Anti-inflammatory therapies in acute coronary syndromes: is IL-1 blockade a solution?

Elevation of circulating levels of C-reactive protein (CRP) at the time of hospital admission predicts a poor outcome in patients with an acute coronary syndrome (ACS) and is thought to reflect an important inflammatory component in the pathogenesis of this condition. C-reactiveprotein is also the preferred systemic inflammatorybiomarker for risk stratification in heart disease. The link between inflammation and ACS is complex. Atherosclerosis, the primary cause of ACS, is a chronic inflammatory disease of coronary arteries, but exacerbations of the inflammatory process within the atherosclerotic plaque may lead to plaque rupture with thrombosis and subsequent myocardial ischaemia. Myocardial injury following an ischaemic event is an additional source for a local and systemic inflammatory response; importantly, the intensity of the systemic response is also a predictor of adverse events. There are therefore at least three potential sources of inflammation in ACS: (i) the baseline chronic inflammation seen in patients at risk and related to hypercholesterolaemia, diabetes, obesity, and others; (ii) the inflammatory events within the atherosclerotic plaques; and (iii) the systemic inflammatory response to ischaemic myocardial injury (Figure 1). As such it is not surprising that inflammatory biomarkers predict adverse outcomes.