University of Oulu

Tikkanen, E., Jägerroos, V., Holmes, M. V., Sattar, N., Ala‐Korpela, M., Jousilahti, P., Lundqvist, A., Perola, M., Salomaa, V., & Würtz, P. (2021). Metabolic Biomarker Discovery for Risk of Peripheral Artery Disease Compared With Coronary Artery Disease: Lipoprotein and Metabolite Profiling of 31 657 Individuals From 5 Prospective Cohorts. In Journal of the American Heart Association (Vol. 10, Issue 23). Ovid Technologies (Wolters Kluwer Health).

Metabolic biomarker discovery for risk of peripheral artery disease compared with coronary artery disease : lipoprotein and metabolite profiling of 31 657 individuals from 5 prospective cohorts

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Author: Tikkanen, Emmi1; Jägerroos, Vilma1; Holmes, Michael V.2,3,3,4,5;
Organizations: 1Nightingale Health Plc, Helsinki, Finland
2Medical Research Council Population Health Research Unit
3Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health
4University of Oxford, United Kingdom; National Institute for Health Research, Oxford Biomedical Research Centre, Oxford University Hospital, Oxford, United Kingdom
5Medical Research Council Integrative Epidemiology Unit at the University of Bristol, United Kingdom
6Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom
7Computational Medicine, Faculty of Medicine, University of Oulu and Biocenter Oulu, Oulu, Finland
8NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland
9Department of Public Health Solutions, Finnish Institute for Health and Welfare, Helsinki, Finland
10Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 2.2 MB)
Persistent link:
Language: English
Published: John Wiley & Sons, 2021
Publish Date: 2022-02-17


Background: Peripheral artery disease (PAD) and coronary artery disease (CAD) represent atherosclerosis in different vascular beds. We used detailed metabolic biomarker profiling to identify common and discordant biomarkers and clarify pathophysiological differences for these vascular diseases.

Methods and results: We used 5 prospective cohorts from Finnish population (FINRISK 1997, 2002, 2007, and 2012, and Health 2000; n=31 657; median follow‐up time of 14 years) to estimate associations between >200 metabolic biomarkers and incident PAD and CAD. Metabolic biomarkers were measured with nuclear magnetic resonance, and disease events were obtained from nationwide hospital records. During the follow‐up, 498 incident PAD and 2073 incident CAD events occurred. In age‐ and sex‐adjusted Cox models, apolipoproteins and cholesterol measures were robustly associated with incident CAD (eg, hazard ratio [HR] per SD for higher apolipoprotein B/A‐1 ratio, 1.30; 95% CI, 1.25–1.36), but not with incident PAD (HR per SD for higher apolipoprotein B/A‐1 ratio, 1.04; 95% CI, 0.95–1.14; Pheterogeneity<0.001). In contrast, triglyceride levels in low‐density lipoprotein and high‐density lipoprotein were associated with both end points (Pheterogeneity<0.05). Lower proportion of polyunsaturated fatty acids relative to total fatty acids, and higher concentrations of monounsaturated fatty acids, glycolysis‐related metabolites, and inflammatory protein markers were strongly associated with incident PAD, and many of these associations were stronger for PAD than for CAD (Pheterogeneity<0.001). Most differences in metabolic profiles for PAD and CAD remained when adjusting for traditional risk factors.

Conclusions: The metabolic biomarker profile for future PAD risk is distinct from that of CAD. This may represent pathophysiological differences.

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Series: Journal of the American Heart Association
ISSN: 2047-9980
ISSN-E: 2047-9980
ISSN-L: 2047-9980
Volume: 10
Issue: 23
Article number: e021995
DOI: 10.1161/JAHA.121.021995
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
3121 General medicine, internal medicine and other clinical medicine
Funding: This work was primarily funded by Nightingale Health Plc. In addition, this research was also supported by Academy of Finland. Dr Salomaa was supported by the Finnish Foundation for Cardiovascular Research. Dr Holmes works in a unit that receives funding from the UK Medical Research Council and is supported by a British Heart Foundation Intermediate Clinical Research Fellowship (FS/18/23/33512) and the National Institute for Health Research Oxford Biomedical Research Centre. Dr Ala-Korpela is supported by a research grant from the Sigrid Juselius Foundation, Finland. We acknowledge study participants for their availability and commitment, and THL biobank for providing the data.
Copyright information: Copyright © 2021 The Authors. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.