Urinary metals linked to higher cardiovascular disease risk and mortality

By Dr. Priyom Bose, Ph.D.Reviewed by Benedette Cuffari, M.Sc.Aug 5 2024

A recent Circulation journal study evaluates the association between urinary metals, cardiovascular disease (CVD), and all-cause mortality.

Study: Association of Urinary Metals With Cardiovascular Disease Incidence and All-Cause Mortality in the Multi-Ethnic Study of Atherosclerosis (MESA). Image Credit: Peter Hermes Furian / Shutterstock.com

Heavy metals and cardiovascular disease risk

Exposure to heavy metals can act as a modifiable risk factor for clinical and subclinical CVD and all-cause mortality. Some of the different mechanisms that may contribute to this cardiotoxicity include atherosclerosis, disruption of enzymatic reactions, metal-induced systemic inflammation, and oxidative stress.

The American Heart Association has recognized arsenic, cadmium, and lead as CVD risk factors. However, there remains a lack of evidence on how low levels of exposure to heavy metals may contribute to the risk of CVD. Likewise, few studies have assessed the impact of essential metals, such as cobalt, copper, and zinc, as well as non-essential metals, like uranium and tungsten, on the risk of CVD.

About the study

The current study's researchers analyzed data on adults in the United States obtained from the Multi-Ethnic Study of Atherosclerosis (MESA) to determine the association between baseline urinary metals and the risk of CVD and all-cause mortality. Altered levels of essential metals in the urine often reflect metabolic dysregulation, whereas non-essential metals are typically measured in urine as biomarkers of exposure.

The study sample comprised 6,599 participants with a mean age of 62.1 years, 53% female. A total of 1,844 participants died, whereas 1,162 participants developed incident CVD during the study follow-up period.

These individuals were more likely to have hypertension or diabetes or be current smokers. Study participants who experienced a CVD event during the follow-up period had higher baseline levels of zinc, copper, cadmium, and tungsten.

Cox proportional hazard models were estimated to calculate adjusted hazard ratios (aHRs) and associated 95% confidence intervals of CVD risk and all-cause mortality. In addition to measuring urinary metal levels, their joint association as a mixture and the resulting 10-year survival probabilities were estimated using Cox Elastic-Net.

Study findings

In models adjusted for clinical and sociodemographic factors, an increased risk of CVD was associated with higher baseline urinary levels of zinc, copper, uranium, cadmium, tungsten, and cobalt.

A linear dose-response curve was observed for cobalt, cadmium, and copper with CVD. Comparatively, a positive association was only observed between CVD risk and high levels of tungsten, uranium, and zinc.

Among individuals who never smoked, a positive association was observed between urinary zinc levels and incident CVD. In other sub-group analyses, the associations were largely consistent. In a fully adjusted machine learning model, a positive association was reported between incident CVD risk and all six urinary metals.

The 10-year survival probability curves for incident CVD and individual metals showed an inverse relationship. Higher baseline urinary levels of zinc, cadmium, tungsten, cobalt, and copper were associated with a consistent decrease in the likelihood of survival. However, these effects were attenuated after adjusting for CVD risk factors.

Fully adjusted models showed an increased risk of all-cause mortality associated with higher baseline urinary levels of all six metals. Comparing the highest with the lowest quartiles of urinary metals, aHRs were highest for cadmium and lowest for tungsten.

The dose-response relationship was mostly linear for copper and cadmium. A positive association was observed between all-cause mortality and high levels of zinc, tungsten, cobalt, and uranium.

The 10-year survival probability curves for all-cause mortality showed a consistent reduction in survival probabilities for cadmium, cobalt, copper, and zinc. These effects were weakened when CVD risk factors were considered in the analysis.

Conclusions

The current study identified associations between the risk of CVD, all-cause mortality, and exposure to individual and mixtures of essential and non-essential urinary metals. These findings, which highlight the role of metals as risk factors for CVD and all-cause mortality, can guide future research on the development of novel strategies to reduce CVD risk by mitigating the adverse effects of metals.

Some key strengths of the current study involve including diverse participants from different geographic locations and large sample size, improving the findings' generalizability. The researchers also investigated the effects of urinary metals as a mixture and alone, with consistent results observed across both approaches.

The main limitation of this study is that it relies on a single-spot measurement of urinary metals, which may be inadequate in capturing long-term exposure patterns. Also, given the observational study design, residual confounding cannot be ruled out.