Conclusions Fibrates have a significantly greater effect in reducing plasma Lp(a ) concentrations than statins .
Addition of fibrates to statins can enhance the Lp(a)-lowering effect of statins
Background Raised plasma lipoprotein(a ) ( Lp(a ) ) concentration is an independent and causal risk factor for atherosclerotic cardiovascular disease .
Several types of pharmacological approaches are under evaluation for their potential to reduce plasma Lp(a ) levels .
There is suggestive evidence that statins and fibrates , two frequently employed lipid-lowering drugs , can lower plasma Lp(a ) .
The present study aims to compare the efficacy of fibrates and statins in reducing plasma concentrations of Lp(a ) using a meta- analysis of r and omized head-to-head trials .
Fibrates increase human apolipoprotein A-II expression through activation of the peroxisome proliferator-activated receptor.
In view of the evidence linking plasma high density lipoprotein (HDL)-cholesterol levels to a protective effect against coronary artery disease and the widespread use of fibrates in the treatment of hyperlipidemia , the goal of this study was to analyze the influence of fibrates on the expression of apolipoprotein ( apo ) A-II , a major protein constituent of HDL . Administration of fenofibrate ( 300 mg/d ) to 16 patients with coronary artery disease result ed in a marked increase in plasma apo A-II concentrations ( 0.34 + /- 0.11 to 0.45 + /- 0.17 grams/liter ; P < 0.01 ) . This increase in plasma apo A-II was due to a direct effect on hepatic apo A-II production , since fenofibric acid induced apo A-II mRNA levels to 450 and 250 % of control levels in primary cultures of human hepatocytes and in human hepatoblastoma HepG2 cells respectively . The induction in apo A-II mRNA levels was followed by an increase in apo A-II secretion in both cell culture systems . Transient transfection experiments of a reporter construct driven by the human apo A-II gene promoter indicated that fenofibrate induced apo A-II gene expression at the transcriptional level . Furthermore , several other peroxisome proliferators , such as the fibrate , Wy-14643 , and the fatty acid , eicosatetraynoic acid ( ETYA ) , also induced apo A-II gene transcription . Unilateral deletions and site-directed mutagenesis identified a sequence element located in the J-site of the apo A-II promoter mediating the responsiveness to fibrates and fatty acids . This element contains two imperfect half sites spaced by 1 oligonucleotide similar to a peroxisome proliferator responsive element ( PPRE ) . Cotransfection assays showed that the peroxisome proliferator activated receptor ( PPAR ) transactivates the apo A-II promoter through this AII-PPRE . Gel retardation assays demonstrated that PPAR binds to the AII-PPRE with an affinity comparable to its binding affinity to the acyl coA oxidase (ACO)-PPRE . In conclusion , in humans fibrates increase plasma apo A-II concentrations by inducing hepatic apo A-II production . Apo A-II expression is regulated at the transcriptional level by fibrates and fatty acids via the interaction of PPAR with the AII-PPRE , thereby demonstrating the pivotal role of PPAR in controlling human lipoprotein metabolism
Conclusions Fibrates have a significantly greater effect in reducing plasma Lp(a ) concentrations than statins .
Addition of fibrates to statins can enhance the Lp(a)-lowering effect of statins
Background Raised plasma lipoprotein(a ) ( Lp(a ) ) concentration is an independent and causal risk factor for atherosclerotic cardiovascular disease .
Several types of pharmacological approaches are under evaluation for their potential to reduce plasma Lp(a ) levels .
There is suggestive evidence that statins and fibrates , two frequently employed lipid-lowering drugs , can lower plasma Lp(a ) .
The present study aims to compare the efficacy of fibrates and statins in reducing plasma concentrations of Lp(a ) using a meta- analysis of r and omized head-to-head trials .