Measures of epigenetic age acceleration (EAA) are associated with incident atrial fibrillation (AF), according to a study published in Circulation.

The meta-analysis included 5600 individuals from 3 population-based cohort studies. The participants were assessed for epigenetic age using 4 clocks (Hannum, Horvath, DNAm PhenoAge, and DNAm GrimAge) as well as DNAm PAI-1, an epigenetic predictor of PAI-1 levels. Researchers also used Cox models to assess associations with incident AF and combined the results with random-effects meta-analysis. Associations between AF and genetic instruments of EAA measures were evaluated using 2-sample summary-level Mendelian randomization analyses.

Patients’ mean age was 65.5 years; 60.1% were women; and 50.7% were Black individuals.


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Among the entire study population, 905 incident AF cases occurred during a mean follow-up of 12.9 years. All 4 epigenetic clocks as well as the DNAm PAI-1 predictor showed statistically significant associations with increased hazards of incident AF. However, their point estimate magnitudes were smaller when compared with chronological age associations.

Each additional 5-year increment of chronological age was associated with a significantly higher hazard ratio of incident AF (hazard ratio [HR] 1.44; 95% CI, 1.34-1.54; P <.0001). For all epigenetic measures except Horvath, pooled EAA estimates showed associations with incident AF with adjustments for race, chronological age, smoking, and sex. After adjusting for potentially mediating AF risk factors, 5-year increases in hazard for incident AF remained significant for DNAm GrimAge (HR 1.19; 95% CI, 1.09-1.31; P =.0002) and DNAmPhenoAge (HR 1.15; 95% CI, 1.05-1.25; P =.0017). No statistically significant associations were found between the EAA measures and AF.

The study was limited by a modest population size, a lack of race-related comparisons, potential differences in association magnitude due to demographic and clinical differences between cohorts, the possibility of undetected AF, and an observational study design and resultant lack of causal inferences.

“Our meta-analysis involving 3 large population-based cohort studies identified associations between epigenetic age measures and incident AF,” the study authors noted. “Measures of accelerated biological aging remained associated with incident AF following adjustment for possible confounders, revealing a potential role for prevention and treatment strategies to mitigate age-related AF risk that otherwise may be perceived as inexorable.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Roberts JD, Vittinghoff E, Lu AT, et al. Epigenetic age and the risk of incident atrial fibrillation. Circulation. Published online September 30, 2021. doi: 10.1161/CIRCULATIONAHA.121.056456