Unsupervised Learning for Automated Detection of Coronary Artery Disease Subgroups.

Journal: Journal of the American Heart Association
Published Date:

Abstract

Background The promise of precision population health includes the ability to use robust patient data to tailor prevention and care to specific groups. Advanced analytics may allow for automated detection of clinically informative subgroups that account for clinical, genetic, and environmental variability. This study sought to evaluate whether unsupervised machine learning approaches could interpret heterogeneous and missing clinical data to discover clinically important coronary artery disease subgroups. Methods and Results The Genetic Determinants of Peripheral Arterial Disease study is a prospective cohort that includes individuals with newly diagnosed and/or symptomatic coronary artery disease. We applied generalized low rank modeling and K-means cluster analysis using 155 phenotypic and genetic variables from 1329 participants. Cox proportional hazard models were used to examine associations between clusters and major adverse cardiovascular and cerebrovascular events and all-cause mortality. We then compared performance of risk stratification based on clusters and the American College of Cardiology/American Heart Association pooled cohort equations. Unsupervised analysis identified 4 phenotypically and prognostically distinct clusters. All-cause mortality was highest in cluster 1 (oldest/most comorbid; 26%), whereas major adverse cardiovascular and cerebrovascular event rates were highest in cluster 2 (youngest/multiethnic; 41%). Cluster 4 (middle-aged/healthiest behaviors) experienced more incident major adverse cardiovascular and cerebrovascular events (30%) than cluster 3 (middle-aged/lowest medication adherence; 23%), despite apparently similar risk factor and lifestyle profiles. In comparison with the pooled cohort equations, cluster membership was more informative for risk assessment of myocardial infarction, stroke, and mortality. Conclusions Unsupervised clustering identified 4 unique coronary artery disease subgroups with distinct clinical trajectories. Flexible unsupervised machine learning algorithms offer the ability to meaningfully process heterogeneous patient data and provide sharper insights into disease characterization and risk assessment. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00380185.

Authors

  • Alyssa M Flores
    Department of Surgery, Division of Vascular Surgery (A.M.F., F.D., N.J.L., E.G.R.), Stanford University School of Medicine, CA.
  • Alejandro Schuler
    Systems Research Initiative, Kaiser Permanente Division of Research, Oakland, California, USA.
  • Anne Verena Eberhard
    Division of Vascular Surgery Department of Surgery Stanford University School of Medicine Stanford CA.
  • Jeffrey W Olin
    Zena and Michael A. Wiener Cardiovascular InstituteMarie-Josée and Henry R. Kravis Center for Cardiovascular HealthIcahn School of Medicine at Mount Sinai New York NY.
  • John P Cooke
    Department of Cardiovascular Sciences, Houston Methodist Research Institute, Houston, Tex; Center for Cardiovascular Regeneration, Houston Methodist DeBakey Heart and Vascular Center, Houston, Tex.
  • Nicholas J Leeper
    Division of Vascular Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, California, USA.
  • Nigam H Shah
    Stanford Center for Biomedical Informatics Research, Stanford University, Stanford, CA, USA.
  • Elsie G Ross
    Division of Vascular Surgery Department of Surgery Stanford University School of Medicine Stanford CA.