Cooling off hot hearts: a specific therapy for vulnerable plaque?

A few decades ago, cardiac pathologists taught us that coronary atheroma can be either stable or vulnerable. The vulnerable plaque has the key histological features of local inflammation: a higher temperature, roughly 4 times more macrophages than stable plaques, and a thin fibrous cap only one-third as thick as stable atheroma (1–4). Because acute oronary syndromes (ACS) are caused by vulnerable laques, therapy targeting the inflammatory process has eemed compellingly rational. The early logical choice among anti-inflammatory therpies was corticosteroids. A 2002 meta-analysis of 11 trials 2,646 patients) revealed a 26% decrease in mortality with orticosteroids in acute myocardial infarction (AMI) (odds atio: 0.74; 95% confidence interval [CI] 0.59 to 0.94), but ensitivity analysis limited to randomized, controlled trials howed lack of efficacy (odds ratio: 0.95; 95% CI: 0.72 to .26) (5). Steroids were abandoned amidst concern for mpaired wall healing resulting in cardiac rupture, although his risk may be lessened with concomitant reperfusion (6). In subsequent years, attention focused on selective and onselective nonsteroidal anti-inflammatory drugs NSAIDs). All of these agents, with the exception of spirin, increase the risk for AMI, especially in those atients known to have coronary heart disease. A recent anish study of 99,187 patients experiencing a first-time MI reported that subsequent NSAID use was persistently ssociated with increased mortality (hazard ratio: 1.63; 95% I: 1.52 to 1.74) over a 5-year period (7). Still, provocative hints remained. The well-documented nti-inflammatory effects of statins may play a role in educing cardiac events, and some anti-inflammatory drugs sed in noncardiac conditions, such as methotrexate in