Context-Dependent Shift in Trace Element Risk Drivers for Carotid Plaque Instability: Copper Supersedes Iron in...

Carotid plaque instability is a critical precursor to ischemic stroke, but the role of trace elements in this process remains incompletely understood. This study aimed to evaluate the association between essential trace element mixtures (iron, copper, zinc, and selenium) and carotid plaque instability, with particular attention to metabolic context-dependent effects.

We conducted a cross-sectional study of 1000 patients (56.8 ± 8.8 years) with carotid atherosclerotic plaques from Huludao Central Hospital. Participants were stratified into stable n = 536 and unstable(n = 464)groups based on carotid ultrasound assessment. Serum Fe, Cu, Zn, and Se were measured using inductively coupled plasma mass spectrometry. weighted quantile sum regression and restricted cubic spline evaluated element mixtures and dose-response relationships, stratified by smoking, hypertension, and diabetes.

Iron and copper exhibited significant positive linear associations with plaque instability (Q4 vs. Q1: OR = 5.39, 95% CI: 3.56- 8.25for iron; OR = 5.38, 95% CI: 3.53-8.29 for copper). Selenium showed a protective effect (Q4 vs. Q1: OR = 0.49, 95% CI: 0.32-0.73), while zinc displayed a non-linear, U-shaped relationship. Crucially, in patients with hypertension or diabetes, copper became the predominant risk driver (49.5% and 61.0% weights, respectively), surpassing iron's weights.

The pathological impact of trace elements on carotid plaque instability is fundamentally context-dependent. This study reveals a "pathological switch" to copper dominance in metabolically compromised subgroups, highlighting the need for precision medicine approaches that consider individual metabolic profiles when assessing plaque vulnerability and designing targeted interventions.