Background
Methods
Study population
Baseline and laboratory measurements
Outcomes
Statistical analysis
Results
Baseline characteristics and biomarker levels
Variable | All | Subjects with major adverse cardiovascular events | Subjects without major adverse cardiovascular events | P value |
---|---|---|---|---|
N | 2275 | 402 | 1873 | |
Age ≥ 65 years | 1400 (62) | 313 (78) | 1087 (58) | < 0.001 |
Male | 1664 (73) | 270 (67) | 1394 (74) | 0.003 |
Current smoker | 289 (13) | 49 (12) | 240 (13) | 0.73 |
T2DM | 1617 (71) | 328 (82) | 1289 (69) | < 0.001 |
Hypertension | 1997 (88) | 380 (95) | 1617 (86) | < 0.001 |
BMI, kg/m2 | 25.8 ± 3.6 | 25.4 ± 3.9 | 25.8 ± 3.6 | 0.054 |
Systolic blood pressure, mmHg | 137 ± 20 | 140 ± 23 | 137 ± 20 | < 0.001 |
Diastolic blood pressure, mmHg | 73 ± 11 | 70 ± 12 | 74 ± 11 | < 0.001 |
Triglycerides, mmol/L | 1.49 ± 1.02 | 1.51 ± 1.11 | 1.49 ± 1.00 | 0.65 |
Total cholesterol, mmol/L | 3.89 ± 0.89 | 3.94 ± 1.01 | 3.88 ± 0.87 | 0.17 |
HDL-cholesterol, mmol/L | 1.18 ± 0.33 | 1.18 ± 0.33 | 1.18 ± 0.33 | 0.79 |
LDL-cholesterol, mmol/L | 2.01 ± 0.73 | 2.06 ± 0.83 | 2.01 ± 0.71 | 0.22 |
HbA1c, % | 7.07 ± 1.39 | 7.41 ± 1.51 | 7.00 ± 1.36 | < 0.001 |
Ln-hs-Tnl, pg/mL | 2.1 ± 1.2 | 2.5 ± 1.4 | 2.1 ± 1.1 | < 0.001 |
Above cutoff (> 14.2 pg/mL) | 511 (22) | 148 (37) | 363 (19) | < 0.001 |
Ln-BNP, pg/mL | 3.8 ± 1.1 | 4.1 ± 1.3 | 3.7 ± 1.1 | < 0.001 |
Above
cutoff (> 56.7 pg/mL) | 877 (39) | 212 (53) | 665 (36) | < 0.001 |
Ln-Enrollment period, month | 3.1 ± 1.0 | 3.5 ± 0.9 | 3.0 ± 1.0 | < 0.001 |
Variables | T2DM | No T2DM | P value |
---|---|---|---|
n | 1617 | 658 | |
Age ≥ 65 years | 1029 (64) | 371 (56) | 0.001 |
Male | 1168 (72) | 496 (75) | 0.13 |
Current smoker | 181 (11) | 108 (16) | 0.001 |
Hypertension | 1557 (96) | 440 (67) | < 0.001 |
BMI, kg/m2 | 26.0 ± 3.6 | 25.2 ± 3.6 | < 0.001 |
Systolic blood pressure, mmHg | 140 ± 21 | 131 ± 18 | < 0.001 |
Diastolic blood pressure, mmHg | 73 ± 11 | 74 ± 11 | 0.066 |
Triglycerides, mmol/L | 1.50 ± 1.02 | 1.46 ± 1.02 | 0.37 |
Total cholesterol, mmol/L | 3.80 ± 0.85 | 4.09 ± 0.97 | < 0.001 |
HDL-cholesterol, mmol/L | 1.16 ± 0.33 | 1.23 ± 0.34 | < 0.001 |
LDL-cholesterol, mmol/L | 1.95 ± 0.67 | 2.17 ± 0.84 | < 0.001 |
HbA1c, % | 7.38 ± 1.36 | 6.34 ± 1.17 | < 0.001 |
Ln-hs-Tnl, pg/mL | 2.2 ± 1.1 | 2.1 ± 1.4 | 0.44 |
Above cut-off (> 14.2 pg/mL) | 376 (23) | 135 (21) | 0.16 |
Ln-BNP, pg/mL | 3.8 ± 1.1 | 3.6 ± 1.2 | < 0.001 |
Above cut-off (> 56.7 pg/mL) | 672 (42) | 205 (31) | <0.001 |
Ln-enrollment period, month | 3.1 ± 0.8 | 2.9 ± 1.3 | <0.001 |
Outcomes | |||
Major adverse cardiovascular events | 328 (20) | 74 (11) | < 0.001 |
Predictive values of cardiac biomarkers for MACE
Variable | Model 1 | Model 2 | Model 3 | Model 4 | Model 5 | |||||
---|---|---|---|---|---|---|---|---|---|---|
HR (95% CI) | P value | HR (95% CI) | P value | HR (95% CI) | P value | HR (95% CI) | P value | HR (95% CI) | P value | |
Age ≥ 65 years | 2.53 (2.00–3.21) | < 0.001 | 2.36 (1.85–2.99) | < 0.001 | 2.29 (1.80–2.91) | < 0.001 | 2.31 (1.82–2.93) | < 0.001 | 2.28 (1.79–2.90) | < 0.001 |
Male | 0.83 (0.68–1.03) | 0.089 | 0.84 (0.68–1.04) | 0.098 | 0.85 (0.69–1.05) | 0.14 | 0.85 (0.69–1.06) | 0.15 | ||
T2DM | – | – | 1.25 (0.95–1.65) | 0.11 | 1.24 (0.94–1.63) | 0.13 | 1.30 (0.99–1.71) | 0.062 | 1.28 (0.97–1.69) | 0.079 |
Hypertension | – | – | 1.58 (1.00–2.50) | 0.051 | 1.54 (0.97–2.45) | 0.065 | 1.57 (0.99–2.49) | 0.055 | 1.55 (0.98–2.46) | 0.063 |
BNP | – | – | – | – | 1.66 (1.36–2.02) | <0.001 | – | – | 1.42 (1.15–1.75) | 0.001 |
hs-Tnl | – | – | – | – | – | – | 1.97 (1.60–2.41) | <0.001 | 1.75 (1.41–2.17) | < 0.001 |
Incremental value of cardiac biomarkers over conventional risk factors for MACE
Model | Feature | AIC | NRI (95% CI) | P value | IDI (95% CI) | P value |
---|---|---|---|---|---|---|
Model 2 | Age ≥ 65 years + Male + T2DM + Hypertension | 5701.9 | – | – | – | – |
Model 3 | Model 2 + BNP | 5678.3 | 34.5% (23.8–45.1%) | < 0.001 | 1.2% (0.7–1.7%) | < 0.001 |
Model 4 | Model 2 + hs-Tnl | 5664.5 | 34.9% (24.8–45.0%) | < 0.001 | 2.4% (1.6–3.2%) | < 0.001 |
Model 5 | Model 2 + hs-Tnl + BNP | 5655.5 | 29.7% (19.2–40.2%) | < 0.001 | 2.9% (2.1–3.8%) | < 0.001 |
Cardiac biomarkers for patients with or without T2DM
Model | Feature | T2DM, AUC (95% CI) | No T2DM, AUC (95% CI) | P value* |
---|---|---|---|---|
Model 2 | Age ≥ 65 years + Male + hypertension | 0.60 (0.57–0.63) | 0.64 (0.59–0.70) | 0.23 |
Model 3 | Model 2 + BNP | 0.63 (0.59–0.66) | 0.72 (0.66–0.78) | 0.009 |
Model 4 | Model 2 + hs-Tnl | 0.64 (0.61–0.67) | 0.72 (0.66–0.78) | 0.016 |
Model 5 | Model 2 + hs-Tnl + BNP | 0.64 (0.61–0.68) | 0.75 (0.69–0.81) | <0.001 |