Troponin Helps Risk-Stratify Heart Disease Patients

August 11, 2020

Incorporating high-sensitivity troponin testing into risk algorithms for patients with atherosclerotic cardiovascular disease (ASCVD) provides enhanced risk stratification and leads to the reclassification of about 12% of patients into a more appropriate risk group, a new study shows.

"A key finding of this study is that risk stratification using hsTnI [high-sensitivity troponin I testing] appears to be complementary to the 13 clinical risk factors in the guideline-based ASCVD framework," the authors state.

"These analyses suggest that incorporating an inexpensive and widely available biomarker into ASCVD risk assessment could both improve risk stratification and ensure that patients are offered risk appropriate medical therapies," they conclude.

The study was published online in JAMA Cardiology on August 5.

The researchers, led by Nicholas Marston, MD, Brigham and Women's Hospital, Boston, Massachusetts, explain that the 2018 American Heart Association/American College of Cardiology cholesterol management guidelines identified two distinct groups of patients with ASCVD. The first is a high-risk group, classified on the basis of the presence of two or more major cardiovascular events or one major event with multiple high-risk conditions. The second group includes the remainder of patients with ASCVD, designated as being at lower risk.

They note that on the basis of this clinical risk stratification, the recommendations for the two groups differ in three important ways. First, patients in the high-risk group are to be treated with a high-intensity statin independently of age. In the lower-risk group, statin therapy is a class I recommendation only for patients aged 75 years or younger.

Second, ezetimibe is a class IIa recommendation for the high-risk group and only a class IIb recommendation for lower-risk patients. Third, PCSK9 inhibitors are recommended as class IIa for patients in the high-risk group with LDL levels of 70 mg/dL or higher but are not recommended for the lower-risk group.

The present study investigated whether the addition of hsTnI to guideline-derived ASCVD risk can improve risk classification and guide downstream treatment recommendations.

The study, a substudy of PEGASUS-TIMI 54 trial, included 8635 patients who had had a myocardial infarction (MI) 1 to 3 years before enrollment, were at least 50 years of age, and had at least one high-risk feature.

They were designated as either high risk or lower risk on the basis of their cardiovascular history and comorbidities, in line with the guidelines. Patients were also classified on the basis of hsTnI level using cut points of 2 ng/L (limit of detection) and 6 ng/L (risk threshold), followed by joint classification on the basis of clinical features and hsTnI level.

The primary endpoint was a composite of cardiovascular death, MI, or stroke.

Results showed that when stratified by clinical criteria, the high-risk group had a primary endpoint 3-year event rate of 8.8%, compared with 5.0% in the lower-risk group (hazard ratio, 2.01; 95% CI, 1.58 – 2.57; P < .001).

However, when patients in the high-risk group were further risk stratified on the basis of hsTnI level, 614 of 6789 patients (9.0%) with an undetectable hsTnI level had a 3-year event rate of 2.7% (<1% per year), which was less than the overall rate in the lower-risk ASCVD group.

In the lower-risk ASCVD group, 417 of 1846 patients (22.6%) with an hsTnI level exceeding 6 ng/L had an event rate of 9.1%, comparable to the overall rate in the high-risk ASCVD group.

The addition of hsTnI to guideline-derived ASCVD risk led to an improved net reclassification index at an event rate of 0.15.

Overall, use of hsTnI reclassified 1031 of 8635 patients (11.9%) and led to 1 of 11 patients originally designated as having high-risk ASCVD and 1 of 4 originally classified as having lower-risk ASCVD being reclassified to the alternate group.

In an accompanying commentary, Harvey White, DSc, Auckland City Hospital, New Zealand, says the incremental information on CVD risk makes hsTn very useful for improving risk assessment.

"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 ischemic heart disease," he comments.

Following the evidence from this and other studies, "the new mantra regarding troponins and their role in modern cardiology should now be that any increase in hs-troponin levels within the normal range, no matter what the cause, is bad," White writes.

"In addition, the study by Marston and coworkers shows that measuring hs-troponin I levels enables a robust improvement of risk stratification, and patients reclassified at very high risk can receive more intensive statin therapy or the addition of ezetimibe or PCSK9 inhibitors, as appropriate. For patients reclassified to be at low risk despite statin therapy, there is no need to add other evidence-based lipid-modifying therapies. This is important for improving patient care and outcomes," he concludes.

The (PEGASUS-TIMI 54 trial was sponsored by AstraZeneca. The troponin assay was provided by Abbott Laboratories. Marston reports receiving grant support from the National Institutes of Health. White reports receiving grant support paid to the institution and personal fees for serving on steering committees of the ACCELERAT Study from Eli Lilly and Company, AEGIS-II study from CSL Behring LLC, CAMELLIA study from Eisai Inc, CLEAR OUTCOMES study from Esperion Therapeutics Inc, DAL-GENE study from DalCor Pharma UK Inc, HEART-FID study from American Regent, ODYSSEY trial from Regeneron Pharmaceuticals, and Sanofi Aventis Australia Pty Ltd, SCORED and SOLOIST-WHF trials from Sanofi Aventis Australia Pty Ltd, and STRENGTH trial from Omthera Pharmaceuticals, Inc; serving on an advisory board for Genentech, Inc; and receiving grants or personal fees from AstraZeneca.

JAMA Cardiol. Published online August 5, 2020 Abstract, Commentary

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