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Published on: August 28, 2018
The role of coronary artery calcification in metal-related cardiovascular disease
Arce Domingo-Relloso1, Katlyn E McGraw2, Irene Martinez-Morata2
1Department of Biostatistics, Columbia University Mailman School of Public Health, New York, NY, USA; Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, New York, NY, USA; IE University School of Science and Technology, Madrid, Spain.
Insights
Urinary metals like cadmium and zinc are linked to cardiovascular disease (CVD) risk, partly through changes in coronary artery calcification (CAC) over time. This finding may help in early CVD detection and prevention strategies.
Area of Science:
- Environmental Health
- Cardiovascular Disease Epidemiology
- Toxicology
Background:
- Metals in urine are linked to cardiovascular disease (CVD), but the exact mechanisms are not fully understood.
- Coronary artery calcification (CAC) is a key indicator of atherosclerosis and a predictor of CVD events.
- Longitudinal changes in CAC may mediate the relationship between metal exposure and CVD incidence.
Purpose of the Study:
- To investigate the role of coronary artery calcification (CAC) trajectory as an intermediate pathway linking urinary metal exposure to incident cardiovascular disease (CVD).
- To quantify the proportion of the association between specific metals and CVD mediated by longitudinal changes in CAC.
Main Methods:
- Utilized data from 6,459 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) with longitudinal CAC measurements (2000-2019).
- Measured baseline urinary concentrations of cadmium, cobalt, copper, uranium, tungsten, and zinc (2000-2002).
- Employed causal inference with a path-specific effects approach for longitudinal mediation analysis, accounting for competing risks.
Main Results:
- Significant mediation of the association between urinary cadmium, cobalt, copper, tungsten, zinc, and incident CVD through CAC trajectory was observed.
- An interquartile range increase in cadmium was associated with 44 additional CVD cases per 100,000 person-years through CAC.
- Approximately half of the association between urinary cadmium and CVD may be mediated by longitudinal CAC changes.
Conclusions:
- Urinary metal exposure contributes to CVD risk, in part, through its impact on the progression of coronary artery calcification over time.
- Findings highlight the potential of urinary metal levels and CAC monitoring for early CVD risk assessment and targeted prevention.
- Specific metals, notably cadmium, demonstrate a substantial mediation effect via CAC trajectory, underscoring their role in CVD pathogenesis.
Abstract:
Metals are associated with cardiovascular disease (CVD), but the underlying pathways remain largely unclear. We evaluated the potential intermediate role of coronary artery calcification (CAC) trajectory on the association between urinary metals and incident CVD, accounting for competing risks by death from other causes. We used data from 6,459 participants of the Multi-Ethnic Study of Atherosclerosis (MESA). CAC was measured longitudinally using the spatially weighted calcium score in five exams, starting in 2000. Participants were followed for CVD events through 2019. Cadmium, cobalt, copper, uranium, tungsten, and zinc were measured in urine at the baseline visit (2000-2002). We used a causal inference algorithm with a path-specific effects approach for longitudinal mediation analysis to evaluate the intermediate role of CAC on the association between metals and incident CVD. The association with incident CVD mediated through the CAC trajectory was statistically significant for cadmium, cobalt, copper, tungsten, and zinc. The number of CVD cases (95% CI) per 100,000 person-years attributable to an interquartile range (IQR) increase in metal levels through the longitudinal trajectory of CAC was 44 (20, 72) for cadmium, 21 (6, 39) for cobalt, 19 (2, 36) for copper, 18 (2, 38) for tungsten, and 43 (26, 62) for zinc. This study supports that part of the association between urinary metals and CVD is attributable to changes in CAC over time. In particular, half of the association between urinary cadmium and CVD might be mediated by longitudinal changes in CAC. This study could inform strategies for early detection and prevention of CVD based on urinary metal levels.
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