Cadmium exposure and cardiovascular disease risk: A systematic review and dose-response meta-analysis

Verzelloni, Pietro; Urbano, Teresa; Wise, Lauren A.; Vinceti, Marco; Filippini, Tommaso

doi:10.1016/j.envpol.2024.123462

Cited by 15 publications

(2 citation statements)

References 82 publications

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“…One possible explanation for this is the increased renal toxicity of Cd in females [44]. Consistent with previous research, our study also suggested a positive correlation between blood Cd levels and cardiovascular mortality [45,46], with this effect being more pronounced in patients with NAFLD aged under 60 years and those with hypertension. Cd may contribute to atherosclerosis through oxidative stress, in ammation, and endothelial cell damage [47].…”

Section: Discussionsupporting

confidence: 92%

Association of blood cadmium levels with all-cause and cause-specific mortality among adults with Non-Alcoholic Fatty Liver Disease: A prospective cohort study

Xu,

Li,

Hao

et al. 2024

Preprint

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Background Cadmium (Cd) accumulates in the body over time, damaging organs such as the liver, kidneys, and brain. Some researchers have suggested that elevated blood Cd levels may contribute to the onset and progression of nonalcoholic fatty liver disease (NAFLD). However, only a few studies have investigated the association between Cd exposure and long-term health outcomes in patients with NAFLD. This study aimed to evaluate the predictive value of blood cadmium levels for mortality risk in patients with NAFLD. Methods This study analyzed data from 13,790 patients with NAFLD in the National Health and Nutrition Examination Survey (NHANES) database, covering the years 1999 to 2018. Patients were categorized into three groups based on their blood Cd levels. The relationship between blood cadmium concentrations and all-cause, cardiovascular, and cancer mortality in NAFLD patients was assessed using Cox proportional hazards regression while accounting for potential confounders. Results were visualised using Kaplan-Meier and restricted cubic spline (RCS) curves. Stratified analyses were performed for validation of the robustness of the results. Results The study included 13,790 individuals. After adjusting for all covariates, blood Cd levels were positively associated with all-cause, cardiovascular, and cancer mortality in patients with NAFLD, showing a significant linear dose-response relationship. Specifically, for each unit increase in Log-transformed blood cadmium concentration, the risk of all-cause mortality increased by 195% (HR = 2.95, 95% CI: 2.43–3.58); cardiovascular mortality risk increased by 173% (HR = 2.73, 95% CI: 1.90–3.93); and cancer mortality risk increased by 277% (HR = 3.77, 95% CI: 2.54–5.59). Stratified analysis confirmed the robustness of these findings, indicating that female patients and those under 60 were more susceptible to the effects of blood cadmium on all-cause mortality. Additionally, patients with hypertension and those under 60 years of age were more vulnerable to cardiovascular mortality. Conclusions Our study suggests that high Blood Cd levels adversely affect the prognosis of patients with NAFLD. Individuals with NAFLD should be aware of Cd exposure and take preventive measures. Moreover, stricter environmental protection policies may be necessary to reduce Cd exposure.

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Section: Discussionsupporting

confidence: 92%

Association of blood cadmium levels with all-cause and cause-specific mortality among adults with Non-Alcoholic Fatty Liver Disease: A prospective cohort study

Xu,

Li,

Hao

et al. 2024

Preprint

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“…Verzelloni et al (2024) conducted a dose–response meta-analysis of data from 26 studies, published from 2005 to 2023, to evaluate the contribution of Cd exposure to the risk of CVD [ 126 ]. They found that the risks of heart failure, coronary heart disease, and stroke were all increased with Cd exposure in a dose-dependent manner.…”

Section: Global Health Threat Of Environmental Cadmiummentioning

confidence: 99%

Modulation of Adverse Health Effects of Environmental Cadmium Exposure by Zinc and Its Transporters

Cirovic,

Yimthiang

et al. 2024

Biomolecules

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Zinc (Zn) is the second most abundant metal in the human body and is essential for the function of 10% of all proteins. As metals cannot be synthesized or degraded, they must be assimilated from the diet by specialized transport proteins, which unfortunately also provide an entry route for the toxic metal pollutant cadmium (Cd). The intestinal absorption of Zn depends on the composition of food that is consumed, firstly the amount of Zn itself and then the quantity of other food constituents such as phytate, protein, and calcium (Ca). In cells, Zn is involved in the regulation of intermediary metabolism, gene expression, cell growth, differentiation, apoptosis, and antioxidant defense mechanisms. The cellular influx, efflux, subcellular compartmentalization, and trafficking of Zn are coordinated by transporter proteins, solute-linked carriers 30A and 39A (SLC30A and SLC39A), known as the ZnT and Zrt/Irt-like protein (ZIP). Because of its chemical similarity with Zn and Ca, Cd disrupts the physiological functions of both. The concurrent induction of a Zn efflux transporter ZnT1 (SLC30A1) and metallothionein by Cd disrupts the homeostasis and reduces the bioavailability of Zn. The present review highlights the increased mortality and the severity of various diseases among Cd-exposed persons and the roles of Zn and other transport proteins in the manifestation of Cd cytotoxicity. Special emphasis is given to Zn intake levels that may lower the risk of vision loss and bone fracture associated with Cd exposure. The difficult challenge of determining a permissible intake level of Cd is discussed in relation to the recommended dietary Zn intake levels.

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Heavy metals: toxicity and human health effects

Jomova,

Alomar,

Nepovimova

et al. 2024

Arch Toxicol

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Heavy metals are naturally occurring components of the Earth’s crust and persistent environmental pollutants. Human exposure to heavy metals occurs via various pathways, including inhalation of air/dust particles, ingesting contaminated water or soil, or through the food chain. Their bioaccumulation may lead to diverse toxic effects affecting different body tissues and organ systems. The toxicity of heavy metals depends on the properties of the given metal, dose, route, duration of exposure (acute or chronic), and extent of bioaccumulation. The detrimental impacts of heavy metals on human health are largely linked to their capacity to interfere with antioxidant defense mechanisms, primarily through their interaction with intracellular glutathione (GSH) or sulfhydryl groups (R-SH) of antioxidant enzymes such as superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione reductase (GR), and other enzyme systems. Although arsenic (As) is believed to bind directly to critical thiols, alternative hydrogen peroxide production processes have also been postulated. Heavy metals are known to interfere with signaling pathways and affect a variety of cellular processes, including cell growth, proliferation, survival, metabolism, and apoptosis. For example, cadmium can affect the BLC-2 family of proteins involved in mitochondrial death via the overexpression of antiapoptotic Bcl-2 and the suppression of proapoptotic (BAX, BAK) mechanisms, thus increasing the resistance of various cells to undergo malignant transformation. Nuclear factor erythroid 2-related factor 2 (Nrf2) is an important regulator of antioxidant enzymes, the level of oxidative stress, and cellular resistance to oxidants and has been shown to act as a double-edged sword in response to arsenic-induced oxidative stress. Another mechanism of significant health threats and heavy metal (e.g., Pb) toxicity involves the substitution of essential metals (e.g., calcium (Ca), copper (Cu), and iron (Fe)) with structurally similar heavy metals (e.g., cadmium (Cd) and lead (Pb)) in the metal-binding sites of proteins. Displaced essential redox metals (copper, iron, manganese) from their natural metal-binding sites can catalyze the decomposition of hydrogen peroxide via the Fenton reaction and generate damaging ROS such as hydroxyl radicals, causing damage to lipids, proteins, and DNA. Conversely, some heavy metals, such as cadmium, can suppress the synthesis of nitric oxide radical (NO·), manifested by altered vasorelaxation and, consequently, blood pressure regulation. Pb-induced oxidative stress has been shown to be indirectly responsible for the depletion of nitric oxide due to its interaction with superoxide radical (O2·−), resulting in the formation of a potent biological oxidant, peroxynitrite (ONOO−). This review comprehensively discusses the mechanisms of heavy metal toxicity and their health effects. Aluminum (Al), cadmium (Cd), arsenic (As), mercury (Hg), lead (Pb), and chromium (Cr) and their roles in the development of gastrointestinal, pulmonary, kidney, reproductive, neurodegenerative (Alzheimer’s and Parkinson’s diseases), cardiovascular, and cancer (e.g. renal, lung, skin, stomach) diseases are discussed. A short account is devoted to the detoxification of heavy metals by chelation via the use of ethylenediaminetetraacetic acid (EDTA), dimercaprol (BAL), 2,3-dimercaptosuccinic acid (DMSA), 2,3-dimercapto-1-propane sulfonic acid (DMPS), and penicillamine chelators.

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Cadmium exposure and cardiovascular disease risk: A systematic review and dose-response meta-analysis

Cited by 15 publications

References 82 publications

Association of blood cadmium levels with all-cause and cause-specific mortality among adults with Non-Alcoholic Fatty Liver Disease: A prospective cohort study

Association of blood cadmium levels with all-cause and cause-specific mortality among adults with Non-Alcoholic Fatty Liver Disease: A prospective cohort study

Modulation of Adverse Health Effects of Environmental Cadmium Exposure by Zinc and Its Transporters

Heavy metals: toxicity and human health effects

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