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Table 4 Cox regression analysis for study endpoints

From: Cardiac resynchronization therapy with a defibrillator (CRTd) in failing heart patients with type 2 diabetes mellitus and treated by glucagon-like peptide 1 receptor agonists (GLP-1 RA) therapy vs. conventional hypoglycemic drugs: arrhythmic burden, hospitalizations for heart failure, and CRTd responders rate

  Univariate analysis Multivariate analysis
HR (95% CI) p value HR (95% CI) p value
a. Multivariate cox regression analysis for parameters associated with all cause deaths
 LVEF 1.060 [0.978–1.148] 0.157 0.994 [0.608–1.625] 0.981
 6MWT 0.989 [0.974–1.003] 0.131 0.975 [0.869–1.093] 0.661
 BNP 1.001 [0.999–1.020] 0.233 0.989 [0.963–1.016] 0.463
 TNF alpha 1.666 [0.650–4.273] 0.288 2.253 [0.001–2.671] 0.939
 GLP-1 2.980 [0.904–9.824] 0.073 5.127 [0.002–12.548] 0.445
 CRP 0.977 [0.933–1.024] 0.336 0.867 [0.002–12.548] 0.548
 IL-6 1.254 [0.811–1.939] 0.308 0.004 [0.545–1.380] 0.961
 GLP-1 agonist 2.373 [1.087–5.182] 0.030 7.619 [0.004–14.031] 0.597
 Age 1.140 [1.082–1.201] 0.001 1.063 [0.805–1.404] 0.665
 Obesity 0.045 [0.001–2.916] 0.347 1.139 [0.001–3.434] 0.945
 NYHA 3 1.518 [0.731–3.151] 0.263 0.037 [0.001–1.358] 0.273
 COPD 3.793 [1.827–7.874] 0.001 0.107 [0.001–1.297] 0.529
 QRS duration 1.005 [0.967–1.044] 0.810 0.981 [0.608–1.128] 0.081
 Hypertension 1.686 [0.689–4.125] 0.252 0.005 [0.001–2.492] 0.087
 Dyslipidemia 0.957 [0.391–2.341] 0.923 0.872 [0.401–4.951] 0.331
 Renal dysfunction 1.054 [0.320–3.476] 0.931 3.854 [0.015–8.201] 0.095
 Hb1Ac 0.756 [0.435–1.347] 0.354 0.416 [0.072–2.415] 0.328
b. Multivariate cox regression analysis for parameters associated with cardiac deaths
 LVEF 0.952 [0.902–1.006] 0.080 0.438 [0.001–8.345] 0.831
 6MWT 0.998 [0.987–1.009] 0.733 1.141 [0.778–1.673] 0.510
 BNP 1.001 [0.989–1.010] 0.853 0.993 [0.935–1.054] 0.831
 TNF alpha 2.277 [1.091–4.752] 0.028 0.201 [0.011–8.955] 0.727
 GLP-1 2.980 [0.904–9.824] 0.073 5.127 [0.002–12.548] 0.445
 CRP 0.961 [0.920–1.004] 0.075 4.282 [0.035–5.287] 0.554
 IL-6 1.364 [0.976–1.906] 0.069 7.623 [0.002–12.782] 0.724
 GLP-1 agonist 1.691 [0.929–3.087] 0.085 0.001 [0.015–1.491] 0.687
 Age 1.307 [1.237–1.381] 0.001 2.680 [0.562–12.791] 0.095
 Obesity 1.018 [0.316–3.282] 0.976 0.013 [0.005–6.410] 0.772
 NYHA 3 8.791 [3.474–22.248] 0.001 0.010 [0.001–7.279 0.633
 COPD 2.041 [1.143–3.646] 0.016 0.421 [0.001–1.760] 0.863
 QRS duration 0.990 [0.959–1.021] 0.528 2.797 [0.333–23.510] 0.344
 Hypertension 1.744 [0.842–3.614] 0.135 0.031 [0.001–2.310] 0.868
 Dyslipidemia 3.473 [1.078–11.195] 0.037 4.939 [0.001–12.181] 0.358
 Renal dysfunction 0.636 [0.197–2.051] 0.449 0.052 [0.003–1.193] 0.422
 Hb1Ac 1.429 [0.911–2.241] 0.120 3.119 [0.384–4.091] 0.167
c. Multivariate cox regression analysis for parameters associated with hospitalization for heart failure
 LVEF 0.978 [0.945–1.012] 0.199 0.927 [0.826–1.041] 0.202
 6MWT 1.003 [0.997–1.010] 0.301 1.013 [0.992–1.034] 0.226
 BNP 1.002 [1.001–1.020] 0.001 1.120 [1.001–1.401] 0.017*
 TNF alpha 1.078 [0.665–1.749] 0.761 0.028 [0.000–1.673] 0.420
 GLP-1 1.719 [1.077–2.744] 0.023 1.143 [0.451–2.900] 0.778
 CRP 0.987 [0.967–1.007] 0.207 0.981 [0.923–1.042] 0.530
 IL-6 1.163 [0.926–1.460] 0.193 1.879 [0.017–2.129] 0.272
 GLP-1 agonist 1.914 [1.335–2.744] 0.001 0.119 [0.028–0.508] 0.004*
 Age 1.005 [0.979–1.033] 0.691 0.977 [0.891–1.072] 0.624
 Obesity 0.997 [0.488–2.039] 0.994 0.923 [0.826–1.742] 0.983
 NYHA 3 1.680 [1.177–2.397] 0.004 1.43 [0.398–1.041] 0.562
 COPD 1.126 [0.776–1.633] 0.533 6.870 [0.639–7.383] 0.112
 QRS duration 1.005 [0.987–1.024] 0.578 1.031 [0.963–1.102] 0.383
 Hypertension 0.875 [0.606–1.265] 0.478 1.381 [0.342–5.583] 0.651
 Dyslipidemia 1.932 [1.128–3.311] 0.016 0.354 [0.081–1.541] 0.166
 Renal dysfunction 0.889 [0.479–1.649] 0.709 0.565 [0.103–3.098] 0.510
 Hb1Ac 1.255 [0.955–1.649] 0.103 0.967 [0.626–1.493] 0.879
d. Multivariate cox regression analysis for parameters associated with CRT responders
 LVEF 1.043 [1.019–1.068] 0.001 1.032 [0.979–1.089] 0.239
 6MWT 1.010 [0.996–1.410] 0.897 0.998 [0.987–1.008] 0.665
 BNP 1.001 [0.989–1.001] 0.487 1.012 [0.989–1.189] 0.962
 TNF alpha 0.950 [0.688–1.312] 0.755 0.508 [0.007–3.712] 0.757
 GLP-1 0.840 [0.660–1.069] 0.156 0.757 [0.510–1.123] 0.166
 CRP 0.997 [0.986–1.008] 0.601 0.997 [0.966–1.029] 0.851
 IL-6 1.007 [0.857–1.183] 0.930 0.823 [0.010–6.662] 0.953
 GLP-1 agonist 1.041 [0.841–1.288] 0.714 3.707 [1.226–14.570] 0.026*
 Age 0.988 [0.972–1.005] 0.154 1.010 [0.957–1.045] 0.992
 Obesity 1.394 [0.934–2.080] 0.104 0.564 [0.192–1.656] 0.297
 NYHA 3 0.711 [0.573–0.881] 0.020 1.222 [0.646–2.313] 0.538
 COPD 0.796 [0.624–1.015] 0.066 2.474 [0.965–6.343] 0.059
 QRS duration 0.989 [0.978–1.001] 0.053 0.999 [0.971–1.027] 0.059
 Hypertension 1.073 [0.850–1.355] 0.554 0.774 [0.430–1.394] 0.394
 Dyslipidemia 0.848 [0.653–1.102] 0.218 1.135 [0.632–2.039] 0.671
 Renal dysfunction 0.937 [0.651–1.349] 0.727 1.685 [0.666–4.260] 0.270
 Hb1Ac 1.028 [0.864–1.222] 0.756 1.170 [0.949–1.442] 0.141
e. Multivariate cox regression analysis for parameters associated with strokes
 LVEF 0.931 [0.866–1.002] 0.055 0.449 [0.033–7.319] 0.758
 6MWT 0.989 [0.973–1.006] 0.203 1.065 [0.232–4.894] 0.935
 BNP 1.001 [0.989–1.020] 0.297 0.991 [0.809–1.214] 0.932
 TNF alpha 1.062 [0.347–3.250] 0.917 0.016 [0.001–6.694] 0.988
 GLP-1 2.315 [0.69–7.761] 0.174 0.020 [0.001–7.072] 0.862
 CRP 0.983 [0.935–1.033] 0.502 1.215 [0.002–7.735] 0.953
 IL-6 0.617 [0.273–1.394] 0.245 2.159 [0.001–3.829] 0.991
 GLP-1 agonist 1.691 [0.740–3.864] 0.213 1.320 [0.001–6.473] 0.913
 Age 0.946 [0.885–1.012] 0.104 1.263 [0.004–4.136] 0.937
 Obesity 5.241 [2.080–13.205] 0.001 0.031 [0.001–2.678] 0.771
 NYHA 3 0.994 [0.447–2.213] 0.989 0.129 [0.001–5.426] 0.960
 COPD 1.764 [0.784–3.972] 0.170 0.212 [0.001–1.878] 0.896
 QRS duration 1.001 [0.960–1.045] 0.951 1.315 [0.059–2.940] 0.960
 Hypertension 1.264 [0.502–3.185] 0.619 2.066 [0.001–11.954] 0.982
 Dyslipidemia 0.699 [0.277–1.762] 0.448 0.948 [0.001–3.020] 0.794
 Renal dysfunction 0.043 [0.001–16.543] 0.301 0.880 [0.001–1.003] 0.880
 Hb1Ac 1.115 [0.412–3.021] 0.830 4.248 [0.001–5.346] 0.752
f. Multivariate cox regression analysis for parameters associated with VT events
 LVEF 1.041 [0.985–1.100] 0.157 1.160 [1.012–1.290] 0.047*
 6MWT 0.993 [0.983–1.040] 0.203 0.993 [0.983–1.004] 0.194
 BNP 1.001 [0.909–1.020] 0.321 1.001 [0.098–1.002] 0.505
 TNF alpha 1.475 [0.749–2.904] 0.261 1.009 [0.484–2.101] 0.981
 GLP-1 1.839 [0.904–3.739] 0.093 0.878 [0.585–1.317] 0.529
 CRP 0.973 [0.940–1.007] 0.121 0.991 [0.958–1.025] 0.609
 IL-6 1.384 [1.034–1.853] 0.029 1.076 [0.780–1.485] 0.654
 GLP-1 agonist 0.332 [0.185–0.597] 0.001 0.964 [0.963–0.992] 0.012*
 Age 1.039 [1.001–1.079] 0.046 1.051 [0.816–1.599] 0.066
 Obesity 5.478 [3.005–9.987] 0.001 0.174 [0.016–1.599] 0.072
 NYHA 3 2.773 [1.562–4.923] 0.001 0.541 [0.281–1.043] 0.067
 COPD 2.345 [1.404–3.915] 0.001 0.846 [0.466–1.538] 0.584
 QRS duration 0.975 [0.948–1.003] 0.080 1.511 [1.160–1.959] 0.026*
 Hypertension 0.805 [0.469–1.380] 0.430 1.031 [0.570–1.863] 0.920
 Dyslipidemia 2.619 [1.048–6.548] 0.039 1.232 [0.715–2.122] 0.452
 Renal dysfunction 1.056 [0.454–2.456] 0.901 0.420 [0.012–1.531] 0.075
 Hb1Ac 1.239 [0.760–2.020] 0.389 1.320 [0.021–3.426] 0.752
g. Multivariate cox regression analysis for parameters associated with AF events
 LVEF 0.964 [0.934–0.994] 0.021 1.593 [1.122–1.986] 0.006*
 6MWT 1.001 [0.994–1.601] 0.977 1.024 [0.995–1.046] 0.712
 BNP 1.020 [1.001–1.100] 0.008 1.101 [1.001–1.210] 0.017*
 TNF alpha 1.180 [0.759–1.836] 0.462 1.298 [0.773–2.180] 0.324
 GLP-1 1.049 [0.720–1.526] 0.804 1.087 [0.829–1.427] 0.962
 CRP 1.010 [0.983–1.180] 0.561 0.997 [0.979–1.015] 0.732
 IL-6 1.016 [0.808–1.277] 0.983 0.936 [0.703–1.247] 0.652
 GLP-1 agonist 0.577 [0.348–0.957] 0.033 0.603 [0.411–0.884] 0.010*
 Age 0.989 [0.964–1.014] 0.388 0.982 [0.957–1.008] 0.182
 Obesity 0.941 [0.479–1.846] 0.859 0.952 [0.493–1.841] 0.885
 NYHA 3 1.044 [0.756–1.441] 0.795 0.942 [0.670–1.324] 0.730
 COPD 1.113 [0.785–1.577] 0.548 1.020 [0.683–1.523] 0.924
 QRS duration 1.020 [1.003–1.037] 0.020 1.182 [1.012–1.552] 0.043*
 Hypertension 0.929 [0.656–1.316] 0.680 1.519 [0.926–2.492] 0.098
 Dyslipidemia 0.828 [0.560–1.223] 0.343 1.232 [0.715–2.122] 0.452
 Renal  dysfunction 0.588 [0.598–1.162] 0.126 0.613 [0.024–1.618] 0.082
 Hb1Ac 1.176 [0.914–1.512] 0.208 1.150 [0.002–2.152] 0.073
  1. GLP-1: glucagone like peptide 1; COPD: chronic obstructive pulmonary disease; NYHA: New York Heart Association; 6MWT: 6 min walking test; CRTd: cardiac resynchronization with a defibrillator; n.s.: not statistical significant; LVEF: left ventricle ejection fraction; ACE: angiotensin converting enzyme; ARS: angiotensin receptor; NOAC: new oral anticoagulant; DPP4: Di-Peptidil-Peptidasi IV; BNP: B type natriuretic peptide; CRP: C reactive protein; IL6: interleukine 6; TNFa: tumor necrosis factor alpha
  2. p value < 0.05 is statistical significant, and marked as *
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