TABLE 1.
Summary of 26 meta-analyses
| Marker | Studies n | Participants n | Mean difference | St. mean difference | Overall effect (p-value) | Tau2 | I2 (%) | Heterogeneity (p-value) | Forest plot |
| Haematological markers | |||||||||
| RDW % | 4 | 427 | 1.83 (1.39–2.26) | 0.98 (0.61–2.17) | <0.00001 | 0.07 | 51 | 0.11 | Figure 2a |
| PDW % | 3 | 245 | 1.42 (0.16–2.67) | 0.81 (0.50–1.12) | <0.00001 | 0.02 | 19 | 0.29 | Figure S2a |
| MPV fL | 5 | 361 | 0.95 (0.76–1.13) | 1.0 (0.81–1.25) | <0.00001 | 0.00 | 0 | 0.68 | Figure S2b |
| 6# | 395 | 0.66 (0.24–1.09) | 0.72 (0.24–1.19) | 0.003 | 0.27 | 78 | 0.0003 | ||
| Thrombocytes (×109 L−1) | 7 | 334 | −23.9 (−38.6– −9.2) | −0.38 (−0.62– −0.15) | 0.001 | 0.01 | 5 | 0.39 | Figure S2c |
| Hb g dL−1 | 9 | 400 | −0.59 (−1.23–0.06) | −0.18 (−0.43–0.07) | 0.15 | 0.04 | 29 | 0.19 | Figure S2d |
| Hct % | 5 | 229 | −1.07 (−3.91–1.76) | −0.21 (−0.76–0.34) | 0.46 | 0.29 | 74 | 0.004 | Figure S2e |
| Leukocytes (×109 L−1) | 7 | 294 | −0.23 (−0.70,0.24) | −0.10 (−0.41–0.21) | 0.52 | 0.07 | 39 | 0.13 | Figure S2f |
| Metabolic markers | |||||||||
| LDL-c mg dL−1 | 6 | 3035 | −15.82 (−26.18– −5.46) | −0.44 (−0.65– −0.22) | <0.00001 | 0.03 | 46 | 0.10 | Figure 2b |
| Total cholesterol mg dL−1 | 4 | 408 | −17.70 (−24.15– −11.26) | −0.52 (−0.73– −0.32) | <0.00001 | 0.00 | 67 | 0.67 | Figure S3a |
| TG mg dL−1 | 4 | 198 | −32.56 (−54.17– −10.94) | −0.52 (−0.87– −0.17) | 0.004 | 0.04 | 34 | 0.21 | Figure S3b |
| Glucose (fasted) mg dL−1 | 3 | 103 | 24.06 (0.54–7.58) | 0.48 (0.08–0.87) | 0.02 | 0.00 | 0 | 0.85 | Figure S3c |
| HDL-c mg dL−1 | 6 | 577 | −6.15 (−2.11–14.40) | −0.53 (−1.20–0.15) | 0.13 | 0.63 | 91 | <0.00001 | Figure S3d |
| Coagulation markers | |||||||||
| D-dimer ng mL−1 | 3 | 142 | 245.99 (148.55–343.43) | 0.69 (0.27–1.11) | 0.001 | 0.04 | 27 | 0.26 | Figure 2c |
| Fibrinogen mg dL−1 | 4 | 227 | 73.75 (−2.58–150.08) | 0.84 (−0.14–1.81) | 0.09 | 0.88 | 90 | <0.00001 | Figure S4 |
| Inflammatory markers | |||||||||
| IL-6 pg mL−1 | 5 | 389 | 5.01 (2.06–7.96) | 0.64 (0.28–0.99) | 0.0005 | 0.08 | 47 | 0.11 | Figure 2d |
| CRP mg L−1 | 8 | 387 | 0.74 (0.13–1,6) | 0.25 (0.04–0.47) | 0.02 | 0.02 | 0 | 0.98 | Figure S5a |
| 9# | 493 | 0.13 (0.10–0.17) | 0.77 (−0.08–1.61) | 0.08 | 1.57 | 94 | <0.00001 | ||
| sVCAM-1 ng mL−1 | 3 | 150 | 626.72 (29.38–1224.07) | 1.03 (0.53–1.52) | <0.00001 | 0.08 | 40 | 0.19 | Figure S5b |
| CXCL-10 pg mL−1 | 3 | 171 | 99.77 (54.53–145.01) | 0.82 (0.49–1.16) | <0.00001 | 0.00 | 0 | 0.46 | Figure S5c |
| TIMP-1 ng mL−1 | 3 | 224 | 15.58 (−2.56–33.72) | 0.40 (0.13–0.67) | 0.003 | 0.00 | 0 | 0.54 | Figure S5d |
| 4# | 329 | 40.15 (1.02–79.29) | 0.67 (0.14–1.21) | 0.01 | 0.24 | 82 | 0.0009 | ||
| sP-selectin ng mL−1 | 4 | 180 | 0.52 (−11.10–12.14) | −0.04 (0.35–0.28) | 0.82 | 0.00 | 0 | 0.72 | Figure S5e |
| Cardiac markers | |||||||||
| NT-proBNP pg mL−1 | 10 | 1152 | 1684 (1035–2330) | 1.13 (0.93–1.33) | <0.00001 | 0.03 | 30 | 0.17 | Figure 2e |
| 11# | 1258 | 1004 (787–1221) | 1.37 (0.96–1.79) | <0.00001 | 0.39 | 85 | <0.00001 | ||
| Renal markers | |||||||||
| UA mg dL−1 | 5 | 441 | 1.77 (1.06–2.48) | 0.89 (0.58–1.12) | <0.00001 | 0.06 | 51 | 0.09 | Figure 2f |
| 6# | 531 | 1.52 (0.77–2.27) | 0.81 (0.53–1.09) | <0.00001 | 0.09 | 59 | 0.03 | ||
| BUN mg dL−1 | 5 | 891 | 1.76 (0.51–3.01) | 0.43 (0.29–0.56) | <0.00001 | 0.00 | 0 | 0.48 | Figure S6a |
| Creatinine mg dL−1 | 10 | 475 | 0.03 (−0.04–0.10) | 0.13 (−0.08–0.34) | 0.23 | 0.02 | 20 | 0.26 | Figure S6b |
| eGFR mL min−1/1.73 m2 | 4 | 180 | 1.70 (5.98–9.37) | 0.09 (−0.32–0.49) | 0.67 | 0.08 | 47 | 0.13 | Figure S6c |
| Hepatic markers | |||||||||
| ALT U L−1 | 3 | 115 | 3.57 (−4.18–11.31) | 0.18 (−0.56–0.92) | 0.37 | 0.30 | 71 | 0.03 | Figure S7 |
Per biomarker the number of studies included, total sample size, mean difference, and the standardised difference between iPAH and non-PH control with 95% confidence interval, p-value of the difference, and heterogeneity of the result (I2, Tau2 and p-heterogeneity) are shown. St. mean difference; standardised mean difference; RDW: red cell distribution width; PDW: platelet distribution width; MPV: mean platelet volume; Hb: haemoglobin; Hct: haematocrit; TG: triglycerides; LDL-c: low density lipoprotein; HDL-c: high density lipoprotein; IL-6: interleukin-6; CRP: c-reactive protein; sVCAM-1: circulating vascular cell adhesion molecule-1; CXCL-10: C-X-C motif chemokine ligand-10; TIMP-1: tissue inhibitors of metalloproteinases-1; NT-proBNP: N-terminal prohormone of brain natriuretic peptide; UA: uric acid; BUN: blood urea nitrogen; eGFR: estimated glomerular filtration rate: ALT: alanine transaminase. #: publication excluded due to heterogeneity.