Does Medical Therapy for Thoracic Aortic Aneurysms Really Work? Are b -Blockers Truly Indicated? CON Steve L. Liao, MD a,b , Sammy Elmariah, MD b , Sarina van der Zee, MD b , Brett A. Sealove, MD b , Valentin Fuster, MD, PhD b,c, * Thoracic aortic aneurysms (TAA) often represent the final manifestation of hereditary or degenerative disease processes. TAA are primarily caused by age-related degenerative changes, although many other factors may play a role. The pathogen- esis of TAA is characterized by an imbalance in the regulatory mechanisms that normally act to stabi- lize aortic wall integrity, and is triggered or acceler- ated by hereditary factors and atherosclerotic risk factors such as smoking, hypertension, age, and male gender. Once an aneurysm develops, anatomic and hemodynamic features contribute to its expansion. 1 Although recent data support inhibition of the renin-angiotensin system in delaying and even reversing aortic dilatation, other medical therapies have shown less convincing efficacy in TAA. In this article, the authors highlight the most common pathophysiologic mechanisms responsible for TAA formation (Fig. 1) and review the paucity of evidence supporting the spectrum of medical ther- apies for TAA other than renin-angiotensin inhibition. ANEURYSM FORMATION Homeostasis of the aortic wall is maintained by several enzymes and growth factors that include transforming growth factor (TGF)-b, matrix metal- loproteinases (MMPs), and tissue inhibitors of matrix metalloproteinases (TIMPs). The TGF- b family of growth factors regulates cell survival, proliferation, differentiation, tissue morphogen- esis, and cellular response to injury, whereas MMPs process or degrade numerous extracellular substrates. 2,3 Almost all types of vascular cells, including endothelial cells, vascular smooth muscle cells (VSMCs), and adventitial fibroblasts, secrete MMPs in normal conditions. The relative concentration of active MMPs and TIMPs deter- mines net proteolytic activity. 3,4 Aging, environmental factors, and connective tissue abnormalities compromise the ability of the aorta to withstand high pressure. 5 The first degenerative change noted in the aging aorta is cystic medial degeneration (CMD), an accumula- tion of mucopolysaccharide cysts within the aortic a James J. Peters Veteran Affairs Medical Center, Cardiovascular Division, Department of Medicine, Bronx, NY, USA b The Zena and Michael A. Wiener Cardiovascular Institute, The Marie-Josee and Henry R. Kravis Center for Cardiovascular Health, The Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1030, New York, NY 10029, USA c Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain * Corresponding author. The Zena and Michael A. Wiener Cardiovascular Institute, The Marie-Josee and Henry R. Kravis Center for Cardiovascular Health, The Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1030, New York, NY 10029. E-mail address: valentin.fuster@mssm.edu KEYWORDS  Aortic aneurysm  Medical therapy  b-Blockers Cardiol Clin 28 (2010) 261–269 doi:10.1016/j.ccl.2010.01.002 0733-8651/10/$ – see front matter. Published by Elsevier Inc. cardiology.theclinics.com