Construction of a 28-Day Mortality Risk Prediction Model in Patients with Acute Left Heart Failure Complicated by Respiratory Failure Based on Serum HIF-1α and CysC

Shifang MO; Yaxin XUE; Jia SONG; Anqi CHEN; Lin WANG

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Shifang MO, Yaxin XUE, Jia SONG, Anqi CHEN, Lin WANG. Construction of a 28-Day Mortality Risk Prediction Model in Patients with Acute Left Heart Failure Complicated by Respiratory Failure Based on Serum HIF-1α and CysC[J]. Journal of Kunming Medical University.

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Construction of a 28-Day Mortality Risk Prediction Model in Patients with Acute Left Heart Failure Complicated by Respiratory Failure Based on Serum HIF-1α and CysC

1.
Department of Cardiology
2.
Department of Respiratory and Critical Care Medicine，Zhuzhou Central Hospital，Zhuzhou Hunan 412007，China

Received Date: 2026-03-23

Abstract

Abstract

Objective To explore the predictive value of serum hypoxia-inducible factor-1alpha （HIF-1α） and Cystatin C （CysC） levels for 28-day mortality risk in patients with acute left heart failure （AHF） complicated with respiratory failure （RF）. Methods A retrospective analysis was conducted on clinical data from 217 AHF patients with concurrent RF admitted between January 2022 and December 2024. Patients were stratified based on 28-day survival status post-discharge into a mortality group （n = 62） and a survival group （n = 155）. General demographic data and serum HIF-1α and CysC levels were compared between the two groups. The influencing factors for 28-day mortality risk in AHF patients with RF and the relationship between serum HIF-1α, CysC levels and 28-day mortality risk were analyzed. Receiver operating characteristic （ROC） curves were used to evaluate the predictive value of HIF-1α and CysC for 28-day mortality risk in AHF with RF patients. Risk stratification and clinical validation were performed based on a combined predictive model. Results The mortality group demonstrated significantly higher Acute Physiology and Chronic Health Evaluation II （APACHE II） scores （16.59±3.05 vs 13.72±2.47, t = 7.214, P < 0.001）, Sequential Organ Failure Assessment （SOFA） scores（12.61±2.24 vs 11.89±2.15, t = 2.202, P = 0.029）, N-terminal pro-B-type natriuretic peptide （NT-proBNP）（507.41±82.44 vs 329.49±70.55 pg/mL, t = 15.975, P < 0.001）, HIF-1α （30.14±4.58 vs 21.37±3.82 ng/L, t = 14.410, P < 0.001） and CysC （1.72±0.35 vs 1.30±0.28 mg/L, t = 9.270, P < 0.001） compared with the survival group. Logistic regression analysis showed that HIF-1α （OR = 1.315, 95%CI: 1.129-1.532） and CysC （OR = 1.260, 95%CI: 1.105-1.437） were independent influencing factors for 28 day mortality risk in AHF with RF patients （P < 0.05）. Restricted cubic spline （RCS） model analysis demonstrated that after adjusting for other variables, serum HIF-1α and CysC levels remained linearly and positively correlated with 28 day mortality risk in AHF with RF patients （P < 0.05）, with mortality risk progressively increasing as serum HIF-1α and CysC levels elevated. ROC curve analysis revealed that the area under the curve （AUC） for predicting 28-day mortality risk were as follows: APACHE II score 0.737 （95% CI: 0.673–0.794）, SOFA score 0.711 （0.646–0.771）, NT-proBNP 0.768 （0.706–0.822）, HIF-1α 0.748 （0.684–0.804）, and CysC 0.753 （0.690–0.809）, with no statistically significant differences in AUC between individual indicators （P>0.05）. Interaction analysis revealed RERI=1.09, AP=0.253, and SI=2.727, indicating a positive additive interaction between HIF-1α and CysC when both were simultaneously elevated, with the combined effect exceeding the sum of individual effects. The combined predictive AUC for serum HIF-1α and CysC for 28-day mortality risk in AHF with RF patients was 0.878, significantly higher than the individual AUCs for APACHE II score, SOFA score, NT-proBNP, HIF-1α, and CysC （P < 0.05）. Calibration curves demonstrated good concordance between predicted and observed risk across the entire risk spectrum（Hosmer-Lemeshow test, χ²=2.224, P = 0.086）. Internal validation via Bootstrap resampling （1000 iterations） yielded a corrected model AUC of 0.877 （95% CI: 0.828–0.927）, with calibration curves demonstrating good agreement between predicted and actual risk. Decision curve analysis （DCA） indicated clinical net benefit within the threshold probability range of 0.2–0.8, and temporal validation demonstrated high model robustness and predictive performance. Patients stratified into low, intermediate, and high-risk groups based on the combined predictive model had actual 28-day mortality rates of 4.17%, 27.40%, and 54.17%, respectively （P<0.05）. Conclusion Serum HIF-1α and CysC levels in AHF patients with concurrent RF are closely associated with 28-day mortality risk. A combined predictive model constructed from these two markers demonstrates excellent discriminative ability.
- Acute left heart failure,
- Respiratory failure,
- 28-day mortality risk,
- Hypoxia-inducible factor-1α,
- Cystatin C

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References(27)

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