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

Tikkanen, E., Jägerroos, V., Holmes, M. V., Sattar, N. , Ala-Korpela, M., Jousilahti, P., Lundqvist, A., Perola, M., Salomaa, V. and 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. Journal of the American Heart Association, 10(23), e021995. (doi: 10.1161/JAHA.121.021995) (PMID:34845932)

Abstract

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.

• Item Type: Articles
• Additional Information: 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.
• Keywords: Metabolomics, biomarker, coronary artery disease, peripheral artery disease, magnetic resonance spectroscopy.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Sattar, Professor Naveed
• Authors: Tikkanen, E., Jägerroos, V., Holmes, M. V., Sattar, N., Ala-Korpela, M., Jousilahti, P., Lundqvist, A., Perola, M., Salomaa, V., and Würtz, P.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Journal of the American Heart Association
• Publisher: American Heart Association
• ISSN: 2047-9980
• ISSN (Online): 2047-9980
• Published Online: 30 November 2021
• Copyright Holders: Copyright © 2021 The Authors and Nightingale Health Plc.
• First Published: First published in Journal of the American Heart Association 10(23): e021995
• Publisher Policy: Reproduced under a Creative Commons License