This study shows that very low circulating levels of cardiac troponin T are detectable in the great majority of patients who have stable coronary artery disease with preserved left ventricular function, that multiple conventional risk factors are associated with higher troponin T concentrations in this population, and that very low circulating levels of troponin T have a graded relationship with the incidence of cardiovascular death and heart failure in such patients. Conversely, the association between troponin T concentrations and incident myocardial infarction was not significant after adjustment for potential confounding factors. This finding stands in stark contrast to observations in patients with acute coronary syndromes, in whom troponins are considered biomarkers of acute cardiovascular injury due to plaque rupture and intracoronary thrombosis17
and more accurately predict recurrent myocardial infarction than they do death or heart-failure events.18
With the use of conventional assays, the prevalence of detectable concentrations of cardiac troponin T in the general population is approximately 0.7%.19
Detectable troponin T levels in such a population are typically associated with established cardiovascular disease, such as left ventricular hypertrophy or dysfunction, or with high-risk conditions such as kidney disease or diabetes. The mechanisms responsible for the release of very low levels of cardiac troponin T in patients with stable coronary artery disease could include transient, clinically silent ischemic episodes and small-vessel occlusions; inflammatory processes; cardiomyocyte apoptosis20
; reduced renal clearance; and increased myocardial strain due to pressure or volume overload. However, the remarkably high prevalence of detectable troponin in this low-risk cohort raises the possibility that some troponin may circulate under normal circumstances in human plasma. Data from population studies will be needed to confirm this hypothesis, and the source of the release of cardiac troponin T will need to be studied in experimental models.
In a previous study, the prognostic value of the highly sensitive cardiac troponin T assay was investigated in patients with chronic symptomatic heart failure and systolic dysfunction.9
A strong and graded association with mortality and the risk of heart failure was observed, even after adjustment for NT-proBNP. The current study extends these findings to a lower-risk population with stable coronary artery disease and no evidence of heart failure or left ventricular systolic dysfunction.
The observations that troponin T was detectable in almost all our patients and that it provided strong prognostic information independently of conventional risk factors and other contemporary biomarkers, such as NT-proBNP and high-sensitivity CRP, suggest that assessment of low-level chronic myocardial injury may represent a new means by which clinicians can stratify risk among patients with stable coronary artery disease and preserved left ventricular function. Unresolved questions that need to be addressed include whether serial testing would enhance the prognostic value of the assay and whether minor changes in very low levels are stronger predictors of events than are absolute values. Moreover, before routine testing is considered, the therapeutic implications will need to be fully explored. Certain negative implications merit consideration as well. As more sensitive assays for troponins are introduced clinically, the specificity of low-level troponin elevation for acute myocardial injury in patients with acute chest pain syndromes may be reduced.
Limitations of our study include the selection of patients participating in a clinical trial (who may not be fully representative of patients in the general population), the use of a noncommercially available prototype assay that may not be perfectly calibrated with existing conventional assays, and the fact that heart-failure events were not a component of the prespecified primary outcome in the original trial design. In addition, we cannot rule out the presence of asymptomatic cardiovascular disease in the group of apparently healthy blood donors whose troponin T values were used for comparison, although anyone who was receiving medication for cardiovascular disease was excluded from this group. Accordingly, we cannot rule out the possibility of a lower 99th percentile value with the use of a more rigorous screening procedure. Moreover, the PEACE study population was predominantly white, and more than 80% of the patients were men. Therefore, extrapolation of our results to other demographic groups should be done with caution.
In conclusion, very low levels of troponin T were detectable in the great majority of patients with stable coronary artery disease. Levels well below the limit of detection of previous assays and below the 99th percentile in apparently healthy blood donors were strongly associated with the incidence of cardiovascular death and heart failure. In contrast, troponin T levels were not independently associated with the incidence of myocardial infarction.