Pauli Ohukainen1, Sanna Kuusisto2, Johannes Kettunen3, Markus Perola4, Marjo-Riitta Järvelin5, Ville-Petteri Mäkinen6, Mika Ala-Korpela7. 1. Computational Medicine, Faculty of Medicine, University of Oulu, Oulu, Finland; Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland; Biocenter Oulu, University of Oulu, Oulu, Finland. 2. Computational Medicine, Faculty of Medicine, University of Oulu, Oulu, Finland; Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland; Biocenter Oulu, University of Oulu, Oulu, Finland; NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland. 3. Computational Medicine, Faculty of Medicine, University of Oulu, Oulu, Finland; Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland; Biocenter Oulu, University of Oulu, Oulu, Finland; National Institute for Health and Welfare, Helsinki, Finland. 4. National Institute for Health and Welfare, Helsinki, Finland; Diabetes and Obesity Research Program, University of Helsinki, Helsinki, Finland; Estonian Genome Center, University of Tartu, Tartu, Estonia. 5. Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland; Biocenter Oulu, University of Oulu, Oulu, Finland; Unit of Primary Health Care, Oulu University Hospital, OYS, Oulu, Finland; Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK; Department of Life Sciences, College of Health and Life Sciences, Brunel University London, UK. 6. Computational and Systems Biology Program, Precision Medicine Theme, South Australian Health and Medical Research Institute, Australia; Hopwood Centre for Neurobiology, Lifelong Health Theme, SAHMRI, Australia. 7. Computational Medicine, Faculty of Medicine, University of Oulu, Oulu, Finland; Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland; Biocenter Oulu, University of Oulu, Oulu, Finland; NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland. Electronic address: mika.ala-korpela@oulu.fi.
Abstract
BACKGROUND AND AIMS: Population subgrouping has been suggested as means to improve coronary heart disease (CHD) risk assessment. We explored here how unsupervised data-driven metabolic subgrouping, based on comprehensive lipoprotein subclass data, would work in large-scale population cohorts. METHODS: We applied a self-organizing map (SOM) artificial intelligence methodology to define subgroups based on detailed lipoprotein profiles in a population-based cohort (n = 5789) and utilised the trained SOM in an independent cohort (n = 7607). We identified four SOM-based subgroups of individuals with distinct lipoprotein profiles and CHD risk and compared those to univariate subgrouping by apolipoprotein B quartiles. RESULTS: The SOM-based subgroup with highest concentrations for non-HDL measures had the highest, and the subgroup with lowest concentrations, the lowest risk for CHD. However, apolipoprotein B quartiles produced better resolution of risk than the SOM-based subgroups and also striking dose-response behaviour. CONCLUSIONS: These results suggest that the majority of lipoprotein-mediated CHD risk is explained by apolipoprotein B-containing lipoprotein particles. Therefore, even advanced multivariate subgrouping, with comprehensive data on lipoprotein metabolism, may not advance CHD risk assessment.
BACKGROUND AND AIMS: Population subgrouping has been suggested as means to improve coronary heart disease (CHD) risk assessment. We explored here how unsupervised data-driven metabolic subgrouping, based on comprehensive lipoprotein subclass data, would work in large-scale population cohorts. METHODS: We applied a self-organizing map (SOM) artificial intelligence methodology to define subgroups based on detailed lipoprotein profiles in a population-based cohort (n = 5789) and utilised the trained SOM in an independent cohort (n = 7607). We identified four SOM-based subgroups of individuals with distinct lipoprotein profiles and CHD risk and compared those to univariate subgrouping by apolipoprotein B quartiles. RESULTS: The SOM-based subgroup with highest concentrations for non-HDL measures had the highest, and the subgroup with lowest concentrations, the lowest risk for CHD. However, apolipoprotein B quartiles produced better resolution of risk than the SOM-based subgroups and also striking dose-response behaviour. CONCLUSIONS: These results suggest that the majority of lipoprotein-mediated CHD risk is explained by apolipoprotein B-containing lipoprotein particles. Therefore, even advanced multivariate subgrouping, with comprehensive data on lipoprotein metabolism, may not advance CHD risk assessment.