5-单硝酸异山梨酯缓释片对老年单纯收缩期高血压的影响
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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。
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.
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。
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.
引文
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29 Stokes GS, Barin ES, Gilfillan KL. Effects of Isosorbide Mononitrateand AII Inhibition on Pulse Wave Reflection in Hypertension. Hypertension, 2003, 41(2): 297-301
30 Stokes GS. Treatment of isolated systolic hypertension. Curr Hypertens Rep, 2006, 8(5): 377-383
31 Chen N, Zhou M, Yang M, et al. Calcium channel blockers versus other classes of drugs for hypertension.Cochrane Database Syst Rev, 2010, 4(8): CD003654
32 Mancia G, De Backer G, Dominiczak A, et al. 2007 ESH-ESC Practice Guidelines for the Management of Arterial Hypertension: ESH-ESC Task Force on the Management of Arterial Hypertension. Hypertens, 2007, 25(9): 1751-1762
33 Morgan TO, Anderson AI, Mac Innis RJ. ACE inhibitors, beta-blockers, calcium blockers, and diuretics for the control of systolic hypertension. A M J Hypentens, 2001, 14(3): 241-247
34 Burges RA, Ddd MG, Gardiner DG. Pharmacological profile of amlodipine. AM J Cardiol, 1989, 64: 101-181
35 Julius S.Amlodipine in hypertion: an overview of the clinical dossier. Cardivasc Pharmacol, 1988, 12(Suppl 7): S27-33
36 Shah SU, Anjum S, Littler WA. Use of diuretics in cardiovascular disease: (2) hypertension. Postgrad Med J, 2004, 80: 271-276
37 Uzu T, Kinura G. Diuretics shift circadian rhythm of blood pressure from nondipper to dipper in essential hypertension.Circulation, 1999, 100: 1635-1638
38 Wright JM. Choosing a first-line drug in the management of elevated blood pressure: what is the evidence? 1: Thiazide diuretics, CMAJ, 2000, 163: 57-60
39 Wright JM, Lee CH, Chambers GK. Systematic review of antihypertensive therapies: does the evidence assist in choosing a first-line drug. CMAJ, 1999, 161: 25-32
40 Weir MR, Flack JM, Applegate WB. Tolerability, safety, and quality of life and hypertensive therapy : the case for low-dose diuretics. Am J Med, 1996, 101: 83S-92S
41 Isla S. Mackenzie, Carmel M. McEniery, Zahid Dhakam, et al. Comparison of the Effects of Antihypertensive Agents on Central Blood Pressure and Arterial Stiffness in Isolated Systolic Hypertension Hypertension, 2009, 54: 409-413
42 Pignoli P, Tremoli E, Poli A, et al. Intimal plus medial thickness of the arterial wall: A direct measurement with ultrasound imaging. Circulation,1986, 74: 1399-1406
43 Asmar R, Benetos A. Assessment of arterial distensibility by automaticpulse wave velocity measurement. Hypertension, 1995, 26(3): 485-490
44 Kaufman R, Nunes I, Bolognese JA, et al. Single-dose effects of isosorbide mononitrate alone or in combination with losartan on central blood pressure. J Am Soc Hypertens, 2010, 4(6): 311-318
45 Mitchell GF, Lacourciere Y, Oellet JP, et al. Determinants of elevated blood pressure in middle-aged and older subjects with uncomplicated systolic hypertension: the role of proximal aortic diameter and the aortic pressure-flow relationship. Circulation, 2003, 108: 1592-1598
46 Virmani R, Avolio AP, Mergner WJ, et al. Effect of aging on aortic morphology in populations with high and low prevalence of hypertension and atherosclerosis. Am J Pathol. 1991, 139: 1119-1129
47 O’Rourke, Nichols WW. Aortic diameter, aortic stiffness, and wave reflection increase with age and isolated systolic hypertension. Hypertension, 2005, 45(part 2): 652-658
48 Mattace-Raso FU, Verwoert GC, Hofman A, Witteman JC.Inflammation and incident-isolated systolic hypertension in older adults: the Rotterdam study. Hypertens, 2010, 28(5): 892-895
49 Stokes GS. Nitrates as adjunct hypertensive treatment. CurrHypertens Rep, 2006, 8: 60-68
50 Stokes GS, Ryan M. Can extended-release isosorbide mononitrate be used as adjunctive therapy for systolic hypertension? An open study employing pulse-wave analysis to determine effects of antihypertensive therapy. Am J Geriat Cardiol, 1997, 6: 11-19
51 Fung HL, Chung SJ, Bauer JA, et al. Biochemical mechanism of organic nitrate action.Am J Cardiol, 1992, 70: 4B-10B
52 Loscalzo J. Antiplatelet and antithrombotic effects of organic nitrates.Am J Cardiol, 1992, 70: 18B-22B
53 Diodati J, The'roux P, Latour JG, et al. Effects of nitroglycerin attherapeutic doses on platelet aggregation in unstable angina pectoris and acute myocardial infarction.Am J Cardiol, 1990, 66: 683-688
54 Abrams J. Mechanism of action of organic nitrates in the treatment of myocardiol infarction.Am J Cardiol, 1992, 70: 683-688
55 Dupuis J. Nitrates in congestive heart failure. Cardiovasc Drugs Ther, 1994, 8: 501-507
56 Bassenge E. Coronary vasomotor responses:role of endothelium and nitovasodilators.Cardiovasc Drugs Ther, 1994, 8: 601-610
57 Bassenge E. Nitrates in different vascular beds, nitrate tolerance, and interactions with endothelial function.Am J Cardiol, 1992, 70: B23-B29
58 Brown BG. Dyanmic mechanisms in human coronary stenosis.Circ J, 1984, 70: 917-922
59 Pupita G, Kaski JC, Galassi AR, et al. Myocardial ischemia caused by distal coronay-artery constriction in stable angina pectoris.N Engl J Med, 1990, 23: 514-520
60 Abrams J, Frishman W. The Organic Nitrates and Nitroprusside// Frishman W, Sonnenblick E, Sica D. Cardiovascular Pharmacotherapeutics.The Second edition. The United State of Amercia. The McGraw-Hill Companies, 2003: 203-214
61 Mueller R, Scheidt S. Nitroglycern// Messerli F. Cardiovascular Drug Threapy. The Second edition. The United State of Amercia. W. B. Saunders Company, 1996: 865-890
62 Stokes GS, Alex andra JB, Natasha H, et al. Longterm effectiveness of extended release nitrate for the treatment of systolic hypertension Hypertension, 2005, 43: 380-384
1 Kaplan NM. New issues in the treatment of isolated systolic hypertension. Circulation, 2000, 102: 1079-1081
2 Laurent S, Boutouyrie P, Benetos A. Patho physiology of hypertension in the elderly. Am J G eriat Cardiol, 2002, 11: 34-39
3 Nichols WW, O'Rourke M F, Avolio AP, et al. Effects of age on ventricular vascular coupling. Am J Cardiol, 1985, 55: 1179-1184
4 Hansson L, Zanchetti A, Carruthers SG, et al. Effects of intensive blood pressure lowering and low dose a spirin in patients with hypertension: Principal results of the Hypertension Optimal treatment (HOT) randomized trial. Lancet, 1998, 351: 1755-1762
5 V bomanski M, Norman J, Wolz M, et al. Cardiovascular risk assessment using pulse pressure in the first national health and nutrition examination survey. Hypertension, 2001 ,38 :793-797
6 Benetos A, Safar M. Pulse pressure a predictor of long-term cardiovascular motality in a French male population. Hypertension, 1997, 30: 1410-1415
7 Mattace-Raso FU, Verwoert GC, Hofman A, et al. Inflammation and incident-isolated systolic hypertension in older adults: the Rotterdam study. Hypertens, 2010, 28(5): 892-895
8 McEniery CM, McDonnell BJ, So A, et al. Aortic calcification is associated with aortic stiffness and isolated systolic hypertension in healthy individuals. Hypertension, 2009, 53: 524-531
9 Kung CF, Luscher TF. Different mechanism of endothelial dysfunction with aging and hypertension in rat aorta. Hypertension, 1995, 25: 194-200
10 Parenbrock M, Hausberg M, Kosch M, et al. A longitudinal study of vessel wall properties in normotensive and hypertensive renal transplant recipients. J H um Hypertens, 1988, 12: 707-711
11 Pignoli P, Tremoli E, Poli A, et al. Intimal plus medial thickness of the arterial wall : A direct measurement with ultrasound imaging Circulation, 1986, 74: 1399-1406
12 Asmar R, Benetos A. Assessment of arterial distensibility by automaticpulse wave velocity measurement. Hypertension, 1995, 26(3): 485-490
13 Stokes GS, Barin ES, Gilfillan KL. Effects of Isosorbide Mononitrate and AII Inhibition on Pulse Wave Reflection in Hypertension. Hypertension, 2003, 41(2): 297-301
14 Morgan TO, Anderson AI, Mac Inni s RJ. ACE inhibitors, beta-blockers, calcium blockers, and diuretics for the control of systolic hypertension.A M J Hypentens, 2001, 14(3): 241-247
15 Isla S. Mackenzie, Carmel M. McEniery, Zahid Dhakam, et al. Comparison of the Effects of Antihypertensive Agents on Central Blood Pressure and Arterial Stiffness in Isolated Systolic Hypertension. Hypertension, 2009, 54: 409-413
16 Kaufman R, Nunes I, Bolognese JA, et al. Single-dose effects of isosorbide mononitrate alone or in combination with losartan on central blood pressure. J Am Soc Hypertens, 2010, 4(6): 311-318.
17 Murrell W. Nitroglycerine as a remedy for angina pectoris.Lancet, 1879, 80: 80-227
18 Pauca AL, Kon ND, O’Rourke MF. Benef it of nitroglycerin on arterial stiffness is directly due to effects on peripheral arteries.Heart, 2005, 91: 1428-1432
19 Brosnan MJ, Hamilton CA, Graham D, et al. Irbesartan lowers superoxide levels and increases nitric oxide bioavailability in blood vessels from spontaneously hypertensive stroke-prone rats. J Hypertens, 2002, 20: 281-286
20 Schiffrin EL, Deng Li Y. Comparison of effects of angiotensin I-converting enzyme inhibition and beta-blockade for 2 years on function of small arteries from hypertensive patients.Hypertension, 1995, 25(part 2): 699-670
21 Ghiadoni L, Magagna A, Versari D, et al. Different effect of antihypertensive drugs on conduit artery endothelial function.Hypertension, 2003, 41: 1281-1286
22 Kiowski W, Linder L, Nuesch R, et al. Effect of cilazopril on vascular structure and function in essential hypertension.Hypertension, 1996, 27(part 2): 371-376
23 Stokes GS, Alex andra JB, Natasha H, et al. Longterm effectiveness of extended release nitrate for the treatment of systolic hypertension. Hypertension, 2005, 43: 380-384
24 Stokes GS. Nitrates as adjunct hypertensive treatment.Curr Hypertens Rep, 2006, 8: 60-68
25 Fung HL, Chung SJ, Bauer JA, et al. Biochemical mechanism of organic nitrate action.Am J Cardiol, 1992, 70: 4B-10B
26 Loscalzo J. Antiplatelet and antithrombotic effects of organic nitrates.Am J Cardiol, 1992, 70: 18B-22B
27 Diodati J, The'roux P, Latour JG,et al. Effects of nitroglycerin at therapeutic doses on platelet aggregation in unstable angina pectoris and acute myocardial infarction.Am J Cardiol, 1990, 66: 683-688
28 Abrams J. Mechanism of action of organic nitrates in the treatment of myocardiol infarction.Am J Cardiol, 1992, 70: 683-688
29 Dupuis J.Nitrates in congestive heart failure.Cardiovasc Drugs Ther, 1994, 8: 501-507
30 Bassenge E. Coronary vasomotor responses:role of endothelium and nitovasodilators.Cardiovasc Drugs Ther, 1994, 8: 601-610
31 Bassenge E. Nitrates in different vascular beds, nitrate tolerance, and interactions with endothelial function. Am J Cardiol, 1992, 70: B23-B29
32 Brown BG. Dyanmic mechanisms in human coronary stenosis.Circ J, 1984, 70: 917-922
33 Pupita G, Kaski JC, Galassi AR, et al. Myocardial ischemia caused by distal coronay-artery constriction in stable angina pectoris.N Engl J Med, 1990, 23: 514-520
34 Abrams J, Frishman W. The Organic Nitrates and Nitroprusside// Frishman W, Sonnenblick E, Sica D. Cardiovascular Pharmacotherapeutics.TheSecond edition. The United State of Amercia. The McGraw-Hill Companies, 2003: 203-214
35 Mueller R, Scheidt S. Nitroglycern// Messerli F. Cardiovascular Drug Threapy. The Second edition. The United State of Amercia. W B. Saunders Company, 1996: 865-890
2 Franklin SS, Khan SA,Wong ND, et al. Is pulse pressure useful inpredicting risk for coronary heart disease? The framingham heart study. Circulation, 1999, 100: 354-360
3 Laurent S, Boutouyrie P, Benetos A. Patho physiology of hypertension in the elderly. Am J G eriat Cardiol, 2002, 11: 34-39
4 Nichols WW, O' Rourke M F, Avolio AP, et al. Effects of age on ventricular vascular coupling. Am J Cardiol, 1985, 55: 1179-1184
5 Alli C, Mariotti G ,Avanzini F, et al. Long-term prognostic impact of repeated measurements over 1 year of pulse pressure and systolicblood pressure in the elderly. J Hum Hypertens, 2005, 19: 355-363
6 Murrell W. Nitroglycerine as a remedy for angina pectoris. Lancet, 1879, 80: 80-227
7 Pauca AL, Kon ND, O’Rourke MF. Benef it of nitroglycerin on arterial stiffness is directly due to effects on peripheral arteries.Heart,2005, 91: 1428-1432
8 Franklin SS, JacobsMJ, Wong ND, et al. Predominance of isolated systolic hypertension among middle-aged and elderly US hypertension: analysis based on National Health and Nutrition Examination Survey (NHANES) III.Hypertension, 2001, 37: 869-874
9 Rocha E, Mello E, Silva A, et al. Isolated systolic hypertension epidemiology and impact in clinical practice.Rev Port Cardiol, 2003, 22: 7-23
10 Franklin SS, Gustin W4th ,Wong ND, et al. Hemodynamic patterns of age-related changes in blood pressure. The Framingham Heart Study. Circulation, 1997, 96: 308-315
11 Vasan RS, BeiserA, Seshadri S, et al. Residual lifetime risk for developing hypertension in middle-aged woman and man. JAMA, 2002, 287 (8):1003-1010
12 McEniery CM, McDonnell BJ, So A, et al. Aortic calcification is associated with aortic stiffness and isolated systolic hypertension in healthy individuals. Hypertension, 2009, 53: 524-531
13 Dart AM. Pulse pressure a review of merchanism and clinical relevance. Am J Coll Cardiol, 2001, 37: 975-984
14 Chemla D, Hebert J, Coirault C, et al. Total arterial compliance estimated by stroke volume to aortic pulse pressure ratio in humans. Am J Phisiol, 1998, 274: H500-H505
15 Kung CF, Luscher TF. Different mechanism of endothelial dysfunction with aging and hypertension in rat aorta. Hypertension, 1995, 25: 194-200
16 Safar ME. Hypothesis on isolated systolic hypertension in the elderly.J Hum Hypertens, 1999, 13: 813-815
17 Parenbrock M, Hausberg M, Kosch M , et al. A longitudinal study of vessel wall properties in normotensive and hypertensive renal transplant recipients. J H um Hypertens, 1988, 12: 707-711
18 Sethi AA, Nordestguard BG,Agerhol mlarsen B, et al. Angiotensinogen polymorphisms and elevated blood pressure in the general populations: the Copenhagen City Heart Study. Hy pertensi on, 2001, 37: 875-881
19 Hanss on L, Zanchetti A, Carruthers G, et al. Effects of intensive blood pressure lowering and low-dose aspirin in patients with hypertension: principal results of the hypertension optimal treatment (HOT) randomized trial. Lancet, 1998, 351: 1755-1762
20 Pepine CJ, Handberg EM, Cooper-DeHoff RM, et al. A calcium antagonist vs a non- calcium antagonist hypertension treatment strategy for patients with coronary artery disease . The international Verapamil-Trandolap ril study ( INVEST): A randomized controlled trial. JAMA, 2003, 290: 2805-2816
21 Messerli FH, Kupfer S, Pepine CJ , et al. J curve in hypertension and coronary artery disease.Am J Cardiol, 2005, 95: 160
22 The ALLHAT Officers and Coordinators for the ALLHAT Collaborat-iveResearch Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic. The antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT). JAMA, 2002, 288: 2981-2997
23 London G, Schmieder R, Calvo C, Asmar R. Indapamide SR versuscandesartan and amlodipine in hypertension: the X-CELLENT Study. Am J Hypertens, 2006, 19: 113-121
24 Stokes GS, Management of hypertension in the elderly patient. Clinical Interventions in Aging, 2009, 4: 379-389
25 Zeglin MA, Pacos J, Bisognano JD: Hypertension in the very elderly:Brief review of management. Cardiol J, 2009, 16: 379-385
26 SHEP Coor perative Research Group. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). JAMA,1991, 265: 3255-3264
27 Celis H, Yodfat Y, ThijsL, et al. Antihy pertensive therapy in older patients with isolated systolic hypertension: the Syst-Eur experience in general practice.Fam Pract, 1996, 13: 138-143
28 Wang JG, Liu G, Wang X, et al. Long-term blood pressure control in older Chinese patients with isolated systolic hypertension: aprogress report on the Syst-China trial. J Hum Hypertens, 1996, 10: 735-742
29 Stokes GS, Barin ES, Gilfillan KL. Effects of Isosorbide Mononitrateand AII Inhibition on Pulse Wave Reflection in Hypertension. Hypertension, 2003, 41(2): 297-301
30 Stokes GS. Treatment of isolated systolic hypertension. Curr Hypertens Rep, 2006, 8(5): 377-383
31 Chen N, Zhou M, Yang M, et al. Calcium channel blockers versus other classes of drugs for hypertension.Cochrane Database Syst Rev, 2010, 4(8): CD003654
32 Mancia G, De Backer G, Dominiczak A, et al. 2007 ESH-ESC Practice Guidelines for the Management of Arterial Hypertension: ESH-ESC Task Force on the Management of Arterial Hypertension. Hypertens, 2007, 25(9): 1751-1762
33 Morgan TO, Anderson AI, Mac Innis RJ. ACE inhibitors, beta-blockers, calcium blockers, and diuretics for the control of systolic hypertension. A M J Hypentens, 2001, 14(3): 241-247
34 Burges RA, Ddd MG, Gardiner DG. Pharmacological profile of amlodipine. AM J Cardiol, 1989, 64: 101-181
35 Julius S.Amlodipine in hypertion: an overview of the clinical dossier. Cardivasc Pharmacol, 1988, 12(Suppl 7): S27-33
36 Shah SU, Anjum S, Littler WA. Use of diuretics in cardiovascular disease: (2) hypertension. Postgrad Med J, 2004, 80: 271-276
37 Uzu T, Kinura G. Diuretics shift circadian rhythm of blood pressure from nondipper to dipper in essential hypertension.Circulation, 1999, 100: 1635-1638
38 Wright JM. Choosing a first-line drug in the management of elevated blood pressure: what is the evidence? 1: Thiazide diuretics, CMAJ, 2000, 163: 57-60
39 Wright JM, Lee CH, Chambers GK. Systematic review of antihypertensive therapies: does the evidence assist in choosing a first-line drug. CMAJ, 1999, 161: 25-32
40 Weir MR, Flack JM, Applegate WB. Tolerability, safety, and quality of life and hypertensive therapy : the case for low-dose diuretics. Am J Med, 1996, 101: 83S-92S
41 Isla S. Mackenzie, Carmel M. McEniery, Zahid Dhakam, et al. Comparison of the Effects of Antihypertensive Agents on Central Blood Pressure and Arterial Stiffness in Isolated Systolic Hypertension Hypertension, 2009, 54: 409-413
42 Pignoli P, Tremoli E, Poli A, et al. Intimal plus medial thickness of the arterial wall: A direct measurement with ultrasound imaging. Circulation,1986, 74: 1399-1406
43 Asmar R, Benetos A. Assessment of arterial distensibility by automaticpulse wave velocity measurement. Hypertension, 1995, 26(3): 485-490
44 Kaufman R, Nunes I, Bolognese JA, et al. Single-dose effects of isosorbide mononitrate alone or in combination with losartan on central blood pressure. J Am Soc Hypertens, 2010, 4(6): 311-318
45 Mitchell GF, Lacourciere Y, Oellet JP, et al. Determinants of elevated blood pressure in middle-aged and older subjects with uncomplicated systolic hypertension: the role of proximal aortic diameter and the aortic pressure-flow relationship. Circulation, 2003, 108: 1592-1598
46 Virmani R, Avolio AP, Mergner WJ, et al. Effect of aging on aortic morphology in populations with high and low prevalence of hypertension and atherosclerosis. Am J Pathol. 1991, 139: 1119-1129
47 O’Rourke, Nichols WW. Aortic diameter, aortic stiffness, and wave reflection increase with age and isolated systolic hypertension. Hypertension, 2005, 45(part 2): 652-658
48 Mattace-Raso FU, Verwoert GC, Hofman A, Witteman JC.Inflammation and incident-isolated systolic hypertension in older adults: the Rotterdam study. Hypertens, 2010, 28(5): 892-895
49 Stokes GS. Nitrates as adjunct hypertensive treatment. CurrHypertens Rep, 2006, 8: 60-68
50 Stokes GS, Ryan M. Can extended-release isosorbide mononitrate be used as adjunctive therapy for systolic hypertension? An open study employing pulse-wave analysis to determine effects of antihypertensive therapy. Am J Geriat Cardiol, 1997, 6: 11-19
51 Fung HL, Chung SJ, Bauer JA, et al. Biochemical mechanism of organic nitrate action.Am J Cardiol, 1992, 70: 4B-10B
52 Loscalzo J. Antiplatelet and antithrombotic effects of organic nitrates.Am J Cardiol, 1992, 70: 18B-22B
53 Diodati J, The'roux P, Latour JG, et al. Effects of nitroglycerin attherapeutic doses on platelet aggregation in unstable angina pectoris and acute myocardial infarction.Am J Cardiol, 1990, 66: 683-688
54 Abrams J. Mechanism of action of organic nitrates in the treatment of myocardiol infarction.Am J Cardiol, 1992, 70: 683-688
55 Dupuis J. Nitrates in congestive heart failure. Cardiovasc Drugs Ther, 1994, 8: 501-507
56 Bassenge E. Coronary vasomotor responses:role of endothelium and nitovasodilators.Cardiovasc Drugs Ther, 1994, 8: 601-610
57 Bassenge E. Nitrates in different vascular beds, nitrate tolerance, and interactions with endothelial function.Am J Cardiol, 1992, 70: B23-B29
58 Brown BG. Dyanmic mechanisms in human coronary stenosis.Circ J, 1984, 70: 917-922
59 Pupita G, Kaski JC, Galassi AR, et al. Myocardial ischemia caused by distal coronay-artery constriction in stable angina pectoris.N Engl J Med, 1990, 23: 514-520
60 Abrams J, Frishman W. The Organic Nitrates and Nitroprusside// Frishman W, Sonnenblick E, Sica D. Cardiovascular Pharmacotherapeutics.The Second edition. The United State of Amercia. The McGraw-Hill Companies, 2003: 203-214
61 Mueller R, Scheidt S. Nitroglycern// Messerli F. Cardiovascular Drug Threapy. The Second edition. The United State of Amercia. W. B. Saunders Company, 1996: 865-890
62 Stokes GS, Alex andra JB, Natasha H, et al. Longterm effectiveness of extended release nitrate for the treatment of systolic hypertension Hypertension, 2005, 43: 380-384
1 Kaplan NM. New issues in the treatment of isolated systolic hypertension. Circulation, 2000, 102: 1079-1081
2 Laurent S, Boutouyrie P, Benetos A. Patho physiology of hypertension in the elderly. Am J G eriat Cardiol, 2002, 11: 34-39
3 Nichols WW, O'Rourke M F, Avolio AP, et al. Effects of age on ventricular vascular coupling. Am J Cardiol, 1985, 55: 1179-1184
4 Hansson L, Zanchetti A, Carruthers SG, et al. Effects of intensive blood pressure lowering and low dose a spirin in patients with hypertension: Principal results of the Hypertension Optimal treatment (HOT) randomized trial. Lancet, 1998, 351: 1755-1762
5 V bomanski M, Norman J, Wolz M, et al. Cardiovascular risk assessment using pulse pressure in the first national health and nutrition examination survey. Hypertension, 2001 ,38 :793-797
6 Benetos A, Safar M. Pulse pressure a predictor of long-term cardiovascular motality in a French male population. Hypertension, 1997, 30: 1410-1415
7 Mattace-Raso FU, Verwoert GC, Hofman A, et al. Inflammation and incident-isolated systolic hypertension in older adults: the Rotterdam study. Hypertens, 2010, 28(5): 892-895
8 McEniery CM, McDonnell BJ, So A, et al. Aortic calcification is associated with aortic stiffness and isolated systolic hypertension in healthy individuals. Hypertension, 2009, 53: 524-531
9 Kung CF, Luscher TF. Different mechanism of endothelial dysfunction with aging and hypertension in rat aorta. Hypertension, 1995, 25: 194-200
10 Parenbrock M, Hausberg M, Kosch M, et al. A longitudinal study of vessel wall properties in normotensive and hypertensive renal transplant recipients. J H um Hypertens, 1988, 12: 707-711
11 Pignoli P, Tremoli E, Poli A, et al. Intimal plus medial thickness of the arterial wall : A direct measurement with ultrasound imaging Circulation, 1986, 74: 1399-1406
12 Asmar R, Benetos A. Assessment of arterial distensibility by automaticpulse wave velocity measurement. Hypertension, 1995, 26(3): 485-490
13 Stokes GS, Barin ES, Gilfillan KL. Effects of Isosorbide Mononitrate and AII Inhibition on Pulse Wave Reflection in Hypertension. Hypertension, 2003, 41(2): 297-301
14 Morgan TO, Anderson AI, Mac Inni s RJ. ACE inhibitors, beta-blockers, calcium blockers, and diuretics for the control of systolic hypertension.A M J Hypentens, 2001, 14(3): 241-247
15 Isla S. Mackenzie, Carmel M. McEniery, Zahid Dhakam, et al. Comparison of the Effects of Antihypertensive Agents on Central Blood Pressure and Arterial Stiffness in Isolated Systolic Hypertension. Hypertension, 2009, 54: 409-413
16 Kaufman R, Nunes I, Bolognese JA, et al. Single-dose effects of isosorbide mononitrate alone or in combination with losartan on central blood pressure. J Am Soc Hypertens, 2010, 4(6): 311-318.
17 Murrell W. Nitroglycerine as a remedy for angina pectoris.Lancet, 1879, 80: 80-227
18 Pauca AL, Kon ND, O’Rourke MF. Benef it of nitroglycerin on arterial stiffness is directly due to effects on peripheral arteries.Heart, 2005, 91: 1428-1432
19 Brosnan MJ, Hamilton CA, Graham D, et al. Irbesartan lowers superoxide levels and increases nitric oxide bioavailability in blood vessels from spontaneously hypertensive stroke-prone rats. J Hypertens, 2002, 20: 281-286
20 Schiffrin EL, Deng Li Y. Comparison of effects of angiotensin I-converting enzyme inhibition and beta-blockade for 2 years on function of small arteries from hypertensive patients.Hypertension, 1995, 25(part 2): 699-670
21 Ghiadoni L, Magagna A, Versari D, et al. Different effect of antihypertensive drugs on conduit artery endothelial function.Hypertension, 2003, 41: 1281-1286
22 Kiowski W, Linder L, Nuesch R, et al. Effect of cilazopril on vascular structure and function in essential hypertension.Hypertension, 1996, 27(part 2): 371-376
23 Stokes GS, Alex andra JB, Natasha H, et al. Longterm effectiveness of extended release nitrate for the treatment of systolic hypertension. Hypertension, 2005, 43: 380-384
24 Stokes GS. Nitrates as adjunct hypertensive treatment.Curr Hypertens Rep, 2006, 8: 60-68
25 Fung HL, Chung SJ, Bauer JA, et al. Biochemical mechanism of organic nitrate action.Am J Cardiol, 1992, 70: 4B-10B
26 Loscalzo J. Antiplatelet and antithrombotic effects of organic nitrates.Am J Cardiol, 1992, 70: 18B-22B
27 Diodati J, The'roux P, Latour JG,et al. Effects of nitroglycerin at therapeutic doses on platelet aggregation in unstable angina pectoris and acute myocardial infarction.Am J Cardiol, 1990, 66: 683-688
28 Abrams J. Mechanism of action of organic nitrates in the treatment of myocardiol infarction.Am J Cardiol, 1992, 70: 683-688
29 Dupuis J.Nitrates in congestive heart failure.Cardiovasc Drugs Ther, 1994, 8: 501-507
30 Bassenge E. Coronary vasomotor responses:role of endothelium and nitovasodilators.Cardiovasc Drugs Ther, 1994, 8: 601-610
31 Bassenge E. Nitrates in different vascular beds, nitrate tolerance, and interactions with endothelial function. Am J Cardiol, 1992, 70: B23-B29
32 Brown BG. Dyanmic mechanisms in human coronary stenosis.Circ J, 1984, 70: 917-922
33 Pupita G, Kaski JC, Galassi AR, et al. Myocardial ischemia caused by distal coronay-artery constriction in stable angina pectoris.N Engl J Med, 1990, 23: 514-520
34 Abrams J, Frishman W. The Organic Nitrates and Nitroprusside// Frishman W, Sonnenblick E, Sica D. Cardiovascular Pharmacotherapeutics.TheSecond edition. The United State of Amercia. The McGraw-Hill Companies, 2003: 203-214
35 Mueller R, Scheidt S. Nitroglycern// Messerli F. Cardiovascular Drug Threapy. The Second edition. The United State of Amercia. W B. Saunders Company, 1996: 865-890