“Our findings highlight the importance of considering metal exposure as a significant risk factor for atherosclerosis and CVD,” said Katlyn E. McGraw, PhD, a postdoctoral research scientist at Columbia University Mailman School of Public Health and lead author of the study. “This could lead to new prevention and treatment strategies that target metal exposure.”

Atherosclerosis is a condition in which the arteries become narrowed and hardened due to a buildup of plaque. This can restrict blood flow and cause clots to form. It’s an underlying cause of heart attacks, strokes, and peripheral artery disease (PAD), the most common forms of cardiovascular disease (CVD). Atherosclerosis causes coronary artery calcium (CAC), which can be measured non-invasively to predict future cardiac events.

“This groundbreaking study underscores the critical associations of metal exposure from environmental pollution to cardiovascular health,” said Harlan M. Krumholz, the Harold H. Hines, Jr. Professor at Yale and Editor-in-Chief of JACC. “It challenges us to broaden our approach to CVD prevention beyond traditional risk factors and to advocate for stronger environmental regulations, and it underscores the need for continued research in this critical area.”

Exposure to environmental pollutants like metals is a newly recognized risk factor for CVD, but there isn’t a lot of research on its association with CAC. Researchers in this study sought to determine how urinary metal levels, biomarkers of metal exposure and internal doses of metals impact CAC.

Researchers used data from the Multi-Ethnic Study of Atherosclerosis (MESA) prospective cohort, tracking 6,418 men and women aged 45-84 from diverse racial backgrounds free from clinical CVD, to measure urinary metal levels at the beginning of the study in 2000-2002. They examined non-essential (cadmium, tungsten, uranium) and essential (cobalt, copper, zinc) metals, both common in U.S. populations and associated with CVD. Widespread cadmium, tungsten, uranium, cobalt, copper, and zinc pollution occurs from agricultural and industrial uses such as fertilizers, batteries, oil production, welding, mining, and nuclear energy production. Tobacco smoke is the main source of cadmium exposure.

Results provided evidence that metal exposure may be associated with atherosclerosis over 10 years by increasing coronary calcification.

Comparing the highest to lowest quartile of urinary cadmium, CAC levels were 51% higher at baseline and 75% higher over the 10-year period. For urinary tungsten, uranium and cobalt, the corresponding CAC levels over the 10-year period were 45%, 39%, and 47% higher, respectively. For copper and zinc, the corresponding estimates dropped from 55% to 33% and from 85% to 57%, respectively, after adjustment for clinical factors.

Non-essential and essential urinary metal levels also varied by demographic characteristics. Higher urinary metal levels were seen in older participants, Chinese participants and those with less education. Participants from Los Angeles had markedly higher urinary tungsten and uranium levels, and somewhat higher cadmium, cobalt, and copper levels.

The study’s analysis also considered traditional CVD risk factors such as smoking, diabetes, and LDL-cholesterol levels. The associations between metals and CAC progression were comparable in magnitude to those for traditional risk factors.

“Pollution is the greatest environmental risk to cardiovascular health,” McGraw said. “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.”

Limitations of the study include the unavailability of plaque transition measures in MESA, changes in exposure sources and other factors causing variability of certain measured metals, and the potential for residual and unknown confounding of time-varying exposure measurements.

In an accompanying editorial comment, Sadeer Al-Kindi, MD, Associate Director of Cardiovascular Prevention and Wellness at the Houston Methodist DeBakey Heart and Vascular Center, said the evidence of the study has important implications for public health, health equity and clinical practice.

“The field of environmental cardiovascular medicine, exemplified by this research, offers an emerging frontier in cardiovascular disease prevention and treatment,” Al-Kindi said. “Addressing environmental risk factors like metal exposure will significantly reduce the global burden of cardiovascular disease and address long-standing health disparities.”