Associations of Metabolic Phenotypes with Cardiac Structure and Clinical Outcomes: Insights from the UK Biobank

Clinical Snapshot

Key Findings

• P Value: Not explicitly reported for primary outcomes

• Effect Size: MUN: aHR 1.55; MUO: aHR 1.95

• Primary Outcome: MACE risk increased in metabolically unhealthy phenotypes

• Nnt Or Sensitivity: All-cause mortality: MHO aHR 1.65 (1.23-2.21), MUN aHR 1.41 (1.05-1.90), MUO aHR 2.10 (1.41-3.15)

• Confidence Interval: MUN: 95% CI 1.16-2.07; MUO: 95% CI 1.28-2.97

Clinical Application

Metabolic phenotyping feasible in routine practice; CMR limited to specialized centers Relevant to Australian obesity epidemic; aligns with RACGP cardiovascular risk assessment guidelines; CMR availability through public and private systems Middle-aged to older adults undergoing cardiovascular risk assessment, particularly those with obesity or metabolic dysfunction

Abstract

CONTEXT: Metabolic syndrome and obesity represent major cardiovascular risk factors, yet their combined effects on cardiac structure and clinical outcomes remain incompletely understood. OBJECTIVE: To examine associations between metabolic phenotypes, cardiac magnetic resonance imaging (CMR), and clinical outcomes. DESIGN: Prospective study with a median 5.1-year follow-up. SETTING: Population-based cohort from the UK Biobank. PARTICIPANTS: A total of 22 789 participants (mean age 64.1 ± 7.5 years, 52.6% female) were categorized as metabolically healthy nonobese (MHN) vs obese (MHO) or unhealthy nonobese (MUN) vs obese (MUO), based on obesity (body mass index ≥30 kg/m²) and metabolic status (prevalent diabetes or both hypertension and hyperlipidemia). MAIN OUTCOME MEASURE(S): Primary and secondary endpoints were major adverse cardiovascular events (MACE) and all-cause mortality, respectively. CMR included left ventricular ejection fraction (LVEF, %), end-diastolic volume (LVEDV, mL), myocardial mass (g), wall thickness (mm), cardiac output (L/min), and left atrial volume (mL). Linear regression and Cox proportional hazards models, adjusted for age, sex, and smoking, assessed associations between metabolic phenotypes, CMR, and clinical outcomes. RESULTS: In adjusted models, all phenotypes demonstrated increased WT (MHO: β=.53 [.50, .55]; MUN: β=.24 [.21, .27]; MUO: β=.66 [.61, .70]), compared to MHN. LVEDV was increased in obesity phenotypes (MHO: β=4.67 [4.07, 5.27]; MUO: β=5.14 [4.05, 6.22]) and decreased in MUN (β=-1.25 [-1.95, -.55]), while MUO showed reduced LVEF (β=-.48 [-.91, -.04]). MACE risk was increased in unhealthy phenotypes (MUN: adjusted hazard ratio (aHR) = 1.55 [1.16-2.07]; MUO: aHR = 1.95 [1.28-2.97]). All phenotypes showed increased all-cause mortality risk (MHO: aHR = 1.65 [1.23-2.21]; MUN: aHR = 1.41 [1.05-1.90]; MUO: 2.10 [1.41-3.15]). CONCLUSION: Metabolic phenotypes show distinct cardiac structural changes and increased mortality risk, supporting their potential in cardiovascular risk stratification.

References

1. 1.Bogner, B., Jung, M., Reisert, M., Maushagen, J., Rospleszcz, S., Nolde, J. M., Schlett, C. L., Bamberg, F., Kammerlander, A., Weiss, J., & Taron, J. (2026). Associations of metabolic phenotypes with cardiac structure and clinical outcomes: Insights from the UK Biobank. The Journal of Clinical Endocrinology and Metabolism. https://doi.org/10.1210/clinem/dgaf684