Abstract Rationale Preserved Ratio Impaired Spirometry (PRISm) is associated with elevated risks of cardiovascular disease (CVD) and progression to chronic obstructive pulmonary disease (COPD), yet the underlying mechanisms remain unclear. Frailty is a key determinant of poor outcomes in COPD, but its relevance to PRISm remains unknown. Objectives To investigate the associations of frailty with cardiovascular outcomes and mortality among individuals with PRISm. Methods We analyzed 8,882 adults (aged 20-79 years) from NHANES 2007-2012. PRISm was defined as FEV1/FVC ≥0.7 with FEV1 80% predicted; 763 participants (8.6%) met these criteria. Frailty was measured using a 21-item laboratory frailty index (FI-LAB, frail ≥0.23). The primary outcomes were major adverse cardiovascular events (MACEs: myocardial infarction, stroke, heart failure, or all-cause mortality) and long-term mortality. Predictors were identified via LASSO regression and assessed using multivariable logistic and Cox models. Nomograms were constructed and validated for risk prediction. Results PRISm participants had a higher prevalence of frailty (53.9% vs. 45.5%, p0.0001) and MACEs (16.2% vs. 6.0%, p0.0001) than those with normal spirometry. Frailty independently predicted MACEs in PRISm (adjusted OR = 18.87, p0.001) and was bidirectionally associated with PRISm (OR = 1.40, p0.001). Over a 9.9-year median follow-up, frail PRISm individuals had markedly higher mortality (15.2% vs. 7.0%, p0.0001; adjusted HR = 30.66, p=0.001). Mortality increased stepwise with frailty severity (7.0% pre-frail to 22.3% severely frail). The mortality nomogram integrating age, frailty, myocardial infarction, and heart failure achieved strong discrimination (10-year AUC=0.81). Conclusions Frailty is a robust, independent predictor of cardiovascular morbidity and mortality in PRISm, suggesting shared systemic vulnerability and overlapping pathophysiology. FI-LAB offers a practical tool for early risk stratification, supporting targeted interventions to reduce CVD burden in this high-risk phenotype. This abstract is funded by: Noncommunicable Chronic Diseases-National Science and Technology Major Project (2023ZD0506200, 2023ZD0506205)
Ren et al. (Fri,) studied this question.