High-sensitivity Cardiac Troponin: A Novel Window to the Heart

The TEAMSTA study² (1), reported on in this issue of Clinical Chemistry, investigated the effect of 2 different antihypertensive treatments on blood concentrations of high-sensitivity cardiac troponin (hs-cTn)³, as a quantitative marker of cardiomyocyte injury, and B-type natriuretic peptide (BNP), as a quantitative marker of hemodynamic cardiac stress, in a randomized controlled trial. After 6 months of treatment, blood pressure was reduced by about 10 mmHg with similar effects in both groups. hs-cTnT concentrations were measurable in 26.2% of the study population, while hs-cTnI was detected in 98.3%. hs-cTnI concentrations were significantly reduced from 4.6 to 4.2 ng/L in the overall population, 4.7 to 4.4 ng/L in the group containing an angiotensin-receptor blocker and a diuretic, and 4.6 to 4.0 ng/L in the group containing an angiotensin-receptor blocker and a calcium antagonist (all P < 0.001). No significant changes of hs-cTnT were observed. BNP and N-terminal-proBNP (NT-proBNP) concentrations decreased from 15.0 to 12.4 ng/L (P < 0.001) and 64.8 to 53.3 ng/L (P < 0.001), respectively, after 6 months. The authors concluded that blood pressure reduction was associated with a decrease of hs-cTnI, BNP, and NT-proBNP concentrations, which might represent a cardiovascular risk reduction.

The TEAMSTA study extends and corroborates other recent pilot studies highlighting the enormous potential of well-characterized cardiac biomarker assays, particularly hs-cTn, beyond their established and approved indication (1–13). The clinical introduction of hs-cTn assays has provided a novel and unique in-vivo window to the heart, quantifying cardiomyocyte injury. While previously thought to be a phenomenon exclusive to acute myocardial infarction, cardiomyocyte injury has also recently been found to be present, to a varying extent, in patients with chronic cardiovascular disorders such as heart failure, valvular and rhythmogenic heart disease, cardiomyopathy, stable coronary artery disease, left ventricular hypertrophy, and even in patients with arterial hypertension without left ventricular hypertrophy as well as completely healthy individuals (1–14).

The pathophysiological processes, other than acute myocardial ischemia, leading to cardiomyocyte injury as quantified by hs-cTn concentrations are incompletely understood, but are likely multifactorial. Irrespective of the predominant mechanisms present in the individual patient, cardiomyocyte injury and therefore hs-cTn concentrations seem to have a continuous and possibly a near-linear association with major adverse clinical events occurring years or even decades later including cardiovascular death, incident heart failure, stroke, and possibly myocardial infarction. The current study investigated the two most widely used hs-cTn assays: hs-cTnT (Elecsys) and hs-cTnI (Architect). While both seem to provide comparable diagnostic accuracy in the early diagnosis of acute myocardial infarction (10–12), the even higher analytical sensitivity and associated ability to reliably quantify hs-cTn and its changes in the low-normal range render hs-cTnI the preferred tool when assessing patients with only small degrees of cardiomyocyte injury as, e.g., seen in patients with arterial hypertension, patients investigated for the presence or absence of exercise-induced myocardial ischemia, and healthy individuals in general (5–10). It is unknown and a matter of ongoing research to what extent these discrepancies relate to differences in the nature of the analytes cTnT and cTnI, the antibody combination of the hs-cTn assay used, or the analytical sensitivity achieved.

It is also unknown whether the subtle difference in the detected cardiomyocyte injury by the high precision of the hs-cTnI assay within 6 months, 0.4 ng/L in the overall population, is clinically meaningful. Assuming that a particular hs-cTn blood concentration reflects a certain amount of cardiomyocyte injury and turnover, and that a healthy human heart is composed of a given number of cardiomyocytes, and that although likely existing, the potential for renewal of cardiomyocytes is limited, it would very likely be preferable to be in the group of persons with lower hs-cTn concentrations (1–14).

Assessing changes in hs-cTn and/or BNP/NT-proBNP concentrations within randomized controlled clinical trial is an attractive, simple, and inexpensive approach to delineate the effects of medical, behavioral, or interventional treatment on relatively well-defined pathophysiological processes such as cardiomyocyte injury and hemodynamic cardiac stress (1, 2). While cardiovascular biomarkers such as hs-cTn can never substitute for hard clinical endpoints when assessing the clinical effects of interventions, they nicely complement clinical assessment and cardiac imaging. The investigators of the TEAMSTA study (1) must be congratulated for their important contribution to this emerging field.

3 Nonstandard abbreviations

 
• hs-cTn

  high-sensitivity cardiac troponin

 
• BNP

  B-type natriuretic peptide

 
• NT-proBNP

  N-terminal-proBNP.

References