University of Oulu

Palaniswamy, S., Piltonen, T., Koiranen, M., Mazej, D., Järvelin, M.-R., Abass, K., … Sebert, S. (2019). The association between blood copper concentration and biomarkers related to cardiovascular disease risk – analysis of 206 individuals in the Northern Finland Birth Cohort 1966. Journal of Trace Elements in Medicine and Biology, 51, 12–18.

The association between blood copper concentration and biomarkers related to cardiovascular disease risk : analysis of 206 individuals in the Northern Finland Birth Cohort 1966

Saved in:
Author: Palaniswamy, Saranya1,2; Piltonen, Terhi3,4; Koiranen, Markku1;
Organizations: 1Center For Life Course Health Research, Faculty of Medicine, University of Oulu, FI-90014, Oulu, Finland
2Biocenter Oulu, University of Oulu, FI-90014, Oulu, Finland
3Department of Obstetrics and Gynecology, Oulu University Hospital, University of Oulu and PEDEGO Research Unit, P.O. Box 23, FI-90029, Oulu, Finland
4Medical Research Center Oulu, Oulu University Hospital and University of Oulu, P.O. Box 8000, FI-90014, Oulu, Finland
5Department of Environmental Sciences, Jozef Stefan Institute, Jamova cesta 39, 1000, Ljubljana, Slovenia
6Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, SW7 2AZ, United Kingdom
7Oulu University Hospital, Unit of Primary Care, FI-90014, Oulu, Finland
8Department of Life Sciences, College of Health and Life Sciences, Brunel University London, Kingston Lane, Uxbridge, Middlesex UB8 3PH, United Kingdom
9Arctic Health, Faculty of Medicine, University of Oulu, FI-90014, Oulu, Finland
10Department of Genomics of Complex Diseases, School of Public Health, Imperial College London, London, SW7 2AZ, United Kingdom
Format: article
Version: accepted version
Access: open
Online Access: PDF Full Text (PDF, 1.2 MB)
Persistent link:
Language: English
Published: Elsevier, 2018
Publish Date: 2019-09-11


Background: Copper is an abundant trace element in humans where alterations in the circulating concentration could inform on chronic disease aetiology. To date, data are lacking to study how copper may associate with cardiovascular disease (CVD) risk factors in young and healthy population. Molecular evidence suggests an important role of copper in liver metabolism, an essential organ in maintaining cardiovascular health and inflammation, therefore supporting copper as an associated biomarker of the risk.

Objective: We performed a cross-sectional analysis to examine the possible associations between blood copper levels and risk factors for CVD and pre-inflammatory process.

Design: The data has been collected from a sub-sample set of the Northern Finland Birth Cohort 1966 (NFBC1966) at 31 years.

Participants: The study included 206 individuals, 116 men and 90 women. To reduce environmental individual variations affecting both copper and the metabolic profile in the study sample, the participants were selected as: i) being born in Finnish Lapland and ii) living in their birth place for the last five years preceding blood sampling.

Main outcome measures: Fasting blood copper concentration was measured by inductively coupled plasma mass spectrometer. The CVD risk factors included 6 metabolic clusters (30 cardiovascular and pro-inflammatory factors) assessed by nuclear magnetic resonance. Multivariate linear regression analysis was performed to test the linear association between blood copper and 6 metabolic clusters for CVD risk. Associations were assessed under correction for multiple testing.

Results: Copper (Cu) levels were comparable in men and women, with no difference between sexes (p-value  <0.60). In multiple regression models, sex adjusted, copper was associated with 9 metabolites from 4 metabolic clusters. After adjustment with BMI, copper was associated with 4 metabolites from 3 metabolic clusters: glutamine, beta-hydroxybutyrate, alpha-1-acid glycoprotein (AGP) and high-sensitive C-reactive protein (hs-CRP). After correction for multiple testing, Cu was found positively associated with only 2 biomarkers of inflammation including AGP [p = 0.04] and hs-CRP [p  = 0.0001].

Conclusions: Considering the strength and limitation of the study design, the present study does not support evidence for an independent role of copper on biomarkers for CVD risk. Nevertheless, we are reporting a robust association of copper with the inflammatory load that is important to consider in light with the inflammatory component of chronic health. In addition, the association of copper with metabolites may be attributable to BMI or environmental factors associated to it, and warrants further research in large population samples.

see all

Series: Journal of trace elements in medicine and biology
ISSN: 0946-672X
ISSN-E: 1878-3252
ISSN-L: 0946-672X
Volume: 51
Pages: 12 - 18
DOI: 10.1016/j.jtemb.2018.09.003
Type of Publication: A1 Journal article – refereed
Field of Science: 3142 Public health care science, environmental and occupational health
Funding: This work was supported by the Academy of Finland (MR.J, grant number 24300796, 24302031); Biocenter Oulu Doctoral Program (S.P), Juho Vainio Foundation (S.P), and Orion Research Foundation sr (S.P); The Finnish Medical Foundation (T.P), and Sigrid Jusélius Foundation (T.P); European Union’s Horizon 2020 research and innovation programme (MR.J, S.S, S.P, grant number 633595) for the DynaHEALTH action and LifeCycle EU, and European Community’s Seventh Framework Programme FP7/2007-2013-Environment (including Climate Change) FP7-ENV-2008-1- under Grant Agreement No: 226534-ArcRisk (A.R and K.A). No funding bodies had any role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
EU Grant Number: (633595) DYNAHEALTH - Understanding the dynamic determinants of glucose homeostasis and social capability to promote Healthy and active aging
(733206) LIFECYCLE - Early-life stressors and LifeCycle health
(226534) ARCRISK - Arctic Health Risks: Impacts on health in the Arctic and Europe owing to climate-induced changes in contaminant cycling
Copyright information: © 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http:/