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

Abstract

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.

Keywords: chronic obstructive pulmonary disease; electronic health record; frailty; healthy longevity; major adverse cardiovascular events.

Figure 1

Study timeline. The index date was defined as the date of the earliest diagnostic code for COPD (ICD-10 codes: J42, J43, and 44). The end of follow-up was defined as the date of the first MACE occurrence, loss to follow-up, or March 31, 2023 (the end of the study period).

Figure 2

Flow diagram of the inclusion/exclusion of COPD participants in this study. For the analysis of the present study, a total of 1527 patients with COPD were enrolled.

Figure 3

The Kaplan–Meier curves show cumulative incidence of MACE (any of acute coronary syndrome, heart failure, and stroke) in COPD patients in four frailty categories: No-frailty, HFRS=0 (blue line); low, HFRS >0 and <5 (green line); intermediate, HFRS ≥5 and <15 (Orange line); high, HFRS ≥15 (red line).