| BACKGROUND:Currently, cardio and cerebrovascular diseases have become the leading cause of death among the Chinese population, and hypertension is one common type of cardiovascular syndrome, in addition to multiple others like stroke, coronary heart disease, heart failure, kidney disease that are harmful to people's lives and health.According to existing epidemiological data, China now has more than 200 million people suffering from hypertension, and this number is growing by 10 million every year, china's national annual direct cost of treatment for high blood pressure exceeds 40 billion yuan(Chinese currency). Hypertension has become a major public health problem in china.However, currently hypertension awareness, treatment and control rates have remained at low levels; various types of antihypertensive drugs are effective only for about 42%-59%. Practice has proved that combination therapy is conducive to effective control of blood pressure; reduce the incidence of adverse drug reactions. The Felodipine Event Reduction (FEVER) study shows that calcium antagonist in combination with diuretics is superior to a single diuretic effect. The study further found that there are differences in incidence in the use of different drug combination programs to reduce blood pressure and cardiovascular risk events. The anglo-scandinavian cardiac outcome trial-blood pressure lowering arm (ASCOT-BPLA) study showed that amlodipine combined with perindopril in patients with risk factors for hypertension is superior to Atenolol combined with bendrofluazide. The American Society of Hypertension recently published a blood pressure lowering drug combination treatment program formal submission, recommended calcium antagonist/ diuretic, ACEI/diuretics, angiotensinⅡreceptor antagonist/calcium antagonists, ACEI /calcium antagonists as first choice combination therapyThe Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) study shows that benazepril-amlodipine combination was superior to the benazepril-hydrochlorothiazide combination in reducing cardiovascular events in patients with hypertension who were at high risk for such events. However the superior effect of calcium antagonists and angiotensin II antagonist combination over that of calcium antagonists and diuretics is not clear.The main cause of long standing hypertension is systemic small artery disease changes coupled with other risk factors, promotes the formation of atherosclerosis, ultimately leading to heart, brain, kidney and other target organ damage and multiple complications. The atherosclerotic pathological changes and multiple common cardiovascular pathophysiological disease basis, are independent predictors of cardiovascular events in hypertensive patients.Many studies show that early diagnosis and intervention can reduce atherosclerosis incidence of cardiovascular events. Such as the determination of arterial pulse wave velocity (PWV), ankle brachial index (ABI), reflected wave augmentation index (AI) and a series of detection technology have been brought forth for the early diagnosis of atherosclerotic diseases has created favorable conditions. ABI (Ankle-Brachial Index, ABI) is the ratio of the systolic blood pressure measured at the ankle to the systolic blood pressure measured at the brachial artery. ABI is based on the principle of peripheral arterial stenosis reaches a critical level and lead to a narrow distal perfusion pressure in the lower level which is roughly proportional to the severity of disease. AHA published estimates as follows:first, bilateral brachial artery systolic blood pressure measurement is done and there should be a difference of 10 mmHg (1 mmHg=0.133 kPa) between each brachial B.P, The brachial systolic pressure in both arms is measured and patient is first allowed to rest for 5-10 minutes in the supine position. BP cuff is placed on the patient's upper arm with the lower edge approximately 1 inch above the antecubital fossa.Brachial pulse is palpated for and conductivity gel is applied over the brachial artery. The tip of the probe is placed into the gel at a 45-60-degree angle until clear arterial pulse sounds are heard. The cuff is inflated to the point that pulse sounds disappear, then go 20 mm Hg above that point. Slowly deflate at a rate of 2 mm Hg per sec and the point where arterial pulse sounds resume is recorded. This is the brachial systolic pressure. This procedure is repeated in the other arm. The higher of the two brachial systolic pressure readings will be used to calculate the ABI. There should be a difference of less than 10 mm Hg between each brachial BP.The posterior tibial and dorsalis pedis systolic pressure in both legs is measured. The BP Cuff is placed on the patient's leg approximately 2 inches above the ankle's medial malleolus.The posterior tibial (PT) pulse is located, a gel is applied, and the Doppler probe is positioned. Systolic pressure is then measured following the same procedure described for the brachial artery. On the same leg, the dorsalis pedis (DP) pulse is located and systolic pressure measured. Measurement of both the PT and DP systolic pressures on the other leg is repeated. The higher of the two ankle readings for each leg (PT or DP) is selected These numbers will serve as the ankle systolic pressures in the ABI calculation. If either the PT or DP ankle pulse is absent, then the measurable reading is used to calculate the ABI.To calculate the ABI, each ankle systolic pressure is divided by the brachial systolic pressure. The higher of the two systolic pressures for each leg is divided by the higher of the two arm pressures to get the right and left ABI respectively.ABI may be an independent predictor of mortality, as it reflects the burden of atherosclerosis. A normal ABI is>0.9. An ABI<0.9 suggests significant narrowing of one or more blood vessels in the leg. The majority of patients with claudication have ABIs ranging from 0.3 to 0.9. Rest pain or severe occlusive disease typically occurs with an ABI <0.5. ABIs<0.2 are associated with ischemic or gangrenous extremities. Conditions such as diabetes mellitus or end stage-renal disease can give falsely elevated ABIs (1.3-1.5). The ABI test approaches 95% accuracy in detecting PAD. However, a normal ABI value does not absolutely rule out the possibility of PAD. Some patients with normal or near-normal ABI results may have symptoms suggesting PAD. If the resting ABI is normal, an exercise ABI should be conducted. PWV is velocity of pulse wave within the blood vessel. It is the velocity at which the pressure wave propagates because it is directly related to arterial stiffness. It is an independent predictive index of arterial stiffness. Reduction of arterial elasticity may lead to a faster transmission of arterial pulse wave velocity. The biomechanical properties of arterial walls, blood vessels geometric properties and density of blood factors to a certain extent have a relationship with arterial stiffness. PWV values change with many physiological factors. Age, respiration and cardiovascular health are some of the factors. As a person ages, his arteries harden gradually and the PWV of an arterial segment increases gradually following a relatively smooth curve. When a person develops cardiovascular problems the PWV deviates from the normal curve.PWV varies with respiration. It is slightly higher during expiration than inspiration due to the fact that blood pressure is slightly increased during the expiratory phase.The baseline value is< 1400cm/s(Normal). there is a certain degree of positive correlation between PWV and arterial stiffness, and the method of measurement is simple, noninvasive, widely used in clinical practice. PWV may well reflect stiffness in large arteries, faster PWV, the difference in the distensibility of arteries, the higher the stiffness, the lesser the flexibility. PWV was measured by measuring the pulse wave transit time and the distance between the two recording sites on the body obtained, calculated as PWV (m/s)= L(distance of two positions on the body) divided by t(time taken to travel in the two positions).for the prevention and treatment of atherosclerosis, there is need to avoid cardiovascular risk through multiple channels, involving a comprehensive intervention, which is an important part of controlling blood pressure, and selecting the "most reasonable" choice of antihypertensive drug programs, on how to determine the "best" program that could effectively control blood pressure and improve vascular function are still unresolved problems.Calcium channel blockers are widely used in china as first-line antihypertensive drugs in patients with hypertension, Syst-China, FEVER and other studies are some of the examples where dihydropyridine calcium antagonist-based drugs have been used. In this study we used different amlodipine-based drug combination program that lower Blood pressure, we evaluated the efficacy, adverse drug reactions and safety of amlodipine based drug programs (compound amiloride/amlodipine and telmisartan/amlodipine) on arterial stiffness in patients with hypertension.Objective:explore the effectiveness of different drug combination programs based on amlodipine to arterial stiffness in hypertensive patients.Materials and Methods:1. Study subjects and methods: In a randomized Prospective Study,106 elderly dyslipidemic hypertensive patients aged 60-79 years were enrolled, from three different communities in Hunan province out of which 99 subjects completed the study and 7 subjects dropped out (lost to follow up due to unclear reasons). A comprehensive physical and medical examination was carried out on them and laboratory tests which included:-Lipid profiles (TC, TG, HDL-C, LDL-C), liver function tests (AST, ALT), renal function tests (creatinine & uric acid) done on all the subjects. In addition, their B.P, brachial-ankle PWV and ABI were measured to assess the degree of arterial stiffness in order to predict cardiovascular events.They were later randomly assigned to two different groups of medications viz:-to telmisartan/amlodipine or amiloride/amlodipine. Subjects were followed up for 12 months of randomized prospective open blind ended treatment(PROBE).In the telmisartan group, oral doses of,(telmisartan 40mg+amlodipine 2.5mg) were administered, taken once daily, every morning, and in the amiloride group (amilodipine 2.5mg+compound amiloride plain tablets-amiloride 1.25mg,hydrochlorothiazide 12.5mg),one tablet once every morning were administered to the study subjects.2. Laboratory examination: Each subject underwent a comprehensive physical and medical examination, and then laboratory examinations where a lipid profile, renal and liver function tests were done. Blood pressure was taken and to measure the degree of arterial sclerosis, BaPWV and ABI measurements were done.3. Statistical Analysis: SPSS for windows version 11.5 soft ware was used for statistical analysis. Data is expressed as mean x±S; to compare and contrast between the two treatment groups before and after treatment,paired t test was performed. (If the variance is incomplete, then it would be compared using two independent samples by the Mann-Whitney U test.).efficiency was compared by using theχ2 test. significant level (P value) was P <0.05 for a statistically significant difference, and if P<0.01 showed an even more significant statistical difference.The effectiveness of these drug programs were assessed by quantification of the stiffness and other properties of the arterial wall which included measurements of the following indicators:-brachial-ankle PWV, ABI, systolic & diastolic blood pressures, lipid profile, liver and renal function tests and relating them to the traditional cardiovascular risk factors. In the final analysis, we compared:-(ⅰ) the effectiveness of B.P reduction in the two treatment groups, (ⅱ) B.P reduction rate in the two groups, (ⅲ) extent of B.P reduction before and after treatment in the two groups, (ⅳ) PWV and ABI for both groups before and after treatment, (ⅴ) treatment compliance in the two treatment groups, (ⅵ) laboratory test results for the two groups before and after treatment.Results:Arterial stiffness comparison for the two groups (2.1) PWV and ABI for both groups after treatment was compared with the baseline values, and PWV was significantly lower (P<0.05), whereas ABI values were not significantly changed (P>0.05). Comparing the values for both groups after treatment, PWV values reduced whereas ABI values increased. The results shows that the difference between the two groups were not statistically significant (P> 0.05) 2.2 Blood pressure comparison for the two groups was2.2.1 Comparison of efficiency in blood pressure reduction for the two groups was that after 12 weeks of treatment the efficiency in the amlodipine/telmisartan group was 90% (45/50), while the efficiency in the amlodipine/amiloride group was 89.8%(44/49).The efficiency rate in blood pressure reduction for the two groups showed no statistically significant difference (P>0.05).2.2.2 Comparison of Blood pressure reduction for the two groups that reached target levels (standard rates)After 12 weeks of treatment, rate of blood pressure reduction that reached target levels in the amlodipine+telmisartan group was 70.0%(35/50), while that in the amlodipine+ amiloride group was 55.1%(27/49), there was no statistically significant difference in blood pressure reduction for both groups that reached target levels (standard rates).The results showed:no significant difference (P> 0.05).2.2.3 Comparison of blood pressure reduction for the two groups before and after treatment.after the treatment, systolic blood pressure in the amlodipine+telmisartan group decreased by (29.1±13.1) mmHg, systolic blood pressure decrease in the amiloride group was (26.3±16.4) mmHg, there was significant difference (P<0.05); in the telmisartan group decrease in diastolic blood pressure was (11.5±7.8) mmHg, diastolic blood pressure decrease in the amiloride group was (10.5±9.5) mmHg, difference between the two groups were not statistically significant (P> 0.05).2.3 Comparison of occurrence of adverse drug reactions in the two groups 106 cases of patients with no history of drug discontinuation due to obvious harmful effects. In the telmisartan group,3 patients dropped out,4 dropped out from the amiloride group. These 7 patients were lost to follow-up. Occurrence of adverse drug reactions was less in both groups. In the telmisartan group, there were 2 cases of dizziness and 2 cases of headache whereas in the amiloride group, there were 4 cases of dizziness and 1 case of headache. The rate of occurrence of ADR in the telmisartan group was 8.0% and 10.2% in the amiloride group respectively.By using X2 test in both groups, the rate of occurrence of Adverse drug reaction was not statistically significant (P>0.05). All adverse drug reaction were characterized by dizziness and headache. These reactions improved on symptomatic treatment, the symptoms disappeared and did not affect further treatment.2.4 Comparison of laboratory results for both groups before and after treatment In the telmisartan group average uric acid before treatment was (329.3±12.0) mmol/L, after treatment it was (288.3±12.2) mmol/L, there was significant difference (P <0.05), while in the amiloride group uric acid levels before and after treatment showed no significant change (P>0.05). Electrolytes, lipids and other biochemistry items before and after treatment had no significant changes (P> 0.05).Conclusion:1. Both combination drug programs help reduce arterial stiffness and improve vascular compliance but failed to improve ABI in the short term.2. Both combination groups are safe & effective in hypertensive patients but telmisartan/amlodipine was more beneficial in lowering systolic blood pressure3. Compared with amiloride/amlodipine, telmisartan/amlodipine may be of more benefit in reducing uric acid levels.
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