In his presentation for the European Society of Cardiology - Acute Cardiovascular Care Biomarker series Prof. David Morrow (Brigham and Women's Hospital, Boston) elaborated on the use of high-sensitivity cardiac Troponin T or I (hs cTn) as quantitative markers of (chronic) cardiomyocyte injury in stable atherosclerotic cardiovascular disease (ASCVD). Elevation in cardiac Troponin (measured by high-sensitivity assays) is consistently shown to be associated with long term risk. Specifically, persistent elevation of cardiac troponin (> 99% upper reference limit) has been associated with long term adverse outcomes, including cardiovascular death, heart failure, myocardial infarction or hospitalisation in several different patient populations ranging from stable coronary artery disease, diabetes and post acute coronary events.1,2,3
Troponin testing can identify patients requiring further diagnostic testing
The DALLAS Heart Study showed that clinical characteristics that mostly contribute to Troponin elevation are male sex, age, renal function, diabetes and left ventricular mass.4 The release of cardiac troponin in conditions other than acute coronary syndrome can have many different underlying mechanisms, reflecting different potential sources of myocardial injury that can be acute or chronic. Management of patients with stable ASCVD could thereby be facilitated by the use of hs cTn T or I, by identifying patients that require further diagnostic testing, such as cardiac stress imaging, magnetic resonance imaging, chest x-ray or coronary angiography. These investigations can help to understand the underlying pathobiology.
Pharmacological treatment options for patients with stable ASCVD and high cardiovascular risk
Although cardiac Troponin elevation predicts long term risk, the question remains how this should influence patient treatment and pathways. In the WOSCOP trial studying men with raised low-density lipoprotein cholesterol (LDL) and no history of myocardial infarction, statin therapy was able to reduce Troponin and LDL levels.5 Interestingly, those patients with highest decline of troponin showed up to 80% of risk reduction for CV events.5 In addition, the Fourier trial showed that use of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors lead to an absolute risk reduction of 2% in patients stratified into “very high risk group” using the 2018 American Heart Association/American College of Cardiology Cholesterol Management Guideline ASCVD risk algorithm that also had elevated Troponin levels.6
Added value of Troponin in clinical risk stratification algorithms
Current guidelines such as ACC/AHA guideline on blood cholesterol patients with clinical established ASCVD do contain risk stratification algorithms to stratify patients into two risk groups: high risk and not high risk, where patients identified as high risk are recommended to receive high intensity statin therapy. However, these risk algorithms currently do not include Troponin values/elevation as a parameter in their risk score.7 Superimposing patients' Troponin levels on the ACC/AHA clinical risk score was able to further stratify patients in the “high-risk group” when TnI was >6ng/L as having highest risk of CV death.8 This suggests that inclusion of troponin to such guideline proposed risk scores could bring additive value for patient risk stratification and potentially future personalised patient care.
What are the next steps to advance ASCVD patient care in the future?
Finally, although there is robust data that cardiac Troponin can improve risk stratification in patients with ASCVD and the case for testing is strong, there is currently a lack of prospective trials that analyse how to apply this in clinical practice, especially considering how treatment should proceed after elevated Troponins have been detected in non-acute settings. Going forward the use of machine learning and other advanced analytical techniques can help to develop improved risk stratification models. Furthermore, moving from binary cut offs for biomarkers (i.e. Troponin) to continuous data as well as developing approaches that are embedded into electronic health record systems could prove useful to facilitate patient care in the clinical setting.
Find the recording of the ESC ACVC Biomarker series with Prof. David Morrow here: ACVC Biomarker Talks: high sensitivity cardiac troponin in stable ASCVD
Please mind that registration to the ESC365 platform is required to watch the recordings.