Introduction
Methods
Clinical and angiographic characteristics
Biomarker assays
Statistical analysis
Results
Baseline characteristics
Caucasian | Chinese | Indian | Malay |
p-value | |
---|---|---|---|---|---|
N
| 1132 | 562 | 158 | 181 | |
Males (%) | 72.5 | 81.0 | 80.4 | 79.6 | < 0.001
|
Age (mean (SD), years) | 64.7 (11.3) | 59.1 (9.9) | 54.4 (9.5) | 55.4 (9.4) | < 0.001
|
BMI (mean (SD), kg/m2) | 27.0 (4.3) | 26.2 (4.7) | 27.5 (5.0) | 28.5 (5.4) | < 0.001
|
Diabetes (%) | 22.6 | 34.0 | 54.4 | 52.5 | < 0.001
|
Hypertension (%) | 56.1 | 65.1 | 63.9 | 64.6 |
0.001
|
Dyslipidaemia (%) | 48.2 | 69.6 | 76.6 | 75.1 | < 0.001
|
Smoking, current (%) | 23.6 | 29.4 | 42.9 | 39.0 | < 0.001
|
Smoking, ex (%) | 31.6 | 19.2 | 11.9 | 16.4 | |
Renal failure (%) | 3.1 | 6.0 | 3.8 | 5.6 |
0.034
|
Medications
| |||||
Platelet inhibitor (%) | 64.6 | 58.4 | 57.6 | 55.8 |
0.016
|
Statin (%) | 58.9 | 44.3 | 43.0 | 43.1 | < 0.001
|
Beta blocker (%) | 25.4 | 26.7 | 24.7 | 19.3 | 0.259 |
RAAS (%) | 51.4 | 35.2 | 40.5 | 43.6 | < 0.001
|
Calcium antagonist (%) | 64.3 | 61.4 | 61.4 | 55.8 | 0.146 |
Medical history
| |||||
Previous PCI (%) | 31.6 | 17.5 | 29.1 | 30.0 | < 0.001
|
Previous CABG (%) | 13.0 | 6.2 | 6.3 | 6.1 | < 0.001
|
Previous ACS (%) | 32.6 | 14.8 | 26.8 | 28.5 | < 0.001
|
History of CVA/TIA (%) | 10.3 | 5.7 | 8.2 | 6.7 |
0.010
|
History of PAD (%) | 11.5 | 2.8 | 4.4 | 5.0 | < 0.001
|
Indication for coronary angiography
| |||||
Stable CAD (%) | 67.4 | 65.9 | 58.8 | 54.8 | < 0.001
|
UA/NSTEMI (%) | 22.5 | 31.6 | 36.6 | 42.9 | |
STEMI (%) | 10.1 | 2.4 | 4.6 | 2.3 | |
CAD severity
| |||||
No/minor CAD (%) | 25.0 | 33.8 | 28.7 | 25.1 | < 0.001
|
Single-vessel disease (%) | 37.3 | 21.7 | 24.0 | 21.1 | |
Double-vessel disease (%) | 25.5 | 23.6 | 25.3 | 27.4 | |
Triple-vessel disease (%) | 12.2 | 20.8 | 22.0 | 26.3 | |
Treatment
| |||||
Conservative (%) | 35.0 | 53.6 | 58.2 | 55.2 | < 0.001
|
PCI (%) | 58.8 | 37.5 | 37.3 | 33.7 | |
CABG (%) | 6.2 | 8.9 | 4.4 | 11.0 | |
Biomarker levels
| |||||
NTproBNP (median [IQR]) | 43.1 [10.5, 138.0] | 37.8 [11.1, 135.2] | 31.5 [8.2, 108.0] | 63.9 [16.3, 201.8] |
0.049
|
hsCRP (median [IQR]) | 1.5 [0.6, 3.8] | 1.3 [0.6, 4.2] | 2.3 [1.0, 6.7] | 2.2 [0.8, 7.3] | < 0.001
|
CysC (median [IQR]) | 0.8 [0.7, 1.1] | 0.7 [0.6, 0.9] | 0.8 [0.6, 0.9] | 0.8 [0.5, 1.0] | < 0.001
|
MPO (median [IQR]) | 28.1 [20.7, 44.8] | 27.0 [20.6, 37.0] | 26.8 [19.8, 35.1] | 30.3 [23.5, 40.9] |
0.001
|
hsTnI (median [IQR]) | 7.8 [3.8, 28.4] | 8.1 [4.2, 48.1] | 7.7 [4.2, 69.1] | 12.2 [4.6, 209.5] |
0.001
|
Outcome
| |||||
SYNTAX score (mean (SD)) | 11.6 (8.2) | 15.2 (10.0) | 14.5 (10.6) | 15.6 (11.3) | < 0.001
|
High SYNTAX score (n (%) ≥ 18 points) | 147 (21.0) | 116 (34.0) | 34 (33.0) | 47 (38.2) | < 0.001
|
FU time (median [IQR], days) | 823 [653, 988] | 930 [734, 1062] | 882 [714, 1044] | 852 [649, 1045] | < 0.001
|
All-cause death (n) | 75 | 36 | 3 | 11 |
Biomarker levels
Biomarker | Caucasian | Chinese | Indian | Malay |
p-value | |
---|---|---|---|---|---|---|
Indication
| ||||||
NTproBNP (pmol/l)
| Stable CAD | 42.7 [13.41, 133.96] | 25.71 [4.04, 60.78] | 22.50 [6.95, 52.11] | 40.35 [15.81, 157.66] | < 0.001
|
UA/NSTEMI | 48.86 [13.29, 162.27] | 77.99 [25.47, 257.85] | 49.85 [6.78, 255.63] | 70.92 [18.95, 289.93] |
0.041
| |
STEMI | 21.64 [3.00, 77.01] | 122.87 [55.78, 446.12] | 119.65 [103.66, 635.87] | 274.25 [206.61, 2245.84] | < 0.001
| |
hsCRP (μg/ml)
| Stable CAD | 1.35 [0.55, 3.10] | 1.01 [0.46, 2.58] | 1.92 [0.98, 3.74] | 1.70 [0.70, 5.00] | < 0.001
|
UA/NSTEMI | 2.11 [0.74, 5.88] | 3.40 [0.80, 11.36] | 3.10 [1.31, 8.81] | 3.65 [1.27, 10.33] | 0.070 | |
STEMI | 1.95 [0.60, 5.20] | 9.42 [1.39, 19.96] | 28.46 [8.97, 61.99] | 21.25 [12.46, 31.37] |
0.002
| |
CysC (μg/ml)
| Stable CAD | 0.84 [0.66, 1.08] | 0.70 [0.58, 0.87] | 0.73 [0.57, 0.88] | 0.76 [0.53, 0.98] | < 0.001
|
UA/NSTEMI | 0.83 [0.65, 1.07] | 0.79 [0.65, 1.02] | 0.80 [0.64, 1.05] | 0.81 [0.59, 1.07] | 0.894 | |
STEMI | 0.75 [0.59, 0.90] | 0.76 [0.64, 0.87] | 0.68 [0.62, 0.86] | 0.55 [0.48, 0.75] | 0.809 | |
MPO (ng/ml)
| Stable CAD | 24.93 [19.29, 33.05] | 25.21 [19.41, 33.61] | 26.8 [19.73, 32.45] | 28.83 [22.51, 38.81] | 0.071 |
UA/NSTEMI | 32.86 [22.94, 55.28] | 30.74 [23.50, 41.80] | 24.98 [20.14, 36.6] | 35.7 [24.98, 45.22] |
0.011
| |
STEMI | 137.68 [62.42, 210.34] | 35.39 [28.93, 37.93] | 27.89 [24.03, 34.51] | 28.7 [22.35, 37.85] | < 0.001
| |
hsTnI (ng/l)
| Stable CAD | 5.60 [3.30, 12.03] | 5.60 [3.50, 11.50] | 4.70 [3.50, 13.5] | 8.30 [4.00, 18.8] |
0.034
|
UA/NSTEMI | 26.10 [7.00, 283.1] | 102.65 [14.80, 1153.83] | 36.35 [7.15, 229.38] | 171.30 [8.25, 1249.40] |
0.002
| |
STEMI | 128.55 [26.43, 944.68] | 78.70 [20.10, 2750.00] | 4065.10 [1651.45, 21301.05] | 1206.25 [956.28, 2135.23] |
0.005
| |
CAD severity
| ||||||
NTproBNP (pmol/l)
| No/minor CAD | 39.83 [8.64, 132.79] | 24.48 [3.00, 80.88] | 8.39 [3.00, 32.06] | 22.71 [3.00, 97.30] |
0.002
|
Single-vessel disease | 40.3 [11.75, 123.41] | 27.39 [7.72, 68.81] | 34.16 [15.73, 84.92] | 34.38 [5.00, 107.95] | 0.351 | |
Double-vessel disease | 39.48 [7.31, 159.11] | 44.86 [19.34, 155.28] | 38.43 [16.08, 105.24] | 66.45 [18.36, 311.30] | 0.315 | |
Triple-vessel disease | 68.93 [22.53, 164.18] | 70.98 [24.12, 233.65] | 61.61 [15.51, 397.78] | 162.41 [35.96, 414.94] | 0.079 | |
hsCRP (μg/ml)
| No/minor CAD | 1.20 [0.55, 3.11] | 1.10 [0.51, 3.30] | 2.66 [1.31, 7.67] | 1.93 [0.69, 6.17] |
0.002
|
Single-vessel disease | 1.41 [0.62, 3.47] | 1.05 [0.48, 3.01] | 2.58 [1.02, 4.51] | 2.19 [1.29, 8.79] |
0.001
| |
Double-vessel disease | 1.47 [0.57, 3.84] | 1.51 [0.60, 5.58] | 1.78 [0.85, 3.67] | 2.74 [0.82, 8.29] | 0.235 | |
Triple-vessel disease | 2.51 [0.80, 5.26] | 1.89 [0.76, 8.28] | 2.70 [1.00, 9.81] | 2.15 [0.90, 6.93] | 0.822 | |
CysC (μg/ml)
| No/minor CAD | 0.80 [0.65, 1.02] | 0.70 [0.58, 0.88] | 0.72 [0.62, 0.87] | 0.63 [0.51, 0.93] | < 0.001
|
Single-vessel disease | 0.82 [0.64, 1.05] | 0.71 [0.56, 0.84] | 0.68 [0.60, 0.85] | 0.67 [0.54, 0.81] | < 0.001
| |
Double-vessel disease | 0.86 [0.68, 1.09] | 0.74 [0.60, 0.95] | 0.75 [0.62, 0.89] | 0.87 [0.57, 1.08] |
0.010
| |
Triple-vessel disease | 0.85 [0.69, 1.07] | 0.77 [0.63, 0.94] | 0.86 [0.63, 1.19] | 0.88 [0.60, 1.14] | 0.266 | |
MPO (ng/ml)
| No/minor CAD | 26.00 [19.99, 37.21] | 25.34 [18.68, 33.80] | 28.90 [21.14, 32.72] | 29.33 [22.55, 38.88] | 0.272 |
Single-vessel disease | 28.01 [21.06, 42.76] | 29.36 [21.40, 40.95] | 27.53 [18.12, 37.14] | 29.53 [24.11, 41.49] | 0.516 | |
Double-vessel disease | 27.87 [20.63, 46.29] | 27.07 [21.13, 37.54] | 23.57 [20.05, 32.82] | 28.19 [23.15, 40.79] | 0.183 | |
Triple-vessel disease | 30.92 [22.88, 74.03] | 29.57 [21.91, 40.13] | 25.80 [19.71, 35.89] | 35.24 [25.66, 40.83] |
0.033
| |
hsTnI (ng/l)
| No/minor CAD | 5.25 [2.80, 12.5] | 5.10 [3.30, 12.08] | 5.00 [3.10, 15.60] | 9.15 [3.60, 19.53] | 0.200 |
Single-vessel disease | 7.10 [3.70, 30.6] | 7.20 [4.00, 54.8] | 14.75 [3.90, 123.50] | 5.90 [3.50, 20.20] | 0.437 | |
Double-vessel disease | 10.50 [4.80, 39.85] | 12.25 [4.53, 109.1] | 7.25 [4.60, 62.73] | 13.80 [5.75, 825.80] | 0.187 | |
Triple-vessel disease | 18.30 [6.60, 228.30] | 33.55 [7.88, 398.03] | 29.10 [7.00, 299.30] | 70.30 [10.50, 776.80] | 0.115 |
Modifying effect of ethnicity on association between biomarker levels and SYNTAX score
Biomarker | Ethnicity | Beta (CI, univariable) |
p-value beta (univ.) | Beta (CI, multivariable) |
p-value beta (multiv.) |
p-value interaction (univ.) |
p-value interaction (multiv.) |
---|---|---|---|---|---|---|---|
NTproBNP (pmol/l)
a
| Caucasian | 0.056 (− 0.002–0.114) | 0.059 | 0.020 (− 0.047–0.087) | 0.560 | Ref. | Ref. |
Chinese | 0.153 (0.053–0.254) |
0.003
| 0.104 (− 0.013–0.221) | 0.081 | 0.094 | 0.115 | |
Indian | 0.088 (− 0.065–0.241) | 0.255 | 0.020 (− 0.119–0.160) | 0.771 | 0.669 | 0.361 | |
Malay | 0.152 (0.011–0.292) |
0.035
| 0.132 (− 0.020–0.284) | 0.088 | 0.157 |
0.032
| |
hsCRP (μg/ml)
| Caucasian | 0.041 (0.009–0.074) |
0.012
| 0.030 (− 0.006–0.066) | 0.103 | Ref. | Ref. |
Chinese | 0.029 (− 0.020–0.077) | 0.243 | 0.035 (− 0.025–0.095) | 0.255 | 0.663 | 0.709 | |
Indian | 0.009 (− 0.095–0.112) | 0.870 | 0.033 (− 0.084–0.150) | 0.578 | 0.505 | 0.627 | |
Malay | − 0.025 (− 0.117–0.066) | 0.584 | − 0.040 (− 0.148–0.069) | 0.471 | 0.113 | 0.621 | |
CysC (μg/ml)
| Caucasian | 0.162 (− 0.015–0.340) | 0.073 | 0.081 (− 0.131–0.293) | 0.454 | Ref. | Ref. |
Chinese | 0.235 (− 0.015–0.485) | 0.066 | 0.154 (− 0.194–0.503) | 0.383 | 0.642 | 0.371 | |
Indian | 0.022 (− 0.449–0.492) | 0.928 | − 0.172 (− 0.700–0.356) | 0.519 | 0.541 | 0.753 | |
Malay | − 0.168 (− 0.923–0.586) | 0.660 | − 0.165 (− 0.935–0.605) | 0.671 | 0.314 | 0.457 | |
MPO (ng/ml)
b
| Caucasian | 0.101 (0.015–0.187) |
0.022
| 0.016 (− 0.095–0.127) | 0.777 | Ref. | Ref. |
Chinese | − 0.008 (− 0.485–0.469) | 0.974 | − 0.079 (− 0.630–0.472) | 0.778 | 0.633 | 0.885 | |
Indian | − 0.077 (− 1.314–1.160) | 0.902 | 0.108 (− 1.099–1.314) | 0.859 | 0.743 | 0.555 | |
Malay | 1.517 (0.451–2.583) |
0.006
| 1.146 (0.023–2.269) |
0.046
|
0.002
|
0.017
| |
hsTnI (ng/l)
a
| Caucasian | 0.044 (0.026–0.062) | < 0.001
| 0.032 (0.012–0.052) |
0.002
| Ref. | Ref. |
Chinese | 0.035 (0.008–0.061) |
0.010
| 0.044 (0.013–0.074) |
0.006
| 0.557 | 0.164 | |
Indian | 0.022 (− 0.023–0.067) | 0.331 | 0.050 (− 0.004–0.104) | 0.067 | 0.328 | 0.958 | |
Malay | 0.003 (− 0.027–0.033) | 0.858 | 0.003 (− 0.027–0.033) | 0.855 |
0.010
| 0.351 |
Biomarker discrimination of high SYNTAX score
Biomarker | Ethnicity | Optimal cut-off | AUC (95 % CI) |
---|---|---|---|
NTproBNP (pmol/l)
| Caucasian | 48.42 |
0.594 (0.543–0.645)
|
Chinese | 120.92 |
0.596 (0.532–0.659)
| |
Indian | 255.77 | 0.584 (0.455–0.712) | |
Malay | 154.41 |
0.621 (0.515–0.726)
| |
hsCRP (μg/ml)
| Caucasian | 2.40 |
0.589 (0.538–0.641)
|
Chinese | 1.69 | 0.547 (0.481–0.613) | |
Indian | 8.95 | 0.550 (0.425–0.675) | |
Malay | 3.04 | 0.502 (0.395–0.608) | |
CysC (μg/ml)
| Caucasian | 0.74 |
0.555 (0.501–0.609)
|
Chinese | 0.86 | 0.527 (0.460–0.594) | |
Indian | 0.85 | 0.602 (0.475–0.728) | |
Malay | 0.60 | 0.571 (0.466–0.677) | |
MPO (ng/ml)
| Caucasian | 30.17 |
0.601 (0.549–0.653)
|
Chinese | 36.84 | 0.532 (0.467–0.598) | |
Indian | 22.11 | 0.525 (0.405–0.644) | |
Malay | 33.40 |
0.611 (0.508–0.715)
| |
hsTnI (ng/l)
| Caucasian | 116.65 |
0.618 (0.566–0.671)
|
Chinese | 60.75 |
0.605 (0.540–0.669)
| |
Indian | 6.65 | 0.614 (0.499–0.729) | |
Malay | 17.15 |
0.711 (0.619–0.804)
|