[Ethical problems in internal medicine]. / Ethische Probleme in der Inneren Medizin.

In medical and scientific work a physician cannot act without first weighing the issues. This is often purely a weighing of utility and risks; sometimes, however, the issues must be weighted against the background of an image of the human being in which psychological and ethical aspects require consideration. Weighing of the issues is therefore possible only on the basis of expert grounding in the latest discoveries in each particular field, and in such cases also on the foundation of anthropological knowledge and awareness of ethical principles ("nil nocere"). In internal medicine weighing of the issues covers the patient's history, diagnostic and therapeutic measures, and prophylaxis. At a time when cost restraint in health care is necessary to preserve the state's finances and therewith the common good, one issue to be weighed is whether a cost-intensive diagnostic or therapeutic measure is justified in the individual case. In therapy the weighing of issues in the clinic may, however, produce a different result from that in general practice.

Psychophysiologic aspects in essential hypertension.

Epidemiologic and experimental studies disclosed that the sympathetic nervous system might play a pivotal role in the pathogenesis of essential hypertension. Although systolic pressure exhibits a weak endogenous rhythm, diurnal fluctuations of arterial pressure are provoked primarily by physical or emotional stress factors. The magnitude of the cardiovascular response, however, varies widely from individual to individual. Subjects at high risk of future hypertension,--such as those with a positive history of familial hypertension, high resting heart rate, or transient increase in arterial hypertension--revealed blood pressure hyperresponsiveness to stress stimuli mediated by an overreactivity of the sympathetic nervous system. Furthermore, cardiovascular reactivity to mental arithmetic tasks and to traffic noise put a patient at high risk of developing arterial hypertension. In women, exaggerated cardiovascular response to stress stimuli appeared to be mitigated by estrogens, whereas oral contraceptives overrode this 'protective' effect of estrogens. At a certain point, repeated episodes of high stress blood pressure could produce structural vascular changes finally inducing sustained hypertension.

Influence of perceived level of stress upon ambulatory blood pressure, heart rate, and respiratory frequency.

The hypothetical advantage of ambulatory blood pressure (BP) recordings over clinical casual BP readings is based on the assumption that it reflects the impact of daily life stress. We investigated the relation of ambulatory BP, heart rate (HR), and respiratory frequency (RF) readings to environmental conditions (work vs. home) and to the perceived level of stress (from 1 = completely relaxed to 5 = extremely stressed) in 34 healthy employed subjects. Systolic and diastolic BP (129 vs. 120 mmHg; 89 vs. 82 mmHg), RF (18 vs. 16 resp/min) and perceived stress (2.3 vs. 1.6 a.u.) differed significantly between work and home. ANOVA revealed a significant effect of perceived stress on SBP (F = 7.87; p less than 0.001), DBP (F = 8.73; p less than 0.001), and HR (F = 7.23; p less than 0.001).

Hemodynamic and neurohumoral effects of low-dose clonidine in mild to moderate hypertension.

To evaluate the role of the sympathetic nervous system in essential hypertension and the influence of clonidine, 28 male subjects with mild to moderate hypertension were either treated with low-dose clonidine (n = 14, mean age: 42.4 +/- 2.1 years) or were randomized to a nontreated control group (n = 14, mean age: 40.2 +/- 2.4 years). Clinical blood pressure and heart rate were assessed, and after 4 weeks of treatment plasma catecholamines and the hemodynamic response to mental arithmetic, cold stimulation, and ergometric exercise were compared between both groups. Under therapy with 0.075 mg of clonidine per day casual blood pressure dropped and diastolic BP was significantly lower than in the control group. Heart rate did not change. After 4 weeks the plasma levels of epinephrine and norepinephrine were the same in both groups. During mental arithmetic total peripheral resistance decreased in the treated group while it did not change in the control group, but both groups did not differ in their percentage changes in the hemodynamic parameters in response to the three stress tests. It has been concluded that clonidine reduces sympathoadrenergic activity, but in a low dosage this effect is obviously restricted to a reduction of arteriolar tone.

Disparate hemodynamic responses to mental challenge after antihypertensive therapy with beta blockers and calcium entry blockers.

The hemodynamic response to mental challenge was studied in 40 male outpatients with mild essential hypertension. The patients were treated randomly either with a beta adrenoreceptor blocker (oxprenolol) or with a calcium entry blocker (nitrendipine). Cardiovascular reactivity was evaluated with two different mental arithmetic tasks before and six months after treatment by continuously measuring systolic and diastolic pressure (ultrasonic Doppler device), heart rate (electrocardiography), and stoke volume (impedance cardiography). Patients in both treatment groups had equal decreases in arterial pressure and the same pressures at rest. In patients receiving calcium entry blockers, mental challenge provoked an increase in stroke volume and a decrease in total peripheral resistance similar to results in the pretreatment phase. In contrast, beta adrenoreceptor blockade reversed the hemodynamic response pattern to a distinct decrease in stroke volume (p less than or equal to 0.05) and an increase in total peripheral resistance (p less than or equal to 0.05). In addition, an attenuated heart rate response (p less than or equal to 0.01) and a larger increase in diastolic pressure (p less than or equal to 0.01) were found in the beta blocker group compared with the calcium entry blocker group. Although beta blockers and calcium blockers produce equal decreases in arterial pressure, beta blockers evoke an abnormal hemodynamic response to mental challenge, whereas calcium entry blockers preserve the physiologic reactivity pattern of the untreated state.

Hemodynamic abnormalities in borderline hypertension during mental stress.

Cardiovascular reactivity to mental stress was studied in 41 male borderline hypertensives in comparison with 37 male normotensives of the same age. In addition to a higher near-basal blood pressure, the borderline hypertensive group showed stronger absolute and percentage increases of systolic and diastolic blood pressure during stress. The increases of heart rate and cardiac output and the decreases of total peripheral resistance were also greater in borderline hypertensives. Stroke volume showed a slight increase only in this group. The reaction of mean arterial pressure correlated in both groups with the increase of cardiac output. The relationship between the reactions of cardiac output and total peripheral resistance was high both in normotensives and borderline hypertensives, and the regression line in normotensives was shifted to the right in borderline hypertensives. The results indicate an increased integrated change of circulatory parameters during mental stress in borderline hypertension, with a dominantly stronger cardiac reaction. They underline the significance of an autonomic imbalance for the pathogenesis of borderline hypertension.

Ambulatory blood pressure in children followed for 3 years. Influence of sex and family history of hypertension.

In 100 children (63 boys and 37 girls) aged 11.3 +/- 0.6 years ambulatory blood pressure (BP) was recorded by a semi-automatic device (Remler) 9 times per year over a period of 3 years. A sex difference in systolic BP was noted from the age of 13 years on with boys having higher values by about 6 mmHg (p less than .05). This could not be explained by differences in weight. In boys parental hypertension was associated with higher systolic values independent on age (p less than .05). Genetic and hormonal factors seem to influence BP during male puberty independently from each other.

Heart rate reactivity under mental stress as a predictor of blood pressure development in children.

Since 1981 the 'Bonn Kinderstudie' has followed blood pressure (BP) development in children. In a subset of 63 healthy boys (aged 10-12 years at the beginning of the study) we examined whether cardiovascular reactivity predicts future BP development. At a 1-year interval BP and heart rate (HR) were measured during mental arithmetic and physical exercise. Ambulatory BP was assessed nine times per year. Among different reactivity scores HR reactivity to mental stress was the most stable variable. Only reactivity of systolic BP to mental stress was different between subjects with parental hypertension and subjects with a negative family history of hypertension. After 1 year high HR reactors developed about 7 mmHg higher ambulatory systolic BP levels than low HR reactors. It is concluded that besides genetic factors HR reactivity to mental stress might indicate the disposition for developing high BP.

Predictors of blood pressure increases after withdrawal of antihypertensive therapy.

We examined possible predictors of the recurrence of high blood pressure (BP) in patients who remained normotensive after withdrawal of drug therapy. Thirty untreated male patients with WHO stage I essential hypertension (mean age 43 +/- 6 years) were randomly allocated to oxprenolol or nitrendipine groups. Before therapy, BP at rest, during mental arithmetic (MA) and during the cold pressor (CP) test was assessed. After 6 months of effective monotherapy, all drugs were withdrawn and casual BP was followed up for 5 months. Two weeks after cessation of therapy 26% were hypertensive again, after 4 weeks 28%, after 12 weeks 48% and after 21 weeks 74%. The two therapeutic groups did not differ in their BP increase after discontinuation of therapy. Predictors for the return of high BP were age, pretreatment BP, systolic and diastolic BP increase to the CP test. Analyses of covariance for age and pretreatment BP confirmed that reactivity to the CP test was a predictor of the return of hypertension.

The protective mechanism of estrogen on high blood pressure.

In 2 series of experiments on 144 SHRSP, the influence of treatment with different doses of 17-beta-estradiolbenzoate (EB) (0.031, 0.125, 0.5 mg/kg EB or placebo) on the development of hypertension from the 9th to 22nd week of life (increase of blood pressure (BP) of untreated male rats from 178 to 252 mm Hg and of untreated female rats from 151 to 192 mm Hg) and in well established hypertension from the 23th to 36th weeks of life (male untreated rats 238 mm Hg (prior to the observation] was investigated. In both series, observation periods consisted of a therapy phase of 14 weeks and a follow-up phase of the same duration. The untreated female rats had a longer life-span (88.5 weeks) than the untreated male rats (68.0 weeks). The estrogen treatment of female animals had an effect on BP only with the highest dose of EB and had no effect on the life-span of the animals. However, in male rats, the development of hypertension was inhibited by EB. Male rats treated at an earlier stage had a life-span equal to that of the female animals. When hypertension was already well-established treatment with EB had an antihypertensive effect in male rats (BP fall: 27-36 mm Hg), but no prolongation of the life-span was obtained.

Family history of hypertension and cardiovascular reactivity to mental stress--effects of stimulus intensity and environment.

Normotensives with hypertensive parents have been reported to exhibit enhanced cardiovascular reactions to mental stress. We have examined the question of why this result was not confirmed in all studies. In addition we have investigated whether appropriate tests can be performed under clinical rather than laboratory conditions. Healthy male subjects were examined. In experiment I, under laboratory conditions, a standard stress test was intensified (n = 30). In experiment II the same test was used in a simplified version which did not require special equipment (n = 19). Blood pressure, heart rate and stroke volume (by impedance cardiography) were measured. In contrast to the results with the standard test, subjects with at least one hypertensive parent exhibited enhanced responses of systolic and diastolic blood pressure and heart rate. We conclude that cardiovascular hyper-reactivity in subjects with hypertensive parents is only apparent using sufficiently intense stimuli. Although less pronounced, these differences can also be observed under clinical conditions.

The influence of monotherapy with oxprenolol and nitrendipine on ambulatory blood pressure in hypertensives.

We investigated whether beta-blockers or calcium-antagonists might be preferred in baseline antihypertensive therapy. In middle-aged male patients with essential BP readings did not differ between patients on Oxprenolol or on Nitrendipine (average BP: 123 +/- 12/81 +/- 14 vs. 129 +/- 17/80 +/- 10 mmHg), when clinical casual BP was within the normotensive range. Average BP at work was lower than clinical casual BP taken at the same day (125 +/- 14/80 +/- 12 vs. 133 +/- 12/87 +/-13 mmHg). A linear dependency between SBP at work and level of self reported physical activity (F(3,413) = 7.6; p less than or equal to 0.001) and arousal was found (F(3,374) = 5.2; p less than or equal to 0.02). Patients on Oxprenolol consistently had lower SBP at a particular level of physical activity and at lower levels of arousal than patients on Nitrendipine. We conclude that both regimen were equally effective as baseline antihypertensive monotherapy.

Reliability and validity of ambulatory blood pressure recording in children.

We investigate whether ambulatory BP (aBP) recording in children reflects situational variations and whether aBP depicts the impact of heightened cardiovascular reactivity under mental challenge, and gender on changes in BP. Results of 19 aBP protocols (2 to 7.30 p.m. after school; 30 min intervals) in 86 children, performed during 2 years of follow-up show that repetitive ambulatory blood pressure (aBP) recording reflects the great variability of environmental stimuli in children. Mean aBP is highly correlated with self-reported physical activity. Systolic aBP correlates with cardiovascular changes under mental arithmetic and - to a lesser degree - during bicycle exercise. Ambulatory BP recording is a sensitive method to detect the influence of hyperreactivity and gender on BP development in children at the age of 10-13 yrs.

Intermittent ambulatory blood pressure recordings in children. Methodological aspects and influence of family history on hypertension.

In 100 children of different school classes (10-12 years, participation rate ca. 50%) ambulatory blood pressure (BP) was recorded by a semi-automatic non-invasive device (Remler system). BP was measured every 1/2 h between 2 and 7.30 p.m. During each measurement the children protocolled their activity. These BP recordings were repeated five times at monthly intervals in 86 children. In the same children casual and near basal BP was determined. The mean ambulatory BP was 103/64 +/- 7/6 mm Hg. The average retest reliability of the monthly mean values was r = 0.57 for systolic and r = 0.45 for diastolic BP. The variability of BP (standard deviation) was not reproducible. Data recording failed in 32% of all single systolic and in 42% of all single diastolic BP measurements. These drop-outs were caused by inappropriate use rather than technical problems. There was a relationship between procolled activities and systolic BP. On average, ambulatory BP was lower than BP under standardized conditions. Under all conditions, children with hypertensive parents exhibited a 6 mm Hg higher systolic BP than children without a similar family history. No sex differences were found.

Efficacy of nitrendipine as baseline antihypertensive therapy.

To determine whether calcium antagonists might be used alternatively to beta-blockers in antihypertensive therapy, we investigated if monotherapy with oxprenolol (160-320 mg/day) and nitrendipine (20-40 mg/day) were equally effective on clinical casual blood pressure (BP), ambulatory BP monitoring (Remler), and BP during mental challenge (video game). In a prospective randomized long-term study, 60 white male civil servants (mean +/- SD = 43 +/- 6 years) with mild essential hypertension only were treated for at least 4 months. Average BP before therapy was 149 +/- 11/97 +/- 11 mm Hg. The antihypertensive effect was not different between the two groups (19/14 versus 21/12 mm Hg). Both groups did not differ in BP at rest, in BP during mental challenge (141 +/- 7/109 +/- 5 versus 146 +/- 9/112 +/- 8 mm Hg, NS), and average ambulatory BP monitoring at work (122 +/- 12/81 +/- 17 versus 132 +/- 14/79 +/- 17 mm Hg, NS), which was identical with the clinical casual BP. Thus, nitrendipine can effectively be used in long-term baseline antihypertensive monotherapy.

Basal blood pressure variability and reactivity of blood pressure to emotional stress in essential hypertension.

Blood pressure variability under basal conditions and blood pressure reactivity to emotional stress were studied in 38 hypertensives and 13 normotensives. Systolic basal blood pressure variability correlated with systolic blood pressure reactivity. Variability increased with higher basal blood pressure. Thus in the hypertension group the blood pressure variability was greater than in the normotension group. Besides, the hypertension group showed a greater reactivity of systolic blood pressure to emotional stress, too. An influence of age on basal blood pressure, blood pressure variability, and reactivity could be evaluated; but no influence of sex on these parameters was detected. The results indicate that variability and reactivity of blood pressure can be referred to a common central nervous blood-pressure-regulating mechanism. As both parameters are increased in hypertension, a greater lability of blood pressure must be assumed. This greater lability may be attributed to a stronger neurogenic influence or to structural changes of peripheral blood vessels.