Strategy of IFCC standardization and use of cardiac markers in acute coronary syndromes

Abstract

Although the use of troponin to diagnose acute myocardial infarction (AMI) has been previously proposed, the Committee on Standardization of Markers of Cardiac Damage (C-SMCD) of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) made a recommendation in 1999 to expand on the enzyme diagnostic criteria for AMI to include cardiac-specific proteins. In September 2000, a joint committee of the European Society of Cardiology and the American College of Cardiology (ESC/ACC) published a new definition of AMI that for first time officially included troponin. According to these criteria, as the best biochemical indicator for detecting myocardial necrosis is "a concentration of cardiac troponin exceeding the decision limit (defined as the 99th percentile of a reference control group) on at least one occasion during the first 24 hours after the onset of clinical event". The use of creatine kinase MB (CK-MB), measured by mass assays, is still considered as an acceptable alternative only if cardiac troponin assays are not available. It is very important to standardize the clinical use of troponin in diagnosis and management of acute coronary syndromes and to clearly define decision thresholds. Two strategies have competed as the most appropriate for the use of new markers. The first relies on the use of a combination of two markers - a rapid rising marker such as myoglobin, and a marker that takes longer to rise but is more specific, such as cardiac troponin - to enable detection of AMI in patients who present early and late after symptom onset. In the second strategy, only measurement of cardiac troponin is suggested. One of the most important problems in the practical use of the cardiac-specific troponin is the right definition of decision limits. As diagnostic cut-off for clinical use, the IFCC C-SMCD recommends for troponin assays a total imprecision, expressed as coefficient of variation (CV), of lt 10% at the 99th percentile of a reference control group. For troponin assays that cannot presently meet the 10% CV at the 99th percentile value, a predetermined higher concentration that meets this imprecision goal should be used as cut-off for AMI until the goal of a 10% CV can be achieved at the 99th percentile. It is very important that clinically relevant biomarker, such as cardiac troponin, on which critical decisions will rest, can be measured with highly reliable and standardized methods. There are problems in assay standardization, imprecision interference, and of pre-analytical variability. Cardiac troponin is currently the most sensitive and specific biochemical marker of myocardial damage and is the best marker for diagnosis, risk stratification, and guidance of therapy in acute coronary syndromes.

Mada su srčani troponini već korišćeni u dijagnozi akutnog infarkta miokarda (AIM), Komitet za standardizaciju markera srčanog oštećenja (Committee on Standardization of Markers of Cardiac Damage, C-SMCD) Međunarodne federacije kliničke hernije i laboratorijske medicine (International Federation of Clinical Chemistry and Laboratory Medicine, IFCC) u svojim preporukama 1999. godine u enzimski dijagnostički kriterijum za AIM uključuje i srčane-specifične proteine. Evropsko udruženje za kardiologiju (European Society of Cardiology) i Američki koledž za kardiologiju (American College of Cardiology) je 2000. godine objavio konsenzus dokument prema kome je najbolji biohemijski pokazatelj za detekciju srčane nekroze "koncentracija srčanog troponina viša od granične vrednosti (definiše se kao 99-ta percentilna vrednost referentne kontrolne grupe) bar jedanput u toku prvih 24 sata posle početka kliničkog događaja". Korišćenje kreatin kinaze MB (CK-MB) određene kao masena koncentracija još se uvek smatra alternativno prihvatljivim samo ukoliko ne postoji mogućnost određivanja troponina. Izbor najpodesnije strategije primene novih markera predstavlja veoma važno pitanje i danas se preporučuju dve strategije. Prva strategija se zasniva na korišćenju dva markera: marker koji brzo raste kao što je mioglobin i marker za čiji rast je neophodno duže vreme, a koji je specifičniji, kao što je to srčani troponin. Pri-menom druge strategije određuje se samo koncentracija troponina. Jedan od najvažnijih problema pri primeni srčanih specifičnih troponina je pravilno definisanje granica odlučivanja. IFCC C-SMCD preporučuje da se u kliničkoj praksi troponin određuje tako da ukupna nepreciznost, izražena kao koeficijent varijacije (Kv) bude niži od 10% na AIM nivou odlučivanja od 99-te percentilne vrednosti, a da proizvođači koji ne mogu da zadovolje ove zahteve kao "cut-off" vrednost preporuče najnižu vrednost pri kojoj se postiže Kv od 10%. Veoma je važno da metode kojima se određuju ovi klinički važni biomarkeri budu visoko pouzdane i standardizovane. Međutim, postoje problemi vezani za standardizaciju nepreciznost određivanja, kao i za postojanje interferencija i preanalitičkih varijacija. Srčani troponini danas se sa pravom smatraju srčano najspecifičnijim biohemijskim markerima oštećenja miokarda i najboljim pokazateljima u dijagnozi, proceni rizika i praćenju terapije u akutnom koronarnom sindromu.