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.

QT dispersion and hypertensive heart disease in the elderly.

AIM: To determine the predictors and risk of increased QT dispersion in the elderly hypertensive patients. METHODS: A 12-lead electrocardiogram (ECG), M-mode echocardiography and ambulatory blood pressure as well as Holter monitoring were performed for 67 patients over 60 years of age with essential hypertension (I and II(o) WHO). The presence of ischaemic changes on ECG was evaluated based on the Minnesota Code. QT intervals were corrected with Bazett's formulae and QT dispersion was determined as the difference between maximal and minimal QTc intervals. Interventricular septal thickness (IVSTd), left ventricular internal diameter (LVDd) and posterior wall thickness (PWTd) were measured and left ventricular mass index (LVMI) was calculated. Subjects were divided according to the median of QTc dispersion (0.10 s). The differences between groups were assessed using chi-squared and Student's t-test. RESULTS: Subjects with increased QTc dispersion did not differ from those with low QTc dispersion when age, gender and body mass index were analysed. Similarly, the average systolic blood pressure, diastolic blood pressure and blood pressure variability were comparable in both groups. The mean QTc interval was similar in both groups. In patients with increased QT dispersion, left ventricular hypertrophy (LVH) and ischaemic changes on ECG were more frequently recognized (respectively 41.2 versus 18.2%, P < 0.001; 47.1 versus 21.2%, P < 0.05). Moreover, these subjects presented a significantly greater number of premature ventricular beats (317.1 +/- 665.6 versus 64.88 +/- 188.6, P < 0.05) and higher classes of Lown's arrhythmia scale (classes III-IV, 23.35% versus 9.1%). LVMI was insignificantly higher in the group with greater QTc dispersion (165.82 +/- 54.5 versus 145.07 +/- 36.47 g/ m2). Other echocardiographic indices of LVH were similar in both groups. On the other hand, the analysis of regression indicated positive correlation between the dispersion of QTc interval and thickness of left ventricle walls (for IVSd - r = 0.37; for PWd - r = 0.31), relative wall thickness (r = 0.28) and LVMI (r = 0.28). CONCLUSIONS: QTc dispersion is increased in the elderly hypertensive individuals, with the presence of LVH and myocardial ischaemia on ECG. These patients are more likely to demonstrate severe ventricular dysrhythmias.

Obesity and blood pressure in the elderly free-living population.

OBJECTIVE: The aim of presented analysis was to determine the relationship between blood pressure (BP) and different indices of obesity in the elderly free-living population. DESIGN AND METHODS: In 317 inhabitants of the randomly chosen area of Cracow (70 years old and older) who could come to the out-patient clinic for an interview, BP, weight and height were taken. Body mass index (BMI) was used to classify the population into lean (BMI < 25 kg/m2), overweight (25 < or = BMI < 30 kg/m2) and obese (BMI > or = 30 kg/m2) subjects. In order to separate the effect of adipose tissue and lean body mass, weight of total adipose tissue (AT) and lean body mass (LBM) were calculated according to the anthropometric CT-calibrated equations. RESULTS: Obese patients had a significantly higher systolic BP (SBP) when compared with lean subjects (respectively SBP [mm Hg] 175.7 +/- 27.5 vs 161.8 +/- 21.8), and higher diastolic BP (DBP) [mm Hg] in comparison with both other groups (obese: 93.7 +/- 12.4 vs lean: 85.34 +/- 10.6, overweight: 87.15 +/- 12.73). The relationship between systolic and diastolic BP, and weight (respectively for SBP: r = 0.256, DBP: r = 0.216), BMI (SBP: r = 0.261, DBP: r = 0.216) and AT (SBP r = 0.269, DBP r = 0.22, P < 0.01) was found only in women but not in men. CONCLUSIONS: Our results suggest that in the elderly the importance of obesity in the pathogenesis of hypertension depends partially on gender and it may be essential in women but not in men.

Long-term study of borderline hypertension among male industrial workers.

Out of 1,236 men aged 40-59 years working in the same industrial plant, 253 (20.5%) had borderline arterial hypertension (BH). These employees and 237 matched normotensives were followed for several years. After 13 years, 343 participants, 70% of the initial number were studied. Arterial hypertension developed in 79.1% of the group with initial BH, most frequently in those with systolic-diastolic, and less often with systolic or diastolic BH. In normotensives, hypertension was diagnosed in 30.0% (P less than 0.001). All participants showed a correlation between blood pressure rise and initial value. A smaller number of men in the group with initial BH (36%) continued to work compared with normotensive men (48.1%) (P less than 0.01). The relationship between ability to work and blood pressure level became more prominent when we took into account final diagnosis: 65.7% of the actual normotensives, 56.4% of the borderline hypertensives and 47.5% of the hypertensives were still working after 13 years. Death rate was also higher in the group with BH (15.4%) than in the controls (8.4%) (P less than 0.01). The highest death rate was found when BH was combined with other coronary risk factors.

Normal blood pressure values as perceived by normotensive and hypertensive subjects.

In spite of considerable progress, the control of hypertension in most countries is still insufficient. One of the reasons may be the poor awareness of the blood pressure (BP) cutoff values that define hypertension. The aim of this report is to verify the hypothesis that patients with hypertension accept higher BP levels as normal. The study was performed during a street-based BP screening project carried out across Poland, in summer 1997. In 444 persons who voluntarily participated in Cracow's part of the project, BP was taken on the left arm, in the sitting position, after a minimum of 5 min of rest, using a semiautomated device (Digital Blood Pressure UA-702). A questionnaire investigated participants' age, weight, height, level of education, history of hypertension and perception of normal values of BP. We compared measured BP values with those perceived as normal, and with the values recommended by WHO/ISH guidelines (<140/90 mmHg). To analyse the data we used Student's t-test and linear regression with adjustment for age and body mass index (BMI). Hypertensive subjects, compared with normotensives, were less aware of normal BP values (47.4 vs 83.9%, P<0.001, for systotic blood pressure, and 77.4 vs 88.4%, P<0.01, for diastotic blood pressure). Measured BP was positively related to BP values stated as normal. A similar relation was observed for age and BMI. In conclusion, poor awareness of normal BP values in hypertensives can be an important factor hindering better BP control. Education strategies might prove to be highly effective in helping to tackle the epidemics of hypertension.

Isolated systolic hypertension: pathophysiology, consequences and therapeutic benefits.

During recent decades the importance of perceiving isolated systolic hypertension (ISH) in cardiovascular pathophysiology has been changed from a benign condition to the major cardiovascular risk factor. Aging is per se associated with the deterioration in arterial compliance through both structural and functional changes in large arteries which mainly involves the intima and media. The observed changes result in a decrease of the lumen-to-wall ratio, the overall lumen cross-sectional area and an increase of arterial stiffness which especially involve the aorta and other elastic arteries. In addition to the structural changes in vessel walls, aging is associated with certain functional changes such as an increase in sympathetic system activity probably due to the age-related decreased sensitivity of beta-receptors. While the function of arterial wall alpha-receptors remains intact, in elderly subjects a shift towards arterial vasoconstriction can be observed. In many of the published studies the definition of ISH was based on the criterion 160/95 mm Hg or 160/90 mm Hg while in recognition of the high risk associated with systolic blood pressure (SBP) the WHO/ISH guidelines and Report of the Sixth Joint National Committee on Hypertension indicated that ISH should be diagnosed with SBP as > or =140 mm Hg and diastolic BP (DBP) as <90 mm Hg. Thus the setting down of normal values of SBP will lead to an earlier diagnosis and treatment of ISH. Several prospective studies, such as the US Hypertension Detection and Follow-up Programme, confirmed this and the Multiple Risk Factor Intervention Trial demonstrated that for any given level of DBP, higher SBP was associated with an increase in cardiovascular risk. Moreover, data from the Framingham Study show that ISH was associated not only with increased mortality but also cardiovascular morbidity. Risk of non-fatal stroke and myocardial infarction was increased three and two-times respectively in the presence of ISH. Three major up-to-date studies that included patients with ISH have been published. In concordance to the previously published SHEP and MCR trials, the most recent, the Systolic Hypertension in the Elderly Trial (SYST-EUR), demonstrated that active treatment significantly reduces the risk of stroke and all fatal and non-fatal cardiac end-points, including sudden death. Of note, these benefits were demonstrated with new anti-hypertensive classes such as dihydropiridyne calcium channel blocker (nitrendipine) and the angiotensin-converting enzyme inhibitor (enalapril). The necessity to carefully balance the benefits and risks of anti-hypertensive therapy in the elderly indicates that patients with suspected ISH should undergo careful BP measurements on at least three different occasions before the diagnosis is established and an orthostatic reaction should be evaluated. If non-pharmacological procedures fail, drug therapy should be considered, especially in elderly patients with a SBP over 160 mm Hg, since their risk of complications is markedly higher. Pharmacological treatment should also be strongly considered in patients with a SBP between 140 and 160 mm Hg with such concomitant cardiovascular risk factors as diabetes, angina pectoris, and left ventricular hypertrophy. The drug regimen should be simple, starting with a low dose of a single drug that is titrated slowly. The selection of the first-line anti-hypertensive agent should be based on a careful assessment of pathophysiological and clinical parameters in each individual geriatric patient.

Influence of long-term treatment with nifedipine on blood pressure, left ventricular mass and cardiac arrhythmias in elderly hypertensive patients.

To determine the benefits of the long-term monotherapy with nifedipine in the elderly hypertensive patients, 100 subjects > 60 years old were included to the trial. Therapeutic efficacy of nifedipine was confirmed in 69% of the patients and resulted in reduction of SBP by 20.9% and DBP by 19.0% of their initial values, from 179.7/101.3 to 142.1/82.9 mmHg (p < 0.001). On the other hand, the range of circadian changes in systolic and diastolic BM did not decrease (67.1 and 37.0 mmHg before treatment and 65.0 and 36.2 mmHg at the end of the trial). Although cardiac output and ejection fraction significantly improved, the patients showed neither a significant reduction of left ventricular mass (313.6 g before and 282.4 g after therapy) nor a decrease in cardiac arrhythmias. Usefulness of long-term monotherapy with nifedipine in elderly patients is diminished by side-effects (11%), as well as a preserved high circadian BP variability and the unchanged left ventricular morphology that may result in persistent cardiac arrhythmias despite of the significant fall in BP.

Ambulatory blood pressure monitoring and postprandial hypotension in elderly patients with isolated systolic hypertension. Systolic Hypertension in Europe (SYST-EUR) Trial Investigators.

The present analysis was undertaken to evaluate postprandial (PP) changes in blood pressure (BP) assessed with ambulatory BP monitoring (ABPM) in elderly subjects with isolated systolic hypertension (ISH) on conventional measurement. A total of 530 patients (335 women and 195 men, aged 60-100 years, median 70 years) who performed an ABPM during the placebo run-in period of the Syst-Eur trial were included into the analysis. The PP changes in BP and heart rate (HR) were calculated by subtracting the mean systolic BP (SBP), diastolic BP (DBP) and HR in the 2 h preceding the main meal from the corresponding means covering the 2 h after the meal. The reproducibility of the postprandial fall in BP and heart rate (PPH) was assessed by contrasting the first and second ABPM in a subgroup of 147 patients who performed two ABPM's during the placebo run-in period. The mean SBP and DBP decreased and reached the nadir 2 h after the main meal while HR did not change. When PPH was assessed by comparing BP in the 2 h before and after the meal, both SBP and DBP decreased significantly (respectively -6.6 mm Hg, -5.4 mm Hg; P < 0.001). In 67.6% of all patients a decrease in SBP was observed and in 24.1% it exceeded 16 mm Hg. The corresponding values for DBP were 71.3% and 24.5% (DBP decreased more than 12 mm Hg). A greater fall in DBP was associated with a greater decrease in HR (r = 0.20, P < 0.001), while changes in SBP and HR were not interrelated. Regression analysis did not identify any significant covariate of PPH. Group means of PPH could be reproduced without significant changes in their values, but the within-subject reproducibility of the PP changes was low. There were no differences in PPH according to the place of residence of the patients. In conclusion, the descriptive analysis of the meal-induced changes in ABPM in elderly subjects with ISH showed that in every day circumstances most of them experience falls in both SBP and DBP within 2 h after the meal.

Acute and long-term treatment of hypertension with nifedipine in the elderly.

The acute hypotensive effect of nifedipine was evaluated, and the possibility of its long-term use in hypertensives over 60 years of age was studied. Sublingual nifedipine in a dose of 20 mg was given to 28 patients, mean age 73.1 yrs, and blood pressure, heart rate, and plasma drug concentration were monitored at 15 min, and every 30 min thereafter for 3 hrs. Systolic and diastolic blood pressure decreased at 15 min by 22.1 and 7.0 mmHg, respectively, reaching a maximal decrease two hours after drug administration. The decrease in blood pressure level did not correlate with nifedipine plasma concentration, but only with the initial systolic blood pressure. Long-term treatment with nifedipine was initiated in 60 patients, with 45 patients completing the study. Mean age was 66.2 years. An initial dose of 30 mg daily had to be increased to 60-80 mg in one-third of the patients. Monotherapy was not satisfactory in some patients. Blood pressure gradually decreased from 173/99 to 148/85 mmHg at three months, and to 141/84 mmHg at six months. Drug tolerance was fairly good. Nifedipine was withdrawn due to a considerable increase in heart rate in three patients and skin allergy in one. The most frequent adverse symptoms were: rash, headache, and leg oedema. Laboratory tests revealed no changes in urea and creatinine, and an increase in fasting glycaemia. Lipid parameters did not change significantly. These data proved that a single dose of 20 mg of nifedipine produced therapeutic plasma concentration of the drug and good hypotensive effect, positively correlating with initial systolic blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

[Involutional osteoporosis--etiopathogenesis and treatment]. / Osteoporoza inwolucyjna--etiopatogeneza i leczenie.

Osteoporosis is a unique disease of old people. It is progressing from 5-th decade of life. The following factors are increasing progress of the disease: estrogen (and androgen) deficiency, low calcium diet, small physical activity, low body weight (body mass index). Disease mainly affects women in whom normal with age loss of bone tissue (average 0.3% of bone mass per year) increases up to 1-2% in postmenopausal period and in every third woman the loss may reach several percent a year. All these factors results in osteoporosis, systemic disease of the skeleton, characterized by low bone mass, damaged microarchitectonics and increase probability of spontaneous fracture of bones. The treatment of this disease is directed towards stimulating osteogenesis and inhibition the resorption of the bone tissue by more active lifestyle, diet rich in calcium (milk and its products), hormone replacement therapy supplemented with calcium and vitamin D3. The most effective drug in osteoporosis with increase bone turnover seems to be calcitonin, which is especially effective in treatment of senile osteoporosis (type II) and in all cases complicated by bone fractures.

[Electrocardiography in elderly inhabitants of Krakow. Epidemiological study]. / Elektrokardiogramy u starszych wiekiem mieszkanców krakowa. Badania epidemiologiczne.

The electrocardiographic records were performed in the randomly chosen area of Cracow. The results were obtained from 512 persons (153 M and 359 F) aged 70-93 years. Normal electrocardiograms observed in 25.4% of the studied population. The prevalence of electrocardiographic abnormalities was as follows: ST segment depression--40.0%, patterns of infarction--17.2% and left ventricular hypertrophy--10.4%. On the contrary right axis deviation, bradycardia, sinus arrest, II and III of a-v blocks were rarely observed. The prevalence of electrocardiographic abnormalities in the aged in Cracow is in the accordance with the findings observed in the countries with high risk of cardiovascular diseases.

[Rhythm and conduction disorders among the adult population. Epidemiologic data]. / Zaburzenia rytmu i przewodnictwa w populacji osób doroslych. Dane epidemiologiczne.

2.487 resting ECG were examined which is 61.3% of randomly chosen group of inhabitants of Cracow, aged from 20 to 93. There were: sinus tachycardia (HR 100)--4.2%, extrasystole--2.7%, fibrillatio atriorum 1.4%, blocks A-VI0--0.9%, intraventricular conduction defects--3.6% (most often LAH). Prevalence of disturbances of rhythm and conduction increases with age, mainly after 60.

[Prevalence of autoantibodies in serum of healthy persons over 85 years of age]. / Czestosc wystepowania autoprzeciwcial w surowicy osób zdrowych, po 85 roku zycia.

Aging is believed to be associated with the increase in the frequency of autoantibodies. However, as the recent studies suggest the immunological defects are not the consequence of the aging process but they could be a result of underlying diseases. We investigated the prevalence of the anti-nuclear (ANA), anti-mitochondrial (AMA), anti-smooth muscle (SMA), antibodies to gastric parietal cells (PCA) and thyroid anti-microsomal autoantibodies (anti-Tg) in the sera of the selected healthy elderly over 85 years of age. We discovered ANA in 10% of subjects, AMA-5% and PCA in 15% in the group that we examined. Anti-smooth muscle and thyroid anti-microsomal antibodies have not been observed. Autoantibodies were less frequent than in other studies, but our results have shown slight increase of some autoantibodies in the healthy elderly.

[Serum lipids in persons over 90 years of age]. / Lipidy surowicy u osób po 90 roku zycia.

UNLABELLED: Because of different views on the significance of the serum lipids as a risk factor of atherosclerosis in the elderly we evaluated the levels of total cholesterol (CH), HDL-cholesterol (HDL-CH) and triglyceride (TG) in the group of 56 very old (over the 90), who were in a good health condition. Desirable values of lipids were found respectively: CH in 55.4% of subjects, HDL-CH in 85.7% and TG in 89.3%. In the elderly with hypercholesterolemia (CH > 250 mg/dl) we simultaneously found high level of HDL-CH (x = 69.3 mg/dl). CONCLUSIONS: The serum lipids levels in the elderly over 90 were generally within the limit of desirable values. On the other hand subjects who had higher level of cholesterol had also high level of HDL-CH (69.3 mg/dl). Considering our results we came to the conclusion that high level of HDL-CH is one of the favoring factors to reach an advanced age.

[Knowledge about hypertension and blood pressure level]. / Wiedza o nadcisnieniu tetniczym a wysokosc cisnienia tetniczego krwi.

BACKGROUND: The improvement of efficacy of the hypertension prevention and patient education largely depend on determination of the hypertension risk factors and increase in knowledge about hypertension. The aim of this study was to assess correlation between the environmental factors and knowledge about hypertension and occasionally measured blood pressure values. MATERIALS AND METHODS: The studied group consisted of 485 subjects, who voluntarily participated in the street-based hypertension screening program in Cracow (summer 1997). All subjects were asked to fill out a questionnaire concerning their health behaviours (i.e. stress, smoking and drinking habits) and a test to evaluate their knowledge about hypertension and its risk factors. The blood pressure measurement were taken using semiautomatic device (Digital Blood Pressure UA-702), in the sitting position, after a rest minimum five minutes. The study group consisted of persons with negative history of hypertension (n = 440), and untreated hypertensive patients (n = 45). In order to assess the influence of different factors on blood pressure level, the subjects were divided into two groups according to the presence or absence of a particular risk factor. In the statistical analysis Student's t-test, chi 2 and linear regression analysis with adjustment for possible confuses were used. All values were presented as mean +/- SD. RESULTS: The mean age was 37.1 +/- 17.8 years. Participants were well educated (75.9% had finished college or high school), and there were more women than men in the study group (57.5% vs 42.5%). 24.1% of participants had blood pressure values exceeding 140/90 mmHg. Multiple linear regression demonstrated that age, body mass index and knowledge about hypertension significantly influenced the level of systolic blood pressure; while only body mass index was among the factors determining diastolic blood pressure. CONCLUSIONS: This study confirms the influence of age, male gender, body mass index, alcohol consumption, stress and the snoring on the blood pressure level. The association between the knowledge about hypertension risk factors or hypertension and occasionally measured blood pressure values has been demonstrated.

[Blood morphology in elderly persons over 90 years old]. / Morfologia krwi u osób po 90 roku zycia.

In order to assess blood cell count in a late senescence we examined 56 persons (44 women and 12 men) in age 90-99, in a good condition. Over 70% of obtained results were in normal range. The most frequent abnormalities were: anemia (28.6%), leukopenia < 4,000 in 1 mm3 16.1%, thrombocytopenia < 125,000 in 1 mm3 -10.7% of subjects. In a white blood count low value of rod neutrophils and monocytes were found. The results show that the haematological diagnosis in elderly does not require any special references intervals.

[Nifedipine level in the blood and its immediate hypotensive effect after its sublingual administration to aged patients]. / Stezenie nifedypiny we krwi a jej dorazny efekt hipotensyjny po podjezykowym podaniu leku u osób w wieku podeszlym.

In 28 aged patients (means = 73.1 years) with arterial hypertension nifedipine has been administered sublingually in a single dose of 20 mg and the hypotensive effect of that drug under the control of its concentration in the blood serum was evaluated. The nifedipine concentration was determined by the use of gas chromatography with electron capture detector. The mean drug concentration increased from 38.1 ng/ml to 82.3 ng/l during the 2nd hour of observation. After 3 hours the lowering of the nifedipine concentration and the decrease of its hypotensive effect was observed. After 15 min from the drug application the systolic pressure lowered by the average 22.1 mmHg whereas the diastolic pressure was 7.0 mmHg lower. The most significant pressure decrease (mean of systolic pressure 52.7 mmHg) 7.03 kPa and that of diastolic pressure 23.2 mmHg (3.1 kPa) occurred after 2 and 1.5 hours. The decrease of pressures after nifedipine correlated with the start-point value of systolic pressure. The frequency of the heart action in the whole group did not altered significantly, however, in individual cases both the acceleration of that action (34 per min) or acceleration (42 systoles per min) was noted. Slight typical side-effects were noted in 5 treated patients. A single-dose sublingual 20 mg nifedipine (Cordafen--Polfa) administration enabled in all the subjects the obtaining of therapeutic drug level in the blood and in the aged patients with hypertension may be regarded as efficacious antihypertensive treatment.