0

The full content of Annals is available to subscribers

Subscribe/Learn More  >
Original Research |

Cardiovascular Mortality in Women With Obstructive Sleep Apnea With or Without Continuous Positive Airway Pressure Treatment: A Cohort Study

Francisco Campos-Rodriguez, MD; Miguel A. Martinez-Garcia, MD; Ines de la Cruz-Moron, MD; Carmen Almeida-Gonzalez, MD; Pablo Catalan-Serra, MD; and Josep M. Montserrat, MD
[+] Article and Author Information

From Valme University Hospital, Seville; La Fe University and Polytechnic Hospital and Requena General Hospital, Valencia; Clinic Hospital, Barcelona; and CIBERes de Enfermedades Respiratorias, Madrid, Spain.


Potential Conflicts of Interest: None disclosed. Forms can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M11-1208.

Reproducible Research Statement:Study protocol: Available in Spanish from Dr. Campos-Rodriguez (e-mail, fracamrod@gmail.com). Statistical code and data set: Not available.

Requests for Single Reprints: Francisco Campos-Rodriguez, MD, Sleep-Disordered Breathing Unit, Respiratory Department, Valme University Hospital, Ctra Cadiz S/N, 41014 Seville, Spain; e-mail, fracamrod@gmail.com.

Current Author Addresses: Drs. Campos-Rodriguez and de la Cruz-Moron: Sleep-Disordered Breathing Unit, Respiratory Department, Valme University Hospital, Ctra Cadiz S/N, 41014 Seville, Spain.

Dr. Martinez-Garcia: Respiratory Department, La Fe University and Polytechnic Hospital, CIBERes de enfermedades respiratorias, Bulevar Sur S/N, 46006 Valencia, Spain.

Dr. Almeida-Gonzalez: Biostatistics and Investigation Unit, Valme University Hospital, Ctra Cadiz S/N, 41014 Seville, Spain.

Dr. Catalan-Serra: Pneumology Unit, Requena General Hospital, Paraje CasaBlanca S/N, 46340 Requena, Valencia, Spain.

Dr. Montserrat: Respiratory Department, IDIBAPS Clinic Hospital, CIBERes de Enfermedades Respiratorias, Villaroel 170, 08036 Barcelona, Spain.

Author Contributions: Conception and design: F. Campos-Rodriguez, M.A. Martinez-Garcia, C. Almeida-Gonzalez.

Analysis and interpretation of the data: F. Campos-Rodriguez, M.A. Martinez-Garcia, I. de la Cruz-Moron, C. Almeida-Gonzalez, P. Catalan-Serra, J.M. Montserrat.

Drafting of the article: F. Campos-Rodriguez, M.A. Martinez-Garcia, I. de la Cruz-Moron, C. Almeida-Gonzalez.

Critical revision of the article for important intellectual content: F. Campos-Rodriguez, M.A. Martinez-Garcia, C. Almeida-Gonzalez, J.M. Montserrat.

Final approval of the article: F. Campos-Rodriguez, M.A. Martinez-Garcia, I. de la Cruz-Moron, C. Almeida-Gonzalez, P. Catalan-Serra, J.M. Montserrat.

Statistical expertise: C. Almeida-Gonzalez.

Collection and assembly of data: F. Campos-Rodriguez, M.A. Martinez-Garcia, I. de la Cruz-Moron, C. Almeida-Gonzalez, P. Catalan-Serra.


Ann Intern Med. 2012;156(2):115-122. doi:10.7326/0003-4819-156-2-201201170-00006
Text Size: A A A

Background: Obstructive sleep apnea (OSA) is a risk factor for cardiovascular death in men, but whether it is also a risk factor in women is unknown.

Objective: To investigate whether OSA is a risk factor for cardiovascular death in women and assess whether continuous positive airway pressure (CPAP) treatment is associated with a change in risk.

Design: Prospective, observational cohort study.

Setting: 2 sleep clinics in Spain.

Patients: All women consecutively referred for suspected OSA between 1998 and 2007.

Intervention: Every woman had a diagnostic sleep study. Women with an apnea–hypopnea index (AHI) less than 10 were the control group. Obstructive sleep apnea was diagnosed when the AHI was 10 or higher (classified as mild to moderate [AHI of 10 to 29] or severe [AHI ≥30]). Patients with OSA were classified as CPAP-treated (adherence ≥4 hours per day) or untreated (adherence <4 hours per day or not prescribed). Participants were followed until December 2009.

Measurements: The end point was cardiovascular death.

Results: 1116 women were studied (median follow-up, 72 months [interquartile range, 52 to 88 months]). The control group had a lower cardiovascular mortality rate (0.28 per 100 person-years [95% CI, 0.10 to 0.91]) than the untreated groups with mild to moderate OSA (0.94 per 100 person-years [CI, 0.10 to 2.40]; P = 0.034) or severe OSA (3.71 per 100 person-years [CI, 0.09 to 7.50]; P < 0.001). Compared with the control group, the fully adjusted hazard ratios for cardiovascular mortality were 3.50 (CI, 1.23 to 9.98) for the untreated, severe OSA group; 0.55 (CI, 0.17 to 1.74) for the CPAP-treated, severe OSA group; 1.60 (CI, 0.52 to 4.90) for the untreated, mild to moderate OSA group; and 0.19 (CI, 0.02 to 1.67) for the CPAP-treated, mild to moderate OSA group.

Limitation: The study was observational and not randomized, and OSA was diagnosed by 2 different methods.

Conclusion: Severe OSA is associated with cardiovascular death in women, and adequate CPAP treatment may reduce this risk.

Primary Funding Source: None.

Figures

Grahic Jump Location
Figure 1.
Study flow diagram.

AHI = apnea–hypopnea index; CPAP = continuous positive airway pressure.

Grahic Jump Location
Grahic Jump Location
Figure 2.
Kaplan–Meier cardiovascular cumulative mortality curves for study groups.

AHI = apnea–hypopnea index; CPAP = continuous positive airway pressure.

* Compared with control group.

Grahic Jump Location

Tables

References

Letters

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).

Comments

Submit a Comment
Analysis by Adherence?
Posted on January 30, 2012
Thomas A., Finucane, Professor of Medicine
Johns Hopkins University School of Medicine
Conflict of Interest: None Declared

To the Editor:

In 1980 the Coronary Drug Project (1) showed that among subjects assigned to placebo, those who faithfully (at least 80% of the time) took the lactose placebo had a roughly 50% reduction in death compared to subjects who took the pill less faithfully. The authors note "the serious difficulty, if not impossibility, of evaluating treatment efficacy in subgroups determined by patient ... adherence ..." Adherent patients seem different from nonadherent patients in ways that are difficult to characterize.

Campos-Rodriguez and colleagues compared cardiovascular mortality rates in women "with obstructive sleep apnea (who) were classified as CPAP -treated (adherence >/= 4 hours per day) or untreated (adherence <4 hours per day or not prescribed.)" CPAP is continuous positive airway pressure. They conclude that "... CPAP treatment is associated with a decrease in mortality risk." They do not tell how many patients in the "untreated group" had not had CPAP prescribed, and how many had it prescribed and did not use it. (2)

Since analyzing patient subgroups on the basis of adherence can lead to misleading results, could the authors analyze their data in ways that do not rely on such an analysis?

Very truly yours,

Thomas E. Finucane, MD Johns Hopkins University School of Medicine

(1)N Engl J Med. 1980 Oct 30;303(18):1038-41. (2)Campos-Rodriguez et al. Ann Intern Med 2012;156(2):115.

Conflict of Interest:

None declared

Re:Analysis by Adherence?
Posted on March 3, 2012
Francisco, Campos-Rodriguez, Miguel A. Martinez-Garcia
Valme Hospital, Sevilla, Spain
Conflict of Interest: None Declared

In Response

We thank Dr Finucane for his comments. He argues that analyzing patient subgroups on the basis of adherence can lead to misleading results. He also wonders how many patients in the untreated group had not had CPAP prescribed and how many were non-compliant.

We agree with Dr Finucane, and it was acknowledged as one of the most important limitations of our study, that the observational design might introduce a selection bias, since inadequate CPAP compliance could be a marker for generally non-adherent behaviour. Nevertheless, it cannot be taken for granted that all women who were not adherent to CPAP were noncompliant with other treatments. A recent publication concluded that adherence to cardiovascular medications was not different in patients with severe OSA whether or not they were treated with CPAP (1). On the other hand, a randomized design would have ethical implications in our study, due to the presence of symptomatic patients in whom CPAP could not be withheld. In fact, 60.5% (507/838) of the women diagnosed with OSA in our cohort had excessive daytime sleepiness, based on an Epworth Score higher than 10.

In our study, CPAP was prescribed according to updated guidelines. These guidelines advise to start CPAP treatment if a patient has severe OSA or associated symptoms (mainly, excessive daytime sleepiness) (2). All 95 women classified as untreated severe OSA were offered CPAP. Eleven of them refused this treatment and the remaining 84 women started CPAP treatment (and eventually, showed bad adherence). Of the 167 women classified as untreated mild to moderate OSA, only 47 (28.1%) began CPAP treatment (all of them had an Epworth score >10), whereas 120 (71.8%) were not offered CPAP. In summary, 91.6% (120/131) of the women who were not started on CPAP treatment had mild to moderate OSA without excessive daytime sleepiness, whereas those who were prescribed CPAP but were non- adherent suffered from severe and/or symptomatic OSA. Both groups were completely different regarding OSA severity and symptoms, so we believe that they cannot be analyzed separately. Had we only analyzed women who did not start CPAP therapy, only 11 cases with severe OSA would have been included, and the association between severe OSA and cardiovascular mortality could not have been assessed.

Sincerely,

Francisco Campos-Rodriguez, MD Valme Hospital, 41014 Sevilla, Spain

Miguel A. Martinez-Garcia, MD La Fe Hospital, 46006 Valencia, Spain

References:

(1) Villar I, Izuel M, Carrizo S, Vicente E, Marin JM. Medication adherence and persistence in severe obstructive sleep apnea. Sleep 2009; 32: 623-8. (2) Grupo Espanol de Sueno (GES). Consenso nacional sobre el sindrome de apneas-hipopneas del sueno. Arch Bronconeumol 2005; 41 (Supl 4): 1-100.

Conflict of Interest:

None declared

Submit a Comment

Summary for Patients

Risk for Death From Cardiovascular Disease in Women With Obstructive Sleep Apnea

The full report is titled “Cardiovascular Mortality in Women With Obstructive Sleep Apnea With or Without Continuous Positive Airway Pressure Treatment. A Cohort Study.” It is in the 17 January 2012 issue of Annals of Internal Medicine (volume 156, pages 115-122). The authors are F. Campos-Rodriguez, M.A. Martinez-Garcia, I. de la Cruz-Moron, C. Almeida-Gonzalez, P. Catalan-Serra, and J.M. Montserrat.

Read More...

Clinical Slide Sets

Terms of Use

The In the Clinic® slide sets are owned and copyrighted by the American College of Physicians (ACP). All text, graphics, trademarks, and other intellectual property incorporated into the slide sets remain the sole and exclusive property of the ACP. The slide sets may be used only by the person who downloads or purchases them and only for the purpose of presenting them during not-for-profit educational activities. Users may incorporate the entire slide set or selected individual slides into their own teaching presentations but may not alter the content of the slides in any way or remove the ACP copyright notice. Users may make print copies for use as hand-outs for the audience the user is personally addressing but may not otherwise reproduce or distribute the slides by any means or media, including but not limited to sending them as e-mail attachments, posting them on Internet or Intranet sites, publishing them in meeting proceedings, or making them available for sale or distribution in any unauthorized form, without the express written permission of the ACP. Unauthorized use of the In the Clinic slide sets will constitute copyright infringement.

Toolkit

Buy Now

to gain full access to the content and tools.

Want to Subscribe?

Learn more about subscription options

Advertisement
Related Articles
Related Point of Care
Topic Collections
PubMed Articles

Buy Now

to gain full access to the content and tools.

Want to Subscribe?

Learn more about subscription options

Forgot your password?
Enter your username and email address. We'll send you a reminder to the email address on record.
(Required)
(Required)