Manidipine-delapril combination in the management of hypertension

High blood pressure (BP) is the major cardiovascular risk factor and the main cause of death around the world. Control of blood pressure reduces the high mortality associated with hypertension and the most recent guidelines recommend reducing arterial BP values below 140/90 mmHg for all hypertensive patients (130/80 in diabetics) as a necessary step to reduce global cardiovascular risk, which is the fundamental objective of the treatment. To achieve these target BP goals frequently requires combination therapy with two or more antihypertensive agents. Although the combination of a diuretic and an angiotensin converting enzyme inhibitor (ACEI) is the most commonly used in the clinical practice, the combination of an ACEI and a calcium channel blocker may have an additive antihypertensive effect, a favorable effect on the metabolic profile, and an increased target organ damage protection. The new oral fixed combination manidipine 10 mg/delapril 30 mg has a greater antihypertensive effect than both components of the combination separately, and in non-responders to monotherapy with manidipine or delapril the average reduction of systolic and diastolic BP is 16/10 mmHg. The combination is well tolerated and the observed adverse effects are of the same nature as those observed in patients treated with the components as monotherapy. However, combination therapy reduces the incidence of ankle edema in patients treated with manidipine.     

Sexual function in hypertensive patients receiving treatment

In many forms of erectile dysfunction (ED), cardiovascular risk factors, in particular arterial hypertension, seem to be extremely common. While causes for ED are related to a broad spectrum of diseases, a generalized vascular process seems to be the underlying mechanism in many patients, which in a large portion of clinical cases involves endothelial dysfunction, ie, inadequate vasodilation in response to endothelium-dependent stimuli, both in the systemic vasculature and the penile arteries. Due to this close association of cardiovascular disease and ED, patients with ED should be evaluated as to whether they may suffer from cardiovascular risk factors including hypertension, cardiovascular disease or silent myocardial ischemia. On the other hand, cardiovascular patients, seeking treatment of ED, must be evaluated in order to decide whether treatment of ED or sexual activity can be recommended without significantly increased cardiac risk. The guideline from the first and second Princeton Consensus Conference may be applied in this context. While consequent treatment of cardiovascular risk factors should be accomplished in these patients, many antihypertensive drugs may worsen sexual function as a drug specific side-effect. Importantly, effective treatment for arterial hypertension should not be discontinued as hypertension itself may contribute to altered sexual functioning; to the contrary, alternative antihypertensive regimes should be administered with individually tailored drug regimes with minimal side-effects on sexual function. When phosphodiesterase-5 inhibitors, such as sildenafil, tadalafil and vardenafil, are prescribed to hypertensive patients on antihypertensive drugs, these combinations of antihypertensive drugs and phosphodiesterase 5 are usually well tolerated, provided there is a baseline blood pressure of at least 90/60 mmHg. However, there are two exceptions: nitric oxide donors and alpha-adrenoceptor blockers. Any drug serving as a nitric oxide donor (nitrates) is absolutely contraindicated in combination with phosphodiesterase 5 inhibitors, due to significant, potentially life threatening hypotension. Also, a-adrenoceptor blockers, such as doxazosin, terazosin and tamsulosin, should only be combined with phosphodiesterase 5 inhibitors with special caution and close monitoring of blood pressure.     

连云港农村社区高血压患者药物干预研究

目的 探讨农村居民使用经济、合理的降压药物提高血压控制率的方法.方法 对连云港两县高血压患者服用降压药物状况进行调查,然后给予研究对象依那普利治疗,收缩压≥160 mmHg和(或)舒张压≥100 mmHg的对象加服尼群地平或氢氯噻嗪,随访3周后观察高血压患者控制率的变化情况.结果 总共调查19 667名高血压患者,高血压治疗率为43.98%,控制率仅为2.73%,联合用药的患者仅占22.18%.共18 771名患者给予3周药物干预,46.48%患者采用联合用药,达标率为41.40%.结论 中国高血压指南推荐的降压药物价格经济,而且可显著提高高血压控制率.     

Summary of the practice guideline 'Hypertension' (third division) from the Dutch College of General Practitioners

The revised practice guideline on hypertension from the Dutch College of General Practitioners has been brought in agreement with the guideline on hypertension from the Dutch Institute for Health Care Improvement. The main changes with regard to the former edition are: The threshold values for the diagnosis 'hypertension' have been lowered to 140 mmHg and 90 mmHg for the systolic and diastolic blood pressures, respectively. Annual screening for hypertension in the elderly is no longer recommended. Henceforth, blood pressure measurement once every five years is considered sufficient, unless the blood pressure is known to be in a borderline area in which treatment is being considered. Often, the decision as to whether a patient should take antihypertensive drugs no longer depends on the presence of hypertension as such: to receive drug treatment, the patient should have at least a 20% risk of developing a cardiovascular disease in the next 10 years. To aid in estimating this risk for individual patients a risk table has been devised. Diuretics and beta-blockers are the drugs of first choice. If the blood pressure remains too high, angiotensin-converting-enzyme (ACE) inhibitors and calcium-channel blockers may be added.     

老年单纯收缩期高血压诊治体会

目的探讨老年收缩期高血压的诊断与治疗,减少心脑血管事件的危险因素。方法对74例在门诊治疗老年单纯收缩期高血压进行血压监测,强调非药物治疗和药物治疗的合理应用。结果单剂用药血压控制率(7例)9%,联合用药血压控制率(25例)34%,改变不良生活方式同时服用降压药血压控制率为32例43%。结论良好的生活习惯和联合用药能保护靶器官控制高血压,有效的减少老年单纯收缩期高血压的致残率和死亡率。     

Fixed combination of losartan and hydrochlorothiazide and reduction of risk of stroke

A fixed-dose combination of losartan/hydrochlorothiazide (HCTZ) therapy may be a logical choice for antihypertensive treatment, including for initial therapy in patients with blood pressure elevation >20/10 mmHg above treatment target. The renin-angiotensin-aldosterone-system-activating effect of hydrochlorothiazide augments the efficacy of blocking the angiotensin II type 1 (AT1) receptor with losartan. Some adverse effects associated with hydrochlorothiazide, including increased risk for new-onset diabetes mellitus, may be offset by losartan. Losartan was frequently administered with hydrochlorothiazide in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study, in which there was a 25% risk reduction for stroke in the losartan-based compared with the atenolol-based treatment group. The efficacy, tolerability, and convenience of losartan/HCTZ combination therapy may increase patient compliance and lower risk for stroke, a devastating outcome in patients with hypertension.     

老年单纯收缩期高血压诊治体会

目的探讨老年收缩期高血压的诊断与治疗，减少心脑血管事件的危险因素。方法对74例在门诊治疗老年单纯收缩期高血压进行血压监测，强调非药物治疗和药物治疗的合理应用。结果单剂用药血压控制率（7例）9％，联合用药血压控制率（25例）34％，改变不良生活方式同时服用降压药血压控制率为32例43％。结论良好的生活习惯和联合用药能保护靶器官控制高血压，有效的减少老年单纯收缩期高血压的致残率和死亡率。     

Trandolapril/verapamil combination in hypertensive diabetic patients

Cardiovascular diseases are directly affected by arterial hypertension. When associated with diabetes mellitus, the potential deleterious effects are well amplified. Both conditions play a central role in the pathogenesis of coronary artery disease, heart failure, stroke, and renal insufficiency. Prevalence of hypertension is much higher among diabetic than non-diabetic patients, and the hypertensive patient is more likely to develop type 2 diabetes. Current international guidelines recommend aggressive reductions in blood pressure (BP) in hypertensive patients with additional risk factors, including cardiovascular risk factors, and emphasize the relevance of intensive reduction in patients with diabetes mellitus; a goal of 130/80 mm Hg is required. To achieve BP target a combination of antihypertensives will be needed, and the use of long-acting drugs that are able to provide 24-hour efficacy with a once-daily dosing confers the noteworthy advantages of compliance improvement and BP variation lessening. Lower dosages of the individual treatments of the combination therapy can be administered for the same antihypertensive efficiency as that attained with high dosages of monotherapy. Angiotensin-converting enzyme inhibitors and calcium-channel blockers as a combination have theoretically compelling advantages for vessel homeostasis. Trandolapril/verapamil sustained release combination has showed beneficial effects on cardiac and renal systems as well as its antihypertensive efficacy, with no metabolic disturbances. This combination can be considered as an effective therapy for the diabetic hypertensive population.     

Managing hypertension in diabetic patients--focus on trandolapril/verapamil combination

Hypertensive diabetes individuals are at higher risk for cardiovascular events and progression to end stage renal disease. Several well conducted clinical trials indicate that aggressive treatment of hypertension in individual with diabetes reduces these complications. Combinations of two or more antihypertensive drugs are frequently required to reach the target blood pressure and to improve the cardiovascular and renal outcomes in these patients. There are physiological and clinical rationales for renin-angiotensin system blockade in hypertensive diabetics. Trandolapril/verapamil sustained released (SR) is a fixed-dose combination of trandolapril and a sustained release formulation of verapamil and indicated in treatment of hypertension in patients who require more than one drug to reach target blood pressure. The antihypertensive efficacy of trandolapril/verapamil SR has been evaluated extensively in large trials. In the INVEST trial, a verapamil SR-based treatment strategy that included trandolapril in most patients was effective in reducing the primary outcome in hypertensive patients with coronary artery disease. The new onset of diabetes was also significantly lower in the verapamil SR/trandolapril treatment group in comparison with those on the atenolol/hydroclorothiazide treatment group. The BErgamo NEphrologic Diabetes Complications Trial (BENEDICT) documented that in hypertensive diabetes and normoalbuminuria, trandolapril plus verapamil or trandolapril alone delayed the onset of microalbuminuria independent of their blood pressure-reducing effect. Thus, trandolapril/verapamil is an effective option for treatment of hypertensive diabetes patients requiring more than one agent to achieve target blood pressure.     

The applicability of home blood pressure measurement in clinical practice: a review of literature

Purpose

To review the literature on home blood pressure measurement (HBPM), to examine its validity and applicability for clinical practice and to provide recommendations regarding HBPM assessment.

Findings

HBPM can eliminate the white coat effect and offers the possibility to obtain multiple measurements under standardized conditions, which increases knowledge of overall blood pressure value. Although it is not entirely capable of replacing ambulatory blood pressure measurement (ABPM), HBPM correlates better with target organ damage and cardiovascular mortality than office blood pressure measurement (OBPM), it enables prediction of sustained hypertension in patients with borderline hypertension, and proves to be an appropriate tool for assessing drug efficacy. Additional advantages of HBPM are that it may increase drug compliance and patient’s awareness of hypertension. Overall, OBPM yield higher blood pressure values than HBPM. Differences between OBPM and HBPM tend to increase with age and are generally higher in patients without antihypertensive treatment than in patients with antihypertensive treatment.

Recommendations

Measurements should be performed according to accepted guidelines and recordings should be performed with a memory equipped automatic validated device. From the data reviewed here, we recommend that HBPM be assessed monthly by taking two measurements in the morning within 1 hour after awakening and two in the evening for three consecutive days, the data from the first day should be dismissed. A subject should be labeled hypertensive if his/her HBPM value is equal to or greater than 137 mmHg systolic and/or 84 mmHg diastolic.     

The practice guideline 'Hypertension' (third revision) from the Dutch College of General Practitioners; a response from the perspective of general practice

In the revised practice guideline on hypertension from the Dutch College of General Practitioners, some changes have been made in the areas of diagnosis and therapy in comparison to the previous edition. Finding people with hypertension is a major goal for the prevention of cardiovascular disease. A systolic blood pressure > 140 mmHg (> 160 mmHg in patients > 60 years) necessitates non-pharmaceutical advice and antihypertensive therapy with diuretics, beta-blockers, angiotensin-converting-enzyme (ACE) inhibitors or calcium antagonists, either as monotherapy or in combination. In view of the ever-increasing importance of ACE inhibitors in antihypertensive therapy, we expect that the next revision of the practice guideline will soon be necessary.     

Hypertension in the nursing home

Hypertension in a nursing home patient is a systolic blood pressure of 140 mm Hg or higher and 130 mm Hg or higher in a patient with diabetes mellitus or chronic renal insufficiency, or a diastolic blood pressure of 90 mm Hg or higher and 80 mm Hg or higher in a patient with diabetes mellitus or chronic renal insufficiency. Numerous prospective, double-blind, randomized, placebo-controlled studies have demonstrated that antihypertensive drug therapy reduces the development of new coronary events, stroke, and congestive heart failure in older persons. The goal of treatment of hypertension in elderly persons is to lower the blood pressure to less than 140/90 mm Hg and to less than 130/80 mm Hg in older persons with diabetes mellitus or chronic renal insufficiency. Elderly persons with diastolic hypertension should have their diastolic blood pressure reduced to 80 to 85 mm Hg. Diuretics should be used as initial drugs in the treatment of older persons with hypertension and no associated medical conditions. The selection of antihypertensive drug therapy in persons with associated medical conditions depends on their associated medical conditions. If the blood pressure is more than 20/10 mm Hg above the goal blood pressure, drug therapy should be initiated with 2 antihypertensive drugs, one of which should be a thiazide-type diuretic. Other coronary risk factors must be treated in patients with hypertension.     

Nutrition and health--hypertension

Hypertension, defined as a blood pressure > or = 140/90 mmHg upon repeated measurement or the use of antihypertensive medication, is present in 14% of Dutch adults. A healthy diet plays an important role in both the prevention and treatment of hypertension. Under controlled conditions, very good results have been obtained with the 'Dietary approaches to stop hypertension' (DASH) combination diet, which has recently been developed in the United States. The DASH combination diet contains large amounts of fruit, vegetables, fish and nuts, low-fat dairy products and reduced levels of total and saturated fat. This dietary pattern yielded blood pressure reductions of 11.4/5.5 mmHg in mildly hypertensive patients. Intervention studies have shown a favourable effect of salt reduction on blood pressure in hypertensive patients, even in the case of mild hypertension. Simultaneous increases in potassium and magnesium intake could have an additional beneficial effect. The use of a low-sodium, high-potassium mineral salt could make a useful contribution to the prevention and treatment of hypertension. In case of hypertension, it is further recommended to reduce the intake of liquorice to less than 50 g per day. These dietary measures, combined with weight loss and physical exercise, may prevent drug treatment in patients with mild hypertension.     

Therapy of diabetic nephropathy

It appears to be confirmed by international studies that the development of end-stage nephropathy, cardiovascular mortality and morbidity can be reduced to a large extent by achieving a target blood pressure of 130/85 mmHg in diabetes hypertension and 125/75 mmHg in diabetic nephropathy. Diuretics, beta-blockers, ACE inhibitors and calcium antagonists are all recommended agents with evidence "A" according to both international and national recommendations. The most efficient nephroprotection and simultaneous intensive and efficient blood pressure reduction can be achieved by ACE inhibitors and AT1 receptor blockers as basic agents. It is often required to use combination treatment to achieve the target blood pressure. In the predialysis stage, tight blood pressure control should be completed with balanced glucose metabolism, restricted protein intake, controlled salt and water metabolism, early treatment of metabolic acidosis and preparation for kidney substitution treatment. The patient and the treating physicians should work together in a coordinated way during the complex nephrology, diabetes, cardiology care to slow down the progress of the disease.     

Prevention of target organ damage with modern antihypertensive agents

This review summarises the recent epidemiological data on hypertension, the aims of the treatment of hypertension, and emphasizes the importance of the modification of target organ damages and accelerated clinical conditions. Because the pathogenesis of hypertension is extremely complex, the therapy most likely requires a combined drug administration. The modern third generation dihydropyridine calcium channel blocker, amlodipine, not only has a favourable antihypertensive and anti-ischemic effect, but anti-atherosclerosis properties as well. There are plenty of evidence which demonstrate that lisinopril, a first line antihypertensive agent, has a positive effect in the treatment of left ventricular hypertrophy, retinopathy and nephropathy, and also has a favourable outcome after myocardial infarction and in heart failure. The combined administration of the two drugs leads to a favourable additive effect, with a decrease in the number and severity of side effects. The results of the ASCOT study proved a favourable effect with amlodipine based, combination therapy with an ACE-inhibitor, compared with the traditional beta-blockers and diuretics. The data of the CAFE sub-study showed, that in spite of the similar peripheral antihypertensive effect, the amlodipine based therapy decreased the central aortic pulse pressure to a greater extent. The central aortic pressure showed a good correlation with the end-points of the study, respectively. The results of the Hungarian multicenter study (HAMLET) proved the effective and safe administration of the two drugs in combination. Based on the above evidence, the fixed-dose combination of the CCB-ACE inhibitor (amlodipine-lisinopril) has not only effective blood pressure reducing properties, but also results in cardiovascular risk reduction, good tolerability and favourable compliance.     

ACE inhibitor-based treatment and antihypertensive effects in patients with type 2 diabetes

AIM: The presence of hypertension significantly increases cardiovascular risk in diabetic patients. Different classes of antihypertensive drugs, by targeting different pathophysiological mechanisms and therapeutic targets, might provide different antihypertensive effects. The authors speculated that drugs specifically targeting the renin-angiotensin-aldosterone system provide better antihypertensive control than other therapeutic agents. METHODS: Fifty consecutive type 2 diabetic patients with hypertension (M:F 29:21) were followed for 3-9 yrs. Antihypertensive treatment was stable for the last 12 months and included angiotensin convertying enzyme (ACE) inhibitors (ACEI) alone in 8 patients (group IA), ACEI combined with other drugs in 11 patients (group IB) and non-ACEI treatment in 31 patients (group II), 23 of whom were treated with Ca-channel blockers and 8 were treated with beta-blockers alone or with diuretics. During the last month of the study a 3-7 days antihypertensive drugs wash-out was performed. Measurements were performed in sitting position in the same ambulatory conditions, in supine position after 20 min of absolute rest, and in motionless standing station after quickly rising up from sitting rest. RESULTS: Groups IA, IB, and II had similar blood pressure values during antihypertensive therapy within the last year. However, blood pressure values after antihypertensive drug wash-out were significantly higher in groups IA and IB vs. group II (SBP and DBP resting sitting position, P=0.039 and P=0.014 respectively; SBP and DBP in standing position, P=0.001 and P=0.016, respectively). CONCLUSION: These data show that the underlying condition in terms of pathophysiologic mechanisms is more severe in groups IA and IB, including a greater increase of peripheral resistance. Thus we may conclude that the antihypertensive effect of ACEI is greater than other classes of antihypertensive drugs.     

机关工作人员高血压患者知晓及患病情况调查

目的了解我区机关工作人员中高血压患病、治疗及血压控制情况,为高血压的防治提供依据。方法对参加健康体检的807名机关工作人员进行血压测定、病史采集和问卷调查,分析不同年龄组人群高血压患病情况、高血压人群对自身是否患有高血压的知晓情况、服用降压药治疗情况及血压控制效果。结果我区机关工作人员高血压患病率为33.71%,其中,男性36.21%、女性18.02%,男性明显高于女性(P<0.01);高血压患者知晓自己患有高血压的知晓率为63.60%,服降压药治疗率为38.24%;服降压药的高血压患者中,血压控制在≤120/80mmHg的占35.58%,血压控制在121~139/81~89mmHg的占32.69%,血压≥140/90mmHg的占31.73%。结论我区机关工作人员中高血压患病率高,知晓率、服药治疗率及血压控制率虽高于文献报道,但仍有待进一步提高。     

福建建阳农村居民高血压知晓、治疗、控制情况及危险度评估

目的了解建阳农村居民高血压危险度及高血压的患病率、知晓率、治疗和控制现状。方法随机抽取建阳市农村地区8个村，年龄35～74岁的常住居民773人，测量血压、身高、体重，检测空腹血糖、血脂并收集其他相关资料。结果建阳市农村居民高血压患病率为23．42％，高血压患病率随着年龄增长而显著上升（P〈0．01）；高血压患者中，22．65％知道自己患有高血压，9．94％正在服用降压药，1．10％（2人）血压得到控制（〈140／90mmHg）。高血压患者并存的心血管病危险因素如高龄、血脂异常、肥胖等所占百分率，显著高于非高血压患者（P〈0．01）；高血压患者中，中危占57．46％，低危、高危和很高危分别占11．05％，12．71％和18．78％。结论建阳农村居民高血压知晓率偏低，而且治疗和控制率很低，高血压危险度评估以中危为主，应加强对高血压患者的综合干预力度。     

Hypertension consensus in The Netherlands

It is known that mild hypertension is a common disorder and there is increasing evidence that it is possible to decrease the incidence of cardiovascular damage by antihypertensive treatment. Stimulated by the controversy on the identification and treatment of patients with mild hypertension, a Dutch hypertension consensus meeting was held on March 16th 1990. Consensus was reached that the decision to treat should be taken on the basis of both the blood pressure level and the individual risk profile, including hypercholesterolaemia, history of smoking, diabetes, or a family history of cardiovascular disease. Subjects at risk should be identified by selective case finding (persons with known additional risk factors) and screening restricted to men aged 55 to 65 years. All patients should be started on non-pharmacological treatment by decreasing sodium intake, and where necessary reducing body weight and alcohol consumption, and stopping smoking. If antihypertensive drugs are to be given, diuretics, beta-blockers, ACE-inhibitors, and (or) calcium antagonists are the drugs of choice.