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. 2022 Jan 14;12(1):110.
doi: 10.3390/jpm12010110.

The Relationship between Epigenetic Age and Myocardial Infarction/Acute Coronary Syndrome in a Population-Based Nested Case-Control Study

Sofia Malyutina  1 , Olga Chervova  2 , Taavi Tillmann  3 , Vladimir Maximov  1 , Andrew Ryabikov  1 , Valery Gafarov  1 , Jaroslav A Hubacek  4 , Hynek Pikhart  5 , Stephan Beck  2 , Martin Bobak  5
Affiliations

The Relationship between Epigenetic Age and Myocardial Infarction/Acute Coronary Syndrome in a Population-Based Nested Case-Control Study

Sofia Malyutina et al. J Pers Med. .

Abstract

We investigated the relationship between 'epigenetic age' (EA) derived from DNA methylation (DNAm) and myocardial infarction (MI)/acute coronary syndrome (ACS). A random population sample was examined in 2003/2005 (n = 9360, 45-69, the HAPIEE project) and followed up for 15 years. From this cohort, incident MI/ACS (cases, n = 129) and age- and sex-stratified controls (n = 177) were selected for a nested case-control study. Baseline EA (Horvath's, Hannum's, PhenoAge, Skin and Blood) and the differences between EA and chronological age (CA) were calculated (ΔAHr, ΔAHn, ΔAPh, ΔASB). EAs by Horvath's, Hannum's and Skin and Blood were close to CA (median absolute difference, MAD, of 1.08, -1.91 and -2.03 years); PhenoAge had MAD of -9.29 years vs. CA. The adjusted odds ratios (ORs) of MI/ACS per 1-year increments of ΔAHr, ΔAHn, ΔASB and ΔAPh were 1.01 (95% CI 0.95-1.07), 1.01 (95% CI 0.95-1.08), 1.02 (95% CI 0.97-1.06) and 1.01 (0.93-1.09), respectively. When classified into tertiles, only the highest tertile of ΔAPh showed a suggestion of increased risk of MI/ACS with OR 2.09 (1.11-3.94) independent of age and 1.84 (0.99-3.52) in the age- and sex-adjusted model. Metabolic modulation may be the likely mechanism of this association. In conclusion, this case-control study nested in a prospective population-based cohort did not find strong associations between accelerated epigenetic age markers and risk of MI/ACS. Larger cohort studies are needed to re-examine this important research question.

Keywords: DNA methylation; HAPIEE project; acute coronary syndrome; epigenetic age; myocardial infarction; nested case-control; population.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Boxplots of differences between chronological and epigenetic age (cases and controls, n = 306).
Figure 2
Figure 2
Scatterplots of chronological vs. epigenetic age by Horvath’s, Hannum’s, PhenoAge and Skin and Blood clocks. Diagonal green line corresponds to the predicted age equal to the chronological age, blue straight line corresponds to the linear regression.
See this image and copyright information in PMC

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