Copper, ceruloplasmin, and long-term cardiovascular and total mortality (The Ludwigshafen Risk and Cardiovascular Health Study)

Abstract

Background. Copper and its main transport protein ceruloplasmin have been suggested to promote the development of atherosclerosis. Most of the data come from experimental and animal model studies. Copper and mortality have not been simultaneously evaluated in patients undergoing coronary angiography. Methods and results. We examined whether serum copper and ceruloplasmin concentrations are associated with angiographic coronary artery disease (CAD) and mortality from all causes and cardiovascular causes in 3253 participants of the Ludwigshafen Risk and Cardiovascular Health Study. Age and sex-adjusted hazard ratios (HR) for death from any cause were 2.23 (95% CI, 1.85–2.68) for copper and 2.63 (95% CI, 2.17–3.20) for ceruloplasmin when we compared the highest with the lowest quartiles. Corresponding hazard ratios (HR) for death from cardiovascular causes were 2.58 (95% CI, 2.05–3.25) and 3.02 (95% CI, 2.36–3.86), respectively. Further adjustments for various risk factors and clinical variables considerably attenuated these associations, which, however, were still statistically significant and the results remained consistent across subgroups. Conclusions. The elevated concentrations of both copper and ceruloplasmin are independently associated with increased risk of mortality from all causes and from cardiovascular causes.

Keywords::

• oxidative stress
• coronary artery disease
• mortality
• copper
• ceruloplasmin
• inflammation

Acknowledgements

We thank the participants of the LURIC Study and the study team either temporarily or permanently involved in patient recruitment, sample and data handling, and the laboratory staff at the Ludwigshafen General Hospital and the Universities of Freiburg (Germany), Ulm (Germany), and Graz (Austria).

Declaration of interest

The authors report no declarations of interest. The authors alone are responsible for the content and writing of the paper.

LURIC has received funding from the 6th Framework Program (integrated project Bloodomics, grant LSHM-CT-2004-503485) and from the 7th Framework Program (Atheroremo, grant agreement number 201668, and RiskyCAD, grant agreement number 305739) of the European Union as well as from the INTERREG IV Oberrhein Program (Project A28, Genetic mechanisms of cardiovascular diseases) with support from the European Regional Development Fund (ERDF) and the Wissenschaftsoffensive TMO.