Interleukin‐1 receptor antagonist levels correlate with extent of myocardial loss in patients with acute myocardial infarction

Abstract

SummaryBackground: Interleukin-1 receptor antagonist (IL-1Ra) levels are elevated early in patients with acute myocardial infarction (MI) and often precede release of markers of necrosis; however, IL-1Ra levels did not correlate previously with infarct size and prognosis in such patients.Hypothesis: The goal of our study was to evaluate prospectively the correlation between IL-1Ra levels upon emergency department (ED) presentation and the extent of myocardial necrosis and prognosis in patients with ST-segment elevation MI.Methods: Levels of IL-1Ra were measured upon ED presentation in 44 consecutive patients (40 men, aged 55 ± 10 years). Peak values of creatine kinase (CK) and CK-MB were determined during hospitalization, and left ventricular ejection fraction (LVEF) was evaluated by echocardiography before discharge. All patients were followed prospectively and underwent clinical and echocardiographic assessment at 42 ± 3 months after the infarction.Results: Levels of IL-1Ra upon ED presentation correlated directly with CK (p = 0.002) and CK-MB (p = 0.01) peak levels and correlated inversely with LVEF before discharge (p = 0.009). Patients with in-hospital adverse events had significantly higher IL-1Ra levels upon ED admission (n = 10, 2620 ± 4706 pg/ml) than those without events (n = 34, 598 ± 457 pg/ml) (p = 0.015).

Anakinra, a Recombinant Human Interleukin-1 Receptor Antagonist, Inhibits Apoptosis in Experimental Acute Myocardial Infarction

“…7 Its levels are elevated early in patients presenting with ST-segment-elevation AMI, 5 and the greater the area of myocardium at risk is, the greater the increase in IL-1Ra levels is. 6 Moreover, in observational studies, higher IL-1Ra levels in patients with acute coronary syndromes were associated with unfavorable outcome. 20,21 Whether IL-1Ra represented a marker of damage, an attempt at cardioprotection by means of antiinflammatory activity, or a mediator of damage remained unclear.…”

“…3,4 Like other acute-phase reactants, IL-1Ra levels increase during AMI, and its levels correlate with prognosis. 5,6 The role of increasing IL-1Ra during AMI is unclear, and speculations have been made that its role ranges from merely a marker of damage to a modulator of the inflammatory response to a potential cytoprotective agent. 5,8 Recently, forced expression of IL-1Ra in an animal model has been shown to be cardioprotective in terms of reduced infarct size and apoptosis.…”

Anakinra in Experimental Acute Myocardial Infarction—Does Dosage or Duration of Treatment Matter?

“…The interleukin-1 (IL-1) system plays a significant role in the myocardial response to ischemia and infarct healing in a delicate balance between pro-and anti-inflammatory mediators [1][2][3][4][5][6][7][8][9][10]. Interleukin-1 receptor antagonist (IL-1Ra) is a naturally occurring antiinflammatory protein, member of the IL-1 family, released during AMI [6,[11][12][13][14]. We have recently shown that administration of the drug anakinra, a recombinant human IL-1 receptor antagonist, within 24 h of experimental AMI in an animal model significantly attenuates cardiac remodelling 7 days after AMI, mainly by inhibition of cardiomyocyte apoptosis [15].…”

Temporal changes in biomarkers and their relationships to reperfusion and to clinical outcomes among patients with ST segment elevation myocardial infarction

“…We used relative change for the primary outcome to control for baseline biomarker levels as many of the investigational biomarkers included in this study have been associated with infarct size [15,17,18]. The primary outcome of interest was the 90-day composite of all-cause death, shock or heart failure (new or worsening).…”