Studies, such as our GOLDN study and others designed to better understand the genetic determinants of variability in the response to FF treatment and lipid levels. As a result several important genetic determinants of lipid levels have been identified. For example, in the GOLDN study SNPs from different genes were significantly associated with baseline lipid levels before treatment (APOA5- rs662799, rs3135506; APOC3- rs5128, rs2854117, rs4520); APOA4- rs5104; PPARA- rs9626730, rs135543, rs11703495; LPL- rs1801177), after treatment PPARA- rs11708495; LPL- rs1801177, and appeared to modulate overall response to FF treatment (NOS3- rs1799983). In this article, we will review the literature leading up to the contemporary use of FF as an agent to manage patients with dyslipidemia and focus on emerging understanding of the genetic variability in response to FF treatment. On the basis of the available evidence, we conclude that FF is of benefit in the treatment of dyslipidemia, especially among those with MetS. However, more work is needed to specifically identify which individuals derive a benefit from FF administration in terms of clinical outcomes and which do not - particularly in the context of type 2 diabetes.

Dataset Information

Regulatory effects of fenofibrate and atorvastatin on lipoprotein A-I and lipoprotein A-I:A-II kinetics in the metabolic syndrome.

Publications

Regulatory effects of fenofibrate and atorvastatin on lipoprotein A-I and lipoprotein A-I:A-II kinetics in the metabolic syndrome.

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