{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T14:23:37Z","timestamp":1790000617012,"version":"4.0.1"},"reference-count":37,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,12,18]],"date-time":"2020-12-18T00:00:00Z","timestamp":1608249600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,12,18]],"date-time":"2020-12-18T00:00:00Z","timestamp":1608249600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100002997","name":"Nierstichting","doi-asserted-by":"publisher","award":["E.033"],"award-info":[{"award-number":["E.033"]}],"id":[{"id":"10.13039\/501100002997","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Clin Investigation"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>In the failing heart, energy metabolism is shifted towards increased ketone body oxidation. Nevertheless, the association of beta\u2010hydroxybutyrate (\u03b2\u2010OHB) with development of heart failure (HF) remains unclear. We investigated the association between plasma \u03b2\u2010OHB and the risk of HF in a prospective population\u2010based cohort.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>Plasma \u03b2\u2010OHB concentrations were measured in 6134 participants of the PREVEND study. Risk of incident HF with reduced (HFrEF) or preserved (HFpEF) ejection fraction was estimated using multivariable\u2010adjusted Cox regression models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      During median follow\u2010up for 8.2\u00a0years, 227 subjects were diagnosed with HF (137 with HFrEF; 90 with HFpEF). Cox regression analyses revealed a significant association of higher \u03b2\u2010OHB concentrations with incident HF (HR per 1 standard deviation increase, 1.40 (95% CI: 1.21\u20101.63;\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a0.001), which was largely attributable to HFrEF. In women, the hazard ratio (HR) for HFrEF per 1 standard deviation increase in \u03b2\u2010OHB was 1.73 (95% confidence interval (CI): 1.17\u20102.56,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a0.005) in age, BMI, type 2 diabetes, hypertension, myocardial infarction, smoking, alcohol consumption, total cholesterol, HDL\u2010C, triglycerides, glucose, eGFR and UAE adjusted analysis. In men, in the same fully adjusted analysis, the HR was 1.14 (CI: 0.86\u20101.53,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a0.36) (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a0.01 for sex interaction). In N\u2010terminal pro\u2010brain natriuretic peptide (NT\u2010proBNP)\u2010stratified analysis, the age\u2010adjusted association with HF was significant in women with higher NT\u2010proBNP levels (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a0.008).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This prospective study suggests that high plasma concentrations of \u03b2\u2010OHB are associated with an increased risk of HFrEF, particularly in women. The mechanisms responsible for the sex differences of this association warrant further study.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/eci.13468","type":"journal-article","created":{"date-parts":[[2020,12,8]],"date-time":"2020-12-08T02:27:28Z","timestamp":1607394448000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Association of beta\u2010hydroxybutyrate with development of heart failure: Sex differences in a Dutch population cohort"],"prefix":"10.1111","volume":"51","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6094-2206","authenticated-orcid":false,"given":"Jose L.","family":"Flores\u2010Guerrero","sequence":"first","affiliation":[{"name":"Department of Internal Medicine Division of Nephrology University of Groningen University Medical Center Groningen Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berend Daan","family":"Westenbrink","sequence":"additional","affiliation":[{"name":"Department of Cardiology University of Groningen University Medical Center Groningen Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margery A.","family":"Connelly","sequence":"additional","affiliation":[{"name":"Laboratory Corporation of America Holdings (LabCorp) Morrisville NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James D.","family":"Otvos","sequence":"additional","affiliation":[{"name":"Laboratory Corporation of America Holdings (LabCorp) Morrisville NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dion","family":"Groothof","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Division of Nephrology University of Groningen University Medical Center Groningen Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Shalaurova","sequence":"additional","affiliation":[{"name":"Laboratory Corporation of America Holdings (LabCorp) Morrisville NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erwin","family":"Garcia","sequence":"additional","affiliation":[{"name":"Laboratory Corporation of America Holdings (LabCorp) Morrisville NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerjan","family":"Navis","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Division of Nephrology University of Groningen University Medical Center Groningen Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudolf A.","family":"de Boer","sequence":"additional","affiliation":[{"name":"Department of Cardiology University of Groningen University Medical Center Groningen Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan J. 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