Table 6Biomarker levels by diagnostic group

Study
Population (N)
Quality
BiomarkerReference Diagnostic Criterion for PAHPatients With PAHPatients Without PAHSummary Measure
NMean (SD) (pg/mL)NMean (SD) (pg/mL)Criteria for Verification by RHC
Allanore, 200827a

SSc patients with echocardiography sPAP <40 mmHg and no NYHA III/IV symptoms (N=101)

Good
NT-proBNPmPAP ≥25 mmHg, PCWP ≤15 mmHg8413 (304)93127 (135)sPAP >40 mmHg, DLCO <50% predicted without pulmonary fibrosis or unexplained dyspnea, negative CT, D-dimer
Bonderman, 201126

Referred for evaluation of suspected PAH; more than half had NYHA III/IV symptoms (N=372)

Good
NT-proBNPmPAP >25 mmHg, PCWP <15 mmHg643648 (6541)571489 (3518)sPAP ≥36 mmHg
Cavagna, 201014

SSc patients; symptoms not described (N=135)

Good
NT-proBNPmPAP >25 mmHg, PCWP <15 mmHg20189 (44 to 665)a11584 (39 to 181)bsPAP ≥36 mmHg
Frea, 201135a

SSc patients with no signs or symptoms of PAH (N=76)

Fair
NT-proBNPmPAP ≥25 mmHg, PCWP ≤15 mmHg4211 (134)34127 (100)TRV ≥3 m/s or sPAP ≥40 mmHg
Ghio, 200473

HIV and confirmed PAH; controls with HIV and no known cardiac or pulmonary disease (N=93)

Fair
NT-proBNPNR161412 (574 to 2326)a7729 (7 to 48)bNR (case-control design)
Simeoni, 200858

Known SSc-associated PAH and controls with SSc but no PAH (N=20)

Poor
NT-proBNPNR1019810103NR (case-control design)
Thakkar, 201281

SSc patients with PAH, at high risk for PAH, with ILD, or SSc controls without PAH (N=94)

Fair
NT-proBNPmPAP ≥25 mmHg, PCWP ≤15 mmHg151818 (2367)19 (ILD)133 (87)Echo sPAP ≥40 mmHg or DLCO ≤50% predicted with FVC >85%, DLCO ≥20% or unexplained dyspnea
30 (SSc)72 (38)
30 (risk)278 (243)
Williams, 200668

SSc patients with PAH and controls with SSc but without PAH (N=109)

Fair
NT-proBNPNR, but PCWP ≤15 mmHg required681474 (2642)41139 (150)NA (case-control design; all patients had RHC)
Cavagna, 201014

SSc patients; symptoms not described (N=135)

Good
BNPmPAP ≥25 mmHg, PCWP <15 mmHg2074.5 (29 to 196)a11530 (18 to 49)bsPAP ≥36 mmHg, DLCO <50%pred, 20% decrease DLCO in 1 yr in absence of pulmonary fibrosis, or unexplained dyspnea, negative CT
Gialafos, 200871

SSc patients; some symptomatic (N=106)

Fair
BNPNR37163 (159)6933 (23)sPAP >40 mmHg (18/37 patients verified by RHC)
Sanli, 201279

Children with unrepaired CHD with or without PAH and healthy controls (N=70)

Fair
ADMAmPAP≥25 mmHg, PCWP ≤ 15 mmHg3023.1 (9.2)2019.6 (7.4) (CHD controls)All patients verified by RHC
2017.1 (5.6) (healthy controls)
Bogdan, 199828

PAH patients (N=19) and controls (N=30)

Poor
Urinary cGMPNR19251 (26) nmol/mmol creatinine3051 (4) healthy controlsNR (case-control design)
771 (8) asthmatic controls
Tutar 199964

Children with left-to-right shunt (N=23) and healthy controls (N=11)

Fair
Plasma endothelin-1 (ratio of pulmonary venous and systemic venous level)Ratio of simultaneous mPAP to aortic mean pressure > 0.591.10 (0.35)140.90 (0.16)NR (case-control design)

ADMA = asymmetric dimethylarginine; CHD = congenital heart disease; CT = computed tomography; DLCO = diffusion capacity of the lung for carbon monoxide; FVC = forced vital capacity; ILD = interstitial lung disease; mmHg = millimeter of mercury; mPAP = mean pulmonary artery pressure; m/s = meters per second; NT-proBNP = N-terminal pro-B-type natriuretic peptide; NYHA = New York Heart Association; PAH = pulmonary arterial hypertension; PCWP = pulmonary capillary wedge pressure; RHC = right heart catheterization; SD = standard deviation; sPAP = systolic pulmonary artery pressure; RHC = right heart catheterization; yr = year/years

a

Studies that assessed baseline NT-proBNP as predictors of future development of PAH.

b

Median interquartile range.

Studies that assessed baseline NT-proBNP as predictors of future development of PAH.

Median interquartile range.

From: Results

Cover of Pulmonary Arterial Hypertension: Screening, Management, and Treatment
Pulmonary Arterial Hypertension: Screening, Management, and Treatment [Internet].
Comparative Effectiveness Reviews, No. 117.
McCrory DC, Coeytaux RR, Schmit KM, et al.

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