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

doi:10.1373/clinchem.2018.299222

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

Research output: Contribution to journal › Article (Academic Journal) › peer-review

18 Citations (Scopus)

247 Downloads (Pure)

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 language	English
Journal	Clinical Chemistry
Early online date	17 Apr 2019
DOIs	https://doi.org/10.1373/clinchem.2018.299222
Publication status	E-pub ahead of print - 17 Apr 2019

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

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

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10.1373/clinchem.2018.299222

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This is the author accepted manuscript (AAM). The final published version (version of record) is available online via AACC at http://clinchem.aaccjnls.org/content/early/2019/04/16/clinchem.2018.299222 . Please refer to any applicable terms of use of the publisher.
Accepted author manuscript, 4.25 MB
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This is the author accepted manuscript (AAM). The final published version (version of record) is available online via AACC at http://clinchem.aaccjnls.org/content/early/2019/04/16/clinchem.2018.299222 . Please refer to any applicable terms of use of the publisher.
Accepted author manuscript, 1.08 MB

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@article{e85d7d19f09b4b37a2658e144e2d1ee1,

title = "Direct Estimation of HDL-Mediated Cholesterol Efflux Capacity From Serum",

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.",

keywords = "Cholesterol, Cholesterol efflux, High-density lipoprotein, Coronary artery disease, Cardiovascular disease, Biomolecular NMR",

author = "Sanna Kuusisto and Holmes, \{Michael V\} and Pauli Ohukainen and Kangas, \{Antti J\} and Mari Karsikas and Mika Tiainen and Markus Perola and Veikko Salomaa and Johannes Kettunen and Mika Ala-Korpela",

year = "2019",

month = apr,

day = "17",

doi = "10.1373/clinchem.2018.299222",

language = "English",

journal = "Clinical Chemistry",

issn = "0009-9147",

publisher = "Oxford University Press",

}

TY - JOUR

T1 - Direct Estimation of HDL-Mediated Cholesterol Efflux Capacity From Serum

AU - Kuusisto, Sanna

AU - Holmes, Michael V

AU - Ohukainen, Pauli

AU - Kangas, Antti J

AU - Karsikas, Mari

AU - Tiainen, Mika

AU - Perola, Markus

AU - Salomaa, Veikko

AU - Kettunen, Johannes

AU - Ala-Korpela, Mika

PY - 2019/4/17

Y1 - 2019/4/17

N2 - 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.

AB - 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.

KW - Cholesterol

KW - Cholesterol efflux

KW - High-density lipoprotein

KW - Coronary artery disease

KW - Cardiovascular disease

KW - Biomolecular NMR

U2 - 10.1373/clinchem.2018.299222

DO - 10.1373/clinchem.2018.299222

M3 - Article (Academic Journal)

C2 - 30996052

SN - 0009-9147

JO - Clinical Chemistry

JF - Clinical Chemistry

ER -

Direct Estimation of HDL-Mediated Cholesterol Efflux Capacity From Serum

Abstract

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Keywords

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