C-reactive protein: a new predictor of adverse outcome in pulmonary arterial hypertension

Abstract

OBJECTIVES: Our aim was to investigate in a prospective study a potential role of C-reactive protein (CRP) in predicting the outcome in pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). BACKGROUND: CRP is a well-known marker of inflammation and tissue damage, widely recognized as a risk predictor of cardiovascular and coronary heart diseases. METHODS: Plasma levels of CRP have been measured in consecutive patients diagnosed with PAH and CTEPH, at the time of right heart catheterization. RESULTS: Circulating CRP levels were increased in CTEPH and PAH patients compared with those in control subjects (4.9 mg l(-1), 95% confidence interval [CI]: 3.9 to 6.2 mg l(-1); 4.4 mg l(-1), 95% CI: 3.5 to 5.4 mg l(-1); and 2.3 mg l(-1), 95% CI: 1.9 to 2.7 mg l(-1), respectively; p < 0.0001). In PAH patients, CRP levels correlated with New York Heart Association functional class (r = 0.23), right atrial pressure (r = 0.25), and 6-min walking distance (r = -0.19) and were significantly higher in nonsurvivors than in survivors (p = 0.003). All PAH, idiopathic PAH, and patients naive for disease-specific medication with CRP levels >5.0 mg l(-1) had a significantly lower survival rate (p = 0.02, p = 0.009, and p < 0.05, respectively). In CTEPH patients, circulating CRP levels significantly decreased 12 months after pulmonary endarterectomy (n = 23, 4.0 mg l(-1), 95% CI: 2.8 to 5.8 mg l(-1), to 1.6 mg l(-1), 95% CI: 2.2 to 3.0 mg l(-1); p = 0.004). PAH patients normalizing their CRP levels under treatment (n = 29), assigned as responders, had a significantly higher survival rate (p < 0.05). The proportion of patients treated with a parenteral prostacyclin-analogue was significantly higher among the responders than the nonresponders (55% vs. 17%, p = 0.002). CONCLUSIONS: This is the first evidence of a role of an inflammatory marker, such as CRP, in predicting outcome and response to therapy in PAH.