Clinical characteristics
Of 3986 patients enrolled in this study, the mean age was 64 ± 11years, and 70% was male. As described in Table 1, 1.5% (n = 2092) of the study patients had UAP, 22% (n = 863) had NSTEMI and 26% (n = 1031) had STEMI. The median level of NT-proBNP was 337 with IQR (111, 1164) pg/ml, and the median values of NT-proBNP in the Q1-Q4 groups were 56, 190, 607, 2706 pg/ml.
Table 1
Clinical characteristics of the cohort grouped by the quartiles of NT-proBNP
Variable | Q1 (n = 999) | Q2 (n = 996) | Q3 (n = 996) | Q4 (n = 995) | P value |
Demographic |
Age, years | 60.3 ± 8.5 | 64.1 ± 10.4 | 63.2 ± 11.4 | 67.7 ± 11.6 | ༜0.001 |
Male, % | 755 (75.6) | 690 (69.3) | 724 (72.7) | 619 (62.2) | ༜0.001 |
Body mass index, kg/m2 | 26.3 ± 3.2 | 26.0 ± 3.3 | 25.8 ± 3.5 | 25.4 ± 3.6 | ༜0.001 |
Past medical history |
Hypertension, n (%) | 675 (67.6) | 715 (71.8) | 651 (65.4) | 653 (65.6) | 0.007 |
Diabetes mellitus, n (%) | 362 (36.2) | 354 (35.5) | 329 (33.0) | 341 (34.3) | 0.450 |
Dyslipidemia, n (%) | 507 (50.8) | 471 (47.3) | 449 (45.1) | 449 (45.1) | 0.036 |
Prior stroke, n (%) | 134 (13.4) | 163 (16.4) | 162 (16.3) | 143 (14.4) | 0.177 |
Smoking, n (%) | 418 (41.9) | 381 (38.3) | 455 (45.7) | 391 (39.3) | 0.004 |
Clinical diagnosis | ༜0.001 |
UAP, n (%) | 899 (90.0) | 707 (71) | 365 (36.6) | 121 (12.2) | ༜0.001 |
NSTEMI, n (%) | 65 (6.5) | 181 (18.2) | 324 (32.5) | 293 (29.4) | ༜0.001 |
STEMI, n (%) | 35 (3.5) | 108 (10.8) | 307 (30.8) | 581 (58.4) | |
Length of stay (days) | 5 (4–6) | 6 (5–8) | 7 (5–8) | 8 (7–10) | ༜0.001 |
Initial presentation |
Heart rate, beats/min | 68 (63–77) | 68 (62–76) | 70 (62–78) | 72 (64–82) | ༜0.001 |
Systolic BP, mmHg | 130 ± 16 | 133 ± 18 | 132 ± 22 | 129 ± 23 | ༜0.001 |
Diastolic BP, mmHg | 77 ± 11 | 76 ± 11 | 75 ± 12 | 73 ± 12 | ༜0.001 |
Laboratory finding |
Peak NT-proBNP, ng/L | 56 (35,83.2) | 190 (146,254) | 607 (445,838.8) | 2706 (1715, 5065) | ༜0.001 |
Fasting glucose, mmol/L | 5.51 (4.88–6.63) | 5.54 (4.85,6.79) | 5.63 (4.85,7.16) | 5.90 (5.03–7.66) | ༜0.001 |
Hemoglobin A1c, % | 6.1 (5.6-7.0) | 6.1 (5.6,7.0) | 6.0 (5.6,7.1) | 6.0 (5.5-7.0) | 0.567 |
Total cholesterol, mmol/L | 4.29 ± 1.08 | 4.31 ± 1.07 | 4.44 ± 1.09 | 4.45 ± 1.06 | ༜0.001 |
LDL-C, mmol/L | 2.40 ± 0.73 | 2.44 ± 0.76 | 2.55 ± 0.80 | 2.58 ± 0.78 | ༜0.001 |
Triglyceride, mmol/L | 1.55 (1.12,2.16) | 1.49 (1.05,2.17) | 1.43 (1.07,2.10) | 1.34 (0.99,1.93) | ༜0.001 |
Creatinine, umol/L | 78(69,87) | 79 (70,89) | 81 (71.5,91) | 83 (72,96) | ༜0.001 |
Peak cTNI, ng/ml | 0.084 (0.008,0.62) | 0.67 (0.12,4.24) | 4.28 (0.95,12.25) | 8.21 (2.42,23.60) | ༜0.001 |
Peak CK-MB, ng/ml | 2.79 (1.33,14.35) | 10.85 (3.16,53.53) | 48.5 (9.91,146.0) | 79.1 (17.0-197.0) | ༜0.001 |
hs-CRP, ng/ml | 1.28 (0.60,3.37) | 1.83 (0.73,4.88) | 3.13 (1.28,9.29) | 7.62 (2.52,18.45) | ༜0.001 |
three-vessel disease, n (%) | 712 (71.5) | 781 (78.4) | 793 (79.6) | 806 (81.0) | ༜0.001 |
Echocardiography |
LAD, cm | 3.60 ± 0.36 | 3.69 ± 0.40 | 3.73 ± 0.43 | 3.76 ± 0.50 | ༜0.001 |
LVEDD, cm | 5.01 ± 0.40 | 5.0 ± 0.43 | 5.06 ± 0.43 | 5.09 ± 0.47 | ༜0.001 |
LVEF, % | 68% (65, 71%) | 67% (63, 71%) | 65% (60, 68%) | 61% (55, 66%) | ༜0.001 |
Medication during follow-up, n (%) |
Aspirin | 882 (88.3) | 879 (88.3) | 863 (86.6) | 850 (85.4) | 0.164 |
P2Y12 receptor antagonist* | 922 (92.3) | 930 (93.4) | 949 (95.3) | 941 (94.56) | 0.028 |
β-blocker | 617 (61.8) | 614 (61.8) | 628 (63.1) | 628 (63.1) | 0.847 |
ACEI/ARB | 459 (45.9) | 546 (54.8) | 560 (56.2) | 574 (57.7) | ༜0.001 |
Statin | 886 (88.7) | 864 (86.7) | 872 (87.6) | 857 (86.1) | 0.349 |
NT-proBNP, N-Terminal pro-brain natriuretic peptide; BP, blood pressure; STEMI, ST-elevation myocardial infarction; NSTEMI, non-ST-segment elevation myocardial infarction; UAP, unstable angina pectoris; LDL-C, low-density lipoprotein cholesterol; cTNI, cardiac troponin I; CK-MB, creatine kinase-MB; hs-CRP, high-sensitivity C-reactive protein; LAD, left atrium diameter; LVEDD, left ventricular end-diastolic diameter; ACEI, angiotensin-converting enzyme inhibitors, LVEF, left ventricular ejection fraction; ARB, angiotensin receptor blockers. |
*P2Y12 receptor antagonist within 12 months after PCI |
Age, heart rate, proportion of patients with STEMI and three-coronary artery lesion increased significantly in the higher quartile groups (Q3-Q4, P < 0.001), while Body mass index (BMI), diastolic blood pressures (BP), proportion of male and UAP decreased significantly (P < 0.001). LVEF declined significantly with the increase of NT-proBNP levels in the Q3-Q4 groups (P < 0.001) although all subjects had LVEF ≥ 50%. Fasting glucose levels at admission were significantly higher in the Q3-Q4 group (P < 0.001), but Hb1C levels were not different in the 4 groups (P = 0.567).
As expected, peak troponin I, CK-MB, and hs-CRP were higher in the higher NT-proBNP quartile groups (Q3-Q4, P < 0.001), also creatinine was higher in the Q3-Q4 groups (P < 0.001). Figure 2A, 2B and 2C illustrate significant positive correlations of Log [NT-proBNP] values and peak cTnI (r = 0.418, P < 0.001), hs-CRP (r = 0.397, P < 0.001), and LVEDD (r = 0.075, P < 0.001), respectively. Figure 2D shows negative correlation between Log [NT-proBNP] values and LVEF (r=-0.426, P < 0.001) in this study cohort.
Not surprisingly, the length of hospital stay was longer in the Q3 and Q4 groups (P < 0.001).Post hospital discharge, P2Y12 receptor antagonist (P = 0.028) and angiotensin-converting-enzyme inhibitors(ACEI) + angiotensin receptor blockers(ARB) (P < 0.001) were used more frequently in the Q3-Q4 groups, and there were no significant differences in the usage of aspirin (P = 0.164), β-blocker (P = 0.847) and statin (P = 0.349) among Q1-Q4 groups.
Incidence of MACCE and NT-proBNP
Overall, the incidence of MACCE was 11.9% (n=476) during the median follow-up period of 35 (IQR: 23,48) months. There were significant differences in the occurrence of primary and secondary endpoints among Q1-Q4 groups: composite MACCE (5.6%, 9.1%, 13.0%, 20.1%, P <0.001), all-cause mortality (1.0%, 2.5%, 4.1%, 8.4%, P <0.001), CV death (0.4%, 0.9%, 1.9%, 4.6%, P <0.001), nonfatal MI (2.0%, 3.4%, 4.8%, 6.2%, P <0.001) and HFRH (1.5%, 2.3%, 4.1%, 5.9%, P <0.001). However, there was no significant difference in stroke in the 4 groups (1.4%,1.4%,1.3%, 2.1%, P =0.438). These differences are also illustrated in detail by Kaplan-Meier curves (Figure 3A-3F).
Prediction of MACCE
As detailed in Table 2, the univariate Cox proportional hazards model including variables listed in Table 1 identified that NT-proBNP, age, sex, BMI, heart rate, systolic BP, history of hypertension and diabetes mellitus, smoking, prior stroke, fasting glucose, creatinine, diagnosis of MI, three-vessel disease, length of stay in hospital were significantly correlated to the risk of composite of MACCE (P <0.05).Then, multivariate Cox regression detected that higher NT-proBNP was a significant and independent predictor of increased risk of MACCE in this study population. For every 337 pg/ml (median) increase in NT-proBNP, the risk of MACCE went up 1.02-fold (95%CI, 1.013-1.026; P <0.001). Compared to Q1 group, hazard ratio (HR) raised to 1.29 (95%CI, 0.92-1.81; P =0.137) in Q2 group; 1.73 (95%CI, 1.25-2.38; P =0.001) and 2.16 (95%CI, 1.57-2.99; P <0.001) in Q3 and Q4 groups respectively. In addition, age, heart rate, history of hypertension and diabetes mellitus, three-vessel disease and length of stay in the hospital (Figure 4) were independently and significantly associated with increased risks of MACCE (p<0.05).