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Epigenetic Liquid Biopsy Marks Atrial Fibrillation: Evidence from the AF Big Picture Study
Riccardo Proietti1,2, Nicola Tidbury1, Joshua Preston1
1Liverpool Centre for Cardiovascular Science at the University of Liverpool, Liverpool John Moores University and Liverpool Heart and Chest Hospital (LHCH), Liverpool L14 3PE, UK.
Insights
Circulating histone dimers like H2A/H2B and H3/H4 are elevated in patients with atrial fibrillation (AF), suggesting they may serve as biomarkers for this common arrhythmia. This finding could improve clinical risk stratification for AF patients.
Area of Science:
- Epigenetics and Molecular Biology
- Cardiovascular Research
- Biomarker Discovery
Background:
- Atrial fibrillation (AF) is a prevalent arrhythmia associated with increased mortality and morbidity.
- Elevated circulating histone levels are observed in acute conditions like stroke and sepsis.
- Improved clinical stratification of AF patients is needed.
Purpose of the Study:
- To investigate if circulating histone levels can be used for diagnostic purposes in patients with atrial fibrillation (AF).
- To assess the potential of histone complexes as epigenetic sentinels for AF.
Main Methods:
- Pilot single-centre study involving 40 patients (20 with persistent AF, 20 hypertensive controls).
- Quantification of five individual histones (H2A, H2B, H3, H4, macroH2A1.1) and dimers (H2A/H2B, H3/H4) using ImageStreamX multi-channel flow imaging.
- Analysis of biochemical and clinical characteristics, including gender, smoking status, diabetes, BMI, and pharmacological therapy.
Main Results:
- Plasma levels of histone dimers H2A/H2B and H3/H4 were significantly elevated in AF patients compared to hypertensive controls (1.8% vs. 1.06%, p=0.03).
- Increased H2A/H2B dimer levels in AF patients were consistent across different demographic and clinical subgroups.
- An inverse correlation was observed between H2A levels and Body Mass Index (BMI) in the overall study population.
Conclusions:
- Circulating histone complexes, particularly dimers, show potential as epigenetic biomarkers for atrial fibrillation (AF).
- These findings offer mechanistic insights into AF pathophysiology and may aid in unmet needs for risk stratification.
- Further research with larger sample sizes is warranted to validate these preliminary results.
Abstract:
Background/Objectives: Atrial fibrillation (AF) is currently the most common arrhythmia worldwide, and it is linked to increased mortality and morbidity, hence the need for a better clinical stratification of AF patients. Histone complexes or nucleosomes, released into the blood circulation, are found elevated in acute conditions such as stroke, trauma, and sepsis. The aim of this pilot single-centre study was to assess whether circulating histone levels could be used for diagnostic purposes in patients with AF. Methods: A total of 40 patients, well characterised for their biochemical and clinical characteristics, were recruited from outpatient clinics. Patients were randomly recruited into two groups (n = 20 per group), i.e., persistent AF and hypertensive controls. A multi-channel flow imaging methodology based on ImageStreamX was used with a well-optimised protocol to image and quantify five individual histones (H2A, H2B, H3, H4, and macroH2A1.1) together with the dimers (H2A/H2B, and H3/H4). Results: In the AF groups, plasma levels of histone dimers H2A/H2B and H3/H4 were elevated compared to hypertensive controls, 1.8% vs. 1.06% (p-value = 0.03). H2A/H2B dimer levels were increased in AF patients irrespective of gender, smoking status, diabetes, and pharmacological therapy. In the overall population, an inverse correlation between H2A and BMI was detected. Conclusions: Our pilot study, although limited in sample size, suggests that circulating histone complexes may be epigenetic sentinels for AF, offering mechanistic insights while addressing unmet needs in risk stratification.
