Heart failure biomarkers: Focus on interleukin-1 receptor-like 1-based blood tests
Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.Drugs of today (Barcelona, Spain: 1998) (Impact Factor: 1.2). 07/2012; 48(7):479-91. DOI: 10.1358/dot.2012.48.7.1811719
Heart failure is a leading cause of morbidity and mortality in the Western world. It is often a progressive disease, and the pathophysiology behind this adverse development is not completely understood. Biomarkers are of increasing importance in heart failure research. Despite a growing number of candidate markers, only a select few have made it into clinical practice. Interleukin-1 receptor-like 1 (IL1RL1), also known as protein ST2, is the receptor for interleukin-33 (IL-33), a cytokine involved in T-cell-mediated immune responses. IL1RL1 expression is induced by cardiomyocyte stretch, and IL1RL1 may thus reflect the activity of two interacting processes in heart failure: inflammation and hemodynamic stress. In recent years, the soluble, truncated IL1RL1 isoform B has been shown to provide prognostic information in heart failure. Although ILRL1 isoform B does not seem to aid in the diagnosis of the disease, an elevated plasma/serum concentration of this marker is firmly associated with adverse outcome in patients with heart failure. This association has been established in different heart failure cohorts and is independent of age, etiology of heart failure and left ventricular function. Ultimately, the IL-33/IL1RL1 pathway may become a therapeutic target in heart failure.
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ABSTRACT: Acute myocardial infarction (AMI) is a common cardiac emergency with high mortality. Serum soluble ST2 (sST2) is a new emerging biomarker of cardiac diseases. The present study is to investigate the predictive value of sST2 and interleukin-33 (IL-33) for risk stratification and prognosis in patients with AMI. Fifty-nine patients with AMI, whose chief complaint was chest pain or dyspnea, were selected for our study. Physical examination, chest radiograph, electrocardiograph (ECG), biomarkers of myocardial infarction, NT-proBNP, echocardiography and other relevant examinations were performed to confirm the diagnosis of AMI. Thirty-six healthy people were chosen as the control group. Serum samples from these subjects (patients within 24 hours after acute attack) were collected and the levels of sST2 and IL-33 were assayed by enzyme-linked immuno-sorbent assay (ELISA) kit. The follow-up was performed on the 7th day, 28th day, 3rd month and 6th month after acute attack. According to the follow-up results we defined the end of observation as recurrence of AMI or any causes of death. Median sST2 level of the control group was 9.38ng/ml and that of AMI patients was 29.06ng/ml. Compared with the control group, sST2 expression in the AMI group was significantly different (P < 0.001). In contrast, the IL-33 level showed no significant difference between the two groups. Serum sST2 was a predictive factor independent of other variables and may provide complementary information to NT-proBNP or GRACE risk score. IL-33 had no relationship to recurrence of AMI. Both sST2 and the IL-33/sST2 ratio were correlated with the 6-month prognosis; areas under the ROC curve were 0.938 and 0.920 respectively. Early in the course (<24 hours) of AMI, sST2 usually increases markedly. The increase of sST2 has an independent predictive value for the prognosis in AMI patients and provides complementary information to NT-proBNP or GRACE risk score. The IL-33/sST2 ratio correlates with the 6-month prognosis of AMI patients. However, there is no significant relationship between IL-33 and the prognosis of AMI patients.
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ABSTRACT: Inflammation has been implicated in the pathogenesis of heart failure (HF). In addition to their direct involvement as mediators in the pathogenesis of HF, inflammatory cytokines and related mediators could also be suitable markers for risk stratification and prognostication in HF patients. Many reports have suggested that inflammatory cytokines may predict adverse outcome in these patients. However, most studies have been limited in sample size and lacking full adjustment with the most recent and strongest biochemical predictor such as NT-proBNP and high sensitivity troponins. Furthermore, a number of pre-analytical and analytical aspects of cytokine measurements may limit their use as biomarkers. This review focuses on technical, informative and practical considerations concerning the clinical use of inflammatory cytokines as prognostic biomarkers of HF. We focus on the predictive value of tumor necrosis factor (TNF) α, the TNF family receptors sTNFR1 and osteoprotegerin, interleukin (IL)-6 and its receptor gp130, the chemokines MCP-1, IL-8, CXCL16 and CCL21 and the pentraxin PTX-3 in larger prospective fully adjusted studies. No single inflammatory cytokine provides sufficient discrimination to justify the transition to everyday clinical use as a prognosticator in HF. However, while subjecting potential new HF markers to rigorous comparisons with "gold-standard" markers, such as NT-proBNP, using receiver operating characteristics (ROCs) and HF risk models, makes sense from a clinical standpoint, it may pose a threat to a broadening of mechanistic insight if the new markers are dismissed solely on account of lower statistical power.
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