High Population Prevalence of Cardiac Troponin I Measured by a High-Sensitivity Assay and Cardiovascular Risk Estimation: The MORGAM Biomarker Project Scottish Cohort

Study Questions:

What is the predictive and clinical applicability of high-sensitivity assayed troponin I (HS TnI) for identifying incident cardiovascular events in a general middle-aged European population?

Methods:

Detection of HS TnI has been found in 80-90% of general populations based on reliable measurements at very low troponin levels. The extent to which this determination predicts outcomes or can be used to guide therapies is unknown. HS TnI was measured in the Scottish Heart Health Extended Cohort (n = 15,340) with 2,171 cardiovascular events (including acute coronary heart disease and probable ischemic strokes), 714 coronary deaths (25% of all deaths), 1,980 myocardial infarctions, and 797 strokes of all kinds during an average of 20 years of follow-up. Advanced statistical modeling correlated HS TnI to these events, while new risk prediction indices (e.g., net reclassification improvement) evaluated incremental changes with including HS TnI in models.

Results:

Detection rate above the limit of detection of 1.9 pg/ml was 74.8% in the overall population, and 82.6% in men and 67.0% in women. HS TnI broken into categories (no detection, 1.9-4.8 pg/ml, 4.8-12.7 pg/ml, and >12.7 pg/ml [the current threshold of detection for contemporary assays) was associated with future cardiovascular risk after full adjustment. Individuals with HS TnI >12.7 pg/ml had 2.5 times the risk compared with those without detectable TnI (p < 0.0001). These associations remained significant even for those individuals in whom troponin I measures were not detectable by contemporary assays. Addition of TnI levels to clinical variables led to significant increases in risk prediction with significant improvement of the c-statistic (p < 0.0001) and net reclassification (p < 0.0001), but these changes were small overall. A threshold of 4.7 pg/ml in women and 7.0 pg/ml in men was suggested to detect individuals at high risk for future cardiovascular events.

Conclusions:

The authors concluded that: “TnI, measured with an HS assay, is an independent predictor of cardiovascular events, and might support selection of at-risk individuals.” However, they also caution that their use in routine clinical practice is “not yet ready for prime time.”

Perspective:

The growing availability of assays for HS TnI raises opportunities and challenges for clinicians. These assays increase the ability to detect troponin at very low levels, which might reflect silent ischemia as well as other cardiac abnormalities, such as left ventricular hypertrophy and left ventricular dysfunction. What is increasingly clear is that they are likely to be detected in large numbers of patients in the general population. Results from this study add to the literature that HS TnI is a possible marker of global cardiovascular risk. From a clinical perspective, however, its application into decision making remains uncertain, as the incremental changes in risk prediction indices was small relative to other available biomarkers. Furthermore, it still needs to be proven that interventions based on these measurements lead to improved patient outcomes.

Keywords: Prevalence, Myocardial Infarction, Stroke, Follow-Up Studies, Biological Markers, Troponin I, Middle Aged, Cardiovascular Diseases, Risk Factors


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