Comparison of three troponins as predictors of future cardiovascular events--prospective results from the FINRISK and BiomaCaRE studies

Abstract

Importance and objective: Besides 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 participants: Troponin 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 outcome: As 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.

Results: Values 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).

Conclusion: Using a super-sensitivity assay, cardiac troponin was detectable in almost all healthy individuals. Its concentration improved risk prediction and reclassification for cardiovascular endpoints.

Figure 1. Kaplan-Meier Curves According to Troponin Categories as Measured by Contemporary-Sensitivity, High-Sensitivity and Super-Sensitivity Assays for MACE and HF after Adjustment for Age and Gender.

Dotted lines indicate the 95% confidence intervals. MACE = major adverse cardiac events, cs-cTnI = troponin I measured by contemporary-sensitivity assay, hs-cTnI = highly sensitive troponin I measured by high-sensitivity assay, ss-cTnI = troponin I measured by super-sensitivity assay. Please see the footnote to Table 2 for the cut points of the troponin categories.

Figure 2. Hazard Ratios from Cox Regression Models for Baseline Troponin Assessed by Contemporary-Sensitivity, High-Sensitivity and Super-Sensitivity Assays for Various Endpoints after Adjustment for the Framingham Risk Score.

** = p value<0.001, * = p value<0.05. MACE = major adverse cardiac events, CVD = cardiovascular disease, MI = myocardial infarction, HF = heart failure, HR = hazard ratio, CI = confidence interval, cs-cTnI = troponin I measured by contemporary-sensitivity assay, hs-cTnI = troponin I measured by high-sensitivity assay, ss-cTnI = troponin I measured by super-sensitivity assay.