Serum-to-hair Zn ratio as an index of zinc dyshomeostasis in HFpEF patients.

BACKGROUND

Heart failure with preserved ejection fraction (HFpEF) is a systemic cardiometabolic syndrome characterized by chronic inflammation, oxidative stress, and endothelial dysfunction. Disturbances in trace element homeostasis, particularly zinc, may contribute to these processes.

OBJECTIVE

To investigate whether the combined assessment of serum and hair zinc provides insight into compartment-specific alterations in zinc homeostasis in HFpEF.

METHODS

In this prospective, single-center study, 53 consecutive patients with exertional dyspnea underwent clinical evaluation, echocardiography, and trace element analysis using ICP-MS. A total of 53 patients were screened. No patients were excluded after application of the predefined exclusion criteria. HFpEF was diagnosed using the HFA-PEFF algorithm. In addition to zinc, a broad panel of trace elements (including Cu, Se, Fe, and others) was analyzed, although only zinc demonstrated consistent and significant compartmental differences. Zinc concentrations were measured in serum and scalp hair, and a serum-to-hair zinc ratio was calculated. A broad panel of trace elements was analyzed; however, only zinc demonstrated consistent compartmental differences.

RESULTS

Thirteen patients were diagnosed with HFpEF and compared with 40 controls. HFpEF patients exhibited significantly higher serum zinc and lower hair zinc concentrations, resulting in a markedly elevated serum-to-hair zinc ratio (p < 0.001). This ratio remained independently associated with HFpEF after adjustment for clinical covariates. ROC analysis demonstrated high apparent discriminative performance (AUC 0.981), although this may be overestimated due to the limited sample size and lack of external validation.

CONCLUSIONS

HFpEF is associated with a dissociation between circulating and long-term zinc compartments, suggesting altered zinc homeostasis rather than simple deficiency or excess. The serum-to-hair zinc ratio represents a promising exploratory biomarker reflecting this dyshomeostasis. This study should be considered a pilot investigation generating hypotheses for future research.