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

Abstract

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.

Fig 1

PRISMA flow diagram of search strategy

Fig 2

Summary of the association of environmental contaminants with cardiovascular outcomes. Pooled risk estimates were calculated using random effects meta-analyses. The relative risk compares the risk for each outcome in individuals in the top third with those in the bottom third of baseline levels of the environmental contaminants (ie, extreme thirds). Risk estimates from separate studies were typically adjusted for basic demographics (eg, age, sex, systolic blood pressure, smoking, history of diabetes, etc)

Fig 3

Association between environmental contaminants and cardiovascular disease. NR=not reported; +=minimally adjusted (typically adjusted for age and sex only); ++=adjusted for at least one non blood based cardiovascular risk factor (eg, systolic blood pressure, body mass index, history of diabetes, etc); +++=additionally adjusted for at least one blood based cardiovascular risk factor (eg, total cholesterol, c-reactive protein, etc)

Fig 4

Association between environmental contaminants and coronary heart disease. NR=not reported; +=minimally adjusted (typically adjusted for age and sex only); ++=adjusted for at least one non blood based cardiovascular risk factor (eg, systolic blood pressure, body mass index, history of diabetes, etc); +++=additionally adjusted for at least one blood based cardiovascular risk factor (eg, total cholesterol, c-reactive protein, etc)

Fig 5

Association between environmental contaminants and stroke. NR=not reported; +=minimally adjusted (typically adjusted for age and sex only); ++=adjusted for at least one non blood based cardiovascular risk factor (eg, systolic blood pressure, body mass index, history of diabetes etc); +++=additionally adjusted for at least one blood based cardiovascular risk factor (eg, total cholesterol, c-reactive protein, etc)