{
  "abstract": "Objective: To (1) identify multivariable longitudinal midlife patterns of systolic and diastolic blood pressure, body mass index, and non–high density lipoprotein cholesterol and (2) assess whether electrocardiogram derived heart age acceleration (δ-age) mediates their associations with incident myocardial infarction (MI), stroke, and all-cause mortality. Patients and Methods: We analyzed 5244 participants from the observational cohort study, the Tromsø Study, who were free of MI or stroke at baseline (Tromsø7, 2015-2016) and attended at least 3 surveys (Tromsø3-7, 1986-2016). Age-standardized risk factor z -scores were modeled with quadratic B-splines and grouped using K-means clustering to identify joint multivariable life-course risk profiles. δ-Age was derived from 12-lead electrocardiograms using a validated neural network. Natural-effects models decomposed hazard ratios between clusters and clinical events (follow-up to 2021) into direct and δ-age mediated components. Results: Four distinct clusters were identified: stable low-risk (cluster 1, n=1604, 30.6%), dyslipidemia (cluster 2, n=1340, 25.6%), hypertension (cluster 3, n=1476, 28.1%), and high-risk trajectory (cluster 4, n=824, 15.7%). Each 1-SD increment in δ-age was associated with 27% to 30% of excess MI, stroke, and death, independent of age and sex. Clusters 3 and 4 carried the greatest excess risk of clinical events, whereas mediation by δ-age was modest (4%-8% of total effect for MI and stroke) and not statistically significant. Conclusion: Joint multivariable life-course clustering of conventional risk factors identified clinically distinct long-term cardiovascular risk phenotypes. Although δ-age adds independent prognostic information, it explained little of the excess risk associated with chronic hypertension, dyslipidemia, or obesity, indicating it functions primarily as a parallel marker and not a causal mediator.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Community Medicine, UiT The Arctic University of Norway, Tromsø, Norway",
    "Akershus University Hospital, Lørenskog, Norway; Institute of Clinical Medicine, Campus Ahus, University of Oslo, Norway",
    "University Hospital of North Norway, Tromsø, Norway",
    "Department of Cardiovascular Medicine and Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN",
    "Department of Noncommunicable Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, United Kingdom",
    "Department of Psychology, University of Oslo, Norway"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Arya Panthalanickal Vijayakumar, MS"
    },
    {
      "affs": [
        0
      ],
      "name": "Tom Wilsgaard, PhD"
    },
    {
      "affs": [
        1
      ],
      "name": "Henrik Schirmer, MD, PhD"
    },
    {
      "affs": [
        2
      ],
      "name": "Haakon Lindekleiv, MD, PhD"
    },
    {
      "affs": [
        3
      ],
      "name": "Zachi I. Attia, PhD"
    },
    {
      "affs": [
        3
      ],
      "name": "Francisco Lopez-Jimenez, MD, MSc, MBA"
    },
    {
      "affs": [
        4
      ],
      "name": "David A. Leon, PhD"
    },
    {
      "affs": [
        5
      ],
      "name": "Olena Iakunchykova, PhD"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/21r5r612t832k.bib",
  "cited_by": 0,
  "doi": "10.1016/j.mcpdig.2026.100425",
  "fulltext_url": "http://www.sciencedirect.com/science/article/pii/S294976122600091X",
  "id": "21r5r612t832k",
  "issns": [
    "2949-7612"
  ],
  "landing_url": "https://doi.org/10.1016/j.mcpdig.2026.100425",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Article"
    ],
    [
      "lcc",
      "R858-859.7"
    ],
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      "openalex",
      "2705|Cardiovascular Health and Risk Factors"
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  "pdf_url": "https://europepmc.org/articles/PMC13718786?pdf=render",
  "pmcid": null,
  "pmid": "42960263",
  "published": "2026-10-05",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/21r5r612t832k.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:43:42Z",
      "native_id": "5735b1e6eb2c495a8c396f85e4b4fce6",
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      "url": "https://doi.org/10.1016/j.mcpdig.2026.100425"
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2705|Cardiovascular Health and Risk Factors",
      "subfield": "cardiovascular"
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  ],
  "title": "Clustering of Cardiovascular Risk Factors in Midlife Forms Trajectories That Affect Heart Aging Biomarker and Incidence of Cardiovascular Disease",
  "title_text": "Clustering of Cardiovascular Risk Factors in Midlife Forms Trajectories That Affect Heart Aging Biomarker and Incidence of Cardiovascular Disease",
  "type": "peer-reviewed",
  "updated_at": "2026-11-02T12:22:45Z",
  "url": "https://research.draconitic.com/paper/21r5r612t832k",
  "venue": "Mayo Clinic Proceedings: Digital Health",
  "versions": []
}