Table 1 A comprehensive table showing the different groups of biomarkers discussed in this review along with the number of subjects, major findings and limitations of the individual studies

Endothelial cell Markers

ADMA

PAH (35)

Increased serum concentration in PAH correlated significantly with mPAP and PVR [54].

CTR (35)

PAH-CHD (30)

No correlation between the significantly increased ADMA concentration in PAHCHD patients and hemodynamic parameters [39].

CHD (20)

CTR (20)

Circulating angiogenic modulatory factors

PAH (97)

Serum concentrations of sEng, sVEGFR1 and CRP were all elevated in PAH patients with sEng having the greatest predictive value for PAH. sEng and CRP were determined to be the most sensitive independent markers for predicting survival [25].

CTR (56)

PCEB-ACE

iPAH (25)

These new techniques allow for the assessment of endothelial function in vivo, but these are currently only for research purposes [32].

PAH-CTD (19)

CTR (23)

Inflammatory markers

GDF-15

PAH-naïve (76)

Significant upregulation in PAH correlated with mean RAP. Plasma concentrations > 1200 ng.L-1 increased the risk of death [30].

PAH-treated (22)

Galectin-3

PAH (15)

Significantly increased in serum of PAH patients which correlated with RV hemodynamics [8].

CTR (10)

OPN

iPAH (70)

Increased plasma concentration in PAH correlated with NYHA functional class. 4 year survival rate increased in concentrations < 34.5 ng.mL-1 [23].

CTR (40)

MIF

Ssc-PAH (15)

Circulating concentration is significantly increased in Ssc-PAH vs. Ssc and correlated with NYHA functional class [44].

Ssc (14)

NLR

PAH (n = 101)

Significant correlation with NYHA functional class and mortality; but not an independent predictor of mortality [34].

Serum BCL-2

Child-PH (35)

Increased sBCL-2 concentration correlated with NYHA functional class [1].

CTR (38)

miR

iPAH (12)

Lists circulating miR that are differentially expressed in PAH vs. control [40].

CTR (10)

Heart function

BNP/NTproBNP and RDW

iPAH (139)

Plasma NT-proBNP is significantly correlated with PVR, CI, and mean RAP. RDW predicted survival independently from NTproBNP and the 6MWD test [37].

CTR (40)

Cystatin C

PAH (14)

Significantly correlates with cardiac and hemodynamic parameters [7].

CTR (10)

Homocysteine

PAH-CHD (30)

Significant increasein PAH-CHD compared to other groups but no hemodynamic correlation was found [39].

CHD (20)

CTR (20)

Cardiac troponin

PAH (167)

Increased concentration of cardiac troponin correlates with mortality [48].

New cardiovascular biomarkers

MRproADM

HF (728)

Significant correlation between increased plasma concentration of MRproADM and mortality [15].

CT-proET1

PAH (28)

Blood concentration increased with WHO functional class and correlated with mortality [43].

Copeptin

PAH (92)

Expression correlated with survival and disease severity [43].

dCTR (39)

hCTR (14)

Oxidative stress

F2-Isoprostanes

PAH (110)

Patients with urine concentration above the median have an increased risk of death [4].

Oxidized lipids

PAH (28)

Significantly increased in serum of PAH patients vs. control [38].

CTR (21)

GSH

PAH (12)

Significantly decreased in plasma of PAH patients [54].

CTR (12)

Metabolic biomarkers

Fisher ratio

PH (140)

Decreases with PH severity. Most measured amino acid levels were significantly higher in patients with PAH [52].

CTR (140)

Tryptophan metabolites

PAH (35)

Anthranilate and Quinolinate were increased with PVR above 2 [21].

CTR (36)

Gherlin

PAH (20)

Plasma levels were significantly increased in PAH and correlated with PASP [53].

CTR (20)

ECM

MMP-2 TIMP-4

PAH (36)

All three proteins were significantly increased in plasma of PAH patients but did not distinguish between functional classes [41].

TNC

CTR (44)

Volatile compounds

PAH (27)

May allow the detection of PAH specific volatile compounds [26].

CTR (30)