[Long-term nitrate therapy in coronary heart disease--loss of effect by developing tolerance]. / Langzeitnitrattherapie bei koronarer Herzkrankheit--Wirkungsverlust durch Toleranzentwicklung?

The therapeutic efficiency of the long-term nitrates in coronary heart disease with exercise-induced heart insufficiency is recently more frequently called in question by observations of a nitrate tolerance. In own long-term studies on 34 patients with coronary heart disease with clinical and haemodynamic evidence (pathologic increase of the end-diastolic pressure of the pulmonary arteries under ergometric load) of an exercise-induced heart insufficiency the efficacy of pentaerythril tetranitrate (PETN) and isosorbide dinitrate (ISDN) in chronic dosage titration use was tested. The oral nitrate therapy evoked a clear decrease of the end-diastolic pressure of the pulmonary arteries. The reduction of the values of the pressure of the pulmonary arteries was correlated with adequate clinical findings (significant decrease of the frequency of pectanginous attacks and of the sublingual need of GTN, regression of the ST segment depression). The own results with particular valuation of the microcatherisation of the right heart on exertion plead against a clinically remarkable nitrate tolerance and confirm the efficiency of the at present usual basic medicamentous therapy in patients with coronary heart disease and exercise-induced heart insufficiency.

[Dose-reduced antihypertensive agents--use in complex nonmedicamentous therapy of hypertension]. / Dosisreduzierte Antihypertensiva--Anwendung bei komplexer nichtmedikamentöser Hochdrucktherapie.

In order to estimate the influence of a non-medicamentous therapy (CNT) on the consumption of medicaments and coronary risk in high blood pressure 73 hypertensives of a medicamentously stabilized CNT-group were examined in comparison to a group of the same size of patients with hypertension who were managed exclusively medicamentously for behaviour of blood pressure, need of antihypertensive drugs and changes of hypertension-associated risk factors. After an exactly controlled 6-month treatment hypertensives with additionally recommended far-reaching CNT showed an economization of medicaments by scarcely the half in comparison to the reference group. By means of suitable control methods a causal non-medicamentously conditioned decrease of blood pressure could be excluded. A different need of antihypertensive drugs was simulated by the exacter intake of medicaments in the index-patients. Notwithstanding the metabolic effects of the additional therapy have induced a positive change of atherogenic lipids. The examinations indicate in general the difficulty of the judgement of efficacy of non-medicamentous therapeutic measures in connection with a rational dose-reduced long-term therapy with antihypertensive drugs.

[The importance of the determination of intraerythrocytic sodium for the differential diagnosis and the control of the progression of essential hypertension]. / Zur Bedeutung der Bestimmung des intraerythrozytären Natriums zur Differentialdiagnose und Verlaufskontrolle der essentiellen Hypertonie.

Intraerythrocytic sodium concentration in 432 patients with essential hypertension under antihypertensive therapy with various drugs was determined. Aim of this investigation was to detect the importance of such finding for diagnosis and control of essential hypertension. According results presented intraerythrocytic sodium should be investigated in beginning of each antihypertensive therapy and later in intervals of 6-8 months to control effectiveness of therapy.

[Nifedipine therapy in uncomplicated essential hypertension and hypertensive problem cases]. / Nifedipin-Therapie bei unkomplizierter essentieller Hypertonie und Hochdruck-Problemfällen.

In altogether 54 patients with high blood pressure of the clinical degrees of severity I-IV the blood pressure-reducing effectiveness of the calcium antagonist nifedipine was investigated both in the framework of an oral long-term therapy and especially in problematic situations of high blood pressure. According to the results of own treatment nifedipine is particularly suited for the antihypertensive combination therapy with beta-receptor blockers. Monotherapeutically favourable possibilities of application exist in hypokinetic types of the regulation of circulation as well as in elderly hypertensives. Therapy-resistant as well as crisis-like developments of high blood pressure react with excessive, well tolerable and persisting reductions of blood pressure. Above all with regard to this still little considered indication in the meantime nifedipine represents an unavoidable enrichment in the therapeutic basis spectre of the hypertonus.

[Results of a 2-year intervention for the modification of atherosclerosis precursors in school children]. / Ergebnisse einer zweijährigen Intervention zur Beeinflussung von Atherosklerosepräkursoren bei Schulkindern.

801 children aged 10-11 years were examined in 1984, before an allocation in two groups (intervention vs. control). The scope of the intervention was to modify mean values of blood pressure, total cholesterol and smoking through relevant modification of knowledge and behavior. An intermediate assessment, conducted 2 years after the first exam, showed better knowledge regarding cardiovascular diseases and more sport practice in the intervention group, although smoking habits were only slightly modified. Diet, body weight, blood pressure and blood lipid levels did not show any significative differences. The study is now ongoing.

Contribution to the pathogenesis of essential hypertension: a multivariate analysis of associated factors.

This study attempts to develop a general aetiological concept of essential hypertension by multidimensional investigation of its various risk factors in childhood and adolescence. The investigation is based on married couples and their children (609 parents and their 639 children, a total of 1248 persons), all of them chosen under special aspects. Familial and environmental characteristics of children and young people with hypertension are compared with those of normotensive volunteers of the same age. The multi-dimensionally interacting factors found to be associated with hypertension in children are: hypertension, diabetes and early infarction in relatives of the first or second degree as well as overweight at birth, obesity, nutritional patterns in the earliest and later stages of life, social environment and physical activity of the children and adolescents. The familial factors most likely lead to a predisposition to hypertension while environmental factors may subsequently contribute to its manifestation.

[Use of propranolol in essential hypertension--results of a 10-year therapeutic course study]. / Propranolol-Anwendung bei essentieller Hypertonic--Resultate einer 10jährigen therapeutischen Verlaufsstudie.

For the control of the antihypertensive efficacy and the long-term tolerance in 1970 156 stable essential hypertensives of the clinical stages I-III were stablized with propranolol (obsidan). After an observation of the course lasting at first one year 58% (n = 90) proved as propranolol responders, 72 of them could be led monotherapeutically over 10 years (maximum mean dose 157 mg/die). The permanent propranolol therapy caused a persisting decrease of blood pressure in the non-hypertensive region (RR less than 160/95 mm Hg) by systolically on an average--44 mm Hg and diastolically--22 mm Hg with an adequate mean reduction of the heart rate of 19% compared with the basis values. Under conditions of the bicycle ergometer (watt-degree test) a significant decrease of the mean values of heart rate and blood pressure depending on the load as well as the tension-time-index could be established; at the same time the physical work capacity increased on an average by 25 Watt. After an abrupt interruption of the chronic propranolol therapy (partial study in 29 hypertensives) blood pressure and heart rate again increased only relatively retardedly. In 10 cases a remaining normotension was observed during the therapy-free phase. There were no paradoxical reactions or discontinuation phenomena; altogether the number of side-effects was low. As a result of our 10-year study of the administration of propranolol the high value of the beta-receptor blockers as a basis medication is to be emphasized in the therapy of hypertension.

[Effectiveness of different intervention measures in children and adolescents with hypertension and lipid metabolism disorders]. / Effektivität unterschiedlicher Interventionsmassnahmen bei Kindern und Jugendlichen mit Hypertonie und Fettstoffwechselstörungen.

141 children and adolescents (7-21 years, mean age 14.2 years) showed values of blood pressure, total cholesterol and triglycerides greater than or equal to 90 percentile and HDL-cholesterol values less than or equal to 10 during an examination of 639 children of parents with distinct coronary risk factors or early percentile infarction. By randomization they were subdivided into two groups. (A and B) and underwent intervention measures of different intensity. While group B got only a unique recommendation concerning the preventive measures, in group A a regular, non medicamentous individual treatment was performed. After one year a decrease of blood pressure could be proved in the two groups. A significant decrease of total and HDL cholesterol was found only in group A. While the blood pressure was most clearly reduced in 7-13-year-old children, the most distinct lipid changes were shown in 14-17-year-old adolescents. An influence on body-weight and triglycerides could not be established. Our results confirm the possibilities and also the limits of preventive measures in childhood and adolescence. Apart from the intended decrease of blood pressure and total cholesterol the simultaneous decrease of HDL-cholesterol refers to open questions in the conception of the primary prevention, particularly in children.

[The effectiveness of a prevention program for cardiovascular diseases]. / Zur Wirksamkeit eines Präventionsprogramms gegen Herz-Kreislauf-Krankheiten.

In 1968 the addresses of all men of the annual courses of birth 1914-1923 of an Erfurt district were registered (n = 2 023). The aim population was according to accident subdivided into an intervention and a control group. The test persons of the intervention group were repeatedly investigated and participated in a preventive programme. Up to the final investigation in 1977 the control group remained absolutely intact. After about 10 years the intervention population had a statistically significantly lower frequency of infarction and a lower proportion of hypertensive values of blood pressure. In the younger five-year age group the total mortality was tendencially lower (not significant!) than in the adequate control group. There are no differences in the mortality from heart and circulatory diseases and in the distribution of other risk factors between intervention and control groups. A positive effect of the preventive programme was to be proved theoretically as well as empirically, though the decrease of the real incidence of infarction which is to be calculated was by far lower than generally was supposed.

[The natural course of atrial septal defects]. / Untersuchungen zum natürlichen Vrlauf des Vorhofseptumdefektes.

61 patients at the age of 18 to 70 years with untreated atrial septum defect were examined 7.5 to 21 (on the average 10.5) years after the first recognition. Subjective symptomatology, clinical picture, size of the heart, mean pressure of the pulmonary artery and shunt volume at the beginning and at the end of the period of observation were analysed. The results reveal an above all favourable prognosis of the congenital malformation. In a course without complications an age can be reached adequate to the average life-expectance. After the 40th year of age, however, in 75% of the patients complaints appeared or their number increased. With growing age the size of the heart and the frequency of disturbances of the cardiac rhythm increased. In the small left-to right-shunt (less than 30% of the pulmonary flow) in the majority of the cases (85%) the prognosis proved to be good. Even in shunt volumes of more than 60% in half of the patients no essential deterioration developed in the period of observation. No clear relations were found between the mean pressure of the pulmonary artery and the clinical degree of severity. The indication to the operative correction of the atrial septum defect diagnosed only at the adult age demands a critical individual judgement, in which case apart from the haemodynamic parameters anamnesis and clinical findings within a cardiological observation of the course are of particular importance.

[Average time prognosis of hypertension in qualitatively different treatment protocols]. / Mittelfristige Prognose der Hypertonie bei qualitativ unterschiedlicher Behandlungsführung.

In 1969 within pilot studies in an Erfurt district altogether 254 patients with definitive hypertension as well as 208 patients with borderline hypertension of the male age groups from 1914 to 1923 were recognized. 135 test persons with definitive hypertension (RR--160/95 Torr) were treated antihypertensively within a clinical and ambulatory preventive programme for 8 years and compared with a control group of the same age (119 males of 45-54 years) concerning the presence of possible complications of hypertension, which was treated with unsatisfactory results. By a strict, permanently normotensive decrease of blood pressure--as pharmacotherapy above all the beta-receptor blocker propranolol alone or in the approved combination therapy with dihydralazine and/or hydrochlorothiazide was used--in connection with suitable measures for the intervention of other individual factors with effect on heart and circulation the risk of complications in definitive hypertension could be reduced. Taking into consideration the own long-term observations the necessity of a possibly early beginning medicamentous, antihypertensive permanent therapy of hypertension is without doubt, in borderline hypertension, however, it still remains actual subject of the discussion.

[Development and drug correction of therapy resistance in chronic antihypertensive use]. / Entwicklung und medikamentöse Korrektur der Therapieresistenz bei chronischer Antihypertensiva-Anwendung.

In the course of a closely controlled ambulatory antihypertensive multicompetent therapy one part of the at first normotensively treated hypertensives reacts with a development of therapy-resistance due to volume expension. A correction of the development of the resistance can be achieved by directed and sufficiently doses parenteral and oral additional application of loop diuretics, aldosterone antagonists and peripheral vasodilators as a hypotensive intensive programme which can be performed in the outpatient department. With the help of observations of courses lasting several years in 16 patients with hypertension who were temporarily resistant to therapy and who could be regulated above all normotensively within the repeated antihypertensive intensive therapy phases, improved possibilities of a long-term effective performance of the therapy under the conditions of an outpatient department were shown.

[Borderline hypertension]. / Grenzwerthypertonie.

As to blood pressure values between 18.66 kPa and 21.14 kPa systolically and/or 11.99 kPa and 12.52 kPa diastolically according to the WHO-definition is spoken of borderline hypertension. In consequence of high rates of prevalence and incidence also in the borderline hypertension a particular preventive-medical interest is present. Own investigations yielded for 50 to 54-year-old males (n = 281) prevalence rates of 29% and for factory populations (n = 6,646 males and females) on an average 20.7%. Parallel to the results in hypertension in borderline hypertension in all age groups higher mean values of the triglycerides and of cholesterol were observed in normotonics. Under hormonal contraception in certain age groups (30--34, 35--39 and 40--49 years) altogether significantly higher systolic and diastolic values of blood pressure were found then in females without oral anticontraceptives. Within a clinical-ambulatory preventive programme performed for 8 years borderline hypertonics did not show any significant differences to the control group concerning the distribution of frequency of essential organ complications and the mortality. According to the present state of knowledge a permanent treatment of the borderline hypertension with substances reducing blood pressure still cannot be justified immediately.

[The correlation of blood pressure, cholesterol and triglyceride concentration with the administration of hormonal contraceptives in women from 2 Erfurt large-scale plants]. / Zur Abhängigkeit des Blutdruckes, der Cholesterol- und Triglyzeridkonzentration von der Einnahme hormonaler Kontrazeptiva bei Frauen aus zwei Erfurter Grossbetrieben.

Within the framework of medical check-ups of heart and circulatory system 1,296 women at the age from 15 to 49 years were examined in two Erfurt large plants. Women with hormonal contraception in the age groups 30-34, 35-39 and 45-49 showed statistically significantly higher mean values of the systolic blood pressure than women without oral contraception. In the same way the difference of the cholesterol mean value of 15.3 mg/100 ml and 11 mg/100 ml depending on the intake of ovulation inhibitors could be statistically ascertained in women at the age of 20-24 and 30-34 years. Women with hormonal contraception have statistically significantly higher triglyceride mean value in the age group 15-24 and 35-44 years than the women without oral contraception.

[Cardiovascular preventive medical check-ups in the large industrial plants of Erfurt. 1. Implementation of the screening phase]. / Herz-Kreislauf-Vorsorgeuntersuchungen in Erfurter Grossbetrieben 1. Mitteilung: Durchführung der Screeningphase.

During a medical check-up for the recognition and treatment of patients with diseases of heart and circulation or their early stages and of patients with factors of risk in two large factories of Erfurt altogether 6,646 men and women were examined. The screening was carried out in November 1975 and 1976 in immediate nearness of the working place. The times during which could not be worked were thus reduced to a minimum. Some organisational problems and their solutions in the preparation and performance of the screening phase as well as first results are reported on.

[Treatment of hypertension with propranolol in combination with other antihypertensive agents]. / Hochdruckbehandlung mit Propranolol in Kombination mit anderen Antihypertensiva

In two separated treatment groups of 18 and 30 hypertensive patients of the clinical degrees of severity II and III after insufficient propranolol monotherapy a combined propranolol/hydralazine or propranolol/hydrochlorothiazide treatment, respectively, was performed during several months. Under the combination therapy on average a clear increase of the effect of the beta-receptor blocker on the systolic as well as on the diastolic blood pressure is achieved. There were no essential side-effects. In accordance with modern opinions in the therapy of hypertension the combination of propranolol with a peripheral vasodilator and/or a salidiuretic should find a wide area of use, above all in hypertensive patients who are diastolically more difficult to be stabilised. The production of an adequate combination preparation is to be taken into consideration.