What is the clinical evidence from this study?

Study design: Cohort. Population: Coronary artery disease (n=398435). Intervention: Fat-to-muscle mass ratio (FMR) vs. Lower fat-to-muscle mass ratio. Primary outcome: Incident coronary artery disease (myocardial infarction, coronary revascularization, or CAD mortality) (HR 3.672, 95% CI 1.958-6.887).

What question did this study set out to answer?

This research aims to explore the relationship between fat-to-muscle mass ratio and the risk of coronary artery disease, along with its metabolic mechanisms.

June 14, 2026Cardiovascular Diabetology0 citationsOpen Access

Association of fat-to-muscle mass ratio with incident coronary artery disease and the potential role of metabolic signatures

KHKaibo HuChinese Academy of Medical Sciences & Peking Union Medical College YSY SongChinese Academy of Medical Sciences & Peking Union Medical College ZLZhangyu LinChinese Academy of Medical Sciences & Peking Union Medical College

Key Result

Elevated leg fat-to-muscle mass ratio was strongly associated with increased incident coronary artery disease risk in women (HR 3.672) and men (HR 2.682), independent of BMI.

Key Points

This research aims to explore the relationship between fat-to-muscle mass ratio and the risk of coronary artery disease, along with its metabolic mechanisms.
Included 398,435 UK Biobank participants free of cardiovascular disease, diabetes, or lipid-lowering therapy.
Quantified total and regional fat-to-muscle mass ratio using bioelectrical impedance analysis.
Conducted mediation analysis using elastic net regression on 251 NMR metabolites.
Observed 10,740 cases of incident coronary artery disease during a median follow-up of 12.61 years.
Leg fat-to-muscle mass ratio was a significant predictor of CAD risk (HR: 3.672 for women, HR: 2.682 for men).
Adding leg fat-to-muscle mass ratio to standard risk factors significantly improved risk reclassification (NRI: 0.142 for women, 0.081 for men; both p < 0.001).

Study Design

Type

Cohort (n=398,435)

Multicenter

Yes

Structured PICO

Does a higher fat-to-muscle mass ratio (FMR) increase the risk of incident coronary artery disease in individuals free of baseline cardiovascular disease?

Population

398,435 UK community-dwelling adults free of baseline cardiovascular disease, diabetes, and lipid-lowering therapy, followed for a median of 12.61 years.

Exposure

Higher total and regional (trunk, arm, leg) fat-to-muscle mass ratio (FMR) quantified via bioelectrical impedance analysis

Comparator

Lower fat-to-muscle mass ratio (FMR)

Outcome

Incident CAD, defined as myocardial infarction, coronary revascularization, or CAD mortalityhard clinical

Elevated fat-to-muscle mass ratio, particularly in the legs, is strongly associated with higher CAD risk independent of BMI and improves risk reclassification.

Main Result

Hazard Ratio: 3.672 (95% CI 1.958–6.887)

Limitations

Body composition was measured using BIA, which is less accurate than DXA or MRI and may be influenced by hydration status.
Temporal mismatch exists as NMR metabolomics data were acquired years after the baseline body composition assessment, precluding definitive causal inference.
Observational study design leaves potential for residual confounding from unmeasured socioeconomic factors, dietary details, or inflammatory markers.
The study population predominantly comprised European Caucasians, limiting generalizability to other ethnic groups.

Abstract

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. 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. 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). 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.

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Cite This Study

Hu et al. (Sat,) conducted a cohort in Coronary artery disease (n=398,435). Fat-to-muscle mass ratio (FMR) vs. Lower fat-to-muscle mass ratio was evaluated on Incident coronary artery disease (myocardial infarction, coronary revascularization, or CAD mortality) (HR 3.672, 95% CI 1.958-6.887). Elevated leg fat-to-muscle mass ratio was strongly associated with increased incident coronary artery disease risk in women (HR 3.672) and men (HR 2.682), independent of BMI.

synapsesocial.com/papers/6a2e69a9bde31496c9a7a720 https://doi.org/https://doi.org/10.1186/s12933-026-03251-8

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