Sex-Specific Differential Responses of Circulating Biomarkers in Obstructive Sleep Apnea Treatment. A Post Hoc Analysis of a Randomized Controlled Trial

Abstract

Rationale: Knowledge of sex-specific changes of cardiovascular biomarkers in response to continuous positive airway pressure (CPAP) therapy for obstructive sleep apnea (OSA) is limited.Objectives: We hypothesized a differential sex-specific cardiovascular biomarker response with CPAP therapy for OSA.Methods: Participants with moderate-severe OSA (apnea-hypopnea index, 15 events/h) were randomized to CPAP versus sham and completed polysomnography and collection of biomarkers of inflammation (myeloperoxidase, fibrinogen, paraoxonase, interleukin [IL]-6, IL-6 soluble receptor, aryl esterase, oxidized low-density lipoprotein, lipoprotein A, plasminogen activator inhibitor 1, and F2-isoprostane urine/creatinine ratio) and vascular measures at baseline and 8 weeks of therapy with either CPAP (n = 72) or sham treatment (n = 70). Post hoc secondary analyses of sex-study arm interaction relative to change in inflammatory biomarkers were evaluated via linear regression with adjustment for baseline biomarker value, age, race, body mass, index, waist circumference, and CPAP adherence. Interactions were further evaluated via sex-stratified analyses.Results: The study sample comprised a total of 149 participants aged 50.8 ± 11.7 years; 55% were male, and 55% were white. Participants had a median apnea-hypopnea index of 26.3 events per hour (interquartile range, 13-37). There were substantial interactions between study arm and sex for myeloperoxidase, paraoxonase, and fibrinogen (P = 0.03, P = 0.03, and P = 0.08, respectively). No significant interactions were found for the vascular measures. Estimates were similar but with decreased power in sex-stratified analyses, with decreased biomarkers in women and increased biomarkers in men.Conclusions: Differential sex-specific responses to CPAP therapy for OSA were observed for circulating inflammatory biomarkers, which persisted after adjustment for confounders. These findings set the stage for validation studies and, if confirmed, biochemical pathway elucidation to inform sex-specific personalized treatment approaches.Clinical trial registered with www.clinicaltrials.gov (NCT00607893).

Keywords: biomarkers; continuous positive airway pressure; heart diseases; inflammation; vascular stiffness.

Figures

Figure 1.

Study flow: recruitment, attrition, and retention. CPAP = continuous positive airway pressure; PAP = positive airway pressure.

Figure 2.

Unadjusted interaction between sex and study arm: change from baseline to 8-week values presented as mean ± standard deviation. P values for interaction are adjusted for age, race, body mass index, waist circumference, and adherence. CPAP = continuous positive airway pressure.