Differential Associations of Seven Circulating Complement Proteins with Heart Failure: A Single-Center Cross-Sectional Study
- 1Department of Cardiology, The First Affiliated Hospital of Nanchang University, Jiangxi Medical College, Nanchang, Jiangxi, People’s Republic of China
- 2Jiangxi Hypertension Research Institute, Nanchang, Jiangxi, People’s Republic of China
- 3Jiangxi Provincial Key Laboratory of Drug Target Discovery and Validation, School of Pharmacy, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People’s Republic of China
Abstract
Background: The complement system is associated with heart failure (HF), but patterns across circulating complement proteins and their sensitivity to covariate adjustment remain unclear.
Methods: In this cross-sectional study, 392 participants (164 chronic HF: 128 HFpEF, 14 HFmrEF, 22 HFrEF; 228 non-HF controls) were enrolled, and seven circulating complement proteins were measured. Spearman correlations with NT-proBNP and LVEF, sequential multivariable logistic regression, and restricted cubic splines were assessed for each protein. Benjamini–Hochberg false discovery rate (FDR) correction was applied to fully adjusted models. Subgroup and restricted-sample sensitivity analyses were performed. Exploratory quasi-Bayesian statistical decomposition assessed whether the C8–HF and CD55–HF associations overlapped with CRP, eGFR, and hemoglobin.
Results: C7 and CD55 showed the strongest positive correlations with NT-proBNP (ρ≈0.32) and weak negative correlations with LVEF. After full adjustment, odds ratios for prevalent HF per 1-SD increase were 1.39 (95% CI 1.06–1.84) for C1r, 1.72 (1.29–2.29) for C7, and 1.47 (1.13–1.92) for C9; FDR-adjusted P values were 0.045, 0.0017, and 0.014. C1s and CD46 were not significant; C8 and CD55 associations attenuated after adjustment. No non-linear associations were found. C1r, C7, and C9 remained significant when restricting to eGFR ≥60 mL/min/1.73 m2 or CRP ≤10 mg/L, but attenuated to non-significance when HF cases were restricted to LVEF ≥50%. Exploratory statistical decomposition suggested that the CD55–HF association partly overlapped with eGFR and hemoglobin, but not CRP; no corresponding overlap was observed for C8.
Conclusion: In this cross-sectional sample, C1r, C7, and C9 were associated with prevalent chronic HF after full adjustment and FDR correction, but estimates attenuated in the LVEF-preserved restricted sample. C8 and CD55 associations attenuated after adjustment, while C1s and CD46 were not significant. These associations require prospective validation and should not be interpreted as causal.
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BibTeX
@article{gong2026differential,
title = {{Differential Associations of Seven Circulating Complement Proteins with Heart Failure: A Single-Center Cross-Sectional Study}},
author = {Shaolin Gong and Xiaoting Jiang and Xia Feng and Nuo Xu and Yongnan Fu and Wenjun Xiong and Xiaoping Peng and Xiang Wang},
journal = {Journal of Inflammation Research},
year = {2026},
month = oct,
doi = {10.2147/jir.s638484},
url = {https://doi.org/10.2147/jir.s638484},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Differential Associations of Seven Circulating Complement Proteins with Heart Failure: A Single-Center Cross-Sectional Study
AU - Shaolin Gong
AU - Xiaoting Jiang
AU - Xia Feng
AU - Nuo Xu
AU - Yongnan Fu
AU - Wenjun Xiong
AU - Xiaoping Peng
AU - Xiang Wang
PY - 2026
DA - 2026/10/30
JO - Journal of Inflammation Research
DO - 10.2147/jir.s638484
UR - https://doi.org/10.2147/jir.s638484
AB - Background: The complement system is associated with heart failure (HF), but patterns across circulating complement proteins and their sensitivity to covariate adjustment remain unclear. Methods: In this cross-sectional study, 392 participants (164 chronic HF: 128 HFpEF, 14 HFmrEF, 22 HFrEF; 228 non-HF controls) were enrolled, and seven circulating complement proteins were measured. Spearman correlations with NT-proBNP and LVEF, sequential multivariable logistic regression, and restricted cubic splines were assessed for each protein. Benjamini–Hochberg false discovery rate (FDR) correction was applied to fully adjusted models. Subgroup and restricted-sample sensitivity analyses were performed. Exploratory quasi-Bayesian statistical decomposition assessed whether the C8–HF and CD55–HF associations overlapped with CRP, eGFR, and hemoglobin. Results: C7 and CD55 showed the strongest positive correlations with NT-proBNP (ρ≈0.32) and weak negative correlations with LVEF. After full adjustment, odds ratios for prevalent HF per 1-SD increase were 1.39 (95% CI 1.06–1.84) for C1r, 1.72 (1.29–2.29) for C7, and 1.47 (1.13–1.92) for C9; FDR-adjusted P values were 0.045, 0.0017, and 0.014. C1s and CD46 were not significant; C8 and CD55 associations attenuated after adjustment. No non-linear associations were found. C1r, C7, and C9 remained significant when restricting to eGFR ≥60 mL/min/1.73 m2 or CRP ≤10 mg/L, but attenuated to non-significance when HF cases were restricted to LVEF ≥50%. Exploratory statistical decomposition suggested that the CD55–HF association partly overlapped with eGFR and hemoglobin, but not CRP; no corresponding overlap was observed for C8. Conclusion: In this cross-sectional sample, C1r, C7, and C9 were associated with prevalent chronic HF after full adjustment and FDR correction, but estimates attenuated in the LVEF-preserved restricted sample. C8 and CD55 associations attenuated after adjustment, while C1s and CD46 were not significant. These associations require prospective validation and should not be interpreted as causal.
SN - 1178-7031
ER -