Direct estimation of HDL-mediated cholesterol efflux capacity from serum

Kuusisto, S.; Holmes, M. V.; Ohukainen, P.; Kangas, A. J.; Karsikas, M.; Tiainen, M.; Perola, M.; Salomaa, V.; Kettunen, J.; Ala-Korpela, M.

doi:10.1101/396929

bioRxiv · 10.1101/396929

Direct estimation of HDL-mediated cholesterol efflux capacity from serum

Kuusisto, S.·Holmes, M. V.·Ohukainen, P.·Kangas, A. J.·Karsikas, M.·Tiainen, M.·Perola, M.·Salomaa, V.·Kettunen, J.·Ala-Korpela, M.

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Abstract

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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Kuusisto, S., Holmes, M. V., Ohukainen, P., Kangas, A. J., Karsikas, M., Tiainen, M., Perola, M., Salomaa, V., Kettunen, J., Ala-Korpela, M.. 2018-08-24. Direct estimation of HDL-mediated cholesterol efflux capacity from serum. https://doi.org/10.1101/396929

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