Clinical Chemistry 64:4 645–655 (2018)Tam metin için tıklayınız

Abstract
This document is an essential companion to the third iteration of the National Academy of Clinical Biochemistry [NACB,8 now the American Association for Clinical Chemistry (AACC) Academy] Laboratory Medicine Practice Guidelines (LMPG) on cardiac markers. The expert consensus recommendations were drafted in collaboration with the International Federation of Clinical Chemistry and Laboratory Medicine Task Force on Clinical Applications of Bio-Markers (IFCC TF-CB). We determined that there is sufficient clinical guidance on the use of cardiac troponin (cTn) testing from clinical practice groups. Thus, in this expert consensus document, we focused on clinical laboratory practice recommendations for high-sensitivity (hs)-cTn assays. This document utilized the expert opinion class of evidence to focus on the following 10 topics: (a) quality control (QC) utilization, (b) validation of the lower reportable analytical limits, (c) units to be used in reporting measurable concentrations for patients and QC materials, (d) 99th percentile sex-specific upper reference limits to define the reference interval; (e) criteria required to define hs-cTn assays, (f) communication with clinicians and the laboratory’s role in educating clinicians regarding the influence of preanalytic and analytic problems that can confound assay results, (g) studies on hs-cTn assays and how authors need to document preanalytical and analytical variables, (h) harmonizing and standardizing assay results and the role of commutable materials, (i) time to reporting of results from sample receipt and sample collection, and (j) changes in hs-cTn concentrations over time and the role of both analytical and biological variabilities in interpreting results of serial blood collections.

Clinical Chemistry Vol. 64, Issue 7 July 2018 tam metin için tıklayınız

BACKGROUND: The overall clinical decision limits of high-sensitivity cardiac troponin I (hs-cTnI; 26 ng/L) and T (hs-cTnT; 14 ng/L) may contribute to underdiagnosis of acute myocardial infarction in women. We performed a systematic review to investigate sex-specific and overall 99th percentiles of hs-cTnI and hs-cTnT derived from healthy reference populations.

CONTENT: We searched in PubMed and EMBASE for original studies, and by screening reference lists. Reference populations designed to establish 99th percentiles of hs-cTnI (Abbott) and/or hs-cTnT (Roche), published between January 2009 and October 2017, were included. Sex-specific and overall 99th percentile values of hs-cTnI and hs-cTnT were compared with overall clinical decision ranges (hs-cTnI, 23–30 ng/L; hs-cTnT, 13–25 ng/L). Twenty-eight studies were included in the systematic review. Of 16 hs-cTnI and 18 hs-cTnT studies, 14 (87.5%) and 11 (61.1%) studies reported lower female-specific hs-cTn cutoffs than overall clinical decision ranges, respectively. Conversely, male-specific thresholds of both hs-cTnI and hs-cTnT were in line with currently used overall thresholds, particularly hs-cTnT (90% concordance). The variation of estimated overall 99th percentiles was much higher for hs-cTnI than hs-cTnT (29.4% vs 80.0% of hs-cTnI and hs-cTnT studies reported values within the current overall clinical decision range, respectively).

SUMMARY: Our data show substantially lower female-specific upper reference limits of hs-cTnI and hs-cTnT than overall clinical decision limits of 26 ng/L and 14 ng/L, respectively. The statistical approach strongly affects the hs-cTnI threshold. Downward adjustment of hs-cTn thresholds in women may be warranted to reduce underdiagnosis of acute myocardial infarction in women.

Clinical Chemistry January 2012 vol. 58 no. 1 54-61

BACKGROUND: Cardiac troponins I (cTnI) and T (cTnT) have received international endorsement as the standard biomarkers for detection of myocardial injury, for risk stratification in patients suspected of acute coronary syndrome, and for the diagnosis of myocardial infarction. An evidence-based clinical database is growing rapidly for high-sensitivity (hs) troponin assays. Thus, clarifications of the analytical principles for the immunoassays used in clinical practice are important.

CONTENT: The purpose of this mini-review is (a) to provide a background for the biochemistry of cTnT and cTnI and (b) to address the following analytical questions for both hs cTnI and cTnT assays: (i) How does an assay become designated hs? (ii) How does one realistically define healthy (normal) reference populations for determining the 99th percentile? (iii) What is the usual biological variation of these analytes? (iv) What assay imprecision characteristics are acceptable? (v) Will standardization of cardiac troponin assays be attainable?

SUMMARY: This review raises important points regarding cTnI and cTnT assays and their reference limits and specifically addresses hs assays used to measure low concentrations (nanograms per liter or picograms per milliliter). Recommendations are made to help clarify the nomenclature. The review also identifies further challenges for the evolving science of cardiac troponin measurement. It is hoped that with the introduction of these concepts, both laboratorians and clinicians can develop a more unified view of how these assays are used worldwide in clinical practice.

Clinical Chemistry. 2009;55:2098-2112

Background: Although cardiac troponin (cTn) is a cornerstone marker in the assessment and management of patients with acute coronary syndrome (ACS) and heart failure (HF), cTn is not diagnostically specific for any single myocardial disease process. This narrative review discusses increases in cTn that result from acute and chronic diseases, iatrogenic causes, and myocardial injury other than ACS and HF.
Content: Increased cTn concentrations have been reported in cardiac, vascular, and respiratory disease and in association with infectious processes. In cases involving acute aortic dissection, cerebrovascular accident, treatment in an intensive care unit, and upper gastrointestinal bleeding, increased cTn predicts a longer time to diagnosis and treatment, increased length of hospital stay, and increased mortality. cTn increases are diagnostically and prognostically useful in patients with cardiac inflammatory diseases and in patients with respiratory disease; in respiratory disease cTn can help identify patients who would benefit from aggressive management. In chronic renal failure patients the diagnostic sensitivity of cTn for ACS is decreased, but cTn is prognostic for the development of cardiovascular disease. cTn also provides useful information when increases are attributable to various iatrogenic causes and blunt chest trauma.

Summary: Information on the diagnostic and prognostic uses of cTn in conditions other than ACS and heart failure is accumulating. Although increased cTn in settings other than ACS or heart failure is frequently considered a clinical confounder, the astute physician must be able to interpret cTn as a dynamic marker of myocardial damage, using clinical acumen to determine the source and significance of any reported cTn increase.

T Klin Tıp Bilimleri 2003, 23:74-80

“Klinik sensitivitelerinin yüksek olması, kalp dokusunda diğer markırlara kıyasla yüksek düzeylerde bulunmaları ve sağlıklı kişilerdeki dolaşım düzeylerinin çok düşük olmasına bağlıdır. Spesifisitelerinin çok yüksek olması ise, kalbe spesifik kardiyak troponin T (cTnT) ve kardiyak troponin I (cTnI) izoformlarından kaynaklanmaktadır. Bu nedenle iskelet kası hasarına bağlı olarak CK ve CK-MB’de görülen yüksek değerlere bağlı olarak gelişen sorunlar kardiyak troponinler için söz konusu olmamaktadır. Kardiyak troponinlerin dolaşımdaki düzeylerinin, 7-14 gün gibi uzun sayılabilecek bir süreç boyunca yüksek seyretmesi, akut miyokard infarktüsü tanısı yanısıra, subakut miyokard infarktüsü tanısında da kullanımlarına olanak sağlamakta ve laktat dehidrogenaz (LD) izoenzimlerine duyulan ihtiyacı ortadan kaldırmaktadır.”

Türk Kardiyol Dern Arş – Arch Turk Soc Cardiol 2008;36(4):269-277

“Kardiyak troponinler (cTn) aktin ve miyozinin kalsiyuma bağlı etkileşimini düzenleyerek miyokard kontraksiyonunda görev alan ve cTn-T, cT-I ve c-Tn-C olmak üzere üç alt formu bulunan düzenleyici proteinlerdir. Bu proteinlerin dokuya özgül birçok izoformu bulunmaktadır. cTn-C’nin düz kasta bulunan troponin izoformu ile aynı olduğu için kardiyak özgüllüğü yoktur. Oysa cTn-T ve I farklı genlerce kodlandıkları için iskelet kasındaki troponinlerden tamamıyla farklıdır. Renal disfonsiyonlu hasta grubu dışında cTn-T ve I’in özgüllük ve duyarlılıkları benzerdir ve miyokard hasarı için oldukça yüksektir. Bu proteinler miyositte, sitozolik havuzda ve kontraktil aparatusta bulunmaktadır. Sitozolik havuzda bulunan cTn miktarı kreatin kinaz-miyokard bandı (CK-MB) izoenziminin miktarı ile aynıdır; ancak, kontraktil aparatusta da önemli miktarda cTn bulunması nedeniyle, miyokardın gramı başına cTn miktarı CK-MB miktarının 13-15 katıdır. Bu durum, erken dönemde c-Tn duyarlılığının CK-MB’den daha fazla olmasını ve 1 gram altındaki miyokard doku hasarında (iskemi, infarkt, travma, toksik hasar veya inflamasyon nedeniyle), periferik kanda CK-MB düzeyleri normalken dahi cTn’nin neden yüksek bulunduğunu açıklar. Bu nedenle, hem ACC (American Collage of Cardiology) hem de ESC (European Society of Cardiology) tarafından akut miyokard infarktüsünün tanısında tercih edilecek biyokimyasal belirteç olarak önerilmektedir. Sağlıklı bir kişide periferik kanda cTn düşük düzeylerdedir; ancak, miyosit hasarı durumunda, erken dönemde sitozolik havuzdan, geç dönemde ise kontraktil aparatustan periferik kana salınma nedeniyle ölçülebilen düzeylere erişmektedir. Akut miyokard hasarı sonrası 2-4 saat içinde kan düzeyleri yükselmekte, 24 saatte zirveye ulaşmakta, sonrasında yaklaşık 2-3 hafta kadar kan cTn düzeyleri yüksek seyretmektedir. CK-MB düzeyinden farklı olarak uzun süreli yüksekliğinin nedeni, cTn’nin geç dönemde kontraktil aparatustan salınımının devam etmesidir.”