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

Abstract

Background: Cardiovascular hemodynamic stress may be associated with alterations in the circulating ionome. We investigated whether a hypothesis-driven multielement composite, the congestion-associated ionomic dysregulation score (CIDS; higher copper and strontium and lower rubidium and iron), was associated with N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cardiorenal–hematologic burden. Methods: This retrospective, single-center, cross-sectional study included 192 patients undergoing cardiovascular evaluation or treatment. Serum trace elements were quantified by inductively coupled plasma mass spectrometry, and CIDS was calculated from standardized element concentrations. Results: Higher CIDS was associated with higher NT-proBNP (ρ = 0.416, FDR-adjusted p < 0.001), worse New York Heart Association (NYHA) functional status (ρ = 0.370, p < 0.001), lower hemoglobin (ρ = −0.287, p < 0.001), lower eGFR (ρ = −0.191, p = 0.012), and higher uric acid (ρ = 0.241, p = 0.002). In the common complete-case sample, each 1-SD increase in CIDS was associated with higher log-transformed NT-proBNP after multivariable adjustment (β = 0.276, 95% CI 0.077–0.475; HC3-robust p = 0.007), and model R2 increased from 0.368 to 0.407. The observed ΔR2 exceeded the median from randomly weighted composites but did not clearly exceed the permutation null distribution (empirical p = 0.063). The referral-stratified estimates differed in magnitude (β = 0.179 versus 0.569), without a significant interaction (p = 0.171). Conclusions: CIDS was associated with myocardial stress and cardiorenal–hematologic burden in this cohort, but the single-center, cross-sectional findings do not establish causality, unique superiority over alternative composites, or external biomarker validity. Because CIDS was standardized internally within this cohort, no externally applicable reference values or clinical cutoffs can currently be defined.