Influence of Hypersensitive C-Reactive Protein on the Effect of Continuous Antihypertensive Pharmacological Therapy.

ABSTRACT: Systemic chronic inflammation, represented by hypersensitive C-reactive protein (hsCRP), is an essential contributing factor to hypertension. However, the influence of hsCRP levels on the effect of antihypertensive pharmacological therapy remains unknown. We evaluated hsCRP levels in 3756 newly diagnosed, untreated hypertensive subjects. Participants were grouped by tertiles of hsCRP and were randomly treated with nitrendipine + captopril, nitrendipine + spironolactone hydrochlorothiazide + captopril, and hydrochlorothiazide + spironolactone. Blood pressure (BP) was recorded every 2 weeks. A multivariate mixed linear model was used to evaluate the impact of baseline hsCRP levels on the continuous antihypertensive effect. After 3, 6, 9, and 12 months of continuous antihypertensive treatment, no significant difference was observed in BP decline among the different hsCRP groups. We identified interactions between baseline hsCRP levels and follow-up time. After adjusting for conventional risk factors and the interactions between hsCRP and follow-up time, there was no significant association between baseline hsCRP level and antihypertensive effects at 0-6 months of follow-up. However, from 6 to 12 months, subjects with higher baseline hsCRP levels exhibited a more marked BP-lowering effect ( P < 0.001 at 9 months, P = 0.002 at 12 months). Overall, there exist interaction effects between baseline hsCRP levels and follow-up time. Individuals with higher baseline hsCRP levels may exhibit a better response to antihypertensive therapy.

Anti-arrhythmic and hemodynamic effects of oxy nifedipine, oxy nimodipine, oxy nitrendipine and oxy nisoldipine.

Our previous studies have established cardio-protective effects of furnidipine and its active metabolites. We therefore decided to compare the influence of oral and intravenous administration of furnidipine, nifedipine, nitrendipine and nimodipine to examine their effects on hemodynamics and arrhythmias. Since dihydropyridines are oxidatively metabolized in the body and the oxidized metabolites are among the final products, we studied the influence of four oxidized dihydropyridines (oxy nifedipine, oxy nimodipine, oxy nitrendipine and oxy nisoldipine) on the same parameters. In vivo model of ischemia- and reperfusion-induced arrhythmias of rats was used. Dihydropyridines were administered 5 mg/kg orally (24 and 1 h before ischemia) or 5 µg/kg intravenously (10 min before ischemia). 20 mg/kg of the oxidized dihydropyridines was given orally (24 and 1 h before ischemia). The dihydropyridines exhibited significant anti-arrhythmic actions after both forms of administration but their influence on blood pressure was differential and contrasting and depended on route of administration. The oxidized dihydropyridines imparted strong protection against lethal arrhythmias while exerting differential influences on blood pressure with oxy nifedipine and oxy nisoldipine being hypertensive and oxy nitrendipine being most normotensive. The differential effects observed with the dihydropyridines after the two routes of administration lend strength to the hypothesis that their metabolites may have a significant role in mediating the actions of the parent drug. The strong anti-arrhythmic action of the oxidized dihydropyridines along with their differential effect on blood pressure could indicate their potential use as cardio-protective drugs in certain groups of patients.

[Analysis of therapeutic effects of rural patients with hypertension by combination administration of low dosage of hydrochlorothiazide and nitrendipine].

OBJECTIVE: To evaluate the therapeutic effects of combination administration of hydrochlorothiazide and nitrendipine at low dosage in the treatment of rural hypertension patients. METHODS: By the method of cluster random sampling, 5292 primary hypertension patients from Fuxin, Liaoning Province were divided into health education group (control group) and drug intervention group in June 2006. The drug intervention group were treated with hydrochlorothiazide, nitrendipine and captopril by stepwise approach and we observe the antihypertensive effect of drug and the effect on the onset of stroke. RESULTS: The average follow-up time was 15 months. At last, 308 patients were lost to follow-up (the lost follow-up rate was 5.8 percent). The 4984 in cohort, including 2530 of intervention group and 2454 of control group, had examination of all indicators. Through health education and drug intervention, the average blood pressure in drug intervention group decreased by 16.1/9.4 mm Hg (1 mm Hg = 0.133 kPa) while the average blood pressure in control group decreased by 6.7/3.5 mm Hg. The control rate of blood pressure in drug intervention group was higher than control group (33.1% vs. 15.1%, P < 0.001). Through drug intervention, the morbidity risk of nonfatal stroke in drug intervention group decreased by 57.3% compared to control group, the total morbidity risk of stroke decreased by 59.4%. The results had significant statistical difference. And, the morbidity of severe hypopotassaemia (K(+) < 3.0 mmol/L) and diabetes mellitus had no significant statistical difference between two groups. CONCLUSIONS: The low-cost antihypertensive program based on thiazide had good antihypertensive effect, high safety and good cost-effect ratio. The program could be used in rural areas of China.

Cost-utility analysis of eprosartan compared to enalapril in primary prevention and nitrendipine in secondary prevention in Europe--the HEALTH model.

OBJECTIVE: To investigate the cost-utility of eprosartan versus enalapril (primary prevention) and versus nitrendipine (secondary prevention) on the basis of head-to-head evidence from randomized controlled trials. METHODS: The HEALTH model (Health Economic Assessment of Life with Teveten for Hypertension) is an object-oriented probabilistic Monte Carlo simulation model. It combines a Framingham-based risk calculation with a systolic blood pressure approach to estimate the relative risk reduction of cardiovascular and cerebrovascular events based on recent meta-analyses. In secondary prevention, an additional risk reduction is modeled for eprosartan according to the results of the MOSES study ("Morbidity and Mortality after Stroke--Eprosartan Compared to Nitrendipine for Secondary Prevention"). Costs and utilities were derived from published estimates considering European country-specific health-care payer perspectives. RESULTS: Comparing eprosartan to enalapril in a primary prevention setting the mean costs per quality adjusted life year (QALY) gained were highest in Germany (Euro 24,036) followed by Belgium (Euro 17,863), the UK (Euro 16,364), Norway (Euro 13,834), Sweden (Euro 11,691) and Spain (Euro 7918). In a secondary prevention setting (eprosartan vs. nitrendipine) the highest costs per QALY gained have been observed in Germany (Euro 9136) followed by the UK (Euro 6008), Norway (Euro 1695), Sweden (Euro 907), Spain (Euro -2054) and Belgium (Euro -5767). CONCLUSIONS: Considering a Euro 30,000 willingness-to-pay threshold per QALY gained, eprosartan is cost-effective as compared to enalapril in primary prevention (patients >or=50 years old and a systolic blood pressure >or=160 mm Hg) and cost-effective as compared to nitrendipine in secondary prevention (all investigated patients).

Effectiveness and tolerability of fixed-dose combination enalapril plus nitrendipine in hypertensive patients: results of the 3-month observational, post-marketing, multicentre, prospective CENIT study.

BACKGROUND AND OBJECTIVE: Monotherapy with any class of antihypertensive drug effectively controls blood pressure (BP) in only about 50% of patients. Consequently, the majority of patients with hypertension require combined therapy with two or more medications. This study aimed to evaluate the effectiveness (systolic BP [SBP]/diastolic BP [DBP] control) and tolerability of the fixed-dose combination enalapril/nitrendipine 10 mg/20 mg administered as a single daily dose in hypertensive patients. METHODS: This was a post-authorization, multicentre, prospective, observational study conducted in primary care with a 3-month follow-up. Patients throughout Spain with uncontrolled hypertension (> or =140/90 mmHg for patients without diabetes mellitus, or > or =130/85 mmHg for patients with diabetes) on monotherapy or with any combination other than enalapril + nitrendipine, or who were unable to tolerate their previous antihypertensive therapy, were recruited. Change from previous to study treatment was according to usual clinical practice. BP was measured once after 5 minutes of rest in the sitting position. Therapeutic response was defined as follows: 'controlled' meant controlled BP (<140/90 mmHg for nondiabetic patients, or <130/85 mmHg for diabetic patients); 'response' meant controlled BP, or a decrease in SBP of > or =20 mmHg and in DBP of > or =10 mmHg. The main laboratory test parameters were documented at baseline and after 3 months. Patients aged >65 years, with diabetes, with isolated systolic hypertension (ISH; SBP > or =140 mmHg for patients without diabetes, SBP > or =130 mmHg for patients with diabetes) and who were obese (body mass index [BMI] > or =30 kg/m2) were analysed separately. RESULTS: Of 6537 patients included, 5010 and 6354 patients were assessed in effectiveness and tolerability analyses, respectively. In the tolerability analysis population, there were 3023 men (47.6%) and 3321 women (52.4%). The mean (+/- SD) age of the tolerability analysis group was 62.8 (+/- 10.7) years. A total of 71.1% of the patients presented at least one clinical cardiovascular risk factor other than hypertension, with the most frequent being dyslipidaemia (42.3%), obesity (29.2%) and diabetes (23.9%). After 3 months of treatment, SBP and DBP showed mean (+/- SD) decreases of 26.5 (+/- 14.4) mmHg and 14.9 (+/- 9.0) mmHg, respectively, and 73.0% of patients responded to treatment while 40.9% achieved BP control (70.8%/36.1% in 2658 patients aged >65 years; 61.7%/46.8% in 1521 patients with diabetes; 55.3%/44.2% in 731 patients with ISH; 72.0%/36.4% in 1762 obese patients). Adverse events were reported in 10.8% of patients (n = 689). During the follow-up period, ten patients died and seven patients had serious adverse events; in no case was a causal relationship attributed to the study product. CONCLUSIONS: The rate of SBP/DBP control achieved demonstrates the effectiveness of the fixed-dose enalapril/nitrendipine 10 mg/20 mg combination administered as a single daily dose in patients with essential hypertension not adequately controlled with monotherapy or with any combination other than enalapril + nitrendipine. The proportion and type of adverse events reported were as expected and have already been described for both components of the enalapril/nitrendipine 10 mg/20 mg combination. These results confirm the effectiveness of a strategy based on a fixed-dose enalapril/nitrendipine 10 mg/20 mg combination in reducing BP and achieving BP control goals.

Calcium entry inhibition during resuscitation from shock attenuates inflammatory lung injury.

Trauma and hemorrhagic shock (T/HS) induce a systemic inflammatory response syndrome (SIRS). Neutrophils (polymorphonuclear leukocytes [PMN]) and other cells involved in acute lung injury (ALI) are activated by Ca2+ entry. Thus, inhibiting Ca2+ entry might attenuate post-traumatic lung injury. Inhibiting voltage-operated (L-type) Ca2+ channels during shock could cause cardiovascular collapse, but PMN are "nonexcitable" cells, lack L-type channels, and mobilize Ca2+ via nonspecific channels. We previously showed that PMN Ca2+ entry requires sphingosine 1-phosphate synthesis by sphingosine kinase and that both sphingosine kinase inhibition and blockade of nonspecific channels attenuate ALI when begun before shock. Pretreatment for clinical injuries, however, is impractical. Therefore, we now studied whether Ca2+ entry inhibition that begun during resuscitation from T/HS could attenuate SIRS and ALI without causing hemodynamic compromise. Male Sprague-Dawley rats underwent laparotomy and fixed-pressure shock (mean arterial pressure, 35 +/- 5 mmHg; 90 min). Sphingosine kinase inhibition or nonspecific Ca2+ channel inhibition was begun after resuscitation with 10% of shed blood. We then studied in vivo PMN activation and associated lung injury in the presence or absence of Ca2+ entry inhibition. Neither treatment worsened shock. Each treatment decreased CD11b expression, respiratory burst, PMN p38 MAP-kinase phosphorylation, PMN sequestration, and lung capillary leak in vivo. The similar results seen with two different forms of inhibition strengthen the conclusion that the biological effects seen were specific for calcium entry inhibition. Ca2+ entry inhibition is a candidate therapy for management of lung injury after shock.

Systolic blood pressure reduction with olmesartan medoxomil versus nitrendipine in elderly patients with isolated systolic hypertension.

OBJECTIVE: The prevalence of isolated systolic hypertension (ISH) is high in the elderly, and the objective of this study was to compare the antihypertensive efficacy of olmesartan medoxomil with that of nitrendipine in elderly (65-74 years) and very elderly (>/= 75 years) male and female patients with ISH. METHODS: Patients were randomized to 24 weeks of treatment with either olmesartan medoxomil 20 mg daily (n = 256) or nitrendipine 20 mg (n = 126) twice daily, with possible dose increase (to 40 mg daily) and addition of hydrochlorothiazide (HCTZ) 12.5 or 25 mg daily if required. RESULTS: On the primary endpoint [reduction in mean sitting systolic blood pressure (SBP) after 12 weeks of treatment], the two treatments were similar (olmesartan medoxomil, -30.0 mmHg; nitrendipine, -31.4 mmHg). No significant difference between the treatment groups was observed, and non-inferiority of olmesartan medoxomil to nitrendipine was demonstrated using an analysis of covariance (ANCOVA) model. Reductions in mean sitting and standing SBP and diastolic blood pressure (DBP) up to week 24 were also similar with both treatments. Blood pressure (BP) goal attainment rates (sitting SBP

Circadian blood pressure variation and antihypertensive medication adjustment in normoalbuminuric type 2 diabetes patients.

BACKGROUND/AIMS: The aim of the study was to assess the effect of an antihypertensive treatment adjustment on 24-hour blood pressure variation in type 2 diabetes patients. METHODS: The study group included 59 hypertensive type 2 diabetes patients subjected to a single one-step antihypertensive agent dose adjustment (increase or decrease). Ambulatory blood pressure monitoring was performed at baseline and 4-6 weeks after the treatment modification. Controls were 41 matched patients, in whom antihypertensive treatment remained unchanged. RESULTS: At baseline, 45 (76%) study group patients and 29 (71%) controls were 'non-dippers'; a similar number of patients in both groups converted to 'dipping' or vice versa: 11 (19%) from the study group and 7 (17%) controls. 'Converters' from the study group were significantly younger (47.5 +/- 3.9 vs. 56.4 +/- 12.2 years; p < 0.05) and had lower 24-hour systolic blood pressure than 'non-converters': 113.7 +/- 7.2 vs. 127.7 +/- 20.3 mm Hg (p < 0.01). CONCLUSION: A single one-step antihypertensive medication adjustment does not affect 'dipping' status in type 2 diabetes patients. However, the assessment of blood pressure variation should be made with greater caution in younger type 2 diabetes subjects with low systolic blood pressure.

Adjunctive treatment with moxonidine versus nitrendipine for hypertensive patients with advanced renal failure: a cost-effectiveness analysis.

BACKGROUND: Systemic hypertension often accompanies chronic renal failure and can accelerate its progression to end-stage renal disease (ESRD). Adjunctive moxonidine appeared to have benefits versus adjunctive nitrendipine, in a randomised double-blind six-month trial in hypertensive patients with advanced renal failure. To understand the longer term effects and costs of moxonidine, a decision analytic model was developed and a cost-effectiveness analysis performed. METHODS: A Markov model was used to extrapolate results from the trial over three years. All patients started in a non-ESRD state. After each cycle, patients with a glomerular filtration rate below 15 ml/min had progressed to an ESRD state. The cost-effectiveness analysis was based on the Dutch healthcare perspective. The main outcome measure was incremental cost per life-year gained. The percentage of patients progressing to ESRD and cumulative costs were also compared after three years. In the base case analysis, all patients with ESRD received dialysis. RESULTS: The model predicted that after three years, 38.9% (95%CI 31.8-45.8) of patients treated with nitrendipine progressed to ESRD compared to 7.5% (95%CI 3.5-12.7) of patients treated with moxonidine. Treatment with standard antihypertensive therapy and adjunctive moxonidine was predicted to reduce the number of ESRD cases by 81% over three years compared to adjunctive nitrendipine. The cumulative costs per patient were significantly lower in the moxonidine group 9,858 euro (95% CI 5,501-16,174) than in the nitrendipine group 37,472 euro (95% CI 27,957-49,478). The model showed moxonidine to be dominant compared to nitrendipine, increasing life-years lived by 0.044 (95%CI 0.020-0.070) years and at a cost-saving of 27,615 euro (95%CI 16,894-39,583) per patient. Probabilistic analyses confirmed that the moxonidine strategy was dominant over nitrendipine in over 98.9% of cases. The cumulative 3-year costs and LYL continued to favour the moxonidine strategy in all sensitivity analyses performed. CONCLUSION: Treatment with standard antihypertensive therapy and adjunctive moxonidine in hypertensive patients with advanced renal failure was predicted to reduce the number of new ESRD cases over three years compared to adjunctive nitrendipine. The model showed that adjunctive moxonidine could increase life-years lived and provide long term cost savings.

Cost-effectiveness of nitrendipine and hydrochlorothiazide or metoprolol to treat hypertension in rural community health centers in China.

OBJECTIVES: The objective of this article is to compare blood pressure (BP)-lowing effects of nitrendipine and hydrochlorothiazide and nitrendipine and metoprolol, and estimate the economic effect of these therapies on hypertension. METHODS: Outpatients (N = 793) 18-70 years of age with stage 2 or severe hypertension (SBP ≥ 160 mmHg and/or DBP ≥ 100 mmHg) were recruited from four randomly selected rural community health centers in Beijing and Jilin. After drug wash out, they were randomly divided into nitrendipine and hydrochlorothiazide group or nitrendipine and metoprolol group. The costs of drug treatment for hypertension were calculated and general estimation, whereas effectiveness was measured as a reduction in SBP and DBP at the end of a 24-week study period. RESULTS: Overall, 623 patients were eligible for the study and after a 24-week follow-up, SBP and DBP were 131.2/82.2 mmHg for the nitrendipine and hydrochlorothiazide group and 131.4/82.9 mmHg for the nitrendipine and metoprolol group and these were not significantly different (P = 0.7974 SBP and P = 0.1166 DBP). Comparing with nitrendipine and metoprolol, the cost of nitrendipine and hydrochlorothiazide was less, and its effectiveness was similar. The cost/effect ratio (US$/mmHg) was 1.4 for SBP and 2.8 for DBP for the nitrendipine and hydrochlorothiazide group, and 1.9 and 3.8 for the nitrendipine and metoprolol group's SBP and DBP values, respectively. The incremental cost per patient for achieving target BP was 5.1. Adverse events were mild or moderate and there were no differences between treatment groups. CONCLUSION: Treating hypertension with nitrendipine and hydrochlorothiazide was cost-effective than nitrendipine and metoprolol, and these data will allow more reasonable and efficient allocation of limited resources in low-income countries.

A case of type 2 diabetes mellitus developing hypothyroidism discovered as a result of a discrepancy between glycated hemoglobin and glycated albumin values.

We report a case of type 2 diabetes mellitus presenting hypothyroidism due to overeating of seaweed that was noticed as a result of a discrepancy between glycated albumin (GA) and glycated hemoglobin (GHb). A 71-year-old woman was undergoing managed treatment with oral medicines and insulin for diabetes mellitus with no sign of thyroid disease. Her thyroid function was euthyroid without aid of thyroid hormone. All of the patient's thyroid autoantibodies were negative. Fifteen weeks prior to indications of hypothyroidism, she had started to consume large amounts (100-200 g dry weight equivalent) of cooked "wakame" seaweed every morning. Just before admission to our hospital, her GA was 26.9%, while GHb and fasting plasma glucose remained within normal ranges (less than 5.6%, and 106 mg, respectively). This discrepancy between GA and GHb drew our attention to the development of complications. Naive interview of the patient led us to believe a thyroid hormone deficiency existed, though without any related complaints or findings, such as non-pitting edema, cold intolerance, or easy fatiguing. Seaweed consumption was stopped and periodic observation of thyroid function started. As thyroid hormone levels moved into normal range, GA and GHb returned to their normal relative ratio after 3 months. Thus, measurement of the relative ratio of GA and GHb may be useful for glycemic monitoring, with the potential as a readily available glycemic control marker for patients with changeable complications.

Effects of eprosartan on target organ protection.

Hypertension is the most important cardiovascular risk factor for stroke. Blood pressure reduction by antihypertensive treatment is clearly efficacious in the prevention of stroke (both primary and secondary), although no clear differences have yet been observed between antihypertensive drug classes. However, a recent study reported the clear superiority of the angiotensin-receptor blocker eprosartan over the calcium channel blocker nitrendipine in cardiovascular protection of hypertensive patients with a previous stroke. Comparative studies using angiotensin-receptor blockers have also suggested the superiority of this class of drugs on primary stroke prevention. This effect may be linked to their beneficial actions on left ventricular hypertrophy, atrial enlargement, and supraventricular arrhythmias, endothelial dysfunction, inflammation, and remodelling, as well as a direct neuroprotective effect mediated through the stimulation of the angiotensin II type-2 receptor. In addition, a sympathoinhibition observed with the renin-angiotensin system blockers and particularly demonstrated with eprosartan, may help to explain the better cardiovascular and cerebrovascular protection in comparison with the calcium antagonist nitrendipine.

Morbidity and Mortality After Stroke, Eprosartan Compared with Nitrendipine for Secondary Prevention: principal results of a prospective randomized controlled study (MOSES).

BACKGROUND AND PURPOSE: In hypertensive stroke patients, for the same level of blood pressure control, eprosartan will be more effective than nitrendipine in reducing cerebrovascular and cardiovascular morbidity and mortality. METHODS: A total of 1405 well-defined, high-risk hypertensives with cerebral event during the last 24 months (proven by cerebral computed tomography scan or nuclear magnetic resonance) were randomized to eprosartan or nitrendipine (mean follow-up 2.5 years). Primary end point was the composite of total mortality and all cardiovascular and cerebrovascular events, including all recurrent events. RESULTS: Randomization was successful without significant differences in the baseline characteristics. Blood pressure was reduced to a comparable extent without any significant differences between the 2 groups during the whole study period (150.7/84 mm Hg and 152.0/87.2 mm Hg with eprosartan and nitrendipine therapy to 137.5/80.8 mm Hg and 136.0/80.2 mm Hg, respectively, confirmed by ambulatory blood pressure monitoring). Moreover, already after 3 months, normotensive mean values were achieved, and 75.5% reached values <140/90 mm Hg with the eprosartan regimen and 77.7% with the nitrendipine regimen. During follow-up, in total, 461 primary events occurred: 206 eprosartan and 255 nitrendipine (incidence density ratio [IDR], 0.79; 95% CI, 0.66 to 0.96; P=0.014). Cardiovascular events were: 77 eprosartan and 101 nitrendipine (IDR, 0.75; 95% CI, 0.55 to 1.02; P=0.06); cerebrovascular events: 102 eprosartan and134 nitrendipine (IDR, 0.75; 95% CI, 0.58 to 0.97; P=0.03). CONCLUSIONS: The Morbidity and Mortality After Stroke, Eprosartan Compared With Nitrendipine for Secondary Prevention (MOSES) study was the first to compare an angiotensin II type 1 receptor antagonist with a calcium antagonist in secondary stroke prevention. In these high-risk hypertensive stroke patients, an early normotensive and comparable blood pressure was achieved. The combined primary end point was significantly lower in the eprosartan group.

Comparison of effects of enalapril and nitrendipine on cardiac sympathetic nervous system in essential hypertension.

OBJECTIVES: The purpose of this study was to assess the effects of enalapril and nitrendipine on the cardiac sympathetic nervous system. BACKGROUND: Angiotensin-converting enzyme inhibitors and long-acting calcium channel blockers have been widely used in the treatment of cardiovascular diseases, in some of which sympathetic overactivity plays a major role in the pathophysiology and prognosis. However, little information is available on the effects of these drugs on the cardiac sympathetic nervous system. METHODS: 123I-metaiodobenzylguanidine (MIBG) cardiac imaging was performed before and 3 months after drug administration in 46 patients with mild essential hypertension. Twenty-two patients were treated with 5 to 10 mg of enalapril once a day, and the other 24 with 5 to 10 mg of nitrendipine once a day. For comparison, 20 normotensive subjects were also studied. RESULTS: There were no significant differences between the basal characteristics in the 2 hypertensive groups. In both hypertensive groups, both systolic and diastolic blood pressures were significantly reduced to similar levels after the 3-month drug treatment. Before the drug treatment, the 2 hypertensive groups had a significantly higher washout rate and lower MIBG uptake than the normotensive subjects. The heart-to-mediastinum ratio significantly increased (p < 0.0001), with decreased (p < 0.002) washout rate after drug treatment in the enalapril group, but with no significant changes in the nitrendipine group. CONCLUSION: Enalapril could suppress cardiac sympathetic activity and nitrendipine had no effect on it. The knowledge of antihypertensive drugs on the cardiac sympathetic nervous system appears to be helpful in selecting appropriate treatment in cardiovascular diseases.

Chinese trial on isolated systolic hypertension in the elderly. Systolic Hypertension in China (Syst-China) Collaborative Group.

BACKGROUND: In 1988, the Systolic Hypertension in China (Syst-China) Collaborative Group initiated the placebo-controlled Syst-China trial to investigate whether antihypertensive drug treatment could reduce the incidence of fatal and nonfatal stroke in older Chinese patients with isolated systolic hypertension. OBJECTIVES: To explore (1) whether the benefits of active treatment were evenly distributed across 4 strata, prospectively defined according to sex and previous cardiovascular complications, and (2) whether the morbidity and mortality results were influenced by age, level of systolic or diastolic blood pressure (BP), smoking or drinking habits, or diabetes mellitus at enrollment. METHODS: Eligible patients had to be 60 years or older with a sitting systolic BP of 160 to 219 mm Hg and diastolic BP less than 95 mm Hg. After stratification for center, sex, and previous cardiovascular complications, 1253 patients were assigned to active treatment starting with nitrendipine (10-40 mg/d), with the possible addition of captopril (12.5-50.0 mg/d), and/or hydrochlorothiazide (12.5-50 mg/d). In the 1141 control patients, matching placebos were used similarly. RESULTS: Male sex, previous cardiovascular complications, older age, higher systolic BP or lower diastolic BP, living in northern China, smoking, and diabetes mellitus significantly and independently increased the risk of 1 or more of the following end points: total or cardiovascular mortality, all fatal and nonfatal cardiovascular end points, all strokes, and all cardiac end points. In the placebo-control group diabetes raised the risk of all end points 2- to 3-fold (P< or =.05). However, active treatment reduced the excess risk associated with diabetes to a nonsignificant level (P values ranging from .12-.86) except for cardiovascular mortality (P = .04). Cox regression with adjustments applied for significant covariates suggested that active treatment may reduce total mortality more (P = .06) in women and stroke more (P = .07) in men and that it may provide better protection against cardiac end points in nonsmokers than smokers (P = .04). Otherwise, the benefits of active treatment were equally manifest, regardless of the enrollment characteristics of the patients, and regardless of whether active treatment consisted of only nitrendipine or of nitrendipine associated with other active drugs. CONCLUSIONS: In elderly Chinese patients with isolated systolic hypertension, stepwise antihypertensive drug treatment, starting with the dihydropyridine calcium channel blocker nitrendipine, improved prognosis. The benefit was particularly evident in diabetic patients; for cardiac end points it tended to be larger in nonsmokers. Otherwise, the benefit of active treatment was not significantly influenced by the characteristics of the patients at enrollment in the trial.

Subgroup and per-protocol analysis of the randomized European Trial on Isolated Systolic Hypertension in the Elderly.

BACKGROUND: In 1989, the European Working Party on High Blood Pressure in the Elderly started the double-blind, placebo-controlled, Systolic Hypertension in Europe Trial to test the hypothesis that antihypertensive drug treatment would reduce the incidence of fatal and nonfatal stroke in older patients with isolated systolic hypertension. This report addresses whether the benefit of antihypertensive treatment varied according to sex, previous cardiovascular complications, age, initial blood pressure (BP), and smoking or drinking habits in an intention-to-treat analysis and explores whether the morbidity and mortality results were consistent in a per-protocol analysis. METHODS: After stratification for center, sex, and cardiovascular complications, 4695 patients 60 years of age or older with a systolic BP of 160 to 219 mm Hg and diastolic BP less than 95 mm Hg were randomized. Active treatment consisted of nitrendipine (10-40 mg/d), with the possible addition of enalapril maleate (5-20 mg/d) and/or hydrochlorothiazide (12.5-25 mg/d), titrated or combined to reduce the sitting systolic BP by at least 20 mm Hg, to below 150 mm Hg. In the control group, matching placebo tablets were employed similarly. RESULTS: In the intention-to-treat analysis, male sex, previous cardiovascular complications, older age, higher systolic BP, and smoking at randomization were positively and independently correlated with cardiovascular risk. Furthermore, for total (P = .009) and cardiovascular (P = .09) mortality, the benefit of antihypertensive drug treatment weakened with advancing age; for total mortality (P = .05), the benefit increased with higher systolic BP at entry, while for fatal and nonfatal stroke (P = .01), it was most evident in nonsmokers (92.5% of all patients). In the perprotocol analysis, active treatment reduced total mortality by 24% (P = .05), reduced all fatal and nonfatal cardiovascular end points by 32% (P<.001), reduced all strokes by 44% (P = .004), reduced nonfatal strokes by 48% (P = .005), and reduced all cardiac end points, including sudden death, by 26% (P = .05). CONCLUSIONS: In elderly patients with isolated systolic hypertension, stepwise antihypertensive drug treatment, starting with the dihydropyridine calcium channel blocker nitrendipine, improves prognosis. The per-protocol analysis suggested that treating 1000 patients for 5 years would prevent 24 deaths, 54 major cardiovascular end points, 29 strokes, or 25 cardiac end points. The effects of antihypertensive drug treatment on total and cardiovascular mortality may be attenuated in very old patients.

The prevention of dementia with antihypertensive treatment: new evidence from the Systolic Hypertension in Europe (Syst-Eur) study.

BACKGROUND: After the double-blind, placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial ended in February 1997, randomized patients were offered active study medication for a further period of observation. OBJECTIVE: To refine the estimates of the long-term effects of antihypertensive therapy on the incidence of dementia. METHODS: Eligible patients had no dementia and were at least 60 years old. Their systolic blood pressure at entry was 160 to 219 mm Hg, with diastolic blood pressure below 95 mm Hg. Antihypertensive therapy was started immediately after randomization in the active treatment group, but only after termination of the double-blind trial in the control patients. Treatment consisted of nitrendipine (10-40 mg/d), with the possible addition of enalapril maleate (5-20 mg/d), hydrochlorothiazide (12.5-25 mg/d), or both add-on drugs. RESULTS: Median follow-up increased from 2.0 years in the double-blind trial to 3.9 years overall. The incidence of dementia doubled from 32 to 64 cases, 41 of whom had Alzheimer disease. Throughout follow-up, systolic/diastolic blood pressure was 7.0/3.2 mm Hg higher in the 1417 control patients than in the 1485 subjects randomized to active treatment. At the last examination, the blood pressure difference was still 4.2/2.9 mm Hg; 48.1%, 26.4%, and 11.4% of the control patients were taking nitrendipine, enalapril, and/or hydrochlorothiazide, whereas in the active treatment group these proportions were 70.2%, 35.4%, and 18.4%, respectively. Compared with the controls, long-term antihypertensive therapy reduced the risk of dementia by 55%, from 7.4 to 3.3 cases per 1000 patient-years (43 vs 21 cases, P<.001). After adjustment for sex, age, education, and entry blood pressure, the relative hazard rate associated with the use of nitrendipine was 0.38 (95% confidence interval, 0.23-0.64; P<.001). Treatment of 1000 patients for 5 years can prevent 20 cases of dementia (95% confidence interval, 7-33). CONCLUSION: The extended follow-up of Syst-Eur patients reinforces the evidence that blood pressure-lowering therapy initiated with a long-acting dihydropyridine protects against dementia in older patients with systolic hypertension.

Effects of enalapril and nitrendipine on the excretion of epidermal growth factor and albumin in hypertensive NIDDM patients.

OBJECTIVE: To compare the effect of the antihypertensive drugs nitrendipine and enalapril on the excretion of epidermal growth factor (EGF) and albumin in hypertensive non-insulin-dependent diabetes mellitus (NIDDM) subjects. RESEARCH DESIGN AND METHODS: After a 4-week washout period, mildly hypertensive (systolic blood pressure [sBP] > or = 140 mmHg and/or diastolic blood pressure [dBP] > or = 90 mmHg) NIDDM patients with albuminuria (15-200 micrograms/min) were randomized into an 8-month-long therapy with either nitrendipine (n = 11) or enalapril (n = 10). Blood pressure, EGF, and microalbumin excretion were measured at baseline and throughout the treatment period. RESULTS: A significant fall in sBP was noticed in the enalapril group and in dBP in the nitrendipine group. In the enalapril group, EGF excretion progressively increased from 188 to 214 nmol/mmol creatinine after 6 weeks and to 274 after 8 months of therapy (P = 0.03). There was a significant fall in albumin excretion while patients were on enalapril, but in the nitrendipine group, neither albuminuria nor EGF excretion changed significantly. There was no correlation of improved EGF excretion with a decrease in albuminuria or BP. CONCLUSIONS: The angiotensin-converting enzyme inhibitor enalapril has been effective in decreasing albumin and increasing EGF excretion. Measurement of urinary EGF may provide a new valuable index of renal function.

Evaluation of the efficacy and tolerability of nitrendipine in reducing both pressure and left ventricular mass in hypertensive type 2 diabetic patients.

OBJECTIVE: To evaluate the efficacy and tolerability of nitrendipine in comparison with captopril in hypertensive diabetic patients with left ventricular hypertrophy (LVH). RESEARCH DESIGN AND METHODS: A total of 75 patients enrolled in this study presented stable type 2 diabetes (not treated with insulin) and mild-to-moderate hypertension with a left ventricular mass > or = 75 g/m2 by two-dimensional echocardiography. After a 4-week washout period, 38 patients were assigned to treatment with captopril, and 37 patients to nitrendipine (random allocation). The duration of follow-up was 36 weeks. RESULTS: Patients of both groups were similar with regard to the duration of diabetes and hypertension, systolic and diastolic blood pressure at rest, degree of LVH, metabolic control, and albumin excretion rate (AER). Both drugs were equally effective in reducing systolic and diastolic blood pressure (captopril: from 165 +/- 13/100 +/- 4 to 147 +/- 11/87 +/- 4 mmHg; nitrendipine: from 167 +/- 17/100 +/- 5 to 143 +/- 9/86 +/- 4 mmHg; P < 0.05) and in reversing LVH (nitrendipine: from 87 +/- 2 to 81 +/- 1 g/m2; captopril: from 89 +/- 2 to 85 +/- 2 g/m2; P = 0.0001). Neither the left ventricular end-diastolic volume index nor the left ventricular ejection fraction changed significantly during the treatment period. CONCLUSION: Nitrendipine is as effective as captopril in reducing both systolic and diastolic blood pressure and in reversing LVH. Neither drug showed any negative side effects on fasting plasma glucose and glycated hemoglobin (HbA1c) levels, and both maintain constant AERs.

[Hypotensive effectiveness of therapy combined enalapril and nitrendipine and influence on the quality of life]. / Skutecznosc hipotensyjna oraz wplyw na jakosc zycia skojarzonej terapii enalaprilem oraz nitrendypina.

UNLABELLED: It has been proved that effectiveness of monotherapy in mild hypertension is about 50%; in the other half of patients the dose of previously used drug should be increased or combined therapy should be recommended. THE AIM OF THE STUDY was to compare treatment with angiotensin convertase enzyme inhibitor--ACE-I (enalapril 10 mg bid--group 1) to therapy with ACE-I combined with calcium antagonist (enalapril 5 mg bid + nitrendipine 20 mg qd--group 2). MATERIAL AND METHODS: In a prospective, open, randomised crossover study we assessed 44 hypertensive subjects (17 women, 27 men), aged 35-69 years (mean age 48.6 years) with poorly controlled hypertension treated with enalapril 5 mg twice daily. Mean initial systolic blood pressure was 150.8 < or = 9.9 mmHg, diastolic 94.7 +/- 5.3 mmHg respectively. The influence of the treatment regimen on the quality of life (QoL) was estimated by a questionnaire. RESULTS: The effectiveness of both used procedures did not differ statistically--in both groups mean blood pressure reduction was similar (14/8 mmHg in 4 weeks), also percentage of patients with well controlled hypertension (about 50%) did not differ significantly. In the group with changes regimen from monotherapy to combined therapy the improvement of systolic blood pressure was found to be statistically significant (p<0.05); in the case of combined therapy replaced with monotherapy such an improvement was not observed. In the subgroup with the isolated systolic hypertension combined therapy was considerably more effective. The improvement of QoL was noted in both groups, mainly in the initial phase of the study. CONCLUSION: In mild hypertension ACE-I and calcium antagonist combination is effective in blood pressure reduction and in the improvement of the quality of life. Nitrendipine in a dose 20 mg in an once daily regimen is a potent and safe hypotensive agent, particularly in isolated systolic hypertension.