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Reviews in Cardiovascular Medicine  2021, Vol. 22 Issue (3): 1009-1017     DOI: 10.31083/j.rcm2203110
Special Issue: State-of-the-Art Cardiovascular Medicine in Asia 2021
Original Research Previous articles | Next articles
Predictive and prognostic value of v-set and transmembrane domain-containing 1 expression in monocytes for coronary artery disease
Xiao-Fei Wang1, Meng-Cheng Xu1, Cheng-Yu Mao1, En-Zhou1, Qing He1, Xing-Qian Qu2, *(), Yu-Qi Fan1, *(), Chang-Qian Wang1, *(), Jun-Feng Zhang1, *()
1Departments of Cardiology, Shanghai Ninth People’s Hospital affiliated to Shanghai Jiao Tong University School of Medicine, 200011 Shanghai, China
2Department of anesthesiology, Shanghai Ninth People’s Hospital affiliated to Shanghai Jiao Tong University School of Medicine, 200011 Shanghai, China
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Abstract:

The aim of this study was to investigate the correlation between v-set and transmembrane domain-containing 1 (VSTM1) expression and incidence of major adverse cardiac events (MACE) in patients with coronary heart disease (CHD). A total of 310 patients were divided into a non-acute coronary syndrome (non-ACS) group (containing the stable angina group, and the asymptomatic coronary artery diseaseand other patients group) and an ACS group (containing unstable angina and acute myocardial infarction patients). Monocytic VSTM1 expression levels (assessed via average fluorescence intensity derived from antibody binding to VSTM1) in each group were detected and analyzed. The cut-off value of monocytic VSTM1 expression to predict the onset of ACS and MACE was confirmed. VSTM1 expression in monocytes from the ACS group was lower than that of the non-ACS group. The incidence of MACEs in the high VSTM1-expression group was much less than that of those in the low VSTM1 expression group at the 1 year follow-up stage. VSTM1 expression had an independent-inversed association with increased incidence of MACE and ACS. VSTM1 expression in monocytes may help to predict the occurrence of ACS in patients with CHD, and moreover it may provide the means to evaluate MACE prognosis during CHD patient follow-up.

Key words:  Coronary artery disease      VSTM1      Predictive and prognostic value      Acute coronary syndrome      Stable coronary artery disease      Atherosclerosis     
Submitted:  20 June 2021      Revised:  09 August 2021      Accepted:  11 August 2021      Published:  24 September 2021     
Fund: 81470546/National Natural Science Foundation of China;81870264/Natural Science Foundation of China;19ZR1429000/Natural Science Foundation of Shanghai Committee of Science and Technology;JYLJ017/Clinical research project of the Ninth people's Hospital Affiliated to Medical School of Shanghai Jiaotong University;18411950500/Shanghai Committee of Science and Technology, China;16CR20348/3-year action plan to promote clinical skills and innovation in municipal hospitals
*Corresponding Author(s):  Xing-Qian Qu,Yu-Qi Fan,Chang-Qian Wang,Jun-Feng Zhang     E-mail:  qxq007777@163.com;moricizine@163.com;wangcqdr17@163.com;junfengzhang9hos@163.com

Cite this article: 

Xiao-Fei Wang, Meng-Cheng Xu, Cheng-Yu Mao, En-Zhou, Qing He, Xing-Qian Qu, Yu-Qi Fan, Chang-Qian Wang, Jun-Feng Zhang. Predictive and prognostic value of v-set and transmembrane domain-containing 1 expression in monocytes for coronary artery disease. Reviews in Cardiovascular Medicine, 2021, 22(3): 1009-1017.

URL: 

https://rcm.imrpress.com/EN/10.31083/j.rcm2203110     OR     https://rcm.imrpress.com/EN/Y2021/V22/I3/1009

Fig. 1.   Flow chart of the study.

Table 1.  Baseline data in each group [measurement data (values represent mean ± SD or n%)].
Non-ACS ACS P
SA (N = 154) N% Asyp (N = 51) N% UA (N = 49) N% AMI (N = 56) N%
Age 64.6 ± 12.47 / 68.18 ± 10.36 / 70.06 ± 10.83 / 64.80 ± 10.28 / 0.229
Male 88 (57.14%) 28.39 33 (64.71%) 10.65 30 (61.22%) 9.68 40 (71.43%) 12.90 0.661
Smoke 31 (20.13%) 10.00 19 (37.25%) 6.13 18 (36.73%) 5.81 27 (48.21%) 8.71 0.024
Hypertension 97 (62.99%) 31.29 27 (52.94%) 8.71 30 (61.22%) 9.68 30 (53.57%) 10.00 0.631
Diabetes 31 (20.13%) 10.00 16 (31.37%) 5.16 15 (30.61%) 4.84 19 (33.93%) 6.13 0.422
Total cholesterol (mg/dL) 172.9 ± 41.8 / 168.7 ± 44.1 / 170.7 ± 47.6 / 190.5 ± 39.4 / 0.031
Triglycerides (mg/dL) 124.2 ± 88.1 / 130.9 ± 91.3 / 132.8 ± 93.0 / 137.8 ± 98.3 / 0.682
LDL cholesterol (g/dL) 95.5 ± 20.1 / 91.2 ± 6.0 / 109.4 ± 25.3 / 119.5 ± 30.9 / 0.004
HDL holesterol (mg/dL) 41.4 ± 10.8 / 39.8 ± 8.1 / 39.4 ± 9.7 / 37.9 ± 6.6 / 0.401
ACS, acute coronary syndrome; SA, stable angina group; Asyp, asymptomatic coronary artery disease or others group; UA, unstable angina group; AMI, acute myocardial infarction group; LDL, low density lipoprotein; HDL, high density lipoprotein; the same abbreviations are used in the other tables.
Fig. 2.  Monocyte identification and VSTM1 expression detection in monocytes using FCM. (A) Identification of monocytes using anti-CD14 and its isotype control. (B) Differential expression of VSTM1 in monocytes from the non-ACS and ACS groups was assessed by FCM (mean fluorescence intensity) using anti-VSTM1. The results revealed that VSTM1 expression in the non-ACS group was higher than the ACS group (P < 0.0001, *P < 0.05, **P < 0.01, *** P < 0.001, **** P < 0.0001).

Table 2.  VSTM1 expression levels in each group (values represent mean ± SD).
Non-ACS ACS P
SA (N = 154) Asyp (N = 51) UA (N = 49) AMI (N = 56)
VSTM1 76284.52 ± 29920.60 77704.48 ± 25361.91 52396.69 ± 28109.62 53179.35 ± 20116.80 <0.001
76637.78 ± 27812.41 52814 ± 24111.32
Fig. 3.  The receiver operating characteristic (ROC) curve to detect the best cut-off value of VSTM1 expression in predicting patients with and without MACE.
Best cut-off: 66657; AUC: 0.658; Sensitivity: 83.3%; Specificity: 49.3%; PPV: 61.94%; NPV: 74.7%.

Table 3.  The patient baseline characteristics grouped according to the cut-off value.
<66657 (N = 95) >66657 (N = 215) P-value
Age 67.21 ± 13.72 66.54 ± 9.87 0.627
Male 66 (69.5%) 125 (58.1%) 0.059
Smoke 46 (48.4%) 49 (22.8%) <0.001
Hypertension 62 (65.3%) 122 (56.7%) 0.159
Diabetes 22 (23.2%) 59 (27.4%) 0.429
LDL cholesterol, mg/dL 116.8 ± 26.7 91.9 ± 24.5 <0.001
Triglycerides, mg/dL 136.0 ± 98.4 130.0 ± 97.0 0.618
SA 30 (31.6%) 124 (57.7%) <0.001
Asyp 8 (8.4%) 43 (20.0%) 0.011
UA 35 (33.3%) 14 (6.5%) <0.001
AMI 48 (50.5%) 8 (3.7%) <0.001
Fig. 4.  Coronary heart disease risk factors. Smoking and serum LDL-c levels were considered risk factors that increased the incidence of ACS (odds ratio [or]: 2.325; 95% confidence interval [CI]: 1.409–3.837, P < 0.001; odds ratio [or]: 1.876; 95% confidence interval [CI]: 1.212–2.321, P = 0.007). VSTM1 showed a protective effect in alleviating incidence of ACS (odds ratio [or]: 0.78; 95% confidence interval [CI]: 0.589–0.924, P = 0.041).

Table 4.  MACE at 1-year follow-up.
Non-ACS ACS
SA (N = 154) Asyp (N = 51) UA (N = 49) AMI (N = 56)
Cardiac death 0 0 0 0
Non-fatal MI 0 0 0 1
TVR 0 0 0 0
TLR 0 2 3 5
MACE, major adverse cardiac event; MI, myocardial infarction; TVR, target vessel revascularization; TLR, target lesion revascularization.
Fig. 5.  Kaplan–Meier graphs comparing event rate between the study groups. The Kaplan-Meier curves for the high VSTM1 and low VSTM1 groups (P = 0.04).

Table 5.  The patient baseline characteristics in the MACE group and the non-MACE group.
Total MACE group Non-MACE group P
(310 patients) (11 patient) (299 patients)
Age 68.04 ± 12.05 69.30 ± 8.92 67.73 ± 12.78 0.687
Man 191 8 183 0.440
Smoke 95 8 87 0.006
Hypertension 184 7 177 0.768
Diabetes 81 6 75 0.067
Total cholesterol, mg/dL 177.2 ± 43.5 199.4 ± 54.8 175.5 ± 42.6 0.072
HDL cholesterol, mg/dL 39.0 ± 15.0 37.5 ± 15.0 39.1 ± 15.0 0.728
LDL cholesterol, mg/dL 107.1 ± 36.9 119.7 ± 20.6 106.2 ± 16.2 0.008
Triglycerides, mg/dL 134.0 ± 80.5 144.2 ± 94.7 133.2 ± 79.4 0.654
HbA1c, % 6.5 ± 1.4 6.7 ± 1.2 6.5 ± 1.5 0.663
Creatinine, mg/dL 1.1 ± 0.8 1.11 ± 1.4 1.1 ± 0.7 0.965
LVEF, % 59.9 ± 11.2 58.4 ± 8.6 60.1 ± 11.4 0.625
Prior MI 15 0 15 0.446
Prior PCI 56 4 52 0.108
Prior CABG 4 0 4 0.699
VSTM1 61093.51 ± 27000.11 53989.84 ± 20349.05 75599.42 ± 22271.97 0.002
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