Background
Methods
Study population
Liver fibrosis scores
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APRI = AST (IU/L)/AST (the upper limit of normal, ULN) × 100 / platelet count (10^9/L)
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AST/ALT ratio = AST (IU/L)/ALT (IU/L)
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Forns score = 7.811–3.131 × log (platelet count [10^9/L]) + 0.781 × log (GGT [IU/L]) + 3.467 × log (age [year]) –0.014 × total cholesterol (mg/dL)
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NFS = − 1.675 + (0.037 × age [years]) + (0.094 * BMI [Kg/m2]) + (1.13 × diabetes [yes = 1, no = 0]) + (0.99 × AST/ALT ratio) – (0.013 × platelet count [109/L]) – (0.66 × albumin [g/dL])
Follow-up and endpoints
Statistical analysis
Results
Baseline characteristics
Liver fibrosis | Low | Intermediate | High | p Value |
---|---|---|---|---|
Clinical characteristics | ||||
Age | 58.7 (10.3) | 57.6 (10.6) | 58.1 (10.7) | 0.028 |
Male | 4235 (75.1) | 542 (82.6) | 70 (76.9) | < 0.001 |
BMI | 25.9 (3.3) | 25.7 (3.2) | 26.1 (2.6) | 0.29 |
Diabetes mellitus | 1700 (30.1) | 176 (26.8) | 22 (24.2) | 0.108 |
Hypertension | 3680 (65.3) | 390 (59.5) | 55 (60.4) | 0.009 |
Hyperlipidemia | 3800 (67.4) | 409 (62.3) | 56 (61.5) | 0.019 |
Smoking | 3267 (57.9) | 407 (62.0) | 52 (57.1) | 0.127 |
Prior PCI | 1310 (23.2) | 161 (24.5) | 30 (33.0) | 0.076 |
Prior CABG | 225 (4.0) | 24 (3.7) | 4 (4.4) | 0.898 |
Prior MI | 772 (13.7) | 84 (12.8) | 9 (9.9) | 0.485 |
Prior cerebrovascular disease | 635 (11.3) | 74 (11.3) | 10 (11.0) | 0.997 |
Peripheral vascular disease | 154 (2.7) | 18 (2.7) | 2 (2.2) | 0.953 |
STEMI | 1139 (20.2) | 277 (42.2) | 58 (63.7) | < 0.001 |
NSTEMI | 357 (6.3) | 84 (12.8) | 8 (8.8) | < 0.001 |
UA | 4143 (73.5) | 295 (45.0) | 25 (27.5) | < 0.001 |
Left ventricular dysfunction | 269 (4.8) | 51 (7.8) | 19 (20.9) | < 0.001 |
Renal insufficiency | 2 (0.0) | 2 (0.3) | 0 (0.0) | 0.032 |
Procedural characteristics | ||||
Chronic total occlusion | 396 (7.0) | 24 (3.7) | 2 (2.2) | 0.001 |
Left main artery disease | 333 (5.9) | 37 (5.6) | 5 (5.5) | 0.952 |
Moderate to severe calcification | 850 (15.1) | 99 (15.1) | 14 (15.4) | 0.997 |
Lesion number | 1.4 (0.7) | 1.4 (0.7) | 1.4 (0.7) | 0.656 |
Lesion length | 28.1 (18.8) | 28.4 (17.2) | 26.7 (17.1) | 0.72 |
Minimum lesion diameter | 0.4 (0.5) | 0.3 (0.3) | 0.2 (0.3) | < 0.001 |
Drug-eluting stent | 5399 (95.7) | 618 (94.2) | 81 (89.0) | 0.002 |
Laboratory tests | ||||
AST, IU/L | 20.0 (7.4) | 56.1 (25.0) | 216.9 (167.1) | < 0.001 |
ALT, IU/L | 28.5 (19.3) | 71.9 (55.6) | 134.2 (142.8) | < 0.001 |
Albumin, g/dL | 42.6 (4.2) | 41.9 (4.7) | 40.7 (4.2) | < 0.001 |
Total bilirubin, μmol/L | 14.4 (5.4) | 15.7 (6.9) | 19.4 (10.5) | < 0.001 |
Triglycerides, mmol/L | 1.8 (1.1) | 1.8 (1.1) | 1.8 (0.8) | 0.499 |
Total cholesterol, mmol/L | 4.2 (1.1) | 4.2 (1.0) | 4.5 (0.8) | 0.043 |
LDL-C, mmol/L | 2.5 (0.9) | 2.5 (0.9) | 2.7 (0.8) | 0.075 |
HDL-C, mmol/L | 1.0 (0.3) | 1.0 (0.3) | 1.1 (0.3) | 0.04 |
Blood glucose, mmol/L | 6.3 (2.3) | 6.8 (3.0) | 8.2 (4.5) | < 0.001 |
High-sensitivity C-reactive protein, mg/L | 3.4 (3.9) | 5.3 (5.0) | 8.7 (5.8) | < 0.001 |
Clinical outcomes according to liver fibrosis scores
Liver fibrosis staged by LFS | MACCE | All-cause death | Cardiac death | Myocardial infarction | Ischemic stroke | Major bleeding | TVR | Stent thrombosis |
---|---|---|---|---|---|---|---|---|
APRI | ||||||||
Low (N = 5639) | 219 (3.9) | 77 (1.4) | 37 (0.7) | 72 (1.3) | 89 (1.6) | 169 (3.0) | 289 (5.1) | 53 (0.9) |
Intermediate (N = 656) | 28 (4.3) | 10 (1.5) | 7 (1.1) | 14 (2.1) | 11 (1.7) | 18 (2.7) | 38 (5.8) | 8 (1.2) |
High (n = 91) | 12 (13.2) | 6 (6.6) | 6 (6.6) | 4 (4.4) | 4 (4.4) | 3 (3.3) | 5 (5.5) | 5 (5.5) |
p value | < 0.001 | < 0.001 | < 0.001 | 0.011 | 0.108 | 0.922 | 0.76 | < 0.001 |
AST/ALT ratio | ||||||||
Low (N = 3352) | 112 (3.3) | 31 (0.9) | 18 (0.5) | 37 (1.1) | 54 (1.6) | 94 (2.8) | 182 (5.4) | 30 (0.9) |
Intermediate (N = 2666) | 116 (4.4) | 48 (1.8) | 23 (0.9) | 41 (1.5) | 43 (1.6) | 87 (3.3) | 123 (4.6) | 27 (1.0) |
High (N = 368) | 31 (8.4) | 14 (3.8) | 9 (2.4) | 12 (3.3) | 7 (1.9) | 9 (2.4) | 27 (7.3) | 9 (2.4) |
p value | < 0.001 | < 0.001 | < 0.001 | 0.003 | 0.913 | 0.481 | 0.06 | 0.02 |
Forns score | ||||||||
Low (N = 763) | 20 (2.6) | 5 (0.7) | 2 (0.3) | 8 (1.0) | 8 (1.0) | 17 (2.2) | 44 (5.8) | 5 (0.7) |
Intermediate (N = 4582) | 188 (4.1) | 58 (1.3) | 32 (0.7) | 66 (1.4) | 83 (1.8) | 135 (2.9) | 242 (5.3) | 45 (1.0) |
High (N = 1041) | 51 (4.9) | 30 (2.9) | 16 (1.5) | 16 (1.5) | 13 (1.2) | 38 (3.7) | 46 (4.4) | 16 (1.5) |
p value | 0.051 | < 0.001 | 0.005 | 0.648 | 0.174 | 0.209 | 0.397 | 0.152 |
NFS | ||||||||
Low (N = 3109) | 92 (3.0) | 33 (1.1) | 17 (0.5) | 33 (1.1) | 37 (1.2) | 86 (2.8) | 157 (5.0) | 24 (0.8) |
Intermediate (N = 2842) | 124 (4.4) | 41 (1.4) | 20 (0.7) | 43 (1.5) | 53 (1.9) | 89 (3.1) | 150 (5.3) | 28 (1.0) |
High (N = 435) | 43 (9.9) | 19 (4.4) | 13 (3.0) | 14 (3.2) | 14 (3.2) | 15 (3.4) | 25 (5.7) | 14 (3.2) |
p value | < 0.001 | < 0.001 | < 0.001 | 0.001 | 0.003 | 0.592 | 0.802 | < 0.001 |
Association between liver fibrosis scores and MACCE
Liver fibrosis staged by LFS | MACCE | All-cause death | Cardiac death | Myocardial infarction | Ischemic stroke | Major bleeding | TVR | Stent thrombosis |
---|---|---|---|---|---|---|---|---|
APRI | ||||||||
Low (N = 5639) | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) |
Intermediate (N = 656) | 1.1 (0.74–1.63) | 1.12 (0.58–2.16) | 1.62 (0.72–3.63) | 1.67 (0.94–2.96) | 1.06 (0.57–1.98) | 0.91 (0.56–1.49) | 1.13 (0.81–1.59) | 1.29 (0.61–2.72) |
p value | 0.638 | 0.743 | 0.242 | 0.079 | 0.855 | 0.717 | 0.471 | 0.498 |
High (n = 91) | 3.69 (2.06–6.6) | 5.14 (2.24–11.8) | 10.59 (4.47–25.09) | 3.65 (1.33–9.99) | 3.05 (1.12–8.3) | 1.16 (0.37–3.65) | 1.13 (0.47–2.74) | 6.24 (2.49–15.61) |
p value | < 0.001 | < 0.001 | < 0.001 | 0.012 | 0.029 | 0.794 | 0.784 | < 0.001 |
AST/ALT ratio | ||||||||
Low (N = 3352) | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) |
Intermediate (N = 2666) | 1.31 (1.01–1.69) | 1.94 (1.24–3.05) | 1.61 (0.87–2.98) | 1.4 (0.9–2.18) | 1 (0.67–1.49) | 1.17 (0.88–1.57) | 0.85 (0.68–1.07) | 1.13 (0.67–1.9) |
p value | 0.044 | 0.004 | 0.132 | 0.141 | 0.995 | 0.288 | 0.161 | 0.641 |
High (N = 368) | 2.59 (1.74–3.85) | 4.15 (2.21–7.8) | 4.59 (2.06–10.21) | 2.99 (1.56–5.74) | 1.2 (0.55–2.64) | 0.89 (0.45–1.75) | 1.39 (0.93–2.08) | 2.75 (1.31–5.8) |
p value | < 0.001 | < 0.001 | < 0.001 | 0.001 | 0.647 | 0.726 | 0.11 | 0.008 |
Forns score | ||||||||
Low (N = 763) | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) |
Intermediate (N = 4582) | 1.59 (1.01–2.53) | 1.95 (0.78–4.87) | 2.69 (0.64–11.21) | 1.39 (0.67–2.9) | 1.76 (0.85–3.64) | 1.34 (0.81–2.22) | 0.92 (0.67–1.27) | 1.52 (0.6–3.82) |
p value | 0.047 | 0.151 | 0.175 | 0.377 | 0.126 | 0.257 | 0.628 | 0.376 |
High (N = 1041) | 1.91 (1.14–3.2) | 4.46 (1.73–11.5) | 5.94 (1.37–25.83) | 1.49 (0.64–3.47) | 1.22 (0.51–2.95) | 1.68 (0.95–2.97) | 0.77 (0.51–1.16) | 2.39 (0.87–6.51) |
p value | 0.015 | 0.002 | 0.018 | 0.36 | 0.655 | 0.077 | 0.214 | 0.09 |
NFS | ||||||||
Low (N = 3109) | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) |
Intermediate (N = 2842) | 1.48 (1.13–1.94) | 1.36 (0.86–2.15) | 1.29 (0.67–2.46) | 1.43 (0.91–2.25) | 1.58 (1.04–2.4) | 1.14 (0.84–1.53) | 1.05 (0.84–1.31) | 1.28 (0.74–2.21) |
p value | 0.004 | 0.192 | 0.445 | 0.124 | 0.034 | 0.401 | 0.688 | 0.377 |
High (N = 435) | 3.43 (2.39–4.92) | 4.14 (2.35–7.28) | 5.5 (2.67–11.32) | 3.06 (1.64–5.72) | 2.75 (1.49–5.08) | 1.27 (0.73–2.2) | 1.16 (0.76–1.77) | 4.2 (2.17–8.12) |
p value | < 0.001 | < 0.001 | < 0.001 | < 0.001 | 0.001 | 0.392 | 0.495 | < 0.001 |
Liver fibrosis staged by LFS | MACCE | All-cause death | Cardiac death | Myocardial infarction | Ischemic stroke | Major bleeding | TVR | Stent thrombosis |
---|---|---|---|---|---|---|---|---|
APRI | ||||||||
Low (N = 5639) | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) |
Intermediate (N = 656) | 1.14 (0.76–1.7) | 0.97 (0.5–1.9) | 1.43 (0.63–3.27) | 1.91 (1.07–3.43) | 1.15 (0.61–2.16) | 0.99 (0.61–1.62) | 1.13 (0.80–1.59) | 1.35 (0.63–2.87) |
p value | 0.524 | 0.931 | 0.394 | 0.029 | 0.676 | 0.977 | 0.495 | 0.438 |
High (n = 91) | 3.73 (2.03–6.87) | 4.03 (1.66–9.78) | 8.87 (3.32–23.72) | 5.05 (1.76–14.5) | 3.32 (1.17–9.43) | 1.4 (0.44–4.45) | 1.08 (0.44–2.66) | 8.87 (3.29–23.94) |
p value | < 0.001 | 0.002 | < 0.001 | 0.003 | 0.024 | 0.572 | 0.862 | < 0.001 |
AST/ALT ratio | ||||||||
Low (N = 3352) | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) |
Intermediate (N = 2666) | 0.92 (0.7–1.22) | 1.13 (0.71–1.82) | 0.92 (0.48–1.75) | 1.14 (0.71–1.82) | 0.69 (0.45–1.05) | 0.89 (0.65–1.21) | 0.87 (0.68–1.1) | 0.99 (0.58–1.72) |
p value | 0.57 | 0.605 | 0.788 | 0.581 | 0.085 | 0.458 | 0.243 | 0.985 |
High (N = 368) | 1.57 (1.02–2.43) | 1.56 (0.77–3.13) | 1.54 (0.62–3.8) | 2.64 (1.29–5.41) | 0.7 (0.3–1.62) | 0.67 (0.33–1.37) | 1.39 (0.90–2.14) | 2.46 (1.06–5.67) |
p value | 0.042 | 0.214 | 0.352 | 0.008 | 0.408 | 0.276 | 0.141 | 0.035 |
Forns score | ||||||||
Low (N = 763) | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) |
Intermediate (N = 4582) | 1.55 (0.98–2.47) | 2.1 (0.84–5.27) | 2.89 (0.69–12.16) | 1.26 (0.6–2.64) | 1.62 (0.78–3.36) | 1.26 (0.76–2.09) | 0.91 (0.66–1.26) | 1.36 (0.54–3.45) |
p value | 0.063 | 0.112 | 0.147 | 0.542 | 0.196 | 0.377 | 0.573 | 0.518 |
High (N = 1041) | 1.77 (1.05–3) | 4.46 (1.71–11.62) | 5.59 (1.26–24.75) | 1.32 (0.56–3.13) | 1.08 (0.44–2.62) | 1.57 (0.88–2.8) | 0.74 (0.49–1.13) | 1.88 (0.68–5.22) |
p value | 0.032 | 0.002 | 0.023 | 0.53 | 0.871 | 0.128 | 0.166 | 0.226 |
NFS | ||||||||
Low (N = 3109) | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) |
Intermediate (N = 2842) | 1.31 (1–1.72) | 1.2 (0.76–1.92) | 1.05 (0.55–2.03) | 1.24 (0.78–1.96) | 1.35 (0.88–2.07) | 1.06 (0.78–1.43) | 1.01 (0.81–1.27) | 1.12 (0.65–1.96) |
p value | 0.052 | 0.434 | 0.875 | 0.364 | 0.168 | 0.702 | 0.928 | 0.679 |
High (N = 435) | 2.73 (1.86–4) | 2.77 (1.51–5.07) | 3.49 (1.61–7.57) | 2.77 (1.44–5.31) | 2.12 (1.12–4.04) | 1.24 (0.7–2.17) | 1.08 (0.70–1.67) | 4.08 (2.05–8.15) |
p value | < 0.001 | 0.001 | 0.002 | 0.002 | 0.022 | 0.462 | 0.719 | < 0.001 |
Non-cirrhosis | Cirrhosis | p value | |
---|---|---|---|
Unadjusted risk | |||
MACCE | 1(reference) | 3.65 (2.05–6.52) | < 0.001 |
All-cause death | 1(reference) | 5.08 (2.22–11.62) | < 0.001 |
Cardiac death | 1(reference) | 9.95 (4.24–23.34) | < 0.001 |
MI | 1(reference) | 3.41 (1.25–9.30) | 0.017 |
Ischemic stroke | 1(reference) | 3.03 (1.11–8.23) | 0.030 |
TVR | 1(reference) | 1.12 (0.46–2.70) | 0.81 |
Major bleeding | 1(reference) | 1.18 (0.38–3.68) | 0.782 |
Stent thrombosis | 1(reference) | 6.06 (2.43–15.07) | < 0.001 |
Adjusted risk | |||
MACCE | 1(reference) | 3.65 (1.99–6.69) | < 0.001 |
All-cause death | 1(reference) | 4.05 (1.68–9.75) | 0.002 |
Cardiac death | 1(reference) | 8.19 (3.11–21.53) | < 0.001 |
MI | 1(reference) | 4.45 (1.55–12.73) | 0.005 |
Ischemic stroke | 1(reference) | 3.24 (1.15–9.17) | 0.026 |
TVR | 1(reference) | 1.06 (0.43–2.60) | 0.90 |
Major bleeding | 1(reference) | 1.40 (0.44–4.45) | 0.57 |
Stent thrombosis | 1(reference) | 8.39 (3.14–22.47) | < 0.001 |