Cardiovascular

A Multielement Ionomic Dysregulation Pattern Is Associated with NT-proBNP and Cardiorenal Burden in Patients with Cardiovascular Disease.

Kang M, Baek S, et al. • Molecules (Basel, Switzerland) • 2026

PubMed 42943661 DOI 10.3390/molecules31203588

TL;DR

A hypothesis-driven multielement composite, the congestion-associated ionomic dysregulation score (CIDS; higher copper and strontium, lower rubidium and iron), was associated with NT-proBNP and cardiorenal-hematologic burden in this single-center cross-sectional cohort, but the findings do not establish causality, unique superiority over alternative composites, or external biomarker validity.

Key Findings

Results

Higher CIDS was associated with higher NT-proBNP and worse NYHA functional status.

Retrospective, single-center, cross-sectional study of 192 patients undergoing cardiovascular evaluation or treatment.
NT-proBNP: ρ = 0.416, FDR-adjusted p < 0.001.
NYHA functional status: ρ = 0.370, p < 0.001.
Serum trace elements were measured by inductively coupled plasma mass spectrometry; CIDS was calculated from standardized element concentrations (higher copper and strontium, lower rubidium and iron).

Results

Higher CIDS was associated with markers of hematologic and renal burden and with higher uric acid.

Hemoglobin: ρ = -0.287, p < 0.001.
eGFR: ρ = -0.191, p = 0.012.
Uric acid: ρ = 0.241, p = 0.002.

Results

CIDS remained independently associated with log-transformed NT-proBNP after multivariable adjustment and improved model fit.

In the common complete-case sample, each 1-SD increase in CIDS corresponded to β = 0.276 (95% CI 0.077-0.475; HC3-robust p = 0.007).
Model R² increased from 0.368 to 0.407 when CIDS was added.

Results

The incremental explanatory value of CIDS exceeded the median of random composites but did not clearly exceed the permutation null distribution.

The observed ΔR² exceeded the median from randomly weighted composites.
Empirical p = 0.063 against the permutation null distribution.
This indicates that unique superiority over alternative composites was not established.

Results

The CIDS–NT-proBNP association differed in magnitude between referral strata, without a significant interaction.

Stratified estimates were β = 0.179 versus 0.569.
Interaction p = 0.171.

Conclusions

The authors state the study's limitations preclude causal inference, external validation, or defining clinical reference values for CIDS.

Single-center, cross-sectional design does not establish causality.
CIDS was standardized internally within this cohort, so no externally applicable reference values or clinical cutoffs can currently be defined.
External biomarker validity was not established.

What This Means

This study looked at whether a combined pattern of trace elements in the blood was linked to heart stress and related health problems. Researchers measured trace elements in 192 patients undergoing heart-related evaluation or treatment, and built a score from four of them: higher copper and strontium, and lower rubidium and iron. They then compared this score with NT-proBNP, a blood marker of heart strain, as well as heart failure symptoms, kidney function, hemoglobin and uric acid. Patients with higher scores tended to have higher NT-proBNP, worse heart-failure symptoms (NYHA class), lower hemoglobin, lower kidney function (eGFR) and higher uric acid. The link with NT-proBNP persisted after accounting for other factors, and adding the score modestly improved how well the model explained NT-proBNP levels (R² from 0.368 to 0.407). However, the score did not clearly outperform randomly weighted combinations of elements in a permutation test (p = 0.063), and the strength of the association varied between patient referral groups, though that difference was not statistically significant. This research suggests that changes in several trace elements together may reflect heart stress and combined heart-kidney-blood problems. Because the study was done at one center at a single point in time, it cannot show that the elements cause or predict anything, and the score was calibrated only within this group, so it cannot yet be used as a clinical test or with set cutoffs. Confirmation in other cohorts would be needed.

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Citation

Kang M, Baek S, Raffa G, Pisano C, Nuzzi V, Kowalewski M, et al.. (2026). A Multielement Ionomic Dysregulation Pattern Is Associated with NT-proBNP and Cardiorenal Burden in Patients with Cardiovascular Disease.. Molecules (Basel, Switzerland). https://doi.org/10.3390/molecules31203588

Key Findings

What This Means

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