Abstract

Acute coronary syndromes (ACS) are a leading cause of deaths worldwide, yet the diagnosis and treatment of this group of diseases represent a significant challenge for clinicians. The epidemiology of ACS is extremely complex and the relationship between ACS and patient risk factors is typically non-linear and highly variable across patient lifespan. Here, we aim to uncover deeper insights into the factors that shape ACS outcomes in hospitals across four Arabian Gulf countries. Further, because anemia is one of the most observed comorbidities, we explored its role in the prognosis of most prevalent ACS in-hospital outcomes (mortality, heart failure, and bleeding) in the region. We used a robust multi-algorithm interpretable machine learning (ML) pipeline, and 20 relevant risk factors to fit predictive models to 4,044 patients presenting with ACS between 2012 and 2013. We found that in-hospital heart failure followed by anemia was the most important predictor of mortality. However, anemia was the first most important predictor for both in-hospital heart failure, and bleeding. For all in-hospital outcome, anemia had remarkably non-linear relationships with both ACS outcomes and patients' baseline characteristics. With minimal statistical assumptions, our ML models had reasonable predictive performance (AUCs > 0.75) and substantially outperformed commonly used statistical and risk stratification methods. Moreover, our pipeline was able to elucidate ACS risk of individual patients based on their unique risk factors. Fully interpretable ML approaches are rarely used in clinical settings, particularly in the Middle East, but have the potential to improve clinicians' prognostic efforts and guide policymakers in reducing the health and economic burdens of ACS worldwide.

Highlights

  • Cardiovascular diseases are responsible for one-third of deaths worldwide, with projected mortalities of up to 7.8 million in 2025 [1]

  • CICE plots (Fig 2D–2F) and feature interaction plots (Fig 3) show that the relationship between anemia and the risk of several Acute coronary syndromes (ACS) outcomes is non-linear and far more complex [20,42]. These results indicate that anemia on admission has both a direct and indirect role in the prognosis of ACS and that the combination of anemia and other baseline characteristics shaped the risk of in-hospital outcomes

  • While we were unable to quantify a distinct relationship between the risk of mortality and bleeding with age (Fig 2F), the individual interaction between mortality and age showed that patients aged greater than 75 years old with initial hemoglobin value less than 10 g/dl are more likely to die from ACS related complication

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Summary

Introduction

Cardiovascular diseases are responsible for one-third of deaths worldwide, with projected mortalities of up to 7.8 million in 2025 [1]. Effective primary prevention is often difficult due to the complexity of cardiovascular disease epidemiology and the dynamic nature of risk profiles that are rapidly changing in response to increasing urbanization and globalization and shifts in demography [3,4]. This is true for Acute coronary syndromes (ACS) that is an important category of cardiovascular disease that includes unstable angina and myocardial infarction. Machine Learning (ML) algorithms can capture these complex relationships to build powerful predictive models that have provided important insights into the clinical epidemiology of cardiovascular diseases generally [5,6]. Interpretable machine learning methods, are rarely used to help predict and interpret ACS risk

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