A randomized controlled trial on ambulatory blood pressure lowering effect of CPAP in patients with obstructive sleep apnea and nocturnal hypertension.

Objective: In a randomised controlled trial, we investigated the blood pressure (BP) lowering effect of continuous positive airway pressure (CPAP) in patients with moderate-severe obstructive sleep apnoea syndrome (OSAS, an apnoea-hypopnoea index, AHI of 15 or higher) and nocturnal hypertension (night-time systolic/diastolic BP ≥120/70 mmHg).Methods: Sixty patients were randomly assigned to CPAP or sham CPAP, while maintaining their antihypertensive treatment. Ambulatory BP monitoring was performed at baseline (first run-in visit) and the end of follow-up. Clinic and home BP were measured at baseline and each of the monthly follow-up visits.Results: Of the 60 patients, 47 completed the 3-month study. CPAP (n = 26), compared with sham CPAP (n = 21), slightly and non-significantly reduced 24-h systolic/diastolic BP by -2.8/-2.5 mmHg (p ≥ 0.27), with a slightly greater between-group difference in the daytime (-4.0/-2.8 mmHg, p ≥ 0.29) than night-time (-0.2/-1.5 mmHg, p ≥ 0.50). The CPAP treatment did not significantly influence clinic or home BP during follow-up (p ≥ 0.27). Nonetheless, simple and partial correlation analyses showed that the ambulatory BP lowering effect was dependent on the daytime pulse rate at baseline (r ≥ 0.47, p ≤ 0.01). In patients with a daytime pulse rate greater than 85 beats/min, the mean changes in daytime systolic BP were significantly greater in the CPAP (n = 10) than sham CPAP group (n = 11), with a between-group mean difference of -10.1 mmHg (p = 0.048).Conclusions: The CPAP treatment did not show significant ambulatory BP lowering effect in patients with moderate-severe OSAS and nocturnal hypertension. However, it may be effective in lowering daytime BP in patients with a faster pulse rate.

Intermittent Hypoxia Disrupts Glucose Homeostasis in Liver Cells in an Insulin-Dependent and Independent Manner.

BACKGROUND/AIMS: Obstructive sleep apnea is associated with diabetes and insulin resistance, but the underlying mechanisms remain unclear. The purpose of the current study was to determine the molecular effects of intermittent hypoxia (IH) on hepatic insulin signaling and glucose homeostasis, and whether c-Jun NH2-terminal-kinase (JNK) contributed to metabolic responses to IH in liver cells. METHODS: The human HepG2 cells and rat FAO cells were exposed to 10, 30, 120, 240 or 360 cycles of IH (1% O2 for 60 s followed by 21% O2 for 60s, 7.5 cycles per hour) or normoxia as a control. In a subgroup, we exposed cells to 360 cycles of IH with the JNK inhibitor SP600125. After IH exposure, cell glycogen content and glucose output were measured using colorimetric assay kits. Canonical insulin signaling and gluconeogenic genes were measured by western blot and quantitative polymerase chain reaction. RESULTS: IH decreased insulin-stimulated protein kinase B (AKT)/glycogen synthase kinase-3ß (GSK-3ß) phosphorylation in a time-dependent manner, while inhibiting forkhead box protein O1 (FOXO1) expression and phosphoenolpyruvate carboxykinase (PEPCK) transcription independent of insulin signaling. JNK inhibitor SP600125 partially restored AKT/ GSK-3ß phosphorylation and glycogen synthesis, but did not affect other IH-induced glucose metabolic changes. CONCLUSION: IH in vitro impaired insulin signal transduction in liver cells as assessed by inhibited AKT/GSK-3ß phosphorylation via JNK activation. IH inhibited FOXO1 and gluconeogenesis in an insulin-independent manner.