A recent study from Columbia University Mailman School of Public Health reveals that higher urinary levels of metals such as cadmium, tungsten, uranium, cobalt, copper, and zinc are correlated with an increased risk of cardiovascular disease (CVD) and mortality. Although it is already known that certain metals are linked to CVD and mortality, previous studies have largely focused on arsenic, cadmium, and lead, with a lack of comprehensive research on a racially diverse demographic. The results were published in the journal Circulation.
The analysis showed that the combination of these six metals led to a 29% rise in the risk of CVD and a 66% increase in the risk of death during an 18-year follow-up period. The study found similar increases in CVD risk and mortality associated with each metal individually.
“Our research represents the largest prospective study analyzing urinary metals and cardiovascular disease so far, highlighting urinary metals as new risk factors for both CVD and overall mortality,” stated Irene Martinez-Morata, MD, PhD, a lead author from the Department of Environmental Health Sciences at Columbia Mailman School. “These findings can assist in enhancing risk prediction and preventative measures aimed at improving cardiovascular health by lowering metal exposure across various populations.”
Metal exposure is widespread with various sources, and climate change can worsen contamination in air, soil, and water, ultimately affecting the food supply. Certain population groups, including non-Hispanic Black, Hispanic/Latino, Chinese, and American Indian communities, as well as those with lower socioeconomic status, tend to have higher metal exposure, indicating that societal, structural, and historical factors contribute to health disparities beyond just individual risk factors like smoking or diet. “Reducing metal exposure can greatly aid these populations, who also face higher rates of CVD mortality,” Martinez-Morata added.
The American Heart Association has acknowledged the harmful effects of toxic metals such as arsenic, cadmium, and lead concerning CVD incidences. However, research on lesser-known metals like copper and zinc—as well as combinations of metals—has been limited until now.
The researchers utilized the Multi-Ethnic Study of Atherosclerosis (MESA) to explore the relationship between six urinary metals and health outcomes in a diverse set of communities across the U.S., including Baltimore, Chicago, Forsyth County, Los Angeles County, Northern Manhattan and the Bronx, and St. Paul from July 2000 to August 2002. Urine samples were evaluated at Columbia University’s Trace Metals Core Laboratory, using innovative machine learning techniques developed at the Department of Biostatistics for combined effect analysis.
The study population included 39% non-Hispanic White, 27% non-Hispanic Black, 22% Hispanic/Latino, and 12% of Chinese descent. By the end of the follow-up period, 1,162 participants had CVD and 1,844 had passed away.
Taking into account known CVD risk factors such as smoking, hypertension, and diabetes, the study found that higher concentrations of the metal mixture were associated with a 29% increased risk of CVD and a 66% increased mortality risk during the follow-up. In terms of individual metals, elevated levels of cadmium were linked to a 25% and 68% higher risk for CVD and mortality, respectively, with similar associations observed for other metals.
“In the U.S., exposure to metals that have not been extensively studied, like tungsten and uranium, is fairly common through drinking water, food, air pollution, and household dust,” Martinez noted. Certain metals, termed biometals, such as copper and zinc, are essential in small quantities but may become harmful at higher levels. “This area remains under investigation, but elevated levels of these essential metals in urine may indicate increased exposure or a depletion of the body’s reserves, which can occur with dysfunctional metabolism associated with early cardiovascular disease stages.”
“To minimize metal exposure, implementing federal regulations for air pollution, drinking water safety, food contamination, and consumer products is crucial, alongside addressing vulnerabilities at the community and individual levels,” said Martinez. “Although regulations for drinking water contaminants have effectively decreased toxic metal levels, more research is needed to fully understand the implications of metals like tungsten and cobalt.”
“One of the strengths of our study is its analysis of urinary metals as a collective mixture,” explained Ana Navas-Acien, MD, PhD, professor and chair of the Department of Environmental Health Sciences at Columbia Mailman School. “In addition to a large, racially diverse sample, we employed cutting-edge laboratory techniques—led by our Trace Metals Core Laboratory—and monitored health outcomes over an extended period. Future studies should include repeated measures of urine metal levels to gain more insights into long-term exposure.”
“These findings highlight the urgent need to reduce environmental exposure to these metals, which have had a disproportionate impact on marginalized and lower-income communities,” remarked Cashell Jaquish, PhD, a genetic epidemiologist at the National Heart, Lung, and Blood Institute (NHLBI) and a program officer for the MESA study. “This research could prompt initiatives to lessen metal exposure in communities, thereby addressing health disparities related to heart disease, the leading cause of death in the United States.”
Co-authors of the study include Kathrin Schilling, Ronald Glabonjat, Arce Domingo-Relloso, Melanie Mayer, Marta Galvez Fernandez, Tiffany Sanchez, Linda Valeri, and Anne Nigra from Columbia Mailman School of Public Health; Joel Kaufman from the University of Washington; Dhananjay Vaidya and Wendy Post from Johns Hopkins University; Miranda Jones from Johns Hopkins Bloomberg School of Public Health; Michael Bancks from Wake Forest University School of Medicine; R. Graham Barr, Daichi Shimbo, and Steven Shea from Columbia University Irving Medical Center.
The Multi-Ethnic Study of Atherosclerosis (MESA) is backed by the National Heart, Lung, and Blood Institute under various grants. For a complete list of organizations contributing to the study, please refer to the published paper.
The authors have disclosed no conflicts of interest.
