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Direct estimation of HDL-mediated cholesterol efflux capacity from serum

By Sanna Kuusisto, Michael V. Holmes, Pauli Ohukainen, Antti J Kangas, Mari Karsikas, Mika Tiainen, Markus Perola, Veikko Salomaa, Johannes Kettunen, Mika Ala-Korpela

Posted 24 Aug 2018
bioRxiv DOI: 10.1101/396929 (published DOI: 10.1373/clinchem.2018.299222)

High-density lipoprotein mediated cholesterol efflux capacity (HDL-CEC) is a functional attribute that may have a protective role in atherogenesis. However, the estimation of HDL-CEC is based on in vitro cell assays that are laborious and hamper large-scale phenotyping. Here, we present a cost-effective high-throughput nuclear magnetic resonance (NMR) spectroscopy method to estimate HDL-CEC directly from serum. We applied the new method in a population-based study of 7,603 individuals including 574 who developed incident coronary heart disease (CHD) during 15 years of follow-up, making this the largest quantitative study for HDL-CEC. As estimated by NMR-spectroscopy, a 1-SD higher HDL-CEC was associated with a lower risk of incident CHD (hazards ratio 0.86; 95%CI 0.79-0.93, adjusted for traditional risk factors and HDL-C). These findings are consistent with published associations based on in vitro cell assays. These corroborative large-scale findings provide further support for a potential protective role of HDL-CEC in CHD, and substantiate this new method and its future applications.

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