{
  "abstract": "Background Guideline recommendations for the prevention of cardiovascular (CV) events in patients with coronary artery disease (CAD) are predominantly one-size-fits-all. Clinically identifiable phenotypes needing specific considerations might exist. The purpose of this study is to identify such clinical phenotypic clusters in patients with CAD and assess their relationship with the risk of recurrent CV events.Methods Unsupervised machine learning through latent class analysis was performed in patients with CAD from the Swedish Web‐System for Enhancement and Development of Evidence‐Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) registry (n=88 894) and Utrecht Cardiovascular Cohort-Second Manifestations of Arterial Disease (UCC-SMART) cohort (n=5506). Characteristics for clustering were based on availability, missingness and clinical relevance. Clustering was performed in SWEDEHEART and validated in UCC-SMART. Association between clusters and the composite of myocardial infarction, stroke or CV death was assessed using Cox proportional hazard models.Results Four phenotypes could be distinguished: cluster 1 (38%, n=33 777) of predominantly younger males with increased body mass index, blood pressure and C-reactive protein, cluster 2 (21%, n=18 775) of smokers with few traditional risk factors, cluster 3 (30%, n=26 501) of older patients with few comorbidities and cluster 4 (11%, n=9841) of patients with multimorbidity. Compared with cluster 1, cluster 4 was at the highest risk (HR 4.38 95% CI (4.01 to 4.78)), followed by cluster 3 (HR 1.78 (1.70 to 1.85)), and cluster 2 (HR 0.97 (0.88 to 1.07)). Validation in UCC-SMART yielded similar results.Conclusion Four distinct and reproducible phenotypes, with differences in the risk of recurrent CV events, were identified among patients with CAD. These may be relevant in practice and warrant research into specific pathophysiology and differences in treatment effects.",
  "authors": [
    {
      "affiliations": [
        "Department of Vascular Medicine, Utrecht University, Utrecht, The Netherlands"
      ],
      "name": "Joris Holtrop"
    },
    {
      "affiliations": [
        "Department of Medicine Sola, Clinical Epidemiology Division, Karolinska Institute, Stockholm, Sweden"
      ],
      "name": "Carl-Emil Lim"
    },
    {
      "affiliations": [
        "Department of Cardiology, University of Amsterdam, Amsterdam, The Netherlands",
        "Department of Medicine, Karolinska Institutet, Stockholm, Sweden"
      ],
      "name": "Alicia Uijl"
    },
    {
      "affiliations": [
        "Department of Medicine Sola, Clinical Epidemiology Division, Karolinska Institute, Stockholm, Sweden"
      ],
      "name": "Peter Ueda"
    },
    {
      "affiliations": [
        "Department of Clinical Sciences, Karolinska Institute, Stockholm, Sweden"
      ],
      "name": "Tomas Jernberg"
    },
    {
      "affiliations": [
        "Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands"
      ],
      "name": "Manon G van der Meer"
    },
    {
      "affiliations": [
        "Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands"
      ],
      "name": "Pim van der Harst"
    },
    {
      "affiliations": [
        "Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands"
      ],
      "name": "Adriaan O Kraaijeveld"
    },
    {
      "affiliations": [
        "Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands"
      ],
      "name": "Jan-Willem Balder"
    },
    {
      "affiliations": [
        "Department of Vascular Medicine, Utrecht University, Utrecht, The Netherlands"
      ],
      "name": "Steven H J Hageman"
    },
    {
      "affiliations": [
        "Department of Vascular Medicine, Utrecht University, Utrecht, The Netherlands"
      ],
      "name": "Frank L J Visseren"
    },
    {
      "affiliations": [
        "Department of Vascular Medicine, Utrecht University, Utrecht, The Netherlands"
      ],
      "name": "Jannick A N Dorresteijn"
    },
    {
      "affiliations": [],
      "name": "on behalf of the UCC-SMART study group"
    }
  ],
  "title": "Identifying clinical phenotype clusters in patients with coronary artery disease",
  "uid": "50245da9-537f-5fa6-a5b0-68d4c2de3ac3"
}