Table 3.
Multiple test‐corrected biomarkers
| Risk model + biomarker | HR (95%CI) | P value | C‐index | ΔC‐index P value | cNRI (95%CI) |
|---|---|---|---|---|---|
| Primary outcome | |||||
| sST2 | 1.50 (1.30–1.74) | <0.0001 | 0.736 | 0.033 | +0.23 (+0.04, +0.39) |
| TR | 1.27 (1.11–1.46) | 0.0002 | 0.736 | 0.005 | 0.10 (−0.15, 0.28) |
| ACE2 | 1.34 (1.17–1.53) | <0.0001 | 0.731 | 0.23 | 0.23 (−0.10, 0.40) |
| AMBP | 0.53 (0.38–0.74) | 0.0002 | 0.730 | 0.24 | 0.03 (−0.17, 0.21) |
| PON3 | 0.77 (0.68–0.88) | 0.0001 | 0.732 | 0.11 | 0.13 (−0.08, 0.27) |
| CV death | |||||
| Notch‐3 | 1.71 (1.31–2.23) | 0.0001 | 0.761 | 0.049 | +0.18 (+0.07, +0.28) |
| IL‐6 | 1.26 (2.32–3.40) | <0.0001 | 0.763 | 0.019 | 0.05 (−0.10, 0.13) |
| OPG | 2.18 (1.62–2.93) | <0.0001 | 0.762 | 0.21 | +0.13 (+0.03, +0.24) |
| OPN | 1.48 (1–20–1.84) | 0.0002 | 0.759 | 0.37 | +0.15 (+0.03, +0.26) |
| ACE2 | 1.55 (1.28–1.88) | <0.0001 | 0.755 | 0.96 | 0.02 (−0.14, 0.10) |
| GDF‐15 | 1.47 (1.22–1.77) | 0.0001 | 0.759 | 0.59 | 0.12 (−0.06, 0.21) |
| AP‐N | 1.87 (1.40–2.49) | <0.0001 | 0.760 | 0.12 | 0.07 (−0.05, 0.18) |
| sST2 | 1.73 (1.41–2.12) | <0.0001 | 0.760 | 0.35 | 0.01 (−0.01, 0.02) |
| IGFBP‐7 | 1.48 (1.22–1.79) | <0.0001 | 0.758 | 0.22 | 0.09 (−0.03, 0.19) |
| All‐cause death | |||||
| GDF‐15 | 1.59 (1.34–1.88) | <0.0001 | 0.753 | 0.026 | +0.12 (+0.02, +0.23) |
| Notch‐3 | 1.64 (1.29–2.09) | 0.0001 | 0.748 | 0.036 | +0.15 (+0.06, +0.26) |
| IL‐6 | 1.31 (1.18–1.44) | <0.0001 | 0.752 | 0.008 | 0.03 (−0.06, 0.15) |
| vWF | 1.23 (1.11–1.37) | 0.0001 | 0.748 | 0.037 | 0.06 (−0.03, 0.18) |
| FGF‐23 | 1.16 (1.08–1.25) | 0.0001 | 0.745 | 0.041 | 0.06 (−0.16, 0.06) |
| OPG | 2.09 (1.59–2.74) | <0.0001 | 0.748 | 0.29 | +0.13 (+0.03, +0.23) |
| IL‐1RT1 | 1.77 (1.33–2.36) | 0.0001 | 0.739 | 0.54 | +0.14 (+0.02, +0.23) |
| OPN | 1.43 (1.18–1.74) | 0.0002 | 0.746 | 0.36 | +0.16 (+0.04, +0.26) |
| IGFBP‐2 | 1.44 (1.18–1.76) | 0.0002 | 0.743 | 0.33 | +0.18 (+0.08, +0.29) |
| ACE2 | 1.50 (1.27–1.79) | <0.0001 | 0.743 | 0.80 | 0.01 (−0.10, 0.11) |
| sST2 | 1.68 (1.40–2.03) | <0.0001 | 0.746 | 0.51 | 0.04 (−0.05, 0.16) |
| IGFBP‐7 | 1.48 (1.24–1.77) | <0.0001 | 0.747 | 0.14 | 0.09 (−0.01, 0.03) |
| LIF‐R | 1.78 (1.34–2.36) | 0.0001 | 0.741 | 0.79 | 0.11 (−0.01, 0.20) |
| HGF | 1.43 (1.19–1.73) | 0.0002 | 0.743 | 0.53 | 0.01 (−0.01, 0.02) |
ACE2, angiotensin‐converting enzyme 2; AMBP, α1‐microglobulin/bikunin precursor; AP‐N, Aminopeptidase N; CI, confidence interval; FGF‐23, fibroblast growth factor 23; GDF‐15, growth differentiation factor 15; IGFBP‐7, insulin‐like growth factor‐binding protein 7; IGFBP‐2, insulin‐like growth factor‐binding protein 2; HGF, human growth factor; IL1RT1, interleukin 1 receptor type 1; IL‐6, interleukin‐6; LIF‐R, LIF receptor; NRI, net reclassification index; Notch‐3, neurogenic locus notch homolog protein 3; OPG, osteoprotegerin; OPN, osteopontin; PON3, paraoxonase‐3; PRELP, prolargin; sST2, soluble suppression of tumorigenicity 2; TR, transferrin receptor protein 1; vWF, von Willebrand factor.
ΔC‐index, c‐index change on the clinical risk model after the addition of the biomarker.
cNRI, continuous net reclassification index.
Dark green: both c‐index and NRI improvement; Green: c‐index improvement only; Light green: NRI improvement only.