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Background & Aims: Wilson disease (WD) is caused by accumulation of copper primarily in the liver and brain. During maintenance therapy of WD with D-penicillamine, current guidelines recommend on-treatment ranges of urinary copper excretion (UCE) of 200-500 µg/24 h and serum non-ceruloplasmin-bound copper (NCC) of 50-150 µg/L. We compared NCC (measured by two novel assays) and UCE from patients with clinically stable WD on D-penicillamine therapy with these recommendations. Methods: This is a secondary analysis of data from the Chelate trial (NCT03539952) that enrolled physician-selected patients with clinically stable WD on D-penicillamine maintenance therapy (at an unaltered dose for at least 4 months). We analyzed laboratory samples from the first screening visit, prior to interventions. NCC was measured by either protein speciation (NCC-Sp) using anion exchange high-performance liquid chromatography protein speciation followed by copper determination with inductively coupled plasma mass spectroscopy or as exchangeable copper (NCC-Ex). NCC-Sp was also analyzed in healthy controls (n = 75). Results: In 76 patients with WD with 21.3±14.3 average treatment-years, NCC-Sp (mean±SD: 56.6±26.2 µg/L) and NCC-Ex (mean±SD: 57.9±24.7 µg/L) were within the 50-150 µg/L target in 61% and 54% of patients, respectively. In addition, 36% and 31%, respectively, were even below the normal ranges (NCC-Sp: 46-213 µg/L, NCC-Ex: 41-71 µg/L). NCC-Ex positively correlated with NCC-Sp (r2 = 0.66, p <0.001) but with systematic deviation. UCE was outside the 200-500 µg/24 h target range in 58%. Only 14/69 (20%) fulfilled both the NCC-Sp and UCE targets. Clinical or biochemical signs of copper deficiency were not detected. Conclusion: Clinically stable patients with WD on maintenance D-penicillamine therapy frequently have lower NCC-Sp or higher UCE than current recommendations without signs of overtreatment. Further studies are warranted to identify appropriate target ranges of NCC-Sp, NCC-Ex and UCE in treated WD. Impact and implications: Chelator treatment of patients with Wilson disease (WD) is currently guided by measurements of non-ceruloplasmin-bound copper (NCC) and 24 h urinary copper excretion (UCE) but validation is limited. In 76 adults with ≈21 years history of treated WD and clinically stable disease on D-penicillamine therapy, NCC was commonly found to be below normal values and recommended target ranges whether measured by protein speciation (NCC-Sp) or as exchangeable copper (NCC-Ex), while UCE values were above the recommended target range in 49%. Common wisdom would suggest overtreatment in these cases, but no clinical or biochemical signs of copper deficiency were observed. Exploratory analysis of liver enzymes suggested that NCC below levels seen in controls may be beneficial, while the relation to UCE was less clear. The data calls for critical re-evaluation of target ranges for treatment of WD, specific for drug and laboratory methodology. Clinical trial number: (NCT03539952).
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The association between serum copper and polycystic ovary syndrome (PCOS) lacks definitive conclusions, and the intricate interactions with in vitro fertilization (IVF) cycle characteristics in infertility remain insufficiently explored. This retrospective study included 560 patients with tubal infertility (no-PCOS) and 266 patients with PCOS undergoing IVF at the Affiliated Suzhou Hospital of Nanjing Medical University from January 2018 to December 2022. Patients' basic characteristics, hormonal and metabolic parameters, essential trace elements, and IVF cycle characteristics were measured and analyzed. The results revealed a significantly elevated serum copper level in the PCOS group compared to the control group [17.27 (15.54, 19.67) vs 15.4 (13.87, 17.35), µmol/L; p < .001]. Spearman correlation analyses revealed a significant positive correlation between serum copper concentration and body mass index (BMI), fasting glucose (FG), triglyceride (TG), total cholesterol (TC), and low-density lipoprotein (LDL) in the no-PCOS group. Additionally, a notable negative correlation with high-density lipoprotein (HDL) was observed (r = -.184, p < .001). Within the PCOS group, serum copper concentration correlated significantly with BMI (r = .198, p = .004) and TG (r = .214, p = .002). The linear trend analysis indicated no significant relationship between serum copper concentration and ovarian response as well as preimplantation outcomes in both groups after adjusting for confounding factors. Our study provided evidence of elevated serum copper concentration in PCOS patients, closely associated with lipid metabolism but showing no correlation with IVF outcomes. These findings provide valuable real-world data, enriching our nuanced understanding of the role of copper in female fertility.
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Background: The rising prevalence of diabetes underscores the need for identifying effective prevention strategies. Recent research suggests environmental factors, particularly heavy metals like copper, significantly influence health outcomes, including diabetes, through mechanisms involving inflammation and oxidative stress. This study aims to explore how serum copper levels affect blood glucose, employing NHANES data from 2011 to 2016, to provide insights into environmental health's role in diabetes prevention and management. Methods: The study analyzed data from 2,318 NHANES participants across three cycles (2011-2016), focusing on those with available data on serum copper, inflammatory markers, and blood glucose levels. We utilized principal component analysis for selecting inflammatory markers, mediation analysis to examine direct and indirect effects, multiple linear regression for assessing relationships between markers and glucose levels, and weighted quantile sum regression for evaluating individual and collective marker effects, adjusting for demographic variables and serum copper. Results: Participants averaged 42.70 years of age, with a near-even split between genders. Average serum copper was 119.50 µg/dL, white blood cell count 6.82 × 109/L, and fasting blood glucose 107.10 mg/dL. Analyses identified significant mediation by inflammatory markers (especially white blood cells: 39.78%) in the copper-blood glucose relationship. Regression analyses highlighted a positive correlation between white blood cells (estimate: 1.077, 95% CI: 0.432 to 2.490, p = 0.013) and copper levels and a negative correlation for monocyte percentage (estimate: -1.573, 95% CI: 0.520 to -3.025, p = 0.003). Neutrophil percentage was notably influential in glucose levels. Sensitive analyses confirmed the study's findings. Conclusion: Serum copper levels significantly impact blood glucose through inflammatory marker mediation, highlighting the importance of considering environmental factors in diabetes management and prevention. These findings advocate for public health interventions and policies targeting environmental monitoring and heavy metal exposure reduction, emphasizing the potential of environmental health measures in combating diabetes incidence.
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Biomarcadores , Glicemia , Cobre , Inflamação , Análise de Mediação , Inquéritos Nutricionais , Humanos , Cobre/sangue , Feminino , Masculino , Adulto , Glicemia/análise , Inflamação/sangue , Biomarcadores/sangue , Pessoa de Meia-Idade , Estados Unidos/epidemiologia , Diabetes Mellitus/sangue , Diabetes Mellitus/epidemiologiaRESUMO
Background: Several studies have shown that serum copper levels are related to coronary heart disease, diabetes, and cancer. However, the association of serum copper levels with all-cause, cause-specific [including cardiovascular disease (CVD) and cancer] mortality remains unclear. Objectives: This study aimed to prospectively examine the association of copper exposure with all-cause, CVD, and cancer mortality among US adults. Methods: The data for this analysis was obtained from the National Health and Nutrition Examination Survey (NHANES) between 2011 and 2014. Mortality from all-causes, CVD, and cancer mortality was linked to US National Death Index mortality data. Cox regression models were used to estimate the association between serum copper levels and all-cause, CVD, and cancer mortality. Results: A total of 2,863 adults were included in the main study. During the mean follow-up time of 81.2 months, 236 deaths were documented, including 68 deaths from cardiovascular disease and 57 deaths from cancer. The weighted mean overall serum copper levels was 117.2â ug/L. After adjusting for all of the covariates, compared with participants with low (1st tertile, <103â µg/L)/medium (2st tertile, 103-124â µg/L) serum copper levels, participants with high serum copper levels (3rd tertile, ≥124â µg/L) had a 1.75-fold (95% CI, 1.05-2.92)/1.78-fold (1.19,2.69) increase in all-cause mortality, a 2.35-fold (95% CI, 1.04-5.31)/3.84-fold (2.09,7.05) increase in CVD mortality and a 0.97-fold (95% CI, 0.28-3.29)/0.86-fold (0.34,2.13) increase in cancer mortality. In addition, there was a linear dose-response association between serum copper concentration with all-cause and CVD mortality (P for nonlinear > 0.05). Conclusions: This prospective study found that serum copper concentrations were linearly associated with all-cause and CVD mortality in US adults. High serum copper levels is a risk factor for all-cause and CVD mortality.
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Background: Oral submucous fibrosis (OSMF) is a recognized potentially malignant oral condition linked to the consumption of areca nut. Chewing areca nut has been shown to elevate soluble copper levels in mouth fluids. Materials and Methods: Participants: The study included a panel of 30 patients with OSMF from Rama Dental College, Kanpur, India, and 30 nonareca chewing individuals serving as controls. Tissue Sample Collection and Analysis: Buccal mucosal biopsies were obtained from both OSMF patients and controls. The tissue copper concentrations were quantified using mass absorption spectrometry (MAS). Additionally, energy-dispersive X-ray microanalysis (EDX) was employed to identify the presence and distribution of copper in the tissue. Statistical Analysis: Statistical comparisons were performed using appropriate methods, with a P-value of less than 0.05 considered statistically significant. Results: MAS analysis revealed that the mean tissue copper level was 6.2 ± 3.1 micrograms per gram (µg/g) in OSMF specimens (n = 30), slightly higher than the 4.5 ± 2.0 µg/g in the nonareca chewing controls (n = 30) (P = 0.1). EDX analysis showed distinct copper peaks in both the epithelium (22/23) and connective tissue (18/23) of OSMF specimens compared to control biopsies. These findings were corroborated by secondary ion mass spectrometry (SIMS) in a subset of samples. Conclusion: The study revealed higher copper concentrations in buccal mucosal tissue of OSMF patients from Rama Dental College, Kanpur, suggesting a potential connection between copper and the initiation of OSMF.
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This graphic depicts the interplay between copper homeostasis and cuproptosis and their role in cardiovascular diseases. Copper is vital for cardiac mitochondrial function, while its dysregulation induces cuproptosis via Ferredoxin1 (FDX1) and lipoic acid synthase (LIAS). Cuproptosis is linked to myocardial ischemia/reperfusion injury, heart failure, atherosclerosis, and arrhythmias. Copper deficiency impacts atherosclerosis markers. Therapeutic interventions include copper chelators (e.g., ammonium tetrathiomolybdate), and oxidative phosphorylation inhibitors like elesclomol and copper ionophores (CuII(atsm), CuII(gtsm), and disulfiram). These interventions modulate intracellular copper, elevate NO, and reduce inflammatory cytokines, contributing to decreased cardiovascular diseases.
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Doenças Cardiovasculares , Morte Celular , Cobre , Animais , Humanos , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/patologia , Cobre/metabolismo , HomeostaseRESUMO
Bone mineral density (BMD) is a key parameter widely used in the assessment of bone health. Although many investigations have explored the relationship between trace elements and BMD, there are fewer studies focused on serum copper and BMD, especially for adolescents. Using data extracted from the National Health and Nutrition Examination Survey, we applied a multiple-linear regression and smooth curve fitting to assess the relationship between serum copper and BMD. A total of 910 participants were finally included in this study. After adjusting for relevant covariates, serum copper was negatively associated with lumbar spine BMD (ß = -0.057, 95% CI: -0.109 to -0.005), trunk bone BMD (ß = -0.068, 95% CI: -0.110 to -0.026), pelvis BMD (ß = -0.085, 95% CI: -0.145 to -0.024), subtotal BMD (ß = -0.072, 95% CI: -0.111 to -0.033), and total BMD (ß = -0.051, 95% CI: -0.087 to -0.016) (p < 0.05). In quartile analysis, the highest level of serum copper was associated with decreased BMD when compared with those at the lowest quartile (p < 0.05). The stratified analysis revealed a significant interaction between age and the effects of serum copper on trunk bone BMD (p = 0.022) and pelvis BMD (p = 0.018). Meanwhile, the higher level of serum copper was negatively associated with BMD in males, and gender modified the relationship (p < 0.001). Future longitudinal studies will be necessary for a more definitive interpretation of our results.
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Densidade Óssea , Cobre , Masculino , Humanos , Adolescente , Estados Unidos/epidemiologia , Cobre/farmacologia , Absorciometria de Fóton/métodos , Inquéritos Nutricionais , Vértebras LombaresRESUMO
Copper is an essential trace element obtained from food. There is a paucity of observational or prospective studies that have investigated the relationship between copper and melanoma risk. Copper serves as a cofactor for pivotal enzymes involved in mitochondrial respiration, antioxidant defense, and neurotransmitter synthesis. Undoubtedly, copper plays an indispensable role in the initiation and progression of tumors, particularly melanoma; however, further investigations are warranted to elucidate the underlying mechanisms linking copper and melanoma risk. Given the availability of dietary copper and serum copper data in the NHANES database, we conducted an investigation into the association between dietary copper intake and serum copper levels with melanoma risk. We enrolled 26,401 individuals with dietary copper data in the 2007-2018 NHANES database. To mitigate confounding variables, a propensity score matching (PSM) was performed. To assess the association between dietary copper intake and melanoma risk, we employed a multivariate logistic regression analysis before and after PSM. The restricted cubic spline analysis was utilized to determine whether there is a non-linear relationship between dietary copper intake and melanoma risk, with subgroup analysis conducted to determine beneficiaries. Then, those with blood copper data from the enrolled population with dietary copper intake were screened out, and subsequently, multivariate logistic regression models were subsequently constructed to investigate the association between serum copper levels and melanoma risk after PSM. Mendelian analysis was further utilized to validate the results of the NHANES database using serum copper as the exposure factor and melanoma as the outcome variable. The study found that melanoma risk was associated with dietary copper intake before and after PSM, demonstrated by multiple logistic regression. The relationship between dietary copper intake and melanoma risk was non-linear, with a reduced risk observed above approximately 2.5 mg/day, as shown by the RCS. The evidence suggests that an increased intake of copper is linked to a decreased risk of melanoma. To clarify the mechanism behind the increased risk of melanoma due to higher dietary copper intake, we analyzed the population data from the NHANES database on serum copper and dietary copper intake. Our results indicated that there is no causal relationship between serum copper and melanoma risk. Mendelian randomization analysis of multi-database data sources confirmed the conclusion of the NHANES database analysis. Dietary copper is a protective factor against melanoma, and serum copper or blood copper is not associated with melanoma risk. This suggests that serum or blood copper is not responsible for the protective effect of dietary copper intake on melanoma risk, and the mechanisms need to be further investigated.
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Copper functions as an essential micronutrient influencing diverse metabolic processes in mammals, encompassing oxidative stress responses, lipid metabolism, and participation in enzymatic reactions. However, the impact of serum copper on non-alcoholic fatty liver disease (NAFLD) remains controversial. Our aim was to explore the precise correlation between serum copper and NAFLD in a large-scale population-based study. A total of 1377 participants from the National Health and Nutrition Examination Survey (NHANES) 2011-2016 were included in our study. The diagnosis of NAFLD and its progress to advanced liver fibrosis were based on serological indexes. One-way ANOVA, Kruskal-Wallis H test, and Chi-square test were used to access variations between quartiles groups of serum copper. We conducted multivariate-adjusted logistic regression models and subgroup analyses to investigate the association between serum copper and NAFLD, along with several metabolic diseases. Among the 1377 participants, 661 were diagnosed with NAFLD, and 141 of whom were classified into advanced liver fibrosis. Higher serum copper levels (≥ 21.00 µmol/L) were associated with an increased incidence of NAFLD (odds ratio (OR) = 2.07 (1.38-3.10), p < 0.001), as well as advanced liver fibrosis (OR = 2.40 (1.17-5.19), p = 0.025). Moreover, serum copper exhibited a positive correlation with hypertension, overweight, and abdominal obesity, all of which have been identified as risk factors of NAFLD. Additionally, female participants, under the age of 60, and with a higher body mass index (BMI) (> 24.9 kg/m2) emerged as the most vulnerable subgroup concerning the relationship between serum copper and NAFLD. In the U.S. population, a notable association has been identified, linking elevated serum copper to an increased susceptibility for both the onset and progression of NAFLD, along with several metabolic disorders associated with NAFLD. The adverse effects of excess copper warrant attention in the context of public health considerations.
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Cobre , Hepatopatia Gordurosa não Alcoólica , Inquéritos Nutricionais , Humanos , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Feminino , Masculino , Cobre/sangue , Pessoa de Meia-Idade , Adulto , Estados Unidos/epidemiologia , Cirrose Hepática/sangue , Cirrose Hepática/epidemiologiaRESUMO
OBJECTIVES: The objective was to explore the association between serum copper levels and the prevalence of stroke. METHODS: Data were obtained from 3 consecutive National Health and Nutrition Examination Survey (NHANES) cycles (2011-2016). Weighted multivariable logistic regression analysis was conducted to evaluate the association between serum copper levels and self-reported stroke. RESULTS: A total of 5,151 adults met the inclusion criteria. A total of 181 (3.51%) stroke patients were identified. In comparison to individuals with serum copper levels in the lowest tertile (<16.4 µmol/l), those with levels in the middle tertile (16.4-19.8 µmol/l) had an odds ratio (OR) of 0.99 (95% confidence interval [CI]: 0.44-2.25), while those with levels in the highest tertile (>19.8 µmol/l) had an OR of 2.36 (95% CI: 1.01-5.52). Furthermore, each standard deviation (SD) increase in serum copper was found to be positively associated with the prevalence of stroke, with an OR of 1.44 (95% CI: 1.11-1.86). Doseâresponse analysis showed a positive linear association between serum copper levels and stroke (Pnonlinearity=0.554). CONCLUSIONS: This cross-sectional study suggested a positive association between serum copper levels and stroke among American adults.
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Cobre , Acidente Vascular Cerebral , Adulto , Humanos , Estados Unidos/epidemiologia , Inquéritos Nutricionais , Fatores de Risco , Estudos Transversais , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologiaRESUMO
Copper is essential for various biological processes. However, excess copper has several adverse health effects. The effects of serum copper on muscle mass are poorly understood. This study aimed to investigate the association between serum copper levels and muscle mass in the US population. We utilized National Health and Nutrition Examination Survey (NHANES) data between 2011 and 2016 for analysis. Data on serum copper, muscle mass (measured using the appendicular skeletal muscle mass index (ASMI)), and covariates were extracted and analyzed. Weighted multivariate linear regression analyses and smooth curve fittings were performed to investigate the association between serum copper levels and ASMI. Subgroup analyses stratified according to age and sex were performed. In the presence of nonlinearity, threshold effect analysis was performed using a two-piecewise linear regression model. A total of 3860 participants were included in the final analysis. Serum copper levels were negatively associated with ASMI in the fully adjusted model. Furthermore, by comparing participants in the highest and lowest tertiles of serum copper levels, we found that the ASMI decreased by 0.292 kg/m2. In the sex-stratified subgroup analysis, we observed an inverse association between serum copper levels and the ASMI in both men and women. When stratified by age, the association remained significant among participants < 40 years of age, but not among those ≥ 40 years old. Smooth curve fitting revealed a nonlinear relationship between serum copper and ASMI, with an inflection point identified at 150.6 µg/dL. Our study revealed an inverse relationship between serum copper levels and muscle mass. This finding improves the current knowledge on the impact of serum copper on muscle loss and highlights the importance of serum copper homeostasis in muscle health.
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Cobre , Músculo Esquelético , Masculino , Humanos , Feminino , Adulto , Inquéritos Nutricionais , Modelos LinearesRESUMO
This study was to assess the individual effects of serum copper levels and environmental tobacco exposure and their joint effects on the risk of overweight and obesity among children and adolescents of 6 to 19 year olds. We analyzed cross-sectional data from 1849 children and adolescents participating in the National Health and Nutrition Examination Survey (NHANES) collected between 2011 and 2016. Environmental tobacco exposure was determined by cotinine levels. The serum copper level was divided into < median group and ≥ median groups according to the median of 109.81 µg/dL. The outcome was overweight/obese in children and adolescents. Weighted multinomial multivariate logistic regression models were used to assess the association of serum copper and cotinine levels, with the risk of overweight/obesity, and the joint effects on the risk of overweight and obesity among children and adolescents. The subgroup analyses based on age, gender, and household smoking status were conducted. Among 1849 children and adolescents, 332 children and adolescents had overweight BMI, and 450 children and adolescents had obese BMI. Higher serum copper levels were associated with the risk of obesity in children and adolescents (odds ratio (OR) 2.96, 95% confidence interval (CI) 1.39-6.31, P = 0.006). A positive association between increasing levels of cotinine levels and the risk of overweight (OR 1.83, 95% CI 1.16-2.87, P = 0.010) and obesity (OR 2.56, 95% CI 1.03-6.40, P = 0.044) in children and adolescents was observed. A remarkable association was found between higher serum copper in combination with higher cotinine levels and the risk of overweight (OR 3.23, 95% CI 1.19-8.83, P = 0.023) and obesity (OR 8.76, 95% CI 2.14-35.87, P = 0.003) in children and adolescents. The subgroup analyses revealed positive associations between high serum copper levels in combination with high cotinine levels and overweight and obesity in children and adolescents aged ≥ 12 years, of female sex, and without smoking family members. There may exist a joint effect of serum copper levels and environmental tobacco exposure on overweight/obesity among children and adolescents. These findings offer an insight that early weight control and reduction of tobacco exposure and the detection of serum copper levels may be important in reducing the risk of obesity in children.
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Cobre , Inquéritos Nutricionais , Sobrepeso , Humanos , Criança , Cobre/sangue , Adolescente , Masculino , Feminino , Sobrepeso/sangue , Sobrepeso/epidemiologia , Estudos Transversais , Cotinina/sangue , Fatores de Risco , Poluição por Fumaça de Tabaco/efeitos adversos , Exposição Ambiental/efeitos adversos , Obesidade Infantil/sangue , Obesidade Infantil/epidemiologia , Adulto Jovem , Obesidade/sangue , Obesidade/epidemiologiaRESUMO
In the last 15 years, among the many reasons given for the development of idiopathic forms of Parkinson's disease (PD), copper imbalance has been identified as a factor, and PD is often referred to as a copper-mediated disorder. More than 640 papers have been devoted to the relationship between PD and copper status in the blood, which include the following markers: total copper concentration, enzymatic ceruloplasmin (Cp) concentration, Cp protein level, and non-ceruloplasmin copper level. Most studies measure only one of these markers. Therefore, the existence of a correlation between copper status and the development of PD is still debated. Based on data from the published literature, meta-analysis, and our own research, it is clear that there is a connection between the development of PD symptoms and the number of copper atoms, which are weakly associated with the ceruloplasmin molecule. In this work, the link between the risk of developing PD and various inborn errors related to copper metabolism, leading to decreased levels of oxidase ceruloplasmin in the circulation and cerebrospinal fluid, is discussed.
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BACKGROUND AND AIM: Certain trace elements have been associated with increased cardiovascular risk. The aim of this study was to evaluate the association between serum copper (S-Cu) levels and the risk of a first event of cardiovascular disease (CVD) in a population of older adults with high cardiovascular risk. METHODS AND RESULTS: We conducted a case-control study nested within the PREDIMED trial. During a median follow-up of 4.8 years, a total of 207 incident cases diagnosed with CVD were matched for sex, age, and intervention group with 436 controls. Personal interviews, reviews of medical records, and validated questionnaires were used to assess known CVD risk factors. Biological serum samples were collected annually. Inductively coupled plasma mass spectrometry analysis was used to determine S-Cu levels. Adjusted odds ratios were calculated using multivariate conditional logistic regression models. All participants had S-Cu levels within the reference values, 750 µg/L to 1450 µg/L. Among men, but not among women, the mean S-Cu concentration was higher in cases 1014.1 µg/L than in controls 959.3 µg/L; (p = 0.004). In men, the multivariable-adjusted odds ratio for CVD was 2.36 (95% CI 1.07-5.20 for the comparison of the highest vs. the lowest quartile; p for trend = 0.02), in women, it was 0.43 (95% CI 0.11-1.70; p for trend = 0.165). CONCLUSION: In older Spanish men with high cardiovascular risk, a significant association was observed between high S-Cu levels, but still within the reference values, and an increased risk of a first event of CVD. Our findings suggest a sex difference in CVD risk and S-Cu levels. To confirm this relationship and to analyze the differences observed between men and women, further studies are needed.
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Background: Despite the fact that several studies have investigated the association between serum copper levels (S-Cu) and the risk of cardiovascular diseases, this relationship remains unclear. The aims of this study were to investigate the association between S-Cu and risk of major adverse cardiovascular events (MACE), including total stroke, ischemic stroke, hemorrhagic stroke, myocardial infarction and cardiovascular mortality, and identify potential sources of results heterogeneity. Methods: We carried out a systematic review and meta-analysis. The selection criteria were: (1) Observational studies (cohort studies, case-control studies and hybrid studies); (2) Studies containing quantitative data about the relationship between S-Cu and risk of MACE; (3) Estimating association measures; and (4) Studies written in English, French or Spanish. Overall pooled Odds ratio (pOR) and 95% confidence intervals (95% CI) of MACE for the highest vs. lowest S-Cu category were calculated using random-effects models. Results: Sixteen studies with a total of 41,322 participants were included in the meta-analysis: 10 prospective cohort studies, 5 nested case-control studies and 1 case-control study. Comparing highest vs. lowest category, high S-Cu levels were associated with total stroke (pOR: 1.49, 95% CI 1.22-1.82; I2 = 0%, p = 0.54), myocardial infarction (pOR: 1.31, 95% CI 1.17-1.46; I2 = 0.0%, p = 0.92) and cardiovascular mortality (pOR: 1.60, 95% CI 1.39-1.86; I2 = 0.0%, p = 0.54). Subgroup analysis showed that studies with a hybrid design had higher risks for cardiovascular mortality (pOR: 3.42, 95% CI 1.98-5.92) and ischemic stroke (pOR: 1.54, 95% CI 1.30-1.83). Conclusion: High S-Cu levels were associated with an increased risk of total stroke, myocardial infarction and cardiovascular mortality. Hybrid studies seems to modify the strength of the association between S-Cu and the risk of cardiovascular mortality and ischemic stroke. Systematic review registration: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022370782], identifier [CRD42022370782].
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Urinary incontinence (UI) is a major health burden to aging patients. The function of the trace element copper in male UI is unclear. To elaborate on the impact of serum copper levels on UI, we investigated the association between serum copper levels and UI using data from the National Health and Nutrition Examination Survey (NHANES), a cross-sectional survey of male participants aged 20 years old and older in the United States from 2011 to 2016. We performed weighted multivariable logistic and linear regression models to evaluate the association between serum copper levels and UI. Compared with serum copper levels in quartile 1 (Q1), serum copper levels in Q2 and Q3 were associated with stress urinary incontinence (SUI) after adjusting for all potential confounders (Q2, odds ratio [OR] = 0.292, 95% confidence interval [CI] = 0.093-0.920, P = 0.047; Q3, OR = 0.326, 95% CI = 0.113-0.937, P = 0.049). No significance was found between serum copper levels and other types of UI. Our findings revealed that the serum copper levels were inversely related to SUI in adult males. Race and education level might modulate this relationship. Further studies are warranted for validation.
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Incontinência Urinária por Estresse , Incontinência Urinária , Humanos , Adulto , Masculino , Estados Unidos/epidemiologia , Adulto Jovem , Inquéritos Nutricionais , Cobre , Estudos TransversaisRESUMO
BACKGROUND AND AIMS: Copper (Cu) is a component of enzymes catalyzing oxidation-reduction reactions. With the persisting burden of cardiovascular disease (CVD), there is evident need to identify biomarkers and potential risk factors for CVD. We therefore examined the association between serum Cu levels and the risk of CVD death in Finnish men and across different body mass index (BMI) categories. METHODS AND RESULTS: This Finnish prospective study is based on 1911 men aged 42-60 years who were free of coronary heart disease at baseline. Cu concentrations (mg/l) were determined using atomic absorption spectrometer and categorized into quartiles (<1.0; 1 to <1.1; 1.1 to <1.21; ≥1.21). Participants were categorized into normal weight <25 kg/m2, pre-obesity 25-29.9 kg/m2, and obesity >30 kg/m2. The association between Cu and CVD death was analyzed using multivariable Cox regression models. During a median follow-up of 25.8 years, 358 CVD deaths occurred. The risk of CVD death increased continuously with increasing Cu levels (for non-linearity, p = 0.64). Using the first quartile as reference after adjustment for covariates, the hazard ratios (HR) (95% confidence interval (CI)) for CVD death for Cu concentrations in second, third and fourth quartiles were 1.45(1.05-2.01), 1.69(1.25-2.27), and 1.68(1.23-2.29), respectively. Obese men in the third quartile of serum Cu concentrations had highest risk of CVD death (HR (95%CI) 2.71(1.27-5.78)). CONCLUSION: Elevated serum Cu level was associated with increased risk of CVD death across all BMI categories in middle-aged and older Finnish men. Serum Cu may have prognostic implication for CVD mortality risk; however, further studies are needed.
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Doenças Cardiovasculares , Pessoa de Meia-Idade , Masculino , Humanos , Idoso , Doenças Cardiovasculares/etiologia , Estudos Prospectivos , Cobre , Finlândia/epidemiologia , Fatores de Risco , Obesidade/diagnóstico , Obesidade/complicaçõesRESUMO
Excessive serum copper has multiple effects on human health, while the association between copper and obesity remains unclear. The objective of this study is to examine the associations of serum copper concentrations with obesity and adiposity measures, including body fat composition and distribution among adults in the USA. This analysis utilized data from the National Health and Nutrition Examination Survey (NHANES) (2011-2016). A total of 7285 adults aged 18 years or older who had serum copper measures were included in this cross-sectional study. Multi-linear regression and logistic regression were used to estimate the independent risky effect of copper on fat deposition and all-cause mortality. Moreover, these associations were analyzed in stratification analysis by gender, age, and physical activity (PA). Generally, we found that participants who were females, non-Hispanic Black, or with inactive PA tended to have a higher serum level of copper. In addition, we observed positive associations between serum copper and adiposity measurements. Furthermore, a serum copper level higher than 133.9 µg/dL was a risk factor for all-cause mortality, which doubled the odds ratio of all-cause mortality compared to the normal serum copper level. Serum copper was positively associated with fat deposition of whole body and regional parts, and all-cause mortality. Furthermore, the effects of copper on fat distribution were also significant and could be modified by age, gender, and PA.
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Cobre , Obesidade , Adulto , Feminino , Humanos , Masculino , Inquéritos Nutricionais , Estudos Transversais , Índice de Massa Corporal , Circunferência da Cintura , Obesidade/epidemiologia , AdiposidadeRESUMO
PURPOSE: Serum copper (Cu), zinc (Zn), and Cu/Zn-ratio have emerged as ageing-related biomarkers. We sought to assess the association between Cu/Zn-ratio and chronic obstructive pulmonary disease (COPD) risk. METHODS: Serum Cu and Zn were measured using atomic absorption spectrometry in 2,503 men aged 42-61 years. RESULTS: During a median follow-up of 27.1 years, 210 COPD cases occurred. Serum Cu/Zn-ratio and Cu concentrations were linearly associated with COPD risk, whereas the relationship was curvilinear for Zn and COPD risk. A unit increase in Cu/Zn-ratio was associated with an increased COPD risk in multivariable analysis (hazard ratio, HR 1.81; 95% CI 1.08-3.05). The corresponding adjusted HR (95% CI) was 3.17 (1.40-7.15) for Cu. Compared to the bottom tertile of Zn, the HRs (95% CIs) were 0.68 (0.48-0.97) and 1.01 (0.73-1.41) for the middle and top tertiles of Zn, respectively. CONCLUSIONS: Increased serum Cu/Zn-ratio and Cu concentrations were linearly associated with an increased COPD risk in men.
Assuntos
Cobre , Doença Pulmonar Obstrutiva Crônica , Masculino , Humanos , Zinco , Estudos de Coortes , BiomarcadoresRESUMO
Evidence for the association between serum copper and zinc status and handgrip strength is very limited only in several observational studies with study participants of specific population or a narrower age range. The aim of this study was to evaluate the association between serum copper, zinc and their ratio and handgrip strength in the general population. This study included adult participants aged 20-80 years with complete data of serum copper and zinc status and handgrip strength from NHANES 2011-2014. Handgrip strength was calculated as the average of the maximum measure obtained in each hand with a grip strength dynamometer and corrected using BMI. Serum copper and zinc levels were measured using inductively coupled plasma dynamic reaction cell mass spectrometry, and their ratios were calculated. The multivariable linear regression and restricted cubic spline models were used. Serum copper level was inversely associated with BMI-corrected handgrip strength, and the beta coefficients (95% confidence intervals) comparing the second, third, and fourth to the lowest quartiles of serum copper level were - 0.17 kg (- 0.26; - 0.08), - 0.22 kg (- 0.32; - 0.13), and - 0.36 kg (- 0.44; - 0.28), respectively (P for trend < 0.001). Non-linear association was detected between serum copper level and BMI-corrected handgrip strength (P < 0.01). Consistent with serum copper, serum copper/zinc ratio was inversely associated with BMI-corrected handgrip strength. However, no significant associations were observed between serum zinc level and BMI-corrected handgrip strength (all P > 0.05). Higher serum copper level and copper/zinc ratios were significantly associated with lower handgrip strength. Further research is needed to address related issues.