High-dimensional machine learning models for prediction of heart failure in more than 400 000 men and women from the UK Biobank

TL;DR

This study compared traditional and machine learning models to predict heart failure risk in over 400,000 people, finding similar performance but identifying new risk factors like spirometry measures.

Contribution

The study reveals that machine learning models can uncover sex-specific and model-specific risk factors for heart failure, including spirometry measures, which are often overlooked.

Findings

Machine learning and Cox models showed comparable performance in predicting 10-year heart failure risk.

Spirometry measures were identified as important risk factors, rarely included in existing models.

Sex-specific and model-specific risk factors were found, highlighting differences in risk prediction.

Abstract

We aimed to compare performances of conventional survival models with machine learning (ML) survival models for incident heart failure (HF) in men and women without prevalent HF, cardiomyopathy (CM) or ischaemic heart disease (IHD), and to identify potential high-risk precursors overlooked by conventional survival models.

We predicted 10-year risk of incident HF in 266 306 women (2894 events) and 212 061 men (4213 events). We constructed multivariable Cox models, first using ∼ 400 baseline characteristics, and subsequently only those remaining after LASSO stability selection. We also used Random Survival Forest (RSF) and eXtreme Gradient Survival Boosting (XGBoost). Performances were assessed using internal cross validation and hold-out sets, with C-indices, calibration curves and net-benefit analyses. Model performances were comparable during internal validation: XGBoost (C-index ± SE) (men: 0.79 ± 0.0040, women: 0.83 ± 0.0023) showed similar performance to the multivariable Cox model (men: 0.80 ± 0.0031, women: 0.83 ± 0.0022) and Cox models after LASSO stability selection, while RSF showed numerically slightly lower performance (men: 0.78 ± 0.0025, women: 0.81 ± 0.0015). Findings were similar in the hold-out sets. Age, cystatin-C, lifetime treatments/medications, other heart disease, systolic blood pressure, and spirometry measures were identified as high-risk factors in both model types for both sexes. Additionally, sex-specific and model-specific risk factors were identified.

Machine learning models and Cox proportional hazard models performed well and similarly for 10-year incident HF risk prediction in the general population. However, sex-specific and model-specific risk predictors were found. Spirometry measures, rarely included in existing models, were identified as important risk factors. Our results suggest that ML models for HF prediction in the general population reveal insights that would otherwise remain unnoticed.

Graphical Abstract

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