A1 Journal article (refereed)
Towards early risk biomarkers : serum metabolic signature in childhood predicts cardio-metabolic risk in adulthood (2021)
Ojanen, X., Cheng, R., Törmäkangas, T., Rappaport, N., Wilmanski, T., Wu, N., Fung, E., Nedelec, R., Sebert, S., Vlachopoulos, D., Yan, W., Price, N. D., Cheng, S., & Wiklund, P. (2021). Towards early risk biomarkers : serum metabolic signature in childhood predicts cardio-metabolic risk in adulthood. EBioMedicine, 72, Article 103611. https://doi.org/10.1016/j.ebiom.2021.103611
JYU authors or editors
Publication details
All authors or editors: Ojanen, Xiaowei; Cheng, Runtan; Törmäkangas, Timo; Rappaport, Noa; Wilmanski, Tomasz; Wu, Na; Fung, Erik; Nedelec, Rozenn; Sebert, Sylvain; Vlachopoulos, Dimitris; et al.
Journal or series: EBioMedicine
ISSN: 2352-3964
eISSN: 2352-3964
Publication year: 2021
Volume: 72
Article number: 103611
Publisher: Elsevier
Publication country: Netherlands
Publication language: English
DOI: https://doi.org/10.1016/j.ebiom.2021.103611
Publication open access: Openly available
Publication channel open access: Open Access channel
Publication is parallel published (JYX): https://jyx.jyu.fi/handle/123456789/78240
Additional information: Available at SSRN: https://ssrn.com/abstract=3782500 or http://dx.doi.org/10.2139/ssrn.3782500
Abstract
Cardiovascular diseases may originate in childhood. Biomarkers identifying individuals with increased risk for disease are needed to support early detection and to optimise prevention strategies.
Methods
In this prospective study, by applying a machine learning to high throughput NMR-based metabolomics data, we identified circulating childhood metabolic predictors of adult cardiovascular disease risk (MetS score) in a cohort of 396 females, followed from childhood (mean age 11·2 years) to early adulthood (mean age 18·1 years). The results obtained from the discovery cohort were validated in a large longitudinal birth cohort of females and males followed from puberty to adulthood (n = 2664) and in four cross-sectional data sets (n = 6341).
Findings
The identified childhood metabolic signature included three circulating biomarkers, glycoprotein acetyls (GlycA), large high-density lipoprotein phospholipids (L-HDL-PL), and the ratio of apolipoprotein B to apolipoprotein A-1 (ApoB/ApoA) that were associated with increased cardio-metabolic risk in early adulthood (AUC = 0·641‒0·802, all p<0·01). These associations were confirmed in all validation cohorts with similar effect estimates both in females (AUC = 0·667‒0·905, all p<0·01) and males (AUC = 0·734‒0·889, all p<0·01) as well as in elderly patients with and without type 2 diabetes (AUC = 0·517‒0·700, all p<0·01). We subsequently applied random intercept cross-lagged panel model analysis, which suggested bidirectional causal relationship between metabolic biomarkers and cardio-metabolic risk score from childhood to early adulthood.
Interpretation
These results provide evidence for the utility of a circulating metabolomics panel to identify children and adolescents at risk for future cardiovascular disease, to whom preventive measures and follow-up could be indicated.
Keywords: cardiovascular diseases; risk factors; biomarkers; metabolic products; childhood; adulthood; longitudinal research
Free keywords: metabolomics; cardio-metabolic risk; children; longitudinal-study; ALSPAC
Contributing organizations
Ministry reporting: Yes
Reporting Year: 2021
JUFO rating: 1
