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Ammous F, Zhao W, Ratliff SM, et al. Epigenetic age acceleration is associated with cardiometabolic risk factors and clinical cardiovascular disease risk scores in African Americans. Clin Epigenetics. 2021;13(1):55doi: 10.1186/s13148-021-01035-3.
Ammous, F., Zhao, W., Ratliff, S. M., Mosley, T. H., Bielak, L. F., Zhou, X., Peyser, P. A., Kardia, S. L. R., & Smith, J. A. (2021). Epigenetic age acceleration is associated with cardiometabolic risk factors and clinical cardiovascular disease risk scores in African Americans. Clinical epigenetics, 13(1), 55. https://doi.org/10.1186/s13148-021-01035-3
Ammous, Farah, et al. "Epigenetic age acceleration is associated with cardiometabolic risk factors and clinical cardiovascular disease risk scores in African Americans." Clinical epigenetics vol. 13,1 (2021): 55. doi: https://doi.org/10.1186/s13148-021-01035-3
Ammous F, Zhao W, Ratliff SM, Mosley TH, Bielak LF, Zhou X, Peyser PA, Kardia SLR, Smith JA. Epigenetic age acceleration is associated with cardiometabolic risk factors and clinical cardiovascular disease risk scores in African Americans. Clin Epigenetics. 2021 Mar 16;13(1):55. doi: 10.1186/s13148-021-01035-3. PMID: 33726838; PMCID: PMC7962278.
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Clin Epigenetics. 2021 Mar 16;13(1):55. doi: 10.1186/s13148-021-01035-3.

Epigenetic age acceleration is associated with cardiometabolic risk factors and clinical cardiovascular disease risk scores in African Americans.

Clinical epigenetics

Farah Ammous, Wei Zhao, Scott M Ratliff, Thomas H Mosley, Lawrence F Bielak, Xiang Zhou, Patricia A Peyser, Sharon L R Kardia, Jennifer A Smith

Affiliations

  1. Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
  2. Memory Impairment and Neurodegenerative Dementia (MIND) Center, University of Mississippi Medical Center, Jackson, MS, USA.
  3. Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
  4. Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA. [email protected].
  5. Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, USA. [email protected].

PMID: 33726838 PMCID: PMC7962278 DOI: 10.1186/s13148-021-01035-3

Abstract

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of mortality among US adults. African Americans have higher burden of CVD morbidity and mortality compared to any other racial group. Identifying biomarkers for clinical risk prediction of CVD offers an opportunity for precision prevention and earlier intervention.

RESULTS: Using linear mixed models, we investigated the cross-sectional association between four measures of epigenetic age acceleration (intrinsic (IEAA), extrinsic (EEAA), PhenoAge (PhenoAA), and GrimAge (GrimAA)) and ten cardiometabolic markers of hypertension, insulin resistance, and dyslipidemia in 1,100 primarily hypertensive African Americans from sibships in the Genetic Epidemiology Network of Arteriopathy (GENOA). We then assessed the association between epigenetic age acceleration and time to self-reported incident CVD using frailty hazard models and investigated CVD risk prediction improvement compared to models with clinical risk scores (Framingham risk score (FRS) and the atherosclerotic cardiovascular disease (ASCVD) risk equation). After adjusting for sex and chronological age, increased epigenetic age acceleration was associated with higher systolic blood pressure (IEAA), higher pulse pressure (EEAA and GrimAA), higher fasting glucose (PhenoAA and GrimAA), higher fasting insulin (EEAA), lower low density cholesterol (GrimAA), and higher triglycerides (GrimAA). A five-year increase in GrimAA was associated with CVD incidence with a hazard ratio of 1.54 (95% CI 1.22-2.01) and remained significant after adjusting for CVD risk factors. The addition of GrimAA to risk score models improved model fit using likelihood ratio tests (P = 0.013 for FRS and P = 0.008 for ASCVD), but did not improve C statistics (P > 0.05). Net reclassification index (NRI) showed small but significant improvement in reassignment of risk categories with the addition of GrimAA to FRS (NRI: 0.055, 95% CI 0.040-0.071) and the ASCVD equation (NRI: 0.029, 95% CI 0.006-0.064).

CONCLUSIONS: Epigenetic age acceleration measures are associated with traditional CVD risk factors in an African-American cohort with a high prevalence of hypertension. GrimAA was associated with CVD incidence and slightly improved prediction of CVD events over clinical risk scores.

Keywords: Age acceleration; Cardiometabolic risk factors; Cardiovascular disease; Clinical risk scores; DNA methylation; Epigenetic age

References

  1. EBioMedicine. 2021 Jan;63:103151 - PubMed
  2. Clin Epigenetics. 2019 Apr 11;11(1):62 - PubMed
  3. Thromb J. 2018 Jun 5;16:12 - PubMed
  4. Circulation. 2014 Jun 24;129(25 Suppl 2):S49-73 - PubMed
  5. Geroscience. 2017 Dec;39(5-6):475-489 - PubMed
  6. JAMA. 2019 Aug 27;322(8):780-782 - PubMed
  7. Aging (Albany NY). 2017 Feb 14;9(2):419-446 - PubMed
  8. J Gerontol A Biol Sci Med Sci. 2020 Nov 19;: - PubMed
  9. Genome Biol. 2013;14(10):R115 - PubMed
  10. J Gerontol A Biol Sci Med Sci. 2020 Feb 14;75(3):466-472 - PubMed
  11. BMC Bioinformatics. 2012 May 08;13:86 - PubMed
  12. Int J Epidemiol. 2019 Dec 1;48(6):1958-1971 - PubMed
  13. Clin Epigenetics. 2020 Jul 31;12(1):115 - PubMed
  14. Nat Rev Genet. 2018 Jun;19(6):371-384 - PubMed
  15. Circulation. 2008 Feb 12;117(6):743-53 - PubMed
  16. Clin Epigenetics. 2019 Nov 15;11(1):160 - PubMed
  17. Aging (Albany NY). 2018 Apr 18;10(4):573-591 - PubMed
  18. Int J Environ Res Public Health. 2019 Aug 28;16(17): - PubMed
  19. JAMA. 1982 May 14;247(18):2543-6 - PubMed
  20. Circ Genom Precis Med. 2018 Mar;11(3):e001937 - PubMed
  21. Clin Epigenetics. 2016 Jun 03;8:64 - PubMed
  22. J Gerontol A Biol Sci Med Sci. 2020 Feb 14;75(3):481-494 - PubMed
  23. Stat Med. 2008 Jan 30;27(2):157-72; discussion 207-12 - PubMed
  24. Aging Cell. 2020 Oct;19(10):e13229 - PubMed
  25. Circulation. 2017 Nov 21;136(21):e393-e423 - PubMed
  26. Mol Cell. 2013 Jan 24;49(2):359-367 - PubMed
  27. Elife. 2020 Feb 11;9: - PubMed
  28. Genome Biol. 2016 Aug 11;17(1):171 - PubMed
  29. Clin Chem. 1972 Jun;18(6):499-502 - PubMed
  30. Clin Epigenetics. 2018 Apr 18;10:56 - PubMed
  31. Thromb Res. 2016 Apr;140:30-35 - PubMed
  32. Stat Med. 2004 Mar 30;23(6):859-74; discussion 875-7,879-80 - PubMed
  33. J Gerontol A Biol Sci Med Sci. 2020 Feb 14;75(3):463-465 - PubMed
  34. Am J Med. 2004 May 15;116(10):676-81 - PubMed
  35. Genome Biol. 2015 Feb 15;16:37 - PubMed
  36. Mol Psychiatry. 2019 Dec 3;: - PubMed
  37. Alzheimers Dement (Amst). 2018 Jun 21;10:429-437 - PubMed
  38. Aging (Albany NY). 2016 Sep 28;8(9):1844-1865 - PubMed
  39. Aging (Albany NY). 2019 Jan 21;11(2):303-327 - PubMed
  40. J Am Coll Cardiol. 2018 May 15;71(19):e127-e248 - PubMed
  41. J Clin Endocrinol Metab. 2019 Jul 1;104(7):3012-3024 - PubMed
  42. F1000Res. 2014 Jul 30;3:175 - PubMed
  43. Am J Epidemiol. 2018 Mar 1;187(3):529-538 - PubMed
  44. BMC Med Genomics. 2019 Oct 22;12(1):141 - PubMed
  45. J Am Soc Nephrol. 2006 Jul;17(7):2048-55 - PubMed
  46. Bioinformatics. 2016 Sep 1;32(17):2659-63 - PubMed
  47. Bioinformatics. 2017 Feb 15;33(4):558-560 - PubMed
  48. Ethn Health. 2009 Oct;14(5):439-57 - PubMed
  49. Front Endocrinol (Lausanne). 2019 Jul 17;10:496 - PubMed
  50. NCHS Data Brief. 2015 Mar;(193):1-8 - PubMed
  51. Peptides. 2008 Apr;29(4):599-605 - PubMed
  52. Eur J Clin Invest. 2018 Feb;48(2): - PubMed
  53. Epigenetics. 2020 Oct 26;:1-14 - PubMed
  54. J Am Coll Cardiol. 2007 Apr 10;49(14):1525-32 - PubMed

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