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Correlation between the serum procalcitonin level and the extension and severity of coronary artery disease in patients with non-ST-segment elevation myocardial infarction

Hashemipour, Seyed-Vahid; Pourhosseini, Hamidreza; Hosseinsabet, Ali

Cardiovascular Endocrinology & Metabolism: June 2019 - Volume 8 - Issue 2 - p 62–66
doi: 10.1097/XCE.0000000000000165
Original Article
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Objectives Research has shown correlations between some, but not all, inflammatory mediators and coronary atherosclerosis burden. Conflicting results have been reported on the correlation between the serum procalcitonin (PCT) level and the severity and extension of coronary artery disease (CAD). We evaluated the correlation between PCT and the severity and extension of CAD in patients with non-ST-elevation myocardial infarction (NSTEMI).

Patients and methods In this prospective cross-sectional study, the serum PCT level was measured 48 h after hospital admission in 131 patients with a diagnosis of NSTEMI. All the patients underwent selective coronary angiography, and the severity and extension of their CAD was evaluated with the Gensini score. The study population was assigned to two groups on the basis of the median of the Gensini score: those with a score higher than the median and those with a score lower than the median.

Results There was no statistically significant difference with regard to the serum PCT level between the two groups (P = 0.511). In the multivariable logistic regression analysis, after adjustment for the potential confounders, the serum PCT level was not a determinant of the Gensini score (P = 0.502).

Conclusion The second 24-h postadmission serum PCT level was not correlated with the severity and extension of CAD according to the Gensini score in our patients with NSTEMI.

Cardiology Department, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran

Received 14 December 2018 Accepted 28 January 2019

Correspondence to Ali Hosseinsabet, MD, Cardiology Department, Tehran Heart Center, Karegar Shomali Street, Tehran, Iran e-mail: ali_hosseinsabet@yahoo.com

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Introduction

Inflammation plays a role in the pathogenesis of atherosclerotic lesions such as coronary artery disease (CAD) [1]. During the atherogenesis process, a large number of inflammatory mediators are released, which can be an indicator of the burden of atherosclerosis [2,3]. One of these inflammatory mediators purported to have a role in atherogenesis is procalcitonin (PCT), a precursor of calcitonin [4,5]. PCT has a peptide structure and is released by mesenchymal cells during bacterial infections [6]. PCT is associated with the prognosis in acute myocardial infarction (MI) [7] and heart failure [8].

The extension and severity of CAD is evaluated with several methods, one of which is coronary angiography [9]. There are also several scoring systems for the assessment of the severity and extension of CAD. The Gensini score has been the most frequently used of all these systems [10]. The Gensini scoring system takes into account the severity, location, and importance of atherosclerotic plaques [11] and has an acceptable correlation with coronary intravascular ultrasound findings [10] and the prognosis in patients with acute coronary syndrome [12].

Research has shown correlations between CAD burden on the basis of the Gensini score and some, but not all, inflammatory mediators [2,3,13]. There is conflicting evidence with regards to the correlation between the serum PCT level and the extension and severity of CAD [14–17]. A thorough investigation of this correlation in various clinical conditions may provide the scientific community with a more in-depth understanding of the inflammation role in atherosclerosis and lead to better risk stratification and clinical decision-making. The aim of this study was to evaluate the correlation between the serum PCT level and the severity and extension of CAD assessed with the Gensini score in patients with non-ST-elevation myocardial infarction (NSTEMI).

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Materials and methods

Study population

The present prospective cross-sectional study recruited 131 patients admitted to our hospital with a final diagnosis of NSTEMI between May 2015 and January 2017. The exclusion criteria comprised a history of cancer, hepatic failure, creatinine more than 1.3 mg/dl, a history of percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery, the evidence of active infection, a history of inflammatory diseases, a history of noncardiac surgery or trauma in the preceding month, a history of antibiotic usage in the preceding month, cardiogenic shock or cardiac arrest at presentation, nonconsent to participation in the study, and nonconsent to selective coronary angiography. NSTEMI was defined according to the third universal definition of MI [18]. Diabetes was defined as antidiabetic drug usage or a minimum fasting blood glucose level of 126 mg/dl in two measurements. Hypertension was defined as antihypertensive drug usage or blood pressure of more than 140/80 mmHg in two separate measurements. A family history was considered to be positive for CAD when at least one of the first-degree relatives of the patient was affected by CAD (male relatives ≤55 years and female relatives ≤65 years).

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Laboratory data

Venous samples for cell blood count, fasting blood glucose, and the lipid profile were drawn after 12 h’ fasting on the morning after admission, and venous samples for PCT were obtained in the second 24 h after admission. These second serum samples were frozen at −70°C. The serum PCT level was assessed using a commercial kit (Roche Diagnostics GmbH, Manheim, Germany) and analyzed by the electrochemiluminescent immunoassay method with an Elecsys 2010 analyzer. The lower limit of detection was 0.020 ng/ml. The cardiac troponin T serum level was measured by the electrochemiluminescent immunoassay method with a commercial kit (Roche Diagnostics GmbH) using an Elecsys 2010 analyzer.

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Coronary angiography

Selective coronary angiography was performed from the femoral artery according to the Judkins technique with a Siemens AXIOM Artis (Erlangen, Germany) or Philips AlluraClarity (Best, The Netherlands) setting. All the injections were administered manually, and Visipaque (GE Health Care, Cork, Ireland) was injected. The severity and extension of CAD was evaluated with the Gensini score [11]. In summary, a location score of 5 was allocated to the left main, 2.5 to the proximal portion of the left anterior descending artery and the left circumflex artery, 1.5 to the midportion of the left anterior descending artery, and one to the coronary segments other than the posterolateral branch and the second diagonal, which were allocated the score of 0.5. These scores multiplied by 1, 2, 4, 8, 16, and 32 were allocated to 25, 50, 75, 90, 99, and 100% stenoses, respectively. The total score for each patient was calculated. A 50% diameter stenosis or more in each epicardial coronary artery was specified as a significant stenosis and demonstrated as a vessel disease (i.e. single-vessel, double-vessel, or triple-vessel disease). The study proposal was approved by the institutional review board, and informed written consent was obtained from the entire study population before collecting the venous samples for PCT. All the treatments, medications, and procedures during the patients’ hospital admission were carried out in accordance with the current guidelines [19,20].

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Statistical analysis

The patients were categorized into two groups on the basis of the median of their Gensini score: the patients with a score higher than the median and those with a score lower than the median. The categorical variables were demonstrated as absolute frequencies and percentages and were compared using the χ2-test or the Fisher exact test, whichever one was indicated. The continuous variables were presented as mean and SD and compared using the Student t-test if they were normally distributed; otherwise, they were expressed as median and interquartile ranges. For the comparisons, the Mann–Whitney U-test was used. The normal distribution of the continuous data was checked with the Kolmogorov–Smirnov test. The variables with a P value of less than 0.20 in that analysis and the clinically important variables were entered into a multivariable logistic regression analysis to assess the association between the serum PCT level and the high Gensini score of the coronary artery in the presence of possible confounders. The Hosmer–Lemeshow goodness of fit was used before the application of this analysis. Odds ratios with 95% confidence intervals were presented. Effect size was computed by standardized mean difference (difference between two groups’ means divided by their pooled SDs), referred to as Cohen’s d. The statistical analyses were conducted with the IBM SPSS statistics for Windows, version 24.0 (IBM Corp., Armonk, New York, USA). A P value of less than 0.05 was considered statistically significant.

The sample-size calculation of our investigation was on the basis of the findings of a study by Ertem et al. [17]. Taking into account the mean and SD of the PCT level in the high and low atherosclerotic burden groups (mean = 0.100 vs. 0.055 μg/l and SD = 0.100 vs. 0.020) to perceive the difference between the two groups (equivalent to an effect size of 0.62) at the level of significance of 0.05 (α = 0.05) and the power of study of 90% (1−β = 0.9), we required two groups each consisting of at least 60 patients. To boost confidence, we chose to select 131 patients.

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Results

The data on the study population’s demographics, drug history, left ventricular ejection fraction, and angiographic examinations are depicted in Table 1. The overall Gensini score in this study population was 57.0 (36.0–85.5). The patients with a Gensini score higher than the median were older than those with a Gensini score lower than the median. The left ventricular ejection fraction was higher in the patients with a low Gensini score. The diuretic usage was more in the patients with a Gensini score higher than the median, although the overall usage was very low. PCI was performed more frequently in the group of patients with a Gensini score lower than the median, whereas coronary artery bypass graft surgery was performed more frequently in the other group, which was concordant with the higher number of patients with triple-vessel disease in the group with a Gensini score greater than the median and the higher number of patients with single-vessel disease in the group with a Gensini score lower than the median. The other variables were not statistically significantly different between the two study groups. The difference between the two groups with respect to the PCT level did not constitute statistical significance. The effect size for PCT was 0.19. The multivariable logistic regression analysis showed that a high Gensini score was not correlated with PCT in the presence of age, sex, diabetes, hypertension, a family history of CAD, cigarette smoking, the low-density lipoprotein level, the hematocrit level, and the left ventricular ejection fraction (Table 2).

Table 1

Table 1

Table 2

Table 2

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Discussion

In this study, we evaluated the Gensini score as a marker of the severity and extension of CAD and the serum PCT level as a marker of inflammation in patients with NSTEMI and found no statistically significant correlation between them. In this study, the observed effect size for PCT was small, which indicated that the power of the study was acceptable.

The association between the severity and extension of CAD and the serum level of PCT was first evaluated by Erren et al. [14]. The authors compared the serum PCT level in patients who were candidated electively for selective coronary angiography. They categorized their study patients, the majority of them with chronic stable angina, according to the presence or absence of CAD and peripheral artery disease, into three groups and found that the PCT level was elevated in the patients with CAD and peripheral arterial disease concomitantly by comparison with the control patients and those with CAD only. In addition, they found no correlation between the serum PCT level and the severity and extension of CAD. However, in a recent study, Kurtul and Elcik [15] evaluated patients candidated for selective coronary angiography because of chronic stable angina and compared the serum PCT level between the patients with low and high SYNTAX scores ( ≥ 23 vs. < 23). Their entire study population had a 50% diameter stenosis in at least one major epicardial coronary artery. In their study, patients with a history of PCI were included in the analysis, and the results showed that the PCT level was associated with a high SYNATX score.

Sentürk et al. [16] evaluated the correlation between the serum PCT level and the number of major epicardial coronary arteries and significant stenosis in 50 patients with acute coronary syndrome – comprising 16 patients with unstable angina (UA), 14 patients with NSTEMI, and 20 patients with STEMI. They measured the serum PCT level at admission and 48 h after admission, and they found that there was no correlation between the PCT level at admission and at 48 h after admission and the number of diseased coronary vessels. However, in a recent study, Ertem et al. [17] measured the serum PCT level at admission in patients with acute coronary syndrome and reported that a comparison of the level between the patients with and without high SYNTAX scores ( < 33 vs. ≥ 33) showed a correlation between the serum PCT level at admission and a high SYNTAX score, independent from the type of acute coronary syndrome (ST-elevation MI vs. NSTEMI or UA). In the comparison of our investigation with the aforementioned study, the following points should be taken into account.

First, Ertem et al. [17] failed to specify whether or not the serum PCT level was correlated with the SYNTAX score in their subgroup of patients with UA/NSTEMI. Second, it has been reported elsewhere that an initial rise in the serum PCT level after MI is followed by a plateau at between 12 and 24 h after MI and, subsequently, a drop to the baseline value at 1 week following MI [21]. Third, Ertem et al. [17] measured the serum PCT level on the first morning after admission, when PCT had not reached its maximal level. It can, thus, be postulated that the serum level of PCT – especially in the patients with NSTEMI or UA – may not have risen significantly and may have merely remained at a range near to the serum level of PCT in those with stable angina, and that the correlation may have been a reflection of a pre-existing association between the serum PCT level and the extension and severity of CAD in a previous stable condition. Fourth, although Ertem et al. [17] regarded NSTEMI and UA as one entity for the purposes of treatment and follow-up, myocardial necrosis occurred in the patients with NSTEMI and not in those with UA; had they considered these conditions to be two separate categories, they might have arrived at a different conclusion altogether. Fifth, Ertem et al. [17] included patients with a history of PCI in their study, which may have confounded their results. Sixth, we and Ertem et al. [17] drew upon different scoring systems for the evaluation of the severity and extension of CAD. Although the use of both of these systems is clinically advocated [22], it should be noted that, whereas the SYNTAX scoring system [23] allocates scores to greater than 50% diameter stenoses, the Gensini scoring system [11] allocates scores to smaller than 25% diameter stenoses. Consequently, lower ranges of the extension and severity of CAD are missed in the SYNTAX score, and a high SYNTAX score can be interpreted as an extreme range of the extension and severity of CAD. The clinical importance of this discrepancy between the Gensini score and the SYANTAX score is particularly highlighted when there is a SYNTAX score of 0 [24]. Moreover, while the SYNTAX scoring system underscores the complexity of stenotic lesions such as bifurcation or trifurcation lesions, which have therapeutic implications [23], the Gensini scoring system focuses upon the functional significance of stenosis [10].

Another possible explanation for our results is that MI by itself can lead to increased PCT levels, which – especially when PCT is measured around its plateau period – can confound the correlation between the serum level of PCT and the severity and extension of CAD. Hence, the plateau level of PCT – unlike the level measured at admission – may not be correlated with the extension and severity of CAD. The difference in the measurement times of the serum PCT level has various prognostic implications. Kelly et al. [25] measured the serum level of PCT in patients with ST-elevation MI and NSTEMI at discharge (median = 5 days) and found, at a median follow-up of 671 days, that PCT was an independent predictor of major adverse cardiovascular events. In a study by Kafkas et al. [21], the PCT level reached its baseline value on the seventh post-MI day; it, therefore, appears that the PCT level in many of their patients may have been near the baseline level. Sinning et al. [26] measured the serum PCT level before coronary angiography in 2131 patients, consisting of 1300 patients with stable angina and 831 with acute coronary syndrome. What is not clear in their results is the measurement times of PCT, but the authors concluded that PCT was not an independent predictor of cardiovascular mortality and events at 3.6 years’ follow-up.

It is noteworthy that the clinical profile of our study population – including age, sex, hypertension, diabetes, cigarette smoking, and a family history of CAD – is not significantly different from that in studies on the correlation between PCT and coronary atherosclerotic burden [15,17]. However, in comparison with western registries [27–30], our patients are younger by about one decade.

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Study limitations

First and foremost among the limitations of this study is its cross-sectional design with its inherent drawbacks. This study being a single-center investigation with a small sample size can be deemed another weakness of note. In addition, our results would have been boosted had we been able to measure the PCT level serially from the admission time and onward or had we evaluated the severity and extension of CAD with other imaging modalities such as intravascular ultrasound rather than solely selective coronary angiography.

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Conclusion

In our patients with NSTEMI, the PCT level on the second postadmission day was not statistically significantly correlated with the extension and severity of CAD assessed with the Gensini score.

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Acknowledgements

This study was financially supported by Tehran University of Medical Sciences.

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Conflicts of interest

There are no conflicts of interest.

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Keywords:

coronary artery disease; Gensini score; myocardial infarction; procalcitonin

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