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3, 187 SCAD patients entered in the final analysis after the exclusion of 21 patients who were lost to follow-up and 1, 085 patients with missing NT-proBNP data (Figure 1), with a mean age of 58.09 ± 10.20 year; number of female patients: 705 (22.12%). This patient cohort included 649 cases of asymptomatic myocardial ischemia (20.36%). On discharge, the majority of patients were being treated using clopidogrel (3, 182 patients, 99.84%) and only four patients were taking ticagrelor (0.13%), and 1 patient did not take any P2Y12 receptor antagonist (0.03%). Almost all enrolled patients took aspirin 3, 146 (98.71%). Most enrolled patients were treated using statins (3, 060 patients, 96.02%). Among these, 2, 947 patients had a LVEF > 50% (92.47%). All patients underwent PCI (100%), and 3, 007 patients (94.35%) were successfully implanted with drug-eluting stents; only nine patients (0.28%) were implanted with bare metal stents, and 171 patients (5.37%) were treated through percutaneous transluminal percutaneous coronary angioplasty alone.
After a 2-year follow-up, 36 patients died (1.13%) and 387 patients experienced MACCE (12.14%). Patients who died were older, had a lower BMI and a more significant previous history of MI, a previous history of PCI, a previous history of CABG, a previous history of congestive heart failure, CrCl < 60 mL/min, lower LVEF and underwent more intra-aortic balloon pump (IABP) treatment. Patients with MACCE were older, and were more likely to demonstrate hyperlipidemia, have a previous history of PCI and a higher baseline SYNTAX score, and more of these patients accepted IABP treatment (Table 1).
Characteristing Death
(n = 36)Survival
(n = 3, 151)P
ValueMACCE
(n = 387)No MACCE
(n = 2, 800)P
ValueAge, y 65.61 ± 11.12 58.00 ± 10.16 < 0.001 59.55 ± 10.62 57.89 ± 10.13 0.003 Female, n (%) 5 (13.89) 700 (22.22) 0.231 75 (19.38) 630 (22.50) 0.166 NT-proBNP (P25, P75, pg/mL) 890.70 (714.70, 1353.25) 547.30 (448.90, 761.90) < 0.001 587.50 (456.80, 815.30) 574.45 (449.20, 761.05) 0.064 BMI, kg/m2 24.68 ± 2.92 26.06 ± 3.18 0.010 25.81 ± 3.36 26.08 ± 3.15 0.122 Hypertension, n (%) 25 (69.44) 2, 060 (65.38) 0.610 261 (67.44) 1, 824 (65.14) 0.373 Diabetes mellitus, n (%) Non Diabetes mellitus 22 (61.11) 2, 132 (67.66) 0.706 245 (63.31) 1, 909 (68.18) 0.137 Non-insulin-treated 9 (25.00) 658 (20.88) 89 (23.00) 578 (20.64) Insulin-treated 5 (13.89) 361 (11.46) 53 (13.70) 313 (11.18) Current smoking, n (%) 23 (63.89) 1, 747 (55.44) 0.311 232 (59.95) 1, 538 (54.93) 0.063 dyslipidemia, n (%) 29 (80.56) 2, 184 (69.31) 0.145 286 (73.90) 1, 927 (68.82) 0.042 Previous MI, n (%) 18 (50.00) 832 (26.40) 0.001 110 (28.42) 740 (26.43) 0.405 Previous PCI, n (%) 16 (44.44) 902 (28.63) 0.037 129 (33.33) 789 (28.18) 0.036 Prevous CABG, n (%) 5 (13.89) 141 (4.47) 0.022 23 (5.94) 123 (4.39) 0.172 Previous stroke, n (%) 5 (13.89) 317 (10.06) 0.631 39 (10.08) 283 (10.11) 0.986 CrCl < 60 mL/min 10 (27.78) 422 (13.50) 0.025 62 (16.10) 370 (13.33) 0.137 LVEF (%) 60.02 ± 9.76 63.66 ± 6.93 0.040 63.03 ± 7.30 63.70 ± 6.93 0.078 CAD extension, n (%) LM extension 1 (2.78) 82 (2.60) 1.000 10 (2.58) 73 (2.61) 0.979 1-vessel disease 29 (80.56) 2, 432 (77.18) 0.631 306 (79.07) 2, 155 (76.96) 0.355 2-vessel disease 6 (16.67) 585 (18.60) 0.767 67 (17.31) 525 (18.75) 0.496 3-vessel disease 0 (0.00) 48 (1.52) 0.954 4 (1.03) 44 (1.57) 0.415 Bridge vascular lesions 0 (0.00) 3 (0.10) 1.000 0 (0.00) 3 (0.11) 1.000 IABP use, n (%) 3 (8.33) 30 (0.95) < 0.001 10 (2.58) 23 (9.82) 0.003 NO. of stents per patient (x ± s) 1.89 ± 1.04 1.84 ± 1.11 0.781 1.85 ± 1.09 1.84 ± 1.11 0.875 Femoral artery puncture, n(%) 4 (11.11) 256 (8.12) 0.730 36 (9.30) 224 (8.00) 0.380 Baseline SYNTAX score (x ± s) 12.25 ± 8.08 12.37 ± 7.91 0.932 13.96 ± 8.40 12.15 ± 7.82 < 0.001 Note.NT-proBNP: N-terminal pro-brain natriuretic peptide; SCAD: stable coronary artery disease; MACCE: major adverse cardiovascular and cerebrovascular events; PCI: percutaneous coronary intervention; BMI: body mass index; MI: myocardial infarction; CABG: coronary artery bypass grafting; CAD: coronary artery disease; CrCl: creatinine clearance; SYNTAX: synergy between percutaneous coronary intervention with taxus and cardiac surgery; IABP: intra-aortic balloon pump. Values are presented as mean ± SD, n (%), or median (P25, P75). Table 1. Baseline Clinical Characteristics in SCAD Patients with Versus without Death or MACCE
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NT-proBNP levels were significantly higher in the death group compared with the survivor group [890.70 pg/mL (714.70, 1353.25) vs. 547.30 pg/mL (448.90, 761.90), P < 0.001]; but there was no significant difference between the MACCE and the non-MACCE group in terms of NT-proBNP levels [587.50 pg/mL (456.80, 815.30) vs. 574.45 pg/mL (449.20, 761.05), P = 0.064].
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NT-proBNP levels were predictive of all-cause death in the SCAD population (AUROC, 0.768; 95% CI, 0.687-0.849; P < 0.001) (Figure 2). However, NT-proBNP levels did not show a significant predictive value for MACCE (AUROC, 0.529; 95% CI, 0.497-0.561; P = 0.064).
Figure 2. Area under the receiver operating characteristic curve of prognostic value of NT-proBNP in evaluating all-cause death in SCAD population. AUROC, 0.768; 95% CI, 0.687-0.849; P < 0.001. NT-proBNP: N-terminal pro-brain natriuretic peptide; SCAD: stable coronary artery disease; AUROC: area under the receiver operating characteristic curve; CI: confidence interval.
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When 732 pg/mL was taken as the NT-proBNP cutoff point, the sensitivity was 75.0%, the specificity was 72.3%, the Youden index was the minimum, the sum of specificity and sensitivity was the maximum, and this value was the optimal cutoff point for predicting death.
A Kaplan-Meier survival curve analysis was performed, with a NT-proBNP cutoff point of 732 pg/mL (Figure 3). There were 2, 279 patients with NT-proBNP levels < 732 pg/mL, including nine patients who died during the follow-up period, with an average event-free survival time of 25.27 months. A total of 872 patients with NT-proBNP ≥ 732 pg/mL suffered 27 deaths during the follow-up period, with an average event-free survival time of 24.92 months. A log-rank test was performed, using the NT-proBNP cutoff of 732 pg/mL, and the results suggested that there was a significant difference in survival time between the two groups (P < 0.001).
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Model 1: Univariate analysis showed that log NT-proBNP was a predictor of death, and the death risk in patients with NT-proBNP levels ≥ 732 pg/mL was 7.73 times higher than the risk in patients with NT-proBNP levels < 732 pg/mL [hazard ratio (HR): 7.73; 95% CI, 3.64-16.44, P < 0.001].
Model 2: After including age and gender variables to be adjusted, log NT-proBNP was still an independent predictor of death, and the death risk for patients with NT-proBNP levels ≥ 732 pg/mL was 6.28 times for those with NT-proBNP levels < 732 pg/mL (HR: 7.73; 95% CI, 2.92-13.50, P < 0.001).
Model 3: Based on model 2, 14 factors have been filtered through a stepwise regression model, including BMI, hypertension, diabetes, current smoking, hyperlipidemia, previous MI, previous PCI, previous CABG, history of stroke, previous vascular disease, anemia, CrCl < 60 mL/min, LVEF, and baseline SYNTAX score. Only previous PCI was independently associated with mortality. Including previous PCI, log NT-proBNP, age and gender in a multivariate analysis indicated that log NT-proBNP was still an independent predictor of death, whereby patients with NT-proBNP levels ≥ 732 pg/mL demonstrated 6.43 times the risk of death compared with those with NT-proBNP levels < 732 pg/mL (HR: 6.43; 95% CI: 2.99-13.82, P < 0.001) (Table 2).
Model, pg/mL HR 95% CI P Value Model 1 < 732 1.00 ≥ 732 7.73 3.64-16.44 < 0.001 Model 2 < 732 1.00 ≥ 732 6.28 2.92-13.50 < 0.001 Model 3 < 732 1.00 ≥ 732 6.43 2.99-13.82 < 0.001 Note.Model 1: Univariate Cox Model analyses; Model 2: Adding age, gender variables to be adjusted; Model 3: Model 2+previous PCI (Using stepwise regression, entry probability = 0.05, deletion probability = 0.10, age, gender and LOG NT-proBNP were forcedly introduced; and screening of BMI, hypertension, diabetes, current smoking, hyperlipidemia, previous myocardial infarction, previous PCI, Previous CABG, Previous Stroke, Previous Vascular Disease, Anemia, CrCl < 60 mL/min, LVEF, SQSS, eventually only previous PCI left in mode). NT-proBNP: N-terminal pro-brain natriuretic peptide; CrCl: creatinine clearance; HR: hazard ratio; CI: confidence interval. Table 2. Univariate and Multivariate Cox Model Analysis between NT-proBNP and Survival