Association between metabolic score for visceral fat and adverse outcomes in chronic obstructive pulmonary disease

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.

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.

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.

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.