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000280965 0247_ $$2doi$$a10.1161/CIRCULATIONAHA.124.073181
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000280965 037__ $$aDZNE-2025-01047
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000280965 1001_ $$00009-0002-4102-5952$$aCarbonneau, Madeleine$$b0
000280965 245__ $$aDNA Methylation Signatures of Cardiovascular Health Provide Insights Into Diseases.
000280965 260__ $$aPhiladelphia, Pa.$$bLippincott, Williams & Wilkins$$c2025
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000280965 520__ $$aThe association of overall cardiovascular health (CVH) with changes in DNA methylation (DNAm) has not been well characterized.We calculated the American Heart Association's Life's Essential 8 score to reflect CVH in 5 cohorts with diverse backgrounds (mean age 54 years, 55% women, and enrollment year ranging from 1989 to 2012). Epigenome-wide association studies (EWAS) for Life's Essential 8 score were conducted, followed by bioinformatic analyses. DNAm loci significantly associated with Life's Essential 8 score were used to calculate a CVH DNAm score. We examined the association of the CVH DNAm score with incident cardiovascular disease (CVD), cardiovascular disease-specific mortality, and all-cause mortality.We identified 609 cytosine-phosphate-guanines (CpGs) associated with Life's Essential 8 score at false discovery rate<0.05 in the discovery analysis and at Bonferroni-corrected P<0.05 in the multicohort replication stage. Most had low to moderate heterogeneity (414 CpGs [68.0%] with heterogeneity <0.2) in replication analysis. Pathway enrichment analyses and a phenome-wide association study search associated these CpGs with inflammatory or autoimmune phenotypes. We observed enrichment for phenotypes in the Epigenome-Wide Association Study Catalog, with 29-fold enrichment for stroke (P=2.4e-15) and 21-fold for ischemic heart disease (P=7.4e-38). Two-sample Mendelian randomization (MR) analysis showed significant association between 141 CpGs and ten phenotypes (261 CpG-phenotype pairs) at false discovery rate<0.05. For example, hypomethylation at cg20544516 (MIR33B [microRNA 33b] and SREBF1 [sterol regulatory element-binding transcription factor 1]) is associated with a lower risk of stroke (P=8.1e-6). In multivariable prospective analyses, the CVH DNAm score was consistently associated with clinical outcomes across participating cohorts. Per SD increase in the CVH DNAm score, the decrease in risk of incident cardiovascular disease, cardiovascular disease mortality, and all-cause mortality ranged from 19% to 32%, 28% to 40%, and 27% to 45%, respectively.We identified new DNAm signatures for CVH across diverse cohorts. Our analyses indicate that multiple biological pathways may be relevant to the observed association between CVH and clinical outcomes.
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000280965 650_7 $$2Other$$aDNA methylation
000280965 650_7 $$2Other$$aLife’s Essential 8
000280965 650_7 $$2Other$$aall-cause mortality
000280965 650_7 $$2Other$$acardiovascular diseases
000280965 650_7 $$2Other$$acardiovascular health
000280965 650_7 $$2Other$$aepigenome-wide association study
000280965 7001_ $$00000-0002-5544-750X$$aLi, Yi$$b1
000280965 7001_ $$00000-0001-5937-3811$$aQu, Yishu$$b2
000280965 7001_ $$00000-0002-2006-7320$$aZheng, Yinan$$b3
000280965 7001_ $$00000-0001-7616-2119$$aWood, Alexis C$$b4
000280965 7001_ $$aWang, Mengyao$$b5
000280965 7001_ $$00000-0002-9160-0153$$aLiu, Chunyu$$b6
000280965 7001_ $$aHuan, Tianxiao$$b7
000280965 7001_ $$00000-0001-5549-9054$$aJoehanes, Roby$$b8
000280965 7001_ $$00000-0002-5264-5068$$aGuo, Xiuqing$$b9
000280965 7001_ $$00000-0002-8822-0651$$aYao, Jie$$b10
000280965 7001_ $$00000-0002-2756-4370$$aTaylor, Kent D$$b11
000280965 7001_ $$00000-0002-0080-2420$$aTracy, Russell P$$b12
000280965 7001_ $$00000-0003-4000-2943$$aDurda, Peter$$b13
000280965 7001_ $$00000-0002-6562-1858$$aLiu, Yongmei$$b14
000280965 7001_ $$00000-0002-3161-3753$$aJohnson, W Craig$$b15
000280965 7001_ $$00000-0002-8655-5204$$aPost, Wendy S$$b16
000280965 7001_ $$aBlackwell, Tom$$b17
000280965 7001_ $$00000-0001-7191-1723$$aRotter, Jerome I$$b18
000280965 7001_ $$00000-0003-3872-7793$$aRich, Stephen S$$b19
000280965 7001_ $$00000-0002-6585-1610$$aRedline, Susan$$b20
000280965 7001_ $$00000-0003-0677-8158$$aFornage, Myriam$$b21
000280965 7001_ $$aWang, Jun$$b22
000280965 7001_ $$00000-0003-1157-6614$$aNing, Hongyan$$b23
000280965 7001_ $$00000-0003-4877-0031$$aHou, Lifang$$b24
000280965 7001_ $$00000-0003-0847-6110$$aLloyd-Jones, Donald$$b25
000280965 7001_ $$00000-0002-8813-6871$$aFerrier, Kendra$$b26
000280965 7001_ $$00000-0003-2470-0004$$aMin, Yuan-I$$b27
000280965 7001_ $$00000-0002-7970-6756$$aCarson, April P$$b28
000280965 7001_ $$00000-0002-7892-193X$$aRaffield, Laura M$$b29
000280965 7001_ $$00000-0002-8309-094X$$aTeumer, Alexander$$b30
000280965 7001_ $$0P:(DE-2719)2811781$$aGrabe, Hans J$$b31
000280965 7001_ $$aVölzke, Henry$$b32
000280965 7001_ $$00000-0002-6678-7964$$aNauck, Matthias$$b33
000280965 7001_ $$00000-0001-7471-475X$$aDörr, Marcus$$b34
000280965 7001_ $$00000-0001-6928-8290$$aDomingo-Relloso, Arce$$b35
000280965 7001_ $$00000-0002-5358-2345$$aFretts, Amanda$$b36
000280965 7001_ $$00000-0002-3850-1228$$aTellez-Plaza, Maria$$b37
000280965 7001_ $$00000-0002-2651-0127$$aCole, Shelley A$$b38
000280965 7001_ $$00000-0001-9824-7797$$aNavas-Acien, Ana$$b39
000280965 7001_ $$00000-0001-8345-9180$$aWang, Meng$$b40
000280965 7001_ $$00000-0002-0192-7516$$aMurabito, Joanne M$$b41
000280965 7001_ $$00000-0001-9730-0306$$aHeard-Costa, Nancy L$$b42
000280965 7001_ $$00000-0002-3805-9070$$aPrescott, Brenton$$b43
000280965 7001_ $$00000-0002-7352-621X$$aXanthakis, Vanessa$$b44
000280965 7001_ $$00000-0001-7958-9492$$aMozaffarian, Dariush$$b45
000280965 7001_ $$00000-0003-1843-8724$$aLevy, Daniel$$b46
000280965 7001_ $$00000-0001-7478-7203$$aMa, Jiantao$$b47
000280965 773__ $$0PERI:(DE-600)1466401-X$$a10.1161/CIRCULATIONAHA.124.073181$$gVol. 152, no. 7, p. 436 - 449$$n7$$p436 - 449$$tCirculation$$v152$$x0009-7322$$y2025
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