Urinary levels of non-essential (i.e., cadmium, tungsten, uranium) and essential metals (i.e., cobalt, copper, zinc) are associated with increased coronary artery calcification (CAC) and are comparable to traditional cardiovascular disease risk factors like smoking and diabetes, according to results from the Multi-Ethnic Study of Atherosclerosis (MESA) published in JACC.

"Our findings highlight the importance of considering metal exposure as a significant risk factor for atherosclerosis and [cardiovascular disease]," said Katlyn E. McGraw, PhD, lead author of the study. "This could lead to new prevention and treatment strategies that target metal exposure."

Researchers continuously measured urinary metal levels in 6,418 individuals aged 45-84 from diverse racial backgrounds who were free from clinical cardiovascular disease over a 10-year period. Results showed CAC levels were 51% higher at baseline and 75% higher over the 10-year period when comparing the highest to lowest quartile of urinary cadmium. 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 cardiovascular disease risk factors such as smoking, diabetes and LDL-C levels. The associations between metals and CAC progression were comparable in magnitude to those for traditional risk factors.

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

In an accompanying editorial comment, Sadeer Al-Kindi, MD, FACC, noted that the "study has important implications for public health, health equity and clinical practice" and 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 Al-Kindi, "future studies should investigate the role of incorporating metal exposure assessment in cardiovascular risk prediction, especially for patients in areas with known contamination or occupational exposures."

"Until we have directed therapies based on these measures, this type of testing should be considered a research enterprise," said Kim A. Eagle, MD, MACC, editor-in-chief of ACC.org.