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PROCAM Study: risk prediction for myocardial infarction using microfluidic high-density lipoprotein (HDL) subfractionation is independent of HDL cholesterol

  • Odilo Mueller , Elaine Chang , David Deng , Torsten Franz , Debra Jing , Robert Kincaid , Yves Konigshofer , Martin Kratzmeier , Michael McNulty , Hao Qian , Juergen Schneider , Helmut Schulte , Udo Seedorf , Xioadan Tian , Mark Van Cleve , Dorothy Yang and Gerd Assmann
Published/Copyright: April 1, 2008

Abstract

Background: High-density lipoprotein (HDL) subfractions are among the new emerging risk factors for atherosclerosis. In particular, HDL 2b has been shown to be linked to cardiovascular risk. This study uses a novel microfluidics-based method to establish HDL 2b clinical utility using samples from the Prospective Cardiovascular Muenster (PROCAM) Study.

Methods: Method performance was established by measuring accuracy, precision, linearity and inter-site precision. Serum samples from 503 individuals collected in the context of the PROCAM study were analyzed by electrophoresis on a microfluidics system. Of these, 251 were male survivors of myocardial infarction (cases), while 252 individuals were matched healthy controls. HDL cholesterol, HDL 2b concentration and HDL 2b percentage were analyzed.

Results: This novel method showed satisfactory assay performance with an inter-site coefficient of variance of <10% for HDL 2b percentage. Parallel patient testing on 52 samples between two sites resulted in a correlation coefficient of r=0.95. Significant differences were observed in the HDL 2b subfraction between cases and controls independent of other risk factors. Including HDL 2b percentage in logistic regression reduced the number of false positives from 64 to 39 and the number of false negative cases from 48 to 45, in the context of this study.

Conclusions: The novel method showed satisfactory assay performance in addition to drastically reduced analysis times and improved ease of use as compared to other methods. Clinical utility of HDL 2b was demonstrated supporting the findings of previous studies.

Clin Chem Lab Med 2008;46:490–8.


Corresponding author: Dr. Odilo Mueller, Agilent Technologies Inc., 5301 Stevens Creek Blvd, Santa Clara, CA 95051, USA Phone: +1-408-553-7016, Fax: +1-408-553-7100,

Received: 2007-9-25
Accepted: 2008-1-8
Published Online: 2008-04-01
Published in Print: 2008-04-01

©2008 by Walter de Gruyter Berlin New York

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