Prognostic Significance of Biomarkers in Pulmonary Arterial Hypertension.
BACKGROUND
Pulmonary arterial hypertension (PAH) is a rare progressive disease of the pulmonary vasculature that is characterized by endothelial dysfunction, inflammation, and right ventricular dysfunction.


OBJECTIVE
The main objective was to determine whether endothelial, inflammatory, and cardiac biomarkers would be associated with the World Health Organization functional assessment and survival in patients with PAH.


METHODS
We performed a retrospective cohort study of patients with PAH enrolled in the Randomized Clinical Trial of Aspirin and Simvastatin for Pulmonary Arterial Hypertension (ASA-STAT). Biomarkers (N-terminal fragment of pro-BNP [NT-pro-BNP], von Willebrand factor [vWF], soluble P selectin, C-reactive protein, total and high-density lipoprotein cholesterol, triglycerides, tumor necrosis factor, IL-6, β-thromboglobulin, and thromboxane B2) were measured at baseline. Patients from the study were followed until lung transplantation, death, or August 1, 2013. Ordinal logistic regression and Cox regression analyses were performed.


RESULTS
Sixty-five patients with PAH were enrolled. The mean age was 51 years, and 86% were women. Higher vWF activity, lower high-density lipoprotein cholesterol, and higher thromboxane B2 levels were associated with worse World Health Organization functional class after adjustment for age, sex, and etiology of PAH. Higher NT-pro-BNP levels, lower vWF activity, and lower total cholesterol were associated with an increased risk of death or lung transplant after adjustment for age, sex, etiology of PAH, and 6-minute-walk distance.


CONCLUSIONS
In patients with PAH, lower vWF activity and cholesterol levels and higher NT-pro-BNP levels at baseline were associated with an increased risk of death or transplantation. Clinical trial registered with www.clinicaltrials.gov (NCT00384865).
1 Department of Medicine, Tufts Medical Center, Boston, Massachusetts.|2 Tufts Clinical and Translational Science Institute, Boston, Massachusetts.|3 Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, Massachusetts.
Nadine
N
Al-Naamani
4 Department of Medicine, and.
Harold I
HI
Palevsky
5 Department of Medicine, College of Physicians and Surgeons, and.
David J
DJ
Lederer
6 Department of Medicine, Weill-Cornell Medical School, New York, New York.
Evelyn M
EM
Horn
7 Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Stephen C
SC
Mathai
1 Department of Medicine, Tufts Medical Center, Boston, Massachusetts.
Kari E
KE
Roberts
8 College of Medicine, University of Vermont, Colchester, Vermont.
Russell P
RP
Tracy
7 Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Paul M
PM
Hassoun
9 Richard DeVos Heart and Lung Transplant Services, Spectrum Health Hospitals, Grand Rapids, Michigan; and.
Reda E
RE
Girgis
10 Center for Behavioral Cardiovascular Health, Department of Medicine, Columbia University, New York, New York.
Daichi
D
Shimbo
11 Department of Medicine, and.|12 Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland.
Wendy S
WS
Post
4 Department of Medicine, and.|13 Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.
Steven M
SM
Kawut
D000328:Adult; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D008076:Cholesterol, HDL / Q000097:blood*; D005080:Exercise Test / Q000379:methods; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood / Q000175:diagnosis / Q000401:mortality / Q000628:therapy; D015850:Interleukin-6 / Q000097:blood; D016040:Lung Transplantation / Q000706:statistics & numerical data*; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D011237:Predictive Value of Tests; D011379:Prognosis; D012129:Respiratory Function Tests / Q000379:methods; D012189:Retrospective Studies; D012307:Risk Factors; D016019:Survival Analysis; D001620:beta-Thromboglobulin / Q000032:analysis; D014841:von Willebrand Factor / Q000032:analysis*
D015415:Biomarkers; D008076:Cholesterol, HDL; D015850:Interleukin-6; C061615:PPBP protein, human; D010446:Peptide Fragments; D001620:beta-Thromboglobulin; C109794:pro-brain natriuretic peptide (1-76); D014841:von Willebrand Factor; D020097:Natriuretic Peptide, Brain; D002097:C-Reactive Protein
World Health Organization functional class; biomarkers; pulmonary arterial hypertension; survival