Associations of serum high-sensitivity C-reactive protein and prealbumin with coronary vessels stenosis determined by coronary angiography and heart failure in patients with myocardial infarction

Background To explore the associations of serum high-sensitivity C-reactive protein (hs-CRP) and prealbumin (PAB) with the number of diseased coronary vessels, degree of stenosis and heart failure in patients with myocardial infarction (MI). Methods A total of 39 MI patients treated in the Cardiology were selected as the observation group, and another 41 patients with normal results of coronary angiography during the same period were selected as the control group. The general data of patients were recorded in detail, the content of serum hs-CRP and PAB in the peripheral blood was detected, and the number of diseased coronary vessels and the degree of stenosis were detected via coronary angiography. Results Compared with those in control group, the blood pressure and heart rate significantly rose, the content of indexes related to the severity of MI were significantly increased, the content of hs-CRP was significantly increased, and the content of PAB was significantly decreased in observation group. Hs-CRP was positively correlated with the number of diseased coronary vessels, degree of stenosis and heart failure in patients, but PAB was negatively correlated with the above factors. The survival rate of MI patients with high content of hs-CRP was obviously lower than that of patients with low content of hsCRP Conclusions Serum hs-CRP and PAB are closely associated with the number of diseased coronary vessels, degree of stenosis and heart failure in MI patients.


Summary
Background: To explore the associations of serum highsensitivity C-reactive protein (hs-CRP) and prealbumin (PAB) with the number of diseased coronary vessels, degree of stenosis and heart failure in patients with myocardial infarction (MI). Methods: A total of 39 MI patients treated in the Cardiology were selected as the observation group, and another 41 patients with normal results of coronary angiography during the same period were selected as the control group. The general data of patients were recorded in detail, the content of serum hs-CRP and PAB in the peripheral blood was detected, and the number of diseased coronary vessels and the degree of stenosis were detected via coronary angiography. Results: Compared with those in control group, the blood pressure and heart rate significantly rose, the content of indexes related to the severity of MI were significantly increased, the content of hs-CRP was significantly increased, and the content of PAB was significantly decreased in observation group. Hs-CRP was positively correlated with the number of diseased coronary vessels, degree of stenosis and heart failure in patients, but PAB was negatively correlated with the above factors. The survival rate of MI patients with high content of hs-CRP was Kratak sadr`aj Uvod: Cilj je bio da se istra`i povezanost serumskog visokoosetljivog C-reaktivnog proteina (hs-CRP) i prealbumina (PAB) sa brojem obolelih koronarnih sudova, stepenom stenoze i sr~anom insuficijencijom kod pacijenata sa infarktom miokarda (MI). Metode: Za posmatra~ku grupu izabrano je ukupno 39 pacijenata sa IM le~enim kardiolo{ki, a za kontrolnu grupu je izabran jo{ 41 pacijent sa normalnim rezultatima koronarne angiografije u istom periodu. Detaljno su evidentirani op{ti podaci pacijenata, detektovan je sadr`aj serumskog hs-CRP i PAB u perifernoj krvi, a koronarografijom je utvr|en broj obolelih koronarnih sudova i stepen stenoze. Rezultati: U pore|enju sa onima u kontrolnoj grupi, znaajno su porasli krvni pritisak i puls, zna~ajno je pove}an sa dr`aj indeksa koji se odnose na te`inu IM, zna~ajno pove}an sadr`aj hs-CRP, a zna~ajno smanjen sadr`aj PAB u posmatra~koj grupi. hs-CRP je bio u pozitivnoj korelaciji sa brojem obolelih koronarnih sudova, stepenom stenoze i sr~anom insuficijencijom kod pacijenata, ali je PAB bio u negativnoj korelaciji sa navedenim faktorima. Stopa pre`ivljavanja pacijenata sa IM sa visokim sadr`ajem hs-CRP bila je o~igledno ni`a nego kod pacijenata sa niskim sadr`ajem hs-CRP.

Introduction
Acute myocardial infarction (AMI) is a heart disease, whose pathogenesis is that persistent myocardial ischemia and hypoxia are caused by interruption or decline in coronary blood flow due to various factors based on the coronary artery disease, ultimately leading to myocardial cell necrosis, usually accompanied by such clinical complications as cardiac insufficiency and heart failure (1,2). With the intensification of population aging in China in recent years, the morbidity rate of AMI has increased year by year, making AMI one of the common diseases causing death and affecting the quality of life (3). It has been a major concern for clinicians and researchers to judge the number of diseased coronary vessels, degree of stenosis and incidence of heart failure through clinical indexes and realize early prevention and treatment.
High-sensitivity C-reactive protein (hs-CRP) is a sensitive marker for inflammation and atherosclerosis in the body. As a cytokine, it is involved in the formation of vascular plaques and the aggregation and adhesion of leukocytes, and it is closely related to the vascular endothelial injury (4) and the occurrence and development of AMI (5). Prealbumin (PAB) synthesized and released by hepatocytes is an acute phase reactive protein, which can effectively reduce the damage of toxic metabolites to the body, and has a close correlation with the severity of AMI (6). Sun et al. (7) found that PAB can be significantly consumed in the case of heart failure, so that the content of PAB in the peripheral blood of patients greatly declines. In this study, the associations of serum hs-CRP and PAB with the number of diseased coronary vessels, degree of stenosis and heart failure in AMI patients were analyzed, so as to provide a theoretical basis for the early diagnosis and treatment of AMI patients in clinic.

Objects of study
AMI patients treated in our hospital were selected, and they met the diagnostic criteria for AMI of the American College of Cardiology (ACC), the European Society of Cardiology (ESC) and the American Heart Association (AHA): >50% stenosis of more than 1 vessel definitely confirmed by coronary angiography. All patients enrolled underwent echocardiography and coronary angiography to confirm the diagnosis. Exclusion criteria: 1) Patients with chronic wasting dis-eases, such as malignant tumors, 2) those with severe dysfunction of liver or kidney, 3) those with acute infections recently or hematological diseases, 4) those with autoimmune diseases, or 5) those with a history of myocardial diseases. In observation group (n=39), there were 21 males and 18 females aged 48-82 years old. Another 41 patients without coronary artery disease according to coronary angiography during the same period were selected as the control group, including 20 males and 21 females aged 46-79 years old. The patients in both groups signed the informed consent and agreed to be enrolled in the study. The experimental scheme in this study was approved by the Ethics Committee of Xianju County Peoples Hospital.

General data of patients
The general data of patients were recorded in detail, including age, gender, height, weight, blood pressure and heart rate at admission, smoking history, medical history and medication history.

Judgment of severity of coronary artery disease
Coronary angiography was performed for all patients by the same physician in the Cardiovascular Intervention Department using the Judkin's method. Each blood vessel was subjected to projection at more than 3 positions, and the severity of disease and the number of diseased coronary vessels were evaluated independently. According to the angiography results, over 50% stenosis indicated the positive. The eight main vascular segments selected included the proximal right coronary artery, the middle right coronary artery, the proximal circumflex branch, the middle circumflex branch, the first diagonal branch, the middle anterior descending branch, the proximal anterior descending branch and the left main coronary artery. The coronary artery diseases were classified into single-vessel disease, double-vessel disease and multivessel disease.

Score of coronary artery stenosis
The degree of coronary artery stenosis was evaluated using the Gensini scoring system according to obviously lower than that of patients with low content of hs-CRP. Conclusions: Serum hs-CRP and PAB are closely associated with the number of diseased coronary vessels, degree of stenosis and heart failure in MI patients.

Laboratory examination
The venous blood was drawn immediately after admission, placed for 30 min and centrifuged at 3,000 rpm for 15 min. The supernatant was harvested and stored in an ultra-low temperature refrigerator for later use. The content of serum hs-CRP and PAB was detected by professional technicians using an automatic electrochemiluminescence immunoassay analyzer (E601, Roche, USA) and a full-automatic biochemical analyzer, respectively, strictly in accordance with the instructions.
The venous blood was drawn immediately after admission, placed for 30 min and centrifuged at 3,000 rpm for 15 min. Then the content of AMI-related indexes was detected, including myoglobin (MYO), creatine kinase-MB (CK-MB), N-terminal probrain natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI).

Follow-up
The patients were followed up during hospitalization and via telephone for 2 years. The incidence of heart failure was recorded, and the patients with heart failure were subjected to Killip cardiac function grading (grade I-IV). Based on the content of hs-CRP, the patients in observation group were divided into high-concentration group and low-concentration group. The survival time of patients was recorded, and the survival curves were plotted. The detailed records about follow-up, examinations and hospitalization were kept.

Statistical analysis
The data in this study were expressed as mean ± standard deviation. Statistical Product and Service Solutions (SPSS) 22.0 software (SPSS Inc., Chicago, IL, USA) was used for the data analysis. c 2 test was performed for the intergroup analysis of enumeration data, and one-way analysis of variance was used for the comparison among groups. Homogeneity test of variance was performed. Bonferroni's method was adopted for pairwise comparison in the case of homogeneity of variance, while Welch's method was adopted in the case of heterogeneity of variance. The survival status of patients was evaluated using Kaplan-Meier analysis, and the associations of indexes were detected using Pearson correlation analysis. P<0.05 suggested that the difference was statistically significant.

General data of patients
The general data of patients in the two groups were recorded in detail after enrollment. As shown in Table I, there were no statistically significant differences in age, gender, body mass index (BMI) and smoking history between observation group and control group (P>0.05). The blood pressure and heart rate in observation group were significantly higher than those in control group (P<0.05).

Content of indexes related to severity of MI
The fasting peripheral blood was drawn in the two groups to detect the content of MI-related indexes. As shown in Table II, the content of MYO, CK-MB, NT-proBNP and cTnI in the peripheral blood significantly rose in observation group compared with those in control group (P<0.01).

Content of serum hs-CRP and PAB
The fasting peripheral blood was drawn in the two groups to detect the content of serum hs-CRP and PAB. The results showed that observation group had obviously increased content of hs-CRP (P<0.01), but obviously decreased content of PAB in the peripheral blood compared with control group (P<0.01) ( Table III).

Analysis of correlations of serum hs-CRP with number of diseased coronary vessels, degree of stenosis and heart failure
According to the Pearson correlation analysis (Figure 1), the content of hs-CRP in the peripheral blood of AMI patients was positively correlated with the number of diseased coronary vessels (r=0.1627, P<0.01), degree of stenosis (r=0.4621, P<0.01) and heart failure (r=0.2126, P<0.01).

Analysis of correlations of PAB with number of diseased coronary vessels, degree of stenosis and heart failure
According to the Pearson correlation analysis (Figure 2), the content of PAB in the peripheral blood of AMI patients was negatively correlated with the number of diseased coronary vessels (r=-0.1554, P<0.01), degree of stenosis (r=-0.1951, P<0.01) and heart failure (r=-0.1122, P<0.01).

Survival analysis
Based on the content of hs-CRP in the peripheral blood, the patients in observation group were divided into high-concentration group and low-concentration group. These patients were followed up for 2 years, and the survival curves were plotted. As shown in Figure 3, the survival rate was far lower in high-concentration group than that in low-concentration group (P<0.05).

Discussion
The pathogenesis of AMI is that secondary thrombosis occurs due to coronary artery erosion or unstable plaque rupture, further causing coronary artery occlusion and myocardial ischemic necrosis (8). hs-CRP is a classic inflammatory marker, and a reactive protein secreted by the liver upon the stimulation of inflammatory factors such as IL-6 and IL-1, which can effectively reflect the degree of coronary sclerosis and the inflammatory process in the body. In clinic, hs-CRP and myocardial injury markers are jointly used to diagnose AMI (9, 10). Ljuca et al. (11) found that cardiovascular events such as ischemic cardiomyopathy and AMI can significantly raise the content of hs-CRP in the peripheral blood of patients. Hs-CRP can be used to effectively assess the inflammatory response in vivo and the severity of AMI, and it is closely related to the morbidity and mortality rates of cardiovascular events (12). Besides, PAB is an acute phase reactive protein able to not only effectively evaluate the synthetic ability of the liver, but also reflect the severity of inflammatory response in patients with cardiovascular disease (13). Matsunaga et al. (14) found that the content of PAB in the peripheral blood of patients with unstable angina pectoris is far lower than that in normal people. In this study, the content of hs-CRP and PAB in the peripheral blood of MI patients was detected. The results manifested that the content of hs-CRP in the peripheral blood of MI patients was obviously higher than that in normal people, while the content of PAB showed the opposite result. The content of hs-CRP was closely related to the severity of MI, and its increase in the peripheral blood of MI patients can significantly raise the mortality rate of patients. Fu et al. (15) showed that the elevation of hs-CRP will increase the incidence rate of adverse cardiovascular events, and cause vascular stenosis or stent thrombosis, and even death of patients.
In a large-scale retrospective study of Kalyoncuoglu et al. (16) on patients who died of cardiovascular events, it was found that hs-CRP is closely related to the mortality rate of patients with cardiovascular disease. Chi et al. (17) argued that hs-CRP has a close correlation with the degree of inflammatory response in the MI region. In this study, the correlations of the content of serum hs-CRP with the number of diseased coronary vessels, degree of stenosis and heart failure in MI patients were analyzed. The results manifested that hs-CRP was positively correlated with the number of diseased coronary vessels, degree of stenosis and heart failure. High-concentration hs-CRP can lead to vascular intima injury, vasoconstriction and unstable plaque shedding, ultimately accelerating the occurrence and development of MI (18). Shimizu et al. (19) studied and found that hs-CPR is one of the best markers predicting MI currently. Furthermore, this study confirmed that the content of PAB in the peripheral blood of MI patients was negatively correlated with the number of diseased coronary vessels, degree of stenosis and heart failure. Wang et al. (20) found that the content of PAB in the peripheral blood is of important significance for predicting the occurrence and development of adverse events in MI patients, and PAB can serve as an independent predictive factor for MI complicated with heart failure. Moreover, Wang et al. (21) found that the content of PAB can reflect the area of MI to a certain extent.

Conclusions
In conclusion, hs-CRP and PAB in the peripheral blood of MI patients are closely correlated with the number of diseased coronary vessels, degree of stenosis and heart failure, so they can be used as predictors of MI, which provide a theoretical basis for the accurate clinical diagnosis of MI.

Conflict of interest statement
All the authors declare that they have no conflict of interest in this work.