High-Sensitivity Cardiac Troponin I and the Diagnosis of Coronary Artery Disease in Patients With Suspected Angina Pectoris

Abstract

BACKGROUND:We determined whether high-sensitivity cardiac troponin I can improve the estimation of the pretest probability for obstructive coronary artery disease (CAD) in patients with suspected stable angina. METHODS AND RESULTS:In a prespecified substudy of the SCOT-HEART trial (Scottish Computed Tomography of the Heart), plasma cardiac troponin was measured using a high-sensitivity single-molecule counting assay in 943 adults with suspected stable angina who had undergone coronary computed tomographic angiography. Rates of obstructive CAD were compared with the pretest probability determined by the CAD Consortium risk model with and without cardiac troponin concentrations. External validation was undertaken in an independent study population from Denmark comprising 487 patients with suspected stable angina. Higher cardiac troponin concentrations were associated with obstructive CAD with a 5-fold increase across quintiles (9%-48%; P<0.001) independent of known cardiovascular risk factors (odds ratio, 1.35; 95% confidence interval, 1.25-1.46 per doubling of troponin). Cardiac troponin concentrations improved the discrimination and calibration of the CAD Consortium model for identifying obstructive CAD (C statistic, 0.788-0.800; P=0.004; χ 2 =16.8 [P=0.032] to 14.3 [P=0.074]). The updated model also improved classification of the American College of Cardiology/American Heart Association pretest probability risk categories (net reclassification improvement, 0.062; 95% confidence interval, 0.035-0.089). The revised model achieved similar improvements in discrimination and calibration when applied in the external validation cohort. CONCLUSIONS:High-sensitivity cardiac troponin I concentration is an independent predictor of obstructive CAD in patients with suspected stable angina. Use of this test may improve the selection of patients for further investigation and treatment. CLINICAL TRIAL REGISTRATION: Presentations with suspected stable angina are common, yet determining an accurate diagnosis is frequently challenging. Patients and clinicians alike are understandably keen to identify the cause of the symptoms in order that these can be treated and hopefully ameliorated. Of equal importance is the concern that these symptoms may reflect prognostically significant atherosclerotic disease with the associated risk of future cardiovascular events. These concerns are appropriate given that 1 in 6 patients will experience coronary death or nonfatal acute coronary syndrome in the 3 years after a diagnosis of stable angina.1 Importantly, this risk remains substantial even in those patients with symptoms deemed noncardiac in origin.1 Consequently, despite the central role of the clinical history and cardiovascular risk factor ascertainment in the assessment process, supplementary investigations are frequently required to provide additional certainty related to the presence or absence of obstructive coronary artery disease (CAD). 2Several national and international bodies have proposed standardized pathways that use risk m...

Response to: ‘Convalescent troponin and cardiovascular death following acute coronary syndrome’ by Kawada

“…First, we agree that when used for risk stratification low cardiac troponin concentrations miss fewer events than applying the sex-specific 99th centile upper reference limit as a single threshold, and indeed we identified the lower troponin threshold of 5 ng/L to be associated with a 5-year negative predictive value for cardiovascular death of 97.1% (95% CI 95.5 to 98.6) 2. Further, in keeping with our prior work using this assay within the suspected acute coronary syndrome and stable ischaemic heart disease settings,3–5 we report that troponin provided a continuous marker of risk, with a Global Registry of Acute Coronary Events (GRACE)-adjusted hazard ratio of 1.36 (95% CI 1.26 to 1.47) per doubling in concentration. We instead refer to the 99th centile threshold only as a readily understood indicator of high risk that will be familiar to the general cardiology readership of Heart .…”

Clinical determinants of plasma cardiac biomarkers in patients with stable chest pain

“…Our findings suggest that cardiac CT can achieve some of the necessary characterisation of biomarker determinants in stable patients. Obstructive coronary artery disease correlates with troponin concentrations in patients with stable angina 24. Here, we applied the CT-adapted Leaman score and demonstrate that, in addition to other clinical characteristics, this association persists after adjustment for left ventricular mass and volume.…”

Comparison between High-Sensitivity Cardiac Troponin T and Cardiac Troponin I in a Large General Population Cohort

“…If troponin is to be utilized for population level cardiovascular disease risk screening, this means older patients will be more frequently identified with increased troponins on screening, and will be more likely to be referred for further cardiovascular testing such as echocardiography or coronary angiography. This may be entirely appropriate as raised troponin in this group may well reflect undiagnosed structural or coronary heart disease (28). Clinicians therefore need to be aware of the effect of age on troponin reference concentrations, and further evaluation of the 99 th centile, or biological equivalents, in older patients with chest pain would be welcome.…”