Table 3.
Summary of biomarkers with the highest association with cardiovascular death from the validation cohort
| Biomarker | RF ranking | Model 1 | Model 2 | Boruta | ||
|---|---|---|---|---|---|---|
| Hazard ratio (95% CI) | P-value | Hazard ratio (95% CI) | P-value | |||
| cTnT-hs | 1 | 1.753 [1.500–2.047] | 1.464e–12 | 1.528 [1.305–1.788] | 1.307e–07 | Confirmed |
| NT-proBNP | 2 | 2.959 [2.297–3.813] | <10e–16e | 2.256 [1.758–2.894] | 1.555e–10 | Confirmed |
| U-PAR | 3 | 2.193 [1.824–2.636] | 1.110e–16 | 1.624 [1.300–2.028] | 1.931e–05 | Confirmed |
| TFF3 | 4 | 1.793 [1.492–2.154] | 4.581e–10 | 1.518 [1.236–1.865] | 7.028e–05 | Confirmed |
| TRAIL-R2 | 5 | 1.343 [1.196–1.508] | 6.012e–07 | 1.256 [1.121–1.407] | 8.435e–05 | Confirmed |
| BNP | 6 | 2.191 [1.673–2.870] | 1.201e–08 | 1.073 [0.741–1.555] | 0.70972 | Confirmed |
| GDF-15 | 7 | 1.980 [1.613–2.431] | 6.749e–11 | 1.383 [1.100–1.739] | 5.506e–03 | Confirmed |
| REN | 8 | 1.825 [1.421–2.343] | 2.385e–06 | 1.772 [1.380–2.274] | 7.224e–06 | Confirmed |
| IL6 | 9 | 1.556 [1.379–1.757] | 8.954e–13 | 1.310 [1.152–1.490] | 3.729e–05 | Confirmed |
| TNF-R1 | 10 | 2.153 [1.771–2.617] | 1.377e–14 | 1.544 [1.207–1.974] | 5.339e–04 | Confirmed |
| CTSL1 | 11 | 1.684 [1.415–2.004] | 4.241e–09 | 1.330 [1.107–1.599] | 2.364e–03 | Confirmed |
| ADM | 12 | 1.681 [1.133–2.494] | 9.867e–03 | 1.092 [0.889–1.343] | 0.40156 | Confirmed |
| TNFRSF11A | 13 | 2.062 [1.691–2.513] | 7.775e–13 | 1.529 [1.210–1.931] | 3.759e–04 | Confirmed |
| ST2 | 14 | 1.622 [1.357–1.940] | 1.127e–07 | 1.266 [1.056–1.517] | 1.065e–02 | Confirmed |
| TIM1 | 15 | 1.584 [1.317–1.904] | 1.023e–06 | 1.317 [1.096–1.582] | 3.317e–03 | Confirmed |
| JAM-A | 16 | 1.425 [1.245–1.632] | 2.819e–07 | 1.168 [0.981–1.391] | 8.162e–02 | Confirmed |
| IGFBP-7 | 17 | 1.560 [1.361–1.788] | 1.606e–10 | 1.178 [0.996–1.394] | 5.635e–02 | Confirmed |
| FGF-23 | 18 | 1.476 [1.288–1.690] | 1.907e–08 | 1.183 [1.023–1.368] | 2.335e–02 | Confirmed |
| TNFRSF10A | 19 | 1.844 [1.519–2.238] | 6.347e–10 | 1.344 [1.078–1.677] | 8.663e–03 | Confirmed |
| GAL-9 | 20 | 1.966 [1.610–2.399] | 3.012e–11 | 1.529 [1.212–1.930] | 3.419e–04 | Confirmed |
| CSTB | 21 | 1.679 [1.432–1.968] | 1.574e–10 | 1.357 [1.113–1.653] | 2.474e–03 | Confirmed |
| FABP4 | 23 | 2.159 [1.697–2.747] | 3.749e–10 | 1.743 [1.347–2.254] | 2.343e–05 | Confirmed |
| IL-1RT1 | 24 | 1.521 [1.260–1.836] | 1.286e–05 | 1.200 [0.999–1.441] | 5.066e–02 | Confirmed |
| PON3 | 25 | 0.684 [0.572–0.818] | 3.159e–05 | 0.794 [0.651–0.969] | 0.02328 | Confirmed |
| BOC | 26 | 1.470 [1.197–1.806] | 2.372e–04 | 1.353 [1.123–1.631] | 1.491e–03 | Confirmed |
| MMP12 | 28 | 1.550 [1.274–1.886] | 1.212e–05 | 1.322 [1.080–1.619] | 6.845e–03 | Confirmed |
| TNF-R2 | 32 | 1.415 [1.188–1.685] | 9.948e–05 | 1.198 [1.009–1.422] | 3.896e–02 | Confirmed |
| CD4 | 40 | 1.799 [1.513–2.139] | 2.923e–11 | 1.385 [1.125–1.704] | 2.139e–03 | Confirmed |
| IGFBP2 | 48 | 2.117 [1.621–2.764] | 3.652e–08 | 1.290 [0.981–1.695] | 6.796e–02 | Confirmed |
All biomarkers confirmed by Boruta analysis included, ranked according to Random Survival Forest (RF) variable importance. Biomarkers in bold indicate biomarkers P ≤ 0.05 in adjusted Cox-regression model 2 and confirmed in Boruta analyses in both cohorts. Model 1: Cox-regression analysis model adjusted for clinical characteristics—age, gender, body mass index, smoking, hypertension, diabetes, prior myocardial infarction, prior stroke/transient ischaemic attack, prior peripheral artery disease, prior heart failure, and randomized treatment. Model 2: same as Model 1 and also adjusted for marker for renal function, Cystatin C, and cardiac markers N-terminal pro-B-type natriuretic peptide (NT-proBNP) + cardiac troponin T (hs-cTnT).