{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T21:15:28Z","timestamp":1793222128459,"version":"4.5.0"},"reference-count":64,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2023,6,20]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">The American Heart Association's framework \u201cideal cardiovascular health\u201d (CVH) focuses on modifiable risk factors to reduce cardiovascular disease (CVD). Metabolomics provides important pathobiological insights into risk factors and CVD development. We hypothesized that metabolomic signatures associate with CVH status, and that metabolites, at least partially, mediate the association of CVH score with atrial fibrillation (AF) and heart failure (HF).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">We studied 3056 adults in the FHS (Framingham Heart Study) cohort to evaluate CVH score and incident outcomes of AF and HF. Metabolomics data were available in 2059 participants; mediation analysis was performed to evaluate the mediation of metabolites in the association of CVH score and incident AF and HF. In the smaller cohort (mean age, 54\u2009years; 53% women), CVH score was associated with 144 metabolites, with 64 metabolites shared across key cardiometabolic components (body mass index, blood pressure, and fasting blood glucose) of the CVH score. In mediation analyses, 3 metabolites (glycerol, cholesterol ester 16:1, and phosphatidylcholine 32:1) mediated the association of CVH score with incident AF. Seven metabolites (glycerol, isocitrate, asparagine, glutamine, indole\u20103\u2010proprionate, phosphatidylcholine C36:4, and lysophosphatidylcholine 18:2), partly mediated the association between CVH score and incident HF in multivariable\u2010adjusted models.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">Most metabolites that associated with CVH score were shared the most among 3 cardiometabolic components. Three main pathways: (1) alanine, glutamine, and glutamate metabolism; (2) citric acid cycle metabolism; and (3) glycerolipid metabolism mediated CVH score with HF. Metabolomics provides insights into how ideal CVH status contributes to the development of AF and HF.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.122.028022","type":"journal-article","created":{"date-parts":[[2023,6,11]],"date-time":"2023-06-11T02:25:45Z","timestamp":1686450345000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":37,"title":["Metabolomic Profiles, Ideal Cardiovascular Health, and Risk of Heart Failure and Atrial Fibrillation: Insights From the Framingham Heart Study"],"prefix":"10.1161","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5544-750X","authenticated-orcid":false,"given":"Yi","family":"Li","sequence":"first","affiliation":[{"name":"Department of Biostatistics, School of Public Health Boston University Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5081-6951","authenticated-orcid":false,"given":"Ayana","family":"Gray","sequence":"additional","affiliation":[{"name":"Harvard University Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9281-4598","authenticated-orcid":false,"given":"Liying","family":"Xue","sequence":"additional","affiliation":[{"name":"Evans Department of Medicine and Whitaker Cardiovascular Institute Boston University Chobanian &amp; Avedisian School of Medicine Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6811-4384","authenticated-orcid":false,"given":"Melissa G.","family":"Farb","sequence":"additional","affiliation":[{"name":"Evans Department of Medicine and Whitaker Cardiovascular Institute Boston University Chobanian &amp; Avedisian School of Medicine Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0480-1249","authenticated-orcid":false,"given":"Nir","family":"Ayalon","sequence":"additional","affiliation":[{"name":"Section of Cardiovascular Medicine, Department of Medicine Boston University Chobanian &amp; Avedisian School of Medicine\/Boston Medical Center Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6019-8627","authenticated-orcid":false,"given":"Charlotte","family":"Andersson","sequence":"additional","affiliation":[{"name":"Section of Cardiovascular Medicine, Department of Medicine Boston University Chobanian &amp; Avedisian School of Medicine\/Boston Medical Center Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1174-7535","authenticated-orcid":false,"given":"Darae","family":"Ko","sequence":"additional","affiliation":[{"name":"Section of Cardiovascular Medicine, Department of Medicine Boston University Chobanian &amp; Avedisian School of Medicine\/Boston Medical Center Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4076-2336","authenticated-orcid":false,"given":"Emelia J.","family":"Benjamin","sequence":"additional","affiliation":[{"name":"Section of Cardiovascular Medicine, Department of Medicine Boston University Chobanian &amp; Avedisian School of Medicine\/Boston Medical Center Boston MA USA"},{"name":"Evans Department of Medicine, Section of Cardiovascular Medicine and Department of Epidemiology Boston University Boston MA USA"},{"name":"Framingham Heart Study Framingham MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1843-8724","authenticated-orcid":false,"given":"Daniel","family":"Levy","sequence":"additional","affiliation":[{"name":"Population Sciences Branch, Division of Intramural Research National Heart, Lung, and Blood Institute, National Institutes of Health Bethesda MD USA"},{"name":"Framingham Heart Study Framingham MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7357-5970","authenticated-orcid":false,"given":"Ramachandran S.","family":"Vasan","sequence":"additional","affiliation":[{"name":"Section of Cardiovascular Medicine, Department of Medicine Boston University Chobanian &amp; Avedisian School of Medicine\/Boston Medical Center Boston MA USA"},{"name":"Evans Department of Medicine, Section of Cardiovascular Medicine and Department of Epidemiology Boston University Boston MA USA"},{"name":"Section of Preventive Medicine and Epidemiology, Department of Medicine Boston University Chobanian &amp; Avedisian School of Medicine Boston MA USA"},{"name":"Framingham Heart Study Framingham MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9631-1254","authenticated-orcid":false,"given":"Martin G.","family":"Larson","sequence":"additional","affiliation":[{"name":"Department of Biostatistics Boston University School of Public Health Boston MA USA"},{"name":"Framingham Heart Study Framingham MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Rong","sequence":"additional","affiliation":[{"name":"Department of Biostatistics Boston University School of Public Health Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7352-621X","authenticated-orcid":false,"given":"Vanessa","family":"Xanthakis","sequence":"additional","affiliation":[{"name":"Section of Preventive Medicine and Epidemiology, Department of Medicine Boston University Chobanian &amp; Avedisian School of Medicine Boston MA USA"},{"name":"Department of Biostatistics Boston University School of Public Health Boston MA USA"},{"name":"Framingham Heart Study Framingham MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9160-0153","authenticated-orcid":false,"given":"Chunyu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biostatistics Boston University School of Public Health Boston MA USA"},{"name":"Framingham Heart Study Framingham MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9286-7538","authenticated-orcid":false,"given":"Jessica L.","family":"Fetterman","sequence":"additional","affiliation":[{"name":"Evans Department of Medicine and Whitaker Cardiovascular Institute Boston University Chobanian &amp; Avedisian School of Medicine Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3534-9360","authenticated-orcid":false,"given":"Deepa M.","family":"Gopal","sequence":"additional","affiliation":[{"name":"Evans Department of Medicine and Whitaker Cardiovascular Institute Boston University Chobanian &amp; Avedisian School of Medicine Boston MA USA"},{"name":"Section of Cardiovascular Medicine, Department of Medicine Boston University Chobanian &amp; Avedisian School of Medicine\/Boston Medical Center Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.192703"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1179\/030801878791925921"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2010.11.041"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1177\/2047487315602015"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amepre.2016.07.003"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.114.009273"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.111.049122"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2015.03.027"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.115.002416"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.116.005180"},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2017.09.033"},{"key":"e_1_3_1_13_2","doi-asserted-by":"publisher","DOI":"10.3390\/nu13093201"},{"key":"e_1_3_1_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2018.05.050"},{"key":"e_1_3_1_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/HCG.0000000000000032"},{"key":"e_1_3_1_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a112813"},{"key":"e_1_3_1_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.echo.2015.07.026"},{"key":"e_1_3_1_18_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197112232852601"},{"key":"e_1_3_1_19_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0148361"},{"key":"e_1_3_1_20_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI44442"},{"key":"e_1_3_1_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2307"},{"key":"e_1_3_1_22_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI64801"},{"key":"e_1_3_1_23_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.117.008424"},{"key":"e_1_3_1_24_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.2517-6161.1995.tb02031.x"},{"key":"e_1_3_1_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-022-00710-w"},{"key":"e_1_3_1_26_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2012101006"},{"key":"e_1_3_1_27_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2018.21973"},{"key":"e_1_3_1_28_2","doi-asserted-by":"publisher","DOI":"10.1515\/em-2012-0010"},{"key":"e_1_3_1_29_2","doi-asserted-by":"publisher","DOI":"10.1097\/EDE.0b013e31821db37e"},{"key":"e_1_3_1_30_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.117.031431"},{"key":"e_1_3_1_31_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.k1453"},{"key":"e_1_3_1_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms7791"},{"key":"e_1_3_1_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2021.04.013"},{"key":"e_1_3_1_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/oby.21448"},{"key":"e_1_3_1_35_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI86013"},{"key":"e_1_3_1_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2012.08.026"},{"key":"e_1_3_1_37_2","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9072257"},{"key":"e_1_3_1_38_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-017-4261-z"},{"key":"e_1_3_1_39_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0142610"},{"key":"e_1_3_1_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2019.03.017"},{"key":"e_1_3_1_41_2","doi-asserted-by":"publisher","DOI":"10.3390\/biom11111663"},{"key":"e_1_3_1_42_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0196709"},{"key":"e_1_3_1_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-34930-6"},{"key":"e_1_3_1_44_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.120.017579"},{"key":"e_1_3_1_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2016.08.010"},{"key":"e_1_3_1_46_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI69600"},{"key":"e_1_3_1_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-019-0191-2"},{"key":"e_1_3_1_48_2","doi-asserted-by":"publisher","DOI":"10.1002\/stem.2047"},{"key":"e_1_3_1_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2021.154778"},{"key":"e_1_3_1_50_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.217349"},{"key":"e_1_3_1_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2020.12.003"},{"key":"e_1_3_1_52_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0214080"},{"key":"e_1_3_1_53_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00887.2007"},{"key":"e_1_3_1_54_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurjhf\/hfs172"},{"key":"e_1_3_1_55_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-020-00296-1"},{"key":"e_1_3_1_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacbts.2022.03.017"},{"key":"e_1_3_1_57_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abc8861"},{"key":"e_1_3_1_58_2","doi-asserted-by":"publisher","DOI":"10.1038\/200169a0"},{"key":"e_1_3_1_59_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvx017"},{"key":"e_1_3_1_60_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.113.002500"},{"key":"e_1_3_1_61_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.120.317883"},{"key":"e_1_3_1_62_2","doi-asserted-by":"publisher","DOI":"10.1093\/ehjqcco\/qcy047"},{"key":"e_1_3_1_63_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.121.009353"},{"key":"e_1_3_1_64_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2022.4091"},{"key":"e_1_3_1_65_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvab367"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.122.028022","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T12:45:18Z","timestamp":1715604318000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.122.028022"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,20]]},"references-count":64,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2023,6,20]]}},"alternative-id":["10.1161\/JAHA.122.028022"],"URL":"https:\/\/doi.org\/10.1161\/jaha.122.028022","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,20]]},"assertion":[{"value":"2022-11-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-04-13","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-06-10","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e028022"}}