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Possible Role of Statins in COPD-Related Pulmonary Hypertension FREE TO VIEW

Robert P. Young, MD, PhD; Raewyn J. Hopkins, RN
Author and Funding Information

From the Department of Medicine, Schools of Medicine and Biological Sciences, University of Auckland.

Correspondence to: Robert P. Young, MD, PhD, Department of Medicine, Auckland Hospital, Private Bag 92019, Auckland, New Zealand; e-mail: roberty@adhb.govt.nz


Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestpubs.org/site/misc/reprints.xhtml).


© 2010 American College of Chest Physicians


Chest. 2010;137(5):1250-1251. doi:10.1378/chest.09-2778
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To the Editor:

We read with interest the recent article by Chaouat et al (September 2009)1 proposing that interleukin-6 (IL-6), through inflammatory effects, might contribute to pulmonary hypertension in patients with COPD. The role of IL-6 in pulmonary inflammation and matrix remodeling underlying COPD is well recognized.2 The findings of Chaouat et al1 further implicate IL-6 and inflammation in pulmonary hypertension, a well recognized complication of COPD. That pulmonary hypertension affects those with mild-to-moderate COPD suggests that hypoxia, secondary to poor lung function, is not the underlying cause. A similar observation is seen with poor exercise tolerance in COPD, wherein inflammation (eg, IL-6) and oxidant load, not lung function, have been directly implicated in skeletal muscle dysfunction (Fig 1).2 The findings of Chaouat et al1 are made more compelling by the close relationship between serum IL-6 level and pulmonary artery pressure (PAP). In addition, they report a relationship between functional IL-6 genotypes and PAP, which might explain why only some patients with COPD develop pulmonary hypertension.

Figure Jump LinkFigure 1. Proposed relationship between IL-6, exercise tolerance, and pulmonary hypertension: possible antiinflammatory effects of statins. IL-6 = interleukin-6.Grahic Jump Location

The link between PAP and inflammation raises a possible therapeutic role for the use of statins that, through inhibition of guanosine triphosphatases (GTPases), lowers serum cytokines such as IL-6.2 It is noteworthy that studies have recently shown that statins lower PAP in humans.3,4 This represents yet another potential benefit of statins in patients with COPD, along with reported reduction in all-cause mortality, mortality from respiratory infection, reduced lung function decline, and lower prevalence of lung cancer.2 The mechanism whereby statins lower PAP is largely unknown but could be mediated through IL-6 inhibition and pulmonary vascular remodeling as suggested by Chaouat et al1 or through inhibition of endothelin-1 by Lee et al.4 In the latter study, the reduction in PAP and endothelin level was associated with an improvement in exercise tolerance of 50%. In a study by the same group, patients with COPD who were randomized to statin therapy experienced a 50% improvement in exercise tolerance that correlated with reduction in serum IL-6.2 Given that IL-6 is known to reduce skeletal muscle function,5 the benefit in exercise tolerance from statins may be through direct effects on skeletal muscle contractility and function.2 Alternatively, through GTPase inhibition, statins might also reduce PAP by abolishing hypoxic pulmonary vasoconstriction.4 Regardless of the mechanism, the study by Chaouat et al1 lends support to the current evidence that systemic antiinflammatory activity (particularly IL-6 inhibition) appears to be an important therapeutic target in patients with COPD.

Chaouat A, Savale L, Chouaid C, et al. Role for interleukin-6 in COPD-related pulmonary hypertension. Chest. 2009;1363:678-687. [CrossRef] [PubMed]
 
Young RP, Hopkins R, Eaton TE. Pharmacological actions of statins: potential utility in COPD. Eur Respir Rev. 2009;18114:222-232. [CrossRef] [PubMed]
 
Kao PN. Simvastatin treatment of pulmonary hypertension: an observational case series. Chest. 2005;1274:1446-1452. [CrossRef] [PubMed]
 
Lee T-M, Chen C-C, Shen H-N, Chang NC. Effects of pravastatin on functional capacity in patients with chronic obstructive pulmonary disease and pulmonary hypertension. Clin Sci (Lond). 2009;1166:497-505. [CrossRef] [PubMed]
 
Yende S, Waterer GW, Tolley EA, et al. Inflammatory markers are associated with ventilatory limitation and muscle dysfunction in obstructive lung disease in well functioning elderly subjects. Thorax. 2006;611:10-16. [CrossRef] [PubMed]
 

Figures

Figure Jump LinkFigure 1. Proposed relationship between IL-6, exercise tolerance, and pulmonary hypertension: possible antiinflammatory effects of statins. IL-6 = interleukin-6.Grahic Jump Location

Tables

References

Chaouat A, Savale L, Chouaid C, et al. Role for interleukin-6 in COPD-related pulmonary hypertension. Chest. 2009;1363:678-687. [CrossRef] [PubMed]
 
Young RP, Hopkins R, Eaton TE. Pharmacological actions of statins: potential utility in COPD. Eur Respir Rev. 2009;18114:222-232. [CrossRef] [PubMed]
 
Kao PN. Simvastatin treatment of pulmonary hypertension: an observational case series. Chest. 2005;1274:1446-1452. [CrossRef] [PubMed]
 
Lee T-M, Chen C-C, Shen H-N, Chang NC. Effects of pravastatin on functional capacity in patients with chronic obstructive pulmonary disease and pulmonary hypertension. Clin Sci (Lond). 2009;1166:497-505. [CrossRef] [PubMed]
 
Yende S, Waterer GW, Tolley EA, et al. Inflammatory markers are associated with ventilatory limitation and muscle dysfunction in obstructive lung disease in well functioning elderly subjects. Thorax. 2006;611:10-16. [CrossRef] [PubMed]
 
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