| 1 Objectives1.1 To evaluate the effect of calcium channel blockers on hypertensive patients with obstructive sleep apnea(OSA), and to assess the effect of Chinese medicine on OSA patients, so as to provide evidences for reasonable medicine selection to lower blood pressure and improve OSA for these patients.1.2 To analyze the correlation among blood pressure variability, endothelial function and obstructive sleep apnea in hypertensive patients with and without OSA, and to observe the effect of Qingxuan granule on these patients, so as to provide clinical basis for the diagnosis and treatment of these patients.2 Methods2.1 Methods of systemic reviewThis study includes two systemic reviews, one is to evaluate the effect of calcium channel blockers on hypertensive patients with obstructive sleep apnea(OSA), and the other is to assess the effect of Chinese medicine on OSA. The two systemic reviews are of the same methods:Databases of CNKI,CBM,VIP,MEDLINE,Embase,CDSR,CCTR were searched for all available data till January 2011. RevMan 5 software was used to conduct meta-analysis. GRADE profiler was used to assess the quality of the included trials.2.2 Clinical trial of Qingxuan granuleThis study is a stratified, randomized, doubled-blind, placebo-controlled clinical trial.2.2.1 90 mild and moderate hypertensive patients with Yin deficiency and Yang hyperactivity syndrome were enrolled into the study. Each one received portable sleep monitoring,24hour Ambulatory Blood Pressure monitoring(ABPM), and blood pressure mean values, blood pressure variability(BPV), blood pressure circadian rhythm and obstructive sleep apnea(OSA) were collected and their correlation was analyzed:endothelial function was evaluated by flow-mediated dilation (FMD), also nitric oxide/endothelin-1(NO/ET-1),high-sensitivity C-reactive protein(hs-CRP),and rein-angiotensin-aldosterone system (RAAS) were tested to explore the functional mechanism. Stepwise regression was used to analyze the correlation of OSA,blood pressure and endothelial function.2.2.2 According to the OSA diagnosis, the hypertensive patients were assigned into two subgroups, one with OSA, the other without OSA; and in each subgroup, patients were randomized into treatment group and control group. All of the patients were treated by amlodpine, in addition, Qingxuan granule was given to the treatment group, and placebo was given to the control goup, respectively. After 2months treatment, the difference (D-value) of the blood pressure, endothelial and OSA index between pretreatment and post-treatment were analyzed by covariance analysis in generalized linear model, so as to investigate the treatment effects of Qingxuan granule, and the impacts of OS A on the D-value in these patients.3 Results3.1 Results of systematic review3.1.1 The effect of calcium channel blockers on hypertensive patients with obstructive sleep apnea(OSA), a Meta-analysis.Compared with control group, though not statistically significance, calcium channel blockers shows a tendency to improve systolic pressure(SBP), diastolic pressure(DBP), (P>0.05) Heart rate was significantly lower after the treatment with calcium channel blockers than the control group; and no significant difference was found in total sleep time, sleep efficiency, deep sleep, and REM stage sleep between these two groups (P>0.05). According to GRADE, the quality of all the results was low or very low.3.1.2 The effect of Chinese medicine on OS A patients, a Meta-analysis. Compared with conventional western treatment, the addition of Chinese medicine could significantly improve the OSA patients'total sleep time, hypopnea index(HI), total hypopnea time, the time of desaturation less than 90% (P<0.05). No significant difference was found in improving clinical efficiency, apnea index(AI), the numbers of times of desaturation less than 90%,mean heart rate (P>0.05). According to GRADE, the quality of all the results was low or very low.The results of clinical trials3.2.1 Comparison of blood pressure between hypertensive patients with OSA and without OSA The blood pressure variability and the occurrence of non-dipper hypertension were significantly higher in hypertensive patients with OSA than those without OSA, while night time blood pressure fall rate was significantly lower in patients with OSA than those without OSA. (P<0.05). AHI had positive correlation with night time SBP and 24 hour SBP SD, and negative correlation with night time SBP fall rate (P<0.05)3.2.2 Comparison of endothelial function between hypertensive patients with OSA and those without OSAFMD%,NO,NO/ET were significantly lower in hypertensive patients with OSA than those without OSA, while ET-1,PRA,A ngâ…¡,ALD were significantly higher in patients with OSA than those without OSA (P<0.05); AHI had positive correlation with PRA and Angâ…¡, and negative correlation with NO/ET ratio (P<0.05)3.2.3 Analysis of Qingxuan granule's curative effect on hypertensive patients with and without OSA3.2.3.1 Analysis of curative effect on treatment group and control group for all patients After subtracting the interference from OSA and index'baseline levels, the following indexes' declined more in treatment group than in control group (P(a)<0.05):24hSBP SD,daytime SBP SD,night time SBP SD,24hDBP SD,24hDBP CV,daytime DBP SD,night time DBP SD,heart rate,ET,Angâ…¡; and the following indexes increased more in treatment group than control group (P(a)<0.05):FMD and NO/ET ratio. 3.2.3.2 Impacts of OSA on curative effectAfter filtering out the interference from different treatments and index'baseline levels, the following indexes declined less in patients with OSA than those without OSA:night time SBP,24hSBP SD,daytimeSBP SD,night timeSBP SD,24hDBP SD,24hDBP CV,daytimeDBP SD,night time DBP SD,night time DBP CV,heart rate,hs-CRP,PRA,Angâ…¡,ALD; and the following indexes increased less in patients with OSA than those without OSA:night time SBP fall rate, night time DBP fall rate, FMD,NO,NO/ET ratio.3.2.3.3 Analysis of subgroupIn hypertensive patients with OSA,the following indexes declined more in treatment group than control group:24hSBP SD,24hDBP SD,daytimeSBP SD,daytimeDBP SD,night timeSBP SD,night time DBP SD,Angâ…¡(P<0.05); and the following indexes increased more in treatment group than control group:NO/ET ratio (P<0.05)In hypertensive patients without OSA, the following indexes declined more in treatment group than control group:24hSBP SD,24hDBP CV,daytimeSBP SD,daytimeDBP SD,night time DBP SD,ET-1,hs-CRP,Angâ…¡; and the following indexes increased more in treatment group than control group:FMD,NO/ET ratio (P<0.05)3.2.3.4 Impact of Qingxuan granule on OSANo significant difference was found in OSA' index after taking Qingxuan granule (P>0.05), with the exception that HI decreased and hypopnea improved (P<0.05)4 Conclusions4.1 The result of systematic review suggest that calcium channel blockers is not superior to control group in improving blood pressure level and OSA (P>0.05), while Chinese medicine could improve OSA to a certain extent (P<0.05); a large number of high quality researches are still needed to prove this result.4.2 In hypertensive patients with OSA the blood pressure variability increased, circadian rhythm was out of order; the endothelial relaxing and contracting function, inflammatory reaction, and RAAS were not normal; OSA could also weaken the curative effect of hypotensive drugs on these indexes.4.3 For hypertensive patients, Qingxuan granule could improve the blood pressure variability, promote the recovery of endothelial function, balance the endothelial relaxing and contracting ratio, control the excessive increase of Angâ…¡; also Qingxuan granule could help to decrease the hypopnea index in OSA, and further study is needed to verify this result.
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