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Although high adiposity and muscle loss\/dysfunction are thought to synergistically increase the risk of cardiovascular disease (CVD), few studies have addressed the association between dynapenic and sarcopenic obesity and CVD. We aimed to investigate the association of dynapenic obesity with incident CVD events using the data from a population\u2010based prospective longitudinal study in Japan.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 2490 community\u2010dwelling Japanese aged 40\u201379\u00a0years (42.5% males, mean age 57.7\u00a0\u00b1\u00a010.6\u00a0years) without a history of CVD were followed up for a median of 24\u00a0years. Handgrip strength was classified as low, medium, or high by age\u2010 and sex\u2010specific tertiles. Body mass index (BMI) levels were categorized as lean (&lt;18.5\u00a0kg\/m<jats:sup>2<\/jats:sup>), normal (18.5\u201324.9\u00a0kg\/m<jats:sup>2<\/jats:sup>), or obese (\u226525.0\u00a0kg\/m<jats:sup>2<\/jats:sup>). Dynapenic obesity was defined as having both low handgrip strength and obesity. The outcomes were defined as the first\u2010ever development of CVD (defined as stroke or coronary heart disease). The hazard ratios (HRs) and their 95% confidence intervals (CIs) for the development of CVD were estimated using a Cox proportional hazards model, in which participants with high handgrip strength and normal BMI were used as a reference group. Mediation analyses used serum high\u2010sensitivity C\u2010reactive protein (hs\u2010CRP) and homeostatic model assessment for insulin resistance (HOMA\u2010IR) as mediators.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>During the follow\u2010up period, 482 participants developed CVD events (324 cases of stroke and 209 of coronary heart disease). The multivariable\u2010adjusted risk of CVD increased significantly among participants with dynapenic obesity compared with the reference group (HR 1.49, 95% CI 1.03\u20132.17). An analysis by age groups showed a further increase in the risk of CVD among participants with dynapenic obesity aged less than 65\u00a0years (HR 1.66, 95% CI 1.04\u20132.65). In mediation analyses for participants aged less than 65\u00a0years, serum hs\u2010CRP was shown to be a significant mediator explaining 13.8% of the association between dynapenic obesity and the development of CVD, while HOMA\u2010IR explained 12.2% of this relationship.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Dynapenic obesity was a significant risk factor for the development of CVD in a general Japanese population. This association was more pronounced among those aged &lt;65\u00a0years. Inflammation, and possibly glucose metabolism, might partly mediate this association. Our findings suggest that preventing muscle dysfunction as well as appropriate weight control, especially in middle\u2010age, are important for preventing the development of CVD.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.13564","type":"journal-article","created":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T17:13:20Z","timestamp":1728407600000},"page":"2338-2348","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Association between dynapenic obesity and risk of cardiovascular disease: The Hisayama study"],"prefix":"10.1002","volume":"15","author":[{"given":"Yu","family":"Setoyama","sequence":"first","affiliation":[{"name":"Department of Epidemiology and Public Health, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"},{"name":"Department of Orthopaedic Surgery, Graduate School of Medical Sciences Kyushu University  Fukuoka 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