| Objective: obstructive sleep apnea(OSA) and hypertension(HTN) have been well-known to increase cardiovascular events and all-cause mortality. Overlapping of the two in clinical settings is common and further increases risk for cardiovascular events in middle age male. As studies have been further focused, target organ damages of OSA complicated with HTN are increasing gradually, and new mechanisms responsible are further being put forward. This current study using a case-control design explores: relationship between sleep architecture and OSA and serum levels of inflammatory cytokines in OSA patients complicated with HTN, effects of sleep architecture on blood pressure variability and glyco-metabolism and the potential relationship between OSA and serum pulmonary surfactant proteins. Methods: This is cross-sectional study, performed according to strict inclusion and exclusion criteria. Anthropometric, polysomnographic and clinical data, and blood were collected from all the subjects to assess the possible differences between case and control group. The first section: sleep stages were evaluated, based on Rechtshaffen and Kales standard, including NREM(N1, 2, 3 and 4) and REM sleep, hypoxia parameters included apnea hypopnea index(AHI), lowest saturation of oxygen(LSaO2), and oxygen desaturation index 3, 4(ODI3, ODI4), and fasting blood glucose and hemoglobin A1 c were measured using standard methods. Serum levels of inflammatory cytokines were evaluated by enzyme-linked immunosorben, relations between sleep architecture and various inflammatory factors level and other sleep parameters were also evaluated. The second section, 1, subjects were divided into two groups via AHI=15event/h, sleep stages were compared between groups, effects of different hypoxia parameters on sleep stages were analyzed and effects of sleep stages on fasting blood glucose and hemoglobin A1 c were assessed. 2, Ambulatory blood pressure monitoring system(ABPM) was used to assess blood pressureand blood pressure variability and wake after sleep onset was evaluated using standard methods(polysomnography). Potential differences in blood pressure and blood pressure variability were compared between OSA and non-OSA groups, possible influences of different hypoxia parameters were analyzed, and the potential correlation between wake after sleep onset and blood pressure variability was evaluated. The third section, 1, serum surfactant proteins encompassing surfactant protein A, B, C and D and Krebs von den lungen-6(KL-6) were measured applying ELISA methods. After divided into two groups via the mean of hypopnea index, serum surfactant protein A and D were compared between two groups with higher and lower hypopnea index and potential relations between different hypoxia parameters and SP-A and-D were analyzed; after divided into two groups via AHI=15 event/h, serum surfactant protein B and C were compared between two groups with higher and lower AHI, potential relations between different hypoxia parameters and SP-B and-C and clinical value of surfactant protein-B as a biomarker to diagnose OSA were analyzed. 2, plethysmograph and impulse oscillometry system were used to assess indicators of lung function and airway resistance and evaluate the potential relationship between airway resistance and serum surfactant proteins-A, B, C and D level. Results: 140 middle-aged hypertensive males were enrolled to the current study. prevalence of OSA, defined as AHI=15events/h, was 45.8%. Mean ages and BMI of subjects were 44.6±7.65 years and 27.77±3.05kg/m2. The first section, 1, percentage of sleep stage 1(N1) in OSA patients is significantly increased, compared to non-OSA subjects; ODI is inversely linearly associated with REM sleep stage; even after adjustment for age and BMI. 2, Compared to lower serum LBP levels group, IL-1, IL-6 TNF-α and are N1 stage significantly increased in higher serum LBP levels group; serum LBP levels is positively associated with ODI3 and ODI4, even after adjusting age, BMI, and AHI. The second part, 1, fasting blood glucose in total subjects is in a significant positive correlation with percentage of N1 stage and in a significant negative correlation with percentage of N4 stage(rN1=0.221, P=0.009; rN4=0.205, P=0.015), even after adjusting for age, BMI and AHI as confounders. Percentage of REM in subjects with AHI <15events/h is in strong positive association with fasting blood glucose(r=0.522, P=0.003) and is in a negative correlation with fasting blood glucose in subjects with AHI ≥30events/h(r=-0.372, P=0.044). Meanwhile, N1 stage is positively related to fasting blood glucose(r=0.524, P=0.001) and correlation coefficient of N 1 stage with hemoglobin A1 C is r=0.372 without statistical significance(P=0.052). 2, variability in diastolic blood pressure is significantly higher not only nocturnally but also diurnally in subjects with OSA(9.57±2.11 vs 10.55±2.85 mmHg, P=0.041) than in subjects without OSA; arousal after sleep onset in subjects with OSA significantly increases not only nocturnal blood pressure variability but also diurnal systolic blood pressure variability, while compared to non-OSA subjects. The third part, 1, in non-smoking group, hypopnea index showed a significant strong negative correlation with surfactant protein-A and-D(r=-0.343, P=0.012, r=-0.504, P=0.001). Multi-variable linear logistic regression analysis showed that hypopnea index is in a significant correlation with SP-A and SP-D, even after adjusting for age and BMI. Serum concentration of surfactant protein-B is significantly decreased in subjects with OSA, compared to non-OSA subjects(44.73± 7.62 vs 41.39±6.01ng/ml, P=0.005), and negatively correlated with severity of OSA assesses by apnea hypopnea index(rAHI=0.221, P=0.009), whereas surfactant protein-C and KL-6 showed no significant differences between OSA and non-OSA groups. Serum concentrations of SP-B showed some valuable aspect in diagnosis of OSA(sensitivity: 75.34%, 95%CI 0.470-0.713); combination of serum SP-B and Epworth Sleepiness Scale further improves the diagnostic sensitivity(84.8%, 95%CI: 0.721-0.922) and specificity(94.44%, CI: 0.836-0.985). Compared to subjects with non-OSA, increased airway resistance and decreased serum SP-A, B, D level were observed in subjects with OSA in all patients with non smoking history. Serum SP-D level was inversely related to R5-R20 in subjects with non smoking history. in further study, the strong relations between serum SP-D level and more indicators of airway resistance in subjects with obesity and non smoking. Conclusion: first, sleep structure of OSA patients combined with hypertension is altered, displaying significantly lengthened N1 and REM sleep stages and shortened REM sleep stage. Severity of OSA(accessed by ODI) is related to shortened REM sleep stage; The difference of sleep fragmentation between OSA and OSA+HTN was not observed. Increase in serum LBP levels might lead to lengthened N1 and deteriorated sleep fragmentation in HTN; these alterations in may secondary to increased nocturnal respiratory events and wake after sleep onset. Lengthened N1 may may elevate fasting blood glucose, severity of OSA may alter relation between sleep architecture and fasting blood glucose. Blood pressure variability is increased in OSA patients complicated with hypertension, which can be observed not only nocturnally but also diurnally. Increases in arousal after sleep onset in hypertensive patients elevated blood pressure variability, which lasts even longer in those with OSA. Third, OSA might repress synthesis of surfactant proteins, presented as decreased serum surfactant proteins. Smoking interferes with the correlation between OSA and surfactant proteins. Serum SP-B might be a potential biomarker for OSA, and combination of SP-B with ESS might help diagnose OSA. Increases in airway resistance(R5-R20) might be correlated with decreased synthesis of surfactant proteins, specially, SP-D. Decrease in SP-D might be the potential mechanism of increased airway resistance in obese subjects with non smoking. |
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