Predictive value of serum YKL-40 and neutrophil/lymphocyte ratio for the severity of coronary artery disease in patients with acute ST-segment elevation myocardial infarction

doi:10.21203/rs.3.rs-1600452/v1

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Predictive value of serum YKL-40 and neutrophil/lymphocyte ratio for the severity of coronary artery disease in patients with acute ST-segment elevation myocardial infarction

https://doi.org/10.21203/rs.3.rs-1600452/v1

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Background: Acute ST-segment elevation myocardial infarction(STEMI) is a life-threatening coronary artery disease, inflammation plays a key role in the occurrence and development of coronary atherosclerosis. Serum YKL-40 and neutrophil-lymphocyte ratios(NLR) are both inflammatory markers. The purpose of this study is to investigate the predictive value of serum YKL-40 and neutrophil/lymphocyte ratio for the severity of coronary artery disease in patients with acute ST-segment elevation myocardial infarction.

Methods: A total of 120 STEMI patients admitted from October 2020 to February 2022 were included in the STEMI group. 71 patients without coronary sclerosis who underwent coronary angiography at the same time were in the control group. They were divided into the high Gensini score group (Gensini score > 64 points) and the low Gensini score group (Gensini score ≤ 64 points). Pearson correlation analysis was used to analyze the correlation between serum YKL-40 and NLR and Gensini score in the STEMI group; Multifactorial logistic regression analysis was used to study the correlation of serum YKL-40 and NLR each with coronary artery lesion degree; Receiver operating characteristic curve (ROC) to evaluate the predictive value of serum YKL-40 and NLR on coronary artery lesion degree.

Results: The serum YKL-40 and NLR in the STEMI group were higher than those in the control group, the serum YKL-40, and NLR in the high Gensini score group were higher than those in the low Gensini score group, and the difference was statistically significant (P<0.05). Pearson correlation analysis showed that serum YKL-40 and NLR were positively correlated with the Gensini score in the STEMI group. Multivariate Logistic regression analysis showed that serum YKL-40 was an independent risk factor for the severity of coronary artery lesions. The ROC curve analysis showed that the area under the curve (AUC) of serum YKL-40 in the diagnosis of a high Gensini score was 0.73; The AUC of NLR in the diagnosis of a high Gensini score was 0.694.

Conclusion: Both serum YKL-40 and NLR correlated with coronary artery lesion degree in STEMI patients, and serum YKL-40 was a better predictor of coronary artery lesion degree in STEMI patients than NLR.

Serum YKL-40

Neutrophil lymphocyte ratio

NLR

Acute ST-elevation myocardial infarction

STEMI

Gensini score

Acute ST-segment elevation myocardial infarction (STEMI) is a life-threatening coronary artery disease and a major cause of morbidity and mortality worldwide (1). Studies have shown that inflammation plays a key role in the development and progression of coronary atherosclerosis (2). Chitinase 3-like protein 1 (YKL-40) is a heparin and chitin-binding glycoprotein secreted by macrophages, neutrophils, vascular smooth muscle cells, and others (3). Serum YKL-40 has been shown to correlate with coronary artery lesion severity as a new inflammatory marker (4). The neutrophil-to-lymphocyte ratio (NLR) is an inflammatory marker that predicts adverse cardiovascular outcomes and has some predictive value for the coronary artery lesion degree (5). Currently, there is no literature reporting the predictive value of serum YKL-40 and NLR on the severity of coronary lesions in STEMI patients. This study aimed to investigate the correlation between serum YKL-40 and NLR and the severity of coronary lesions in acute ST-segment elevation myocardial infarction and to clarify the predictive value of serum YKL-40 and NLR on the severity of coronary lesions in STEMI patients.

1. Study population

A total of 120 STEMI patients admitted from October 2020 to February 2022 were included in the STEMI group.; 93 of them were male, with an average age of 62 years. Inclusion criteria: the diagnosis of STEMI was following the treatment guidelines published by the American College of Cardiology in 2013 (6). Including ① chest pain symptoms within 24 hours before admission, lasting > 30 minutes; ② electrocardiogram suggesting ≥ 2 consecutive leads of ST-segment elevation and/or abnormal Q wave and new left bundle branch block; ③ serum biochemical markers creatine kinase isoenzyme (CK-MB) and/or myocardial Troponin T (cTnT) was elevated within 24 hours after the onset of chest pain. Exclusion criteria: ① previous history of percutaneous coronary angiography (PCI); ② previous chronic heart failure, cardiomyopathy, heart valve disease, arrhythmia, congenital heart disease; ③ renal insufficiency in the decompensated stage; ④ history of chronic liver disease or liver insufficiency; ⑤ asthma, chronic obstructive pulmonary disease; ⑥ autoimmune disease and acute and chronic infection; ⑦ patients with malignancy. 71 patients who underwent negative coronary angiography at the same time were in the control group; 54 of them were males, with a mean age of 62 years. The STEMI group was divided into two groups according to the median Gensini score, with Gensini score ≤ 64 being the low score group, of which 46 were males with a mean age of 62 years; Gensini score > 64 being the high score group, of whom 47 were males with a mean age of 62 years. This study has been approved by the hospital ethics committee(Approval No.: 2020-ke-058). All methods were performed in accordance with the Declaration of Helsinki.

2. General information about patients

The baseline information of patients was recorded in detail through the hospital electronic case system, including age, gender, BMI, history of diabetes mellitus, history of hypertension, history of smoking, and family history of coronary heart disease; all patients took venous blood for routine blood tests within 24 hours after admission, and detected leukocytes, neutrophils, lymphocytes, and platelets, and calculated NLR based on neutrophils and lymphocytes; the next day fasting tests of biochemical indexes, including Serum total cholesterol, triglyceride, LDL-C, HDL-C, fasting blood glucose, blood creatinine, blood uric acid.

3. Study methods

3.1 Serum YKL-40 assay

5 ml of fasting elbow venous blood was collected from STEMI patients before emergency PCI and controls in normal biochemical tubes, centrifuged at a radius of 15 cm and 2500 r/min for 10 min at 4°C, and the serum was separated in sterile EP tubes and stored in a refrigerator at -80°C for testing. The specimens were tested in the same batch and thawed well at room temperature for the first time. Serum YKL-40 level was measured by enzyme-linked immunosorbent assay (ELISA), and the kit was provided by Wuhan Huamei Biological Engineering Co. The procedure was carried out strictly according to the instructions.

3.2 Coronary angiography and coronary artery lesion scoring

After successful puncture of the radial artery, coronary angiography was performed selectively in multiple angles and positions, and the results were judged jointly by two nominally experienced interventionalists. The coronary artery lesion degree was evaluated by the Gensini score, and the Gensini score criteria were as follows: 1 point for 1%-25%, 2 points for 26%-50%, 4 points for 51%-75%, 8 points for 76%-90%, 16 points for 91%-99%, and 32 points for 100% stenosis; different coefficients were calculated for different lesion sites: left main stem × 5, proximal anterior descending branch × 2.5, and middle segment × 2.5. The product of the stenosis score of each coronary artery and the corresponding coefficient is the Gensini score of individual vessels. If the patient has a multivessel lesion, the sum of the lesion scores is the total Gensini score to evaluate the severity of the coronary lesion. The patients were grouped according to the median Gensini score: 60 cases in the high Gensini score group (Gensini score > 64) and 60 cases in the low Gensini score group (Gensini score ≤ 64).

4. Statistical methods

SPSS 26.0 was used for analysis, and the measurement data were tested for normality, which was in line with normal distribution and expressed as mean ± standard deviation and independent samples t-test was used for comparison between two groups; measurement data that are not normally distributed are represented by the median (interquartile range, IQR), Comparisons between groups were performed using the Mann-Whitney U test; the enumeration data were expressed by rate, and the comparison between the two groups was by the chi-square test; Pearson correlation analysis was used to analyze the correlation between serum YKL-40 and NLR and Gensini score in the case group; multivariate Logistic regression analysis to study the correlation between serum YKL-40 and NLR and the severity of coronary artery lesions; the predictive value of serum YKL-40 and NLR in the coronary artery lesion degree was evaluated by the receiver operating characteristic (ROC) curve. All statistics were two-sided, and P < 0.05 was considered statistically significant.

1. Comparison of clinical data between the STEMI group and the control group

Compared with the control group, there were no statistical differences in age, gender, BMI, hypertension, family history of coronary artery disease (CAD), lymphocytes, hemoglobin, platelets, triglycerides, total cholesterol, LDL-C, uric acid in the STEMI group (P > 0.05); history of diabetes, history of smoking, leucocytes, neutrophils, NLR, creatinine, fasting blood glucose, HDL-C, serum YKL-40 were statistically different (P < 0.05), as shown in Table 1.

2. Comparison of clinical data between the high Gensini score group and the low Gensini score group

Compared with the low Gensini score group, there were no statistical differences in age, gender, BMI, history of diabetes, history of hypertension, history of smoking, family history of coronary heart disease, leukocytes, lymphocytes, platelets, triglycerides, total cholesterol, uric acid in the high Gensini score group (P > 0.05); neutrophils, NLR, hemoglobin, LDL-C, HDL-C, blood creatinine, fasting glucose, and serum YKL-40 were statistically different (P < 0.05), as shown in Table 2.

3. Correlation analysis between serum YKL-40 and NLR and Gensini score in STEMI group

Serum YKL-40 and NLR were positively correlated with Gensini score in STEMI patients (r = 0.386, P < 0.001; r = 0.293, P = 0.001), shown in Fig. 1.Due to the collinearity of NLR with neutrophils. therefore, neutrophils count was not included in the logistic regression analysis. Multifactorial Logistic regression analysis showed that serum YKL-40 was an independent risk factor for coronary lesion severity (OR = 1.002, 95% CI 1.001–1.003, P < 0.001); NLR was not an independent risk factor for the coronary artery lesion degree (OR = 1.076, 95% CI 0.878–1.318, P = 0.481), as shown in Table 3.

4. Predictive value of serum YKL-40 and NLR on the severity of coronary artery lesions

Using the low Gensini score group as the negative group and the high Gensini score group as the positive group, the ROC curve analysis was established, and the area under the ROC curve of serum YKL-40 was 0.73, with a sensitivity of 0.65 and specificity of 0.783; the area under the ROC curve predicted by NLR was 0.694, with a sensitivity of 0.85 and specificity of 0.483, as shown in Table 4 and Fig. 2.

Acute ST-segment elevation myocardial infarction (STEMI) is a severe coronary artery disease that refers to acute myocardial ischemic necrosis, which can lead to acute inflammation and stress response and is a major cause of death.

Neutrophils, the most important subpopulation of leukocytes, are considered to be a marker of inflammation and a mediator of tissue destruction in the inflammatory response. Previous studies have shown that neutrophils play a key role in the development and progression of atherosclerotic plaques (7, 8). Therefore, there is an increasing interest in the role of neutrophils as new biomarkers of cardiovascular disease. Studies have shown that not only elevated neutrophil counts are associated with poor clinical outcomes in patients with acute ST-segment elevation myocardial infarction (9) but also lymphocytopenia is associated with poor clinical outcomes. The neutrophil-to-lymphocyte ratio (NLR), which contains both neutrophil and lymphocyte subtypes of leukocytes, better reflects the inflammatory response of the vasculature than a single indicator. NLR, as one of the indicators of inflammation, is closely associated with cardiovascular disease. Related studies have shown that NLR not only predicts long-term mortality in patients with acute ST-segment elevation myocardial infarction (10) but also reflects the severity of coronary artery disease and correlates with the SYNTAX score and Gensini score (11). A study also demonstrated that NLR is an independent predictor of recurrence-free and an indicator of hospitalization and long-term prognosis (12). In STEMI patients, NLR was an independent predictor of high residual SYNTAX score and an independent predictor of coronary artery disease severity after PCI (13). Recent studies have found that in acute coronary syndromes, NLR values are associated with the prognosis of ACS. the higher the NLR value, the worse the prognosis of patients with ACS (14). NLR may be a better predictor of disease than a single leucocyte count and has a higher clinical predictive value. A total of 120 patients with acute myocardial infarction were included in this study. The results of the study showed that leukocytes, neutrophils, and NLR were higher in the case group than in the control group, with statistically significant differences (P < 0.05); lymphocytes were lower than in the control group, which is consistent with the results of previous studies (15). In this study, the difference between NLR in the high Gensini score group and the low Gensini score group was statistically significant (P < 0.05), and Pearson correlation analysis showed a positive correlation between NLR and Gensini score (r = 0.293, P = 0.001), which is consistent with the results of other studies (16, 17), suggesting that NLR can be used as an assessment of indicator of the coronary artery lesion degree in STEMI patients.

YKL-40, also known as chitinase-3-like protein 1 (CHI3L1), is a highly conserved protein that is mainly secreted by a variety of cells, including macrophages, and chondrocytes, neutrophils, and vascular smooth muscle cells (18). As an inflammatory glycoprotein, YKL-40 is involved in endothelial dysfunction by promoting chemotaxis, cell adhesion and migration, reorganization, and extracellular matrix reconstitution (19). Local inflammation caused by infiltrating macrophages in the vessel wall plays a crucial role in the development of atherosclerosis, and YKL-40 induces the maturation of monocytes into macrophages during the early and late stages of the atherosclerotic process, which are secreted by activated macrophages during the later stages of differentiation (20, 21). It has been confirmed that YKL-40 and hs-CRP are involved in the process of plaque damage in patients with coronary artery disease, are closely related to the development of coronary artery disease, and that YKL-40 is a better independent predictor of plaque damage compared to hs-CRP (22). In agreement with the results of previous studies (23), the results of the present study showed that serum YKL-40 levels were significantly higher in patients in the case group than in the control group. This indicates that serum YKL-40 is involved in the development and progression of coronary atherosclerosis. The results of this study showed that the serum YKL-40 level was significantly higher in the high Gensini score group than in the low Gensini score group and the difference was statistically significant; Pearson correlation analysis showed that the serum YKL-40 level was positively correlated with the Gensini score (r = 0.377, P < 0.001); further indicating that serum YKL-40 was associated with STEMI patients with coronary artery lesion severity. This result is consistent with previous studies (24–26).

To investigate the risk factors for coronary artery lesion severity in STEMI patients, logistic regression analysis was performed in this study, and the results showed that both serum YKL-40 and NLR were risk factors for coronary artery lesion severity in the univariate regression analysis; after including significant variables from the univariate regression analysis for multivariate regression analysis, the results showed that serum YKL-40 was an independent risk factor for coronary artery lesion severity, while NLR was no longer an independent risk factor for coronary artery lesion severity. This is contrary to the results of some previous studies (27, 28), which may be explained by the fact that the present study was a single-center, small sample size study, and some bias was inevitable. Meanwhile, ROC curve analysis showed that serum YKL-40 predicted the area under the curve (AUC) of coronary artery lesion severity in STEMI patients with a sensitivity of 0.73, a sensitivity of 0.65, and a specificity of 0.783; NLR predicted the area under the curve (AUC) of coronary artery lesion severity in STEMI patients with a sensitivity of 0.694, a specificity of 0.85, and a sensitivity of 0.483. 0.483, which is generally consistent with the results of previous studies (29).

In conclusion, both serum YKL-40 and NLR can reflect the coronary artery lesion degree in STEMI patients, and compared with NLR, serum YKL-40 may be a better predictor of coronary artery lesion severity.

This study is a single-center cross-sectional study with a small sample size, and some bias is inevitable causing the results to differ from previous studies, which needs to be further validated in a multicenter, large-sample prospective study.

Ethics approval and consent to participate: This study has been approved by the Second People's Hospital of Hefei ethics committee(Approval No.: 2020-ke-058).All methods were performed in accordance with the Declaration of Helsinki.

Consent for publication: Not applicable.

Availability of data and materials: The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Competing interests: All of the authors have no conflict of interest.

Funding: This research is funded by the Natural Science Project of Bengbu Medical College in 2020 (2020byzd322).

Authors' contributions: Caoyang Fang and Zhenfei Chen wrote the main manuscript text and Xiaoqin Jin,Mengsi Yang,Luyao Huang prepared figures 1-2 and Table 1-4. All authors reviewed the manuscript.

Acknowledgments: We would like to extend our sincere thanks to Zhenfei Chen.Jing Zhang for his contribution to statistical analysis. We’d also like to extend our gratitude to Jianyuan Pan, Xiaoqin Jin, Mengsi Yang, and Luyao Huang, for their contributions.

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Tables 1 to 4 are available in the Supplementary Files section.

No competing interests reported.

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Predictive value of serum YKL-40 and neutrophil/lymphocyte ratio for the severity of coronary artery disease in patients with acute ST-segment elevation myocardial infarction

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