Document Detail


Clustering by plasma lipoprotein profile reveals two distinct subgroups with positive lipid response to fenofibrate therapy.
MedLine Citation:
PMID:  22719863     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Fibrates lower triglycerides and raise HDL cholesterol in dyslipidemic patients, but show heterogeneous treatment response. We used k-means clustering to identify three representative NMR lipoprotein profiles for 775 subjects from the GOLDN population, and study the response to fenofibrate in corresponding subgroups. The subjects in each subgroup showed differences in conventional lipid characteristics and in presence/absence of cardiovascular risk factors at baseline; there were subgroups with a low, medium and high degree of dyslipidemia. Modeling analysis suggests that the difference between the subgroups with low and medium dyslipidemia is influenced mainly by hepatic uptake dysfunction, while the difference between subgroups with medium and high dyslipidemia is influenced mainly by extrahepatic lipolysis disfunction. The medium and high dyslipidemia subgroups showed a positive, yet distinct lipid response to fenofibrate treatment. When comparing our subgroups to known subgrouping methods, we identified an additional 33% of the population with favorable lipid response to fenofibrate compared to a standard baseline triglyceride cutoff method. Compared to a standard HDL cholesterol cutoff method, the addition was 18%. In conclusion, by using constructing subgroups based on representative lipoprotein profiles, we have identified two subgroups of subjects with positive lipid response to fenofibrate therapy and with different underlying disturbances in lipoprotein metabolism. The total subgroup with positive lipid response to fenofibrate is larger than subgroups identified with baseline triglyceride and HDL cholesterol cutoffs.
Authors:
Kees van Bochove; Daniël B van Schalkwijk; Laurence D Parnell; Chao-Qiang Lai; José M Ordovás; Albert A de Graaf; Ben van Ommen; Donna K Arnett
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-06-12
Journal Detail:
Title:  PloS one     Volume:  7     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2012  
Date Detail:
Created Date:  2012-06-21     Completed Date:  2012-12-13     Revised Date:  2013-07-12    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e38072     Citation Subset:  IM    
Affiliation:
Department of Microbiology and Systems Biology, TNO, Zeist and Leiden, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
Cluster Analysis
Dyslipidemias / blood,  drug therapy*
Female
Fenofibrate / therapeutic use*
Humans
Hypolipidemic Agents / therapeutic use*
Lipoproteins / blood*,  classification
Male
Grant Support
ID/Acronym/Agency:
U01HL72524/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Hypolipidemic Agents; 0/Lipoproteins; 49562-28-9/Fenofibrate
Comments/Corrections

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