Clinical study of patients with coronary artery disease combined multivessel disease

Background: To investigate the clinical prognosis of patients with coronary artery disease combined multivessel disease. Methods: The patients who were diagnosed with multivessel disease by coronary angiography were selected in this study. The clinical datas about the clinical prognosis and the incidence of adverse cardiovascular events within ve-year follow-up were analyzed. Results: A total of 230 participants were included in this study, includeing 129 male (56.09%) and 101 female (43.91%), the average age was 69.73 ± 10.93. The outcomes showed that the patients with three-vessel lesions had signicantly higher rate of diabetes history (51.32% vs. 34.62%, P=0.018), unstable angina pectoris history ( 73.03% vs. 55.13%, P=0.008), and signicantly higher risk of cardiogenic mortality (7.24% vs. 1.28%, P=0.045) when compared with patients who had two-vessel lesions. The patients with CTO had signicantly higher rate of diabetes history (58.54% vs. 42.86%, P=0.049), unstable angina pectoris history ( 80.49% vs. 64.02%, P=0.029), MI history ( 48.78% vs. 25.40%, P=0.003), signicantly lower LVEF (58.73±11.30 vs. 64.23±9.49, P=0.001) and signicantly higher risk of recurrent myocardial infarction (12.20% vs. 3.2%, P=0.043) when compared with those patients without CTO. The patients with left main lesions had signicantly older age (73.61±9.95 vs. 69.02±10.98, P=0.018) and signicantly higher risk of cardiogenic mortality (13.89% vs. 3.61%, P=0.025) when compared with those patients without left main lesions. Conclusions: Among patients with coronary artery disease combined multivessel disease, patients with CTO had signicantly lower LVEF


Background
Multi-vessel coronary artery disease (MVD) refers to a lesion with more than 50% of the diameter of the main coronary artery or its branches in two or more epicardium [1][2] . Multivessel disease accounts for about 50% -60% of all coronary angiography results [3] . Recently, MVD is the focus and di culty in the eld of coronary artery disease. However, the long-term prognosis of paitents with different kinds of MVD remians unclear in China, such as three-vessel lesions, chronic total occlusive disease (CTO) or left main lesions. Three-vessel lesions refers to three vessels, such as the right coronary artery, the left anterior descending coronary artery, the left coronary artery cyclotron branch have more serious lesions. Left main lesion (unprotected left main diseases) refers to the degree of left main coronary artery angiography stenosis greater than or equal to 50% of the lesions, and at the same time does not exist unblocked blood vessel bridge good collateral circulation or their right to left. CTO is a dynamic process from quantitative change to qualitative change after coronary artery atherosclerosis, the lesions usually begin with the rupture of the "vulnerable plaque" in the coronary arteries, forming clots at both ends of the plaque and which endly leading to complete occlusion of the coronary arteries [4][5][6][7][8] .
Therefore, we conducted this study to investigate the ve-year clinical prognosis of patients with coronary artery disease combined multivessel disease.

Subjects
From January 2014 to January 2015, patients who were diagnosed as multivessel disease diagnosed by coronary angiography in Beijing Dongzhimen Hospital were indcluded in this study. The clinical follow-up was 5 years. The clinical datas about the clinical prognosis and the incidence of adverse cardiovascular events within ve-year follow-up were analyzed. This study had been approved by our institutional ethics committee (the ethical committee of Beijing Hospital of Traditional Chinese medicine, Capital Medical University). The informed consent (written) was obtained from all participants.

Inclusion And Exclusion Criterias
Inclusion criterias: (1) patients who were diagnozed as multivessel disease by coronary angiography; (2) age was older than 18 years old; (3) patients who had signed the informed consent. Exclusion criteria: (1)patients with congenital heart disease; (2) patients with advanced malignant tumors; (3) patients who were pregnant or lactating women; (4) patients whose datas were incomplete.

Main Indicators
The main indicators of this study include the patient's gender; age; coronary angiography results, such as double-branch disease, triple-branch disease, left main disease; LVEF; previous medical history, such as history of smoking, history of hyperlipidemia, history of diabetes, history of hypertension, history of cerebrovascular disease, history of unstable angina pectoris, history of myocardial infarction; clinical treatment options, such as conservative medication, percutaneous coronary intervention (PCI), coronary artery bypass surgery (CABG); clinical prognosis, such as the incidence of major cardiovascular adverse events (MACE), all-cause mortality, cardiogenic mortality, incidence of myocardial infarction, incidence of cerebrovascular events, incidence of revascularization, incidence of postoperative restenosis, the incidence of rehospitalization due to angina pectoris.

Statistical Analysis
We used the software program SPSS 25.0 (IBM, Chicago, USA) to conduct the statistical analysis. The continuous variables of normal distribution were expressed as mean ± standard deviation, the continuous variables of non-normal distribution were expressed as median (interquartile range[IQR]), the categorical variables were expressed as frequency (percentage[%]). For two comparisons, each value was compared by t-test when each datum conformed to normal distribution, while the non-normally distributed continuous data were compared using non-parametric tests. The counting data were tested by chi-square test. A value of P < 0.05 was considered statistically signi cant.

The general characteristics
A total of 263 patients who were diagnosed with multivessel disease by coronary angiography were recruited in this study. 20 patients were excluded because 5 of them had congenital heart disease, 7 of them had advanced malignant tumors and 8 of them lacked complete clinical information. Another 13 patients were lost follow up during the ve-year follow-up. In the end, a total of 230 patients who were diagnosed with multivessel disease by coronary angiography were included for quantitative analysis in this study (Fig. 1

The subgroup analysis of patients with three-vessel lesion and two-vessel lesion
Among these 230 participants, 152 patients have been diagnozed as three-vessel lesions by coronary angiography, 78 patients have been diagnozed as two-vessel lesions by coronary angiography. When compared with patients who had two-vessel lesions, the patients with three-vessel lesions had signi cantly higher rate of diabetes history (51.32% vs. 34.62%, P = 0.018) and unstable angina pectoris history ( 73.03% vs. 55.13%, P = 0.008). Furthermore, the patients with three-vessel lesions were assocaited with signi cantly higher risk of cardiogenic mortality (7.24% vs. 1.28%, P = 0.045) than those patients with two-vessel lesions. The details were listed in the Table 1.

Discussion
Recently, CTO is the focus and di culty in the eld of coronary artery disease. Clinical studies have shown that chronic complete occlusion of coronary arteries accounts for 1/3 of all coronary angiography patients and 10%-20% of all cardiac interventional therapy patients [6][7] . Less than 8% of patients receive interventional therapy and revascularization [8] . Our study presented that the patients with CTO had signi cantly higher rate of diabetes history, unstable angina pectoris history and MI history. Yahagi, et al.
reported that there was a relationship between diabetes and coronary artery atherosclerosis and vascular calci cation [9] . Our study con rmed that patients with diabetes really had a higher risk of three-vessel lesions among coronary artery disease.
Besides, our study found that patients with CTO had signi cantly lower LVEF when compared with those patients without CTO. Previous scholars have suggested that multivessel disease may be one of the reasons for lowering the left ventricular ejection fraction [10][11] . However, the effects of reduced left ventricular ejection fraction on the clinical prognosis of patients with multivessel disease remians unclear. Our study found that patients patients with CTO was really a risk factor for lower LVEF among patients with coronary artery disease.
De et al [12] found that the mortality of patients with multivessel disease combined with CTO was signi cantly higher than that of patients with multivessel disease without CTO, and proposed that multivessel disease combined with CTO could be used as predict factor for the one-year mortaligy of patients with multiple vessels. However, the long-term mortality of patients with CTO remains unknown. Based on the results of previous studies, our study did not found that patients with CTO have higher mortality within ve-year follow-up. However, we found that patients with CTO had signi cantly higher risk of recurrent myocardial infarction when compared with those patients without CTO. Therefore, CTO is not only a risk factor for the one-year death of patients with multivessel disease [13][14][15] , but also a risk factor for recurrent myocardial infarction within ve years.
The results of this study showed that the patients with three-vessel lesions had signi cantly higher rate of diabetes history and unstable angina pectoris history when compared with patients who had two-vessel lesions. Furthermore, the patients with three-vessel lesions had higher cardiogenic mortality than patients with two-vessel lesions during the ve-year follow-up. Previously, there were no enough datas aobut the difference between three-vessel lesions and two-vessel lesions among patients with multivessel disease in China. Our study found that the patients with three-vessel lesions were assocciated with higher risk of cardiogenic mortality than two patients with two-vessel lesions.
Left main lesion (unprotected left main diseases) refers to the degree of left main coronary artery angiography stenosis greater than or equal to 50% of the lesions, and at the same time does not exist unblocked blood vessel bridge good collateral circulation or their right to left. Left main coronary disease is seen in 4%-6% of patients undergoing coronary angiography for an ischemic evaluation and is a potentially fatal condition if not promptly identi ed and treated [16] . In our study, we found that the patients with left main lesions had signi cantly higher risk of cardiogenic mortality when compared with those patients without left main lesions which was consistent with previous studies. Besides, we also found that the patients with left main lesions had signi cantly older age than those patients without left main lesions. The results of Harada et al [17] showed that coronary artery disease with multivessel disease was prone to occur in elderly patients. With the gradual aging of China in these years, the number of patients with multivessel disease of coronary heart disease is increasing year by year, which deserves clinical attention [18][19][20][21][22][23][24] .
There were several limitations in this study. Firstly, this study was not a randomized controlled trial. Therefore, there was still a certain risk of bias. Secondly, this study was a single-center clinical study with a small sample size. Another multi-center clinical trial with large sample size was still needed in the future.

Consent to publish
All of the authors were consent to publish.

Availability of data and materials
The data supporting our ndings can be found by our email.

Competing interests
All of the authors had no any personal, nancial, commercial, or academic con icts of interest separately.

Funding
No any funding.
Authors' Contributions YH Z was the rst author and corresponding author. YY W and YY L was the co-rst author. XX S was the Co-corresponding author. All of these authors were contributed to this paper.
YH Z: had substantial contributions to the conception; design of the work; the acquisition, analysis; interpretation of data; have drafted the work and substantively revised it. YY W: had substantial contributions to the interpretation of data and substantively revised it. YY L: had substantial contributions to the the acquisition, analysis. XX S : had substantial contributions to the conception; design of the work; the acquisition, analysis; interpretation of data. MF S had substantial contributions to the conception; design of the work.
All authors have read and approved the manuscript.