{"title":"Association of fat-to-muscle mass ratio with incident coronary artery disease and the potential role of metabolic signatures.","authors":"Kaibo Hu, Yanjun Song, Zhangyu Lin, Zechen Liu, Hao Wang, Kefei Dou","doi":"10.1186/s12933-026-03251-8","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The fat-to-muscle mass ratio (FMR) reflects the balance between metabolic burden and capacity. However, the associations of total and regional FMR with incident coronary artery disease (CAD) and their underlying metabolic mechanisms remain unclear.</p><p><strong>Methods: </strong>We included 398,435 UK Biobank participants free of baseline cardiovascular disease, diabetes, or lipid-lowering therapy. Total and regional (trunk, arm, leg) FMR were quantified via bioelectrical impedance analysis. Participants were stratified by sex and classified based on FMR thresholds derived from restricted cubic splines and BMI categories. Primary outcome was incident CAD, defined as myocardial infarction, coronary revascularization, or CAD mortality. Metabolic signatures were constructed using elastic net regression on 251 NMR metabolites.</p><p><strong>Results: </strong>During a median follow-up of 12.61 years, 10,740 incident CAD cases were documented. Higher total and regional FMR were significantly associated with increased CAD risk in both sexes. Leg FMR exhibited the strongest independent association; after mutual adjustment for BMI, it remained a significant predictor in both women (HR: 3.672, 95% CI 1.958-6.887) and men (HR: 2.682, 95% CI 1.682-4.275), whereas associations for other FMR types were attenuated. Mediation analysis suggested that metabolic signatures partially accounted for the association between FMR and CAD, explaining over 70% of the statistical effect. Furthermore, adding leg FMR to standard risk factors significantly improved risk reclassification (NRI: 0.142 for women, 0.081 for men; both p value < 0.001).</p><p><strong>Conclusions: </strong>Elevated FMR, particularly leg FMR, is strongly associated with higher CAD risk independent of BMI. These findings suggest that altered body composition may reflect underlying metabolic dysregulations, and assessing leg FMR could provide additive value for risk reclassification, particularly in women.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":" ","pages":""},"PeriodicalIF":15.6000,"publicationDate":"2026-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13491944/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cardiovascular Diabetology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12933-026-03251-8","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
引用次数: 0
Abstract
Background: The fat-to-muscle mass ratio (FMR) reflects the balance between metabolic burden and capacity. However, the associations of total and regional FMR with incident coronary artery disease (CAD) and their underlying metabolic mechanisms remain unclear.
Methods: We included 398,435 UK Biobank participants free of baseline cardiovascular disease, diabetes, or lipid-lowering therapy. Total and regional (trunk, arm, leg) FMR were quantified via bioelectrical impedance analysis. Participants were stratified by sex and classified based on FMR thresholds derived from restricted cubic splines and BMI categories. Primary outcome was incident CAD, defined as myocardial infarction, coronary revascularization, or CAD mortality. Metabolic signatures were constructed using elastic net regression on 251 NMR metabolites.
Results: During a median follow-up of 12.61 years, 10,740 incident CAD cases were documented. Higher total and regional FMR were significantly associated with increased CAD risk in both sexes. Leg FMR exhibited the strongest independent association; after mutual adjustment for BMI, it remained a significant predictor in both women (HR: 3.672, 95% CI 1.958-6.887) and men (HR: 2.682, 95% CI 1.682-4.275), whereas associations for other FMR types were attenuated. Mediation analysis suggested that metabolic signatures partially accounted for the association between FMR and CAD, explaining over 70% of the statistical effect. Furthermore, adding leg FMR to standard risk factors significantly improved risk reclassification (NRI: 0.142 for women, 0.081 for men; both p value < 0.001).
Conclusions: Elevated FMR, particularly leg FMR, is strongly associated with higher CAD risk independent of BMI. These findings suggest that altered body composition may reflect underlying metabolic dysregulations, and assessing leg FMR could provide additive value for risk reclassification, particularly in women.
背景：脂肪与肌肉质量比（FMR）反映了代谢负担和代谢能力之间的平衡。然而，总的和局部FMR与冠心病（CAD）的关系及其潜在的代谢机制尚不清楚。方法：我们纳入了398,435名无基线心血管疾病、糖尿病或降脂治疗的英国生物银行参与者。通过生物电阻抗分析定量测定全身和局部（躯干、手臂、腿部）FMR。参与者按性别分层，并根据限制性三次样条和BMI分类得出的FMR阈值进行分类。主要终点是冠心病的发生率，定义为心肌梗死、冠状动脉血运重建术或冠心病死亡率。利用弹性网回归对251种核磁共振代谢物构建代谢特征。结果：在中位随访12.61年期间，记录了10,740例CAD事件。无论男女，较高的总FMR和局部FMR与冠心病风险增加显著相关。下肢FMR表现出最强的独立关联；在相互调整BMI后，它仍然是女性（HR: 3.672, 95% CI 1.958-6.887）和男性（HR: 2.682, 95% CI 1.682-4.275）的显著预测因子，而其他FMR类型的相关性减弱。中介分析表明，代谢特征部分解释了FMR和CAD之间的关联，解释了70%以上的统计效应。此外，将腿部FMR添加到标准危险因素中，显著改善了风险重新分类（女性的NRI为0.142，男性为0.081；两者的p值均为p值）。结论：FMR升高，尤其是腿部FMR，与较高的CAD风险密切相关，独立于BMI。这些发现表明，身体成分的改变可能反映了潜在的代谢失调，评估腿部FMR可以为风险重新分类提供附加价值，特别是在女性中。
期刊介绍：
Cardiovascular Diabetology is a journal that welcomes manuscripts exploring various aspects of the relationship between diabetes, cardiovascular health, and the metabolic syndrome. We invite submissions related to clinical studies, genetic investigations, experimental research, pharmacological studies, epidemiological analyses, and molecular biology research in this field.
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