Relationship between surfactant proteins B and C and obstructive sleep apnea: is serum SP-B concentration a potential biomarker of obstructive sleep apnea?

BACKGROUND: Surfactant proteins B and C are mainly synthesized, secreted by alveolar type II cells, and affected by hypoxia and mechanical stretches. We hypothesized that their serum levels might be altered by intermittent hypoxia and swing of intrathoracic pressure of obstructive sleep apnea (OSA). METHODS: Consecutive 140 middle-aged males, suspicious of OSA determined by polysomnography, were studied. Surfactant proteins B and C were determined by ELISA. RESULTS: Surfactant protein B (41.39 ± 6.01 vs 44.73 ± 7.62 ng/L, p = 0.005), not C (32.60 ± 6.00 vs 32.43 ± 6.44 ng/L, p = 0.61), significantly lowered in moderate to severe OSA subjects than in non to mild OSA subjects. Severity of OSA is inversely correlated with serum surfactant protein B. Adjusting age, body mass index, and smoking history, compared to subjects with surfactant protein B (SP-B) ≥43.35 ng/L, those with SP-B <43.35 ng/L showed significantly increased 1.528-fold risk for moderate to severe OSA (p = 0.009), whereas no association between surfactant protein C and OSA was observed. Prevalence of moderate to severe OSA in lower SP-B group is higher than that in higher SP-B group (62.7 vs 38.4 %, p = 0.003). Serial and parallel tests on Epworth sleep scale (ESS) and SP-B evaluation can be complementary and prove helpful with high specificity (94.44 %) and sensitivity (84.48 %) to detect moderate to severe OSA. CONCLUSIONS: Serum surfactant protein B, rather than C, is decreased in some individuals with moderate to severe OSA, compared to non to mild OSA subjects. Serum surfactant protein B might be a potential biomarker to diagnose OSA.

What do changes in concentrations of serum surfactant proteins A and D in OSA mean?

PURPOSE: Previous studies have shown that surfactant proteins are affected by oxygen concentration and mechanic stretches, although the alteration of serum surfactant proteins in individuals with obstructive sleep apnea (OSA) is still unclear. Therefore, the aim of this study is to examine whether serum concentrations of surfactant proteins A and D are altered and related to hypopnea index (HI) in OSA. METHODS: This is a cross-sectional study. Consecutive 140 males, suspicious of OSA, were studied. OSA was determined by PSG and polysomnographic data examined. Subjects with HI ≥ 10.1/h were classified as higher HI group and those with HI < 10.1/h as lower HI group. Hs-CRP, HbA1C, and FBG were determined by standard methods and Krebs von den Lungen-6 (KL-6), surfactant protein-A (SP-A), and surfactant protein-D (SP-D) by ELISA. RESULTS: OSA was diagnosed in 110 patients (78.5%). Mild, moderate, and severe OSA constitutes 26.4, 27.8, and 24.3%, respectively. Mean age was 44.6 ± 7.65 years. Subjects with higher HI had lower SP-A (139.54. ± 32.94 vs 158.2 ± 38.9 ng/L, p = 0.005) and SP-D (16.54 ± 3.67 vs 18.10 ± 3.48 ng/L, p = 0.014) compared to those with lower HI. Nocturnal HI was strongly correlated with serum levels of SP-A (r = 0.343, p = 0.012) and SP-D (r = 0.504, p < 0.001) and are inversely associated with circulating SP-A and SP-D levels, even after adjusting for age and body mass index in nonsmoking subjects. CONCLUSIONS: Circulating SP-A and SP-D levels are decreased in some individuals with higher HI in OSA, possibly reflecting severity of hypoxia in OSA.

[Association of glucose transporter 4 gene polymorphism with hypoxia caused by obstructive sleep apnea syndrome and with related inflammatory factors].

OBJECTIVE: To investigate the relationship between genetic polymorphisms of glucose transporter 4 (GLUT4) and hypoxia caused by obstructive sleep apnea syndrome (OSAS) as well as with related inflammatory factors. METHODS: Consecutive hypertension patients diagnosed at the People's Hospital of Xinjiang Uygur Autonomous Region were selected from January to December 2010. A total of 859 subjects with possible OSAS base on their histories and physical examination findings udner went the polysomnography and inflammatory factor determination, of whom 616 (72%) were diagnosed with moderate and severe hypoxia with OSAS (case group) and 243 (28%) without hypoxia or OASA (control group). Ninty-six patients from the case group underwent DNA sequencing at the functional domain of GLUT4 gene to screen for representative mutations. TaqMan PCR was used to genotyping then analyzed the relationship between locis of GLUT4 and hypoxia. RESULTS: GLUT4 genome sequencing was performed in 96 severe OSAS patients and 4 mutated sites were found, among which 3 mutated sites (rs5415, rs4517, and rs5435) were selected according to the principle of linkage disequilibrium (r² > 0.8) and minimum gene allele frequency > 5%. All of single nucleotide polymorphisms (SNP) satisfied Hardy-Weinberg equilibrium (P>0.05). A significant association of GLUT4 SNP rs5417 allele carried in control subjects, compared with moderate and severe hypoxia in OSAS patients (P<0.05); AA+AC genotype relative to CC with low oxygen levels in subjects significantly reduced. The difference existed in overweight and obese patients, as well as in those aged more than 50 years (P<0.05). AA was still an independent protective factor for hypoxia caused by OSAS (OR=0.385, 95%CI = 0.210-0.704, P=0.002). Male (OR=1.635, 95% CI=1.037-2.577, P=0.034) and total cholesterol (OR=1.600, 95% CI=1.287-1.987, P<0.001) were independent risk factors associated with hypoxia. Normal weight(OR=0.059, 95% CI=0.037-0.094, P<0.001) and high density lipoprotein cholesterol (OR=0.337, 95% CI=0.171-0.666, P=0.002)were independent protective factors for hypoxia. The levels of monocyte chemoattractant protein-1 and C-reaction protein above CC were significantly higher than AA+AC (P<0.05). CONCLUSION: Hypoxia caused by OSAS is associated with GLUT4 gene SNP rs5417.

[Association of interleukin-1ß genetic polymorphisms with obstructive sleep apnea syndrome].

OBJECTIVE: To investigate the association between interleukin (IL)-1ß genetic polymorphisms and obstructive sleep apnea syndrome (OSAS). METHODS: Totally 850 individuals with hypertension were included. All of them were checked by polysomnography in the Hypertension Center of People's Hospital of Xinjiang Uygur Autonomous Region from January to December in 2010. According to the results of polysomnography, these subjects were divided into non-OSAS group (n=225)and OSAS group (n=625). Genetic variations were sequenced and screened at loci over functional region of IL-1ß gene in 96 patients with severe OSAS.The typical loci were selected for genotyping by TaqMan-polymerase chain reaction in 850 subjects. RESULTS: One novel and 5 known variations in the IL-1ß gene were identified, and then three representative mutation loci were selected for genotyping.The allele frequency distribution of rs1143633 was significantly different between the OSAS and non-OSAS groups in the total and male populations (χ(2)=9.258, P=0.002;χ(2)=5.119, P=0.024, respectively). Although the parameters of sleep apnea monitoring showed no significant difference in individuals with CC, CT, and TT genotypes of rs1143633 in total, male, and female populations (P>0.05), the median of the apnea hypopnea index of CT genotype was significantly higher than that of CC and TT in total and male populations and the mean of the lowest blood oxygen saturation increased in individuals with CC, CT, and TT genotypes of rs1143633 in total and male populations.Haplotype was no significantly associated with OSAS in total,male,and female populations(P>0.05).Logistic regression analysis showed that CT genotype of rs1143633 variation was a risk factor for OSAS in total and male populations (OR=1.574,95% CI=1.061-2.437,P=0.042;OR=1.887,95% CI=1.091- 3.265,P=0.023). CONCLUSION: The rs1143633 polymorphism in IL-1ß gene may be associated with OSAS.

[Etiology analysis for hospitalized hypertensive patients: 10 years report from the department of hypertension (1999 - 2008)].

OBJECTIVE: To analyze etiology of hospitalized hypertensive patients in the department of hypertension from 1999 to 2008. METHODS: This retrospective study was performed to analyze the etiology of hospitalized hypertensive patients in department of hypertension and to show the distribution change of hypertension from 1999 to 2008. RESULTS: (1) There were 5867 (75.1%) patients with essential hypertension and 1942 (24.9%) patients with secondary hypertension (SH). (2) The prevalence rate of SH increased significantly during the 10 years (χ(2) = 387.621, P < 0.001) and was higher in 2008 than in 1999 (39.3% vs. 9.5%, P < 0.05). The prevalence of obstructive sleep apnea syndrome (OSAS) and primary aldosteronism (PA) in 2008 increased 38.3 and 1.8 times respectively than in 1999 (χ(2) = 304.025, P < 0.001; χ(2) = 42.845, P < 0.001) and other SH remained unchanged. (3) The prevalence of PA complicated with OSAS increased significantly in recent five years (χ(2) = 26.376, P < 0.001). Incidence of OSAS was 23.9% in PA patients and incidence of PA was 6.7% in OSAS patients. CONCLUSIONS: With the insights gained on hypertension mechanism and the development of new diagnostic technology, percent of diagnosed SH increased remarkably in recent years in hospitalized hypertensive patients in our department of hypertension. OSAS and PA are the leading causes of SH.

Detection of Secondary Causes and Coexisting Diseases in Hypertensive Patients: OSA and PA Are the Common Causes Associated with Hypertension.

BACKGROUND: Since the control rate of blood pressure is lower in mainland China, the aim of this study is to investigate the proportion of secondary causes and coexisting diseases of hypertension in hypertensive patients. METHODS: Data on consecutive patients with hypertension who visited the Hypertension Center. Diseases were detected using an established strict screening protocol. RESULTS: Detection rate of secondary causes and coexisting diseases of hypertension was 39.5% among 3003 hypertensive patients. Obstructive sleep apnea (OSA) was the most common, accounting for 24.7% of patients, followed by primary aldosteronism (PA) (5.8%) and PA + OSA (4.9%). Endocrine hypertension accounted for 12.1% of patients, including 10.7% of patients with PA, 1.1% with hypothyroidism, 0.1% with pheochromocytoma, 0.1% with Cushing's syndrome, and 0.1% with hyperthyroidism, respectively. Those who smoke, those who are obese, and those who have diabetes accounted for 31.3%, 27.5%, and 16.6% of total patients, respectively. There were overlapping conditions in secondary causes and coexisting diseases of hypertension. OSA was the most common in each age- and BMI-stratified group. CONCLUSION: Findings from the current study suggest an increasing frequency of secondary forms of hypertension, highlighting the burden of OSA and PA in hypertensive patients.

Plasma aldosterone concentration is positively associated with pulse pressure in patients with primary hypertension.

Increasing evidence showed a link between arterial elasticity and stiffness and pulse pressure (PP), in which plasma aldosterone may play a role. The observational study aimed to explore the potential relations between plasma aldosterone concentration (PAC) and PP in patients with hypertension. We evaluated the relation between PP and PAC in supine, seated, and upright positions in 195 patients with primary hypertension who underwent postural stimulation test. They were divided into 3 groups by tertiles of PP: PP ≤ 44 mm Hg (n = 70), 44 mm Hg < PP ≤ 51 mm Hg (n = 63), and PP ≥ 51 mm Hg (n = 62). The PAC in different postures was compared, respectively. The results showed the following. First, segregated by tertiles of PP, serum K⁺, 24-hour systolic blood pressure, 24-hour diastolic blood pressure, sex, upright PAC, and seated PAC showed statistically significant differences in groups. Second, the PAC were significantly different in 3 levels of PP regardless of postures, the individuals with PP ≥ 51 mm Hg had the highest PAC. On contrast, the patients with PAC > 12 ng/dL showed greater PP than those with PAC ≤ 12 ng/dL. Third, weak associations between PP and upright (r = 0.288, P < 0.001), seated (r = 0.265, P < 0.001), and supine postures (r = 0.191, P = 0.008) were detected by simple correlation analysis. After corrected serum K⁺, age, and sex, the partial correlation coefficients did not change greatly. Fourth, the logistic regression model was constructed with PP ≥ 40 mm Hg or PP < 40 mm Hg as the dependent variable; the serum K⁺[OR = 0.043, 95% CI: 1.09(1.00-1.12)] and PAC [OR = 0.025, 95%CI: 0.35(0.13-0.88)] were included as significant contributing factors. The results showed that higher PAC was weakly, but significantly, correlated to greater PP regardless of different postures, suggesting that higher PAC may be a risk factor of reduced arterial elasticity in patients with hypertension.