{
  "abstract": "Cardiovascular disease remains the leading cause of mortality, yet current clinical predictors miss substantial disease-risk. While the immune system contributes to this residual risk, its complexity has hindered broadly applicable, clinically scalable metrics of immune-state. Here, we establish the prognostic relevance of IMM-AGE, a system-level metric of immune-aging, to cardiovascular disease. We learn reference-free, low-dimensional representations of IMM-AGE across cell, protein, and mRNA measurements, enabling high-fidelity quantification across modalities, blood fractions, and platforms, including standard hospital flow cytometers. Among UK-Biobank participants, 56.9% of IMM-AGE variation remained unexplained by routine clinical measures, and across diverse cohorts totaling ~48,000 individuals, elevated IMM-AGE was independently associated with future cardiovascular risk, intervention outcomes, and mortality. Moreover, incorporation of IMM-AGE into the PREVENT 10-year risk equation significantly improved risk stratification. These findings establish immune-aging as an independent biological dimension of cardiovascular disease-risk and support IMM-AGE as a practical tool for precision risk assessment.",
  "abstract_shown": true,
  "affiliations": [
    "Technion - Israel Institute of Technology"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 25,
  "authors": [
    {
      "name": "E. Feldman"
    },
    {
      "name": "E. J. Santana"
    },
    {
      "name": "B. Celestin"
    },
    {
      "name": "N. Golden"
    },
    {
      "name": "S. Bagherzadeh"
    },
    {
      "name": "S. Maysel"
    },
    {
      "name": "K. Mathi"
    },
    {
      "name": "S. Short"
    },
    {
      "name": "M. Caroll"
    },
    {
      "name": "S. S. Sullivan"
    },
    {
      "name": "M. Lukacisin"
    },
    {
      "name": "X. Ji"
    },
    {
      "name": "Y. Klein"
    },
    {
      "name": "O. Caspi"
    },
    {
      "name": "P. Nguyen"
    },
    {
      "name": "W. F. Fearon"
    },
    {
      "name": "B. Kim"
    },
    {
      "name": "S. Shah"
    },
    {
      "name": "K. W. Mahaffey"
    },
    {
      "name": "H. T. Maecker"
    },
    {
      "name": "M. M. Davis"
    },
    {
      "name": "N. Milman"
    },
    {
      "name": "T. J. Few-Cooper"
    },
    {
      "name": "F. Haddad"
    },
    {
      "affs": [
        0
      ],
      "name": "S. S. Shen-Orr"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/16d2bnb7qex8f.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.05.18.725733",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.05.18.725733v2.full",
  "id": "16d2bnb7qex8f",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.05.18.725733v2",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "immunology"
    ],
    [
      "openalex",
      "2403|Atherosclerosis and Cardiovascular Diseases"
    ]
  ],
  "openalex": "W7161852555",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.05.18.725733v2.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-05-18",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/16d2bnb7qex8f.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:45Z",
      "native_id": "10.64898/2026.05.18.725733",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.05.18.725733v2"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:immunology",
      "subfield": "immunology"
    }
  ],
  "title": "Immune Aging is an Independent Risk Factor for Cardiovascular Disease",
  "title_text": "Immune Aging is an Independent Risk Factor for Cardiovascular Disease",
  "type": "preprint",
  "updated_at": "2026-10-30T12:19:45Z",
  "url": "https://research.draconitic.com/paper/16d2bnb7qex8f",
  "venue": "bioRxiv",
  "versions": []
}