Sanna Kuusisto1,2, Michael V Holmes3,4,5,6, Pauli Ohukainen1, Antti J Kangas7, Mari Karsikas1, Mika Tiainen7, Markus Perola8,9,10, Veikko Salomaa8, Johannes Kettunen1,8, Mika Ala-Korpela11,2,6,12,13,14. 1. Computational Medicine, Faculty of Medicine, University of Oulu and Biocenter Oulu, Oulu, Finland. 2. NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland. 3. Medical Research Council Population Health Research Unit, University of Oxford, Oxford, UK. 4. Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK. 5. National Institute for Health Research, Oxford Biomedical Research Centre, Oxford University Hospital, Oxford, UK. 6. Medical Research Council Integrative Epidemiology Unit at the University of Bristol, Bristol, UK. 7. Nightingale Health Ltd., Helsinki, Finland. 8. Department of Health, National Institute for Health and Welfare, Helsinki, Finland. 9. Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland. 10. Estonian Genome Center, University of Tartu, Tartu, Estonia. 11. Computational Medicine, Faculty of Medicine, University of Oulu and Biocenter Oulu, Oulu, Finland; mika.ala-korpela@baker.edu.au. 12. Population Health Science, Bristol Medical School, University of Bristol, Bristol, UK. 13. Systems Epidemiology, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia. 14. Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, The Alfred Hospital, Monash University, Melbourne, VIC, Australia.
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.
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.
Authors: Holger Thiele; Petra Buettner; Wenke Cheng; Maciej Rosolowski; Julia Boettner; Steffen Desch; Alexander Jobs Journal: Lipids Health Dis Date: 2022-05-28 Impact factor: 4.315
Authors: Sanna Kuusisto; Minna K Karjalainen; Therese Tillin; Antti J Kangas; Michael V Holmes; Mika Kähönen; Terho Lehtimäki; Jorma Viikari; Markus Perola; Nishi Chaturvedi; Veikko Salomaa; Olli T Raitakari; Marjo-Riitta Järvelin; Johannes Kettunen; Mika Ala-Korpela Journal: J Intern Med Date: 2022-03-22 Impact factor: 13.068