Response to antihypertensive therapy in older patients with sustained and nonsustained systolic hypertension. Systolic Hypertension in Europe (Syst-Eur) Trial Investigators.

BACKGROUND: The goal of the present study was to assess the effect of antihypertensive therapy on clinic (CBP) and ambulatory (ABP) blood pressures, on ECG voltages, and on the incidence of stroke and cardiovascular events in older patients with sustained and nonsustained systolic hypertension. METHODS AND RESULTS: Patients who were >/=60 years old, with systolic CBP of 160 to 219 mm Hg and diastolic CBP of <95 mm Hg, were randomized into the double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) Trial. Treatment consisted of nitrendipine, with the possible addition of enalapril, hydrochlorothiazide, or both. Patients enrolled in the Ambulatory Blood Pressure Monitoring Side Project were classified according to daytime systolic ABP into 1 of 3 subgroups: nonsustained hypertension (<140 mm Hg), mild sustained hypertension (140 to 159 mm Hg), and moderate sustained hypertension (>/=160 mm Hg). At baseline, patients with nonsustained hypertension had smaller ECG voltages (P<0.001) and, during follow-up, a lower incidence of stroke (P<0.05) and of cardiovascular complications (P=0.01) than other groups. Active treatment reduced ABP and CBP in patients with sustained hypertension but only CBP in patients with nonsustained hypertension (P<0.001). The influence of active treatment on ECG voltages (P<0.05) and on the incidence of stroke (P<0.05) and cardiovascular events (P=0.06) was more favorable than that of placebo only in patients with moderate sustained hypertension. CONCLUSIONS: Patients with sustained hypertension had higher ECG voltages and rates of cardiovascular complications than did patients with nonsustained hypertension. The favorable effects of active treatment on these outcomes were only statistically significant in patients with moderate sustained hypertension.

Symptoms reported by elderly patients with isolated systolic hypertension: baseline data from the SYST-EUR trial. Systolic Hypertension in Europe.

OBJECTIVES: To determine the symptomatic well-being of elderly persons with isolated systolic hypertension. DESIGN AND SETTING: Well-being determined during the placebo run-in period prior to entry to the Systolic Hypertension in Europe (SYST-EUR) trial. SUBJECTS: 641 People, 60 years or older with an average sitting blood pressure of 173/86 mm Hg. OUTCOME MEASURES: 33 Symptomatic complaints determined by a standard interview. RESULTS: The 437 women complained of 25% of the symptoms and the 204 men 21% (P<0.001). A markedly higher prevalence was observed in women compared with men for: pain in the joints of the hands (35% of women complained of this against 22% of men); 'racing heart' (33% against 17%); dry eyes (16% against 6%); blurring of vision (35% against 23%); cramps in the legs (43% against 31%); and a sore throat (15% against 7%). Nocturia was the most frequent complaint (68% in both sexes). Eight symptoms increased with age and one (rash) tended to decline. With increasing systolic pressure women also reported more headaches, unsteadiness, blurring of vision, irregular heart beat and 'racing heart' but, of these, only headaches increased with diastolic pressure. These observations were made after adjusting for age, blood sugar and body mass index (BMI) and were not observed in men. Higher blood sugars were associated with mouth ulcers, 'racing heart', blurring of vision and cramps in the legs. A higher BMI was associated with six symptoms, and a lower age of leaving education with eight. In men, alcohol consumption was related to 'racing heart', and smoking to wheezing and having a dry cough. CONCLUSIONS: A high level of complaint was associated with female gender, increasing age, blood sugar and BMI and a low age of leaving education.

Correlates of cognitive status of old patients with isolated systolic hypertension: the Syst-Eur Vascular Dementia Project.

OBJECTIVE: To assess cognitive functions and their correlates for a dementia-free cohort of old patients with isolated systolic hypertension. DESIGN: Cross-sectional data from the randomization period of the European Trial in Elderly with Systolic Hypertension (Syst-Eur Vascular Dementia Project). SETTING: Sixteen European countries and Israel. PARTICIPANTS: We studied 2252 patients aged 60-100 years (mean 70). MAIN OUTCOME MEASURES: Mini Mental State Examination (MMSE) and Spearman correlation of MMSE scores to demographic data or blood pressure. RESULTS: The MMSE was successfully completed for 1474 women and 751 men. The baseline blood pressure averaged 173 +/- 10/86 +/- 6 mmHg (means +/- SD). Median age at which education of patients at school had stopped was 15 years. Men and women who consumed alcohol (28%) had median intakes of 8 and 3 g/day, respectively. The median MMSE score was 29 (range 15-30). The maximum score of 30 was attained by 609 (30%) subjects. Fifty-nine (3%) patients had a MMSE score of 23 or less. The MMSE score decreased with advancing age (r = -0.21, P < 0.001). Both for men and for women, it was positively correlated to the level of education (r = 0.30 and r = 0.32, P < 0.001). For women after adjustment for age and the level of education, the score was correlated negatively to systolic blood pressure (r = -0.07, P < 0.05) but positively to intake of alcohol (r = 0.06, P < 0.05). CONCLUSION: In a cohort of elderly patients with isolated systolic hypertension, baseline cognitive function measured in terms of the MMSE score was high, probably due to selective recruitment of patients who were not clinically demented. Blood pressure was a weak contributor to cognitive status compared with age and level of education. Baseline cognitive function of women was negatively and independently correlated to systolic blood pressure.

Calcium channel blockade and cardiovascular prognosis in the European trial on isolated systolic hypertension.

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

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.

Therapy in old patients with isolated systolic hypertension: fourth progress report on the Syst-Eur trial.

The Syst-Eur trial is a multicentre, randomized, double-blind, placebo controlled therapeutical trial in patients at least 60 years old and with isolated systolic hypertension. Its scope is to investigate the effects of modern antihypertensive drug treatment on morbidity and mortality and to assess possible adverse effects of the drugs used. Patients were recruited in 22 countries in western and eastern Europe and Israel. At three run-in visits 1 month apart their sitting systolic blood pressure (SBP) on single-blind placebo treatment averaged 180-219 mm Hg with diastolic blood pressure (DBP) lower than 95 mm Hg. After stratification for sex and the presence of cardiovascular complications, the patients were randomized either to active treatment or placebo. Active treatment consisted of nitrendipine (10-40 mg/day) with the possible addition of enalapril (5-20 mg/day) and/or hydrochlorothiazide (12.5-25 mg/day), titrated or combined to reduce the sitting SBP by at least 20 mm Hg to below 150 mm Hg. Matching placebos were employed similarly. The present progress report is based on the data received at the Coordinating Office before 1 March 1996. At that time 3433 subjects had been randomized. A total of 2015 patients had been followed for at least 1 year on double-blind treatment and 1298 patients for at least 2 years. At baseline BP was similar in both treatment groups and averaged 174/86 mm Hg. According to a per-protocol analysis at 1 year, BP fell (P < 0.001) on average by 22.6 +/- 15.7/6.0 +/- 8.0 mm Hg in the active treatment group and by 12.2 +/- 15.9/1.7 +/- 7.3 mm Hg in the placebo group. At 2 years BP was 10.2/5.7 mm Hg lower (P < 0.001) on active treatment than on placebo. At 1 year the percentage of patients who had reached goal BP was 19.9% in the placebo group and 41.4% in the active treatment group. At 2 years these percentages were 20.9 and 43.2 respectively.

Ambulatory monitoring uncorrected for placebo overestimates long-term antihypertensive action. Systolic Hypertension in Europe (SYST-EUR) Trial Investigators.

This study compares blood pressure (BP) changes during active antihypertensive treatment and placebo as assessed by conventional and ambulatory BP measurement. Older patients (> or = 60 years, n=337) with isolated systolic hypertension by conventional sphygmomanometry at the clinic were randomized to placebo or active treatment consisting of 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). At baseline, clinic systolic/diastolic BP averaged 175/86 mm Hg and 24-hour and daytime ambulatory BPs averaged 148/80 and 154/85 mm Hg, respectively. After 13 months (median) of active treatment, clinic BP had dropped by 22.7/7.0 mm Hg and 24-hour and daytime BPs by 10.5/4.5 and 9.7/4.3 mm Hg, respectively (P<.001 for all). However, clinic (9.8/1.6 mm Hg), 24-hour (2.1/1.1 mm Hg), and daytime (2.9/1.0 mm Hg) BPs decreased also during placebo (P<.05, except for daytime diastolic BP); these decreases represented 43%/23%, 20%/24%, and 30%/23% of the corresponding BP fall during active treatment. After subtraction of placebo effects, the net BP reductions during active treatment averaged only 12.9/5.4, 8.3/3.4, and 6.8/3.2 mm Hg for clinic, 24-hour, and daytime BPs, respectively. The effect of active treatment was also subject to diurnal variation (P<.05). Changes during placebo in hourly systolic and diastolic BP means amounted to (median) 21% (range, -1% to 42%) and 25% (-3% to 72%), respectively, of the corresponding changes during active treatment. In conclusion, expressed in millimeters of mercury, the effect of antihypertensive treatment on BP is larger with conventional than with ambulatory measurement. Regardless of whether BP is measured by conventional sphygmomanometry or ambulatory monitoring, a substantial proportion of the long-term BP changes observed during active treatment may be attributed to placebo effects. Thus, ambulatory monitoring uncorrected for placebo or control observations, like conventional sphygmomanometry, overestimates BP responses in clinical trials of long duration.

Early kinetics of antibody response to inactivated influenza vaccine.

The aim was to examine the rapidity of haemagglutination inhibiting (HI) antibody response induced by immunization with a current inactivated trivalent influenza vaccine. Five to six sequential serum samples collected in autumn 1992 from each of 68 vaccinees in three age groups were studied for HI antibodies to ten influenza virus strains representing vaccine and epidemic viruses. Geometric mean titres, response rates and protection rates are presented. Response rates of > 70% were overall, but not until two weeks after the vaccination. Significant two- and four-day post-vaccination antibody responses were detected only occasionally. In previously vaccinated persons, average antibody titres to some of the viruses decreased during the first days after the vaccination. In the subsequent samples, the titres remained lower than in persons who were not vaccinated against influenza in preceding years. Protection against influenza infection may be frequently developed not until two weeks after vaccination. This has relevance to prophylactic administration of amantadine and rimantadine when an influenza A outbreak is imminent and the vaccination is late.