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 - Funding Information:
The CARDIA study (Coronary Artery Risk Development in Young Adults) is conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with the University of Alabama at Birmingham (HHSN268201800005I and HHSN268201800007I), Northwestern University (HHSN268201800003I), University of Minnesota (HHSN268201800006I), and Kaiser Foundation Research Institute (HHSN268201800004I). CARDIA is also partially supported by the Intramural Research Program of the National Institute on Aging (NIA) and an intra-agency agreement between NIA and NHLBI (AG0005). The laboratory work and analytical component were funded by the American Heart Association (17SFRN33700278 and 14SFRN20790000, L. Hou, Northwestern University, Principle Investigator [PI]). The mediation analysis in this work was partially supported by R21 AG063370 (PI: L. Liu and L. Hou). J. Ma was supported by the National Heart, Lung, and Blood Institute Career Transition Award (1K22HL135075-01). L. Liu was supported by the Longer Life Foundation (grant No. 2019-008). B.T. Joyce was partially supported by an American Heart Association Career Development Award (grant No. 19CDA34630050).
Publisher Copyright:
© 2021 Lippincott Williams and Wilkins. All rights reserved.
PY - 2021
Y1 - 2021
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
UR - http://www.scopus.com/inward/record.url?scp=85116767509&partnerID=8YFLogxK
U2 - 10.1161/CIRCRESAHA.121.318965
DO - 10.1161/CIRCRESAHA.121.318965
M3 - Article
C2 - 34428927
AN - SCOPUS:85116767509
SN - 0009-7330
SP - 770
EP - 781
JO - Circulation Research
JF - Circulation Research
ER -