الفهرس 
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Abstract
Coronary artery disease (CAD), also referred to as ischemic heart disease (IHD), is the main global cause of death, accounting for more than 9 million deaths in 2016 according to the World Health Organization (WHO) estimates. CAD used to be known as a disease of the elderly but this concept changed nowadays. Globally, CAD was the leading killer in the age group ≥60 years. Now it is estimated that about 4–10 % of individuals with documented CAD are less than 45 years of age with 1,332,000 deaths in adults aged 15–59 years.
Acute coronary syndrome (ACS) is a broad term representing a common end result which is acute myocardial ischemia. The use of multivariate risk score models has been shown to represent the most accurate way to predict risk, being superior to the subjective clinical impression. The Global Registry of Acute Coronary Events (GRACE) risk prediction model was developed from an earlier cohort of GRACE patients and has been extensively validated and shown to be a strong predictor of in hospital mortality across the spectrum.
The use of imaging to directly measure the burden of atherosclerosis can provide a more personalized risk assessment than using risk factor-based calculators. Coronary artery calcium scoring (CACS) using computed tomography (CT) can be used to determine the actual presence and extent of calcified coronary artery plaque.
The aim of our study is to enhance patient risk stratification which can potentially influence the treatment strategy. Our objective is to evaluate the correlation of the GRACE risk score, the coronary artery calcium (CAC) score and their use combined with the extent and severity of obstructive CAD in patients with non-ST segment elevation acute coronary syndrome (NSTE-ACS).
This is a cross sectional observational study that included 202 Patients coming to Ain Shams University Hospitals with NSTE-ACS and planned for coronary angiograph. Patients were subjected to history taking, examination, blood samples and electrocardiogram to calculate the GRACE score and CACS using CT to calculate CAC score.
Following the calculation of the GRACE score, patients were divided into 3 groups according to the predicted in-hospital and post-discharge to 6 months mortality risk into low, intermediate and high risk groups. Patients then underwent CACS using CT and were divided into 4 groups according to their Agatston score. According to the findings of invasive coronary angiography, patients were divided into 2 groups depending on whether or not there was at least one significant stenosis. Patients who had significant stenosis were then divided into 4 subgroups according to the number of vessels affected; one-vessel disease, two-vessel disease, multi-vessel disease and left main CAD.
134 patients were males representing 66.3% of the participants. The mean age of the whole group was 57.00 ± 10.42. After obtaining results of serum creatinine and cardiac enzymes levels, GRACE score was calculated for all patients and the median value was 97.5 (78-116). Regarding the in-hospital mortality risk 131 patients (64.9%) were in the low risk group, 52 patients (25.7%) were in the intermediate risk group and 19 patients (9.4%) were in the high risk group. Regarding the post discharge to 6 months mortality risk, 82 patients (40.6%) were in the low risk group, 77 patients (38.1%) were in the intermediate risk group and 43 patients (21.3%) were in the high risk group. All patients then underwent CACS and the median calcium score of the whole study group was 56.5 (3 – 254). 46 (22.8%) patients had a CAC score of zero.
As previously mentioned, following invasive coronary angiography, patients were divided into 2 subgroups depending on whether or not there was at least one significant stenosis. 122 patients had at least one vessel with significant stenosis.
Each of the CAC score and the GRACE score was then numerically and categorically compared with each subgroup. The CAC score yielded a highly significant difference between the two subgroups with a median CAC score of 183.6 (49.7 – 402) in the subgroup with significant stenosis and a median score of 1.5 (0.0 – 20.5) in the subgroup with no significant stenosis (p-value 0.000). This suggests that the accuracy of CACS to detect significant CAD was good, with an area under the receiver-operating characteristic (ROC) curve of 0.896. In our study population, the absence of coronary artery calcium i.e. a CAC score of zero had a highly significant relationship with the absence of significant stenosis on invasive coronary angiography (p value <0.001). A CACS of zero had a negative predictive value of 84.8% [95% Confidence Interval (CI): 72.4% to 92.2%], a positive predictive value of 73.7(95% CI: 69.3% to 77.7%), a sensitivity of 94.3 %(95% CI: 88.5% to 97.7 %), and a specificity of 48.8% (95% CI: 37.4% to 60.2%).
In addition, when the median GRACE score was compared between the two subgroups, a highly significant difference was detected with a median GRACE score of 108(88-122) among the subgroup with significant stenosis and a median score of 83.5 (68.5 – 99) among the subgroup with no significant stenosis (p-value <0.001). According to our study, most of the patients with significant stenosis had at least an intermediate risk for in-hospital and post discharge to 6 months mortality while among the group with no significant stenosis, 86.2% of the patients had low risk for in-hospital mortality and 61.2% had low risk for post discharge mortality. We then tested the use of zero CAC to exclude obstructive CAD in patients with low in-hospital and post discharge mortality risk. We detected that the use of zero CAC to rule out obstructive CAD in the low risk group had a higher specificity and negative predictive values compared to its use to exclude obstructive CAD in the other risk groups.
However, exactly 47.5% of the patients with no significant stenosis had a CAC of more than zero and less than 100. Therefore, in an attempt to detect a more accurate cut-off value, in addition to the ROC curve plotted for the CAC score, an ROC curve was plotted for the GRACE score and for the CAC score combined with the GRACE score. It was used to suggest a cut-off value for each score below which obstructive CAD can be excluded in patients presenting with NSTE-ACS. from this curve, it could be concluded that the use of CACS in combination with the GRACE score improves the sensitivity, specificity, positive and negative predictive value in comparison to the use of the GRACE score alone. Furthermore, in comparison to the zero CAC score, the CAC score cut-off value of 35 had higher specificity and positive predictive value but on the other hand had lower sensitivity and negative predictive values and cannot therefore exclude obstructive CAD as reliably as zero CAC score.
Furthermore, as previously mentioned, patients who had significant stenosis were then divided into 4 subgroups according to the number of vessels affected; one-vessel disease, two-vessel disease, multi-vessel disease and left main CAD.
Comparing the CAC score and the GRACE score between the four sub-groups showed a highly significant difference when compared numerically and categorically with a similar p-value of 0.00. We observed that the greater the number of affected coronaries the higher was the median CAC score. With a CAC score of 100 or more, only 3 patients had no obstructive CAD while in the group of patients with a CAC score of 400 or more, the majority of patients (76.6%) a had a multi-vessel disease. Similarly, when we compared the median GRACE score between the four subgroups, it was concluded that a higher GRACE score was associated with a more extensive CAD which aided us to detect a statistically significant relationship between the predicted mortality risk with the extent of CAD. For instance, regarding the predicted in-hospital mortality risk, 53.1% of the patients with a predicted low risk had no obstructive CAD while 61.1% of the patients with a predicted high risk had multi-vessel disease.
This could also be applied to left main CAD because when patients with or without left main CAD were compared regarding the CAC score and GRACE score, it was observed that patients with left main CAD had higher CAC and GRACE scores yielding a high statistical significance with a p-value of 0.00 and 0.01 respectively.
Finally, dyslipidemia was found to be significantly related to higher calcium scores and a more extensive obstructive CAD including left main CAD. Using Spearman correlation coefficient, there was a positive correlation between each of elevated total cholesterol, LDL-C and reduced HDL-C with the CAC score. The strongest correlation was found between LDL-C level and the CAC score; the higher the LDL-C level, the higher was the CAC score. However, there was no correlation between the triglyceride level and the CAC. Similarly, elevated cholesterol and LDL-C were significantly associated with multivessel disease including left main CAD.
To summarize, our study concluded that CAC score is highly sensitive, but less specific for the detection of obstructive CAD, and therefore, excellent for ruling out disease especially in the low risk group. A CAC of zero could not reliably exclude obstructive CAD in only a minority of patients presenting to the emergency department (ED) with NSTE-ACS.
Our study detected that a higher calcium score was able to significantly predict a more extensive obstructive CAD or a left main disease. In comparison to CAC score, the use of GRACE score alone to predict obstructive CAD showed a statistical significance in predicting the presence of a significant stenosis and a strongly positive correlation with the number of vessels affected. However, the use of GRACE score alone was less sensitive than CAC score. Therefore, combining CAC score with GRACE score improved the latter’s ability to predict obstructive CAD which was not studied in previous studies and thus it can be used as a new tool for cardiovascular risk stratification.