Evidence map›Paper›PMID 41692751›Full record

ArticleClinical epigenetics2026

Epigenetic age acceleration in young adults with congenital heart disease.

Parag N Jain, Beryl C Zhuang, Joanne Whitehead, Julia L MacIsaac, Kristy Dever, Mallory Gahm, Peter Ermis, Thomas W McDade, Michael S Kobor, Paul A Checchia

Abstract read
In one paragraph

Article in Clinical epigenetics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Parag N Jain *Division of Cardiology, Heart Center, Children's Health, Department of Pediatrics, UT Southwestern Medical Center, 1935 Medical District Drive, Dallas, TX, 75235, USA. Parag.Jain@UTSouthwestern.edu.
Beryl C Zhuang *Edwin S.H. Leong Centre for Healthy Aging, University of British Columbia, Vancouver, BC, V6T 1Z4, Canada.
Joanne WhiteheadEdwin S.H. Leong Centre for Healthy Aging, University of British Columbia, Vancouver, BC, V6T 1Z4, Canada.
Julia L MacIsaacEdwin S.H. Leong Centre for Healthy Aging, University of British Columbia, Vancouver, BC, V6T 1Z4, Canada.
Kristy DeverEdwin S.H. Leong Centre for Healthy Aging, University of British Columbia, Vancouver, BC, V6T 1Z4, Canada.
Mallory GahmTexas Children's Hospital and Baylor College of Medicine, Houston, TX, USA.
Peter ErmisTexas Children's Hospital and Baylor College of Medicine, Houston, TX, USA.
Thomas W McDadeDepartment of Anthropology, Northwestern University, Evanston, IL, USA.
Michael S KoborEdwin S.H. Leong Centre for Healthy Aging, University of British Columbia, Vancouver, BC, V6T 1Z4, Canada.
Paul A ChecchiaTexas Children's Hospital and Baylor College of Medicine, Houston, TX, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAdults with congenital heart disease (ACHD) having undergone palliative surgery experience chronic stress due to altered physiology and repeated surgical interventions since infancy.

objectivesTo investigate whether ACHD, who had experienced chronic physiological stress from their underlying condition and early-life cardiac surgeries, was associated with epigenetic age acceleration (EAA) and other DNA methylation (DNAm)-based biomarkers, and to assess the potential contribution of derived inflammatory markers to EAA.

methodsA case-control study comparing ACHD patients and healthy adults. Whole blood DNAm profile was used to estimate DNAm-based blood cell type proportions, multiple epigenetic age measures, and interleukin-6 (IL-6) and C-reactive protein (CRP) scores. Two ACHD subgroups were recruited: one with multiple palliative surgeries since birth (Fontan group, n = 13), and another with a single corrective surgery as an infant (SS group, n = 5). Healthy controls (n = 20) had no chronic medical conditions. EAA was calculated using four epigenetic clocks (Horvath, Hannum, GrimAge, PhenoAge) and the pace of aging (DunedinPACE). Comparisons were made across groups using robust linear regression models, adjusting for age, sex, self-reported ethnicity, and estimated cell type proportions. Associations between DNAm-based IL-6 and CRP scores and surgery group were tested, and their potential contribution to differences in EAA was evaluated.

resultsParticipants were 20-30 years (25.6 ± 2.7 years), predominantly non-Hispanic white. After controlling for age/sex/ethnicity/immune-cell-type proportions, the Fontan group had significantly higher GrimAge (Cohen's f = 0.90, p < 0.001) and PhenoAge (Cohen's f = 0.82, p < 0.001) and higher DunedinPACE (Cohen's f = 0.69, p = 0.01). The Fontan group also had statistically higher predicted IL-6 (Cohen's f = 0.84, p < 0.001) and CRP scores (Cohen's f = 0.62, p < 0.001).

conclusionsYoung ACHD patients who undergo multiple childhood surgeries for Fontan palliation were associated with accelerated aging. These changes could reflect the long-term effects of underlying CHD condition, early-life physiological stress and other factors, potentially involving inflammatory pathways. Further research is needed to identify and validate the key factors contributing to EAA in this population and to clarify the role of chronic stress and physiological alterations over time.

Indexed as

AgingDNA MethylationEpigenesis, GeneticHeart Defects, CongenitalAdultBiomarkersCase-Control StudiesC-Reactive ProteinFemaleHumansInterleukin-6MaleStress, PhysiologicalYoung AdultBiomarkersC-Reactive ProteinIL6 protein, humanInterleukin-6Congenital heart diseaseEpigenetic age accelerationEpigenetic clocksFontan circulation

Identifiers

PMID41692751
PMCPMC13202995

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.