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

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.