The Research On The Levels Of High Sensitivity C-reactive Protein In Patients With Obstructive Sleep Apnea-hypopnea Syndrome

Background and ObjectiveObstructive sleep apnea-hypopnea syndrome (OSAHS) is the increase in airway resistance breathing, cause shallow breathing slow and even suspended, leading to repeated episodes of hypoxia, hypercapnia, allowing the body to a series of pathophysiology of the clinical syndrome. Epidemiological investigation:in the population over the age of40, the United States OSAHS prevalence rate was2%to4%, more men than women, a higher prevalence of the elderly. Crowd survey shows that the actual prevalence to be higher than previously reported2%to4%. The clinical characteristics of OSAHS mainly to sleep snoring associated with apnea, daytime sleepiness, and behavioral and psychological abnormalities, obesity and so on, and (or) performance associated with systemic organ damage, such as hypertension, coronary atherosclerotic heart disease(crown heart disease), pulmonary heart disease (cor pulmonale) and respiratory failure, ischemic or hemorrhagic cerebrovascular disease, diabetes and mental disorders. The OSAHS patients often cardiovascular system abnormalities as the first signs and symptoms. Numerous studies show that OSAHS is an independent risk factor for cardiovascular disease, such as high blood pressure, coronary heart disease, pulmonary heart disease and stroke. Polysomnography (PSG) is the gold standard for the diagnosed OSAHS, and can determine the type and severity. Nasal-continuous positive airway pressure (n-CPAP) is the preferred method for the treatment of moderate to severe OSAHS patients, nasal continuous positive airway pressure aspirated airways can increase the patient’s functional residual capacity, and reduce upper airway resistance by stimulating airway receptors increase the tension of the upper airway, thus preventing upper airway collapse sleep. It can effectively eliminate snoring at night, improve sleep structure, improve nocturnal apnea and hypopnea, correct nocturnal hypoxemia, also significantly improve daytime sleepiness, headaches and memory loss and other symptoms.OSAHS is receiving in-creased attention because it is associated with a variety of long-term consequences such as high rates of morbidity and mortality, mostly due to excessive diurnal somnolence and cardiovascular and metabolic diseases.It has been shown that there is increased risk for cardiovascular and cerebrovascular conditions and events in patients with OSAHS, recent studies have found that it may be related to increased sympathetic activity, endothelial dysfunction, inflammatory processes and other factors. In sleep, recurring hypoxia caused by apnea and hypopnea of OSAHS patients allows the body to produce excessive reactive oxygen species (ROS), ROS is a molecules or groups with a high degree of chemical activity, react with the nucleic acid, lipids and proteins, and thereby preventing the cell metabolism, leading to cell damage, changing the physiological processes of the cell, including the functiong of the change of the film, the generation and activation of the protein kinase and some gene transcription atart and adjust, thus triggering a series of inflammatory process. Since1997, Vgontzas, et al creported that the levels of the inflammatory cytokines(such as interleukin-6, IL-6an tumor necrosis factor-a, TNF-a) in the patients with sleep-disordered breathing were elevated, the relationship between the patients with sleep-disordered breathing and the inflammatory cytokines was attracted attention. Many experiments from different angles confirmed that there was the higher levels of inflammatory cytokines in patients with OSAHS, these inflammatory cytokines including acute reactive protein, leptin, TNF-a, IL-6, IL-8and adhesion molecule, and it prompted that there was a systemic inflammation in OSAHS patients.C-reactive protein (CRP) is a member of the pentraxin protein family and is an important marker of endothelial dysfunction in the pathogenesis of coronary artery disease. It is an acute phase reactive protein, the body’s important defense molecule, mainly produced by the liver and secreted in human serum, cerebrospinal fluid, pleural effusion, and other body fluids can be measured, participate in a variety of inflammation and immune response in the body. Increased CRP levels have been shown to be an independent risk predictor for peripheral vascular disease, myocardial infarction, stroke, and vascular death. Unlike other inflammation markers, CRP levels are quite stable in individuals after being produced for24h, and an increase may reflect the level of inflammatory response. CRP which continues to rise prompts chronic inflammation or autoimmune diseases in body, it does not rise in viral infection, and the variation is not the patient’s individual differences body condition and treatment of drug. CRP levels are usually measured by immuno-nephelometric or immunoturbidimetric assays. These methods measure CRP levels above3-5mg/L, a level of sensitivity that is adequate to monitor infection but is useless in the prediction of the risk of coronary and cerebrovascular disease in healthy populations. Recently, ELISA and latex to enhance immune scattering or transmittance cloud technology, making the detection ability of CRP to0.15mg/L, the ELISA method can be detected even0.007mg/L, so called high-sensitivity C-reactive protein(hsCRP). In recent years, a number of large-scale prospective studies confirmed that hsCRP is a strongest independent predictor of the future occurrence of myocardial infarction and stroke in the healthy population.It has been shown in the report by Shamsuzzaman et al. that there is a significant correlation between the apnea-hypopnea index (AHI) and serum CRP levels. In recent years, there is a growing number of reports about the OSAHS plasma hsCRP level, while there are also contradictions. In Sharma’s study, there are97subjects in New Delhi, India, between April2005and March2006, all subjects excluding diabetes, hypertension, coronary heart disease, fingertip hypertrophy, thyroid dysfunction disease, chronic renal failure, congestive heart failure, and smoking history, in the multiple linear regression analysis, only BMI significantly was associated with hsCRP (beta=0.02, p=0.01), they think increased hsCRP has significant correlations with obesity. In McLaughlin’s study, hsCRP levels were significantly increased and decreased with weight loss in the obese patients. While, in Firat Guven’s study, levels of hsCRP in OSAHS patients (4.03±3.58mg/L) was significantly higher than that in the control group(2.41±1.95mg/L)(p=0.013), and in the regression analysis, levels of hsCRP was associated with the severity of OSAHS independent of obesity.The purpose of this work was to evaluate the relationship between hsCRP levels and the OSAHS patients who were admitted to a sleep disorders center with a clinical suspicion of sleep apnea.Subjects and methods1. Subject SelectionSeventy-four subjects who were admitted to our sleep disorders center with a clinical suspicion of obstructive sleep apnea were enrolled in the study. The Institutional Ethics Committee approved the study. Full-night polysomnography (PSG) was applied to all patients between January2010and April2012in sleep disorders laboratory at the Sleep Medicine Center, Nanfang Hospital, Southern Medical University.Patients with diagnosis of diabetes, hypertension, coronary heart disease, congestive heart failure, cerebrovascular diseases, CSAS, asthma, infectious diseases, tumor, peripheral vascular disease, rheumatic autoimmune diseases, acute or chronic renal failure were excluded. Because these were factors that would affect detection of hsCRP levels.Body mass index (BMI) was calculated by dividing the body weight in kilograms by the square of the height in meters; subjects with a BMI≥30kg/m2were classified as obese, a BMI25.0-29.9kg/m2as overweight, and a BMI18.5～24.9kg/m2as normal.2. methods2.1PolysomnographyFull-night PSG records of patients were recorded by digital PSG system (Embla). The subjects were advised not to sleep during the day, not to consume caffeine-containing beverages, and not to take medication that might affect their sleeping pattern. Mainly the physiological changes related to sleep and respiration were recorded. For evaluation of sleep and sleep stages, electroencephalography, electrooculogram, and submental electromyelography (EMG) recordings were used. Orinasal breathing thermoster was placed in the nose for monitoring airflow. Thoracoabdominal movements were recorded via sensors of the thoracoabdominal effort. Oxygen saturation and heart rate were obtained by pulse oximeter and electrocardiography electrodes, respectively. Analysis of leg movements was made with EMG sensors placed on the anterior tibialis muscle. Sleep stages were scored manually based on the guidelines of the American Academy of Sleep Medicine.2.2. Sample CollectionVenous blood samples were obtained from all patents in the morning of PSG (at08:00-09:00a.m.), and then were analyzed in the laboratory.2.3. Statistical AnalysisThe means and standard deviation (SD) were determined for continuous variables, and the percentages were determined for categorical variables. The Independent-Samples T test was used to determine the significance of the differences between two groups. Correlations were analyzed using Pearson’s correlation coefficient. All statistical analyses were carried out using statistical software (SPSS, version13.0for Windows). Differences were considered significant at p<0.05.Results1. General comparison between the OSAHS group and the control group1.1Age and BMI comparision between OSAHS group and the control groupA total of74subjects were included in the study, with19in the control group (AHI<5) and55in the OSAHS group (AHI>5). The mean age of the OSAHS group was42.0±9.5years, and the mean age of the control group was43.4±10.9years (p=0.325). The mean BMI in the OSAHS group was27.1±3.6kg/m2, and in the control group, it was25.5±5.6kg/m2(p=0.117). The OSAHS and control groups were similar with regard to demographics (age and BMI).1.2Comparison of respiratory parameters between OSAHS group and the control groupThe mean AHI of the OSAHS group was31.4±23.1events per hour, and in the control group, it was2.2±1.5events per hour (p=0.000). The mean LSpO2of the OSAHS group was77.6±10.8%, and in the control group it was90.4±4.9% (p=0.003).2. Comparison of hsCRP between OSAHS group and the control groupThe plasma hsCRP levels were significantly higher in the OSAHS group (1.88±1.80mg/L) than in the control group (1.01±1.40mg/L)(p=0.038).3. Comparison of hsCRP in OSAHS groupThe plasma hsCRP levels were significantly higher in the moderately severe OSAHS group (2.13±1.89mg/L) than in the mild OSAHS group (1.02±0.82mg/L)(p=0.003).4. Comparison of hsCRP between Obesity group and the control groupThe plasma hsCRP levels were significantly higher in the Obesity group (2.85±1.30mg/L) than in the control group (1.30±1.36mg/L)(p=0.000).5. Pearson’s correlation coefficientPearson’s correlation coefficient showed that there were significant correlations between serum hsCRP levels and both BMI and AHI (r=0.306, P=0.008and r=0.369, P=0.001, respectively). The hsCRP levels had significant negative correlations with the lowest arterial oxygen saturation (r=-0.29, P=0.012).6. Stepwise regression analysisTo assess the relative strength of the association between OSAHS and hsCRP levels, we employed a stepwise regression analysis using the patients with OSAHS as a single group. In this analysis, we used the plasma hsCRP levels as dependent variables and evaluated the order of inclusion in this model with the following independent variables:BMI and lowest oxygen saturation during sleep. In stepwise regression analysis, hsCRP levels were associated with AHI independent of obesity (F=6.419, P=0.014). The regression equation:hsCRP=l.072+0.026AHI.Conclusions 1. Levels of hsCRP were significantly higher in patients with OSAHS than that in control subjects, and higher in patients with moderate to severe OSAHS than that in mid OSAHS, and higher in patients with obesity than that in control subjects.2. The good correlation between elevated hsCRP and OSAHS severity, prompted the systemic inflammatory response in OSAHS patients.3. Leveels of hsCRP was associated with the severity of OSAHS independent of obesity, OSAHS itself is the main reason for elevated CRP.