COPD and Cardiac Death: Pressure (NT-proBNP), Inflammation (CRP) or Both?

BNP and inactive NT-proBNP. Very high levels of NTproBNP are useful markers of pulmonary edema (volume overload), and mildly elevated levels occur with pulmonary hypertension [6, 7] . CRP was the first acute-phase protein to be identified [4] . Its name comes from its ability to precipitate the somatic C-polysaccharide of Streptococcus pneumoniae , suggesting a role for CRP in modulating inflammation. Plasma CRP is produced in the liver under transcriptional control by the cytokine IL-6. In COPD, activated pulmonary macrophages and airway epithelial cells release IL-6 [8] . CRP may protect the lungs from inflammation caused by bacteria and apoptic cells, both important issues in the pathogenesis of COPD. Increased CRP levels, though, suggest a poor prognosis [8, 9] . The results reported by Wieshammer et al. fit nicely into an intriguing series of observations linking NTproBNP and CRP. Pulmonary artery pressures remain low even as we age [10] . In most patients with COPD, pulmonary artery pressures also remain within the normal range. In one study of stable COPD patients (mean FEV 1 about 45% predicted) only 25% (33 of 131) had pulmonary hypertension (mean pulmonary artery pressure 6 20 mm Hg) [11] . Similarly, only 23% of more severe COPD patients (mean FEV 1 of about 20% predicted) were found In this issue of Respiration , Wieshammer et al. examine the relationship between levels of C-reactive protein (CRP) and N-terminal pro-brain natriuretic peptide (NTproBNP) in patients who were evaluated for dyspnea [1] . About 25% of these patients had elevated CRP levels ( 1 5.8 mg/l). Patients with an elevated CRP level were more likely to have heart and lung disease, but more specifically pulmonary hypertension and moderately severe airway obstruction. Patients with an elevated CRP level were also more likely to have an increased NT-proBNP level. Exploring a relationship between NT-proBNP and CRP might provide insights into better defining the prognosis of chronic obtructive pulmonary disease (COPD), because COPD is associated with both shortened life expectancy [2] and cardiac death [3, 4] . NT-proBNP and CRP are biomarkers which reflect different processes. BNP was first identified in 1988 from porcine brain tissue [5] . In 1991 it was shown to be a normal cardiac hormone secreted by the ventricles. Volume expansion or pressure overload stimulate pre-proBNP synthesis in the ventricles which is physiologically appropriate because BNP opposes the sodium retention and antidiuretic effects of the activated renin-angiotensin-aldosterone system. After synthesis, pre-proBNP is metabolized to proBNP and then into the biologically active Published online: January 28, 2010