Interleukin-6 as a predictor of cardiovascular events in troponin-negative non-ST elevation acute coronary syndrome patients.

AIM: Risk stratification in acute coronary syndrome without ST-segment elevation (NSTE-ACS) and troponin-negative remains a challenge. We evaluated the value of interleukin-6 (IL-6) and amino-terminal pro-B-type natriuretic peptide (NT-proBNP) in the prognosis assessment of low-moderate risk NSTE-ACS and troponin-negative, and whether these biomarkers could improve the predictive performance of the established thrombolysis in myocardial infarction (TIMI) risk score. METHODS: A total of 212 low-moderate risk patients with NSTE-ACS and troponin-negative were prospectively studied. Clinical follow up at 6 months was performed for adverse endpoints. RESULTS: A total of 28 patients (13.5%) presented adverse clinical events. Those with adverse clinical events were associated with higher levels of IL-6 [8.58 (5.13-20.95) ng/l vs. 6.12 (4.16-9.14) ng/l, p = 0.043] and NT-proBNP [275.3 (108.6-548.2) ng/l vs. 126.8 (55.97-430.20) ng/l, p = 0.046]. In moderate risk group, we observed a higher event rate in patients with troponin-negative but elevated levels of IL-6 (p = 0.024). Only elevated IL-6 (> 12.40 ng/l) was an independent predictor of adverse outcomes [hazard ratios: 3.62, 95% confidence interval (CI) 1.69-7.75, p = 0.001]. The addition of IL-6 and history of ischaemic heart disease (IHD) to TIMI risk score significantly improved both the discrimination (integrated discrimination improvement, p = 0.003) and reclassification (Clinical Net reclassification improvement, p = 0.010) of the model for adverse events. CONCLUSIONS: Interleukin-6 is an independent predictor of adverse events in low-moderate risk patients with NSTE-ACS and troponin-negative. Its use identifies a higher risk population in moderate-risk patients. This provides together with history of IHD a better discrimination and reclassification beyond that achieved with clinical risk variables from TIMI risk score in these patients.

New perspectives in antiplatelet therapy.

Platelet activation is a complex mechanism of response to vascular injury and atherothrombotic disease, leading to thrombus formation. A wide variety of surface receptors -integrins, leucine-rich family receptors, G protein coupled receptors, tyrosine kinase receptors- and intraplatelet molecules support and regulate platelet activation. They are potential targets of antiplatelet therapy for the prevention and treatment of arterial thrombosis. Despite the overall clinical benefit of established antiplatelet drugs targeting cyclooxigenase-1 (COX-1), glycoprotein integrin αIIbß3, and the purinergic P2Y(12) receptor of adenosine diphosphate, a significant proportion of treated patients continue to experience recurrent ischaemic events. This may be in partly attributed to insufficient inhibition of platelet activation. In addition, it should not be underestimated that these drugs are not immune from bleeding complications. The substantial progress in understating the regulation of platelet activation has played a key role in the development of novel antiplatelet agents. Current examples of drug under development and evaluation include: novel P2Y(12) receptor inhibitors (prasugrel, ticagrelor, cangrelor, and elinogrel), thrombin receptor PAR-1 antagonists (vorapaxar, atopaxar), new integrin glycoprotein IIb/IIIa inhibitors, and inhibitors targeting the thromboxane receptor (TP), phosphodiesterases, the collagen receptor glycoprotein VI, and intraplatelet signalling molecules. This review summarizes the mechanisms of action and current clinical evaluation of these novel antiplatelet agents.

A multimarker risk stratification approach to non-ST elevation acute coronary syndrome: implications of troponin T, CRP, NT pro-BNP and fibrin D-dimer levels.

INTRODUCTION: Biomarkers have emerged as interesting predictors of risk in non-ST elevation acute coronary syndromes (non-ST ACS). The aim of this study was to define the utility of the combined measurement of troponin T (TnT), C-reactive protein (CRP), NT pro-brain natriuretic peptide (NT pro-BNP) and D-dimer as biomarkers to predict adverse events. METHODS: We included 358 consecutive patients admitted in two hospitals for non-ST ACS. Baseline measurements of TnT (associated with myocardial injury, positive, if > or =0.1 ng mL(-1)), CRP (a marker of inflammation), NT-proBNP (associated with left ventricular (dys)function) and fibrin D-dimer (and index of thrombogenesis) were performed. A positive CRP, NT-proBNP and D-dimer test was considered upper than the 75th percentile of our population. The risk for major events (death, new ACS, revascularization and heart failure) at 6 months' follow-up was analysed. RESULTS: Troponin T, NT pro-BNP and CRP were predictors of adverse events in the multivariate analysis [hazards ratio (HR): 2.00 (1.30-3.07), P = 0.0016; HR: 2.27 (1.47-3.50), P = 0.0002; HR: 1.90 (1.24-2.92), P = 0.0034 respectively], but not D-dimer levels [HR: 1.26 (0.79-2.02), P = 0.337). After adjusting for baseline characteristics and electrocardiographic changes, multimarker risk approach was associated with adverse events at 6 months, especially with the presence of three positive biomarkers [HR 2.80 (95%CI 1.68-4.68), P < 0.001]. When we divided patients by risk groups [Thrombolysis in Myocardial Infarction (TIMI) risk score], patients with two or three elevated biomarkers had higher event rates [HR 2.59 (95% CI 1.37-4.91), P = 0.004]. CONCLUSION: A multimarker approach based on TnT, CRP and NT-proBNP provides added information to the TIMI risk score in terms of ACS prognosis at 6 months, with a worse outcome for those with two or three elevated biomarkers.

Angiogenin: a review of the pathophysiology and potential clinical applications.

Angiogenin is a member of the ribonuclease (RNase) superfamily: enzymes of innate substrate specificity, but divergent functional capacities. Angiogenin is a normal constituent of the circulation and contained in a vasculature that rarely undergoes proliferation, but in some physiological and pathological conditions its levels increase in blood, promoting neovascularization. Hence, angiogenesis is a common pathophysiological attribute of angiogenin. In malignant disease, the most studied pathological state in regard to angionenin, abnormally high levels are seen, which may be of prognostic significance. Angiogenin has also been studied in other non-malignant pathological states. The aim of this review article is to provide an overview of the biochemistry and physiology of angiogenin, specifically in relation to the human pathological states where angiogenin has been implicated and finally, its potential clinical applications.