Table 2.
Summary of biomarkers with the highest association with cardiovascular death from the identification cohort
| Biomarker | RF ranking | Model 1 | Model 2 | Boruta | ||
|---|---|---|---|---|---|---|
| Hazard ratio (95% CI) | P-value | Hazard ratio (95% CI) | P-value | |||
| cTnT-hs | 1 | 1.890 [1.630, 2.193] | <10e–16e | 1.596 [1.355, 1.880] | 2.174e–08 | Confirmed |
| NT-proBNP | 2 | 2.081 [1.772, 2.444] | <10e–16e | 1.628 [1.373, 1.931] | 2.179e–08 | Confirmed |
| BNP | 3 | 2.016 [1.718, 2.365] | <10e–16e | 1.361 [1.047, 1.769] | 2.148e–02 | Confirmed |
| FGF-23 | 4 | 1.451 [1.341, 1.571] | <10e–16e | 1.209 [1.096, 1.332] | 1.408e–04 | Confirmed |
| IGFBP-2 | 5 | 1.788 [1.499, 2.133] | 1.099e–10 | 1.288 [1.077, 1.540] | 5.509e–03 | Confirmed |
| HGF | 6 | 1.268 [1.183, 1.358] | 1.835e–11 | 1.085 [0.986, 1.194] | 9.345e–02 | Confirmed |
| U-PAR | 7 | 1.783 [1.550, 2.050] | 5.551e–16 | 1.378 [1.158, 1.641] | 3.105e–04 | Confirmed |
| TFF3 | 8 | 1.528 [1.376, 1.697] | 2.109e–15 | 1.269 [1.101, 1.462] | 9.769e–04 | Confirmed |
| REN | 9 | 1.168 [1.000, 1.366] | 5.061e–02 | 1.152 [0.976, 1.360] | 9.456e–02 | Confirmed |
| TNF-R1 | 10 | 1.598 [1.395, 1.831] | 1.336e–11 | 1.207 [1.008, 1.447] | 4.087e–02 | Confirmed |
| LIF-R | 11 | 1.616 [1.410, 1.852] | 5.666e–12 | 1.229 [1.055, 1.433] | 8.316e–03 | Confirmed |
| IL-6 | 12 | 1.575 [1.410, 1.760] | 9.992e–16 | 1.288 [1.126, 1.474] | 2.338e–04 | Confirmed |
| PTX3 | 13 | 1.555 [1.357, 1.781] | 2.031e–10 | 1.261 [1.091, 1.459] | 1.733e–03 | Confirmed |
| TRAIL-R2 | 14 | 1.357 [1.249, 1.474] | 4.613e–13 | 1.183 [1.043, 1.343] | 9.037e–03 | Confirmed |
| NT-3 | 15 | 1.228 [1.123, 1.343] | 6.769e–06 | 1.103 [0.993, 1.225] | 6.652e–02 | Confirmed |
| IGFBP-7 | 16 | 1.430 [1.284, 1.593] | 8.415e–11 | 1.204 [1.068, 1.358] | 2.487e–03 | Confirmed |
| LEP | 17 | 0.783 [0.652, 0.939] | 8.545e–03 | 0.833 [0.686, 1.010] | 6.275e–02 | Confirmed |
| PI3 | 18 | 1.238 [1.110, 1.380] | 1.219e–04 | 1.153 [1.024, 1.298] | 1.904e–02 | Confirmed |
| IL1RL2 | 20 | 0.764 [0.667, 0.876] | 1.170e–04 | 0.794 [0.689, 0.914] | 1.305e–03 | Confirmed |
| GDF-15 | 21 | 1.749 [1.532, 1.996] | 1.110e–16 | 1.243 [1.050, 1.471] | 1.142e–02 | Confirmed |
| TR | 22 | 1.476 [1.308, 1.665] | 2.637e–10 | 1.299 [1.141, 1.479] | 8.092e–05 | Confirmed |
| EGFR | 23 | 0.831 [0.757, 0.912] | 9.443e–05 | 0.861 [0.774, 0.959] | 6.415e–03 | Confirmed |
| TNFRSF13B | 24 | 1.289 [1.176, 1.414] | 6.732e–08 | 1.185 [1.064, 1.320] | 1.949e–03 | Confirmed |
| JAM-A | 25 | 1.333 [1.210, 1.469] | 5.954e–09 | 1.167 [1.031, 1.320] | 1.423e–02 | Confirmed |
| MMP-2 | 26 | 1.304 [1.133, 1.501] | 2.211e–04 | 1.033 [0.904, 1.181] | 6.340e–01 | Confirmed |
| 4E-BP1 | 30 | 1.331 [1.181, 1.499] | 2.555e–06 | 1.202 [1.056, 1.369] | 5.497e–03 | Confirmed |
| EN-RAGE | 32 | 1.267 [1.111, 1.444] | 3.973e–04 | 1.147 [0.991, 1.327] | 6.511e–02 | Confirmed |
| ACE2 | 33 | 1.396 [1.234, 1.580] | 1.211e–07 | 1.148 [1.000, 1.318] | 5.018e–02 | Confirmed |
| SLAMF1 | 34 | 1.237 [1.116, 1.372] | 5.327e–05 | 1.112 [0.987, 1.251] | 8.000e–02 | Confirmed |
| TNFSF13B | 40 | 1.257 [1.118, 1.412] | 1.262e–04 | 1.097 [0.975, 1.235] | 1.242e–01 | Confirmed |
| CTSL1 | 42 | 1.365 [1.207, 1.544] | 7.328e–07 | 1.220 [1.069, 1.392] | 3.173e–03 | Confirmed |
| TGFA | 44 | 1.384 [1.214, 1.579] | 1.210e–06 | 1.115 [0.983, 1.266] | 9.156e–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).