卡托普利对高血压患者颈动脉粥样硬化的消退作用

目的:探讨卡托普利对高血压患者颈动脉粥样硬化(AS)的逆转作用。方法:将70例经彩色多普勒超声证实有颈AS的高血压患者随机均分为治疗组和对照组,治疗组35例在对照组常规治疗基础上服用卡托普利12．5 mg,tid,治疗6个月及12个月经彩色多普勒超声测定颈动脉内膜中膜厚度(IMT)、斑块病变类型、血管内径及血流参数,并与治疗前对比。结果:①2组患者血脂水平治疗前后无明显改变。②治疗组中Ⅰ型患者治疗后12个月从治疗前的57．14％减少到20％(P<0．05),而对照组无明显改变;治疗组患者治疗前后相比,或与同期对照组比较差异有统计学意义(P<0．05),2组Ⅱ-Ⅳ型患者治疗前后均无明显改变。③治疗组治疗后1MT 降低,血管内径增加;且随疗程延长,效果更明显,而对照组却无相应变化。④治疗组治疗后颈总动脉、颈内动脉的血管阻力指数均较治疗前明显降低,收缩期峰速度、舒张期末速度和血管搏动指数则较治疗前呈显著性增加, 且随疗程延长,有进一步降低或增加趋势,但对照组却无类似变化。结论:卡托普利可减轻血管IMT,改善血管的顺应性,降低血管阻力,改善颈动脉血流,随着治疗时间延长其效应更为显著。     

复方替米沙坦对单药控制不良高血压患者的有效性和安全性

目的 评价复方替米沙坦在替米沙坦单药治疗无充分反应时中国高血压患者中的有效性和安全性.方法 多中心、随机、双盲、双模拟临床试验.经1周安慰剂筛选期,699例符合入选标准的轻、中度高血压患者进入80 mg替米沙坦单药开放治疗期.345例对替米沙坦单药开放治疗8周无充分反应[平均坐位舒张压≥90 mm Hg(1 mm Hg=0.133 kPa)]的患者进入为期8周的随机双盲治疗期.175例患者进入复方替米沙坦治疗组(80 mg替米沙坦加12.5 mg氢氯噻嗪),170例进入80 mg替米沙坦单药治疗组.每次随访测量坐位和立位的收缩压和舒张压谷值,记录不良事件.筛选期以及开放和随机双盲治疗期结束时进行实验室和心电图检查.结果 (1)与开放治疗期结束(基线)比较,随机双盲治疗8周后,复方替米沙坦组坐位舒张压谷值平均下降10.1 mm Hg,替米沙坦单药组平均下降7.7 mm Hg,两组间比较P=0.0017.复方替米沙坦组坐位收缩压谷值平均下降14.2 mm Hg,替米沙坦单药组平均下降7.4 mm Hg,两组间比较P＜0.0001.(2)与基线比较,随机双盲治疗8周后,复方替米沙坦组立位舒张压和收缩压谷值平均下降幅度大于替米沙坦单药组,两组间比较P=0.0350和P＜0.0001.(3)按照平均坐位舒张压谷值＜90 mm Hg和(或)与基线值相比降低≥10 mm Hg评价,随机双盲治疗8周后,复方替米沙坦组有效率为74.6%(129例患者),替米沙坦单药组为59.2%(100例患者),两组间比较P=0.0016.(4)在随机双盲期,两组与试验药物有关的不良事件发生率分别为3.5%和3.6%,两组间比较P＞0.05.结论 替米沙坦单药治疗无充分反应的中国高血压患者,复方替米沙坦每日口服一次能够进一步降低血压,且安全性良好.     

Additive beneficial cardiovascular and metabolic effects of combination therapy with ramipril and candesartan in hypertensive patients.

AIMS: Ramipril and candesartan have distinct mechanisms of action to improve endothelial function. Therefore, we hypothesized that combination therapy has additive beneficial effects to simultaneously improve endothelial dysfunction and adipocytokine profiles in patients with hypertension. METHODS AND RESULTS: Thirty-four patients were given ramipril 10 mg and placebo, ramipril 10 mg and candesartan 16 mg, or candesartan 16 mg and placebo daily in a randomized, double-blind, placebo-controlled cross-over trial with three treatment arms and two washout periods (each 2 months). Ramipril, candesartan, or combination therapy reduced blood pressure, improved flow-mediated dilation, and increased plasma adiponectin levels when compared with baseline values. However, combination therapy improved these outcome measures to a greater extent than either ramipril or candesartan alone (P < 0.001 and P = 0.016 for systolic and diastolic blood pressure, P < 0.001 and P = 0.048 for flow-mediated dilation and adiponectin levels by ANOVA). In addition, combination therapy reduced plasma leptin levels to a greater extent than either ramipril or candesartan alone (P = 0.042 by ANOVA). There were correlations between percent changes in adiponectin levels and percent changes in insulin sensitivity (determined by QUICKI) (r = 0.319, P = 0.066) following ramipril therapy, percent changes in QUICKI (r = 0.374, P = 0.029) following combination therapy, and percent changes in QUICKI (r = 0.607, P < 0.001) following candesartan therapy. CONCLUSION: Ramipril in combination with candesartan improves blood pressure, endothelial function, and adipocytokine profiles to a greater extent than monotherapy with either drug in hypertensive patients.     

Beneficial effect of combination therapy with antihypertensive drugs in patients with hypertension

BACKGROUND: Cardiac hypertrophy and failure are major complications of hypertension. OBJECTIVES: The beneficial effect of treatment with antihypertensive drugs on serum levels of brain natriuretic peptide (BNP) was examined in patients with essential hypertension. METHODS: Antihypertensive drugs were administered to 88 hypertensive patients (44 diabetic and 44 nondiabetic) whose systolic blood pressure was greater than 140 mmHg and/or diastolic blood pressure was greater than 90 mmHg. Other antihypertensive drugs were added every two months until the blood pressure fell below 130/85 mmHg. Candesartan, benidipine, bisoprolol or celiprolol, and bunazosin were administered in this order. RESULTS: The mean systolic blood pressure was reduced from 163.7+/-11.6 mmHg to 121.8+/-7.5 mmHg after 12 months in patients with diabetes and from 167.6+/-12.3 mmHg to 122.8+/-7.5 mmHg in patients without diabetes. The mean diastolic blood pressure was also significantly reduced in patients with and without diabetes. Serum BNP levels were reduced from 52.2+/-38.8 pg/mL to 38.8+/-30.9 pg/mL in patients with diabetes and from 47.1+/-34.2 pg/mL to 35.8+/-22.5 pg/mL in patients without diabetes. In patients older than 70 years of age, serum BNP levels were reduced from 56.3+/-39.3 pg/mL to 40.2+/-23.0 pg/mL in those with diabetes and from 54.6+/-32.9 pg/mL to 38.0+/-16.0 pg/mL in those without diabetes. CONCLUSIONS: These results indicate that combination therapy with antihypertensive drugs is usually necessary to reduce blood pressure to below 130/85 mmHg and to improve serum BNP levels.     

缬沙坦联合胺碘酮对持续性心房颤动复律及复律后窦性心律维持率的影响

目的观察缬沙坦联合胺碘酮对持续性心房颤动复律及复律后窦性心律维持率的影响。方法选择持续性心房颤动患者96例,随机分为两组,治疗组49例,给予缬沙坦及胺碘酮治疗,对照组47例给予安慰剂及胺碘酮治疗。随访1年,观察两组心房颤动转复率和转复后3、12个月时心房颤动复发率,以及转复时及转复后12个月左心房内径（LAD）、左心室射血分数（LVEF）变化。结果心房颤动转复率治疗组（87．8％）与对照组（85．1％）差异无统计学意义（P〉0．05）。心房颤动复发率转复后3个月及12个月治疗组（14．0％、2312％）均小于对照组（32．5％、54．5％）（P〈0．05或0．01）,转律后12个月LAD治疗组[（44．3±065）mm）]较对照组[（469±0．54）mm]变小（P〈0＋05）,LVEF治疗组[（56．8±8．64）％]较对照组[（52．3±908）％]升高（P〈0．05）。结论缬沙坦联合胺碘酮治疗持续性心房颤动在减少心房颤动的复发率以及改善心功能方面优于单独使用胺碘酮。     

肠源性内毒素血症对慢性乙型肝炎患者调节性T淋巴细胞/辅助性T淋巴细胞17的影响

目的探讨肠源性内毒素血症(IETM)对慢性乙型肝炎(CHB)患者调节性T淋巴细胞(Treg)/辅助性T淋巴细胞(Th)17的影响。方法选取2014年12月-2015年10月在山西医科大学第一医院住院治疗的CHB患者(CHB组)80例,同时选取健康体检者(HC组)20例作为对照。根据内毒素(ET)水平将CHB组分为ET阳性组和ET阴性组。测定外周血单个核细胞中叉头样转录因子(Foxp3)、维甲酸相关孤核受体γt(RORγt)mRNA的表达,Treg和Th17百分比,以及ALT、HBV DNA水平。计量资料两组间比较采用独立样本t检验,多组间比较用单因素方差分析,进一步两两比较采用SNK-q检验,计数资料组间比较采用χ2检验。结果 CHB组Treg、Th17百分比、Foxp3、RORγt相对表达量与HC组比较均明显增高[(6.51±1.18)%vs(5.91±1.29)%,(4.99±1.07)%vs(4.18±0.87)%,2.12±0.83 vs 1.60±0.70,1.56±0.77 vs 1.09±0.59],P值均0.05。ET阳性组Treg、Th17百分比、Foxp3、RORγt相对表达量、Th17/Treg、RORγt/Foxp3、ALT水平与ET阴性组比较均明显增高[(6.75±1.17)%vs(6.21±1.14)%,(5.39±1.03)%vs(4.48±0.91)%,2.29±0.90 vs 1.91±0.70,1.84±0.76 vs 1.23±0.64,0.82±0.19 vs 0.74±0.16,0.95±0.38 vs 0.74±0.54,(220.16±115.82)U/L vs(170.86±99.69)U/L],P值均0.05。ET阳性组HBV DNA载量比ET阴性组增高,但差异无统计学意义(P0.05)。相关分析表明,CHB患者ET水平与Th17、Treg及ALT呈正相关(r值分别为,P值均0.05),而与HBV DNA无相关性。结论 CHB患者体内存在的IETM可能通过调控Foxp3、RORγt mRNA表达增加,导致外周血Treg、Th17百分比升高,进而Treg/Th17比例失衡,使HBV难以清除而导致慢性化。     

Th17/Treg细胞功能轴在抑郁性精神压力诱导老年人动脉粥样硬化中的中介效应

[目的]探讨Th17/Treg细胞功能轴在抑郁性精神压力诱导老年人动脉粥样硬化中的中介效应。[方法] 2018年5月—2019年8月在山东济南地区入选60岁及以上社区老年受试者539例,采用老年抑郁量表(GDS)评估受试者的抑郁性精神压力。依据GDS得分五分位将受试者分为低抑郁压力组(n=349)和高抑郁压力组(n=190)。采用颈总动脉内膜中膜厚度(CCA-IMT)及颈-股动脉脉搏波传导速度(cfPWV)评估动脉粥样硬化和僵硬度。检测受试者高敏C反应蛋白(hs-CRP)及外周血Th17和Treg细胞频率及其效应因子。[结果]与低抑郁压力组比较,高抑郁压力组的CCA-IMT、cfPWV、hs-CRP、Th17细胞频率、白细胞介素17(IL-17)、肿瘤坏死因子α(TNF-α)、IL-6、IL-23、维甲酸相关核孤儿受体(RORγt)mRNA表达及Th17/Treg细胞比率分别升高了24.58%、18.22%、51.59%、44.79%、77.60%、55.94%、61.49%、41.13%、72.11%和150.00%(均P<0.001);Treg细胞频率、IL-10、转化生长因...     

基于miRNA表达谱解析细粒棘球蚴病患者体内Th17/Treg失衡机制

目的　观察细粒棘球蚴病患者血清微小RNA（miRNA）表达水平、探讨miRNA对辅助性T 细胞17（Th17）/调节性T细胞（Treg）失衡的影响,以阐明细粒棘球蚴慢性感染并长期致病的机制。方法　提取细粒棘球蚴病患者与健康对照者血清总RNA,采用Illumina测序平台进行高通量测序。分别采用miRBase数据库和miRDeep2工具进行已知miRNA注释和新miRNA预测,并进行差异分析。采用miRanda软件和TargetScan软件分别预测差异表达miRNA靶基因后取交集,进行基因本体（GO）富集分析以及京都基因和基因组百科全书（KEGG）通路分析。在差异表达变化倍数居前20位的miRNA中,匹配可靶向决定Th17细胞和Treg细胞生成的关键转录因子（RORC和FOXP3）或重要调控通路（PI3K⁃Akt和mTOR通路）相关基因的miRNA。结果　细粒棘球蚴病患者与健康对照血清中共有53个差异表达miRNA,其中47个上调表达miRNA、6个下调表达miRNA。GO富集分析显示,差异表达miRNA功能涉及DNA转录翻译、细胞成分、细胞形态、神经发育及代谢分解等过程。KEGG富集分析显示,这些差异表达miRNA靶基因涉及的主要信号通路包括MAPK、PI3K⁃Akt、mTOR等信号通路。在差异表达变化倍数居前20位的miRNA中,有3个潜在靶向调控RORC的miRNA、15个潜在靶向PI3K⁃Akt、mTOR信号通路的miRNA。结论　细粒棘球蚴感染后可使患者血清miRNA表达谱出现明显改变,差异表达miRNA可能通过靶向Th17/Treg关键转录因子或PI3K⁃Akt、mTOR通路而导致Th17/Treg免疫失衡,进而利于细粒棘球蚴在宿主体内长期寄生并慢性致病。     

Central blood pressure lowering effect of telmisartan‐rosuvastatin single‐pill combination in hypertensive patients combined with dyslipidemia: A pilot study

This multicenter, phase 4, Prospective Randomized Open, Blinded End‐point (PROBE) study aimed to evaluate safety and efficacy of telmisartan/rosuvastatin single‐pill combination (SPC) therapy on lowering central blood pressure (BP) compared with telmisartan monotherapy in hypertensive patients with dyslipidemia in Korea. Study was terminated earlier than planned due to COVID‐19 pandemic, thus should be considered as a pilot study. Among 125 patients who met the inclusion criteria of hypertension and dyslipidemia (defined as 10‐year Atherosclerotic Cardiovascular Disease risk score over 5%), 80 patients went through 4‐week single‐group run‐in period with telmisartan 40–80 mg, then randomized to telmisartan 80 mg + rosuvastatin (10 or 20 mg) SPC group or telmisartan 80 mg monotherapy group. The central/brachial BP, brachial‐ankle pulse wave velocity (baPWV), and augmentation index (AIx) were assessed at baseline and 16 weeks later. Mean brachial SBP changed from 135.80 ± 14.22 mmHg to 130.69 ± 13.23 mmHg in telmisartan/rosuvastatin group and from 134.37 ± 12.50 mmHg to 133.75 ± 12.30 mmHg in telmisartan monotherapy group without significant difference (between‐group difference p = .149). Mean central SBP were reduced significantly in the telmisartan/rosuvastatin group with change from 126.72 ± 14.44 mmHg to 121.56 ± 14.56 mmHg while telmisartan monotherapy group showed no significant change (between‐group difference p = .028). BaPWV changed from 1672.57 ± 371.72 m/s to 1591.75 ± 272.16 m/s in telmisartan/rosuvastatin group and from 1542.85 ± 263.70 m/s to 1586.12 ± 297.45 m/s in telmisartan group with no significance (between‐group difference p = .078). Change of AIx had no significant difference (between‐group difference p = .314). Both groups showed excellent compliance rate of 96.9 ± 4.5% with no significant difference in adverse rate. Telmisartan/rosuvastatin SPC therapy was more effective in lowering central BP compared with the telmisartan monotherapy. The results of this study showed benefit of additive statin therapy in hypertensive patients combined with dyslipidemia.     

Comparison of effects of azelnidipine and trichlormethiazide in combination with olmesartan on blood pressure and metabolic parameters in hypertensive type 2 diabetic patients

Aims/Introduction: Angiotensin II type 1 receptor blockers (ARB) are regarded as first‐line treatment for type 2 diabetes with hypertension. However, lowering blood pressure to the target level often requires more than one antihypertensive agent as recommended by the guideline. In this open‐label, prospective, crossover clinical trial, we compared the effects of combination treatment of ARB with a calcium channel blocker (CCB) or with a low‐dose thiazide diuretic on blood pressure (BP) and various metabolic parameters in hypertensive patients with type 2 diabetes. Materials and Methods: A total of 39 Japanese type 2 diabetics with hypertension treated with olmesartan (20 mg/day) for at least 8 weeks were recruited to this study. At study entry, treatment was switched to either olmesartan (20 mg/day)/azelnidipine (16 mg/day) or olmesartan (20 mg/day)/trichlormethiazide (1 mg/day) and continued for 12 weeks. Then, the drugs were switched and treatment was continued for another 12 weeks. We measured clinical blood pressure and various metabolic parameters before and at the end of each study arm. Results: Compared with the olmesartan/trichlormethiazide treatment, treatment with olmesartan/azelnidipine achieved superior clinical blood pressure and pulse rate control. In contrast, the treatment with olmesartan/trichlormethiazide resulted in increased HbA_1c, serum uric acid and worsening of estimated glomerular filtration rate, though there were no differences in other metabolic parameters including urine 8‐hydroxy‐2′‐deoxyguanosine, C‐reactive protein and adiponectin between the two treatments. Conclusions: Our results show that the combination of ARB with azelnidipine is more beneficial with regard to blood pressure control and metabolic outcome than the combination of olmesartan with low dose trichlormethiazide. This trial was registered with UMIN clinical trial registry (no. UMIN000005064). (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2011.00135.x, 2011)