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January 10, 2026BMC Cardiovascular Disorders1 citationsOpen Access

Proteomic signatures and machine learning based-prediction models for cardiovascular risk in survivors of myocardial infarction

SXShizhen XiangYYYuge YeXCXi Cao

Key Result

Machine learning models using plasma proteins predicted all-cause mortality (AUC=0.79), heart failure (AUC=0.81), and ischemic stroke (AUC=0.76) in myocardial infarction survivors.

Key Points

  • The central aim is to identify protein biomarkers and create predictive models for cardiovascular outcomes in myocardial infarction survivors.
  • Included 30,135 myocardial infarction survivors from the UK Biobank
  • Used multivariate Cox regression to assess associations with plasma proteins
  • Constructed machine learning models based on protein levels for risk prediction
  • Identified 570 proteins linked to all-cause mortality, 172 to heart failure, and 13 to ischemic stroke
  • Determined that 12 proteins are associated with all three outcomes under specific statistical significance
  • Achieved high predictive performance with AUC values of 0.79 for mortality, 0.81 for heart failure, and 0.76 for ischemic stroke using machine learning models

Structured PICO

Do plasma protein biomarkers integrated with machine learning models improve the prediction of all-cause mortality, heart failure, and ischemic stroke in survivors of myocardial infarction compared to traditional risk factors?

P
Population
30,135 survivors of myocardial infarction (MI) aged 40-69 years from the UK Biobank (UKB) prospective cohort.
I
Intervention
Machine learning prediction models (Random Forest, LightGBM, XGBoost) incorporating up to 2,920 plasma protein levels measured via proximity extension assay.
C
Comparator
Baseline prediction model incorporating traditional risk factors (age, sex, BMI, smoking status, alcohol consumption, education level, Townsend deprivation index, and physical activity).
O
Outcome
All-cause mortality, new-onset heart failure (HF), and new-onset ischemic stroke (IS).hard clinical

Integrating high-throughput plasma proteomics with machine learning significantly improves the prediction of long-term adverse cardiovascular events in myocardial infarction survivors compared to traditional risk factors.

Abstract

Survivors of myocardial infarction (MI) are still at risk for adverse long-term outcomes such as all-cause mortality, heart failure (HF), and ischemic stroke (IS) after acute phase treatment. This study aimed to identify specific protein markers and construct risk prediction models for the main cardiovascular events in survivors of MI. A total of 30,135 survivors of MI were included in this study, all of whom had available follow-up data from the UK Biobank (UKB). Multivariate Cox regression analysis was used to assess the clinical associations between plasma proteins and MI-related outcomes, including all-cause mortality, HF and IS. Subsequently, prediction models with machine learning were constructed based on the plasma protein levels to further evaluate these associations. We identified 570 proteins significantly associated with all-cause mortality, 172 with HF, and 13 with IS in survivors of MI. Among these proteins, 12 proteins were associated with three outcomes ( P < 1.71×10 − 5 ). Pathway enrichment analysis showed that these proteins were mainly involved in pathophysiological processes such as inflammatory response, fibrosis and myocardial remodeling. Machine learning models based on 117, 73 and 82 plasma protein showed good predictive performance for all-cause mortality (XGBoost: AUC = 0.79), HF (LightGBM: AUC = 0.81) and IS (Random Forest: AUC = 0.76) in survivors of MI, respectively. Finally, we systematically identified 52 plasma proteins associated with all-cause mortality, 14 with HF, and 4 with IS in survivors of MI through integrated Cox regression and machine learning modeling. Our integrated study with predictive modeling have identified the plasma protein biomarkers associated with adverse outcomes in survivors of MI, and subsequently developed predictive models to facilitate early risk stratification.

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Cite This Study

Xiang et al. (2026) studied this question. Machine learning models using plasma proteins predicted all-cause mortality (AUC=0.79), heart failure (AUC=0.81), and ischemic stroke (AUC=0.76) in myocardial infarction survivors.

synapsesocial.com/papers/696321b391e05aa366cb7ed9https://doi.org/10.1186/s12872-025-05487-w
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