Urinary metal mixtures linked to 29% higher cardiovascular disease risk and 66% higher mortality in largest prospective study to date
核心洞察
A six-metal urinary mixture of cadmium, tungsten (搜索), uranium (搜索), copper, cobalt, and zinc was associated with a 29% increased risk of cardiovascular disease (搜索) and a 66% increased risk of death over 18 years of follow-up.
The study, using the Multi-Ethnic Study of Atherosclerosis (MESA), is the largest prospective investigation of urinary metals and cardiovascular disease (搜索) to date, with 1,162 CVD events and 1,844 deaths recorded.
Higher levels of cadmium alone were linked to up to a 25% higher risk of CVD and 68% higher mortality, with similar associations observed for each metal individually.
A six-metal mixture measured in urine—cadmium, tungsten (搜索), uranium (搜索), copper, cobalt, and zinc—was associated with a 29% increased risk of cardiovascular disease (搜索) (CVD) and a 66% increased risk of death over an 18-year follow-up period, according to the largest prospective study of urinary metals and cardiovascular disease conducted to date.
The findings, led by Irene Martinez-Morata, MD, PhD, of the Department of Environmental Health Sciences at Columbia Mailman School of Public Health (搜索), draw on the Multi-Ethnic Study of Atherosclerosis (MESA), which enrolled participants from six urban and suburban U.S. communities between July 2000 and August 2002. Urine samples were analyzed at the Trace Metals Core Laboratory at Columbia University.
"Our study presents the results from the largest prospective study of urinary metals and cardiovascular disease (搜索) to date and supports the role of urinary metals as novel risk factors for CVD and all-cause mortality risk," said Martinez-Morata. "Our findings can inform risk prediction and preventive strategies to improve cardiovascular health by reducing metal exposures across diverse populations."
Metal mixtures and individual metal risks
To assess the joint effect of urinary metals as a mixture, the researchers conducted additional analyses using a machine learning approach recently developed at the Department of Biostatistics at Columbia University. After accounting for established CVD risk factors such as smoking, hypertension, and diabetes, higher levels of the six-metal mixture were associated with a 29% increased risk of CVD and a 66% increased risk of mortality over the study follow-up.
For individual metals, higher levels of cadmium were associated with up to a 25% higher risk of CVD and a 68% higher risk of mortality. Similar associations were identified for all of the other metals studied.
"Exposure to less studied metals such as tungsten (搜索) and uranium (搜索) is common in the U.S. and can occur through drinking water, food, air pollution, and indoor dust," observed Martinez-Morata. While some metals, known as biometals, such as copper and zinc are needed in small amounts by the body, high levels in the urine can be harmful. "While this is an ongoing field of study, high levels of essential metals in the urine can indicate an excess in exposure or loss of body reserves of these nutrients, which can occur when the metabolism is starting to malfunction, as it occurs in early stages of cardiovascular disease (搜索)."
A diverse study population
Of the population analyzed, 39% were non-Hispanic White, 27% non-Hispanic Black, 22% Hispanic/Latino, and 12% Chinese descent. Over the study follow-up period, 1,162 participants developed CVD and 1,844 participants died.
The American Heart Association recently recognized the toxic metals arsenic, cadmium, and lead as associated with some incidence of CVD. However, until now, studies assessing the effects of less studied metals—including biometals such as copper and zinc, and metal mixtures more likely to mimic real-life exposures—have been limited.
Disparities in exposure and disease burden
Exposure to metals is widespread, with sources and routes of exposure that vary and can be exacerbated by climate change leading to contamination of air, soil, and water, and ultimately the food chain. Higher burdens of metal exposure have been documented across population groups such as non-Hispanic Black, Hispanic/Latino, Chinese, and American Indians, and among communities with lower socioeconomic status, revealing that sociopolitical, historical, and structural factors contribute to disparities beyond individual-level factors such as smoking, occupation, and diet.
"Interventions to reduce metal exposure can particularly benefit these population groups who also suffer a higher burden of CVD mortality," added Martinez-Morata.
Policy implications and study strengths
"Implementing policies and regulations for air pollution, drinking water and food contamination, and consumer products at the federal level, in addition to addressing community and household vulnerability factors, and individual behavioral changes can reduce exposure to metals," noted Martinez-Morata. She added that further analyses will help inform prevention strategies and interventions, including those directed at less studied and unregulated metals such as tungsten (搜索) or cobalt.
"While federal regulations for lowering maximum contaminant levels for drinking water and banning leaded gasoline, for example, have successfully reduced exposure to toxic metals such as arsenic, cadmium, and lead in water and air, much more study is needed to understand the contributions of such metals as tungsten (搜索) and cobalt."
Ana Navas-Acien, MD, PhD, professor and chair of the Columbia Mailman School Department of Environmental Health Sciences, highlighted the methodological strengths of the work. "A strength of our study is how we assessed the association of urine metals as a mixture. In addition to sampling a large population size and a racially and diverse participant base, we used state-of-the-art laboratory methods—led by our Trace Metals Core Laboratory, and we analyzed outcomes over a long follow-up. However, future studies using repeated measures of urine metal levels can provide even more advanced information about exposure over time."
Cashell Jaquish, PhD, a genetic epidemiologist at the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health (NIH), and a program officer with the MESA study, underscored the public health significance. "The findings underscore the importance of reducing environmental exposure to these metals, which have disproportionately affected minority and poorer communities. The results could lead to efforts to reduce metal exposure in our communities and thereby reduce health disparities in heart disease, the leading cause of death in this country."