Immune Aging is an Independent Risk Factor for Cardiovascular Disease
- 1Technion - Israel Institute of Technology
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.
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BibTeX
@misc{feldman2026immune,
title = {{Immune Aging is an Independent Risk Factor for Cardiovascular Disease}},
author = {E. Feldman and E. J. Santana and B. Celestin and N. Golden and S. Bagherzadeh and S. Maysel and K. Mathi and S. Short and M. Caroll and S. S. Sullivan and M. Lukacisin and X. Ji and Y. Klein and O. Caspi and P. Nguyen and W. F. Fearon and B. Kim and S. Shah and K. W. Mahaffey and H. T. Maecker and M. M. Davis and N. Milman and T. J. Few-Cooper and F. Haddad and S. S. Shen-Orr},
howpublished = {bioRxiv},
year = {2026},
month = may,
doi = {10.64898/2026.05.18.725733},
url = {https://www.biorxiv.org/content/10.64898/2026.05.18.725733v2},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Immune Aging is an Independent Risk Factor for Cardiovascular Disease
AU - E. Feldman
AU - E. J. Santana
AU - B. Celestin
AU - N. Golden
AU - S. Bagherzadeh
AU - S. Maysel
AU - K. Mathi
AU - S. Short
AU - M. Caroll
AU - S. S. Sullivan
AU - M. Lukacisin
AU - X. Ji
AU - Y. Klein
AU - O. Caspi
AU - P. Nguyen
AU - W. F. Fearon
AU - B. Kim
AU - S. Shah
AU - K. W. Mahaffey
AU - H. T. Maecker
AU - M. M. Davis
AU - N. Milman
AU - T. J. Few-Cooper
AU - F. Haddad
AU - S. S. Shen-Orr
PY - 2026
DA - 2026/05/18
PB - bioRxiv
DO - 10.64898/2026.05.18.725733
UR - https://www.biorxiv.org/content/10.64898/2026.05.18.725733v2
AB - 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.
ER -