Mortality prediction by a metabolomics score and health- and lifestyle-related factors combined

The ageing society and worldwide rise of chronic disease make adequate early identification of at-risk individuals and preventive intervention highly relevant to public health. Molecular indicators of global health have been developed, such as metabolomics-based MetaboHealth. A shortcoming of molecular biomarkers may be their lack of integration of lifestyle and environmental factors relevant for health span. Hence, we explored the MetaboHealth biomarker and a range of health- and lifestyle factors, including plant based diet index, physical activity, alcohol use, smoking, medication use, 25(OH)D status and socioeconomic position and education in a subpopulation (n=35,192, mean age=56 years) from the UK Biobank cohort. We analysed which of these factors associated independently with mortality; which associated with the MetaboHealth score and which of the independent factors improve mortality prediction by MetaboHealth. By applying multivariate Cox regression modelling we found that all factors associated independently with prospective survival, except for physical activity and education level. Sex, smoking and income were most strongly associated with both mortality and the MetaboHealth score. By cross-validation we subsequently assessed contribution of all independent health- and lifestyle-related factors to MetaboHealth-based mortality prediction and computed a weighted score. We found income and medication intake to be the most and diet the least prominently adding contributors. In conclusion, MetaboHealth partly reflects the effect of health- and lifestyle-related factors, while identification of at-risk individuals is improved by the information on income and medication use. Insights in these factors can be attained non-intrusively and may therefore be taken into account in the context of population health management.