Upregulation of peripheral blood mononuclear cells resistin gene expression in severe obstructive sleep apnea and obstructive sleep apnea with coexisting type 2 diabetes mellitus.

PURPOSE: Obstructive sleep apnea (OSA) is characterised by increased systemic inflammation, and is often accompanied with type 2 diabetes mellitus (T2DM) and cardiovascular disease. The aim of this investigation was to evaluate gene expression of resistin, its receptor CAP1 and CD36 as the indicators of the inflammatory changes in PBMCs in relation to the severity of OSA, and the presence of type 2 diabetes mellitus (T2DM) in OSA. METHODS: Severity of OSA was defined by the apnea/hypopnea index (AHI): AHI < 30: mild to moderate OSA (MM-OSA), AHI ≥ 30: severe OSA (S-OSA). Presence of T2DM was captured: OSA with T2DM (OSA + T2DM), OSA without T2DM (OSA-T2DM). PBMC resistin, CAP1, and CD36 mRNA were determined by real-time PCR. RESULTS: Resistin mRNA was significantly upregulated in S-OSA (N = 54) compared to the MM-OSA (N = 52, P = 0.043); CAP1 and CD36 mRNA levels did not differ between the groups (P = 0.302; P = 0.166, respectively). Resistin mRNA was significantly upregulated in OSA + T2DM (N = 29) compared to the OSA-T2DM (N = 77, P = 0.029); CAP1 and CD36 mRNA levels did not differ between the groups (P = 0.662; P = 0.108, respectively). AHI and T2DM were independent predictors of resistin mRNA above the 75th percentile (OR = 3.717 [1.152-11.991]; OR = 3.261 [1.000-10.630], P = 0.042 respectively). CONCLUSION: Resistin gene upregulation in S-OSA indicates its possible contribution to increased inflammation in S-OSA and makes it a possible marker of the disease severity. Resistin gene upregulation in OSA + T2DM suggests that a joint effect of these two comorbidities may have a major contribution to increased inflammation and complications that arise from this state.

Alterations of cholesterol synthesis and absorption in obstructive sleep apnea: Influence of obesity and disease severity.

BACKGROUND AND AIMS: Obstructive sleep apnea (OSA) is closely linked to obesity and related adverse metabolic changes, including dyslipidemia. However, it is not clear whether OSA is an independent contributing factor to dyslipidemia, or the observed association is a reflection of a concomitant presence of obesity. Additionally, dyslipidemia is usually evaluated through measurement of parameters of routine lipid status, while more precise evaluation of lipid homeostasis is rarely performed in OSA. In this study, we analyzed markers of cholesterol synthesis and absorption in patients with OSA with respect to the presence of obesity and the disease severity. METHODS AND RESULTS: This study enrolled 116 OSA patients. Concentrations of non-cholesterol sterols (NCS), measured by LC-MS/MS, were used as markers of cholesterol synthesis and absorption. Apnea-hypopnea index (AHI) and oxygen saturation (SaO2) were utilized as markers of OSA severity. Serum lipid status parameters were determined by routine enzymatic methods. Markers of cholesterol synthesis were increased (P = 0.005), whilst markers of cholesterol absorption decreased (P = 0.001) in obese OSA patients. Cholesterol synthesis/absorption ratio was elevated in obese subjects (P < 0.001). Concentration of cholesterol synthesis marker lathosterol was significantly higher in subjects with severe OSA (P = 0.014) and we observed a trend of decreased cholesterol absorption in these patients. AHI was revealed as an independent determinant of lathosterol concentration (P = 0.022). CONCLUSIONS: Our results suggest that the presence of obesity and severe forms of OSA is characterized by elevated endogenous cholesterol synthesis. AHI was singled out as an independent determinant of the serum level of cholesterol synthesis marker lathosterol.

Effects of Apnea, Obesity, and Statin Therapy on Proprotein Convertase Subtilisin/Kexin 9 Levels in Patients with Obstructive Sleep Apnea.

OBJECTIVES: Obstructive sleep apnea (OSA) is a common condition closely related to obesity, insulin resistance, dyslipidemia, and cardiovascular disease. The aim of this study was to explore the possible relationship between OSA and proprotein convertase subtilisin/kexin type 9 (PCSK9). METHODS: Full-night polysomnography was performed on 150 participants who were divided into three groups: controls, OSA patients on statin therapy, and OSA patients not on statin therapy. Biochemical markers, plasma low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subclasses, and PCSK9 were determined. RESULTS: PCSK9 was highest in OSA patients on statins compared to the control group and to OSA patients not on statins (p = 0.036 and p = 0.039, respectively), after adjustment for body mass index (BMI). LDL diameter was greater in OSA patients not on statins compared to OSA patients on statins (p = 0.032). PCSK9 was highest in the group of patients with all three risk factors (diagnosed OSA, statins, BMI ≥25 kg/m2) compared to groups with no, one, and two risk factors (p = 0.031, p = 0.001, and p = 0.029, respectively). Presence of OSA, statin therapy, and BMI ≥25 kg/m2 when combined were independently associated with higher levels of PCSK9 when adjusted for antihypertensive therapy, small dense LDL, and HDL 3c subclass (odds ratio = 2.849; interquartile range [1.026-7.912], p = 0.044). CONCLUSION: Statin therapy was closely related to PCSK9. OSA along with obesity and statin use induces elevation of PCSK9.

Early left ventricular systolic and diastolic dysfunction in patients with newly diagnosed obstructive sleep apnoea and normal left ventricular ejection fraction.

UNLABELLED: The aim of the study was to evaluate whether obstructive sleep apnea (OSA) contributes directly to left ventricular (LV) diastolic and regional systolic dysfunction in newly diagnosed OSA with normal left ventricle ejection fraction. METHODS: 125 consecutive patients were prospectively enrolled in the study. Control group consisted of 78 asymptomatic age-matched healthy subjects who did not have any cardiovascular and respiratory diseases. All patients had undergone overnight polysomnography and standard transthoracic and tissue Doppler imaging echocardiogram. RESULTS: The E/A ratio and the peak E wave at mitral flow were significantly lower and the peak A wave at mitral flow was significantly higher in OSA patients compared with control subjects. Left ventricle isovolumetric relaxation time (IVRT) and mitral valve flow propagation (MVFP) were significantly longer in OSA patients than in controls. Tissue Doppler derived S' amplitude of lateral part at mitral valve (S'Lm) and E' wave amplitudes both at the lateral (E'Lm) and septal parts of the mitral valve (E'Sm) were significantly lower in OSA patients compared to controls. CONCLUSION: Newly diagnosed OSA patients with normal global LV function have significantly impaired diastolic function and regional longitudinal systolic function. OSA is independently associated with these changes in LV function.

Lung hamartoma--diagnosis and treatment.

Pulmonary hamartoma, the most common benign tumor of the lung, is most often presented as a solitary pulmonary nodule of a peripheral localization. We report a case of a large, centrally located, invisible in chest X-ray, hystopathologicaly (PH) verified hamartoma. A 63-year-old male was admitted for hospital treatment with obvious symptoms and signs of right-sided lobar pneumonia. His treatment was started with a combination of antibiotics Ceftriaxone and Ciprofloxacin. Because of his obviously bad condition with wheezing and bronchial secret in his lungs, an urgent bronchoscopy was performed. A huge amount of bronchial secret was found in his bronchial tree and, surprisingly, a tumor in the upper left lobe. For further evaluation computed tomography (CT) scan was performed and it verified right pneumonia but, it also revealed large (13.3 x 11.2 mm) endobronchial tumor in upper left lobe which wasn't clinically or radiographically presented. From a bronchobiopsy, we received an inconclusive PH finding. It was concluded that the best treatment is a surgical sleeve resection lobectomy, which was performed. Definite pathohistological finding was hamartoma and the patient was successfully healed.