Summary of 26 meta-analyses

MarkerStudies nParticipants nMean differenceSt. mean differenceOverall effect (p-value)Tau2I2 (%)Heterogeneity (p-value)Forest plot
Haematological markers
RDW %44271.83 (1.39–2.26)0.98 (0.61–2.17)<0.000010.07510.11Figure 2a
PDW %32451.42 (0.16–2.67)0.81 (0.50–1.12)<0.000010.02190.29Figure S2a
MPV fL53610.95 (0.76–1.13)1.0 (0.81–1.25)<0.000010.0000.68Figure S2b
6#3950.66 (0.24–1.09)0.72 (0.24–1.19)0.0030.27780.0003
Thrombocytes (×109 L−1)7334−23.9 (−38.6– −9.2)−0.38 (−0.62– −0.15)0.0010.0150.39Figure S2c
Hb g dL−19400−0.59 (−1.23–0.06)−0.18 (−0.43–0.07)0.150.04290.19Figure S2d
Hct %5229−1.07 (−3.91–1.76)−0.21 (−0.76–0.34)0.460.29740.004Figure S2e
Leukocytes (×109 L−1)7294−0.23 (−0.70,0.24)−0.10 (−0.41–0.21)0.520.07390.13Figure S2f
Metabolic markers
LDL-c mg dL−163035−15.82 (−26.18– −5.46)−0.44 (−0.65– −0.22)<0.000010.03460.10Figure 2b
Total cholesterol mg dL−14408−17.70 (−24.15– −11.26)−0.52 (−0.73– −0.32)<0.000010.00670.67Figure S3a
TG mg dL−14198−32.56 (−54.17– −10.94)−0.52 (−0.87– −0.17)0.0040.04340.21Figure S3b
Glucose (fasted) mg dL−1310324.06 (0.54–7.58)0.48 (0.08–0.87)0.020.0000.85Figure S3c
HDL-c mg dL−16577−6.15 (−2.11–14.40)−0.53 (−1.20–0.15)0.130.6391<0.00001Figure S3d
Coagulation markers
D-dimer ng mL−13142245.99 (148.55–343.43)0.69 (0.27–1.11)0.0010.04270.26Figure 2c
Fibrinogen mg dL−1422773.75 (−2.58–150.08)0.84 (−0.14–1.81)0.090.8890<0.00001Figure S4
Inflammatory markers
IL-6 pg mL−153895.01 (2.06–7.96)0.64 (0.28–0.99)0.00050.08470.11Figure 2d
CRP mg L−183870.74 (0.13–1,6)0.25 (0.04–0.47)0.020.0200.98Figure S5a
9#4930.13 (0.10–0.17)0.77 (−0.08–1.61)0.081.5794<0.00001
sVCAM-1 ng mL−13150626.72 (29.38–1224.07)1.03 (0.53–1.52)<0.000010.08400.19Figure S5b
CXCL-10 pg mL−1317199.77 (54.53–145.01)0.82 (0.49–1.16)<0.000010.0000.46Figure S5c
TIMP-1 ng mL−1322415.58 (−2.56–33.72)0.40 (0.13–0.67)0.0030.0000.54Figure S5d
4#32940.15 (1.02–79.29)0.67 (0.14–1.21)0.010.24820.0009
sP-selectin ng mL−141800.52 (−11.10–12.14)−0.04 (0.35–0.28)0.820.0000.72Figure S5e
Cardiac markers
NT-proBNP pg mL−11011521684 (1035–2330)1.13 (0.93–1.33)<0.000010.03300.17Figure 2e
11#12581004 (787–1221)1.37 (0.96–1.79)<0.000010.3985<0.00001
Renal markers
UA mg dL−154411.77 (1.06–2.48)0.89 (0.58–1.12)<0.000010.06510.09Figure 2f
6#5311.52 (0.77–2.27)0.81 (0.53–1.09)<0.000010.09590.03
BUN mg dL−158911.76 (0.51–3.01)0.43 (0.29–0.56)<0.000010.0000.48Figure S6a
Creatinine mg dL−1104750.03 (−0.04–0.10)0.13 (−0.08–0.34)0.230.02200.26Figure S6b
eGFR mL min−1/1.73 m241801.70 (5.98–9.37)0.09 (−0.32–0.49)0.670.08470.13Figure S6c
Hepatic markers
ALT U L−131153.57 (−4.18–11.31)0.18 (−0.56–0.92)0.370.30710.03Figure 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.