scholarly journals Derivation and External Validation of a High‐Sensitivity Cardiac Troponin–Based Proteomic Model to Predict the Presence of Obstructive Coronary Artery Disease

2020 ◽  
Vol 9 (16) ◽  
Author(s):  
Cian P. McCarthy ◽  
Johannes T. Neumann ◽  
Sam A. Michelhaugh ◽  
Nasrien E. Ibrahim ◽  
Hanna K. Gaggin ◽  
...  

Background Current noninvasive modalities to diagnose coronary artery disease (CAD) have several limitations. We sought to derive and externally validate a hs‐cTn (high‐sensitivity cardiac troponin)–based proteomic model to diagnose obstructive coronary artery disease. Methods and Results In a derivation cohort of 636 patients referred for coronary angiography, predictors of ≥70% coronary stenosis were identified from 6 clinical variables and 109 biomarkers. The final model was first internally validated on a separate cohort (n=275) and then externally validated on a cohort of 241 patients presenting to the ED with suspected acute myocardial infarction where ≥50% coronary stenosis was considered significant. The resulting model consisted of 3 clinical variables (male sex, age, and previous percutaneous coronary intervention) and 3 biomarkers (hs‐cTnI [high‐sensitivity cardiac troponin I], adiponectin, and kidney injury molecule‐1). In the internal validation cohort, the model yielded an area under the receiver operating characteristic curve of 0.85 for coronary stenosis ≥70% ( P <0.001). At the optimal cutoff, we observed 80% sensitivity, 71% specificity, a positive predictive value of 83%, and negative predictive value of 66% for ≥70% stenosis. Partitioning the score result into 5 levels resulted in a positive predictive value of 97% and a negative predictive value of 89% at the highest and lowest levels, respectively. In the external validation cohort, the score performed similarly well. Notably, in patients who had myocardial infarction neither ruled in nor ruled out via hs‐cTnI testing (“indeterminate zone,” n=65), the score had an area under the receiver operating characteristic curve of 0.88 ( P <0.001). Conclusions A model including hs‐cTnI can predict the presence of obstructive coronary artery disease with high accuracy including in those with indeterminate hs‐cTnI concentrations.

Cardiac troponin is the preferred biomarker for myocardial infarction, thanks to its sensitivity and absolute specificity for the heart. The availability of high-sensitivity assays (hs-cTnT and hs-cTnI), capable of measuring with excellent analytical precision very low levels of circulating troponin, raised the issue of whether transient ischemia is a sufficient stimulus for troponin release. For this purpose, in a series of patients submitted to a stress test (exercise ECG/echo test; dipyridamole echo test; dobutamine echo test), we measured plasma levels of hs-cTnT at baseline and 6 hours after the end of the test. Plasma concentrations of hs-cTnT significantly increased in the vast majority of patients after the test. Significant elevations were documented in response to each stressor, regardless of the test result, after both positive and negative tests. Moreover, troponin significantly increased in response to the stress, both in patients with and in patients without obstructive coronary artery disease. Despite a good sensitivity (80% and 89%), troponin showed a very low specificity (32% and 47%) for stress-induced ischemia and coronary artery disease, respectively. Myocardial release of troponin is a multifactorial process, mediated not only by cardiomyocyte necrosis, but also through several different mechanisms such as myocardial ischemia, increase in cardiac work, and hemodynamic overload. Transient elevation of high sensitivity cardiac troponin is not a useful tool for detecting spontaneous or stress-induced ischemia. L


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
H W Zhang ◽  
Y X Cao ◽  
J L Jin ◽  
Y L Guo ◽  
Y Gao ◽  
...  

Abstract Background It has been reported that coronary artery disease (CAD) is characterized by inflammation and non-obstructive CAD (NOCAD) increases the risk of cardiovascular events (CVEs) compared with ones with normal or near-normal coronary arteries (NNCA), even is similar to obstructive CAD (OCAD). We hypothesized that elevated high-sensitivity C-reactive protein (hs-CRP) may be linked to CVEs in those patients with NOCAD. Purpose To investigate the predictive role of hs-CRP in patients with NOCAD. Methods Of 7,746 consecutive patients with angina-like chest pain admissions, 4,662 eligible patients were enrolled who received coronary artery angiography (CAG) and followed up for the CVEs comprising all-cause mortality, myocardial infarction, stroke and late revascularization. According to the results of CAG, the patients were classified as NNCA group (<20% stenosis, n=698, 15.0%), NOCAD group (20–49% stenosis, n=639, 14.3%), and OCAD group (≥50% stenosis, n=3325, 70.7%). They were further subdivided into 3 groups according to baseline hs-CRP levels (<1, 1–3 and >3 mg/L). Proportional hazards models were used to assess the risk of CVEs in all patients enrolled. Results A total of 338 patients (7.3%) experienced CVEs during an average of 13403 person-years follow-up. Patients with NOCAD and OCAD had higher rates of CVEs compared to those with NNCA (p<0.05, respectively). In Cox's models after adjustment of confounders, the risk of CVEs elevated with the increasing degrees of CAD with hazard ratio of 2.01 [95% confidence interval (95% CI): 1.07–3.79, p=0.03] for patients with NOCAD and 2.81 (95% CI: 1.60–4.93, p<0.001) for patients with OCAD compared with the NNCA group. Moreover, elevated hs-CRP levels were associated with the severity of coronary lesions and an elevated increased risk of CVEs in patients with NOCAD and OCAD compared those with NNCA (p<0.05, respectively). Conclusions Patients with NOCAD had indeed worse outcomes and hs-CRP levels were positively in relation to the CVEs in those with NOCAD, which may help to the risk assessment in ones with NOCAD. Acknowledgement/Funding This study was partly supported by Capital Health Development Fund (201614035) and CAMS Innovation Fund for Medical Sciences (2016-I2M-1-011) awarded


2021 ◽  
Vol 54 (3) ◽  
pp. 239-243
Author(s):  
Haroon Ishaq ◽  
Bilal Akhtar ◽  
Mukesh Kumar ◽  
Ghulam Shabbir Shar ◽  
Abdul Hakeem ◽  
...  

Objectives: The objective of this study was to determine the predictive value of GRACE score for predicting obstructive coronary artery disease in patients with non ST-segment elevation myocardial infarction (NSTEMI). Methodology: This cross-sectional study was conducted at the largest public sector cardiac care center of the Pakistan between January 2020 and June 2020. In this study, we included adult patients diagnosed with NSTEMI and correlation of GRACE score was assessed with angiographic finding of obstructive CAD defined as ≥50% stenosis in the left main or ≥70% stenosis in other coronary arteries. Results: A total of 227 patients were included in this study, out of whom 72.2% (164) were male patients and mean age was 55.77 ± 9.15 years. Mean GRACE score was found to be 95.89 ± 21.15. On coronary angiography obstructive CAD was present in 84.6% (192) of the patients. Area under the cure for predicting obstructive CAD was 0.669 [0.552 to 0.785]. The optimal cutoff value of GRACE score was ≥ 84 with sensitivity of 79.7% [73.3% to 85.1%] and specificity of 57.1% [39.3% to 73.7%]. GRACE score of ≥ 84 was found to be an independent predictor of obstructive CAD with odds ratio of 4.33 [1.61 - 11.64; p=0.004] adjusted for gender, age, hypertension, diabetes, family history of CAD, and smoking. Conclusion: GRACE score has a moderate predictive value in predicting obstructive CAD in patients with NSTEMI. The optimal cutoff value of 84 is an independent predictor with good sensitivity but moderate specificity in predicting obstructive CAD.


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