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

BMJ 2018; 362 doi: (Published 29 August 2018) Cite this as: BMJ 2018;362:k3310
  1. Rajiv Chowdhury, principal researcher1,
  2. Anna Ramond, post doctoral researcher1,
  3. Linda M O’Keeffe, research fellow2 3,
  4. Sara Shahzad, doctoral researcher1,
  5. Setor K Kunutsor, research fellow4 5 6 ,
  6. Taulant Muka, senior epidemiologist7,
  7. John Gregson, assistant professor8,
  8. Peter Willeit, assistant Professor1 9,
  9. Samantha Warnakula, senior epidemiologist1,
  10. Hassan Khan, cardiologist10,
  11. Susmita Chowdhury, medical officer1,
  12. Reeta Gobin, lecturer11,
  13. Oscar H Franco, professor7,
  14. Emanuele Di Angelantonio, reader1 12 13
  1. 1Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge CB1 8RN, UK
  2. 2MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK
  3. 3Bristol Population Health Science Institute, Bristol Medical School, Bristol, UK
  4. 4National Institute for Health Research Bristol Biomedical Research Centre, Bristol, UK
  5. 5University Hospitals Bristol NHS Foundation Trust, Bristol, UK
  6. 6Translational Health Sciences, Bristol Medical School, Musculoskeletal Research Unit, University of Bristol, Bristol, UK
  7. 7Institute of Social and Preventive Medicine, Bern, Switzerland
  8. 8Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK
  9. 9Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria
  10. 10Emory University, Atlanta, Georgia, USA
  11. 11University of Guyana, Georgetown, Guyana
  12. 12National 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
  13. 13NHS Blood and Transplant, Cambridge, UK
  1. Correspondence to: S Shahzad ss2231{at}
  • Accepted 4 July 2018


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

Design Systematic review and meta-analysis.

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

Review methods 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.

Results 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.

Conclusion 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.


  • Contributors:RC and ED designed the study. AR, LMO, SS, SKK, RC, and ED acquired, analysed, and interpreted the data. RC, AR, SS, and ED drafted the manuscript. AR and SKK performed the statistical analysis. RC and ED supervised the study. All authors had full access to the data in the study and can take responsibility for the integrity of the data and the accuracy of the data analysis. RC is the guarantor.

  • Funding: This work was not supported by any external grants or funding.

  • 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.

  • Ethical approval: Not required.

  • Data sharing: Dataset is available from the corresponding author.

  • Transparency: The manuscripts guarantor (RC) affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned have been explained.

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