Angiotensin Receptor Blockers Restore Skeletal Muscle in Patients with Chronic Obstructive Pulmonary Disease

Abstract

Age-related muscle decline, called sarcopenia, and hypertension are commonly observed in patients with chronic obstructive pulmonary disease (COPD). Angiotensin receptor blockers (ARBs) are common antihypertensive medications with muscle protective effects. However, the anti-sarcopenic potential and associated mechanisms of ARBs in hypertensive patients with COPD are unknown. We aimed to investigate the potential contribution of neuromuscular junction (NMJ) stability as a driving mechanism of ARBs-induced muscle protection. We categorized 236 patients with COPD into normotensive (n = 79) and hypertensive, based on treatment with ARB (n=82), and other antihypertensive drugs (n = 75). Hypertensive patients with COPD were evaluated at two time points one year apart. Handgrip strength (HGS), body composition, short physical performance battery (SPPB), and plasma c-terminal agrin fragment-22 (CAF22) as a marker of NMJ degradation were measured. Patients with COPD exhibited reduced HGS and SPPB scores, and higher levels of CAF22 than controls, regardless of hypertension status. ARBs treatment improved HGS and gait speed and reduced plasma CAF22 levels in hypertensive patients with COPD (all p <0.05). ARBs also prevented the decline in SPPB components, including maintaining balance, gait speed, and the ability to rise from a chair in hypertensive patients with COPD (all p <0.05). We also found dynamic associations of plasma CAF22 with HGS, gait speed, and SPPB scores in hypertensive patients with COPD. Altogether, ARB treatment preserves skeletal muscle health and functional capacity in hypertensive patients with COPD by reducing plasma CAF22 and possibly repairing NMJs.