Metal/protein ratio determination in the Rhodobacter capsulatus cytoplasmic pyrophosphatase enzyme by particle induced X-ray emission.

Inorganic pyrophosphatases are divided in two families, which differ both in structure and mechanism. All of them incorporate in its structure divalent metal cations. In 2003, it was reported for the first time that Rhodobacter capsulatus cytoplasmic pyrophosphatase belongs to family II. It is expected then, that this enzyme contains metal elements in its structure; however, this characterization has not been carried out yet. A fine application of accelerators is the use of proton beams to induce X-ray emission (PIXE) for analyzing the composition of biological macromolecules. The purpose of this work is to complement R. capsulatus cytoplasmic pyrophosphatase characterization by determining the presence of metal elements in its structure. Three different strategies were used: PAGE-PIXE, PAGE-Digestion-PIXE, and Dialysis-PIXE and when metals were found the metal/enzyme ratio was calculated. Only cobalt was found to be associated to the enzyme chemical structure in a ratio 3 Co/enzyme.

Risk and benefit of treatment of isolated systolic hypertension in the elderly: evidence from the Systolic Hypertension in Europe Trial.

The Syst-Eur trial investigated whether active treatment starting with the dihydropyridine calcium channel blocker (CCB) nitrendipine, could reduce the cardiovascular complications of isolated systolic hypertension (ISH) in the elderly. The intention-to-treat analysis showed that active treatment improved outcome. The per-protocol analysis largely confirmed these results. The effect of treatment on total and cardiovascular mortality might be attenuated in very old patients. Further analysis also suggested benefit in those patients who remained on nitrendipine monotherapy. Active treatment was more beneficial in patients with diabetes as compared with those without diabetes at entry and reduced the incidence of dementia by 50%. Analyses of data from the Ambulatory Blood Pressure Monitoring (ABPM) Side Project suggested that most of the benefit of treatment was seen in patients with a daytime systolic BP > or = 160 mm Hg. Finally, a meta-analysis partly based on Syst-Eur data showed that in older hypertensive patients pulse pressure and not mean pressure is the major determinant of cardiovascular risk.

Interaction between nonsteroidal anti-inflammatory drug intake and calcium-channel blocker-based antihypertensive treatment in the Syst-Eur trial.

OBJECTIVE: To assess the relationship between chronic intake of nonsteroidal anti-inflammatory drugs (NSAID) and outcome, in particular (gastrointestinal) bleeding and to investigate whether the effect of chronic NSAID intake was similar in untreated and treated elderly hypertensives. METHODS: Eligible patients (> or = 60 years, with systolic blood pressure 160-219 mm Hg and diastolic blood pressure < 95 mm Hg) were randomised to active treatment or placebo. Active treatment consisted of nitrendipine, with the possible addition of enalapril, hydrochlorothiazide, or both, titrated or combined to reduce the sitting systolic blood pressure by at least 20 mm Hg to below 150 mm Hg. Patients never taking NSAIDs (n = 2882) were compared with patients on chronic NSAID intake (n = 861), defined as reporting NSAID intake on at least 50% of the patient forms. RESULTS: There was a tendency towards lower mortality (relative hazard rate (95% confidence interval (CI), 0.77 (0.56-1.06)) and higher incidence of bleeding (1.13 (0.63-2.05) with chronic NSAID intake. Although there was no significant interaction between calcium-channel blocker (CCB)-based treatment and chronic NSAID intake for any of the end points, chronic NSAID intake tended to be associated with a lower incidence of bleeding on active treatment as compared to placebo (P-value of the interaction term = 0.07). CONCLUSION: The effect of chronic NSAID intake on outcome was similar in patients on active treatment based on a dihydropyridine CCB or on placebo. However, chronic NSAID intake might have a less deleterious effect on bleeding on active treatment as compared to placebo.

Dihydropyridine calcium-channel blockers for antihypertensive treatment in older patients--evidence from the Systolic Hypertension in Europe Trial.

OBJECTIVE: The Syst-Eur study investigated whether active antihypertensive treatment could reduce cardiovascular complications in elderly patients with isolated systolic hypertension. DESIGN: Randomised, placebo-controlled, double-blind outcome trial. SETTING: Hypertension clinics or general practitioners' surgeries in 198 centres in 23 Western and Eastern European countries. SUBJECTS: Patients aged > or = 60 years with sitting systolic blood pressure (BP) 160-219 mmHg and sitting diastolic BP < 95 mmHg during run-in phase. METHODS AND RESULTS: Four thousand, six hundred and ninety-five patients were randomly assigned to active treatment (N = 2,398), i.e. nitrendipine, with the possible addition of enalapril and hydrochlorothiazide, or to matching placebos (N = 2,297). In the intention-to-treat analysis, the between-group difference in blood pressure (BP) amounted to 10.1/4.5 mmHg (P < 0.001). Active treatment reduced the incidence of fatal and non-fatal stroke (primary endpoint) by 42% (P = 0.003). On active treatment all cardiac endpoints decreased by 26% (P = 0.03) and all 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). For total (P = 0.009) and cardiovascular mortality (P = 0.09), the benefit of antihypertensive treatment weakened with advancing age, and for total mortality it decreased with lower systolic BP at entry (P = 0.05). The benefits of active treatment were not independently related to sex or to the presence of cardiovascular complications at entry. The antihypertensive regimen was more effective in patients with diabetes than in those without diabetes at entry. Further analyses also suggested benefit in patients who were taking nitrendipine as the sole therapy. The per-protocol analysis largely confirmed the intention-to-treat results. Active treatment reduced all strokes by 44% (P = 0.004), all cardiac endpoints by 26% (P = 0.05) and all cardiovascular endpoints by 32% (P < 0.001). Total mortality was reduced by 26% (P = 0.05), but a similar reduction in cardiovascular mortality did not reach statistical significance in this analysis. Compared with placebo, active treatment also reduced the incidence of dementia by 50%. CONCLUSION: Stepwise antihypertensive drug treatment, starting with the dihydropiridine calcium-channel blocker nitrendipine, improves prognosis in elderly patients with isolated systolic hypertension.

Characterization of the inorganic pyrophosphatase from the pathogenic bacterium Helicobacter pylori.

A cytoplasmic pyrophosphatase [E.C. 3.6.1.1.] was partially purified from Helicobacter pylori. The molecular mass was estimated to be 103 kDa by gel filtration. Results of SDS-PAGE suggested that the enzyme consists of six identical subunits of 19.1 kDa each. The enzyme specifically catalyzed the hydrolysis of pyrophosphate and was very sensitive to NaF, but not to sodium molybdate. The optimal pH for activity was 8.5. Mg2+ was required for maximal activity; Mn2+, Co2+, and Zn2+ poorly supported hydrolytic activity. The pyrophosphatase had an apparent K(m) for Mg-PP(i)2 hydrolysis of 90 microM, and a Vmax estimated at 24.0 micromol P(i) min(-1) mg(-1).

The international database of self-recorded blood pressures in normotensive and untreated hypertensive subjects.

OBJECTIVES: To pool data from individual subjects in an attempt to determine an operational threshold for making clinical decisions based on the self-recorded blood pressure (SRBP) and to examine how many hypertensive subjects, diagnosed by conventional blood pressure (CBP) measurement, would have a self-recorded blood pressure within the normotensive range if the proposed thresholds were applied. DATA SOURCES: Thirteen research groups studied 4668 untreated subjects. RESULTS: In total 2401 subjects were normotensive, 494 were borderline hypertensive and 1773 were definitely hypertensive. Hypertension had been diagnosed from the mean of 1-6 (median 3) CBP measurements obtained during 1-3 (median 1) visits. The reference values for SRBP measurements determined from the 95th percentiles of the distributions for normotensive subjects were 137 mmHg systolic and 85 mmHg diastolic. Of the subjects with systolic hypertension, 16% had systolic SRBP

Implications of the Systolic Hypertension in China trial.

In 1988, the Systolic Hypertension in China (Syst-China) Collaborative Group started to investigate whether active treatment could reduce the incidence of stroke and other cardiovascular complications of isolated systolic hypertension. After stratification for center, sex and previous cardiovascular complications, alternate patients (n = 1253) were assigned nitrendipine 10-40 mg daily, with the possible addition of captopril 12.5-50.0 mg daily, or hydrochlorothiazide 12.5-50.0 mg daily, or both drugs. In 1141 control patients, matching placebos were employed similarly. At entry, sitting blood pressure averaged 170 mm Hg systolic and 86 mm Hg diastolic, age averaged 66 years, and total serum cholesterol was 5.1 mmol/L. At 2 years, the between-group differences were 9.1 mm Hg systolic (95% confidence interval: 7.6-10.7 mm Hg) and 3.2 mm Hg diastolic (2.4-4.0). Active treatment reduced total stroke by 38% (p=0.01), all-cause mortality by 39% (p=0.003), cardiovascular mortality by 39% (p=0.03), stroke mortality by 58% (p=0.02) and all fatal and nonfatal cardiovascular endpoints by 37% (p=0.004). In conclusion, antihypertensive treatment prevents stroke and other cardiovascular complications in older Chinese patients with isolated systolic hypertension. Treatment of 1000 Chinese patients for 5 years could prevent 55 deaths, 39 strokes, or 59 major cardiovascular endpoints.

Systolic Hypertension in Europe (Syst-Eur) trial phase 2: objectives, protocol, and initial progress. Systolic Hypertension in Europe Investigators.

The Systolic Hypertension in Europe (Syst-Eur) trial proved that blood pressure (BP) lowering therapy starting with nitrendipine reduces the risk of cardiovascular complications in older (> or = 60 years) patients with isolated systolic hypertension (systolic BP > or = 160 mm Hg and diastolic BP < 95 mm Hg). After the completion of the Syst-Eur trial on 14 February 1997, 3506 consenting patients (93.0% of those eligible) were enrolled in phase 2 of the Syst-Eur trial. This open follow-up study aims to confirm the safety of long-term antihypertensive therapy based on a dihydropyridine. To lower the sitting systolic BP below 150 mm Hg (target BP), the first-line agent nitrendipine (10-40 mg/day) may be associated with enalapril (5-20 mg/day), hydrochlorothiazide (12.5-25 mg/day), both add-on study drugs, or if required any other antihypertensive agent. On 1 November 1998, 3248 patients were still being followed, 86 patients had proceeded to non-supervised follow-up, and 43 had died. The median follow-up in Syst-Eur 2 was 14.3 months. At the last available visit, systolic/diastolic BP in the patients formerly randomised to placebo (n = 1682) or active treatment (n = 1824), had decreased by 13.2/5.2 mm Hg and by 4.6/1.6 mm Hg, respectively, so that the between-group BP difference was 1.7 mm Hg systolic (95% Ci: 0.8 to 2.6 mm Hg; P < 0.001) and 0.9 mm Hg diastolic (95% Cl: 0.4 to 1.5 mm mm Hg; P < 0.001). At the beginning of Syst-Eur 2, the goal BP was reached by 25.4% and 50.6% of the former placebo and active-treatment groups; at the last visit these proportions were 55.9% and 63.1%, respectively. At that moment, 45.9% of the patients were on monotherapy with nitrendipine, 29.3% took nitrendipine in combination with other study drugs. Until the end of 2001, BP control of the Syst-Eur 2 patients will be further improved. Cardiovascular complications and adverse events, such as cancer or gastro-intestinal bleeding, will be monitored and validated by blinded experts.

The epidemiology of the association between hypertension and menopause.

Menopause is a normal aging phenomenon in women and consists of the gradual transition from the reproductive to the non-reproductive phase of life. The median age at the menopause is currently around 50 years. As a result of the increasing life expectancy in the first and second worlds, many women will be postmenopausal for over one-third of their lives. The influence of menopause per se on blood pressure remains uncertain. Recent experimental and epidemiological evidence supports the hypothesis that oestrogen deficiency may induce endothelial and vascular dysfunction and potentiate the age-related increase in systolic pressure, possibly as a consequence of a reduced compliance of the large arteries. However, the latter hypothesis requires further investigation.

Triphenyltin as an inhibitor of membrane-bound pyrophosphatase of Rhodospirillum rubrum.

The effect of triphenyltin on the activity of membrane-bound pyrophosphatase of Rhodospirillum rubrum was investigated. Triphenyltin inhibits the hydrolysis of chromatophore membrane-bound pyrophosphatase in a pH-dependent pattern, being maximal at pH 9-10. At basic pH values, the inhibition produced by this organotin on membrane-bound pyrophosphatase is very similar to that produced on the chromatophore H+ATPase (I50 = 14.4 and 10 microM, respectively). Detergent-solubilized membrane-bound pyrophosphatase is also inhibited by triphenyltin, but the cytoplasmic enzyme of R. rubrum is inhibited only slightly. The inhibitory effect of triphenyltin on membrane-bound pyrophosphatase is the same with Mg-PPi or Zn-PPi, and is dependent on the chromatophore membrane concentration. Triphenyltin modified mainly the Vmax of the enzyme, and only slightly its Km. Free Mg2+ does not reverse the inhibition. Reducing agents prevent triphenyltin inhibition of the membrane-bound pyrophosphatase, but their effect is due to an alteration of the inhibitor, and not to a modification of thiol groups of the enzyme. The most likely site for triphenyltin inhibition in chromatophore membrane-bound pyrophosphatase is a component either within or closely associated with the membrane.

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.

Reference values for self-recorded blood pressure: a meta-analysis of summary data.

BACKGROUND: The widespread clinical use of self-recorded blood pressure measurement is limited by the lack of generally accepted reference values. The purpose of this study was therefore to perform a meta-analysis of summary data in an attempt to determine an operational threshold for self-recorded blood pressures. STUDIES AND METHODS: Seventeen studies, including a total of 5422 subjects, were reviewed. Eight of these 17 studies included both normotensive and untreated hypertensive subjects, while the other 9 reports included normotensive subjects only. Within each study an operational cutoff point between normotension and hypertension was derived by means of the mean+2 SDs and the 95th percentiles of the self-recorded blood pressure in normotensive subjects. These 2 methods were contrasted with 2 other techniques that have been applied in the literature to calculate (1) the self-recorded pressures equivalent to a conventional pressure of 140 mm Hg systolic and 90 mm Hg diastolic by means of regression analysis and (2) the self-recorded blood pressures at the percentiles corresponding to a conventional pressure of 140/90 mm Hg. The latter 2 methods were applied in untreated subjects not selected on the basis of their blood pressure. RESULTS: With weighting for the number of subjects included in the various studies, the self-recorded blood pressure averaged 115/71 mm Hg in normotensive persons and 119/74 mm Hg in untreated subjects not selected on the basis of their blood pressure. The reference values for self-recorded blood pressures determined by the mean+2 SDs (137/89 mm Hg) or the 95th percentile (135/86 mm Hg) of the distribution in normotensive subjects were concordant within 2/3 mm Hg, whereas the cutoff points derived with the regression and percentile methods were considerably lower, ie, 125/79 and 129/84 mm Hg, respectively. CONCLUSIONS: Until the relationship between self-recorded pressure and the incidence of cardiovascular morbidity and mortality is further clarified by prospective studies, a mean self-recorded blood pressure above 135 mm Hg systolic or 85 mm Hg diastolic may be considered hypertensive.

Conventional and ambulatory measurements of blood pressure in old patients with isolated systolic hypertension: baseline observations in the Syst-Eur trial.

OBJECTIVES: To compare clinic and am measurements of blood pressure in old patients with isolated systolic hypertension and their reproducibilities. PATIENTS: In total 610 patients aged >/= 60 years with isolated systolic hypertension detected by clinic measurement were monitored during the placebo run-in phase of the Syst-Eur trial. METHODS: The time-weighted 24 h blood pressure, clock-time day and night blood pressures, the cumulative-sum-derived crest and trough blood pressures and the high and low blood pressure levels according to the square-wave model were computed. The daily alteration between the high and low spans of blood pressure was quantified using the day-night difference, the cumulative-sum-derived magnitude of circadian alteration, the Fourier amplitude and the difference between the high and low blood pressure levels of the square-wave model. RESULTS: The daytime am systolic blood pressure was, on average, 21 mmHg lower than the clinic systolic blood pressure, whereas diastolic pressure was, on average, similar with both techniques of measurement. Clinic levels of blood pressure in the 141 patients who underwent repeat measurements and the parameters describing the difference between the daily high and low spans of blood pressure were equally reproducible. However, both were less reproducible than the ambulatory blood pressure levels. The reproducibility coefficients, expressed as percentages of near maximum variation, were 49 and 50% for the clinic systolic and diastolic blood pressures, 30 and 32% for the mean 24 h systolic and diastolic blood pressures and 45-55% for the parameters describing the daily alteration between the high and low spans of blood pressure. CONCLUSION: Values of blood pressure in old patients with isolated systolic hypertension were more reproducible for ambulatory than they were for clinic measurements. Levels in patients selected because they have a high clinic blood pressure may be substantially higher with conventional than they are with daytime ambulatory measurement. The prognostic significance of this difference for the present patients is currently under investigation.

For how many days should blood pressure be measured at home in older patients before steady levels are obtained?

This study investigated the period of time that blood pressure (BP) should be measured at home in older patients in order to obtain steady BP values. Thirty-six men and 38 women (> or =60 years) were recruited at one family practice. At one office visit the family physician measured supine, sitting and standing BPs three times consecutively in each position. During 10 consecutive days, BP was measured at home five times daily. The supine and standing BPs were measured once in the morning and in the evening and the sitting BP once at noon. These home BP values were averaged over the first day (1-day), over the first 3 days (3-day) and all 10 days (10-day) of measurements. In both the supine (-5.1 mm Hg) and sitting (-3.8 mm Hg) positions the 10-day average systolic home BP was significantly lower than the corresponding office BP. The opposite was observed for the 10-day average standing home BP values (+7.3/+3.4 mm Hg). Comparison of the 3-day and 10-day average home BP values showed only a significantly lower 10-day than 3-day systolic BP level in the supine position (-1.1 mm Hg, 95% CI -1.9 to -0.2 mm Hg). Repeated measures ANOVA, showed a small but significant decrease over time only for the supine systolic home BP (-0.29 mm Hg per day, 95% CI -0.49 to -0.08 mm Hg per day). We conclude that in older subjects, 3 days of home measurements may suffice to obtain steady values for the sitting and standing BPs. A longer interval might be required for the supine BP.

Antihypertensive treatment based on conventional or ambulatory blood pressure measurement. A randomized controlled trial. Ambulatory Blood Pressure Monitoring and Treatment of Hypertension Investigators.

CONTEXT: Ambulatory blood pressure (ABP) monitoring is used increasingly in clinical practice, but how it affects treatment of blood pressure has not been determined. OBJECTIVE: To compare conventional blood pressure (CBP) measurement and ABP measurement in the management of hypertensive patients. DESIGN: Multicenter, randomized, parallel-group trial. SETTING: Family practices and outpatient clinics at regional and university hospitals. PARTICIPANTS: A total of 419 patients (> or =18 years), whose untreated diastolic blood pressure (DBP) on CBP measurement averaged 95 mm Hg or higher, randomized to CBP or ABP arms. INTERVENTIONS: Antihypertensive drug treatment was adjusted in a stepwise fashion based on either the average daytime (from 10 AM to 8 PM) ambulatory DBP (n=213) or the average of 3 sitting DBP readings (n=206). If the DBP guiding treatment was above (>89 mm Hg), at (80-89 mm Hg), or below (<80 mm Hg) target, 1 physician blinded to the patients' randomization intensified antihypertensive treatment, left it unchanged, or reduced it, respectively. MAIN OUTCOME MEASURES: The CBP and ABP levels, intensity of drug treatment, electrocardiographic and echocardiographic left ventricular mass, symptoms reported by questionnaire, and cost. RESULTS: At the end of the study (median follow-up, 182 days; 5th to 95th percentile interval, 85-258 days), more ABP than CBP patients had stopped antihypertensive drug treatment (26.3% vs 7.3%; P<.001), and fewer ABP patients had progressed to sustained multiple-drug treatment (27.2% vs 42.7%; P<.001). The final CBP and 24-hour ABP averaged 144.1/89.9 mm Hg and 129.4/79.5 mm Hg in the ABP group and 140.3/89.6 mm Hg and 128.0/79.1 mm Hg in the CBP group. Left ventricular mass and reported symptoms were similar in the 2 groups. The potential savings in the ABP group in terms of less intensive drug treatment and fewer physician visits were offset by the costs of ABP monitoring. CONCLUSIONS: Adjustment of antihypertensive treatment based on ABP monitoring instead of CBP measurement led to less intensive drug treatment with preservation of blood pressure control, general well-being, and inhibition of left ventricular enlargement but did not reduce the overall costs of antihypertensive treatment.

Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. The Systolic Hypertension in Europe (Syst-Eur) Trial Investigators.

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.

Ambulatory blood pressure monitoring in clinical trials.

Ambulatory blood pressure monitoring is increasingly being used in clinical trials. Trials with ambulatory monitoring, just like clinical experiments based on conventional sphygmomanometry, need to be controlled properly, because ambulatory blood pressure measurements are not completely devoid of placebo-like effects. The trough: peak ratio might be a useful instrument for assessment of the durations of action of antihypertensive drugs. However, its error term and confidence interval need to be reported and its determination in clinical trials requires further standardization. Ambulatory compared with conventional blood pressure measurements are characterized by a higher reproducibility. This property makes a reduction in sample size possible in cross-over but not in parallel group trials, if instead of the conventional blood pressure the 24 h or daytime blood pressures are compared. Trials focusing on the full course of the blood pressure through the day need a larger sample size than do those just concerning the conventional blood pressure level.

Antihypertensive therapy in older patients with isolated systolic hypertension: the Syst-Eur experience in general practice. The Syst-Eur Investigators.

BACKGROUND AND OBJECTIVE: This interim report from the Syst-Eur trial investigated the level of blood pressure control achieved during the double-blind period in patients followed in general practices. METHODS: In the Syst-Eur trial elderly patients (60 years or older) with isolated systolic hypertension were randomized to either active or placebo treatment. Active treatment consisted of nitrendipine combined with enalapril and/or hydrochlorothiazide to reduce systolic pressure to < 150 mmHg and by > or = 20 mmHg. Matching placebos were used in the control group. RESULTS: This analysis was restricted to patients of general practitioners who had been followed for at least 12 months. The placebo (N = 204) and active treatment (N = 217) groups had similar characteristics at randomization. At one year, the difference in sitting pressure between the two treatment groups was 10 mmHg systolic and 4 mmHg diastolic. Fewer patients remained on monotherapy in the placebo than in the active treatment group and on placebo the second and third line medications were started earlier. Nitrendipine tablets were discontinued in 10 patients on placebo and in 21 patients assigned to active treatment (P < 0.001 for all comparisons). CONCLUSIONS: A significant blood pressure reduction can be achieved and maintained in older patients with isolated systolic hypertension followed by general practitioners. Whether this blood pressure reduction results in a clinically meaningful decrease of cardiovascular complications is under investigation.

Conventional and ambulatory blood pressure measurement in older patients with isolated systolic hypertension:second progress report on the ambulatory blood pressure monitoring project in the Syst-Eur trial.

OBJECTIVES: To compare clinic and ambulatory blood pressure measurement and the reproducibility of these measurements in older patients with isolated systolic hypertension.PATIENTS: A total of 477 patients aged >/= 60 years with isolated systolic hypertension on clinic measurement were monitored during the placebo run-in phase of the Syst-Eur trial. METHODS: The time-weighted 24 h blood pressure, clock time day and night blood pressure, the cumulative sum-derived crest and trough blood pressure and the high and low blood pressure levels of the square-wave model were computed. The daily alteration between the high and low blood pressure spans was quantified using the clock time day-night difference, the cumulative sum-derived circadian alteration magnitude, the Fourier amplitude and the difference between the high and low blood pressure levels of the square-wave model. RESULTS: The daytime ambulatory systolic blood pressure was, on average, 21 mmHg lower than the clinic blood pressure, whereasthe diastolic blood pressure was, on average, similar with both techniques of measurement. In the 132 patients who underwent repeat measurements, clinic blood pressure levels and the parameters describing the difference betgween the daily high and low blood pressure spans were equally reproducible. However, both were less reproducible than the ambulatory blood pressure levels. The repeatability coefficients, expressed as percentages of near maximum variation, were 50 and 51% for the clinic systolic and diastolic blood pressures, 30 and 33% for the mean 24 h systolic and diastolic blood pressures and between 44 and 54% for the parameters describing the daily alteration between the high and low blood pressure spans. CONCLUSION: In older patients with isolated systolic hypertension, clinic and ambulatory systolic blood pressure may differ greatly; the prognostic significance of this difference remains to be elucidated. Furthermore, the level of blood pressure in these patients is more reproducible by ambulatory measurement than it is by clinic measurement.

Antihypertensive therapy in older patients with isolated systolic hypertension: the Syst-Eur experience in general practice

Background and objective. This interim report from the Syst-Eur trial investigated the level of blood pressure control achieved during the double-blind period in patients followed in general practices. Methods. In the Syst-Eur trial elderly patients (60 years or older) with isolated systolic hypertension were randomized to either active or placebo treatment. Active treatment consisted of nitrendipine combined with enalapril and/or hydrochlorothiazide to reduce systolic pressure to Results. This analysis was restricted to patients of general practitioners who had been followed for at least 12 months. The placebo (N = 204) and active treatment (N = 217) groups had similar characteristics at randomization. At one year, the difference in sitting pressure between the two treatment groups was 10 mmHg systolic and 4 mmHg diastolic. Fewer patients remained on monotherapy in the placebo than in the active treatment group and on placebo the second and third line medications were started earlier. Nitrendipine tablets were discontinued in 10 patients on placebo and in 21 patients assigned to active treatment (P Conclusions. A significant blood pressure reduction can be achieved and maintained in older patients with isolated systolic hypertension followed by general practitioners. Whether this blood pressure reduction results in a clinically meaningful decrease of cardiovascular complications is under investigation. Keywords. Antihypertensive treatment, general practice, isolated systolic hypertension, randomized clinical trial.