Plasma copper/zinc ratio: an inflammatory/nutritional biomarker as predictor of all-cause mortality in elderly population

Abstract

Associations have been reported between plasma Cu and Zn levels and the incidence of the most important age-related diseases. Previously proposed methods of using plasma Cu/Zn as a predictor of all-cause mortality have been derived from populations in which old and very old subjects were underrepresented. The purpose of this paper is to estimate the usefulness of plasma Cu/Zn as a sensitive biomarker of harmful inflammatory or nutritional changes in the elderly and its incremental prognostic utility as a predictor of all-cause mortality in a functionally independent elderly Italian cohort. The association between plasma Cu/Zn and inflammatory (CRP, ESR, IL-6) or nutritional (albumin, BMI) markers was studied in 498 elderly subjects. Blood samples were taken from 164 healthy 20- to 60-year-old volunteer controls. A 3.5 years prospective follow-up study of mortality by age-related diseases was performed in n = 218 over 70-year-olds. Plasma Cu/Zn ratio was associated with all the inflammatory markers studied, as well as with serum albumin, and predicted 3.5 years mortality in subjects over 70. Plasma Cu/Zn was higher in women than men and increased with advancing age. Subjects with stable cardiovascular disease (CVD) displayed higher plasma Cu/Zn than those without, due mainly to increased plasma Cu. However, most of the age-related changes of Cu/Zn resulted from a progressive decline of plasma Zn. Cu/Zn ratio may be considered an important clinical inflammatory-nutritional biomarker as well as a significant predictor of all-cause mortality in over 70-year-olds.

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Abbreviations

CVD:

Cardiovascular disease

CRP:

C-reactive protein

ESR:

Erythrocytes sedimentation rate

IL-6:

Interleukin-6

BMI:

Body mass index

NSAIDs:

Non-steroidal anti-inflammatory drugs

ACE:

Angiotensin converting enzyme

ICP-MS:

Induction coupled plasma mass spectrometer

IRP:

Immune risk phenotype

CMV:

Cytomegalovirus

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Acknowledgments

This paper was supported by INRCA, Fondazione CASSA RISPARMIO DI LORETO (Loreto, Italy), PFIZER Italia (Rome, Italy), and EU Commission (ZINCAGE project, contract n.FOOD-CT-2004-506850; Coordinator Dr. Eugenio Mocchegiani).

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Correspondence to Eugenio Mocchegiani.

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Malavolta, M., Giacconi, R., Piacenza, F. et al. Plasma copper/zinc ratio: an inflammatory/nutritional biomarker as predictor of all-cause mortality in elderly population. Biogerontology 11, 309–319 (2010). https://doi.org/10.1007/s10522-009-9251-1

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Keywords

  • Zinc
  • Copper
  • Inflammation
  • Biomarker
  • Mortality
  • Elderly