糖尿病合并难治性高血压抗AT1受体自身抗体阳性患者缬沙坦靶向治疗疗效研究

目的观察糖尿病合并难治性高血压抗AT1受体自身抗体阳性患者缬沙坦靶向治疗的降压疗效。方法以合成的AT1受体多肽片段为抗原,应用ELISA技术,检测糖尿病合并2级以上高血压患者169例,正常对照组60例。糖尿病合并难治性高血压患者抗AT1受体自身抗体阳性者为治疗组,阴性者为对照组,两组均给予尼群地平、氢氯噻嗪、肠溶阿司匹林、缬沙坦。结果（1）糖尿病合并难治性高血压98例（抗AT1受体自身抗体阳性者61例,占62.2%）,糖尿病合并非难治性高血压71例（抗AT1受体自身抗体阳性者11例,占15.5%）,两组比较具有显著性统计学意义。糖尿病合并难治性高血压抗AT1受体自身抗体阳性组（61例,治疗组）缬沙坦降压疗效明显优于抗AT1受体自身抗体阴性组（37例,对照组）,两组有统计学差异。（2）临床降压效果评定,治疗组总有效率为95.1%,对照组为32.4%,差异具有极显著性意义（P〈0.001）。结论检测糖尿病合并难治性高血压患者的抗AT1受体自身抗体,有针对性地选择降压药物缬沙坦,降压效果好,且较安全。     

老年高血压患者颈动脉顺应性随增龄及脉压变化的研究

目的 研究老年高血压患者脉压和增龄与颈动脉顺应性及斑块形成的关系。方法 95例高血压患者分为非老年组50例和老年组45例，老年组按年龄分为60～69岁（1组）21例；70～74岁（2组）12例；≥75岁（3组）12例，并与正常对照组30例进行颈动脉超声检查。再根据颈动脉有无斑块情况分为斑块组30例，无斑块组65例，比较2组间的年龄及脉压分布有无统计学差异。结果 高血压组的颈动脉顺应性明显低于正常对照组，而老年组的颈动脉顺应性明显低于非老年组，并随年龄的增加而降低；老年组的颈总动脉内膜-中层厚度（IMT）及斑块发生率明显高于非老年组和正常对照组，并随年龄的增加而增加。结论 老年高血压患者颈动脉顺应性随增龄而降低；年龄增大，脉压增加，颈动脉斑块发生率增高。     

Effects of long-term nicardipine treatment on hemodynamics of large arteries in essential hypertension

Summary The effects of the calcium-entry blocker nicardipine on brachial hemodynamics were studied in 22 patients (18 male, 4 female) with essential hypertension, who were treated with 20 mg tid for 1 year. Compliance, characteristic impedance, vascular resistances, and tangential tension were measured before treatment and after 1, 3, and 12 months of treatment by an automatic recording from a B-mode, high-resolution, real-time scanner and pulsed Doppler velocimetry for the calculation of the flow volume. We observed statistically significant variations in compliance and impedance after 1 month (3.21±0.59 dyn^–1 cm⁴ 10^–7 vs. 1.26±0.16 dyn^–1 cm⁴ 10^–7 and 50.6±4.7 dyn s cm^–510² vs. 91.4 ±7.3 dyn s cm^–5 10², respectively; mean±SEM; p<0.001), while tangential tension was significantly reduced after only 3 months (23.2±2.2 mmHg vs. 25.4±2.3 mmHg cm; p<0.05). The correlation between variations in mean blood pressure and in the hemodynamic parameters studied remained statistically significant throughout the study. Nicardipine improved the parameters of large-artery hemodynamics that favor a normal systolic pulse.     

血管紧张素Ⅱ1型受体基因多态性与高龄原发性高血压的相关性

目的研究血管紧张素Ⅱ1型受体(AT1R)基因A1166C多态性与汉族高龄原发性高血压的相关关系。方法采用PCR-RFLP方法,对山东省章丘地区高龄原发性高血压患者104例(高龄高血压组)和体检正常老年人98例(正常对照组)的外周血白细胞DNA,进行AT1R基因A1166C多态性检测,观察AA、AC和CC不同基因型以及该点A、C不同等位基因频率在两组中的分布。结果AA、AC和CC基因型在高龄高血压组的分布为83(79.81%)、20(19.23%)和1(0.96%),正常对照组为82(83.67%)、16(16.33%)和0,两组比较差异无显著性意义(χ2=0.50,P>0.05);A1166与C1166等位基因频率在高龄高血压组中分别为186(89.42%)和22(10.58%),正常对照组为180(91.84%)和16(8.16%),两组比较差异无显著性意义(χ2=1.38,P>0.05)。结论AT1R基因A1166C分子变异与山东省章丘地区汉族高龄原发性高血压无相关性。     

不同时期氯沙坦短暂治疗对自发性高血压大鼠心脏AT1受体、AT2受体表达的影响

目的 观察不同时期氯沙坦短暂治疗对自发性高血压大鼠(SHR)的血压变化及心脏AT1受体、AT2受体表达的影响,探讨血管紧张素Ⅱ 1型受体(AT1R)、血管紧张素Ⅱ2型受体(AT2R)在高血压发病机制中的作用,为早预防、早治疗高血压开辟新的途径.方法 选用4周龄SHR及京都Wistar大鼠(WKY),分成4组:氯沙坦4周...     

沙库巴曲缬沙坦钠对射血分数减低的心力衰竭合并高血压患者血压及相关指标变化的研究

目的 研究射血分数减低的心力衰竭(HFrEF)合并高血压患者经沙库巴曲缬沙坦钠治疗后血压及心力衰竭(心衰)指标的变化及不良反应.方法 选择HFrEF患者116例,按照随机数表法分为观察组58例,对照组58例,对照组给予血管紧张素转换酶抑制剂(ACEI)/血管紧张素受体阻滞剂(ARB)和β受体阻滞剂以及醛固酮受体拮抗剂等...     

Tolerability and treatment compliance with angiotensin II receptor antagonists

Several studies and intervention trials performed during the past 30 years have provided evidence that hypertension-related cardiovascular risk is not irreversible. This is because the reduction in blood pressure (BP) induced by antihypertensive drugs has been shown to be accompanied by a clear-cut decrease in the rate of cardiovascular events and complications. There is also evidence that BP control in the population is far from being optimal, and that no more than one quarter of treated hypertensive patients display BP values <140/90 mm Hg. The reasons for inadequate BP control are multiple, involving a combination of factors such as inadequate compliance with treatment, intolerance to side effects of currently prescribed drugs, and insufficient clinical use of combination drug treatment.

This article focuses on three major areas. It first provides an overview of the current status of BP control in treated hypertensive persons. It then examines the factors potentially responsible for this phenomenon, with particular emphasis on the relevance of the so-called “compliance factor.” Finally it provides an overview of the tolerability and compliance profile of the angiotensin II receptor antagonists, a new class of antihypertensive drugs characterized by an efficacy and safety profile.     

高血压联合降压治疗与动脉弹性的关系

目的了解以钙通道阻滞剂（CCB）为基础的不同降压药物联合治疗方案在降压达标后对中老年高血压患者动脉弹性的影响,评估其防治心脑血管危险的效果。方法 156例中老年高血压患者被随机分为两组,经5～7d药物洗脱期后分别接受CCB＋血管紧张素转换酶抑制剂（ACEI）或血管紧张素受体阻滞剂（ARB）以及CCB＋利尿剂（D）联合治疗,4周常规剂量治疗后血压未达标者加用小剂量β受体阻滞剂（β-B）至血压达标。治疗前和治疗后1年分别检测治疗组患者血压、心率、大动脉弹性指数（C1）和小动脉弹性指数（C2）,比较各治疗组间血压、心率、C1和C2的变化。以36例中老年健康者1年前后的C1和C2为对照,排除因增龄所致的动脉弹性改变。结果①各治疗组治疗后收缩压、舒张压、脉压均明显降低,差异有统计学意义（P均〈0.01）。②治疗后CCB＋ACEI/ARB＋β-B（C＋A＋B）组和CCB＋D＋β-B（C＋D＋B）组心率明显减慢,差异有统计学意义（P均〈0.01）;CCB＋ACEI/ARB（C＋A）组心率减慢,差异有统计学意义（P〈0.05）。③治疗后C＋A组C1减小,差异有统计学意义（P〈0.05）;治疗后C＋A＋B组和C＋D＋B组C2均增大,P〈0.05,差异有统计学意义。④健康对照组1年前后各项指标血压、心率、C1和C2均无变化（P〉0.05）。结论在降压达标情况下,C＋A和C＋D联合治疗对中老年高血压患者的动脉弹性无明确改善,C＋A＋B和C＋D＋B联合治疗可改善中老年高血压患者的小动脉弹性,小剂量β受体阻滞剂与其它常用降压药物联用对中老年高血压患者动脉弹性改善有益。     

运用BiFC技术检测LOX-1与AT1受体的相互作用

目的运用双分子荧光互补(bimolecular fluorescence complementation,BiFC)技术探讨氧化低密度脂蛋白(ox-LDL)介导血凝素样氧化低密度脂蛋白受体-1(LOX-1)和血管紧张素Ⅱ1型受体(AT1)之间的相互作用,推测其可能是参加动脉粥样硬化等心血管疾病过程的重要机制之一。方法将LOX-1与AT1受体质粒共转染COS7细胞,给予ox-LDL(50ug/ml)刺激后,检测细胞中p-ERK表达水平。根据BiFC载体和AT1、LOX-1基因序列设计引物,将AT1、LOX-1基因克隆到BiFC特异性的荧光载体上,得到重组BiFC质粒:phmKGN-MN-AT1,phmKGC-MN-AT和phmKGC-MC-LOX-1,phmKGN-MC-LOX-1,配对共转染HEK293细胞,用ox-LDL(50ug/ml)刺激,研究AT1受体和LOX-1的相互作用;构建G蛋白偶联受体家族中另一蛋白肾上腺素受体β2(β2-adrenergi creceptor,β2AR)的BiFC重组质粒:phmKGN-MN-β2AR和phmKGC-MN-β2AR,分别与LOX-1对应的BiFC质粒转染HEK...     

原发性高血压分级与胰岛素抵抗、血浆内皮素-1的关系

目的探讨血浆内皮素-1(endothelin-1,ET-1)、胰岛素抵抗(insulin resistance,IR)和原发性高血压(高血压)分级之间的关系。方法入选150例门诊及体检科新发现的高血压患者,按照2010年《中国高血压防治指南》诊断标准和血压分级原则,分为高血压1级组(52例)、高血压2级组(50例)、高血压3级组(48例),分别检测患者的血浆ET-1、空腹血糖(fasting blood glucose,FBG)、空腹血清胰岛素(fasting serum insulin,FINS)浓度。IR检测采用HOMA法,计算胰岛素敏感指数(insulin sensitivity index,ISI)。结果高血压3级组ISI明显小于高血压2级组和高血压1级组,差异有统计学意义(0.31±0.07 vs.0.43±0.06 vs.0.52±0.03,P<0.05);高血压2级组ISI明显小于高血压1级组,差异有统计学意义(P<0.05)。高血压3级组血浆ET-1浓度明显高于高血压2级组和高血压1级组,差异有统计学意义[(166.27±10.58)ng.L-1vs.(156.74±12.11)ng.L-1vs.(148.62±11.45)ng.L-1,P<0.05];高血压2级组血浆ET-1浓度明显高于高血压1级组,差异有统计学意义(P<0.05)。相关分析结果显示,ISI与收缩压呈负相关(r=-0.58,P<0.05),与舒张压也呈负相关(r=-0.56,P<0.05);ET-1与收缩压呈正相关(r=0.60,P<0.05),与舒张压也呈正相关(r=0.59,P<0.05)。结论 IR及血浆ET-1浓度升高与高血压血压分级有密切关系。     

贝那普利对高血压并糖尿病肾病抗AT1受体自身抗体阳性患者肾脏的保护作用

目的探讨抗血管紧张素转换酶抑制剂贝那普利对高血压并糖尿病肾病（DN）抗AT1受体自身抗体阳性患者血压及尿蛋白的影响。方法以合成的AT1受体多肽片段为抗原,应用酶联免疫吸附测定技术,检测71例高血压并DN患者和51例糖尿病患者,及正常对照组40例血清抗AT1受体自身抗体。对抗AT1受体自身抗体阳性和阴性的DN患者分别在原胰岛素降糖方案治疗基础给予贝那普利10mg,口服,1次／d;尼群地平10mg,口服,3次／d;双氯噻嗪12．5mg,口服,1次／d;阿司匹林100mg,口服,1次／d。观察贝那普利对AT1受体自身抗体阳性组和阴性组临床降压及尿蛋白的疗效。6个月为一疗程,治疗前后进行24h尿微量白蛋白测定。结果高血压并DN组抗AT1受体自身抗体阳性率（43．7％,31／71）明显高于2型糖尿病组（13．7％,7／51）和对照组（10％,4／40）。临床降压疗效总评定,DN抗AT1受体自身抗体阳性组和阴性组贝那普利治疗总有效率分别为85．6％和45．0％;临床降蛋白尿的疗效总有效率分别为87．1％（27／31）和42．5％（17／40）,两组比较差异具有显著的统计学意义（P〈0．01）。结论贝那普利对高血压合并DN抗AT1受体自身抗体阳性组降压和减少蛋白尿的疗效明显优于阴性组,有针对性的治疗具有重要的临床价值。     

β_1肾上腺素能受体Gly389Arg多态性与原发性高血压的关系

目的探讨汉族人群β1肾上腺素能受体Gly389Arg多态性与原发性高血压的关系。方法采用聚合酶链反应-限制性长度片段多态性技术分析原发性高血压患者和正常人群β1肾上腺素能受体Gly389Arg多态性。结果高血压组Arg/Arg,Arg/Gly,Gly/Gly基因型频率分别为59.06%、35.09%、5.85%,正常对照组分别为43.55%、45.97%、10.48%;两组间三种基因型频率分布有统计学差异(χ2=7.420,P<0.05);高血压组Arg等位基因频率为76.61%,Gly等位基因频率为23.39%,正常对照组分别为66.53%、33.47%,两组间等位基因频率分布存在统计学差异(χ2=7.299,P<0.05);高血压组Arg纯合子基因型频率和Arg等位基因频率均明显高于对照组。结论β1肾上腺素能受体Gly389Arg多态性可能与原发性高血压发病有关。     

原发性高血压患者福辛普利治疗前后血清胰岛素样生长因子-1水平的变化

目的：探讨原发性高血压（EH）患者福辛普利治疗前后血清胰岛素样生长因子-1（IGF-1）水平的变化及其与EH心肌肥厚形成的关系。方法：用放射免疫分析法测定46例EH患者（EH组）福辛普利治疗前后、治疗3个月及18例正常血压者（对照组）的血清IGF-1水平。结果：EH患者的血清IGF-1为（13．28±3．59）nmol/L,明显高于对照组（9．50±l．65）nmol/L（P＜0．001）。Ⅱ期EH患者的平均血清IGF-1水平（14．73±3．21）nmol／L明显高于Ⅰ期患者（11．58±3．48）nmol/L（P＜0．005）;伴左室肥厚（LVH）者IGF-1为（15．83±3．36）nmol／L,高于无LVH者［（1．69±2．29）nmol/L）（P＜0．01）;与对照组比较均P＜0.00I。EH患者血清IGF-1水平与左室重量指数（LVMI）呈显著正相关（r＝0．811,P＜o．001）。福辛普利治疗3个月后,血清IGF-1水平降到（10．93±2．44）nmol／L（P＜0.00I）,与对照组比较P＜0．05;LVH者仍高于无LVH者［（12．67±1．79）比（10．62±1．98）nmol／L,P＜0．OI〕。结论：EH患者血清IGF-1水平升高,尤其是伴LVH的患者,经福辛普利治疗后其水平下降,说明IGF-1可能参与EH心肌肥厚的形成。     

Beta1-adrenergic receptor gene polymorphisms and response to beta1-adrenergic receptor blockade in patients with essential hypertension

BACKGROUND: Studies suggest that the Ser49Gly and Arg389Gly polymorphisms in the beta1-adrenergic receptor might be of functional importance for the cardiovascular system. Both have been associated with altered receptor activity in vitro, and with hypertension and cardiac failure in vivo. HYPOTHESIS: The aim of this study was to test whether these polymorphisms were associated with the change in heart rate or blood pressure in patients with essential hypertension and left ventricular (LV) hypertrophy treated with the beta1-adrenergic receptor blocker atenolol. METHODS: Blood pressure and heart rate were measured in 101 hypertensive patients with echocardiographically verified LV hypertrophy, randomized in a double-blind study to treatment with either the beta1-adrenergic receptor blocker atenolol or the angiotensin II type I receptor antagonist irbesartan. Changes in blood pressure and heart rate were evaluated after 12 weeks. Beta1-adrenergic receptor genotyping was performed using polymerase chain reaction and restriction fragment length polymorphism. RESULTS: We found no significant associations between the changes in the measured variables and either of the two polymorphisms. However, carriers of the 49Gly allele showed a tendency toward a greater reduction in heart rate compared with patients with the Ser/Ser49 genotype (p = 0.06). CONCLUSIONS: The Ser49Gly and Arg389Gly beta1-adrenergic receptor polymorphisms do not seem to exert a major effect on the changes in heart rate and blood pressure during 12 weeks of treatment with atenolol in patients with essential hypertension and LV hypertrophy.     

高血压病患者动脉顺应性改变及其影响因素的研究

目的 探讨高血压病(EH)患者动脉顺应性的改变及其与血压、糖代谢、脂代谢之间的关系。方法 采用美国HDI公司CVProfilorTM DO-2020型动脉弹性功能测定仪检测133例EH患者和147例正常人大动脉顺应性(C1)、小动脉顺应性(C2)、糖代谢、脂代谢,并对可能影响动脉顺应性的因素进行多元逐步回归分析与偏相关分析。结果 不同年龄与性别组中,EH患者的C1和C2均较正常对照组降低;EH患者体重指数及空腹血糖增高,胰岛素敏感指数(ISI)下降(P<0.05);EH组中脉压、脉率、体表面积(BSA)和ISI是C1的决定因素,平均动脉压、BSA、血清总胆固醇是C2的决定因素,而在正常人群中年龄与ISI是正常人群C2的决定因素。结论 动脉顺应性在EH时降低,除受血压水平影响外,还与年龄、体表面积、血糖、脂代谢等因素有关。     

Angiotensin II type 1 receptor blockers prevent aortic arterial stiffness in elderly patients with hypertension

Backgrounds and aims: Increased arterial stiffness may increase cardiovascular morbidity and mortality. Angiotensin II type 1 receptor blockers (ARBs) are potentially useful in controlling the central blood pressure and arterial stiffness in mild to moderate essential hypertension, while the effects of ARBs in aged patients with essential hypertension are not entirely investigated.

Methods: The carotid-femoral arterial pulse wave velocity (PWV) was measured in aged patients with essential hypertension.

Results: In a cross-sectional study, PWV value was significantly higher in these old patients with essential hypertension, compared to patients without essential hypertension. In correlation analysis, PWV was associated positively with age, hypertension duration, and carotid atherosclerosis. However, there was no relationship between PWV and gender in aged patients with essential hypertension. In a perspective study, 6–12 months administration of ARBs (losartan, 50 mg/day; telmisartan, 40 mg/day; valsartan 80 mg/day; irbesartan, 150 mg/day) remarkably reduced PWV in aged patients with essential hypertension. Regression analyses of multiple factors indicated that the effects of ARBs on arterial stiffness were not associated with the reduction of blood pressure.

Conclusion: ARB treatment is a negative risk factor of arterial stiffness in aged patients with essential hypertension.     

原发性高血压血清sICAM—1和sVCAM—1水平及意义

目的 检测老年早期原发性高血压清可溶性细胞间粘附分子－1(sICAM-1)和可溶性血管间粘附分子－1(sVCAM-1)的水平并分析它们与老年原发性高血压的关系。方法 用ELISA法测定老年原发性高血压患者,正常老年人,正常年轻人血清sICAM-1和sVCAM-1的浓度。结果 老年原发性高血清sICAM-1和sVCAM-1的浓度高于正常老年人和正常年轻人（P＜0．01）,另外正常老年人的sICAM-1和sVCAM-1的水平高于正常年轻人（P＜0．01）。结论 老年原发性高血压患者中血清sICAM-1,sVCAM-1的水平明显升高,提示在老年原发性高血压患者中存在内皮细胞结构和功能的改变。我们认为血清sICAM-1,sVCAM-1可作为原发性高血压病发展过程中内皮细胞功能紊乱的一个比较敏感的观察指标。     

Efficacy and safety of the Angiotensin receptor blocker valsartan in children with hypertension aged 1 to 5 years

The efficacy and safety of valsartan were studied in 90 children (mean age: 3.2 years; 60% male; 30% black) with systolic blood pressure (SBP) > or =95th percentile. Nineteen percent received valsartan in addition to previous antihypertensive therapy. Subjects were randomly assigned to low-, medium-, or high-dose valsartan for 2 weeks (phase 1) and then reassigned randomly to placebo or to remain on the same valsartan dose for 2 additional weeks (phase 2). After this, subjects were enrolled into a 52-week, open-label phase during which valsartan was dosed to achieve SBP <95th percentile. Statistically significant reductions in SBP and diastolic blood pressure of approximately 8.5 mm Hg and 5.7 mm Hg, respectively, were observed at the end of phase 1 in all of the valsartan dose groups. SBP and diastolic blood pressure were also significantly lower during phase 2 in valsartan recipients compared with placebo recipients. SBP <95th percentile was achieved in 77.3% of subjects during the open-label phase. Adverse events were minor and occurred at similar frequencies in each of the 3 dose groups in phase 1 and at equal frequencies in the valsartan and placebo arms in phase 2. Serious adverse events and drug-related adverse events occurred infrequently during both the double-blind (2.2% and 5.6%, respectively) and open-label (14.8% and 6.8%, respectively) portions of the study. Valsartan treatment had no demonstrable negative effects on growth and development. In this study, the first trial of an antihypertensive agent conducted in children <6 years of age, valsartan effectively lowered SBP and diastolic blood pressure compared with placebo.     

咪达普利和缬沙坦联合治疗对原发性高血压患者左心室肥厚的逆转

目的:探讨咪达普利和缬沙坦联合治疗对原发性高血压(EH)患者左心室肥厚(LVH)的逆转。方法:将137例伴LVH的EH患者随机分成咪达普利组、缬沙坦组和联合治疗组。设定血压达标值为收缩压(SBP)<140mmHg(1mmHg=0.133kPa)和舒张压(DBP)<90mmHg。3组患者分别口服起始剂量咪达普利10mg/d、缬沙坦80mg/d和咪达普利10mg/d加缬沙坦80mg/d。随访周期为2周,若血压未能达标,则增加剂量直至联合治疗,最大剂量为咪达普利20mg/d加缬沙坦160mg/d。3组患者均口服氢氯噻嗪12.5mg/d。总疗程24周。检测治疗前后24h动态血压、左室质量指数(LVMI)和心率(HR)。结果:①3组治疗后24hSBP、24hDBP均分别较治疗前显著降低(均P<0.01),而3组治疗前后24hSBP、DBP的降低幅度差异均无统计学意义(均P>0.05)。②3组治疗后LVMI和HR均分别较治疗前显著性降低(均P<0.01)。联合治疗组治疗前后LVMI和HR的降低幅度均分别大于咪达普利组和缬沙坦组,差别均具有统计学意义(均P<0.05)。结论:咪达普利和缬沙坦联合治疗在逆转LVH和抑制心脏交感活性方面较咪达普利或缬沙坦单药治疗具有更加显著的作用,且这些作用独立于降压疗效之外。