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BMJ. 2018 Aug 29;362:k3310. doi: 10.1136/bmj.k3310.

Environmental toxic metal contaminants and risk of cardiovascular disease: systematic review and meta-analysis.

Author information

Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge CB1 8RN, UK.
MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
Bristol Population Health Science Institute, Bristol Medical School, Bristol, UK.
National Institute for Health Research Bristol Biomedical Research Centre, Bristol, UK.
University Hospitals Bristol NHS Foundation Trust, Bristol, UK.
Translational Health Sciences, Bristol Medical School, Musculoskeletal Research Unit, University of Bristol, Bristol, UK.
Institute of Social and Preventive Medicine, Bern, Switzerland.
Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK.
Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
Emory University, Atlanta, Georgia, USA.
University of Guyana, Georgetown, Guyana.
National Institute for Health Research Blood and Transplant Research Unit in Donor Health and Genomics, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
NHS Blood and Transplant, Cambridge, UK.



To conduct a systematic review and meta-analysis of epidemiological studies investigating the association of arsenic, lead, cadmium, mercury, and copper with cardiovascular disease.


Systematic review and meta-analysis.


PubMed, Embase, and Web of Science searched up to December 2017.


Studies reporting risk estimates for total cardiovascular disease, coronary heart disease, and stroke for levels of arsenic, lead, cadmium, mercury, or copper were included. Two investigators independently extracted information on study characteristics and outcomes in accordance with PRISMA and MOOSE guidelines. Relative risks were standardised to a common scale and pooled across studies for each marker using random effects meta-analyses.


The review identified 37 unique studies comprising 348 259 non-overlapping participants, with 13 033 coronary heart disease, 4205 stroke, and 15 274 cardiovascular disease outcomes in aggregate. Comparing top versus bottom thirds of baseline levels, pooled relative risks for arsenic and lead were 1.30 (95% confidence interval 1.04 to 1.63) and 1.43 (1.16 to 1.76) for cardiovascular disease, 1.23 (1.04 to 1.45) and 1.85 (1.27 to 2.69) for coronary heart disease, and 1.15 (0.92 to 1.43) and 1.63 (1.14 to 2.34) for stroke. Relative risks for cadmium and copper were 1.33 (1.09 to 1.64) and 1.81 (1.05 to 3.11) for cardiovascular disease, 1.29 (0.98 to 1.71) and 2.22 (1.31 to 3.74) for coronary heart disease, and 1.72 (1.29 to 2.28) and 1.29 (0.77 to 2.17) for stroke. Mercury had no distinctive association with cardiovascular outcomes. There was a linear dose-response relation for arsenic, lead, and cadmium with cardiovascular disease outcomes.


Exposure to arsenic, lead, cadmium, and copper is associated with an increased risk of cardiovascular disease and coronary heart disease. Mercury is not associated with cardiovascular risk. These findings reinforce the importance of environmental toxic metals in cardiovascular risk, beyond the roles of conventional behavioural risk factors.

[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work. RC is the Co-Principal Investigator for the UK Research Council UK’s £8.1M CAPABLE Global Health Programme, which is investigating the roles of toxic metals and air pollutants on future noncommunicable disease outcomes in Bangladesh and elsewhere.

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