Development of pulmonary hypertension in a high-risk population with systemic sclerosis in the Pulmonary Hypertension Assessment and Recognition of Outcomes in Scleroderma (PHAROS) cohort study.
OBJECTIVE
PHAROS registry is a prospective longitudinal cohort study to understand the natural history of pulmonary hypertension (PH) in systemic sclerosis (SSc).


METHODS
"At-risk" pulmonary arterial hypertension (PAH) is defined by these entry criteria: echocardiogram (echo) systolic pulmonary arterial pressure (sPAP) >40 mmHg, diffusion lung capacity of carbon monoxide (DLco) <55% predicted, or ratio of percentage forced vital capacity (FVC)/percentage DLco >1.6, as measured by pulmonary function testing (PFT). Patients were followed up annually and right heart catheterization (RHC) performed if PH was suspected. We used descriptive statistics and Kaplan-Meier estimate of time to PH diagnosis.


RESULTS
A total of 251 "at-risk" subjects were enrolled between 2005 and 2012 and followed up for mean of 2.5 ± 1.2 years. The mean age at entry was 56.7 ± 11.0 and disease duration was 9.9 ± 8.7 years. Overall, 82 patients had RHC, and 35 were confirmed to have new PH. There were no differences in age, gender, SSc subtypes, antibodies, and disease duration between the "at-risk" and new PH groups. Using Kaplan-Meier survival, the time to PH was 10% at 2 years, 13% at 3 years, and 25% at 5 years. Most new PH patients at entry met the PFT criteria (76%), had significantly higher sPAP (p = 0.013), had shorter 6-min walk distance, and had exercise-induced hypoxia (p = 0.003) than "at-risk" PAH group.


CONCLUSIONS
A low DLco, high FVC/DLco, exercise-induced hypoxia and entry echo sPAP > 40 were strongly associated with future PH, though RHC was necessary to confirm PH. This ongoing prospective study confirms that these high-risk factors do predict future PH.
Department of Medicine, Division of Rheumatology, Adult Clinical Research Center, Rutgers-RWJ Medical School, Acute Care Building, 51 French St, New Brunswick, NJ 08903. Electronic address: hsuvm@rwjms.rutgers.edu.
Vivien M
VM
Hsu
Department of Medicine, Division of Immnunology & Rheumatology, Stanford University, Stanford, CA.
Lorinda
L
Chung
Department of Medicine, Division of Rheumatology, Johns Hopkins University, Baltimore, MD.
Laura K
LK
Hummers
Department of Medicine, Division of Rheumatology, Johns Hopkins University, Baltimore, MD.
Fredrick
F
Wigley
Department of Medicine, Division of Rheumatology, Boston University, Boston, MA.
Robert
R
Simms
Department of Medicine, Division of Rheumatology, Medical University of South Carolina, Charleston, SC.
Marcy
M
Bolster
Department of Medicine, Division of Rheumatology, Medical University of South Carolina, Charleston, SC.
Rick
R
Silver
Department of Medicine, Division of Rheumatology, National Jewish Health, University of Colorado, Denver, CO.
Aryeh
A
Fischer
Department of Medicine, Division of Rheumatology, Northwestern University, Chicago, IL.
Monique E
ME
Hinchcliff
Department of Medicine, Division of Rheumatology, Northwestern University, Chicago, IL.
John
J
Varga
Department of Medicine, Division of Rheumatology, North Shore-LIJ Health System, Long Island, NY.
Avram Z
AZ
Goldberg
Department of Medicine, Division of Rheumatology, Jefferson Medical College, Philadelphia, PA.
Chris T
CT
Derk
Department of Medicine, Division of Rheumatology, University of Michigan, Ann Arbor, MI.
Elena
E
Schiopu
Department of Medicine, Division of Rheumatology, University of Michigan, Ann Arbor, MI.
Dinesh
D
Khanna
Department of Medicine, Division of Rheumatology, Albany Medical College, Albany, NY.
Lee S
LS
Shapiro
Department of Medicine, Division of Rheumatology, University of Pittsburgh, Pittsburgh, PA.
Robyn T
RT
Domsic
Department of Medicine, Division of Rheumatology, University of Pittsburgh, Pittsburgh, PA.
Thomas
T
Medsger
Department of Medicine, Division of Rheumatology, University of Texas, Houston, TX.
Maureen D
MD
Mayes
Department of Medicine, Division of Rheumatology, University of California, Los Angeles, CA.
Daniel
D
Furst
Department of Medicine, Division of Rheumatology, Medical College of Wisconsin, Milwaukee, WI.
Mary E
ME
Csuka
Department of Medicine, Division of Rheumatology, University of Minnesota, Minneapolis, MN.
Jerry A
JA
Molitor
Department of Medicine, Division of Rheumatology, University of Massachusetts Medical School, Worcester, MA.
Firas
F
Alkassab
Department of Medicine, Division of Rheumatology, Immunology & Allergy, Georgetown University, Washington, DC.
Virginia D
VD
Steen
D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000209:etiology*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011928:Raynaud Disease / Q000209:etiology*; D012042:Registries; D012306:Risk; D012595:Scleroderma, Systemic / Q000150:complications*
Pulmonary arterial hypertension; Registry; Scleroderma; Systemic