# Serum Heavy Metal Burden and Its Association With Angiographic Severity and Six-Month Outcomes in Coronary Artery Disease: A Prospective Observational Study From North India

## TL;DR

This study from North India found no direct link between heavy metal levels and coronary artery disease severity, but noted higher levels in specific patient groups.

## Contribution

The study explores heavy metal associations with CAD severity and outcomes in an Indian population, revealing potential links to disease phenotype.

## Key findings

- Higher cadmium levels were found in patients with acute coronary syndrome compared to stable CAD patients.
- Elevated arsenic and mercury levels were observed in hypertensive patients.
- No significant association was found between heavy metal levels and six-month cardiovascular outcomes.

## Abstract

Background: Heavy metal exposure is a silent yet significant cardiovascular risk factor, particularly in low- and middle-income countries with evolving environmental and dietary patterns. Metals like cadmium, arsenic, and mercury contribute to atherogenesis through oxidative stress, inflammation, and endothelial dysfunction. However, their association with coronary artery disease (CAD) severity and clinical outcomes remains underexplored in Indian populations. This study evaluated serum levels of six heavy metals and their relation to angiographic complexity and six-month cardiovascular outcomes.

Methods: In this single-center, prospective study, 497 patients undergoing coronary angiography for CAD were enrolled and stratified by the SYNTAX score: SYNTAX score <23 and SYNTAX score ≥23. Serum levels of arsenic, antimony, mercury, lead, nickel, and cadmium were quantified using inductively coupled plasma mass spectrometry (ICP-MS). SYNTAX score, clinical parameters, and six-month outcomes for major adverse cardiovascular events (MACE) were recorded.

Results: Mean SYNTAX scores did not differ significantly across quartiles of any heavy metal (all p > 0.05). Adjusted analysis showed no association between metal levels and high SYNTAX score (adjusted OR = 1.07, 95% CI 0.89-1.30, for cadmium per SD increase). However, subgroup analysis revealed higher cadmium levels in patients with acute coronary syndrome (ACS) compared to stable CAD patients (median = 0.78 (IQR 0.65-0.94) µg/L vs. 0.62 (IQR 0.54-0.75) µg/L; p = 0.006), and elevated arsenic and mercury levels in hypertensive patients (mean difference = +1.21 µg/L (95% CI 0.58-1.84), p = 0.001; +0.34 µg/L (95% CI 0.15-0.53), p = 0.0013). At the six-month follow-up, MACE occurred in 6.6% of patients and were associated with a high SYNTAX score (OR = 4.4 (95% CI 1.7-11.5), p = 0.002), but not with any metal level (all p > 0.1).

Conclusion: Serum heavy metal levels were not associated with angiographic CAD severity. Nevertheless, higher cadmium levels in ACS patients and elevated arsenic/mercury levels in hypertensive patients suggest that metal exposure may influence disease phenotype rather than plaque burden. These exploratory findings warrant validation in larger longitudinal cohorts.