Dataset Information

Elevated plasma CXCL12? is associated with a poorer prognosis in pulmonary arterial hypertension.

ABSTRACT:

Rationale

Recent work in preclinical models suggests that signalling via the pro-angiogenic and pro-inflammatory cytokine, CXCL12 (SDF-1), plays an important pathogenic role in pulmonary hypertension (PH). The objective of this study was to establish whether circulating concentrations of CXCL12? were elevated in patients with PAH and related to mortality.

Methods

Plasma samples were collected from patients with idiopathic pulmonary arterial hypertension (IPAH) and PAH associated with connective tissue diseases (CTD-PAH) attending two pulmonary hypertension referral centres (n = 95) and from age and gender matched healthy controls (n = 44). Patients were subsequently monitored throughout a period of five years.

Results

CXCL12? concentrations were elevated in PAH groups compared to controls (P<0.05) and receiver-operating-characteristic analysis showed that plasma CXCL12? concentrations discriminated patients from healthy controls (AUC 0.80, 95% confidence interval 0.73-0.88). Kaplan Meier analysis indicated that elevated plasma CXCL12? concentration was associated with reduced survival (P<0.01). Multivariate Cox proportional hazards model showed that elevated CXCL12? independently predicted (P<0.05) earlier death in PAH with a hazard ratio (95% confidence interval) of 2.25 (1.01-5.00). In the largest subset by WHO functional class (Class 3, 65% of patients) elevated CXCL12? independently predicted (P<0.05) earlier death, hazard ratio 2.27 (1.05-4.89).

Conclusions

Our data show that elevated concentrations of circulating CXCL12? in PAH predicted poorer survival. Furthermore, elevated circulating CXCL12? was an independent risk factor for death that could potentially be included in a prognostic model and guide therapy.

SUBMITTER: McCullagh BN

PROVIDER: S-EPMC4391833 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Publications

Elevated plasma CXCL12α is associated with a poorer prognosis in pulmonary arterial hypertension.

McCullagh Brian N BN Costello Christine M CM Li Lili L O'Connell Caroline C Codd Mary M Lawrie Allan A Morton Allison A Kiely David G DG Condliffe Robin R Elliot Charles C McLoughlin Paul P Gaine Sean S

PloS one 20150409 4

<h4>Rationale</h4>Recent work in preclinical models suggests that signalling via the pro-angiogenic and pro-inflammatory cytokine, CXCL12 (SDF-1), plays an important pathogenic role in pulmonary hypertension (PH). The objective of this study was to establish whether circulating concentrations of CXCL12α were elevated in patients with PAH and related to mortality.<h4>Methods</h4>Plasma samples were collected from patients with idiopathic pulmonary arterial hypertension (IPAH) and PAH associated w ...[more]

PMID: 25856504

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