Impact of Frailty on Major Adverse Cardiovascular Events in Chronic Obstructive Pulmonary Disease

PURPOSE: Chronic obstructive pulmonary disease (COPD) is associated with frailty and leads to poor outcomes. The relationship between COPD and cardiovascular events is well established. However, the impact of frailty on cardiovascular events in COPD patients remains unknown. We aimed to evaluate the long-term association between frailty, assessed using the hospital frailty risk score (HFRS), and major adverse cardiovascular events (MACE) in COPD patients. PATIENTS AND METHODS: We recruited Japanese patients with COPD between 2013 and 2023 from Sado-Himawari Net, a regional electronic health record system in Sado City, Niigata Prefecture, Japan. MACE were defined as a composite of acute coronary syndrome, heart failure, and stroke. We classified the participants into four frailty categories according to HFRS: no-frailty with HFRS=0, low with HFRS >0 and <5, intermediate with HFRS ≥5 and <15, and high with HFRS ≥15. We used a Cox regression model adjusted for age, sex, inhaled treatments, and comorbidities to evaluate the hazard ratio (HR) for MACE. RESULTS: We recruited 1527 patients with COPD. In multivariable analysis, COPD was associated with MACE as follows: no-frailty versus low HFRS (HR, 1.47 [95% confidence interval, 1.01-2.14], p<0.05), intermediate HFRS (HR 2.00 [1.34-2.97], p<0.001), and high HFRS (HR 2.62 [1.50-4.59], p<0.001). Similar relationships were observed even after adjusting for the severity of airflow limitation and COPD exacerbation. CONCLUSION: Frailty was independently associated with MACE in COPD patients during the 10-year follow-up period. Frailty assessment supports the identification of patients with COPD at risk of MACE.