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

Abstract

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 proinflammatory 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.

The Association between Zinc and Copper Circulating Levels and Cardiometabolic Risk Factors in Adults: A Study of Qatar Biobank Data

“…The current study also reported that the increase in Cu level was significantly associated with a decrease in the prevalence of low HDL. A cohort study found no association between low and high HDL and Cu when adjusted for sex and BMI [ 91 ]. Also, no association was found between low HDL and serum Cu levels after adjustment for multiple variables in another study [ 45 ].…”

Copper homeostasis and copper-induced cell death in the pathogenesis of cardiovascular disease and therapeutic strategies

“… Year Location Number of patients Age (years) Sex Follow- up (years) Disease Substance of experiment Findings Ref. 1967 Finland 206 >31 Both <1 CVD High-sensitivity C-reactive protein (10 mg/l) Copper is strongly associated with inflammatory burden [ 138 ] 1989 Finland 2492 42–61 Male 5 CVD Copper ion concentration 1.11 ± 0.18 mg/l Association between high serum copper levels and increased risk of atherosclerotic CVD [ 139 ] 1999 Japan 58,646 40–79 Both 10 CVD The average copper intake of all patients is 1.33 ± 0.27 mg/day Dietary copper intake is positively associated with cardiovascular mortality in men and women [ 140 ] 2001 Finland 1866 42–61 Male 3 HF Streptozotocin (55 mg/kg) Increased serum Cu/Zn ratio is associated with increased HF risk in a linear dose-response fashion and may improve HF risk assessment [ 141 ] 2010 Japan 196 80–98 Both 3 CVD – Decreased MCTs are associated with greater serum copper levels [ 142 ] 2014 USA 1427 13–19 Both 3 CVD 111.7–129.7 μg/dl Serum copper concentration correlates with total cholesterol concentration in adolescents [ 143 ] 2018 USA <...…”

Association of the dietary copper intake with all-cause and cardiovascular mortality: A prospective cohort study

“…The correlations of trace minerals with the risk of developing CVD have gained a considerable deal of interest in recent years [1,[8][9][10]. There are controversies on the impact of the consumption of certain metals in one's diet on risk factors and CVD-related events [11].…”

“…There are controversies on the impact of the consumption of certain metals in one's diet on risk factors and CVD-related events [11]. Numerous research reports have pointed to a correlation between levels of metals and risk factors and events associated with CVD [8,[12][13][14], while other studies show little indication that Cu has an independent influence on the biological markers that predict CVD risk [8,10,11]. Interestingly, one case-control study illustrated that higher consumption of Cu in the diet was linked to a reduced incidence of stroke [15].…”