Long‐Acting Beta‐Agonist Use is Associated with Lower Carotid Artery Stiffness and Greater Carotid Artery Compliance in Individuals with Chronic Obstructive Pulmonary Disease

Abstract

BackgroundCardiovascular disease (CVD) is the most prevalent comorbidity in individuals with chronic obstructive pulmonary disease (COPD). Elevated large elastic artery stiffness (i.e. carotid and aorta) is a robust predictor of CVD events and mortality and is associated with airway obstruction in COPD patients, suggesting that large artery stiffness may contribute, at least in part, to the high CVD risk in COPD. Previous studies demonstrate that in COPD patients, bronchodilator therapy improves respiratory symptoms, lowers the risk of exacerbations and reduces aortic stiffness, as measured by carotid‐femoral pulse wave velocity (CFPWV), in COPD patients with a very high CFPWV (≥ 11 m/s). However, the long‐term benefits of bronchodilator therapy on cardiovascular risk remain controversial. We hypothesized that individuals with COPD who reported using a long‐acting beta‐agonist (LABA) or an inhaled corticosteroid (ICS) would have lower carotid artery stiffness/greater compliance compared with COPD patients not on LABAs or ICSs.MethodsSixty‐three adults with COPD (age 70 ± 7 yrs; 23M/40F; GOLD stage 1–4; 6% stage 1, 47% stage 2, 24% stage 3, 23% stage 4) completed measurements of common carotid artery stiffness and compliance (carotid artery ultrasound and tonometry) and were retrospectively stratified by self‐report of LABA and ICS use.ResultsThirty‐two (49%) participants reported using a LABA/ICS combination bronchodilator. Seven (11%) of patients reported using a LABA alone and 7 (11%) of patients reported using an ICS alone. COPD patients using a LABA/ICS combination bronchodilator had significantly lower carotid β‐stiffness (8.7 ± 0.5 vs. 10.9 ± 0.9 U, P=0.04) and greater carotid compliance (0.11 ± 0.01 vs. 0.08 ± 0.01 mm/mmHg, P=0.01) compared with patients not using a LABA/ICS. This difference remained significant after adjusting for age, gender, BMI, oxygen use and smoking pack‐years (carotid β‐stiffness P=0.04; carotid compliance P=0.05). BP, heart rate and oxygen saturation did not differ between COPD patients using vs. not using a LABA/ICS. Furthermore, patients that reported using a LABA alone, and not in combination with an ICS, had significantly lower carotid β‐stiffness (6.9 ± 0.6 vs. 10.1 ± 0.6 U, P<0.01), but not greater carotid compliance (0.11 ± 0.01 vs. 0.09 ± 0.01 mm/mmHg, P=0.2) compared with those not using a LABA. In contrast, there was no difference in carotid β‐stiffness (9.0 ± 1.2 vs. 9.9 ± 0.6 U, P=0.60) or carotid compliance (0.10 ± 0.01 vs. 0.10 ± 0.01 mm/mmHg, P=0.93) between COPD patients that reported using vs. not using an ICS.ConclusionThese data indicate that COPD patients who are taking a LABA, either in combination with an ICS or alone, have lower carotid artery stiffness than those not taking a LABA. This finding raises the possibility that LABAs may be beneficial in reducing the CVD risk observed in COPD, however randomized, controlled clinical trials are needed to test whether LABAs impact CVD risk.Support or Funding InformationNIH K23 HL095658, R01 HL089897, NIH/NCATS CTSI UL1 TR001082This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.