Immuno-Proteomic Age of Cardiovascular Etiology (iPACE) Signature Predicts Cardiovascular Risk in Elderly Patients
Despite advances in clinical care, cardiovascular disease (CVD) remains the leading cause of disability and mortality worldwide. While age alone is a primary risk factor for CVD, accumulating evidence suggests the immune system influences the initiation and progression of CVD pathophysiology, particularly in heart failure with preserved ejection fraction (HFpEF) and atherosclerotic CVD (ASCVD). Here, using two independent cohorts of older adults, we develop a thirty-protein signature of age based on serum immune proteomics, which correlates with HFpEF and ASCVD risk and mortality (Immuno-Proteomic Age of Cardiovascular Etiology, iPACE). We find aging-related circulating immune proteins associated with ASCVD and HFpEF-specific resilience and susceptibility that may be used as potential prognostic, diagnostic, or therapeutic targets.
Authors
- François Haddad (ORCID: https://orcid.org/0000-0002-9648-7671)
- Daniel A. Winer (ORCID: https://orcid.org/0000-0002-8702-0957)
- Nazish Sayed (ORCID: https://orcid.org/0000-0002-8229-721X)
- Jordan J. Baechle (ORCID: https://orcid.org/0000-0002-4498-6647)
- Nir Barzilai (ORCID: https://orcid.org/0000-0002-7787-6268)
- David Furman (ORCID: https://orcid.org/0000-0002-3654-9519)
- Holden Terry Maecker (ORCID: https://orcid.org/0000-0003-0795-9946)
- Benjamin Davies Horne (ORCID: https://orcid.org/0000-0002-2656-0263)
- Stacey Knight (ORCID: https://orcid.org/0000-0003-0092-7327)
- Kirk U. Knowlton (ORCID: https://orcid.org/0000-0003-3544-4130)
- Mark Davis
- Fei Wu (ORCID: https://orcid.org/0000-0002-8353-7676)
- Jennifer Arthur
- Matias Fuentealba
- Khiem Nguyen
Institutions
- Intermountain Healthcare (US)
- Albert Einstein College of Medicine (US)
- Buck Institute for Research on Aging (US)
- University of Toronto (CA)
- Trường ĐH Nguyễn Tất Thành (VN)
- Stanford Medicine (US)
- Toronto General Hospital Research Institute (CA)
- Stanford University (US)
Publication Details
- Journal
- bioRxiv (Cold Spring Harbor Laboratory)
- Published
- 2026-11-02
- DOI
- https://doi.org/10.64898/2026.10.27.762320
- Primary Topic
- Heart Failure Treatment and Management
- Type
- preprint
Funders
- Buck Institute for Research on Aging
- Canadian Institutes of Health Research