Emerging Anti-Inflammatory COPD Treatments: Potential Cardiovascular Impacts

Abstract

Chronic obstructive pulmonary disease (COPD) is a progressive inflammatory condition often complicated by cardiovascular disease (CVD) due to shared inflammatory pathways. This review explores the cardiovascular impacts of emerging anti-inflammatory therapies in COPD. Phosphodiesterase (PDE) inhibitors may offer anti-inflammatory effects with improved lung function but pose potential risks for arrhythmias when PDE3 is inhibited although PDE4 inhibitors reduce cardiovascular events by improving endothelial function and reducing thrombosis. Similarly, p38 mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) inhibitors target COPD-related inflammation and may benefit COPD patients with CVD. p38 MAPK inhibitors reduce cardiac fibrosis, enhance contractility and lower the risk of arrhythmia. PI3K inhibitors target the PI3K/Akt pathway, which drives atherosclerosis and cardiac fibrosis, and thus potentially mitigate both plaque instability and fibrosis. Biologic therapies, including monoclonal antibodies that inhibit IL-5, IL-13/IL-4, thymic stromal lymphopoietin, IL-33, and IL-17A, show promise in reducing exacerbations but require close cardiovascular monitoring due to their immunomodulatory effects. Single-target inhibitors of neutrophil elastase or matrix metalloproteinases show limited efficacy in COPD but may aid cardiovascular patients by stabilizing atherosclerotic plaques through promoting vascular smooth muscle cell proliferation. However, their tendency to degrade the extracellular matrix and attract immune cells may heighten plaque rupture risk, contraindicating use in CVD. Alpha-1 antitrypsin replacement therapy holds promise, potentially reducing COPD exacerbations and providing cardiovascular protection, especially in myocardial injury. Understanding the influence of these innovative therapies on CVD is vital, making it imperative to examine these molecules in COPD patients with CVD at an early stage.