【作者】 赵雅静；

【导师】 姜志安；

【作者基本信息】 河北医科大学 ， 内科学， 2011， 硕士

【摘要】 目的:收缩压增高,脉压大是老年人高血压最常见的类型,尤其在高龄患者,其主要的病理改变是大动脉的硬化,血管的顺应性及弹性的降低,血管僵硬度的增加,导致不能缓冲收缩压并保持舒张压,因此,老年人常见在收缩压增高的同时,舒张压降低,脉压增宽。近年来大量的研究证明,脉压是老年高血压患者心脑血管事件的独立危险因子,其预测作用甚至远远大于收缩压和舒张压。老年人基线脉压与总死亡、心血管死亡、脑卒中和冠心病发病均呈显著正相关,控制收缩压可显著减少心脑血管事件,但老年单纯收缩期高血压患者在降压治疗时,可能面临收缩压下降的同时,伴随舒张压的过度下降,研究显示老年高血压患者的舒张压与其预后呈负相关,舒张压下降过低,可能导致心脑血管事件增加。研究发现,脉压是反映大动脉僵硬度的指标,血管内皮功能与动脉僵硬度密切相关,因此如何在降低周围血管阻力的同时,阻止血管病变的发生发展,降低大动脉僵硬度,缩小脉压,成为老年单纯收缩期高血压患者治疗的主要目标。老年人由于球旁器的退化,血管肾素活性逐渐降低,多属于低肾素型高血压,所以老年单纯收缩期高血压患者在治疗上首选长效钙离子拮抗剂和利尿剂。硝酸酯类药物是百年来治疗心绞痛和急性心力衰竭的有效药物,该类药物的主要作用机制是,其在血管平滑肌与细胞内-SH基结合,产生一氧化氮,激活鸟苷酸环化酶,使鸟苷酸(cGMP)生产增加,而后者又使平滑肌钙离子内流减少,从而松弛血管平滑肌特别是小血管平滑肌,使周围血管舒张,外周阻力因此减少,同时回心血量减少,心排血量降低,心脏负荷较前减轻,使得心肌氧耗量减少,从而使心肌缺血症状得到改善。而其疗效则是主要通过患者心绞痛症状的改善或运动耐量的提高给予以间接评估。近来有研究表明,硝酸酯类药物可通过产生一氧化氮,参与动脉僵硬度的调节,改善老年高血压患者的动脉弹性,并用于辅助治疗老年单纯性收缩性高血压,降低脉压取得较好的疗效,但有关这方面的深入研究报道不多。本研究通过对比氨氯地平和氢氯噻嗪加用与不加用5-单硝酸异山梨酯缓释片两种方案对老年单纯收缩期高血压(ISH)的降压疗效,探讨5-单硝酸异山梨酯缓释片ISH患者血压的影响。方法:本实验选用于我院就诊的老年ISH患者60例。男性38例,年龄68~82岁;女性22例,年龄66~85岁;患者随机分为实验组30例,对照组30例,两组临床资料差异无统计学意义(P>0.05)。实验组:给予5-单硝酸异山梨酯缓释片60mg/d,氨氯地平5mg/d,氢氯噻嗪12.5mg/d,对照组:给予氨氯地平5mg/d,氢氯噻嗪12.5mg/d。两组均连续用药2周,患者在测定2周内,不再服用其他降压药物,禁吸烟、饮酒和喝含有咖啡因的饮料。血压测量在上午8:00~11:00进行,测3次取均值,脉压(PP)=SBP-DBP。所有资料采用SPSS18.0软件进行统计分析,采用t检验,计量资料x-±s表示。P<0.05为有统计学意义。结果:实验组与对照组收缩压、舒张压及脉压均较治疗前下降,均有统计学意义(P<0.05);实验组:收缩压下降30.4±11.0mmHg,舒张压下降7.1±6.5mmHg,脉压下降23.3±10.9mmHg;对照组:收缩压下降24..8±9.3mmHg,舒张压下降10.7±8.9mmHg,脉压下降14.1±10.1mmHg。实验组与对照组比较收缩压下降差异有统计学意义(P<0.05),舒张压下降差异无统计学意义(P>0.05),脉压下降差异有统计学意义(P<0.05),即两组应用药物治疗后收缩压、舒张压、脉压均有下降,然而加用5-单硝酸异山梨酯缓释片治疗组脉压下降更为明显。结论:本实验通过2周的连续用药,观察到5-单硝酸异山梨酯缓释片、氨氯地平、氢氯噻嗪三种药物联合应用或氨氯地平、氢氯噻嗪两种药物联合应用均可使老年ISH患者收缩压降至正常范围,同时两组脉压均有下降,钙离子拮抗剂和利尿剂在降低收缩压的同时可适当降低脉压,然而却同时也降低了舒张压,而本实验数据显示加用5-单硝酸异山梨酯缓释片组与对照组相比,治疗前后实验组收缩压下降更为明显,舒张压下降无明显差异,脉压减小更为明显。证实了,硝酸酯类可使收缩压降低,而舒张压降低不明显,从而使脉压减少,而5-单硝酸异山梨酯缓释片尤其适用于舒张压偏低的老年ISH患者,与氨氯地平、氢氯噻嗪联合应用对ISH患者有良好的降压作用。更多还原

【Abstract】 Objective: The rising of isolated systolic blood pressure and pulse pressure of arteries and veins are the most common types of hypertension for big old people , especially for senior patients.The main pathological changes are the vascular sclerosis, the decreasing of vascular compliance and flexibility as well as the increase of vascular stiffness, which in combination result in the loss of buffering of systolic and diastolic pressure .It is in this case that the systolic pressure keeps rising and the diastolic pressure is lower for common old people ,resulting the widening of pulse pressure . In recent years a number of studies have proved that the rising pulse pressure is an independent risk factor for heart attack in the old patients with hypertension.Its predictive and prognosis function is far greater than systolic blood pressure and diastolic blood pressure. The baseline pulse pressure is in positive correlation with total death ,cardiovascular death, stroke and coronary heart disease. Although the control of systolic blood pressure is of high significance in reducing the incidence of heart attack and stroke, it is also clear that in the antihypertensive therapy for isolated systolic hypertension patients we are facing the predicament that the diastolic pressure may drop even greater than systolic pressure itself which likely leads to the occurrence of heart attack and stroke. Studies have found that pulse pressure is an powerful indication for .The function of vessel endothelium is closely related with the arterial stiffness.It is for this reason that we should prevent the occurrence of vascular lesions, reduce artery stiffness, and narrow the pulse pressure in our process of reducing peripheral vascular resistance ,which has become the priorities for the aged isolated systolic hypertension patients. Because of the degeneration of juxtaglomerular apparatus for the elderly and the gradual decrease of chemical activity of vascular renin, the preferable treatment for older isolated systolic hypertension patients is long-term calcium antagonists and diuretics. Nitrates has been an effective treatment for acute heart failure and angina for years,the mechanism of which is their combination with cellular SH base in vascular smooth cells ,producing nitric oxide(NO) and later activating guanylyl cyclase-C(cGMP). The booming of cGMP is able to retard the inflow of calcium to the vascular smooth cells and ultimately contribute to the relaxation of vascular smooth muscle especially the small ones. With this process comes the dilation of peripheral vascular and the decrease of peripheral resistance. Meanwhile the blood return is lowered ,and the heart load is reduced ,which is a low-oxygen-consuming state.The effectiveness of Nitrates is evaluated indirectly by the improvement of myocardial ischemia symptoms and the exercise tolerance. Recent studies have shown that nitrates are able to adjust arterial stiffness by means of the production of nitric oxide, greatly improving the artery elasticity for elderly patients with hypertension. They can be a supplementary treatment for simple contractile hypertension.They have shown their specific advantages in reducing pulse pressure a, but researches on this aspect is still in scarity.This research focuses on the comparative antihypertensive efferct in groups of ammonia chloride and hydrochlorothiazide with or without 5-isosorbide mononitrate sustained release tablets in the treatment of elderly isolated systolic hypertension (ISH). This paper will discuss the antihypertensive effect of 5-isosorbide mononitrate sustained release tablets on the blood pressure in ISH patients.Methods: In this experiment we choose 60 cases with ISH admitted in our hospital with 38 male and 22 female,aged 68 ~ 82 years old and 66 ~ 85years old respectively.Patients were randomly divided into the experimental group and the control groups with 30 cases respectively. There is statistical significance between the clinical data in each groups (P > 0.05). The experimental group is administrated with 5-isosorbide mononitratesustained release tablets 60mg/d, amlodipine 5mg/d, and hydrochlorothiazide 25mg/d; the control group with amlodipine 5mg/d, hydrochlorothiazide 25mg/d. In this two-weeks time, the drugs is adminstrated persistently. No other antihypertensive medications, smoking, drinking caffeinated drinks are allowed. Blood pressure measurement is carried out during 8:00-11:00am. Take the average value of 3 measurements. Pulse pressure (PP) = SBP - DBP. All data is processed and statistically analysed in SPSS18.0 software with t-test. Measurement data is expressed in the form of x-±s. P < 0.05 signifies statistical significance.Results: Systolic pressure, diastolic pressure and pulse pressure have all dropped compared with preoperative data in both two groups(P < 0.05). Experimental group: systolic blood pressure drops 30.4±11.0 mmHg, diastolic pressure drops 7.1±6.5 mmHg, pulse pressure drops 23.3±10.9 mmHg; The control group: systolic blood pressure drops 24.8±9.3 mmHg, diastolic pressure drops 10.7±8.9 mmHg, pulse pressure drops 14.1±10.1mmHg . There is statistical significance between the two groups in terms of systolic blood pressure drop (P < 0.05) as well as pulse pressure drop (P < 0.05),but no difference when it comes to diastolic pressure decline (P > 0.05) In other words, systolic blood pressure, diastolic blood pressure and pulse pressure are all lowered after medication in these two groups.However, the additional administration of 5-isosorbide mononitratesustained release tablets has shown extra advantage in reducing pulse pressure ,which is exhibited in experimental group.Conclusion: After continuous administration of medicine for 2 weeks, we can see that both the combination of 5-isosorbide mononitrate sustained release tablets, amlodipine, hydrochlorothiazide and the combination of only amlodipine, hydrochlorothiazide are able to not only reduce the systolic pressure to normal range, but also decrease senile pulse pressure .While calcium channel blockers and diuretic jointly could lower systolic blood pressure and pulse pressure ,it can also reduce diastolic blood pressure, which is not desirable.Our experimental data reveals that the application of additional 5 -isosorbide mononitrate sustained release tablets is able to reduce diastolic pressure to a greater extent without too much lowering of diastolic pressure, making the decreasing of pulse pressure is of obvious significance between the two groups. It is thus confirmed that nitrates can lower systolic without too much diastolic blood pressure changes, thereby shrinking pulse pressure. 5-isosorbide mononitrate sustained release tablet is especially suitable for low ISH diastolic blood pressure patients. It has shown that its combination with amlodipine, hydrochlorothiazide in ISH patients could produce ideal anti-hypertension effect.更多还原