Comparison of Three Troponins as Predictors of Future Cardiovascular Events – Prospective Results from the FINRISK and BiomaCaRE Studies

Abstract

Importance and ObjectiveBesides their role in diagnosis of acute myocardial infarction (MI), troponins may be powerful biomarkers for risk stratification in the general population. The objective of our study was to compare the performance of three troponin assays in cardiovascular disease (CVD) risk prediction in a population-based cohort without a history of CVD events.Design, Setting and ParticipantsTroponin I concentrations were measured using a contemporary-sensitivity, high-sensitivity, and super-sensitivity assay in 7,899 participants of the general-population based FINRISK 1997 cohort. We used Cox proportional hazards regression to determine relative risks, followed by measures of discrimination and reclassification using 10-fold cross-validation to control for over-optimism.Main OutcomeAs outcome measures we used CVD, MI, ischemic stroke, heart failure (HF), and major adverse cardiac events (MACE). During the follow-up of 14 years 1,074 incident MACE were observed.ResultsValues above the lower limit of detection were observed in 26.4%, 81.5% and 93.9% for the contemporary-sensitivity, high-sensitivity and super-sensitivity assay, respectively. We observed significant associations of troponin concentrations with the risk of future CVD events and the results tended to become stronger with increasing assay sensitivity. For the super-sensitivity assay the multivariate adjusted hazard ratios (per one standard deviation increase) for different outcomes were: MI 1.24 [95% CI 1.11–1.39], stroke 1.14 [1.01–1.28], CVD 1.15 [1.07–1.24], HF 1.28 [1.18–1.39], and MACE 1.18 [1.11–1.25]. In subjects with intermediate risk, we found an improvement of net reclassification for HF (10.2%, p<0.001), and MACE (5.1%, p<0.001).ConclusionUsing a super-sensitivity assay, cardiac troponin was detectable in almost all healthy individuals. Its concentration improved risk prediction and reclassification for cardiovascular endpoints.

NT-proBNP and Troponin T Levels Differ after Haemodialysis with a Low versus High Flux Membrane

“…Notable is that TnT has molecular size of 37 kDa but also exists as fragments ranging in size from 8 kDa to 30 kDa (26,27), and troponin I has size between 21 kDa to 24 kDa (28). The cardiac markers are all predictors of increased risk of mortality (13,17,18,21,24,(29)(30)(31)(32).…”

Clinically Significant Novel Biomarkers for Prediction of First Ever Myocardial Infarction

“…Acceptable assay performance criteria required the standard curve be near [4][5] log Event Photons at the lower limit of detection, and 6-7 log Event Photons at the upper limit of detection, with a minimum of 2 logs linear range. A sample spiked with analyte, titrated within the linear range was required to have a slope parallel to that of the standard curve, and 80-120% recovery of the analyte was required for acceptance.…”

“…The use of cardiac troponin I has revealed a high prognostic potential of low troponin concentrations, but their clinical value in risk prediction has not been established. 5 On the other hand, elevated blood levels of N-terminal prohormone of brain natriuretic peptide indicate that individuals already have cardiovascular disease, and yet do not, as individual biomarkers, add any information beyond the TRFs in terms of unaccounted risk or new risk associated with unrecognized events.Assessment of the clinical utility of these and other novel biomarkers across populations is complicated by differences in study sample characteristics and, perhaps most importantly, by the definition of the outcome. Using a composite end point, such as ischemic stroke, myocardial infarction (MI), coronary ischemia requiring revascularization, heart failure, and cardiovascular death, may increase the power of the study to detect signal, but can result in a loss of information from biomarkers associated with specific disease pathogenesis.…”

“…The use of cardiac troponin I has revealed a high prognostic potential of low troponin concentrations, but their clinical value in risk prediction has not been established. 5 On the other hand, elevated blood levels of N-terminal prohormone of brain natriuretic peptide indicate that individuals already have cardiovascular disease, and yet do not, as individual biomarkers, add any information beyond the TRFs in terms of unaccounted risk or new risk associated with unrecognized events.…”

Fully Automated Ultrasensitive Digital Immunoassay for Cardiac Troponin I Based on Single Molecule Array Technology

“…A comparative assessment of the utility of 3 cTnI assays in primary prevention-based screening of asymptomatic individuals was addressed in the 14-year FINRISK (Financial Risk Institute) and BiomaCaRE (Biomarker for Cardiovascular Risk Assessment in Europe) studies, in which 7899 participants were tested using a medium-sensitivity assay (STAT Troponin I, Abbott Diagnostics), a high-sensitivity assay (ARCHITECT STAT highly sensitive Troponin I, Abbott), and an ultrasensitive cTnI assay (Erenna cTnI, Singulex) (21 ). Baseline cTnI was found to be a significant predictor of cardiovascular events, and risk prediction was strongest using the ultrasensitive assay, which was able to measure baseline cTnI in 93.9% of the tested population, compared with 26.4% and 81.5% for medium-and high-sensitivity assays, respectively.…”