Abstract
BACKGROUND: The metabolic score of visceral fat (METS-VF) is linked to chronic obstructive pulmonary disease (COPD) incidence, while its association with mortality and adverse outcomes in patients with COPD remains unclear. MATERIALS AND METHODS: We analysed 7246 participants with COPD from the UK Biobank and 869 from US National Health and Nutrition Examination Survey (US NHANES) (1999-2018). METS-VF was categorised into quartiles. In UK Biobank, outcomes included all-cause, cardiovascular disease (CVD), COPD-specific mortality, pulmonary heart disease (PHD), pulmonary embolism (PE) and heart failure (HF); in NHANES, only all-cause and CVD mortality were evaluated. UK Biobank analyses used Cox models, restricted cubic splines, Kaplan-Meier curves, time-dependent receiver operating characteristic (ROC) curves and mediation analysis (C reactive protein (CRP), white blood cell count (WBC), platelet count (PLT)). NHANES served as an external validation cohort using survey-weighted Cox models, subgroup and sensitivity analyses and time-dependent ROC for the two mortality outcomes. RESULTS: In UK Biobank, restricted cubic splines identified non-linear associations of METS-VF with all-cause and CVD mortality, with a common inflection point at 7.03, and linear associations with secondary outcomes. Compared with the lowest quartile, the highest METS-VF quartile showed significantly higher risks of all-cause mortality (HR 1.467), CVD mortality (HR 3.000), COPD-specific mortality (HR 1.952), PHD (HR 3.505), PE (HR 2.301) and HF (HR 2.567). Similar positive associations were observed in NHANES, where the highest METS-VF quartile remained significantly associated with all-cause mortality (HR 3.337) and CVD mortality (HR 3.011). Time-dependent ROC analyses demonstrated modest but stable discrimination across follow-up in both cohorts. Mediation analyses showed that CRP and WBC partially mediated the associations of METS-VF with mortality and cardiopulmonary outcomes, whereas PLT did not exhibit significant mediation effects. CONCLUSIONS: Elevated METS-VF is consistently associated with increased long-term risks of mortality and cardiopulmonary complications in COPD across independent discovery and validation cohorts. METS-VF may serve as a practical prognostic biomarker for risk stratification in the clinical management of COPD.