Alarmingly high occurrence and case fatality of acute coronary heart disease events in Estonia: results from the Tallinn AMI register 1991-94.

OBJECTIVE: The purpose of this study was to produce stable estimates for the incidence, attack and mortality rates and case fatality of acute myocardial infarction (AMI) in Tallinn, the capital of Estonia. RESEARCH DESIGN AND METHODS: The Tallinn AMI register covers the population aged 25-64 years and official residents of Tallinn. The register follows the WHO MONICA project protocols in the data collection and diagnostic evaluation of the suspected AMI events and CHD death. RESULTS: Age-standardized annual incidence, attack rate and mortality in men aged 35-64 years were high, varying from (per 100000 per year) 352, 499 and 208, respectively, in 1991 to 438, 628 and 317, respectively, in 1993. In addition, in women, annual incidence, attack rate and mortality were high, varying from (per 100000 per year) 82, 100 and 31, respectively, in 1991 to 110 and 142 in 1993 for the incidence and attack rate, and to 61 in 1992 for mortality. The percentage of out-of-hospital coronary death (sudden death) increased in men from 33 to 52% and in women from 24 to 42% during 1991-94, and the 28-day case fatality increased in men from 42 to 58%, and in women from 32 to 50%. In Tallinn, women with AMI were treated as actively as men with invasive treatment (thrombolysis, angioplasty, bypass surgery) during the acute phase of MI. CONCLUSIONS: The incidence, attack rate and mortality of AMI were high in both men and women in Tallinn. The high 28-day case fatality observed was primarily due to the high proportion of out-of-hospital deaths.

Prevention of dementia in randomised double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial.

BACKGROUND: Systolic hypertension increases the risk of dementia in elderly people. The vascular dementia project, set up in the framework of the double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial, investigated whether antihypertensive drug treatment could reduce the incidence of dementia. METHODS: Eligible patients had no dementia, were at least 60 years old, and had a blood pressure when seated of 160-219 mm Hg systolic and below 95 mm Hg diastolic. Active treatment consisted of nitrendipine (10-40 mg/day) with the possible addition of enalapril (5-20 mg/day), hydrochlorothiazide (12.5-25 mg/day), or both drugs, titrated or combined to reduce the systolic blood pressure by at least 20 mm Hg to reach a value below 150 mm Hg. Cognitive function was assessed by the mini mental state examination (MMSE). If the MMSE score was 23 or less, diagnostic tests for dementia were done (DSM-III-R criteria). The cause of dementia was established by the modified ischaemic score with brain imaging or the Hachinski score. FINDINGS: Median follow-up by intention to treat was 2.0 years. Compared with placebo (n=1180), active treatment (n=1238) reduced the incidence of dementia by 50% from 7.7 to 3.8 cases per 1000 patient-years (21 vs 11 patients, p=0.05). The median MMSE score at randomisation was 29 in both treatment groups. At the last available assessment, systolic and diastolic blood pressure were, respectively, 8.3 mm Hg and 3.8 mm Hg lower (p<0.001) in the active-treatment group, but on average the MMSE scores did not change in either group. In the control patients, however, the MMSE decreased (p=0.04) with decreasing diastolic blood pressure, whereas in the active-treatment group MMSE scores improved slightly (p=0.01) with greater reduction in diastolic blood pressure (p=0.002 for between-group difference). INTERPRETATION: In elderly people with isolated systolic hypertension, antihypertensive treatment was associated with a lower incidence of dementia. If 1000 hypertensive patients were treated with antihypertensive drugs for 5 years 19 cases of dementia might be prevented.

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.

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.

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.

Acute myocardial infarction in Estonia: first results from the Tallinn AMI Register.

The acute myocardial infarction (AMI) register of Tallinn, the capital of Estonia, started in 1990. The register follows methodology recommended by the WHO MONICA Project for the registration of coronary events. By standardizing its procedures with the FINMONICA AMI register, the Tallinn AMI register aims at producing data comparable with those of the centers participating in the WHO MONICA Project. This article presents incidence, attack rates, and mortality rates of AMI in Estonia during the first year of registration in Estonians and non-Estonians (mostly Russians) of the study area. The total number of registered AMI events was 493 among men and 117 among women. The age-standardized mortality from AMI (per 100,000 population) was 249 (95% confidence interval, 201-297) in Estonian men and 234 (189-279) in non-Estonian men. In women the corresponding rates were 35 (20-50) and 39 (23-55), respectively. The incidence and attack rate of AMI were not different in Estonians and non-Estonians. The incidence of AMI seems to be relatively high in international comparison. The registration period of our study is thus far rather short, but it is the first investigation of the incidence of AMI in Estonia based on standardized data collection procedures. This study provides a basis for the development of surveillance of cardiovascular disease in Estonia.

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.

Diurnal blood pressure profile in older patients with isolated systolic hypertension. The SYST-EUR Investigators.

This study describes the diurnal blood pressure (BP) profile and identifies its correlates in older patients with isolated systolic hypertension (ISH). The ambulatory BP readings of 408 patients, aged > or = 60 years, with ISH on clinic measurement, enrolled in the placebo run-in phase of the Syst-Eur Trial were examined. The time-weighted 24 h BP, daytime and night-time BP and the cusum-derived crest and trough BP were computed to express the BP level. The daily alteration between the high and low BP span was estimated from the day-night BP difference, the cusum derived circadian alteration magnitude and plot height, as well as the amplitude of the Fourier curve. The 24 h SBP and DBP tended to be higher in men (150 +/- 15/82 +/- 9 mm Hg) than in women (147 +/- 17/79 +/- 10 mm Hg), but the sex difference was only significant for DBP. In multiple regression analysis, the 24 h SBP increased (P < 0.05) by 3 mm Hg for each 10 year increment in age and was also 10 mm Hg higher (P < 0.001) in smokers than in non-smokers; the 24 h DBP was 2 mm Hg higher (P < 0.05) in men than in women and decreased (P < 0.05) by 1.5 mm Hg for each 10 year increment in age. The day-night difference in SBP increased with 2 mm Hg for each 10 mm Hg increase in the conventional pressure, decreased with 5 mm Hg for each 10 year increment in age and was 6 mm Hg higher in smokers than in non-smokers; the day-night difference in diastolic pressure was 2 mm Hg greater in women than in men. We conclude that the main determinants of the diurnal BP variation in older patients with isolated systolic hypertension were sex, age, smoking habits and the level of pressure on conventional measurement.