J Clin Endocrinol Metab. 2025 Dec 22:dgaf684. doi: 10.1210/clinem/dgaf684. Online ahead of print.
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: 22,789 participants (mean age 64.1±7.5 years, 52.6% female) were categorized as metabolically healthy non-obese (MHN) vs. obese (MHO), unhealthy non-obese (MUN) vs. obese (MUO), based on obesity (BMI ≥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 (LVM, g), wall thickness (WT, mm), cardiac output (CO, L/min), and left atrial volume (LAV, 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=0.53 [0.50, 0.55]; MUN: β=0.24 [0.21, 0.27]; MUO: β=0.66 [0.61, 0.70]), 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, -0.55]), while MUO showed reduced LVEF (β=-0.48 [-0.91, -0.04]). MACE risk was increased in unhealthy phenotypes (MUN: 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]).
CONCLUSIONS: Metabolic phenotypes show distinct cardiac structural changes and increased mortality risk, supporting their potential in cardiovascular risk stratification.
PMID:41428372 | DOI:10.1210/clinem/dgaf684