J Korean Med Sci.  2010 Oct;25(10):1487-1491. 10.3346/jkms.2010.25.10.1487.

Plasma C-Reactive Protein and Endothelin-1 Level in Patients with Chronic Obstructive Pulmonary Disease and Pulmonary Hypertension

• Kwon YS
• Chi SY
• Shin HJ
• Kim EY
• Yoon BK
• Ban HJ
• Oh IJ
• Kim KS
• Kim YC
• Lim SC

• KMID: 2157854
• DOI: http://doi.org/10.3346/jkms.2010.25.10.1487

Abstract

Pulmonary hypertension is a frequent complication of chronic obstructive pulmonary disease (COPD) and associated with a worse survival and increased risk of hospitalization for exacerbation of COPD. However, little information exists regarding the potential role of systemic inflammation in pulmonary hypertension of COPD. The purpose of the present study was to investigate the degree of C-reactive protein (CRP) and endothelin-1 (ET-1) levels in COPD patient with and without pulmonary hypertension. The levels of CRP and ET-1 were investigated in 58 COPD patient with pulmonary hypertension and 50 patients without pulmonary hypertension. Pulmonary hypertension was defined as a systolic pulmonary artery pressure (Ppa) > or =35 mmHg assessed by Doppler echocardiography. Plasma CRP and ET-1 levels were significantly higher in patients with pulmonary hypertension than in patients without hypertension. There were significant positive correlations between the plasma ET-1 level and CRP level in the whole study groups. For COPD patients, systolic Ppa correlated significantly with plasma CRP levels and plasma ET-1 levels. These findings support a possibility that CRP and ET-1 correlate to pulmonary hypertension in COPD patients.

Keyword

Chronic Obstructive Pulmonary Disease; Pulmonary Hypertension; C-Reactive Protein; Endothelin-1

MeSH Terms

Aged
Blood Pressure
C-Reactive Protein/*analysis
Echocardiography, Doppler
Endothelin-1/*blood
Female
Humans
Hypertension, Pulmonary/*blood/complications
Male
Middle Aged
Pulmonary Disease, Chronic Obstructive/*blood/complications

Figure

• 

  Fig. 1 Plasma levels of CRP in COPD patients without and with pulmonary hypertension. There is significant difference between the two groups (P=0.026). Plasma CRP levels are expressed as the median and interquartile range. •, outlier extending >1.5 box-lengths from the edge of the box; Ppa, pulmonary artery pressure; CRP, C-reactive protein.

• 

  Fig. 2 Plasma levels of ET-1 in COPD patients without and with pulmonary hypertension. There is significant difference between the two groups (P=0.001). Plasma ET-1 levels are expressed as the median and interquartile range. •, outlier extending >1.5 box-lengths from the edge of the box; Ppa, pulmonary artery pressure; ET-1, endothelin-1.

• 

  Fig. 3 The relationship between plasma levels of ET-1 and CRP in this study. There is significant correlation between ET-1 and CRP levels (P=0.001). CRP, C-reactive protein; ET-1, endothelin-1.

• 

  Fig. 4 The relationship between systolic Ppa and plasma CRP levels (A) and ET-1 levels (B). Systolic Ppa correlate significantly with plasma CRP levels (r=0.461, P=0.001) and serum ET-1 levels (r=0.531, P=0.001). Ppa, pulmonary artery pressure; CRP, C-reactive protein; ET-1, endothelin-1.

Reference

1. Wright JL, Levy RD, Churg A. Pulmonary hypertension in chronic obstructive pulmonary disease: current theories of pathogenesis and their implications for treatment. Thorax. 2005. 60:605–609.

2. Jung HS, Lee JH, Chun EM, Moon JW, Chang JH. Predictors of long-term mortality after hospitalization for acute exacerbation of COPD. Tuberc Respir Dis. 2006. 60:205–214.

3. Jyothula S, Safdar Z. Update on pulmonary hypertension complicating chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis. 2009. 4:351–363.

4. Barberà JA, Riverola A, Roca J, Ramirez J, Wagner PD, Ros D, Wiggs BR, Rodriguez-Roisin R. Pulmonary vascular abnormalities and ventilation-perfusion relationships in mild chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1994. 149:423–429.

5. Santos S, Peinado VI, Ramírez J, Melgosa T, Roca J, Rodriguez-Roisin R, Barberà JA. Characterization of pulmonary vascular remodelling in smokers and patients with mild COPD. Eur Respir J. 2002. 19:632–638.

6. Joppa P, Petrasova D, Stancak B, Tkacova R. Systemic inflammation in patients with COPD and pulmonary hypertension. Chest. 2006. 130:326–333.

7. Chaouat A, Savale L, Chouaid C, Tu L, Sztrymf B, Canuet M, Maitre B, Housset B, Brandt C, Le Corvoisier P, Weitzenblum E, Eddahibi S, Adnot S. Role for interleukin-6 in COPD-related pulmonary hypertension. Chest. 2009. 136:678–687.

8. Ballou SP, Lozanski G. Induction of inflammatory cytokine release from cultured human monocytes by C-reactive protein. Cytokine. 1992. 4:361–368.

9. Cermak J, Key NS, Bach RR, Balla J, Jacob HS, Vercellotti GM. C-reactive protein induces human peripheral blood monocytes to synthesize tissue factor. Blood. 1993. 82:513–520.

10. Yanagisawa M, Kurihara H, Kimura S, Tomobe Y, Kobayashi M, Mitsui Y, Yazaki Y, Goto K, Masaki T. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature. 1988. 332:411–415.

11. Allen SW, Chatfield BA, Koppenhafer SA, Schaffer MS, Wolfe RR, Abman SH. Circulating immunoreactive endothelin-1 in children with pulmonary hypertension. Association with acute hypoxic pulmonary vasoreactivity. Am Rev Respir Dis. 1993. 148:519–522.

12. Cernacek P, Stewart DJ. Immunoreactive endothelin in human plasma: Marked elevations in patients with cardiogenic shock. Biochem Biophys Res Commun. 1989. 161:562–567.

13. Bacakoğlu F, Atasever A, Ozhan MH, Gurgun C, Ozkilic H, Guzelant A. Plasma and bronchoalveolar lavage fluid levels of endothelin-1 in patients with chronic obstructive pulmonary disease and pulmonary hypertension. Respiration. 2003. 70:594–599.

14. Rabe KF, Hurd S, Anzueto A, Barnes PJ, Buist SA, Calverley P, Fukuchi Y, Jenkins C, Rodriguez-Roisin R, van Weel C, Zielinski J. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2007. 176:532–555.

15. Rubin LJ. Primary pulmonary hypertension. Chest. 1993. 104:236–250.

16. Barst RJ, McGoon M, Torbicki A, Sitbon O, Krowka MJ, Olschewski H, Gaine S. Diagnosis and differential assessment of pulmonary arterial hypertension. J Am Coll Cardiol. 2004. 43:12 Suppl S. 40S–47S.

17. Sekhon HS, Wright JL, Churg A. Cigarette smoke causes rapid cell proliferation in small airways and associated pulmonary arteries. Am J Physiol. 1994. 267:L557–L563.

18. Man SF, Connett JE, Anthonisen NR, Wise RA, Tashkin DP, Sin DD. C-reactive protein and mortality in mild to moderate chronic obstructive pulmonary disease. Thorax. 2006. 61:849–853.

19. de Torres JP, Pinto-Plata V, Casanova C, Mullerova H, Córdoba-Lanús E, Muros de Fuentes M, Aguirre-Jaime A, Celli BR. C-reactive protein levels and survival in patients with moderate to very severe COPD. Chest. 2008. 133:1336–1343.

20. Giaid A, Yanagisawa M, Langleben D, Michel RP, Levy R, Shennib H, Kimura S, Masaki T, Duguid WP, Stewart DJ. Expression of endothelin-1 in the lungs of patients with pulmonary hypertension. N Engl J Med. 1993. 328:1732–1739.

21. Cacoub P, Dorent R, Nataf P, Carayon A, Riquet M, Noe E, Piette JC, Godeau P, Gandjbakhch I. Endothelin-1 in the lungs of patients with pulmonary hypertension. Cardiovasc Res. 1997. 33:196–200.

22. Fujii T, Otsuka T, Tanaka S, Kanazawa H, Hirata K, Kohno M, Kurihara N, Yoshikawa J. Plasma endothelin-1 level in chronic obstructive pulmonary disease: relationship with natriuretic peptide. Respiration. 1999. 66:212–219.

23. Mullol J, Baraniuk JN, Logun C, Benfield T, Picado C, Shelhamer JH. Endothelin-1 induces GM-CSF, IL-6 and IL-8 but not G-CSF release from a human bronchial epithelial cell line (BEAS-2B). Neuropeptides. 1996. 30:551–556.

24. Redington AE, Springall DR, Ghatei MA, Lau LC, Bloom SR, Holgate ST, Polak JM, Howarth PH. Endothelin in bronchoalveolar lavage fluid and its relation to airflow obstruction in asthma. Am J Respir Crit Care Med. 1995. 151:1034–1039.

25. Chalmers GW, Thomson L, Macleod KJ, Dagg KD, McGinn BJ, McSharry C, Patel KR, Thomson NC. Endothelin-1 levels in induced sputum samples from asthmatic and normal subjects. Thorax. 1997. 52:625–627.

26. Goldie RG, Knott PG, Carr MJ, Hay DW, Henry PJ. The endothelins in the pulmonary system. Pulm Pharmacol. 1996. 9:69–93.

27. Wang C, Liu J, Guo F, Ji Y, Liu N. Endothelin-1 induces the expression of C-reactive protein in rat vascular smooth muscle cells. Biochem Biophys Res Commun. 2009. 389:537–542.

28. Katayama T, Yano K, Nakashima H, Takagi C, Honda Y, Suzuki S, Iwasaki Y. Clinical significance of acute-phase endothelin-1 in acute myocardial infarction patients treated with direct coronary angioplasty. Circ J. 2005. 69:654–658.

29. Gemici G, Erdim R, Tokay S, Tezcan H, Fak AS, Oktay A. Interaction between C-reactive protein and endothelin-1 in coronary artery disease. Cardiology. 2007. 107:340–344.