Metal Exposure Also Linked to More Coronary Artery Calcium

Exposure to metals, essential or not, was associated with the progression of subclinical atherosclerosis, according to longitudinal data from a geographically diverse cohort.

Study participants with the highest urinary metal levels tended to also have the highest coronary artery calcium (CAC), reported Katlyn McGraw, PhD, of Columbia University Mailman School of Public Health in New York City, and colleagues in the Journal of the American College of Cardiology.

Higher CAC levels — at baseline and with repeat measures taken over a 10-year period — were evident comparing the highest vs lowest quartile of urinary metals:

• Cadmium (nonessential): CAC 51% higher at baseline and 75% higher cumulatively over 10 years
• Tungsten (nonessential): CAC 13% higher and 45% higher, respectively
• Uranium (nonessential): CAC 17% higher and 39% higher, respectively
• Cobalt (essential): CAC 29% higher and 47% higher, respectively
• Copper (essential): CAC 15% higher and 33% higher, respectively
• Zinc (essential): CAC 54% higher and 57% higher, respectively

“These results support that metal exposure and/or metabolism, as reflected in urine, may be associated with the progression of atherosclerosis by increasing coronary calcification in diverse U.S. adults,” McGraw’s group wrote.

The study thus extends the link with cardiovascular disease (CVD) and all-cause mortality to earlier-stage subclinical atherosclerotic cardiovascular disease (ASCVD).

“The findings of McGraw et al have important implications for public health, health equity, and clinical practice. The study provides additional support for the need of large-scale public health action to lower acceptable limits of metals in air and water and improve enforcement of metal pollution reduction, particularly in communities experiencing disproportionate exposures,” according to a trio led by Sadeer Al-Kindi, MD, of Houston Methodist.

“Addressing environmental risk factors will significantly reduce the global burden of cardiovascular disease and address long-standing health disparities,” the group added in an accompanying editorial.

Al-Kindi and colleagues explained that metals may exert harm through mechanisms related to the induction of oxidant stress, directly or indirectly, and epigenetic regulation.

“Given the importance of metal exposure in CVD outcomes, which is comparable to traditional risk factors, as supported in this study, further investigation in large, longitudinal studies with repeated measures of metals and CAC is necessary to further characterize this association across multiple populations, in particular, to evaluate potential gene-environment interactions, characterize associations for subgroups, and inform relevant interventions,” study authors concluded.

From their study, they highlighted the essential metals copper and zinc in particular for having substantially weakened ties to CAC after adjustment for clinical factors.

Al-Kindi’s group said “the differential effects observed for essential and nonessential metals highlight the potential complex interplay between nutritional status and environmental exposures in ASCVD pathogenesis.” They suggested that “these essential metals may interact with, or be mediated by, other processes in ways that are not yet fully understood.”

The verdict on arsenic, cadmium, and lead exposure as CVD risk factors is more clear, as this is the official position of the American Heart Association based on years of evidence.

McGraw’s group noted that cadmium, tungsten, uranium, cobalt, copper, and zinc pollution occurs widely due to agricultural and industrial processes such as oil production, welding, mining, and nuclear energy production. In particular, cadmium is a known carcinogen with adverse effects on the kidneys, liver, and lungs. Tobacco smoking is the major source of cadmium.

For their study, McGraw and colleagues relied on the Multi-Ethnic Study of Atherosclerosis (MESA), a well-described multicenter prospective cohort of people recruited in six urban communities who were free of clinical CVD and ages 45 to 84 at baseline.

Eligible participants were 6,418 people in MESA with at least several spot urinary metal tests done starting in 2000-2002. At baseline, their median CAC was 6.3 and approximately half had CAC scores over 0.

Urinary metal levels tended to be higher among females, older participants, Chinese people, and those with less education.

It was possible that exposure misclassification of certain metals occurred in the study, however. The investigators also cautioned that residual confounding may not be excluded due to the non-randomized study design.

Al-Kindi’s group added that spot urine samples may not fully capture long-term metal exposure patterns, and that urinary results for metals such as copper, zinc, and cobalt, urinary values may not reflect the major route of elimination.

“Pollution is the greatest environmental risk to cardiovascular health,” McGraw maintained in a press release. “Given the widespread occurrence of these metals due to industrial and agricultural activities, this study calls for heightened awareness and regulatory measures to limit exposure and protect cardiovascular health.”

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