{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T15:24:10Z","timestamp":1766157850924,"version":"3.48.0"},"reference-count":44,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"24","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2025,12,16]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">The role of circulating metabolites in heart failure (HF) mechanisms and their clinical utility remain unclear. We aimed to examine the associations between serum metabolites and incident HF and assess their performance in improving HF risk prediction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      A total of 23\u2009571 serum metabolomic spectral variables were measured using untargeted proton nuclear magnetic resonance spectroscopy. Participants from MESA (Multi\u2010Ethnic Study of Atherosclerosis; discovery cohort) and RS (Rotterdam Study; replication cohort) with metabolomic data and without prevalent HF at baseline were included. Cause\u2010specific proportional hazards models were used to estimate the associations between metabolomic features and incident HF, with false discovery rate\u2013adjusted\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      values for multiple comparisons. We further assessed how adjusting for cardiovascular risk factors influenced these associations. Correlations among metabolites were tested. Discriminative performance of risk prediction was evaluated using Harrell\u2019s C\u2010statistic.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      We included 3942 MESA and 1515 RS participants, with a median of 15\u2009years follow\u2010up. In MESA, 15 metabolites were significantly associated with incident HF (false discovery rate\u2013adjusted\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      &lt;0.01), with 5 replicating in RS (false discovery rate\u2013adjusted\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      &lt;0.05). However, after further adjusting for diabetes or hypertension, observed associations lost statistical significance. Methanol, glucose, proline, and acetoacetate showed significant correlations with fasting glucose (Pearson coefficients, 0.41\u20130.89). Incorporating the 5 replicated metabolites or all 15 metabolites identified from MESA into PREVENT\u2010HF (Predicting Risk of Cardiovascular Disease Events\u2013Heart Failure) did not significantly improve C\u2010statistics in either cohort.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">Fifteen proton nuclear magnetic resonance\u2013measured metabolites were associated with incident HF, but these associations were not independent of diabetes or hypertension. These metabolites provided minimal predictive utility beyond PREVENT\u2010HF equations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.125.044211","type":"journal-article","created":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T10:38:52Z","timestamp":1765449532000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Serum Metabolites and Heart Failure Risk: MESA and RS"],"prefix":"10.1161","volume":"14","author":[{"given":"Fang","family":"Zhu","sequence":"first","affiliation":[{"name":"National Institutes of Health","place":["Bethesda, USA"]},{"name":"Erasmus MC, University Medical Center Rotterdam","place":["Rotterdam, the Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arjun","family":"Sinha","sequence":"additional","affiliation":[{"name":"Northwestern University Feinberg School of Medicine","place":["Chicago, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0876-3876","authenticated-orcid":false,"given":"Gon\u00e7alo","family":"Gra\u00e7a","sequence":"additional","affiliation":[{"name":"Imperial College London","place":["London, UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2831-3618","authenticated-orcid":false,"given":"Ian J.","family":"Neeland","sequence":"additional","affiliation":[{"name":"University Hospitals Cleveland and Case Western Reserve University School of Medicine","place":["Cleveland, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9651-3836","authenticated-orcid":false,"given":"Ambarish","family":"Pandey","sequence":"additional","affiliation":[{"name":"University of Texas Southwestern Medical Center","place":["Dallas, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4275-9328","authenticated-orcid":false,"given":"Ioanna","family":"Tzoulaki","sequence":"additional","affiliation":[{"name":"Imperial College London","place":["London, UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9341-8155","authenticated-orcid":false,"given":"Ibrahim","family":"Karaman","sequence":"additional","affiliation":[{"name":"Imperial College London","place":["London, UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0080-2420","authenticated-orcid":false,"given":"Russell P.","family":"Tracy","sequence":"additional","affiliation":[{"name":"University of Vermont College of Medicine","place":["Burlington, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8756-6995","authenticated-orcid":false,"given":"Joao A. C.","family":"Lima","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine","place":["Baltimore, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5655-8201","authenticated-orcid":false,"given":"Sanjiv J.","family":"Shah","sequence":"additional","affiliation":[{"name":"Northwestern University Feinberg School of Medicine","place":["Chicago, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7670-6400","authenticated-orcid":false,"given":"David","family":"Herrington","sequence":"additional","affiliation":[{"name":"Wake Forest University School of Medicine","place":["Winston\u2010Salem, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3694-6060","authenticated-orcid":false,"given":"Michael P.","family":"Bancks","sequence":"additional","affiliation":[{"name":"Wake Forest University School of Medicine","place":["Winston\u2010Salem, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adovich S.","family":"Rivera","sequence":"additional","affiliation":[{"name":"Northwestern University Feinberg School of Medicine","place":["Chicago, USA"]},{"name":"Northwestern University Feinberg School of Medicine","place":["Chicago, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6327-2439","authenticated-orcid":false,"given":"Philip","family":"Greenland","sequence":"additional","affiliation":[{"name":"Northwestern University Feinberg School of Medicine","place":["Chicago, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardfail.2023.07.006"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.m2688"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2016.09.972"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/circheartfailure.123.010896"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-015-0661-3"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehz235"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehaa270"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.111.060368"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/ehf2.12923"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2015.02.018"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/circgen.123.004398"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.118.314338"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.123.067626"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000677"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jproteome.6b00125"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-023-01094-1"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwf113"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1021\/ac5025039"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchf.2018.07.009"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCIMAGING.122.014323"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-130-6-199903160-00002"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1114248"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v045.i03"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.2115"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000001063"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgae812"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.2337\/diaspect.25.3.141"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-019-05001-w"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.120.315898"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc13-0800"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2024.105264"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tjnut.2023.05.030"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.numecd.2021.05.004"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.124.039750"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcha.2019.100432"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgab562"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2013.10.029"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajcnut.2023.08.011"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nutres.2023.03.004"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehs424"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.2337\/db18-1076"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1002\/ehf2.14700"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-50125-2"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-71329-y"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.125.044211","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T15:15:50Z","timestamp":1766157350000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.125.044211"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,16]]},"references-count":44,"journal-issue":{"issue":"24","published-print":{"date-parts":[[2025,12,16]]}},"alternative-id":["10.1161\/JAHA.125.044211"],"URL":"https:\/\/doi.org\/10.1161\/jaha.125.044211","relation":{},"ISSN":["2047-9980"],"issn-type":[{"type":"electronic","value":"2047-9980"}],"subject":[],"published":{"date-parts":[[2025,12,16]]},"assertion":[{"value":"2025-06-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e044211"}}