TY - JOUR
T1 - Epigenetic Age Acceleration Reflects Long-Term Cardiovascular Health
AU - Joyce, Brian T.
AU - Gao, Tao
AU - Zheng, Yinan
AU - Ma, Jiantao
AU - Hwang, Shih Jen
AU - Liu, Lei
AU - Nannini, Drew
AU - Horvath, Steve
AU - Lu, Ake T.
AU - Bai Allen, Norrina
AU - Jacobs, David R.
AU - Gross, Myron
AU - Krefman, Amy
AU - Ning, Hongyan
AU - Liu, Kiang
AU - Lewis, Cora E.
AU - Schreiner, Pamela J.
AU - Sidney, Stephen
AU - Shikany, James M.
AU - Levy, Daniel
AU - Greenland, Philip
AU - Hou, Lifang
AU - Lloyd-Jones, Donald
N1 - Publisher Copyright:
© 2021 American Heart Association, Inc.
PY - 2021/10/1
Y1 - 2021/10/1
N2 - Rationale: Epigenetic aging is a novel measure of biological age, reflecting exposures and disease risks independent of chronological age. It may serve as a useful biomarker of cardiovascular health (CVH) or cardiovascular disease risk for early detection or prevention. Objective: To examine associations between GrimAge acceleration (GrimAA), a measure of epigenetic aging calculated from the residuals of GrimAge regressed on chronological age, and 2 repeated CVH measures: a full score for the AHA Life's Simple 7 (diet, smoking, physical activity, body mass index, blood pressure, total cholesterol, and glucose) and a clinical CVH score (body mass index, blood pressure, cholesterol, and glucose). Methods and Results: We used Illumina array DNA methylation data from 2 prospective cohort studies, the CARDIA study (Coronary Artery Risk Development in Young Adults) and FHS (Framingham Heart Study), to calculate GrimAA and model associations with CVH. CARDIA randomly selected 1118 participants for assays at Y15 (2000-2001; mean age, 40 years) and Y20 (2005-2006); in FHS, 2106 Offspring participants had DNA methylation measured at exam 8 (2005-2008; mean age, 66 years). We examined multiple cross-sectional and longitudinal models of GrimAA and each CVH score measured at CARDIA Y0 to Y20 and FHS exams 7 to 8. In CARDIA, clinical CVH score from Y0 to Y20 was associated with Y15 and Y20 GrimAA (β range, -0.41 to -0.21 years per 1-point increase in CVH; P range, <0.01-0.01), as was full score (β range, -0.65 to -0.67 years; P<0.01 for all). These findings were validated in FHS (clinical score β range, -0.51 to -0.54 years; full score β range, -0.76 to -0.83 years; P<0.01 for all). Conclusions: Our data demonstrate that faster GrimAA is associated with the loss of CVH from young age. Epigenetic age may be a useful biomarker of cardiovascular disease risk and provides biological insight into the role of epigenetic mechanisms linking age-related CVH loss and cardiovascular disease.
AB - Rationale: Epigenetic aging is a novel measure of biological age, reflecting exposures and disease risks independent of chronological age. It may serve as a useful biomarker of cardiovascular health (CVH) or cardiovascular disease risk for early detection or prevention. Objective: To examine associations between GrimAge acceleration (GrimAA), a measure of epigenetic aging calculated from the residuals of GrimAge regressed on chronological age, and 2 repeated CVH measures: a full score for the AHA Life's Simple 7 (diet, smoking, physical activity, body mass index, blood pressure, total cholesterol, and glucose) and a clinical CVH score (body mass index, blood pressure, cholesterol, and glucose). Methods and Results: We used Illumina array DNA methylation data from 2 prospective cohort studies, the CARDIA study (Coronary Artery Risk Development in Young Adults) and FHS (Framingham Heart Study), to calculate GrimAA and model associations with CVH. CARDIA randomly selected 1118 participants for assays at Y15 (2000-2001; mean age, 40 years) and Y20 (2005-2006); in FHS, 2106 Offspring participants had DNA methylation measured at exam 8 (2005-2008; mean age, 66 years). We examined multiple cross-sectional and longitudinal models of GrimAA and each CVH score measured at CARDIA Y0 to Y20 and FHS exams 7 to 8. In CARDIA, clinical CVH score from Y0 to Y20 was associated with Y15 and Y20 GrimAA (β range, -0.41 to -0.21 years per 1-point increase in CVH; P range, <0.01-0.01), as was full score (β range, -0.65 to -0.67 years; P<0.01 for all). These findings were validated in FHS (clinical score β range, -0.51 to -0.54 years; full score β range, -0.76 to -0.83 years; P<0.01 for all). Conclusions: Our data demonstrate that faster GrimAA is associated with the loss of CVH from young age. Epigenetic age may be a useful biomarker of cardiovascular disease risk and provides biological insight into the role of epigenetic mechanisms linking age-related CVH loss and cardiovascular disease.
KW - DNA methylation
KW - blood pressure
KW - cardiovascular diseases
KW - humans
KW - young adult
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U2 - 10.1161/CIRCRESAHA.121.318965
DO - 10.1161/CIRCRESAHA.121.318965
M3 - Article
C2 - 34428927
AN - SCOPUS:85116767509
SN - 0009-7330
VL - 129
SP - 770
EP - 781
JO - Circulation research
JF - Circulation research
IS - 8
ER -
