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.

By Baechle, Arthur, Nguyen +12Nov 2, 2026

Score████░░░░░░4.3

Caveats

Not randomized: its findings are associations.
Preprint; not yet peer reviewed.

VerdictWorth a reader's time today.

Read the original PDF

Abstract

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.

J. J. Baechle, J. Arthur, K. Nguyen, F. Wu, M. Fuentealba, K. U. Knowlton, S. Knight, B. Horne, N. Sayed, H. Maecker, D. A. Winer, N. Barzilai, M. M. Davis, F. Haddad, D. Furman

The editor's rubric

Heuristic review

Leverage3 / 5: A method or resource many groups across the field will adopt within a year.; 24% of this desk’s rubric
Magnitude2 / 5: Solid incremental gain on a meaningful problem.; 16% of this desk’s rubric
Evidence3 / 5: Solid: multiple benchmarks or cohorts, ablations, fair baselines, released code or data.; 20% of this desk’s rubric
Novelty2 / 5: A new combination of known ideas.; 20% of this desk’s rubric
Trajectory2 / 5: Some room to improve with obvious engineering.; 10% of this desk’s rubric
Stakes4 / 5: Large-scale human impact: millions of people, or a major industry.; 10% of this desk’s rubric

Dimension	Level	Weight	What that level means
Leverage	███░░3/5	24%	A method or resource many groups across the field will adopt within a year.
Magnitude	██░░░2/5	16%	Solid incremental gain on a meaningful problem.
Evidence	███░░3/5	20%	Solid: multiple benchmarks or cohorts, ablations, fair baselines, released code or data.
Novelty	██░░░2/5	20%	A new combination of known ideas.
Trajectory	██░░░2/5	10%	Some room to improve with obvious engineering.
Stakes	████░4/5	10%	Large-scale human impact: millions of people, or a major industry.

Editor’s rationale

Heuristic triage from title and abstract text only, not a reading of the paper. Cues found: method (we propose, we report); verification (multiple benchmarks, independent replication); stakes (global scale, mortality, major disease). Red flags: not randomized.

How the score was computed

rank-2026-10-18

Score████░░░░░░4.3

Score = 10 × (75% × adjusted merit / 10 + 15% × attention + 10% × freshness)

Desks place stronger verdicts first, then use this score to order work within the same verdict.

Merit: 5.3 / 10; Weighted rubric, evidence-gated.
Adjusted merit: 4.6 / 10; Shrunk toward the desk prior by editor confidence (46%).
Attention: 0%; Citations, upvotes, points, mentions.
Freshness: 88%; Half-life decay since publication.

No attention signals recorded yet.

The record

Reviewed by heuristic-v10 on Nov 3, 2026, 05:48 UTC. Paper type: clinical.
Categories: immunology
BRIEF, No.7 in the Biology edition of November 3, 2026.