Frailty as a Key Determinant of Cardiovascular Risk and Mortality in Preserved Ratio Impaired Spirometry: A Nationally Representative Study

BACKGROUND: Preserved ratio impaired spirometry (PRISm) is associated with elevated cardiovascular disease (CVD) risk and progression to COPD, but the underlying mechanisms remain unclear. Frailty is known to worsen outcomes in COPD; however, its role in PRISm has not been well defined. This study examined factors associated with cardiovascular events and mortality in PRISm and developed risk models. METHODS: < 80% predicted). Frailty was assessed using the 23-item laboratory frailty index (FI-LAB; cut-off ≥ 0.23). The primary outcome was all-cause mortality, obtained from linked National Death Index records; the secondary outcome was major adverse cardiovascular events (MACEs: myocardial infarction, stroke, heart failure, or angina), assessed cross-sectionally. LASSO regression and multivariable logistic/Cox models were used to identify variables independently associated with the outcomes, and nomograms were constructed. RESULTS: PRISm participants had higher frailty prevalence (53.9% vs. 45.5%) and more MACEs (16.2% vs. 6.0%) than those with normal spirometry (both p < 0.0001). Frailty was independently associated with prevalent MACEs (adjusted OR = 18.87, p < 0.001) and was bidirectionally associated with PRISm (OR = 1.40, p < 0.001). Key factors independently associated with MACEs included frailty index, age, sex, anemia, and emphysema (AUC = 0.786). Over 9.9 years, mortality was higher in frail vs. non-frail PRISm individuals (15.2% vs. 7.0%; adjusted HR = 30.66). Frailty severity demonstrated a clear mortality gradient, and a mortality nomogram integrating age and frailty achieved an AUC of 0.81. CONCLUSION: Frailty is strongly and independently associated with cardiovascular morbidity and mortality. FI-LAB offers a practical tool for risk stratification and may help guide targeted preventive strategies.