A recent study published in Circulation has revealed a significant association between urinary metal levels and the risk of cardiovascular disease (CVD) and all-cause mortality. Conducted by researchers using data from the Multi-Ethnic Study of Atherosclerosis (MESA), this research highlights the potential of both essential and non-essential metals as modifiable risk factors for CVD and mortality, underscoring the need for increased awareness and further investigation.
Metals from natural and human-made sources are widespread contaminants impacting global health. While heavy metals like arsenic, cadmium, and lead are known CVD risk factors, the effects of low-level exposure and the roles of essential metals like cobalt, copper, and zinc, as well as non-essential metals like uranium and tungsten, are less understood. Metals vary in their redox activity, influencing toxicity; for example, cobalt and copper generate reactive oxygen species linked to CVD, while cadmium depletes protective antioxidants. Additionally, some metals disrupt the endocrine and vascular systems, potentially contributing to atherosclerosis through various pathways.
To address these knowledge gaps, the researchers analyzed baseline urinary metal levels in a diverse cohort of 6,599 U.S. adults with a mean age of 62.1 years, 53% of whom were female. During the follow-up period, 1,844 participants died, and 1,162 developed incident CVD. Notably, those who experienced CVD events were more likely to have pre-existing conditions like hypertension or diabetes or to be current smokers
The results indicated that higher baseline urinary levels of zinc, copper, uranium, cadmium, tungsten, and cobalt were associated with an increased risk of cardiovascular disease. A linear dose-response relationship was observed for cobalt, cadmium, and copper with CVD, while high levels of tungsten, uranium, and zinc were linked to a higher risk of developing the disease. Interestingly, among individuals who never smoked, a positive association was found between urinary zinc levels and incident CVD.
Machine learning model further confirmed a positive association between incident CVD risk and all six urinary metals, suggesting that these metals, even when present in mixtures, may significantly impact cardiovascular health. The 10-year survival probability curves revealed an inverse relationship between higher baseline urinary levels of zinc, cadmium, tungsten, cobalt, and copper and survival likelihood, although these effects were attenuated after adjusting for CVD risk factors.
Regarding all-cause mortality, the study found a consistent association with higher baseline urinary levels of all six metals. The adjusted hazard ratios were highest for cadmium and lowest for tungsten when comparing the highest to the lowest quartiles of urinary metals. The dose-response relationship was primarily linear for copper and cadmium, with a positive association between high levels of zinc, tungsten, cobalt, and uranium and all-cause mortality. The 10-year survival probability curves for all-cause mortality also showed a consistent reduction in survival probabilities for cadmium, cobalt, copper, and zinc, although these effects were weakened when considering CVD risk factors.
The findings suggest that both essential and non-essential metals are related to the development of CVD, at least in part, through increased arterial calcification. Arterial calcification, a key factor in the progression of atherosclerosis, is linked to higher risks of heart attacks and strokes. These findings emphasize the need for public health actions from governments and public health agencies to lower acceptable limits of metals in air, water, and soil. Improving enforcement of metal pollution reduction is particularly crucial in communities experiencing disproportionate metal exposures, where the burden of CVD may be higher due to environmental factors. Educational campaigns to raise awareness about the risks of metal exposure and promote safer practices are also important.
References
- Martinez-Morata I, Schilling K, Glabonjat RA, Domingo-Relloso A, Mayer M, McGraw K, et al. Association of Urinary Metals With Cardiovascular Disease Incidence and All-Cause Mortality in the Multi-Ethnic Study of Atherosclerosis (MESA). Circulation [Internet]. [cited 2024 Aug 9];0(0). Available from: https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.124.069414
- McGraw KE, Schilling K, Glabonjat RA, Galvez-Fernandez M, Domingo-Relloso A, Martinez-Morata I, et al. Urinary Metal Levels and Coronary Artery Calcification: Longitudinal Evidence in the Multi-Ethnic Study of Atherosclerosis (MESA). medRxiv. 2023 Nov 1;2023.10.31.23297878.