{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T06:20:01Z","timestamp":1793859601036,"version":"4.6.1"},"reference-count":61,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T00:00:00Z","timestamp":1754352000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Swiss Government Excellence Scholarship","award":["2021.0899"],"award-info":[{"award-number":["2021.0899"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Iron levels imbalances are linked to cardiovascular outcomes. We aimed to assess the association between genetically predicted lifelong higher iron levels and cardiovascular outcomes, employing a two-sample Mendelian randomization (MR) approach to account for confounding biases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>We used a study involving 257 953 subjects across six cohort studies that identified genetic variants consistently associated with iron biomarkers, including ferritin, serum iron, total iron binding capacity (TIBC), and transferrin saturation (TSAT). The UK Biobank study was used to investigate the association between the same genetic variants and left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular ejection fraction (LVEF), left ventricular mass (LVM), and left ventricular mass-to-end-diastolic volume ratio (LVMVR). Two-sample MR approach was used in our main analysis. Heterogeneity, pleiotropy, bidirectional MR, MR-Egger, weighted median, and weighted mode were explored in the sensitivity analysis. One standard deviation (SD) increase in genetically predicted serum iron levels was associated with lower LVEDV (beta (95%CI): \u22120.11, (\u22120.19, \u22120.03), P-value = 0.006) and lower LVESV (\u22120.11 (\u22120.19, \u22120.03), P-value = 0.007). Moreover, one SD increase in genetically predicted TSAT was associated with higher LVMVR (0.09, (0.03, 0.15), P-value = 0.005). Heterogeneity, pleiotropy, and bidirectional effects were not observed. The identified associations were explained by HFE, TMPRSS6, TF, and TFR2 genes. No other associations were identified between iron biomarkers and cardiovascular outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our study provides MR evidence that iron status may alter cardiovascular function and structure. HFE, TMPRSS6, TF and TFR2 genes play a crucial role in the identified associations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/eurjpc\/zwaf498","type":"journal-article","created":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T11:22:23Z","timestamp":1754306543000},"page":"394-403","source":"Crossref","is-referenced-by-count":3,"title":["Genetically predicted iron status and cardiovascular function and structure: a Mendelian randomization study"],"prefix":"10.1093","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0641-7718","authenticated-orcid":false,"given":"Hugo G","family":"Quezada-Pinedo","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Division of Neonatology, Erasmus MC-Sophia Children's Hospital, Generation R Study Group, Na-2907; PO Box 2040, University Medical Center Rotterdam , Rotterdam 3015 ,","place":["The Netherlands"]},{"name":"Department of Population Health Sciences, Duke University School of Medicine , Durham, NC 27701 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0213-6935","authenticated-orcid":false,"given":"Kim N","family":"Cajachagua-Torres","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, New York University Grossman School of Medicine , New York, NY ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noushin Sadat","family":"Ahanchi","sequence":"additional","affiliation":[{"name":"Institute of Social and Preventive Medicine (ISPM), University of Bern , Bern ,","place":["Switzerland"]},{"name":"Graduate School for Health Sciences, University of Bern , Bern ,","place":["Switzerland"]},{"name":"Department of Internal Medicine, Internal Medicine, Lausanne University Hospital and University of Lausanne , Lausanne ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3589-1168","authenticated-orcid":false,"given":"Farnaz","family":"Khatami","sequence":"additional","affiliation":[{"name":"Institute of Social and Preventive Medicine (ISPM), University of Bern , Bern ,","place":["Switzerland"]},{"name":"Graduate School for Health Sciences, University of Bern , Bern ,","place":["Switzerland"]},{"name":"Community Medicine Department, Tehran University of Medical Sciences , Tehran ,","place":["Iran"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3235-3073","authenticated-orcid":false,"given":"Taulant","family":"Muka","sequence":"additional","affiliation":[{"name":"Epistudia , Bern ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Huicho","sequence":"additional","affiliation":[{"name":"Centro de Investigacion en Salud Materna e Infantil and Centro de Investigacion Para el Desarrollo Integral y Sostenible, Universidad Peruana Cayetano Heredia , Lima 150135 ,","place":["Peru"]},{"name":"Facultad de Medicina \u2018Alberto Hurtado\u2019, Universidad Peruana Cayetano Heredia , Lima 150135 ,","place":["Peru"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5976-6519","authenticated-orcid":false,"given":"Maryam","family":"Kavousi","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam , Rotterdam ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele F","family":"Eisenga","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, University of Groningen , Groningen 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