Opportunistic screening for incident cardiometabolic disease in metabolically healthy non-obese individuals: a prospective cohort study.

Abstract

Background: Metabolically healthy non-obese (MHN) individuals are considered at low cardiometabolic risk, yet a subset may harbor unfavorable visceral adiposity not captured by conventional anthropometric measures, including waist circumference (WC) and BMI.

Methods: We conducted a prospective cohort study of 22,040 UK Biobank participants (median follow-up 4.2 years [interquartile range 3.4-5.6]) defined as MHN (BMI < 30 kg/m², absence of diabetes or concurrent hypertension and hyperlipidemia). Visceral (VAT) and subcutaneous adipose tissue (SAT) volumes were quantified from whole-body MRI using a validated deep learning framework. Sex-specific VAT/SAT ratio cutoffs were derived from the German National Cohort based on prevalent cardiometabolic disease and applied to the UK Biobank. The primary outcome was incident major adverse cardiovascular events (MACE); the secondary outcome was incident type 2 diabetes. Categorical net reclassification improvement (NRI), quantifying the net proportion of individuals correctly reclassified between predefined risk categories, compared VAT/SAT ratio versus WC as competing classification approaches. Cox proportional hazards models assessed associations with outcomes after stepwise adjustment for age, sex, smoking, WC, and BMI. Nested models with and without VAT/SAT ratio were compared to test for added value beyond other factors.

Results: The VAT/SAT ratio improved risk classification over WC for MACE (NRI 0.088, 95%CI 0.019-0.158, p = 0.013) and diabetes (NRI 0.102, 95% CI 0.024-0.181, p = 0.010). High VAT/SAT ratio independently predicted MACE (adjusted hazard ratio [aHR] 1.30, 95%CI 1.02-1.66, p = 0.037) and diabetes (aHR 1.77, 95% CI 1.34-2.33, p < 0.001) after full adjustment. Adding VAT/SAT to fully adjusted models improved discrimination for MACE (C-index 0.694 vs. 0.690, p = 0.036) and diabetes (C-index 0.723 vs. 0.715, p < 0.001).

Conclusion: The VAT/SAT ratio identifies MHN individuals at elevated cardiometabolic risk beyond conventional anthropometric measures, with particularly strong associations for incident diabetes. These findings support the concept of opportunistic imaging-based risk assessment and provide the prognostic foundation for future trials investigating whether targeted intervention in VAT/SAT-reclassified individuals improves outcomes.