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Potential mediators between obesity and NICM were also investigated. Methods: Two-sample Mendelian randomisation was used to explore the causal relationship between eight obesity-related traits and NICM and assess their impact on cardiac MRI indicators. The study also used validation dataset analysis and multivariable Mendelian randomisation to ensure robustness, and mediation Mendelian randomisation analysis to identify metabolic markers as potential mediators. Results: All eight obesity-related traits demonstrated a causal relationship with NICM, with the relationship between BMI and NICM persisting after adjustment for LDL cholesterol, urate level and hypertension (HTN). These traits also influenced arterial and cardiac structure and function, especially with regard to left ventricular mass. HTN was identified as a significant mediator, with a mediation effect ratio of 31%. Conclusion: There is a robust causal association between obesity and NICM, and with abnormalities in myocardial structure and function. HTN emerges as a pivotal mediator in the obesity\u2013NICM pathway, underscoring the critical role of managing obesity and HTN in preventing NICM progression.<\/jats:p>","DOI":"10.15420\/cfr.2024.26","type":"journal-article","created":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T06:24:36Z","timestamp":1747031076000},"source":"Crossref","is-referenced-by-count":4,"title":["Obesity Phenotypes Causally Affect Cardiac MRI Structure and Induced Non-ischaemic Cardiomyopathy"],"prefix":"10.15420","volume":"11","author":[{"given":"Long","family":"Peng","sequence":"first","affiliation":[{"name":"Department of Cardiology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Key Laboratory of Liver Disease of Guangdong Province, The Third Af\ufb01liated Hospital of Sun Yat-Sen University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enxi","family":"Quan","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Guangzhou First People\u2019s Hospital, Guangzhou Medical University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shufang","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Key Laboratory of Liver Disease of Guangdong Province, The Third Af\ufb01liated Hospital of Sun Yat-Sen University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Key Laboratory of Liver Disease of Guangdong Province, The Third Af\ufb01liated Hospital of Sun Yat-Sen University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheqi","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaojun","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8899-0103","authenticated-orcid":false,"given":"Yunyue","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"6096","published-online":{"date-parts":[[2025,5,9]]},"reference":[{"key":"ref0","unstructured":"NCD Risk Factor Collaboration (NCD-RisC). 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