Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a complex chronic inflammatory respiratory disease with multiple pathogenic factors and high morbidity and mortality. Serum levels of nuclear factor-κB (NF-κB), hypoxia-inducible factor-1 alpha (HIF-1α), and surfactant protein D (SPD) were investigated in OSAHS patients, to determine their clinical significance and correlation with the pathogenesis. Patients were classified into a mild and moderate OSAHS group (n = 25) and severe OSAHS group (n = 33). Twenty healthy patients served as a control group. Peripheral blood levels of NF-κB, HIF-1α, and SPD were determined by Western blot, and a correlation analysis was performed. Severe OSAHS patients received nasal continuous positive airway pressure (nCPAP) therapy and were followed up after 2 months. NF-κB p65, HIF-1α, and SPD expression levels were determined after valid nCPAP therapy. NF-κB p65 and HIF-1α expression was significantly higher in severe OSAHS group than in the other two groups (p < 0.01), and was positively correlated with the apnea-hypopnea index (AHI) (r = 0.696, p < 0.001; r = 0.634, p < 0.001). SPD expression was significantly lower in severe OSAHS group than in the control group (p < 0.01) and mild and moderate OSAHS group (p < 0.01), and was negatively correlated with AHI (r = -0.569, p < 0.001). OSAHS pathogenesis was associated with changes in NF-κB, HIF-1α, and SPD protein expression levels. nCPAP therapy could improve the clinical characteristics of the patients, lower serum NF-κB and HIF-1α levels, and increase serum SPD levels. We conclude that OSAHS is related to the expression of NF-κB, HIF-1, and SPD.
BackgroundChinese Uygur, Kazakh, Mongolian and Han populations represent >90% of the total population of Xinjiang Uygur Autonomous Region, and their genetic backgrounds, customs, culture, and food consumption are different. The effect of ethnic differences on cardiovascular disease risk factors (CRFs; hypertension, obesity, diabetes, dyslipidemia, smoking) can be striking but is rarely studied. We report here the findings of the relationship among these ethnic groups and their CRFs across the four largest ethnic groups of Xinjiang.MethodsA cross-sectional survey of representative samples was conducted 2002–2008 in Chinese Uygur, Kazakh, Mongolian and Han populations (age >30 years; 4,421 Kazakh, 3884 Han, 3,218 Uygur, and 892 Mongolian individuals) in Xinjiang.ResultsA total of 90.4% of Kazakh, 91.9% of Uygur, 90.4% of Mongolian, 85.1% of Han individuals had at least one CRF. Clustering of ≥2 or ≥3 of these risk factors was noted in 65.2% or 32.1% of Kazakh, 64.8% or 33.0% of Uygur, 66.9% or 36.5% of Mongolian as well as 62.0% or 28.3% of Han subjects, respectively. Compared with the Han population, the adjusted odds ratios of ≥1, ≥2, and ≥3 CRFs for Kazakh, Uygur and Mongolian populations were higher (all P<0.001). The age-standardized prevalence of the clustering of ≥1, ≥2, and ≥3 CRFs in Kazakh, Uygur, Mongolian, and Han populations was lower than their counterparts in the NHANES Ш study (USA) but higher than in the InterASIA Study (China).ConclusionsEthnic groups living in Xinjiang had striking differences in CRFs. Ethnic-specific strategies should be developed to prevent cardiovascular disease in different ethnic groups.
BackgroundHypertension is a complex disease influenced by multiple genetic and environmental factors. The Kazakh ethnic group is characterized by a relatively high prevalence of hypertension. Previous research indicates that the FURIN gene may play a pivotal role in the renin-angiotensin system and maintaining the sodium-electrolyte balance. Because these systems influence blood pressure regulation, we considered FURIN as a candidate gene for hypertension. The purpose of this study was to systematically investigate the association between genetic variations in the FURIN gene and essential hypertension in a Xinjiang Kazakh population.MethodsWe sequenced all exons and the promoter regions of the FURIN gene in 94 hypertensive individuals to identify genetic variations associated with the disorder. Genotyping was performed using the TaqMan polymerase chain reaction method for four representative common single nucleotide polymorphisms (SNPs, -7315C > T, 1970C > G, 5604C > G, 6262C > T) in 934 Kazakh Chinese people. One SNP (1970C > G) was replicated in 1,219 Uygur Chinese people.ResultsNine novel and seven known single nucleotide polymorphisms were identified in the FURIN gene. The results suggest that 1970C > G was associated with a hypertension phenotype in Kazakh Chinese (additive model, P = 0.091; dominant model, P = 0.031, allele model, P = 0.030), and after adjustment with logistic regression analysis, ORs were 1.451 (95%CI 1.106-1.905, P = 0.008) and 1.496 (95% 1.103-2.028, P = 0.01) in additive and dominant models, respectively. In addition, the association between 1970C > G and hypertension was replicated in Uygur subjects (additive model, P = 0.042; dominant model, P = 0.102; allele model, P = 0.027) after adjustment in additive and dominant models, ORs were 1.327 (95% 1.07-1.646), P = 0.01 and 1.307 (95%CI 1.015-1.681, P = 0.038), respectively. G allele carriers exhibited significant lower urinary Na+ excretion rate than non-carriers in the Kazakh Chinese population (152.45 ± 76.04 uM/min vs 173.33 ± 90.02 uM/min, P = 0.007).ConclusionOur results suggest that the FURIN gene may be a candidate gene involved in human hypertension, and that the G allele of 1970C > G may be a modest risk factor for hypertension in Xinjiang Kazakh and Uygur populations.
BackgroundEven through narrowing of the upper-airway plays an important role in the generation of obstructive sleep apnea (OSA), the peripheral airways is implicated in pre-obese and obese OSA patients, as a result of decreased lung volume and increased lung elastic recoil pressure, which, in turn, may aggravate upper-airway collapsibility.MethodsA total of 263 male (n = 193) and female (n = 70) subjects who were obese to various degrees without a history of lung diseases and an expiratory flow limitation, but troubled with snoring or suspicion of OSA were included in this cross-sectional study. According to nocturnal-polysomnography the subjects were distributed into OSA and non-OSA groups, and were further sub-grouped by gender because of differences between males and females, in term of, lung volume size, airway resistance, and the prevalence of OSA among genders. Lung volume and respiratory mechanical properties at different-frequencies were evaluated by plethysmograph and an impulse oscillation system, respectively.ResultsFunctional residual capacity (FRC) and expiratory reserve volume were significantly decreased in the OSA group compared to the non-OSA group among males and females. As weight and BMI in males in the OSA group were greater than in the non-OSA group (90 ± 14.8 kg vs. 82 ± 10.4 kg, p < 0.001; 30.5 ± 4.2 kg/m2 vs. 28.0 ± 3.0 kg/m2, p < 0.001), multiple regression analysis was required to adjust for BMI or weight and demonstrated that these lung volumes decreases were independent from BMI and associated with the severity of OSA. This result was further confirmed by the female cohort. Significant increases in total respiratory resistance and decreases in respiratory conductance (Grs) were observed with increasing severity of OSA, as defined by the apnea-hypopnea index (AHI) in both genders. The specific Grs (sGrs) stayed relatively constant between the two groups in woman, and there was only a weak association between AHI and sGrs among man. Multiple-stepwise-regression showed that reactance at 5 Hz was highly correlated with AHI in males and females or hypopnea index in females, independently-highly correlated with peripheral-airway resistance and significantly associated with decreasing FRC.ConclusionsTotal respiratory resistance and peripheral airway resistance significantly increase, and its inverse Grs decrease, in obese patients with OSA in comparison with those without OSA, and are independently associated with OSA severity. These results might be attributed to the abnormally increased lung elasticity recoil pressure on exhalation, due to increase in lung elasticity and decreased lung volume in obese OSA.Electronic supplementary materialThe online version of this article (doi:10.1186/s12890-015-0063-6) contains supplementary material, which is available to authorized users.
Objective— We aimed to examine whether baseline homocysteine (Hcy) concentrations affect antihypertensive responses to enalapril treatment among previously untreated hypertensive patients (n=10 783) in the CSPPT (China Stroke Primary Prevention Trial). Approach and Results— After a 3-week run-in treatment with a daily dose of 10 mg enalapril, eligible hypertensive patients were randomly assigned to a double-blind daily treatment of a tablet of either enalapril (10 mg) and folic acid (0.8 mg) or enalapril (10 mg) alone for a median of 4.5 years. After the 3-week treatment period with enalapril alone, the systolic blood pressure–lowering effect was significantly reduced by 1.39 (95% confidence interval 0.40–2.37) and 3.25 (95% confidence interval 1.98–4.52) mm Hg, respectively, in those with baseline Hcy concentrations of 10 to 15 and ≥15 μmol/L ( P for trend <0.001) as compared with those with Hcy concentration of <10 μmol/L. Similar results were observed after a 15-week treatment period with enalapril alone. After a median 4.5-year enalapril-based antihypertensive treatment period, compared with those with Hcy concentration of <10 μmol/L, the systolic blood pressure–lowering effect was still significantly reduced by 0.77 (95% confidence interval 0.01–1.53) and 1.70 (95% confidence interval 0.72–2.68) mm Hg, respectively, in those with Hcy concentrations of 10 to 15 and ≥15 μmol/L ( P for trend <0.001). In addition, participants with higher baseline Hcy concentrations had persistently higher systolic blood pressure levels across the entire study treatment period. Similarly, baseline Hcy concentrations were inversely associated with diastolic blood pressure reduction during the short-term enalapril alone treatment. However, the inverse association between baseline Hcy and diastolic blood pressure reduction was attenuated and became insignificant after the long-term enalapril-based treatment period. Conclusions— Elevated Hcy concentrations significantly decreased the antihypertensive effect of the short-term and long-term enalapril-based antihypertensive treatment in previously untreated hypertensive patients.
BackgroundThe prevalence of population-wide hypertension, obesity and dyslipidemia has not been well studied in the pasture area of Xinjiang. The present epidemiological study was performed to determine the prevalence of hypertension, obesity and dyslipidemia in minority populations from the pasture area of Xinjiang and to discuss the potential risk factors for hypertension.MethodsA population-based, cross-sectional study in the Xinjiang pasture area was performed which included 2251 participants aged over 30 years (90.33% participation rate) of whom 71.26% were Kazaks. Several risk factors were considered: hypertension (defined as systolic or diastolic blood pressure or both of at least 140/90 mmHg measured on one occasion or treatment for hypertension) overweight/obesity (body mass index ≥ 25 kg/m2) alcohol intake, smoking/tobacco use and dyslipidemia. Outcomes were prevalence of hypertension, obesity and dyslipidemia and the associated risk factors of hypertension detected by multivariate logistic regression analysis taking into account various metabolic and lifestyle characteristics.ResultsThe prevalence of hypertension, overweight/obesity and dyslipidemia in all participants from the pasture area of Xinjiang was 51.9%, 47.9% and 49.2% respectively. Independently, the prevalence and awareness of hypertension was 52.6% and 15.3% among Kazaks (n = 1604), 54.6% and 14.1% among Uygurs (n = 418), 39.5% and 16.1% among Mongolians (n = 81) and 43.9% and 18.2% among non-Xinjiang-born Han immigrants (n = 148). The prevalence of overweight/obesity in Kazaks, Uygurs, Mongolians and Han immigrants was 46.7%, 48.9%, 62.5% and 50.3%, respectively. The prevalence of dyslipidemia in the four ethnic groups mentioned was 53.5%, 34.8%, 49.3% and 47.3%, respectively. The mean blood pressure in all participants was 136/86 mmHg (pre-hypertensive), the mean BMI was 24.7 kg/m2. Based on multiple logistic regression analysis, the significant risk factors for hypertension were age [1.07(1.06-1.09), P < 0.0001], overweight/obesity [overweight: 1.61(1.22-2.13), p = 0.0007; obesity: 1.95 (1.33-2.87), p = 0.0007], hypercholesterolemia [1.30(1.15-1.47), p < 0.0001] and an alcohol intake of over 30 g/day [2.22(1.43-3.45), p = 0.0004].ConclusionsThe considerably high prevalence of hypertension, overweight/obesity and dyslipidemia among the minority population aged over 30 from the pasture area of Xinjiang calls for effective preventive measures. Age, increased body mass index, hypercholesterolemia and ≥30 g/d alcohol intake can be counted as risk factors for hypertension, but further genetic or environmental clarification would be desirable to explain the unusually high prevalence of the conditions mentioned above.
IntroductionMasked uncontrolled hypertension (MUCH) carries an increased risk of cardiovascular (CV) complications and can be identified through combined use of office (O) and ambulatory (A) blood pressure (BP) monitoring (M) in treated patients. However, it is still debated whether the information carried by ABPM should be considered for MUCH management. Aim of the MASked-unconTrolled hypERtension management based on OBP or on ambulatory blood pressure measurement (MASTER) Study is to assess the impact on outcome of MUCH management based on OBPM or ABPM.Methods and analysisMASTER is a 4-year prospective, randomised, open-label, blinded-endpoint investigation. A total of 1240 treated hypertensive patients from about 40 secondary care clinical centres worldwide will be included -upon confirming presence of MUCH (repeated on treatment OBP <140/90 mm Hg, and at least one of the following: daytime ABP ≥135/85 mm Hg; night-time ABP ≥120/70 mm Hg; 24 hour ABP ≥130/80 mm Hg), and will be randomised to a management strategy based on OBPM (group 1) or on ABPM (group 2). Patients in group 1 will have OBP measured at 0, 3, 6, 12, 18, 24, 30, 36, 42 and 48 months and taken as a guide for treatment; ABPM will be performed at randomisation and at 12, 24, 36 and 48 months but will not be used to take treatment decisions. Patients randomised to group 2 will have ABPM performed at randomisation and all scheduled visits as a guide to antihypertensive treatment. The effects of MUCH management strategy based on ABPM or on OBPM on CV and renal intermediate outcomes (changing left ventricular mass and microalbuminuria, coprimary outcomes) at 1 year and on CV events at 4 years and on changes in BP-related variables will be assessed.Ethics and disseminationMASTER study protocol has received approval by the ethical review board of Istituto Auxologico Italiano. The procedures set out in this protocol are in accordance with principles of Declaration of Helsinki and Good Clinical Practice guidelines. Results will be published in accordance with the CONSORT statement in a peer-reviewed scientific journal.Trial registration number NCT02804074; Pre-results.
We aimed to investigate the relationship between the Chinese visceral adiposity index (CVAI) and the risk of new-onset myocardial infarction (MI) in patients with hypertension and obstructive sleep apnoea (OSA) and to inspect possible modifiers of the effect. Methods: The Cox regression model was used to evaluate the relationship between baseline CVAI and risk of new-onset MI. A generalized additive model was used to identify the nonlinear relationship. Besides, we conducted subgroup analyses and interaction tests. Results: A total of 2177 patients with hypertension and OSA undergoing polysomnography were enrolled in this study. During a median follow-up period of 87 months, 82 participants developed new-onset MI. Overall, CVAI was positively related to the risk of new-onset MI (per 1 SD increase; HR = 1.54, 95% CI: 1.28-1.85). In multivariable-adjusted models, the risk of new-onset MI increased with quartiles of CVAI, with an HR of 3.64 (95% CI: 1.94-6.83) for quartile 4 compared with quartile 1. The generalized additive model and smoothed curve fit revealed a nonlinear relationship between CVAI and risk of new-onset MI with an inflection point of approximately 112. None of the stratification variables had a significant effect on the relationship between CVAI and newonset MI. Similar outcomes were observed in the sensitivity analysis. The addition of CVAI significantly improved reclassification and discrimination over the conventional model, with a category-free NRI of 0.132 (95% CI 0.021 to 0.236, P = 0.021) and an IDI of 0.012 (95% CI 0.005 to 0.023, P < 0.001). Conclusion:This study demonstrated a nonlinear relationship between CVAI and the risk of new-onset MI in patients with hypertension and OSA. Higher CVAI was significantly associated with the risk of new-onset MI when CVAI was ≥112.
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