| Title: | Circulating excitation-contraction coupling proteins and incident cardiovascular outcomes: associations and incremental predictive performance in the UK Biobank |
| Journal: | Frontiers in Cardiovascular Medicine |
| Published: | 12 Aug 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/42656608/ |
| DOI: | https://doi.org/10.3389/fcvm.2026.1841253 |
| URL: | https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2026.1841253/pdf |
Publication 21158
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Abstract
Introduction: Excitation-contraction coupling is central to cardiovascular physiology, but the prospective relevance of circulating proteins involved in this pathway remains uncertain.</p>
Methods: We evaluated a prespecified seven-protein excitation-contraction coupling panel (EC7: NEXN, SLMAP, ITPR1, CACNB1, HRC, RYR1, and CACNA1C) in the UK Biobank proteomics cohort in relation to incident stroke, heart failure, acute myocardial infarction, and angina recorded during the available observation period. Outcome-specific logistic-regression models estimated odds ratios per 1-standard-deviation higher relative protein level after adjustment for demographic and clinical factors, with false-discovery-rate correction across 28 primary tests. Predictive analyses used locked training/test partitions, screening of 13 candidate algorithms, nested cross-validation, frozen calibration and thresholds, and comparisons with clinical features and five established cardiovascular proteins.</p>
Results: Among 52,995 participants in the analysis source proteomics cohort, 39,691 had complete EC7 measurements. Higher ITPR1 (odds ratio, 1.088; 95% confidence interval, 1.033-1.146; q = 0.022) and HRC (odds ratio, 1.246; 95% confidence interval, 1.191-1.305; q < 0.001) were associated with incident heart failure; no other primary association survived correction. Logistic regression was selected for all outcomes. Adding EC7 proteins to clinical features did not improve locked-test predictive performance after multiplicity correction; for heart failure, changes were +0.0054 in ROC-AUC (q = 0.112) and +0.0084 in average precision (q = 0.217). Established comparator proteins consistently outperformed EC7 in biomarker-only comparisons.</p>
Discussion: Circulating excitation-contraction coupling proteins showed outcome-specific associations, particularly with heart failure, but limited incremental predictive performance. These findings support further mechanistic investigation and validation in independent cohorts.</p>
10 Authors
- Dan Hu
- Yang Gao
- Jing Wang
- Quan Guo
- Zhuocheng Shi
- Donghui Chen
- Dongsheng Xia
- Muwei Li
- Xiaohu Wang
- Bingchuan Geng
1 Application
| Application ID | Title |
|---|---|
| 1034464 | Microcirculation and Systemic Vascular Health: Genetic and Epidemiological Insights from the UK Biobank |
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