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Use and abuse of biomarkers in acute coronary syndromes

Cardiac biomarkers have a pivotal role in acute coronary syndromes ( ACS ) in many ways: they are key in diagnosis, as far as the universal definition of myocardial infarction is concerned; have a strategic importance in risk assessment and prognostic stratification; and last but not least, dictate the efficacy of antiplatelet and antithrombotic therapies, as well as of an early invasive strategy. The benchmark for a biomarker, in relation to its possible clinical use, is represented by the possibility to be easily and precisely measured, by the new information it carries and by its role in influencing patient management.

Acute Coronary Syndromes (ACS)


Troponins
Dr. Giannitsis from Heidelberg ( Germany ) talked about troponins, the most widely used biomarker in the field of ACS . The new universal definition of myocardial infarction puts troponins – Tn(s) - at the center of the diagnostic process: they are the preferred biomarker to be used and the decision limit has been decreased from the 10% coefficient of variation (a precision measure of the local laboratory) to the 99th percentile of the distribution of Tn(s) in the normal reference population. Even using this lower cutoff value, Tn(s) maintain their prognostic role in ACS , with a strong difference in MACE and even in mortality according to the quartile of Tn(s) level in ACS patients (pts).


The link between troponin levels and thrombus formation in the coronaries is the reason why efficacy of antiplatelet therapy, like  infusion of GP IIb/IIIa antagonists, varies according to the Tn(s) blood levels, with very good efficacy in pts with elevated Tn(s) and no effect in those with normal Tn(s) level. Problems with Tn(s) are related to the still widely used biomarker CKMB, with imprecision in assays at low level and with the great number of non-coronary heart diseases and non-cardiac diseases that present with high levels of Tn(s). Examples of these diseases, out of quite a long list, include chronic kidney disease or pulmonary embolism: differential diagnosis is not always easy in pts with high Tn(s), but in any case, Tn(s) maintain their very strong prognostic role, even in non-coronary and in non-cardiac diseases.


C-reactive protein
Prof. Crea, from Rome (Italy) addressed the issue of C-reactive protein (CRP), the most important of a wide bunch of inflammatory biomarkers. CRP is certainly linked to outcome, as an expression of inflammatory mechanisms that are not adequately treated by current pharmacological therapy of ACS. Because inflammatory mechanisms and markers are redundant, CRP does not have a prognostic role independent of other markers of inflammation, and lacks specific anti-inflammatory therapy. As far as markers of inflammation are concerned, it is possible that we have to move from blood to cellular markers, such as specific nasty T cell populations (CD4+CD28null), shown to infiltrate unstable plaques and to be associated to clinical instability and long term outcome. It is possible that blocking the inflammatory triggers could yield better results than blocking inflammatory markers.


Natriuretic peptides
Dr. Weber, from Bad Nauheim (Germany) talked about natriuretic peptides (NPs) and their important role in pts with heart failure. NPs have a very important role in ED, in pts with dyspnoea and in those with chest pain, as well as a very important prognostic role in ACS: quartiles of NP(s) levels (both BNP and NT-pro-BNP) present a positive and quite linear correlation with death in the follow-up of ACS pts. There are still problems related to cut-off levels and decision limits for NP(s), because they can vary according to age, gender and other factors, as well as the timing of blood withdrawal. High levels of NP(s) are linked to the benefit of invasive strategies, both in pts with high and with normal Tn(s).


Creatinine
The last presentation was by Prof. Jernberg (Stockholm, Sweden), about creatinine and renal biomarkers in general. Outcome of ACS pts is strongly linked to renal function, as quartiles of glomerular filtration rate (GFR) demonstrate, and even the bleeding risk is related to renal insufficiency, as well as the probability of a contrast induced nephropathy (CIN) with the use of the contrast medium during invasive procedures. We have three possible ways to determine renal function: creatinine blood levels; GFR estimation (eGFR) (through the Cockcroft/Gault or the MDRD formulas); cystatin C. eGRF is able to determine mortality within each subset of creatinine level and while MDRD is more accurate, the Cockcroft-Gault calculation is more widely validated when dosing many drug therapies for ACS.  Moreover, in pts with moderate chronic kidney disease (CKD), the in-hospital mortality is higher with Cockcroft-Gault than with MDRD. Cystatin C, the newest marker of renal disease, is a cysteine protease inhibitor which is freely filtered and metabolized in the proximal tubuli: a linear association has been demonstrated between cystatin C quartiles and mortality for cardiovascular diseases, for ACS and even from non cardiac causes: cystatin C showed a stronger association with mortality than creatinine or eGFR.

References


163-164-165-166

SessionTitle:

Use and abuse of biomarkers in acute coronary syndromes

Notes to editor


This congress report accompanies a presentation given at the ESC Congress
2008. Written by the author himself/herself, this report does not
necessarily reflect the opinion of the European Society of Cardiology

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.