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A number of trials and meta-analyses have demonstrated clear benefits of blood pressure (BP) reduction in patients aged <80 years with regard to the reduction in stroke and cardiovascular events. However, a variety of studies have suggested that the positive relationship between BP and cardiovascular mortality is weakened or indeed reversed in the very elderly. Most intervention trials to date have either excluded or not recruited sufficient patients aged > or =80 years to determine whether there is a significant benefit from treatment in this age group. A meta-analysis of intervention trials that recruited patients aged > or =80 years has suggested a benefit in terms of stroke reduction but has also raised the possibility of an increase in total mortality. The benefit to risk ratio therefore needs to be clearly established before recommendations can be made for treating very elderly patients with hypertension. The Hypertension in the Very Elderly Trial (HYVET) pilot recruited 1283 patients aged > or =80 years and showed the feasibility of performing such a trial in this age group. It was a Prospective Randomised Open Blinded End-Points (PROBE) design but the main trial has additional pharmaceutical sponsorship to run a double-blind trial. Therefore, the main trial is a randomised, double-blind, placebo-controlled trial designed to assess the benefits of treating very elderly patients with hypertension. It compares placebo with a low dose diuretic (indapamide sustained release 1.5mg daily) and additional ACE inhibitor (perindopril) therapy if required. As in the pilot trial, the primary end-point is stroke events (fatal and non-fatal) and the trial is designed to determine whether or not a 35% difference occurs between placebo and active treatment. The main objective will be achieved with 90% power at the 1% level of significance. Secondary outcome measures will include total mortality, cardiovascular mortality, cardiac mortality, stroke mortality and skeletal fracture. 2100 patients aged > or =80 years are to be recruited and followed up for an average of 5 years. Entry BP criteria after 2 months of a single-blind placebo run-in period are a sustained sitting systolic BP (SBP) of 160 to 199mm Hg and a diastolic BP of 90 to 109mm Hg. The standing SBP must be >140mm Hg. The trial will be carried out in accordance with the principles of Good Clinical Practice. We describe in detail the protocol for the main trial and discuss the reasons for the changes from the pilot, the use of the drug regimen, and the BP criteria to be used in the trial. [ABSTRACT FROM AUTHOR]

A number of trials and meta-analyses have demonstrated clear benefits of blood pressure (BP) reduction in patients aged <80 years with regard to the reduction in stroke and cardiovascular events. However, a variety of studies have suggested that the positive relationship between BP and cardiovascular mortality is weakened or indeed reversed in the very elderly. Most intervention trials to date have either excluded or not recruited sufficient patients aged ≥80 years to determine whether there is a significant benefit from treatment in this age group. A meta-analysis of intervention trials that recruited patients aged ≥80 years has suggested a benefit in terms of stroke reduction but has also raised the possibility of an increase in total mortality. The benefit to risk ratio therefore needs to be clearly established before recommendations can be made for treating very elderly patients with hypertension. The Hypertension in the Very Elderly Trial (HYVET) pilot recruited 1283 patients aged ≥80 years and showed the feasibility of performing such a trial in this age group. It was a Prospective Randomised Open Blinded End-Points (PROBE) design but the main trial has additional pharmaceutical sponsorship to run a double-blind trial. Therefore, the main trial is a randomised, double-blind, placebo-controlled trial designed to assess the benefits of treating very elderly patients with hypertension. It compares placebo with a low dose diuretic (indapamide sustained release 1.5mg daily) and additional ACE inhibitor (perindopril) therapy if required. As in the pilot trial, the primary end-point is stroke events (fatal and non-fatal) and the trial is designed to determine whether or not a 35% difference occurs between placebo and active treatment. The main objective will be achieved with 90% power at the 1% level of significance. Secondary outcome measures will include total mortality, cardiovascular mortality, cardiac mortality, stroke mortality and skeletal fracture. 2100 patients aged ≥80 years are to be recruited and followed up for an average of 5 years. Entry BP criteria after 2 months of a single-blind placebo run-in period are a sustained sitting systolic BP (SBP) of 160 to 199mm Hg and a diastolic BP of 90 to 109mm Hg. The standing SBP must be >140mm Hg. The trial will be carried out in accordance with the principles of Good Clinical Practice. We describe in detail the protocol for the main trial and discuss the reasons for the changes from the pilot, the use of the drug regimen, and the BP criteria to be used in the trial. [ABSTRACT FROM AUTHOR]

Context: The clinical use of ambulatory blood pressure (BP) monitoring requires further validation in prospective outcome studies.Objective: To compare the prognostic significance of conventional and ambulatory BP measurement in older patients with isolated systolic hypertension.Design: Substudy to the double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) Trial, started in October 1988 with follow up to February 1999. The conventional BP at randomization was the mean of 6 readings (2 measurements in the sitting position at 3 visits 1 month apart). The baseline ambulatory BP was recorded with a noninvasive intermittent technique.Setting: Family practices and outpatient clinics at primary and secondary referral hospitals.Participants: A total of 808 older (aged > or =60 years) patients whose untreated BP level on conventional measurement at baseline was 160 to 219 mm Hg systolic and less than 95 mm Hg diastolic.Interventions: For the overall study, patients were randomized to nitrendipine (n = 415; 10-40 mg/d) with the possible addition of enalapril (5-20 mg/d) and/or hydrochlorothiazide (12.5-25.0 mg/d) or to matching placebos (n = 393).Main Outcome Measures: Total and cardiovascular mortality, all cardiovascular end points, fatal and nonfatal stroke, and fatal and nonfatal cardiac end points.Results: After adjusting for sex, age, previous cardiovascular complications, smoking, and residence in western Europe, a 10-mm Hg higher conventional systolic BP at randomization was not associated with a worse prognosis, whereas in the placebo group, a 10-mm Hg higher 24-hour BP was associated with an increased relative hazard rate (HR) of most outcome measures (eg, HR, 1.23 [95% confidence interval [CI], 1.00-1.50] for total mortality and 1.34 [95% CI, 1.03-1.75] for cardiovascular mortality). In the placebo group, the nighttime systolic BP (12 AM-6 AM) more accurately predicted end points than the daytime level. Cardiovascular risk increased with a higher night-to-day ratio of systolic BP independent of the 24-hour BP (10% increase in night-to-day ratio; HR for all cardiovascular end points, 1.41; 95% CI, 1.03-1.94). At randomization, the cardiovascular risk conferred by a conventional systolic BP of 160 mm Hg was similar to that associated with a 24-hour daytime or nighttime systolic BP of 142 mm Hg (95% CI, 128-156 mm Hg), 145 mm Hg (95% CI, 126-164 mm Hg) or 132 mm Hg (95% CI, 120-145 mm Hg), respectively. In the active treatment group, systolic BP at randomization did not significantly predict cardiovascular risk, regardless of the technique of BP measurement.Conclusions: In untreated older patients with isolated systolic hypertension, ambulatory systolic BP was a significant predictor of cardiovascular risk over and above conventional BP. [ABSTRACT FROM AUTHOR]

Presents an abstract of the study "Socio-Demographic Characteristics, Smoking and Alcohol Consumption in Very Elderly Hypertensives-Baseline Data From the Hypertension in the Very Elderly Trial (HYVET)," by R. Peters, N. Beckett, W. Banya, M. Nunes, E. Pinto, R. Antikaïnen, C. Nachev, A. Fletcher and C. Bulpitt.

Background: Isolated systolic hypertension occurs in about 15% of people aged 60 years or older. In 1989, the European Working Party on High Blood Pressure in the Elderly investigated whether active treatment could reduce cardiovascular complications of isolated systolic hypertension. Fatal and non-fatal stroke combined was the primary endpoint.Methods: All patients (> 60 years) were initially started on masked placebo. At three run-in visits 1 month apart, their average sitting systolic blood pressure was 160-219 mm Hg with a diastolic blood pressure lower than 95 mm Hg. After stratification for centre, sex, and previous cardiovascular complications, 4695 patients were randomly assigned to nitrendipine 10-40 mg daily, with the possible addition of enalapril 5-20 mg daily and hydrochlorothiazide 12.5-25.0 mg daily, or matching placebos. Patients withdrawing from double-blind treatment were still followed up. We compared occurrence of major endpoints by intention to treat.Findings: At a median of 2 years' follow-up, sitting systolic and diastolic blood pressures had fallen by 13 mm Hg and 2 mm Hg in the placebo group (n = 2297) and by 23 mm Hg and 7 mm Hg in the active treatment group (n = 2398). The between-group differences were systolic 10.1 mm Hg (95% CI 8.8-11.4) and diastolic, 4.5 mm Hg (3.9-5.1). Active treatment reduced the total rate of stroke from 13.7 to 7.9 endpoints per 1000 patient-years (42% reduction; p = 0.003). Non-fatal stroke decreased by 44% (p = 0.007). In the active treatment group, all fatal and non-fatal cardiac endpoints, including sudden death, declined by 26% (p = 0.03). Non-fatal cardiac endpoints decreased by 33% (p = 0.03) and all fatal and non-fatal cardiovascular endpoints by 31% (p < 0.001). Cardiovascular mortality was slightly lower on active treatment (-27%, p = 0.07), but all-cause mortality was not influenced (-14%; p = 0.22).Interpretation: Among elderly patients with isolated systolic hypertension, antihypertensive drug treatment starting with nitrendipine reduces the rate of cardiovascular complications. Treatment of 1000 patients for 5 years with this type of regimen may prevent 29 strokes or 53 major cardiovascular endpoints. [ABSTRACT FROM AUTHOR]

Background: The risks and benefits of treating hypertension in individuals older than 80 years are uncertain. A meta-analysis has suggested that a reduction in stroke events of 36% may have to be balanced against a 14% increase in total mortality., Objectives: To report the results of the pilot study of the Hypertension in the Very Elderly Trial (HYVET), which is in progress to address these issues., Methods: The HYVET-Pilot was a multicentre international open pilot trial. In 10 European countries, 1283 patients older than 80 years and with a sustained blood pressure of 160-219/90-109 mmHg were allocated randomly to one of three treatments: a diuretic-based regimen (usually bendroflumethiazide; n = 426), an angiotensin-converting enzyme inhibitor regimen (usually lisinopril; n = 431) or no treatment (n = 426). The procedure permitted doses of the drug to be titrated and diltiazem slow-release to be added to active treatment. Target blood pressure was < 150/80 mmHg and mean follow-up was 13 months., Results: In the combined actively treated groups, the reduction in stroke events relative hazard rate (RHR) was 0.47 [95% confidence interval (CI) 0.24 to 0.93] and the reduction in stroke mortality RHR was 0.57 (95% CI 0.25 to 1.32). However, the estimate of total mortality supported the possibility of excess deaths with active treatment (RHR 1.23, 95% CI 0.75 to 2.01)., Conclusions: The preliminary results support the need for the continuing main HYVET trial. It is possible that treatment of 1000 patients for 1 year may reduce stroke events by 19 (nine non-fatal), but may be associated with 20 extra non-stroke deaths.

Objective: To examine the association of clinic and ambulatory heart rate with total, cardiovascular, and noncardiovascular death in a cohort of elderly subjects with isolated systolic hypertension from the Systolic Hypertension in Europe Trial., Methods: A total of 4682 patients participated, whose untreated blood pressure on conventional measurement at baseline was 160 to 219 mm Hg systolic and lower than 95 mm Hg diastolic. Clinic heart rate was the mean of 6 readings during 3 visits. Ambulatory heart rate was recorded with a portable intermittent technique in 807 subjects., Results: Raised baseline clinic heart rate was positively associated with a worse prognosis for total, cardiovascular, and noncardiovascular mortality among the 2293 men and women taking placebo. Subjects with heart rates higher than 79 beats/min (bpm) (top quintile) had a 1.89 times greater risk of mortality than subjects with heart rate lower than or equal to 79 bpm (95% confidence interval, 1.33-2.68 bpm). In a Cox regression analysis, predictors of time to death were heart rate (P<.001), age (P<.001), serum creatinine level (P =.001), presence of diabetes (P =.002), previous cardiovascular disease (P =.01), triglyceride readings (P =.02), smoking (P =.04), and elevated systolic blood pressure (P =.05), while total cholesterol level was found to be nonsignificant in the model. In the ambulatory monitoring subgroup, clinic and ambulatory heart rates predicted noncardiovascular but not cardiovascular mortality. However, in a Cox regression analysis in which clinic and ambulatory heart rates were included, a significant association with noncardiovascular mortality was found only for clinic heart rate (P =.004). In the active treatment group, the weak predictive power of clinic heart rate for mortality disappeared after adjustment for confounders., Conclusions: In untreated older patients with isolated systolic hypertension, a clinic heart rate greater than 79 bpm was a significant predictor of all-cause, cardiovascular, and noncardiovascular mortality. Ambulatory heart rate did not add prognostic information to that provided by clinic heart rate.

We enrolled 808 older patients with isolated systolic hypertension (160 to 219/71 <95 mm Hg) to investigate whether ambulatory measurement of pulse pressure and mean pressure can refine risk stratification. The patients (> or =60 years) were randomized to nitrendipine (10 to 40 mg/day) with the possible addition of enalapril (5 to 20 mg/day) or hydrochlorothiazide (12.5 to 25 mg/day) or to matching placebos. At baseline, pulse pressure and mean pressure were determined from six conventional blood pressure (BP) readings and from 24-h ambulatory recordings. With adjustment for significant covariables, we computed mutually adjusted relative hazard rates associated with 10 mm Hg increases in pulse pressure or mean pressure. In the placebo group, the 24-h and nighttime pulse pressures consistently predicted total and cardiovascular mortality, all cardiovascular events, stroke, and cardiac events. Daytime pulse pressure predicted cardiovascular mortality, all cardiovascular end points, and stroke. The hazard rates for 10 mm Hg increases in pulse pressure ranged from 1.25 to 1.68. Conventionally measured pulse pressure predicted only cardiovascular mortality with a hazard rate of 1.35. In the active treatment group compared with the placebo patients, the relation between outcome and ambulatory pulse pressure was attenuated to a nonsignificant level. Mean pressure determined from ambulatory or conventional BP measurements was not associated with poorer prognosis. In conclusion, in older patients with isolated systolic hypertension higher pulse pressure estimated by 24-h ambulatory monitoring was a better predictor of adverse outcomes than conventional pulse pressure, whereas conventional and ambulatory mean pressures were not correlated with a worse outcome.

Several reports suggest that markers of renal function such as serum creatinine, serum uric acid, and urinary excretion of protein may be related to cardiovascular complications and mortality. This study analyzed the data from the Syst-Eur trial, which was a randomized, placebo-controlled, double-blind intervention trial in elderly patients with isolated systolic hypertension. The purpose was to evaluate whether serum levels of creatinine and uric acid and urinary protein excretion at entry are related to subsequent morbidity and mortality. Incidence rates of total mortality, cardiovascular mortality, stroke (fatal as well as nonfatal), coronary events, and all cardiovascular endpoints were calculated for each quintile of serum creatinine or serum uric acid or for each category of protein excretion (none, trace, and overt). Crude and adjusted relative hazard rates were also determined for each 20 micro M increase in serum creatinine, each 50 micro M increase in serum uric acid, and for each protein excretion category. Even when adjusted for age, gender, and various other covariates, serum creatinine was significantly associated with a worse prognosis. There was an U-shaped relationship between serum uric acid and total mortality, but otherwise no obvious relationships were detected between serum uric acid levels and complications when appropriate adjustments were made for confounding variables. Proteinuria at entry was a significant predictor of total mortality and all cardiovascular endpoints. It is concluded that higher levels of serum creatinine and trace or overt proteinuria are associated with an increased number of cardiovascular events and with a higher mortality in patients with isolated systolic hypertension.

Objectives: In the European Project on Genes in Hypertension (EPOGH) standardized epidemiological methods were used to determine complex phenotypes consisting of blood pressure (BP) in combination with other traits. In this report, we present the quality control of one of the BP phenotypes., Methods: In seven European countries eight different research groups recruited random samples of nuclear families. Trained observers measured the BP five times consecutively with the participants in the seated position at each of two separate home visits, 1 to 3 weeks apart, according to the guidelines of the British Hypertension Society. Quality assurance and quality control of this BP phenotype were implemented according to detailed instructions defined in the protocol of the EPOGH study., Results: On 31 August 2001, BP measurements of 2476 subjects were available for analysis. Fewer BP readings than the five planned per visit occurred in one of the eight centres, but only in 0.4% of the home visits. Across centres the relative frequency of identical consecutive readings for systolic or diastolic blood pressure varied from 0 to 6%. The occurrence of odd readings ranged from 0 to 0.1%. Of the 49,488 systolic and diastolic BP readings, 24.0% ended on a zero (expected 20%). In most EPOGH centres there was a progressive decline in the BP from the first to the second home visit. Overall, these decreases averaged 2.36 mmHg [95% confidence interval (CI): 1.98-2.74, P < 0.001] for systolic BP and 1.74 mmHg (95% CI: 1.46-2.02, P < 0.001) for diastolic BP., Conclusions: Quality assurance and control should be planned at the design stage of a project involving BP measurement and implemented from its very beginnings until the end. The procedures of quality assurance set up in the EPOGH study for the BP measurements resulted in a well-defined BP phenotype, which was consistent across centres., (Copyright 2002 Lippincott Williams & Wilkins)

Objective: To investigate the reasons for withdrawal from double-blind randomized trials, and the reasons for changing treatment within a randomized therapeutic group., Design: The Syst-Eur trial, in which 4695 older patients with systolic hypertension were randomized to active or placebo treatment., Methods: The reasons for withdrawal from the trial were examined, both for patient-initiated and investigator-initiated withdrawals. In addition, the reasons for stopping the first-line treatment (nitrendipine), the second-line treatments (enalapril and hydrochlorothiazide) and the corresponding placebos, were determined., Results: A total of 135 patients (6%) were withdrawn by the investigators from placebo treatment because their blood pressure was too high, and, similarly, 36 (1.6%) through patient initiation. The corresponding results for the actively treated patients were 14 (0.6%) and 7 (0.3%). Very few patients were withdrawn from the trial because of the adverse effects of treatment. However, 39 (4%) stopped taking active nitrendipine because of ankle oedema, compared with 4 (0.5%) on placebo. Similarly, 28 versus three stopped due to flushing. Forty-one (10%) stopped taking enalapril because of cough, against eight (2%) for enalapril placebo. In all, 15.0% stopped active nitrendipine, 20.2% enalapril and 6.3% hydrochlorothiazide, versus placebo 7.1, 9.1 and 5.1%., Conclusions: The numbers withdrawn from the trial for adverse treatment consequences were small in comparison to the cardiovascular benefits. Nevertheless the numbers stopping individual treatments were higher than expected.

BACKGROUND: The randomised, double-blind, placebo-controlled Systolic Hypertension in Europe trial (Syst-Eur 1) proved that blood pressure (BP) lowering therapy starting with nitrendipine reduces the risk of cardiovascular complications in elderly patients with isolated systolic hypertension. In an attempt to confirm the safety of long-term antihypertensive therapy based on a dihydropyridine, the Syst-Eur patients remained in open follow-up after the end of Syst-Eur 1. This paper presents the second progress report of this follow-up study (Syst-Eur 2). It describes BP control and adherence to study medications. METHODS: After the end of Syst-Eur 1 all patients, treated either actively or with placebo, were invited either to continue or to start antihypertensive treatment with the same drugs as previously used in the active treatment arm. In order to reach the target BP (sitting SBP <150 mmHg), the first line agent, nitrendipine, could be associated with enalapril and/or hydrochlorothiazide. RESULTS: Of the 3787 eligible patients, 3516 (93%) entered Syst-Eur 2. At the last available visit, 72% of the patients were taking nitrendipine. SBP/DBP at entry in Syst-Eur 2 averaged 160/83 mmHg in the former placebo group and 151/80 mmHg in the former active-treatment group. At the last follow-up visit SBP/DBP in the patients previously randomised to placebo or active treatment had decreased by 16/5 mmHg and 7/5 mmHg, respectively. The target BP was reached by 74% of the patients. CONCLUSION: Substantial reductions in systolic BP may be achieved in older patients with isolated systolic hypertension with a treatment strategy starting with the dihydropyridine calcium-channel blocker, nitrendipine, with the possible addition of enalapril and/or hydrochlorothiazide.

The insulin producing tumors are rare diseases and sometimes the diagnostics is very difficult. We present two cases of insulinoma treated as psychiatric diseases. We discuss the difficulties and particularities in the diagnostic process.

Background: One of the suggested mechanisms of increased cardiovascular risk in postmenopause is a loss of the antioxidant effects of estrogens. It has been shown that classical cardiovascular risk factors increase oxidative stress on the arterial wall, and that endothelial cells react to this insult by increased expression of cellular adhesion molecules (CAM), which in turn are markers of arterial wall inflammation., Methods: A randomized, placebo-controlled, double-blind study was performed in 60 postmenopausal women with high cardiovascular risk profiles, but free from clinical atherosclerotic disease. Patients were randomized to either antioxidant supplementation (using a combination of natural antioxidants; n = 30) or placebo (n = 30), and followed for 12 weeks. The concentrations of the adhesion molecules sVCAM-1 and sICAM-1 were measured by ELISA at baseline and at the end of the study, as well as total cholesterol, LDL, HDL, triglycerides and blood pressure., Results: 27 women in the antioxidant supplementation group and 29 on placebo completed the study. At baseline, there were no significant differences in measured parameters between the groups: sICAM-1 concentrations were 341.8 +/- 116.9 vs. 349.9 +/- 104.6 ng/ml (active treatment vs. placebo; p = n.s.) and sVCAM-1 concentrations were 780.5 +/- 325.8 vs. 761.0 +/- 333.7 ng/ml (p = n.s.). In contrast, at the end of the study, sICAM-1 concentrations were 301.6 +/- 56.0 vs. 356.0 +/- 134.8 ng/ml (active treatment vs. placebo; p = 0.053) and sVCAM-1 concentrations were 656.0 +/- 326.5 vs. 818.5 +/- 381.0 ng/ml (p = 0.04). There were no significant differences between or changes within the groups in measured cholesterol and blood pressure., Conclusion: Antioxidant supplementation reduces serum concentrations of endothelium-derived adhesion molecules sICAM-1 and sVCAM-1 in postmenopausal women with high cardiovascular risk profiles.

High affinity IgG autoantibodies (ABs) against oxLDLs and lag-phase of serum oxidation were tested in patients with coronary heart disease (CHD). Fifty one (37 M/14 F) patients with CHD defined as Q-wave myocardial infarction and/or stenosis of more than 50% and 51 (34 M/17 F) healthy blood donors as controls participated in this study. LDLs were isolated by gradient ultracentrifugation and oxidized with CuSO4. The modified LDLs (oxLDLs) or native LDLs (nLDLs) were used as antigens in an enzyme immunoassay (ELISA) to detect IgG ABs in both groups. The serum was oxidized by CuSO4 and the oxidation was monitored spectrophotometrically at lambda = 234 nm to follow the formation of conjugated diens. The lag-phase (in minutes) is the interval between the addition of CuSO4 to the serum and the beginning of extensive oxidation (increasing absorbance at 234 nm). The concentrations of total cholesterol, triglycerides, HDL-cholesterol, apo-A and apo-B were measured as well. The mean level of ABs against oxLDLs (expressed as optical density units) was 0.590 +/- 0.330 in CHD-patients vs 0.244 +/- 0.200 in controls (p < 0.001). The lag-phase in minutes was 47.00 +/- 27.19 in CHD-patients and 80.23 +/- 26.30 in controls (p < 0.001). A negative correlation between ABs levels and lag-phase was established in CHD-patients (r = -0.69, p < 0.001) and controls (r = -0.62, p < 0.001). A poor correlation was established between ABs levels or lag-phase, on one hand, and other measured parameters. In conclusion, the lag-phase of serum oxidation by Cu2+ could be informative for LDL susceptibility to modification and the extent of consequent humoral immune response.

In the double-blind Systolic Hypertension in Europe (Syst-Eur) Trial, active treatment was initiated with nitrendipine (10 to 40 mg/d) with the possible addition of enalapril (5 to 20 mg/d) and/or hydrochlorothiazide (12.5 to 25 mg/d) titrated or combined to reduce sitting systolic blood pressure by at least 20 mm Hg to <150 mm Hg. In the control group, matching placebos were used similarly. In view of persistent concerns about the use of calcium channel blockers as first-line antihypertensive drugs, this report explored to what extent nitrendipine, administered alone, prevented cardiovascular complications. Age at randomization averaged 70.2 years and systolic/diastolic blood pressure 173.8/85.5 mm Hg. Of 2398 actively treated patients, 1327 took only nitrendipine (average dose, 23.4 mg/d), and 1042 progressed to other treatments including nitrendipine (n=757; 35.7 mg/d), enalapril (n=783; 13.4 mg/d), and/or hydrochlorothiazide (n=294; 21.0 mg/d). Compared with the whole placebo group (n=2297), patients receiving monotherapy with nitrendipine had 25% (P=0.05) fewer cardiovascular end points, and those progressing to other active treatments showed decreases (P