Dietary treatment of patients with mild to moderate hypertension in a general practice: a pilot intervention study (2). Beyond three months

In a general primary care practice the feasibility and the effects of dietary counselling in mild and moderate hypertension were studied for a period of 18 months. Significant decreases in blood pressure and sodium excretion compared to baseline occurred, while serum lipids showed transient improvement. Of the original 35 participants, 28 finished the study.     

A dose-response study of amlodipine in mild to moderate hypertension

The antihypertensive efficacy and suitability for once daily dosing of amlodipine, a new calcium antagonist, was studied in a series of 205 patients with mild to moderate hypertension. The study was conducted double-blind in 13 centres. The starting doses of amlodipine were 1.25, 2.5 and 5 mg, respectively, which were doubled after 4 weeks if normotension or a preset target blood pressure was not reached. Target blood pressure was reached in 25% of patients with placebo, 41% with 2.5 mg of amlodipine, 56% with 5 mg of amlodipine and 73% with 10 mg of amlodipine once daily. The drug was well tolerated at all dose levels and no changes occurred in heart rate, body weight or electrocardiogram during treatment. Amlodipine is a useful new calcium antagonist for the treatment of hypertension producing smooth, dose-dependent blood pressure reductions with convenient once daily dosing.     

Effects of Sho-Saiko-to on hepatocarcinogenesis and 8-hydroxy-2'-deoxyguanosine formation

Oxidative stress plays an important role in hepatocarcinogenesis. Although Sho-saiko-to (TJ-9), a Japanese herbal medicine which has been recently administered to patients with chronic liver disease in Japan, prevents hepatocarcinogenesis, the mechanism by which TJ-9 protects against cancer development is not fully understood. 8-Hydroxy-2'-deoxyguanosine (8-OHdG), a DNA adduct by reactive oxygen species, is known as a parameter of genetic risk for hepatocarcinogenesis. To clarify whether the preventive effect on hepatocarcinogenesis by TJ-9 is dependent on 8-OHdG, the effect on 8-OHdG levels by TJ-9 was examined by using high-performance liquid chromatography-mass spectrometry (LC-MS) in a diethylnitrosamine (DEN)-induced hepatocarcinogenesis model of male Fisher rats. TJ-9 reduced the number of preneoplastic cells, detected as the glutathione S transferase P (GST-P)-positive hepatocytes, and inhibited the development of liver tumors. TJ-9 also significantly decreased the formation of 8-OHdG, as indicated by LC-MS and immunohistochemical analysis. In addition, ornithine decarboxylase (ODC) activity and the number of proliferating cell nuclear antigen (PCNA)-positive cells were not altered. An electron paramagnetic resonance spin-trapping technique showed that TJ-9 scavenges hydroxyl radicals in a dose-dependent manner. In conclusion, the results of the present study suggest that TJ-9 prevents hepatocarcinogenesis in association with inhibition of 8-OHdG formation.     

8-hydroxy-2'-deoxyguanosine and lipid peroxidation in patients with heart failure

INTRODUCTION AND OBJECTIVES: Heart failure is associated with increased free radical production, which leads to a state of oxidative stress. Known markers of oxidative stress include 8-hydroxy-2'-deoxyguanosine, which reflects oxidative damage to DNA, and lipid peroxidation, which can be used to quantify damage to lipid-rich structures. The aims of this study were to compare 8-hydroxy-2'-deoxyguanosine and lipid peroxidation levels in heart failure patients and healthy subjects and to assess how these levels are influenced by heart failure etiology. METHODS: The study included 78 patients (57 male, age 64 [14] years) with heart failure and 12 control subjects. Patients completed a questionnaire and were graded according to the New York Heart Association classification. Doppler echocardiography was performed and blood samples were obtained. 8-hydroxy-2'-deoxyguanosine and lipid peroxidation levels were determined. RESULTS: Significant differences were observed between patients and control subjects in 8-hydroxy-2'-deoxyguanosine and lipid peroxidation levels, at 0.34 (0.54) ng/mL vs 0.04 (0.07) ng/mL (P<.05), and 18 (10) microM vs 8 (3) microM (P<.01), respectively. Subsequent analysis showed that heart failure etiology had a significant effect on the levels of the two markers (P<.05), which were highest in patients with hypertensive cardiomyopathy. CONCLUSIONS: Levels of 8-hydroxy-2'-deoxyguanosine and lipid peroxidation were higher in heart failure patients than in control subjects. The most significant increases were found in patients with hypertensive cardiomyopathy.     

Low-dose captopril in mild to moderate geriatric hypertension

The safety and efficacy of captopril in geriatric patients with mild to moderate hypertension was examined in an eight-week multicenter study of 99 patients. Following a placebo period, patients were treated with captopril 25 mg twice daily. Patients who were uncontrolled after two weeks of active therapy were randomized to either captopril 25 mg plus hydrochlorothiazide 15 mg or captopril 50 mg twice daily. The average decrease in blood pressure at study completion was--16.9/11.9 mmHg. At the conclusion of the trial, 75.8% of patients responded to therapy. Captopril was well tolerated and believed to be a good therapeutic alternative for treating hypertension in the elderly population.     

Dietary treatment of patients with mild to moderate hypertension in a general practice: a pilot intervention study (1). The first three months

Thirty-five patients with mild to moderate hypertension were randomised into a three months' dietary advised and a three months' control group. The diet was of a composition currently considered to be appropriate, and was monitored by a dietitian. Statistically significant decreases in diastolic blood pressure, mean arterial pressure, sodium excretion, and low density lipoprotein (LDL)-cholesterol occurred in the intervention group, although differences in change between the intervention and the control group were, except for LDL-cholesterol, not statistically significant. Thus, it did not become clear whether and to what extent change in diet was responsible for the lowering of the blood pressure in the intervention group.     

卡维地洛治疗老年轻中度原发性高血压疗效观察

目的本研究以高选择性β受体阻滞剂比索洛尔为对照药，研究了卡维地洛治疗轻中度原发性高血压的临床疗效及安全性。方法选择轻中度原发性高血压患者60例，分别随机给予卡维地洛和比索洛尔口服治疗。结果2组在治疗2周时诊室血压均有所下降，在治疗6～8周末下降最明显，并维持至24周。卡维地洛组和比索洛尔组降压总有效率分别为93．3％和90％，总显效率分别为70％和56．7％。卡维地洛主要的不良反应有头晕（13％）、乏力（2％）、嗜睡（2％）。在服药过程中逐渐减轻，无因药物不良反应而终止者。结论本研究中的原发性高血压患者每日口服1次卡维地洛12．5～50mg，降压疗效明显，耐受性及安全性好。     

Significance of 8-hydroxy-2'-deoxyguanosine levels in patients with idiopathic dilated cardiomyopathy

BackgroundAlthough oxidative stress mediated by reactive oxygen species plays an important role in the pathogenesis of heart failure (HF), good clinical markers for reactive oxygen species in patients with HF have not been established. 8-hydroxy-2′-deoxyguanosine (8-OHdG) is formed from deoxyguanosine in DNA by hydroxyl free radicals and might serve as a sensitive biomarker of intracellular oxidative stress in vivo. Thioredoxin (TRX) is known to be induced in cells as a radical scavenger against oxidative stress. The aim of this study is to evaluate the clinical significance of the serum 8-OHdG and TRX of patients with chronic HF with idiopathic dilated cardiomyopathy (DCM).Methods and ResultsWe estimated serum 8-OHdG and TRX levels using enzyme-linked immunosorbent assay in 32 patients with DCM and investigated the impact of these markers to the clinical characteristics of these patients. Serum levels of 8-OHdG, but not TRX were significantly correlated with New York Heart Association functional class, left atrial diameters, left ventricular end-diastolic diameters, left ventricular end-systolic diameters, and plasma levels of brain natriuretic peptide.ConclusionThese data suggest oxidative DNA damage is increased in patients with DCM according to the severity of HF. Serum levels of 8-OHdG may represent clinically useful markers of left ventricular remodeling.     

Comparative double-blind study of ramipril and captopril in mild to moderate essential hypertension

The angiotensin converting enzyme inhibitors ramipril and captopril were administered in doses of 10 mg once daily and 50 mg twice daily, respectively, to patients with mild to moderate essential hypertension. After a 4-week single-blind placebo washout period, patients were treated for 12 weeks with 1 of the drugs under double-blind conditions. Patients who did not respond after 6 weeks of treatment were given 50 mg hydrochlorothiazide concomitantly. The ramipril group showed greater decreases in blood pressure compared with baseline values: 20.1/14.9 mm Hg (ramipril) compared with 16.5/13.5 mm Hg (captopril). A further 6 weeks of treatment lowered the blood pressure even more: 22.5/20.0 mm Hg (ramipril) compared with 20.5/18.6 mm Hg (captopril). Concomitant hydrochlorothiazide given to nonresponders reduced the blood pressure levels in 24 of 40 patients in the ramipril group and in 20 of 36 patients in the captopril group. At the end of the study the overall response to treatment with ramipril alone and ramipril plus hydrochlorothiazide was 77.1%. The overall response rate in the captopril group was 82.7%. No clinically relevant adverse reaction occurred in any patient. Ramipril given once daily was as effective as captopril given twice daily in lowering blood pressure. Both drugs proved to be safe during treatment for 12 weeks.     

Long-term nopharmacological treatment for mild to moderate hypertension

Ninety-one middle-aged men and women with untreated mild hypertension were allocated to a nopharmacological treatment group or to a control group. Members of the treatment group were instructed to reduce daily sodium intake to less than 70 mmol, to reduce the intake of saturated fat, to lose weight if necessary and to perform regular physical exercise and relaxation training. Adherence to and effects of the programme on blood pressure and serum lipids were monitored for 12 months. In the treatment group, daily sodium excretion decreased to and remained at 50% of its original level (P less than 0.001), and there was a significant reduction in saturated fat intake. The average weight reduction was modest. Adherence to physical exercise and relaxation training regimens was poor. The net decreases (difference in changes between treatment and control group) in blood pressure were greatest during the first 3 months: in men the decrease in systolic blood pressure was 11.3 mmHg (P less than 0.001) and in diastolic blood pressure 8.3 mmHg (P less than 0.001); in women the decrease in systolic blood pressure was 10.8 mmHg (P less than 0.01) and in diastolic blood pressure 6.4 mmHg (P less than 0.01). However, this decrease diminished during the last 3 months to approximately one half owing to blood pressure reduction in controls. Low density lipoprotein cholesterol levels decreased significantly in treated men and women.     

Dose titration study of isradipine in Chinese patients with mild to moderate essential hypertension

Summary In order to assess the effective dose, tolerability, and safety of isradipine as a monotherapeutic antihypertensive agent for Chinese patients in Taiwan, an open trial was carried out. This study consisted of a 2-week, placebo, run-in period and an 8-week active treatment period, starting with isradipine 1.25 mg twice daily (bid) for the first 4 weeks, followed by 2.5 mg bid if the blood pressure was not normalized (diastole <90 mmHg). One hundred and one patients (M/F=48:53) were valid for efficacy analysis. Their age ranged from 30 to 64 years (mean±SD, 52±8). The blood pressure before active treatment was 160±2/104±1 mmHg. At the end of treatment period I (week 4), 12–14 hours after the last dose, 38 (37.6%) patients were normalized and 47 (46.5%) subjects responded (diastolic blood pressure reduction 10 mmHg). At week 8, 68 (67.3%) patients were normalized and 79 (78.2%) subjects responded. Isradipine reduced both systolic and diastolic blood pressures within 2 weeks of treatment. There were no significant differences in blood pressure reduction between both genders and among age groups. Safety analysis showed two subjects with severe flushing, dizziness, and palpitation who used the dose of 1.25 mg bid. They withdrew from the study. The adverse reactions of other patients were transient, mild, and tolerable. Most of the side effects were related to vasodilatation, but edema was not found. There was no change in body weight or heart rate, nor any atrioventricular conduction disturbances. In conclusion, isradipine in a dose of 1.25 or 2.5 mg bid proved to be an effective and well-tolerated antihypertensive agent for Chinese subjects in Taiwan with mild to moderate essential hypertension. This finding is similar to those reported in Caucasian patients.     

Comparison of enalapril and atenolol in mild to moderate hypertension

PURPOSE: Short-term therapy with angiotensin converting enzyme (ACE) inhibitors for hypertension is effective and well tolerated, and compared with beta blockers, may cause fewer adverse reactions. Furthermore, enalapril has been observed to have a greater effect on systolic blood pressure than beta blockers. We therefore decided to compare the ACE inhibitor enalapril and the beta blocker atenolol as monotherapy in a double-blind study of patients with mild to moderate hypertension. PATIENTS AND METHODS: After a four-week placebo run-in period, 162 patients were allocated randomly to receive atenolol (50 to 100 mg daily) or enalapril (20 to 40 mg daily) for 12 weeks. To assess the influence of these drugs on quality of life, a series of psychologic tests was performed, and a subset of patients also underwent treadmill exercise and pulmonary function tests. RESULTS: In 147 patients who completed the study, enalapril reduced supine blood pressure by 19/12 mm Hg, compared with 9/7 mm Hg for atenolol (p less than 0.001/p less than 0.005). The modest blood pressure response to atenolol was not due to poor compliance. A target blood pressure of 140/90 mm Hg or less was achieved by 35 percent of enalapril-treated atenolol (p less than 0.01). The frequency and severity of adverse effects with the two drugs were similar, and few important differences emerged from the quality-of-life assessments. CONCLUSION: At the doses used, enalapril induced a greater short-term blood pressure response than atenolol; long-term studies of its safety and efficacy are required.     

Potassium supplementation in blacks with mild to moderate essential hypertension

Potassium chloride (KCl) salt (65 mmol) daily reduced BP from 153/104 to 146/101 mmHg in 32 hypertensive black females during a 6-week placebo controlled crossover study. The fall in BP was independent of the order of randomization and was significant for systolic (SBP; P less than 0.01) and diastolic (DBP; P less than 0.05) pressure after 4 weeks. Analysis of the 95% confidence intervals in this and in five other studies, two of which were reported as showing no beneficial effect, suggests that potassium supplementation does lower BP, but that the change is small and within the confidence levels of all six trials. Thus, apparent discrepancies in the literature are not genuine statistically.     

Chronic effect of ketanserin in mild to moderate essential hypertension

Ketanserin, an antagonist highly selective for 5-hydroxytryptamine (serotonin) type 2 (S2) receptors, was given as monotherapy in a dose of 40 mg b.i.d. to 24 subjects with mild to moderate essential hypertension. Its effects were evaluated in a placebo-controlled double-blind crossover study. The effect on blood pressure in 18 subjects was monitored by 24-hour ambulatory intra-arterial measurements. Systolic and diastolic intra-arterial pressures were significantly lowered by ketanserin both during the day and at night, whereas heart rate was unchanged. Cuff pressure readings (triplicate measurements) with the London School of Hygiene sphygmomanometer and an automatic device (12 measurements in 1 hour) in the outpatient clinic also showed a significant effect on both supine and standing pressures. No postural hypotension was noted. Ketanserin had no effect on endogenous creatinine clearance, serum cholesterol levels, and the plasma levels of norepinephrine, renin, and aldosterone. The only side effect that was significantly more common with ketanserin than with placebo treatment was an increase in body weight. Ketanserin may have a place in the treatment of mild to moderate essential hypertension.