LAUSR

This compendium presents a broad overview of aortic aneurysms with reviews ranging from basic mechanism of disease to therapies. We have specifically focused on thoracic aortic aneurysms (TAAs) and abdominal aortic aneurysms (AAAs) because they are the most common in clinical practice and the major focus of current research efforts. Although these 2 diseases share some features in common, it will become evident from reading this compendium that they are distinct diseases with only partial overlap of disease mechanism and therapy. Aortic aneurysms are defined as a localized dilation exceeding at least 50% of the normal diameter of the aorta, and the infrarenal abdominal aorta is the most common site of aneurysm formation in the aorta. AAAs predominantly affect elderly males with a prevalence of 4% to 7% and an incidence of 55 per 100 000 people per year in individuals aged 65 to 74 years. AAA incidence increases to 112 per 100 000 people per year and 298 per 100 000 people per year, in males aged 75 to 85 years and >85 years, respectively. Females aged 65 to 80 years have an AAA prevalence of 1.3%, 6× lower than that of males. TAAs are less common than AAAs, with a prevalence of 0.16% to 0.34% and an incidence of 7.6 per 100 000 people per year. The mean age at diagnosis is 67.3±14.8, and men are predominantly affected. However, TAA growth rate is faster, and rupture and death are more common in women compared with men. In contrast to AAA, ≈20% of patients with TAA have a familial nonsyndromic variant of TAA. Familial nonsyndromic TAAs are diagnosed at a younger age, have a faster growth rate compared with sporadic TAA, and autosomal dominant is the most common mode of inheritance described. Thus, TAAs are the result of much more heterogeneous disease processes. There are both common and disparate risk factors for AAA and TAA. Tobacco use is the strongest lifestyle-related risk factor associated with AAA formation, and the number of pack-years positively correlates with the risk of AAA formation. Smoking less than half a pack of cigarettes per day for 10 years significantly increased the odds (odds ratio, 2.61) of developing an AAA. These odds increase ≤12.13 in individuals who smoked >1 pack per day for >35 years. Other risk factors associated with AAA development are male sex, advanced age, white race, family history, and to a lesser degree, atherosclerotic cardiovascular disease. Sporadic TAA and AAA development share multiple risk factors, including smoking and atherosclerotic cardiovascular disease, but there are distinct differences in terms of the magnitude of the impact of these risk factors and the contribution of hypertension. Female sex and nonwhite race are considered protective factors for AAA formation, whereas only female sex is protective in sporadic TAA. Diabetes mellitus—a well-known risk factor for atherosclerosis—is a protective factor for both AAA and TAA formation. Additionally, exposure to fluoroquinolone antibiotics has recently been associated with increased risk of aortic aneurysms. Research on aortic aneurysms has involved a wide range of approaches, including studies of isolated cells and animal models, the use of human specimens to study the pathology, biology, and genetics of these diseases, and ultimately clinical trials to study the efficacy of surgical and pharmacological therapeutics. The 3 articles focused on disease mechanism, Cellular Mechanisms of Aortic Aneurysm Formation, Role of Noncoding RNAs in the Pathogenesis of Abdominal Aortic Aneurysm: Possible Therapeutic Targets?, and Genetics of Thoracic and Abdominal Aortic Diseases: Aneurysms, Dissections, and Ruptures, review our current understanding of the pathogenesis of aneurysms and highlight the unknowns in these areas and areas for further study. Animal models have played a major role in developing our current knowledge base and have opened new avenues of investigation that have led to an explosion in publications. Common methodologies that are in use employ elastase infusion, application of CaCl 2 , angiotensin II administration, and lysl oxidase inhibitors to produce aneurysms. Unfortunately, none of the current models of abdominal or thoracic aneurysms completely recapitulate the human diseases. Similarly, unique genetic models used either alone or in combination with the inducible models are very helpful for causality but are sometimes limited by defining necessary but not sufficient contributions of specific genes. Studies utilizing human materials have been much more common in the study of TAA and have led to great insights into the genetic basis of familial and syndromic thoracic aneurysms. In the study of mechanisms of both TAA and AAA, we need to continue to explore new models of disease and to correlate these with findings form human tissues. In addition, we should not automatically assume that defining the mechanisms of disease initiation in an animal model will lead to a successful therapeutic strategy because mechanisms may differ between initiation, growth and rupture, or dissection. As clearly pointed out in the section of this compendium on Pharmacological Management The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association. From the Division of Cardiology, Department of Medicine (R.A.Q., W.R.T.) and Wallace H. Coulter Department of Biomedical Engineering Georgia Institute of Technology (W.R.T.), Emory University School of Medicine, Atlanta, GA; and Division of Cardiology, Atlanta VA Medical Center, Decatur, GA (W.R.T.). Correspondence to W. Robert Taylor, MD, PhD, Division of Cardiology, Emory University School of Medicine, 101 Woodruff Cir, Suite 319 WMB, Atlanta, GA 30322. Email [email protected] Editorial