Gender differences in the association of sleep apnea and inflammation

Abstract

Over the last 15years, many studies have established an association of sleep apnea with inflammation and metabolic aberrations. However, no controlled studies have examined potential gender effects in this association. We recruited 120 middle-aged, predominantly non-obese mild-to-moderate sleep apneics and controls (62 males, 58 females). All participants underwent a clinical history, physical examination, and 1-night 8-h polysomnography recording and provided a single fasting blood sample for assessment of interleukin-6 (IL-6), tumor necrosis factor receptor 1 (TNFR1), C-reactive protein (CRP), leptin, and adiponectin levels. Among non-sleep apneics, females had higher levels of TNFR1 (p=0.01), CRP (p=0.005), leptin (p<0.001), and adiponectin (p<0.001) compared to males, independent of age and body mass index. When analyzed separately by gender, sleep apneic men had elevated TNFR1 (p=0.04), CRP (p=0.06) and IL-6 (p=0.11) relative to control men; in sleep apneic females, only CRP was elevated (p=0.04). Furthermore, CRP was associated with apnea severity in a dose-response manner (p-linear=0.04 in both genders) and was independently associated with comorbid hypertension in apnea (p-linear=0.005 for women; p-linear=0.09 for men). In conclusion, although women have naturally higher levels of inflammatory and metabolic markers than men, sleep apneic men appear to have a more severe inflammatory profile compared to women. Our findings suggest that these markers should be analyzed and interpreted separately in men and women, and that a single measure of plasma CRP appears to be a clinically-useful marker of apnea severity and comorbid cardiovascular morbidity.

Keywords: Apnea; CRP; Gender; Hypertension; Inflammation; Sleep.

Figure 1. C-reactive protein levels are elevated with increasing sleep apnea severity

Mean C-reactive protein concentrations in males and females, stratified by sleep apnea severity. Data adjusted for age and BMI. Error bars represent standard error of the mean. AHI = apnea/hypopnea index. CRP = C-reactive protein. * p < 0.05

Figure 2. Association of C-reactive protein with sleep apnea and comorbid hypertension in males and females

Mean C-reactive protein concentrations of controls, sleep apneics without hypertension, and sleep apneics with hypertension. Data adjusted for age and BMI. Error bars represent standard error of the mean. HTN = hypertension. ** p < 0.01, T < 0.1