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Application of High-Sensitivity Troponin in the ASCVD Framework of Cholesterol Guidelines
Quick Takes
- Estimating risk of CV death, MI, and stroke in established ASCVD is more intuitive than in primary prevention and related to CHF, LVEF, diabetes, blood pressure, renal function, statins, aspirin, and noninvasive testing rather than 10-year risk estimates of ASCVD based on weighted point-scores for CV risk factors.
- That the very inexpensive biomarker hsTnI can result in reclassification from very high-ASCVD annual risk (about 3%) to lower risk (<1%) in 12% and from lower risk to very high-ASCVD risk in 25% makes this a very cost-effective strategy.
- Further studies and possibly outcomes trials are necessary to evaluate the impact of cTnI on CV death, MI, and stroke post-ACS, particularly considering effort tolerance, left and right ventricular function, ischemic burden, other biomarkers, and evidence-based treatments.
Study Questions:
Does the addition of high-sensitivity troponin (hsTn) testing to guideline-derived risk assessment in persons with atherosclerotic cardiovascular disease (ASCVD) improve risk classification and downstream treatment recommendations?
Methods:
A nested prospective cohort biomarker substudy was performed in PEGASUS-TIMI 54, a trial in persons with a myocardial infarction (MI) 1-3 years earlier, which compared ticagrelor to placebo in the background of aspirin. Patients were assigned to risk groups of either very high-risk ASCVD (≥2 prior CV events defined as acute coronary syndrome [ACS] in the past 12 months, MI prior to 12 months, ischemic stroke or peripheral vascular disease, or a single major event plus multiple high-risk conditions and ASCVD, and lower risk having a prior MI without the major risk factors). Patients were also classified on the basis of hsTnI level (ARCHITECT assay; Abbott) 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. Participants were ≥50 years of age with ≥1 high-risk feature. The prespecified primary endpoint of the trial was a composite of CV death, MI, or stroke. The dates of analysis were June 2019–January 2020.
Results:
Among 8,635 patients, the median age was 65 years (interquartile range, 58-71 years), and 6,614 (76.6%) were men; 8,340 (96.6%) were white and 176 (2.0%) were black individuals. Patients meeting clinical criteria for the very high-risk ASCVD group had a primary endpoint 3-year event rate of 8.8% compared with 5.0% in the lower-risk ASCVD group (hazard ratio, 2.01; 95% confidence interval [CI], 1.58-2.57; p < 0.001). When patients in the very high-risk ASCVD group were further risk stratified by hsTnI level, 614 of 6,789 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. Analogously, in the lower-risk ASCVD group, 417 of 1,846 patients (22.6%) with an hsTnI level >6 ng/L had an event rate of 9.1%, comparable to the overall rate in the very high-risk ASCVD group. The addition of hsTnI to guideline-derived ASCVD risk led to a net reclassification index at an event rate of 0.15 (95% CI, 0.10-0.21). Overall, use of hsTnI reclassified 1,031 of 8,635 patients (11.9%) (1 in 11 with very high-risk ASCVD and 1 in 4 with lower-risk ASCVD).
Conclusions:
The findings of this cohort substudy suggest that a strategy incorporating hsTn into a guideline-derived established ASCVD risk algorithm provides enhanced risk stratification and reclassifies 11.9% of patients into a more appropriate risk group. This application of hsTn testing might be used to optimize the care of patients with ASCVD.
Perspective:
While there is not a clear answer, cardiac troponin I (cTnI) and cTnT are becoming an attractive tool for predicting outcome in the healthy elderly, hypertension, diabetes, stable coronary heart disease, and post-MI, and have major implications for optimizing a cost-effective decision process for intensity of treatment (e.g., PCSK9 antibody, sacubitril-valsartan, icosapent ethyl), and use and predictive value of other diagnostic studies.
Clinical Topics: Acute Coronary Syndromes, Dyslipidemia, Prevention, ACS and Cardiac Biomarkers, Lipid Metabolism, Nonstatins, Hypertension
Keywords: Acute Coronary Syndrome, Aspirin, Atherosclerosis, Biomarkers, Brain Ischemia, Cholesterol, Coronary Disease, Hypertension, Myocardial Infarction, Myocardial Ischemia, Primary Prevention, Risk Assessment, Risk Factors, Stroke, Troponin, Vascular Diseases
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