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

Abstract

Aims: Our 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 results: Based 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.

Conclusion: In individuals free of cardiovascular disease, the addition of troponin I to variables of established risk score improves prediction of cardiovascular death and cardiovascular disease.

Keywords: Biomarker for Cardiovascular Risk Assessment in Europe; Cardiovascular risk; High-sensitivity assayed troponin I; MONICA Risk Genetics Archiving and Monograph; Mortality.

Figure 1

Survival curves according to fifths of the troponin I distribution in the study population. The P-value given in the survival curves is for the log-rank test. The troponin I quintiles, computed in the overall population via linear quantile mixed models, are 2.5, 2.8, 5.4, and 5.9 ng/L. The number of cohorts contributing to the figure decreases gradually over the 28 years, and includes only the Glostrup cohort at the end of follow-up. The number of persons at risk at 27 years of the follow-up according to troponin I fifths in increasing order is 1288, 162, 669, 30, 155 for cardiovascular mortality and total mortality, and 1201, 145, 601, 26, 136 for cardiovascular disease.

Figure 2

Hazard ratios according to fifths of the troponin I distribution in the study population. The troponin I quintiles, computed in the overall population via linear quantile mixed models, are 2.5, 2.8, 5.4, and 5.9 ng/L. The hazard ratios come from Cox models adjusted for variables of the ESC SCORE (cardiovascular mortality, total mortality) and ACC/AHA score (cardiovascular disease). Age was used as the time scale. The models were stratified by sex and cohort. ns stands for non-significant (P ≥ 0.05), *0.01 ≤ P < 0.05, **0.001 ≤ P < 0.01, ***0.0001 ≤ P < 0.001, and ****P < 0.0001.

Figure 3

Net reclassification improvement of 10-year risk prediction by troponin I over model with variables used in the ESC SCORE (cardiovascular mortality, total mortality, and cardiovascular disease) in the overall cohort and according to age groups. The risk categories used are <1%, 1 to <5%, 5 to <10%, and ≥10%. Net reclassification improvement is presented as a number with a theoretical range between −2 and 2.