Osteopontin in patients with idiopathic pulmonary hypertension.
BACKGROUND
Osteopontin (OPN) is a pleiotropic cytokine that has been postulated to play a role in the pathogenesis of idiopathic pulmonary arterial hypertension (IPAH). OPN plasma levels may be related to disease severity and mortality in patients with PAH.


METHODS
OPN plasma levels obtained during right-sided heart catheterization were assessed by a commercially available enzyme-linked immunosorbent assay and related to hemodynamics, exercise capacity, N-terminal pro-brain natriuretic peptide (NT-pro-BNP) level, uric acid level, C-reactive protein level, and survival in two cohorts of patients with IPAH: a 4-year retrospective cohort (n = 70) and a prospective cohort (n = 25) followed for 3 months after initiation of therapy. Forty apparently healthy individuals served as control subjects.


RESULTS
Baseline OPN levels were elevated in patients with IPAH compared with healthy control subjects (50.2 ± 35.9 vs 23.7 ± 2.8 ng/mL, P < .0001). In the retrospective as well as in the prospective cohort, OPN levels correlated with mean right atrial pressure and NT-BNP. In the retrospective cohort, OPN levels also correlated with age (r = 0.3, P = .02), 6-min walking distance (r=-0.4, P = .05), and New York Heart Association class (r = 0.4, P = .001). Multivariate Cox analysis demonstrated that baseline OPN levels were independent predictors of mortality (P = .02). When patients were divided according to their baseline OPN values, being normal or elevated at baseline (below or above 34.5 ng/mL), proportional survival rates were 100% vs 80% after 1 year and 77% vs 51% after 3 years, respectively.


CONCLUSIONS
Circulating OPN predicts survival in patients with IPAH and is associated with a higher New York Heart Association class. OPN, thus, may be useful as a biomarker in IPAH.
Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany. Electronic address: J.M.Lorenzen@gmail.com.
Johan M
JM
Lorenzen
Department of Respiratory Medicine, Centre of Internal Medicine, Hannover Medical School, Hannover, Germany.
Nils
N
Nickel
Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany.
Robert
R
Krämer
Department of Respiratory Medicine, Centre of Internal Medicine, Hannover Medical School, Hannover, Germany.
Heiko
H
Golpon
Department of Respiratory Medicine, Centre of Internal Medicine, Hannover Medical School, Hannover, Germany.
Volker
V
Westerkamp
Department of Respiratory Medicine, Centre of Internal Medicine, Hannover Medical School, Hannover, Germany.
Karen M
KM
Olsson
Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany.
Hermann
H
Haller
Department of Respiratory Medicine, Centre of Internal Medicine, Hannover Medical School, Hannover, Germany.
Marius M
MM
Hoeper
D000328:Adult; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood* / Q000401:mortality; D008875:Middle Aged; D053495:Osteopontin / Q000097:blood*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012189:Retrospective Studies
D053495:Osteopontin