Troponin I and cardiovascular risk prediction in the general population: the BiomarCaRE consortium

Abstract

AimsOur aims were to evaluate the distribution of troponin I concentrations in population cohorts across Europe, to characterize the association with cardiovascular outcomes, to determine the predictive value beyond the variables used in the ESC SCORE, to test a potentially clinically relevant cut-off value, and to evaluate the improved eligibility for statin therapy based on elevated troponin I concentrations retrospectively.Methods and resultsBased on the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) project, we analysed individual level data from 10 prospective population-based studies including 74 738 participants. We investigated the value of adding troponin I levels to conventional risk factors for prediction of cardiovascular disease by calculating measures of discrimination (C-index) and net reclassification improvement (NRI). We further tested the clinical implication of statin therapy based on troponin concentration in 12 956 individuals free of cardiovascular disease in the JUPITER study. Troponin I remained an independent predictor with a hazard ratio of 1.37 for cardiovascular mortality, 1.23 for cardiovascular disease, and 1.24 for total mortality. The addition of troponin I information to a prognostic model for cardiovascular death constructed of ESC SCORE variables increased the C-index discrimination measure by 0.007 and yielded an NRI of 0.048, whereas the addition to prognostic models for cardiovascular disease and total mortality led to lesser C-index discrimination and NRI increment. In individuals above 6 ng/L of troponin I, a concentration near the upper quintile in BiomarCaRE (5.9 ng/L) and JUPITER (5.8 ng/L), rosuvastatin therapy resulted in higher absolute risk reduction compared with individuals <6 ng/L of troponin I, whereas the relative risk reduction was similar.ConclusionIn individuals free of cardiovascular disease, the addition of troponin I to variables of established risk score improves prediction of cardiovascular death and cardiovascular disease.

The 99th percentile of reference population for cTnI and cTnT assay: methodology, pathophysiology and clinical implications

“…These patients may be expected to be at "intermediate" risk (i.e. between the extremely low risk of individuals with cTn values near to the LoD value and the higher risk of individuals with cTn values significantly higher than 99th URL values) [110][111][112][113]. Therefore, unsurprisingly, the APACE study reported that patients with misdiagnosis of AMI with two or more cTnI assays were at an intermediate risk, evaluated by Kaplan-Meyer survival curve analysis (i.e.…”

“…Several recent studies have demonstrated the association between the risk of major cardiovascular events and detectable, presumably still normal, cTn values measured with highly sensitive cTnI and cTnT assays [110][111][112][113]147]. These studies give rise to the question of whether there is a myocardial injury threshold beyond which individual risk increases thus being of potential clinical utility in cardiovascular risk prediction.…”

Measurement of Troponin in Cardiomyopathies

“…97 Even in individuals free of cardiovascular disease, the addition of TnI to the established ESC SCORE (Systematic COronary Risk Evaluation) has been shown to improve prediction of cardiovascular death and disease in the general population. 98 In the cardiomyopathies, elevated Tn levels are almost invariably related to poor prognosis (Table 6). Several characteristics associated with its release in HCM indicate its inclusion in risk prediction models, such as HCM Risk-SCD, 99 should be formally evaluated.…”

High-sensitivity cardiac troponin testing for primary care: analytical assay considerations required before widespread implementation

“…In the largest study of troponin testing among the general population published to date, Blankenberg et al measured cardiac troponin I in over 74,000 patients and showed that when the traditional biomarkers of cardiovascular risk were included, cardiac troponin remained as an independent predictor, with hazard ratios of 1.37 for cardiovascular mortality and 1.23 for cardiovascular disease (11). Using the upper quintiles of results, they established a crosssectional cardiac troponin cutoff of 6.0 ng/L.…”