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. 2023 Nov 1;23(1):2138.
doi: 10.1186/s12889-023-17018-3.

Association of serum copper (Cu) with cardiovascular mortality and all-cause mortality in a general population: a prospective cohort study

Xiaozhong Li #  1 , Jitao Ling #  2 , Qingwen Hu  1 , Changchang Fang  1 , Kaibo Mei  3 , Yifan Wu  1 , Jingyi Huang  1 , Qin Ling  1 , Yixuan Chen  2 , Peng Yu  2 , Xiao Liu  4   5   6 , Juxiang Li  7
Affiliations

Association of serum copper (Cu) with cardiovascular mortality and all-cause mortality in a general population: a prospective cohort study

Xiaozhong Li et al. BMC Public Health. .

Abstract

Background: Copper (Cu) homeostasis and Cu-induced cell death are gaining recognition as crucial processes in the pathogenesis of cardiovascular disease (CVD). Circulating Cu associated with CVD and mortality is yet to be fully elucidated.

Objective: This national prospective cohort study is to estimate relationship between serum Cu and the risk of CVD and all-cause mortality.

Methods: This study included participants from the National Health and Nutrition Examination Survey 2011-2016. Weighted Cox proportional hazards regression analysis and exposure-response curves were applied.

Results: This included 5,412 adults, representing 76,479,702 individuals. During a mean of 5.85 years of follow-up (31,653 person-years), 96 CVD and 356 all-cause mortality events occurred. Age and sex-adjusted survival curves showed that individuals with higher levels of serum Cu experienced increased CVD and all-cause death rates (tertiles, p < 0.05). Compared with the participant in tertile 1 of serum Cu (< 16.31 mol/L), those in tertile 3 (≥ 19.84 mol/L) were significantly associated with CVD mortality (HR: 7.06, 95%CI: 1.85,26.96), and all-cause mortality (HR: 2.84, 95% CI: 1.66,4.87). The dose-response curve indicated a linear relationship between serum Cu and CVD mortality (p -nonlinear = 0.48) and all-cause (p -nonlinear = 0.62). A meta-analysis included additional three prospective cohorts with 13,189 patients confirmed the association between higher serum Cu and CVD (HR: 2.08, 95% CI: 1.63,2.65) and all-cause mortality (HR: 1.89, 95%CI: 1.58,2.25).

Conclusion: The present study suggests excessive serum Cu concentrations are associated with the risk of CVD and all-cause mortality in American adults. Our findings and the causal relationships require further investigation.

Keywords: Cardiovascular Diseases; Copper; NHANES.

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Conflict of interest statement

The authors declare no competing financial interests.

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Study selection from the NHANES 2011–2016; workflow and major findings of this study Abbreviations: NHANES: National Health and Nutrition Examination Survey; CVD: cardiovascular disease; Cu: copper.
Fig. 2
Fig. 2
Age- and sex-adjusted Kaplan–Meier curves of tertiles of serum Cu with CVD and all-cause mortality. (A) CVD mortality. (B) all-cause mortality Abbreviations: Cu: copper; CVD: cardiovascular disease
Fig. 3
Fig. 3
Cox proportional hazards regression model of serum copper with CVD (A) and all-cause mortality (B). The serum copper distribution was depicted using the histogram. Adjusted hazard ratios (95% CI) for CVD and all-cause mortality are shown with red curves. The serum copper level considered for this analysis was 18.1 µmol/L. The model cubic spline curves have 3 knots. Adjustments included age, sex, marital, education, BMI, eGFR, HbA1c, UA, CHD, diabetes mellitus, hypertension, dyslipidemia, moderate PA, smoking status, and drinking status Abbreviations: CVD: cardiovascular disease; BMI: body mass index; eGFR: estimated glomerular filtration rate; HDL-C: high-density lipoprotein cholesterol; UA: uric acid; CHD: coronary heart disease; PA: Physical activity
Fig. 4
Fig. 4
Association of serum copper (T3 vs. T1) with CVD and all-cause mortality in different subgroups. A: CVD mortality; B: all-cause mortality. The results are adjusted for age, sex, marital, education, BMI, eGFR, HbA1c, UA, CHD, diabetes mellitus, hypertension, dyslipidemia, moderate PA, smoking status, and drinking status, if the above variables are not adjusted Abbreviations: CVD: cardiovascular disease; BMI: body mass index; eGFR: estimated glomerular filtration rate; HDL-C: high-density lipoprotein cholesterol; UA: uric acid; PA: Physical activity
Fig. 5
Fig. 5
Forest plot of the pooled results between serum Cu and CVD and all-cause mortality by Fixed-effects model (highest vs. lowest). A: CVD mortality; B: All-cause mortality Note: Li 2023 refer to present study. TE: logHR; SE: selogHR. Cu: copper; CVD: Cardiovascular diseases. Referents for lowest of serum Cu were the individuals reporting with lowest of serum Cu within the specific study
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