Van Tassell et al IL-1 and Heart Disease 1911 progression of coronary artery disease and impaired function. Nevertheless, reports of an inflammatory response during heart disease began to emerge several decades ago. 18–20 Patients with acute coronary events have increased inflammatory markers, including C-reactive protein (CRP), which serves a surrogate for IL-1 activity. 21 For example, early studies observed that high CRP levels (> 3 mg/L) in patients with unstable angina predicted a significantly worse prognosis. 19 Subsequent studies validated that elevated CRP also predicted heart failure–related mortality in patients with impaired systolic function (ejection fraction< 30%) and clinical recurrence after coronary revascularization procedures such as balloon angioplasty, coronary artery stenting, and coronary artery bypass graft surgery, 22, 23 as well as in apparently healthy subjects and even in patients with levels of CRP previously considered normal. 24–27 Moreover, polymorphisms in the genes coding for IL-1β, IL-1Ra, and other genes have been associated with premature onset of atherosclerosis and acute myocardial infarction (AMI). 28 The natural history of heart disease is not linear. 29 Evidence shows that changes in the vessel wall and the heart start decades before the disease becomes clinically evident, and a chronic subclinical inflammation may promote or accelerate the disease (Figure 1). 29 The atherothrombotic event leading to AMI is a rather stochastic event occurring on a predisposed substrate: a vulnerable plaque that experiences an intolerable stress, leading to rupture and acute thrombosis. An enhanced inflammatory response may predispose the plaques to rupture, and a heightened inflammatory response during myocardial injury may affect the degree of healing and progression to heart failure. Clinically stable patients with prior acute events and symptomatic heart failure display evidence of chronic inflammation, which may further aggravate the cardiac dysfunction or predispose the patient to further decompensation (Figure 1).