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The correlates and mediators of heart failure risk in individuals with diabetes need more elucidation in large population-based cohorts with long follow-up times and a wide panel of biologically relevant biomarkers.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>In a population-based sample of 3834 diabetic and 90,177 non-diabetic individuals, proportional hazards models and mediation analysis were used to assess the relation of conventional heart failure risk factors and biomarkers with incident heart failure.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Over a median follow-up of 13.8\u00a0years, a total of 652 (17.0%) and 5524 (6.1%) cases of incident heart failure were observed in participants with and without diabetes, respectively. 51.4% were women and the\u00a0mean age at baseline was 48.7 (standard deviation [SD] 12.5) years. The multivariable-adjusted hazard ratio (HR) for heart failure among diabetic individuals was 2.70 (95% confidence interval, 2.49\u20132.93) compared to non-diabetic participants. In the multivariable-adjusted Cox models, conventional cardiovascular disease risk factors, such as smoking (diabetes: HR 2.07 [1.59\u20132.69]; non-diabetes: HR 1.85 [1.68\u20132.02]), BMI (diabetes: HR 1.30 [1.18\u20131.42]; non-diabetes: HR 1.40 [1.35\u20131.47]), baseline myocardial infarction (diabetes: HR 2.06 [1.55\u20132.75]; non-diabetes: HR 2.86 [2.50\u20133.28]), and baseline atrial fibrillation (diabetes: HR 1.51 [0.82\u20132.80]; non-diabetes: HR 2.97 [2.21\u20134.00]) had the strongest associations with incident heart failure. In addition, biomarkers for cardiac strain (represented by nT-proBNP, diabetes: HR 1.26 [1.19\u20131.34]; non-diabetes: HR 1.43 [1.39\u20131.47]), myocardial injury (hs-TnI, diabetes: HR 1.10 [1.04\u20131.16]; non-diabetes: HR 1.13 [1.10\u20131.16]), and inflammation (hs-CRP, diabetes: HR 1.13 [1.03\u20131.24]; non-diabetes: HR 1.29 [1.25\u20131.34]) were also associated with incident heart failure. In general, all these associations were equally strong in non-diabetic and diabetic individuals. However, the strongest mediators of heart failure in diabetes were the direct effect of diabetes status itself (relative effect share 43.1% [33.9\u201352.3] and indirect effects (effect share 56.9% [47.7-66.1])\u00a0mediated by obesity (BMI, 13.2% [10.3\u201316.2]), cardiac strain\/volume overload (nT-proBNP, 8.4% [-0.7\u201317.4]), and hyperglycemia (glucose, 12.0% [4.2\u201319.9]).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>The findings suggest that the main mediators of heart failure in diabetes are obesity, hyperglycemia, and cardiac strain\/volume overload. Conventional cardiovascular risk factors are strongly related to incident heart failure, but these associations are not stronger in diabetic than in non-diabetic individuals. Active measurement of relevant biomarkers could potentially be used to improve prevention and prediction of heart failure in high-risk diabetic patients.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12933-021-01378-4","type":"journal-article","created":{"date-parts":[[2021,9,28]],"date-time":"2021-09-28T17:12:58Z","timestamp":1632849178000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Diabetes status-related differences in risk factors and mediators of heart failure in the general population: results from the MORGAM\/BiomarCaRE consortium"],"prefix":"10.1186","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2529-3332","authenticated-orcid":false,"given":"Matti A.","family":"Vuori","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaakko","family":"Reinikainen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"S\u00f6derberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellinor","family":"Bergdahl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pekka","family":"Jousilahti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugh","family":"Tunstall-Pedoe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Zeller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Westermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susana","family":"Sans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan","family":"Linneberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Licia","family":"Iacoviello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Costanzo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veikko","family":"Salomaa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Blankenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kari","family":"Kuulasmaa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teemu J.","family":"Niiranen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,9,28]]},"reference":[{"issue":"1","key":"1378_CR1","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/0002-9149(74)90089-7","volume":"34","author":"WB Kannel","year":"1974","unstructured":"Kannel WB, Hjortland M, Castelli WP. 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URN:NBN:fife20041529.\nAvailable from URL: https:\/\/www.thl.fi\/publications\/morgam\/manual\/contents.htm"}],"container-title":["Cardiovascular Diabetology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12933-021-01378-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12933-021-01378-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12933-021-01378-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,7]],"date-time":"2023-02-07T00:04:29Z","timestamp":1675728269000},"score":1,"resource":{"primary":{"URL":"https:\/\/cardiab.biomedcentral.com\/articles\/10.1186\/s12933-021-01378-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,28]]},"references-count":47,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["1378"],"URL":"https:\/\/doi.org\/10.1186\/s12933-021-01378-4","relation":{},"ISSN":["1475-2840"],"issn-type":[{"value":"1475-2840","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,28]]},"assertion":[{"value":"8 June 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 September 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 September 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The included studies have been approved by local ethic committees as follows: MORGAM FINRISK: 1980s: no ethics approval required for observational studies (but current laws allow the use of these data for public health research), 1990s: Ethics committee of the National Public Health Institute (KTL), 2002: Ethics Committee of Epidemiology and Public Health in Hospital District of Helsinki and Uusimaa. MORGAM DAN-MONICA: Ethics Committee of the Capital Region (formerly Copenhagen County), Denmark. MORGAM Northern Sweden: Research Ethics Committee of Ume\u00e5 University. MORGAM Moli-sani: Universit\u00e0 Cattolica del Sacro Cuore Facolt\u00e0 di Medicina e Chirurgia \u201cAgostino Gemelli\u201d, Rome. MORGAM SHHEC: Ethical approval was received from all relevant medical research ethics committees covering the individual populations involved.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"VS has received honoraria from Novo-Nordisk and Sanofi for consulting. He also has ongoing research collaboration with Bayer Ltd (all outside this work). SSg has received consultancy and speaker\u2019s honoraria from Actelion (outside this work). DW has receiver honoraria from Abiomed, AstraZeneca, Bayer and Novartis. All other authors declared no competing of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"195"}}