Direct Estimation of HDL-Mediated Cholesterol Efflux Capacity From Serum

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

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Abstract

BACKGROUND: HDL-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.

METHODS: 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 7603 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.

RESULTS: 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.

CONCLUSIONS: 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.

Original languageEnglish
JournalClinical Chemistry
Early online date17 Apr 2019
DOIs
Publication statusE-pub ahead of print - 17 Apr 2019

Keywords

  • Cholesterol
  • Cholesterol efflux
  • High-density lipoprotein
  • Coronary artery disease
  • Cardiovascular disease
  • Biomolecular NMR

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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. (2019). Direct Estimation of HDL-Mediated Cholesterol Efflux Capacity From Serum. Clinical Chemistry. https://doi.org/10.1373/clinchem.2018.299222