0
Correspondence |

Response FREE TO VIEW

Virend K. Somers, MD, PhD, FCCP; Katsunori Ishida, MD; Masahiko Kato, MD, PhD
Author and Funding Information

From the Mayo Clinic (Dr Somers); and Tottori University (Drs Ishida and Kato).

Correspondence to: V. K. Somers, MD, PhD, FCCP, Division of Cardio vas cular Disease, Mayo Clinic College of Medicine, 200 First St SW, Rochester, MN 55905; e-mail: somers.virend@mayo.edu


Financial/nonfi nancial disclosures: The authors have reported to CHEST the following confl icts of interest: Dr Somers has served as a consultant for ResMed, Respironics, Medtronic, GlaxoSmith-Kline, Sepracor, Boston Scientifi c, and Cardiac Concepts. He has received research grants from the ResMed Foundation, the Respironics Sleep and Breathing Foundation, ELA Medical, and Select Research, Inc. Dr Ishida and Dr Kato have reported no confl icts of interest that 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.chestjournal.org/site/misc/reprints.xhtml).


© 2010 American College of Chest Physicians


Chest. 2010;137(2):497-498. doi:10.1378/chest.09-2440
Text Size: A A A
Published online

To the Editor:

We appreciate some of the comments in the letter by Ryan and McNicholas, but we are surprised and disappointed by misrepresentations of our work, as noted in the latter paragraphs of our response below. They suggest that we understate the controversy regarding the relationship between obstructive sleep apnea (OSA) and C-reactive protein (CRP). We agree that we could have addressed further the question of whether OSA raises CRP. However, the focus of our study1 was the effect of continuous positive airway pressure (CPAP) on CRP. We specify clearly that “the available data are controversial,” and we refer to “the inconsistency found in prior studies.” Indeed, it is this very lack of consensus that strengthens the justification for our study. Our manuscript was not intended, nor should it be misinterpreted, as any kind of comprehensive review.

We did not cite the Ryan and colleagues review,2 nor the randomized study by Kohler et al,3 as both were published after acceptance of our manuscript. Regarding whether OSA causes an increase in CRP, Ryan and McNicholas fail to clarify that only 111 subjects in the Sleep Cohort Study4 had an apnea-hypopnea index > 15, with far fewer having an apnea-hypopnea index approaching 46, the approximate mean in our 55 subjects. Furthermore, they ignore several other relevant studies cited in Table 1.5-7 We agree that whether it is obesity or OSA, or an interaction between the two, that contributes to the elevated CRP awaits a definitive answer. Nevertheless, the issue may be of considerably less relevance, given recent data arguing against a causal role of CRP in coronary artery disease.8

Table Graphic Jump Location
Table 1 —Studies Suggesting C-Reactive Protein Is Elevated in Obstructive Sleep Apnea Independent of Obesity

CRP = C-reactive protein; ODI = oxygen desaturation index; OSA = obstructive sleep apnea.

Their criticism of the “small patient numbers (n = 15) in the poor compliance group” is somewhat justified. However, publishing data from small sample sizes is not outside the norm, as exemplified in many studies by Ryan et al,9-13 which report data from as few as eight to 10 subjects.11,12 Indeed, our study had a larger overall sample size than their similar but much shorter (6 weeks) study of CPAP effects on CRP,10 which is not cited in their letter. On the other hand, the question of outliers is very reasonable. Even after excluding these three subjects, CRP was reduced (P = .0123).

In comparing our data with the excellent study by Kohler et al,3 Ryan and McNicholas overlook several important and fundamental differences between our studies, as outlined in Table 2. The “great interest” with which they read our work is hard to reconcile with their assertion that we “do not provide important baseline and follow-up information on potential confounding variables that may have influenced CRP levels such as medications and changes in lipid and glucose profiles at follow-up.” Lipid and glucose data were in fact presented in Table 1 (baseline data) and Table 2 (changes after therapy).1 Furthermore, we state explicitly that patients using statins were excluded and that “we did not add or change any medications” during the study.

Table Graphic Jump Location
Table 2 —Differences Between Studies by Kohler et al3 vs Ishida et al1

CPAP = continuous positive airway pressure. See Table 1 for expansion of the other abbreviation.

Ryan and McNicholas seem unconcerned that neither lipids nor glucose nor changes in statins/medications are described in the Kohler et al manuscript, but inappropriately chastise us for this. More remarkable is that they make no mention of either statins or changes in lipids and glucose in their own study of CRP before and after CPAP.10 Criticism that is thoughtful, fair, and well-informed is always welcome. Otherwise it is simply tedious in the reading, time consuming in the rebuttal, and adds little that is constructive to the literature.

Ishida K, Kato M, Kato Y, et al. Appropriate use of nasal continuous positive airway pressure decreases elevated C-reactive protein in patients with obstructive sleep apnea. Chest. 2009;1361:125-129. [CrossRef] [PubMed]
 
Ryan S, Taylor CT, McNicholas WT. Systemic inflammation: a key factor in the pathogenesis of cardiovascular complications in obstructive sleep apnoea syndrome? Thorax. 2009;647:631-636. [PubMed]
 
Kohler M, Ayers L, Pepperell JCT, et al. Effects of continuous positive airway pressure on systemic inflammation in patients with moderate to severe obstructive sleep apnoea: a randomised controlled trial. Thorax. 2009;641:67-73. [CrossRef] [PubMed]
 
Taheri S, Austin D, Lin L, Nieto FJ, Young T, Mignot E. Correlates of serum C-reactive protein (CRP)—no association with sleep duration or sleep disordered breathing. Sleep. 2007;308:991-996. [PubMed]
 
Yao M, Tachibana N, Okura M, et al. The relationship between sleep-disordered breathing and high-sensitivity C-reactive protein in Japanese men. Sleep. 2006;295:661-665. [PubMed]
 
Punjabi NM, Beamer BA. C-reactive protein is associated with sleep disordered breathing independent of adiposity. Sleep. 2007;301:29-34. [PubMed]
 
Lui MM, Lam JC, Mak HKF, et al. C-reactive protein is associated with obstructive sleep apnea independent of visceral obesity. Chest. 2009;1354:950-956. [CrossRef] [PubMed]
 
Elliott P, Chambers JC, Zhang W, et al. Genetic loci associated with C-reactive protein levels and risk of coronary heart disease. JAMA. 2009;3021:37-48. [CrossRef] [PubMed]
 
Ryan S, Taylor CT, McNicholas WT. Selective activation of inflammatory pathways by intermittent hypoxia in obstructive sleep apnea syndrome. Circulation. 2005;11217:2660-2667. [CrossRef] [PubMed]
 
Ryan S, Nolan GM, Hannigan E, Cunningham S, Taylor C, McNicholas WT. Cardiovascular risk markers in obstructive sleep apnoea syndrome and correlation with obesity. Thorax. 2007;626:509-514. [CrossRef] [PubMed]
 
Ryan S, Ward S, Heneghan C, McNicholas WT. Predictors of decreased spontaneous baroreflex sensitivity in obstructive sleep apnea syndrome. Chest. 2007;1314:1100-1107. [CrossRef] [PubMed]
 
Ryan S, Taylor CT, McNicholas WT. Predictors of elevated nuclear factor-kappaB-dependent genes in obstructive sleep apnea syndrome. Am J Respir Crit Care Med. 2006;1747:824-830. [CrossRef] [PubMed]
 
Ward S, Ryan S, Mc Nicholas WT, Heneghan C. Comparison of baroreflex sensitivity measures for assessing subjects with obstructive sleep apnea. Conf Proc IEEE Eng Med Biol Soc. 2006;1:3572-3575. [PubMed]
 
Steiropoulos P, Kotsianidis I, Nena E, et al. Long-term effect of continuous positive airway pressure therapy on inflammation markers of patients with obstructive sleep apnea syndrome. Sleep. 2009;324:537-543. [PubMed]
 
Drager LF, Bortolotto LA, Figueiredo AC, Krieger EM, Lorenzi GF. Effects of continuous positive airway pressure on early signs of atherosclerosis in obstructive sleep apnea. Am J Respir Crit Care Med. 2007;1767:706-712. [CrossRef] [PubMed]
 

Figures

Tables

Table Graphic Jump Location
Table 1 —Studies Suggesting C-Reactive Protein Is Elevated in Obstructive Sleep Apnea Independent of Obesity

CRP = C-reactive protein; ODI = oxygen desaturation index; OSA = obstructive sleep apnea.

Table Graphic Jump Location
Table 2 —Differences Between Studies by Kohler et al3 vs Ishida et al1

CPAP = continuous positive airway pressure. See Table 1 for expansion of the other abbreviation.

References

Ishida K, Kato M, Kato Y, et al. Appropriate use of nasal continuous positive airway pressure decreases elevated C-reactive protein in patients with obstructive sleep apnea. Chest. 2009;1361:125-129. [CrossRef] [PubMed]
 
Ryan S, Taylor CT, McNicholas WT. Systemic inflammation: a key factor in the pathogenesis of cardiovascular complications in obstructive sleep apnoea syndrome? Thorax. 2009;647:631-636. [PubMed]
 
Kohler M, Ayers L, Pepperell JCT, et al. Effects of continuous positive airway pressure on systemic inflammation in patients with moderate to severe obstructive sleep apnoea: a randomised controlled trial. Thorax. 2009;641:67-73. [CrossRef] [PubMed]
 
Taheri S, Austin D, Lin L, Nieto FJ, Young T, Mignot E. Correlates of serum C-reactive protein (CRP)—no association with sleep duration or sleep disordered breathing. Sleep. 2007;308:991-996. [PubMed]
 
Yao M, Tachibana N, Okura M, et al. The relationship between sleep-disordered breathing and high-sensitivity C-reactive protein in Japanese men. Sleep. 2006;295:661-665. [PubMed]
 
Punjabi NM, Beamer BA. C-reactive protein is associated with sleep disordered breathing independent of adiposity. Sleep. 2007;301:29-34. [PubMed]
 
Lui MM, Lam JC, Mak HKF, et al. C-reactive protein is associated with obstructive sleep apnea independent of visceral obesity. Chest. 2009;1354:950-956. [CrossRef] [PubMed]
 
Elliott P, Chambers JC, Zhang W, et al. Genetic loci associated with C-reactive protein levels and risk of coronary heart disease. JAMA. 2009;3021:37-48. [CrossRef] [PubMed]
 
Ryan S, Taylor CT, McNicholas WT. Selective activation of inflammatory pathways by intermittent hypoxia in obstructive sleep apnea syndrome. Circulation. 2005;11217:2660-2667. [CrossRef] [PubMed]
 
Ryan S, Nolan GM, Hannigan E, Cunningham S, Taylor C, McNicholas WT. Cardiovascular risk markers in obstructive sleep apnoea syndrome and correlation with obesity. Thorax. 2007;626:509-514. [CrossRef] [PubMed]
 
Ryan S, Ward S, Heneghan C, McNicholas WT. Predictors of decreased spontaneous baroreflex sensitivity in obstructive sleep apnea syndrome. Chest. 2007;1314:1100-1107. [CrossRef] [PubMed]
 
Ryan S, Taylor CT, McNicholas WT. Predictors of elevated nuclear factor-kappaB-dependent genes in obstructive sleep apnea syndrome. Am J Respir Crit Care Med. 2006;1747:824-830. [CrossRef] [PubMed]
 
Ward S, Ryan S, Mc Nicholas WT, Heneghan C. Comparison of baroreflex sensitivity measures for assessing subjects with obstructive sleep apnea. Conf Proc IEEE Eng Med Biol Soc. 2006;1:3572-3575. [PubMed]
 
Steiropoulos P, Kotsianidis I, Nena E, et al. Long-term effect of continuous positive airway pressure therapy on inflammation markers of patients with obstructive sleep apnea syndrome. Sleep. 2009;324:537-543. [PubMed]
 
Drager LF, Bortolotto LA, Figueiredo AC, Krieger EM, Lorenzi GF. Effects of continuous positive airway pressure on early signs of atherosclerosis in obstructive sleep apnea. Am J Respir Crit Care Med. 2007;1767:706-712. [CrossRef] [PubMed]
 
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543