To the editor

We read with great interest the article by Geng et al¹ on the association between elevated serum copper levels and optical coherence tomography–defined high‑risk plaque in patients with chronic coronary syndrome (CCS), published recently in Polish Archives of Internal Medicine. The study is clinically relevant and methodologically careful in several respects, particularly in its attempt to connect plaque morphology with a measurable circulating factor. However, we believe that an important translational issue deserves further attention before copper is considered a practical biomarker for routine risk stratification.

The main concern is that the level of copper was measured not in peripheral venous blood but in coronary blood sampled from the site of the target plaque during angiography. This design may be informative from a mechanistic perspective, because lesion‑adjacent sampling could appropriately reflect the local inflammatory and metabolic environment. At the same time, it substantially limits the clinical interpretation of the findings—a marker intended for noninvasive risk stratification in CCS should ideally be measurable in a standard peripheral blood sample obtained before invasive imaging. Coronary sampling is inherently procedure‑dependent and unavailable in the very population in whom triage is most needed. For this reason, the reported cutoff and the performance of the combined model may not be directly transferable to outpatient practice. Prior studies linking blood copper levels to atherosclerosis and cardiovascular risk have generally relied on systemic, not intracoronary samples.²

The biological interpretation of total serum copper in this setting also requires caution—total copper is not a simple readout of a single pathogenic pathway. Most of the circulating copper is protein‑bound, largely to ceruloplasmin, and its concentration is shaped by hepatic handling, nutritional status, and inflammatory activation.³ The observed associations with interleukin (IL)-6 and IL‑10 are intriguing, but they also leave open the possibility that copper is functioning here primarily as an integrated acute‑phase signal rather than a plaque‑specific marker. Without additional information on ceruloplasmin or other indices of copper speciation, it remains difficult to determine whether the measured analyte reflects biologically active copper relevant to plaque destabilization or a broader systemic response.

The predictive model also merits cautious interpretation—the combined panel including copper, low‑density lipoprotein cholesterol, and IL‑6 levels achieved a strong area under the curve, but model development, threshold selection, and performance testing were all conducted in the same small cohort. Under such circumstances, apparent discrimination is often optimistic, especially when no internal resampling or external validation is performed.⁴ The findings are therefore best viewed as hypothesis‑generating rather than immediately practice‑changing.

These points do not diminish the value of the study, but they do show what still needs to be done. It would be important to see whether the findings hold in peripheral blood samples, and whether the model works outside this single group of patients, before copper can be considered a useful clinical biomarker.