Rudolph Virchow (1821-1902) recognized inflammation in histological preparations of coronary arteries and proposed that inflammation plays a causal role in atherosclerosis. Despite this seminal observation, the main focus of research and drug development programs has been cholesterol alone, and inflammation received less attention over time. However, during the past several decades extensive observations supported the importance of inflammation in the development and destabilization of atherosclerosis. Studies in patients affected by rheumatological diseases suggested an interaction between chronic inflammation and atherosclerotic cardiovascular disease. Randomized clinical studies with lipid lowering agents suggested that part of the beneficial effect may have been related to reduction in inflammation. More recently, a few studies were designed to directly address the role of anti-inflammatory treatments in reducing risk of atherosclerotic heart disease beyond traditional risk factors. In this article, we review the pathophysiologic contribution of inflammation to atherosclerosis, biomarkers of inflammation and the evidence collected in observational studies regarding the role of chronic inflammation in the development of atherosclerotic heart disease. Finally, we discuss the most recent randomized clinical trials of anti-inflammatory agents directed at stemming atherosclerotic cardiovascular disease.

Background-We sought to investigate the use of a new parameter, the projected effective orifice area (EOA proj ) at normal transvalvular flow rate (250 mL/s), to better differentiate between truly severe (TS) and pseudo-severe (PS) aortic stenosis (AS) during dobutamine stress echocardiography (DSE). Changes in various parameters of stenosis severity have been used to differentiate between TS and PS AS during DSE. However, the magnitude of these changes lacks standardization because they are dependent on the variable magnitude of the transvalvular flow change occurring during DSE. Methods and Results-The use of EOA proj to differentiate TS from PS AS was investigated in an in vitro model and in 23 patients with low-flow AS (indexed EOA Ͻ0.6 cm 2 /m 2 , left ventricular ejection fraction Յ40%) undergoing DSE and subsequent aortic valve replacement. For an individual valve, EOA was plotted against transvalvular flow (Q) at each dobutamine stage, and valve compliance (VC) was derived as the slope of the regression line fitted to the EOA versus Q plot; EOA proj was calculated as EOA proj ϭEOA rest ϩVCϫ(250ϪQ rest ), where EOA rest and Q rest are the EOA and Q at rest. Classification between TS and PS was based on either response to flow increase (in vitro) or visual inspection at surgery (in vivo). EOA proj was the most accurate parameter in differentiating between TS and PS both in vitro and in vivo. In vivo, 15 of 23 patients (65%) had TS and 8 of 23 (35%) had PS. The percentage of correct classification was 83% for EOA proj and 91% for indexed EOA proj compared with percentages of 61% to 74% for the other echocardiographic parameters usually used for this purpose. Conclusions-EOA