High-Sensitivity Troponin Testing Could Improve ASCVD Risk Stratification

August 6, 2020

Analysis of PEGASUS-TIMI 54 patients indicates incorporating the biomarker into guideline-based risk assessment could improve risk classification and care.

New research indicates incorporating high-sensitivity troponin (hsTn) testing into an American Heart Association/American College of Cardiology (AHA/ACC) cholesterol management guideline-based algorithm for patients with atherosclerotic cardiovascular disease (ASCVD) could improve risk stratification and help optimize care.

When examining use of the biomarker-testing approach in patients from the PEGASUS-TIMI 54 trial, investigators determined incorporation of hsTn testing resulted in the reclassification of 11.9% of patients into a more appropriate risk group.

In an effort to understand whether addition of hsTn testing to guideline-derived ASCVD risk classification, a team led by investigators of the TIMI study group designed and conducted a prospective cohort biomarker substudy of patients from the PEGASUS-TIMI 54 trial. From the 21,162 patients included in the original trial, 8635 were included in the current substudy

The median age of the study cohort was 65 years (IQR, 58-71 years), 76.6% were men, and 96.6% were White individuals. All patients included in the study experienced myocardial infarction 1-3 years prior to enrollment, were at least 50 years of age, and had at least 1 high-risk feature.

For the analysis, patients were assigned to AHA/ACC guideline-derived risk groups classified as very-high risk ASCVD or a lower-risk ASCVD based on their cardiovascular history and comorbidity. Patients were also classified according to hsTnI levels, with threshold points of 2 ng/L and 6 ng/L, which was defined as an undetectable level and the increased risk threshold, respectively. This was followed by a joint classification on the basis of clinical features and hsTnI level.

The primary end point of the analysis was a composite of cardiovascular death, myocardial infarction, or stroke. Upon analysis, patients meeting the criteria for the very high-risk ASCVD group had a 3-year event rate of 8.8% when assessing for the primary end point. In comparison, the rate among patients in the lower-risk group was 5.0% (HR, 2.01; 95% CI, 1.58-2.57; P <.001).

When stratifying patients according to hsTnI level, 9.0% of patients in the very high-risk group had an undetectable hsTnI level and these patients had a corresponding 3-year event rate of 2.7%, which investigates noted was lower than the overall rate in the lower-risk group. Among patients in the lower-risk group, 22.6% had an hsTnI level exceeding the 6 ng/L risk threshold and these patients had a corresponding 3-year event rate of 9.1%, which investigators noted was comparable to the rate seen in the very high-risk group.

Based on these results, investigators determined the addition of hsTnI levels to guideline-derived ASCVD risk assessments led to a net reclassification index at event rate of 0.15 (95% CI, 0.10-0.21). Furthermore, results indicated use of hsTnI led to reclassification of 11.9% of patients in the substudy.

In a related editorial published in JAMA Cardiology, Harvey White, DSc, of the Auckland City Hospital and University of Auckland in New Zealand, highlights the potential of adding the biomarker to risk assessment algorithms but also warns against over-interpretation of results.

“It is not clear from the study by Marston and coworkers why increased hs-troponins within the normal range were associated with increased CVD risk. However, even without a complete understanding of the underlying mechanisms for the increased hs-troponin levels, the incremental information on CVD risk makes it very useful for improving risk assessment,” White wrote. “Troponin levels should not be viewed just as a marker for myocardial injury and diagnosis of MI in acute coronary syndrome but should be used more frequently for assessing CVD risk in stable patients with IHD.”

This study, “Clinical Application of High-Sensitivity Troponin Testing in the Atherosclerotic Cardiovascular Disease Framework of the Current Cholesterol Guidelines,” was published in JAMA Cardiology.