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Association between triglyceride and high-density lipoprotein cholesterol change following fibrate therapy
M W Collins1, C S König2, A Abbas3
1School of Engineering and Design, Brunel University, London UB8 3PH, United Kingdom.
Insights
Fibrate therapy significantly reduces triglycerides (TG) regardless of baseline HDL-C. Pre-treatment TG and TC levels predict TG change, highlighting distinct mechanisms for TG and HDL-C regulation by fibrates.
Area of Science:
- Cardiovascular Medicine
- Pharmacology
- Lipid Metabolism
Background:
- Fibrates' role in cardiovascular risk reduction is debated due to mixed trial outcomes.
- Subgroup analyses indicate benefits in patients with low HDL-C and high TG.
- Previous work identified factors influencing HDL-C changes with fibrates.
Purpose of the Study:
- To investigate triglyceride (TG) changes following fibrate therapy.
- To explore associations between TG change and baseline/changes in HDL-C and TC.
- To understand fibrate mechanisms influencing lipid profiles.
Main Methods:
- Retrospective analysis of 248 patients initiated on fibrates (2002-2008).
- Data collected from lipid clinic case notes.
- Regression analyses used to identify factors associated with TG change.
Main Results:
- TG change was significantly associated with pre-treatment TG and TC levels.
- Pre-treatment TG association remained significant after adjusting for covariates.
- Significant TG reduction was observed irrespective of baseline HDL-C levels.
Conclusions:
- Fibrate effects on TG and HDL-C may be mediated by different mechanisms.
- PPAR-α activation by fibrates might influence TG and HDL-C through distinct pathways.
Background:
Debate surrounding the role of fibrates has followed mixed outcomes from several randomised controlled trials. Subgroup analysis of even the negative trials reveals significant reduction in cardiovascular risk amongst patients with low HDL-C and high TG. We previously described factors associated with HDL-C change following fibrates. As fibrates influence both HDL-C and TG levels via their action on PPAR-α, we now wished to study TG change following fibrate therapy and any associations with baseline and change in HDL-C and TC levels.
Methods:
Data was collected from case notes of patients started on fibrates (n=248) between 2002 and 2008 in the lipid clinics at Heart of England NHS Foundation Trust. Regression analyses were carried out to determine factors associated with changes in TG.
Results:
Multiple regression analysis revealed that TG change was associated with pre-treatment TG (p<0.001) and TC levels (p=0.029). The association between TG change and pre-treatment TG remained significant when all factors including gender, concurrent statin treatment, diabetes and baseline HDL-C were entered into the regression model. Our previous study demonstrated significant post-fibrate HDL-C change in the group with baseline HDL-C values <1.0mmol/l. In our present study significant TG reduction was observed regardless of the baseline patient characteristics including HDL-C levels.
Conclusions:
The actions of fibrates are considered to be mediated via PPAR-α, but our data suggest that the effects on TG and HDL-C are different. Thus, the mechanisms mediating the changes of these lipids following fibrate treatment may vary.
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