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

## TL;DR

Frailty is a strong predictor of cardiovascular risk and death in people with preserved ratio impaired spirometry, suggesting it should be used to guide prevention strategies.

## Contribution

This study identifies frailty as a novel and significant independent risk factor for cardiovascular events and mortality in PRISm patients.

## Key findings

- Frailty was independently associated with cardiovascular events (adjusted OR = 18.87) in PRISm individuals.
- Frailty severity showed a clear mortality gradient, with frail PRISm individuals having a 30.66-fold higher risk of death.
- A mortality nomogram integrating age and frailty achieved an AUC of 0.81, demonstrating good predictive accuracy.

## Abstract

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.

We analyzed 8882 adults (aged 20–79 years) from NHANES 2007–2012, identifying 763 (8.6%) with PRISm (FEV1/FVC ≥ 0.70 and FEV1 < 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.

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.

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.

In adults with preserved ratio impaired spirometry (PRISm), frailty was common and strongly associated with increased cardiovascular events and all‐cause mortality. Frailty significantly improved risk stratification beyond traditional clinical factors. A frailty‐based nomogram demonstrated good discrimination and calibration, highlighting frailty as a key determinant of adverse outcomes in PRISm.