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We hypothesized that plasma adiponectin is associated observationally and causally, genetically with risk of heart failure, atrial fibrillation, aortic valve stenosis, and myocardial infarction.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>In the Copenhagen General Population Study, we examined 30 045 individuals with plasma adiponectin measurements observationally and 96 903 individuals genetically in one-sample Mendelian randomization analyses using five genetic variants explaining 3% of the variation in plasma adiponectin. In the HERMES, UK Biobank, The Nord-Tr\u00f8ndelag Health Study (HUNT), deCODE, the Michigan Genomics Initiative (MGI), DiscovEHR, and the AFGen consortia, we performed two-sample Mendelian randomization analyses in up to 1 030 836 individuals using 12 genetic variants explaining 14% of the variation in plasma adiponectin.<\/jats:p>\n                  <jats:p>In observational analyses modelled linearly, a 1 unit log-transformed higher plasma adiponectin was associated with a hazard ratio of 1.51 (95% confidence interval: 1.37\u20131.66) for heart failure, 1.63 (1.50\u20131.78) for atrial fibrillation, 1.21 (1.03\u20131.41) for aortic valve stenosis, and 1.03 (0.93\u20131.14) for myocardial infarction; levels above the median were also associated with an increased risk of myocardial infarction, and non-linear U-shaped associations were more apparent for heart failure, aortic valve stenosis, and myocardial infarction in less-adjusted models. Corresponding genetic, causal risk ratios were 0.92 (0.65\u20131.29), 0.87 (0.68\u20131.12), 1.55 (0.87\u20132.76), and 0.93 (0.67\u20131.30) in one-sample Mendelian randomization analyses, and no significant associations were seen for non-linear one-sample Mendelian randomization analyses; corresponding causal risk ratios were 0.99 (0.89\u20131.09), 1.00 (0.92\u20131.08), 1.01 (0.79\u20131.28), and 0.99 (0.86\u20131.13) in two-sample Mendelian randomization analyses, respectively.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Observationally, elevated plasma adiponectin was associated with an increased risk of heart failure, atrial fibrillation, aortic valve stenosis, and myocardial infarction. However, genetic evidence did not support causality for these associations.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cvr\/cvad162","type":"journal-article","created":{"date-parts":[[2023,10,28]],"date-time":"2023-10-28T15:08:05Z","timestamp":1698505685000},"page":"95-107","source":"Crossref","is-referenced-by-count":26,"title":["Plasma adiponectin levels and risk of heart failure, atrial fibrillation, aortic valve stenosis, and myocardial infarction: large-scale observational and Mendelian randomization evidence"],"prefix":"10.1093","volume":"120","author":[{"given":"Maria Booth","family":"Nielsen","sequence":"first","affiliation":[{"name":"Department of Clinical Biochemistry, Copenhagen University Hospital\u2014Herlev and Gentofte , Borgmester Ib Juuls Vej 73, Entrance 7, 4. Floor, M3 , DK-2730 Herlev, Copenhagen, Denmark"},{"name":"The Copenhagen General Population Study, Copenhagen University Hospital\u2014Herlev and Gentofte , Borgmester Ib Juuls Vej 73, Entrance 7, 4. Floor, M3, DK-2730 Herlev, Copenhagen , Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen , Blegdamsvej 3B, DK-2200 Copenhagen N, Copenhagen , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunus","family":"\u00c7olak","sequence":"additional","affiliation":[{"name":"The Copenhagen General Population Study, Copenhagen University Hospital\u2014Herlev and Gentofte , Borgmester Ib Juuls Vej 73, Entrance 7, 4. Floor, M3, DK-2730 Herlev, Copenhagen , Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen , Blegdamsvej 3B, DK-2200 Copenhagen N, Copenhagen , Denmark"},{"name":"Department of Respiratory Medicine, Copenhagen University Hospital\u2014Herlev and Gentofte , Copenhagen , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1701-595X","authenticated-orcid":false,"given":"Marianne","family":"Benn","sequence":"additional","affiliation":[{"name":"The Copenhagen General Population Study, Copenhagen University Hospital\u2014Herlev and Gentofte , Borgmester Ib Juuls Vej 73, Entrance 7, 4. Floor, M3, DK-2730 Herlev, Copenhagen , Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen , Blegdamsvej 3B, DK-2200 Copenhagen N, Copenhagen , Denmark"},{"name":"Department of Clinical Biochemistry, Copenhagen University Hospital\u2014Rigshospitalet , Copenhagen , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Mason","sequence":"additional","affiliation":[{"name":"Medical Research Council Biostatistics Unit, University of Cambridge , Cambridge , United Kingdom"},{"name":"British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge , Cambridge , United Kingdom"},{"name":"Heart and Lung Research Institute, University of Cambridge , Cambridge , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5365-8760","authenticated-orcid":false,"given":"Stephen","family":"Burgess","sequence":"additional","affiliation":[{"name":"Medical Research Council Biostatistics Unit, University of Cambridge , Cambridge , United Kingdom"},{"name":"British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge , Cambridge , United Kingdom"},{"name":"Heart and Lung Research Institute, University of Cambridge , Cambridge , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1954-7220","authenticated-orcid":false,"given":"B\u00f8rge Gr\u00f8nne","family":"Nordestgaard","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, Copenhagen University Hospital\u2014Herlev and Gentofte , Borgmester Ib Juuls Vej 73, Entrance 7, 4. 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