Alpha-1 Adrenergic-Antagonist Use Increases the Risk of Sleep Apnea: A Nationwide Population-Based Cohort Study

Po-Lan Su; Wen-Kuei Lin; Cheng-Yu Lin; Sheng-Hsiang Lin

doi:10.5664/jcsm.8014

Alpha-1 Adrenergic-Antagonist Use Increases the Risk of Sleep Apnea: A Nationwide Population-Based Cohort Study

J Clin Sleep Med. 2019 Nov 15;15(11):1571-1579. doi: 10.5664/jcsm.8014.

Authors

Po-Lan Su^{1

2}, Wen-Kuei Lin², Cheng-Yu Lin^{2

3

4}, Sheng-Hsiang Lin^{5

6

7

4}

Affiliations

¹ Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
² Sleep Medicine Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
³ Department of Otolaryngology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
⁴ Contributed equally.
⁵ Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
⁶ Biostatistics Consulting Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
⁷ Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

Abstract

Study objectives: Decreased upper-airway muscle responsiveness is one of the major phenotypes of obstructive sleep apnea. Use of α1-adrenergic antagonists is correlated with decreased muscle responsiveness in animal studies, but this association has not yet been demonstrated in humans. This study examined whether use of α1-adrenergic antagonists is an independent risk factor for sleep apnea in humans.

Methods: Data for this retrospective cohort study were obtained from the National Health Insurance Research Database from Taiwan. Between 2000 and 2012, 25,466 patients with hypertension and 18,930 patients without hypertension were enrolled. These groups were divided into α1-adrenergic antagonist users and nonusers, matched by age, sex, and index year. Individuals were monitored for diagnosis of sleep apnea until 2013.

Results: After adjusting for propensity score and potential confounders, including age, geographic location, enrollee category, income, urbanization level, comorbidities, and medication, the adjusted hazard ratios (HRs) for development of sleep apnea with α1-adrenergic antagonist use were 2.38 (95% confidence interval [CI] 1.82-3.10) and 2.82 (95% CI 1.79-4.44) in the hypertension and nonhypertension groups, respectively. Similarly, the adjusted HRs for development of severe sleep apnea with α1-adrenergic antagonist use were 2.74 (95% CI 1.78-4.22) and 4.23 (95% CI 1.57-11.40) in hypertension and nonhypertension patient groups, respectively. The interaction between α1-adrenergic-antagonist user and patients with hypertension was tested using multivariable Cox regression. The results showed that there are positive additive interactions for developing sleep apnea and severe sleep apnea, respectively.

Conclusions: Our study suggests that patients with hypertension using α1-adrenergic antagonists have a higher risk of sleep apnea. Routine sleep apnea screening would be beneficial for patients with hypertension who take α1-adrenergic antagonists.

Keywords: hypertension; sleep apnea; α 1-adrenergic antagonist.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adrenergic alpha-1 Receptor Antagonists / adverse effects*
Adrenergic alpha-1 Receptor Antagonists / therapeutic use
Adult
Age Factors
Female
Humans
Hypertension / drug therapy
Male
Middle Aged
Propensity Score
Retrospective Studies
Risk Factors
Sleep Apnea Syndromes / chemically induced*
Sleep Apnea Syndromes / epidemiology
Taiwan / epidemiology

Substances

Adrenergic alpha-1 Receptor Antagonists