[Long-term blood pressure measurement for evaluating the first dose response of captopril and ramipril in patients with a stimulated renin system]. / Langzeitblutdruckmessung zur Beurteilung der First-dose-response von Captopril und Ramipril bei Patienten mit stimuliertem Renin-System.

First-dose-response of captopril 1 x 25 mg (no prodrug) and ramipril 1 x 2.5 mg (prodrug) were compared in two groups of 17 patients with moderate or severe hypertension and stimulated renin-angiotensin system (because of continuous diuretic therapy) by means of 24-h blood-pressure measurement at the 1st and 7th day of therapy. In the ramipril-group the antihypertensive effect started after 2 h, had its maximum (mean: -13/-8 mmHg) after 4 h and remained unchanged for 8 h. The antihypertensive effect was significant for 24 h. There was a slightly but not significant improved blood-pressure reduction at the 7th day compared to the 1st. The captopril-group showed a fast and marked decrease of blood pressure within the first hour, and reached its maximum (mean: -18/-10 mmHg) after 2 h. After 7 h there was no antihypertensive effect detectable. At the 7th day blood-pressure reduction was less pronounced compared to the 1st day. The results show that initial decrease of blood pressure in risk-patients is less severe with prodrug-ACE-inhibitors with slow onset of action so that counterregulation can be activated and prevent severe, fast, ACE-inhibitor-induced hypotension. 24-h-blood-pressure measurement is a sufficient method to evaluate first-dose-response of ACE-inhibitors.

[Comparison of 24-hour blood pressure measurement with ergometry in patients with hypertension]. / Vergleich der 24-Stunden-Blutdruckmessung mit der Ergometrie bei Patienten mit Hypertonie.

24-h-Ambulatory blood pressure monitoring and bicycle ergometry were compared in 112 patients with untreated mild to moderate essential hypertension. Patients with high blood-pressure values above 220 mmHg during ergometry showed a significantly higher number of blood-pressure peaks above 180 mmHg. There was no significant correlation between the level of the blood-pressure rise during ergometry and the mean values of blood pressure during the 24-h period neither in the night- or the daytime period, nor of the peak values of the 24-h profile. Blood-pressure values during ergometry in patients with high numbers of systolic blood-pressure peaks above 180 mmHg during ambulatory monitoring did not differ significantly from patients with blood-pressure peaks above 180 mmHg during ambulatory monitoring. Patients with marked blood-pressure rise during ergometry seem to demonstrate a higher number of blood-pressure peaks during daytime. On the other hand, patients with an elevated number of blood-pressure peaks do not necessarily show a high blood-pressure rise during ergometry.

[Diagnostic significance of absent nocturnal blood pressure decrease in 24-hour long-term blood pressure measurement]. / Diagnostische Bedeutung des fehlenden nächtlichen Blutdruckabfalls in der 24-Stunden-Langzeitblutdruckmessung.

Patients (pts) with essential hypertension normally exhibit a typical diurnal variation with a nocturnal blood-pressure (BP) decreased. A lack of this periodicity is often reported in pts with secondary hypertension. 24-h BP measurement was therefore performed in 308 pts with essential hypertension, and in 172 pts with secondary hypertension, in order to evaluate the diagnostic value of nocturnal BP decrease. Diagnoses of the secondary hypertensives were: renoparenchymatous hypertension (n = 29), diabetic nephropathy (n = 24), morbus Conn (n = 6), renal artery stenosis (n = 32), pheochromocytoma (n = 5), hemodialysis pts (n = 30), and kidney transplantation (n = 44). Pts with essential hypertension showed a mean systolic and diastolic BP decrease during the nighttime period of 22 +/- 7 mmHg and 17 +/- 5 mmHg, respectively. In contrast, the corresponding values in secondary hypertension were 5.7 +/- 9.2 mmHg (systolic decrease) and 5.2 +/- 5.9 (diastolic decrease). Pts with pheochromocytoma who had a nighttime increase in BP demonstrated the greatest difference from the essential hypertensives, followed by pts with either diabetic nephropathy or after kidney transplantation. A lack of nocturnal BP decline (less than 10% of the daytime values) was detected in 69.8% of pts with secondary hypertension, but only in 5.2% of pts with essential hypertension. In summary, these results suggest that the absence of a nighttime decline in BP during 24-h ambulatory monitoring is an indication of secondary hypertension and should lead to further investigations. Furthermore, a nightly hypertension is associated with a higher risk of complications.(ABSTRACT TRUNCATED AT 250 WORDS)

[Importance of 24-hour blood pressure monitoring in secondary hypertension]. / Bedeutung der 24-Stunden-Blutdruckmessung bei sekundärer Hypertonie.

A typical diurnal variation in blood pressure is observed in patients with essential hypertension. Attenuation or lack of circadian periodicity might be expected in patients with secondary hypertension. Therefore, non invasive ambulatory blood-pressure monitoring was performed in 172 patients with secondary hypertension and in 201 patients with essential hypertension. The following patients with secondary hypertension were investigated: renoparenchymatous nephropathy (n = 29), diabetic nephropathy (n = 24), morbus Conn (n = 6), renal artery stenosis (n = 32), pheochromocytoma (n = 5), hemodialysis patients (n = 30), and patients after kidney transplantation (n = 44). In addition, 36 pregnant women (17 normotensives, 19 hypertensives) were studied. 98.5% of patients with essential hypertension showed a nightly decline in blood pressure of at least 15 mmHg (systolic + diastolic), whereas 70% of patients with secondary hypertension showed either an attenuated circadian rhythm or no circadian rhythm. Patients with pheochromocytoma who had a nighttime increase in blood pressure demonstrated the greatest difference in the essential hypertension collective, followed by patients with diabetic nephropathy and patients after kidney transplantation. After successful treatment of the condition leading to hypertension, circadian periodicity returned in some patients. In summary, these results suggest that the absence of a nighttime decline in blood pressure during 24-h-ambulatory monitoring is an indication of secondary hypertension, which should be further investigated. As a practical consequence, antihypertensive drugs should also be applied in an evening dose in secondary hypertensives. Noninvasive ambulatory blood-pressure monitoring is recommended for treatment control, especially in patients who need an efficient blood-pressure control.

Rhabdomyolysis after suicidal ingestion of an overdose of caffeine, acetaminophen and phenazone as a fixed-dose combination (Spalt N).

Rhabdomyolysis without renal failure was noted after suicidal ingestion of 29 tablets of Spalt N containing 7.25 g of acetaminophen, 7.25 g of phenazone and 1.45 g of caffeine by a 29 year-old weighing 73 kg. The maximum serum creatine kinase was 1920 U/L, serum myoglobins were 49 to 167 ng/mL. Acetaminophen, phenazone and caffeine were quantified and identified in serum by gas chromatography and gas chromatography/mass spectrometry. It is suggested that rhabdomyolysis might have been caused by caffeine.

[The significance of 24-hour blood pressure monitoring in the diagnosis and therapy of arterial hypertension]. / Bedeutung der 24-Stunden-Blutdruckmessung in der Diagnostik und Therapie der arteriellen Hypertonie.

The use of ABPM allows an improved assessment of blood pressure (BP) and therefore of the individual cardiovascular risk. It is able to identify patients who truly need therapy more exactly. Mostly patients with white coat hypertension who don't need therapy are identified. Furthermore, ABPM correlates more closely to target organ damage and to cardiovascular morbidity and mortality. This may be helpful to treat especially those patients who truly need therapy. BP exhibits a typical circadian rhythm with the highest values during the early morning hours and a decline during the night. A change of the day/night rhythm during shift work leads to an adaptation of BP rhythm. The early morning rise of BP and heart rate is accompanied by hemodynamic, rheological and biochemical alterations, which together may contribute to the increased frequency of vascular complications during the morning hours. The nightly decline of BP is often absent in patients with secondary hypertension and cardiac or renal organ damage. A lack of the nocturnal BP decline should therefore lead to further patients' evaluation. Elevated nocturnal BP seems to worsen the prognosis. ABPM offers better individual control of BP in patients on treatment and therefore is helpful to optimize the treatment. A more exact individual BP control during the awakening and sleeping period is possible as well as an avoidance of overtreatment. Patients could be protected both from prescription of too many drugs and from lowering BP too much. A further advantage lies in an improved control of patients with nocturnal hypertension.

Comparison of the antihypertensive efficiency of nitrendipine, metoprolol, mepindolol and enalapril using ambulatory 24-hour blood pressure monitoring.

In a randomized 6-month study of 201 patients, the antihypertensive efficiency of the calcium antagonist nitrendipine, the beta 1-selective blocker metoprolol, mepindolol, the beta blocker with intrinsic activity and the angiotensin-converting enzyme inhibitor enalapril were compared as monitored by 24-hour ambulatory blood pressure (BP) measurements. The study was designed so that a comparable decrease in casual BP values was obtained with all 4 drugs. If normotension was not achieved with monotherapy, a diuretic also was administered. Pretreatment casual BP and mean 24-hour ambulatory BP values did not differ between the 4 groups. Normotension as assessed by casual BP measurements was observed in all 4 groups after 6 months of therapy, there being no significant differences between the groups. However, significantly more diuretics were required in the mepindolol (n = 14) and in the enalapril (n = 20) groups compared to the nitrendipine (n = 5) and metoprolol (n = 7) groups. Despite comparable casual BP control, the 4 groups differed significantly in their mean 24-hour measurements. The greatest systolic and diastolic BP decreases were seen in the metoprolol group. Metoprolol was also the most effective drug in decreasing the frequency of systolic pressure peaks greater than 180 mm Hg. Both beta blockers and enalapril significantly decreased the morning BP increase compared to the values before treatment, while nitrendipine did not. These data show that casual BP measurement is not a good predictor of 24-hour BP in patients taking hypertensive therapy. Despite an equal degree of "office" BP control, different antihypertensive regimens do not confer the same degree of "nonoffice" BP control.

[Plasma endothelin in normal probands and patients with nephrologic-rheumatologic and cardiovascular diseases]. / Plasma-Endothelin bei Normalpersonen und Patienten mit nephrologisch-rheumatologischen und kardiovaskulären Erkrankungen.

Plasma concentrations of the recently isolated potent vasoconstrictory peptide endothelin were measured in 382 patients. The investigations were performed by means of a sensitive radioimmunoassay specific for Endothelin-1, 2. The results from 110 healthy volunteers displayed a normal range of 44.67 +/- 3.51 pg/ml. Significantly raised levels were found in 33 patients with chronic end-stage renal failure both before and after hemodialysis. In contrast, 35 patients with compensated renal insufficiency did not differ from the normals. Sixty-five patients after kidney transplantation revealed significantly elevated levels, as did 27 patients with acute myocardial infarction, 8 after coronary bypass surgery, and 5 with liver cirrhosis. The mean values of 27 patients with untreated hypertension, 22 with secondary hypertension, of various causes and 16 with coronary artery disease were comparable to the normal population. The values were significantly decreased in 9 pregnant women with hypertension and proteinuria. A marked decline was found in 5 patients with systemic lupus erythematodes, while 20 patients with rheumatoid arthritis demonstrated only a slight decrease. The pathophysiological role of endothelin as a local or circulating hormone in regulating systemic blood pressure or release of other hormones remains to be determined.

Low atrial natriuretic peptide plasma concentrations in 100 patients with essential hypertension.

Although atrial natriuretic peptide (ANP) plays a key role in electrolyte and volume regulation and causes direct vasorelaxation, controversial results have been reported in hypertensive patients. We studied 58 men and 42 women, aged 19 to 78 years, with essential hypertension (blood pressure: 150 to 210/95 to 110 mm Hg) using 24 h blood pressure recording, treadmill exercise and x-ray of the chest. In 70 patients ANP plasma concentrations were found to be completely within the normal range of healthy controls (17 to 38 fmol/mL; n = 50) and 52% were detected within the lower third or even below the normal range. In mild to moderate essential hypertension a diminished secretion of ANP may be responsible for an elevated blood pressure in these patients.

[24-hour blood pressure behavior in patients with untreated and treated hypertension in comparison with normotensive patients]. / 24-h-Blutdruckverhalten bei Patienten mit unbehandelter und behandelter Hypertonie im Vergleich zu normotonen Patienten.

Blood pressure was continuously monitored over 24 h in 201 patients with mild to moderate essential hypertension using a noninvasive method. Measurements were made both before and after 6 months of antihypertensive treatment and the data were compared to results from 100 normotensive patients. The frequency with which blood pressure values above 140/90 mm Hg occurred during the 24-h period proved to be the most reliable parameter for distinguishing between hypertensive and normotensive profiles. The blood pressures of all patients could be normalized (less than 140/90 mm Hg) on single or combined drug therapy as assessed by casual measurement. However, significant differences were observed between the 24-h profiles of the treated patients and the control group. The mean 24-h blood pressure, the mean day and nighttime blood pressures, the mean hourly pressure, and the frequency of increased blood pressure values were all significantly higher in the patients on medication as compared to the normotensive controls. This would suggest that normotension, as defined by the control group, cannot be attained with antihypertensive medication. In conclusion, 24-h continuous blood pressure monitoring allows a better evaluation of blood pressure profiles and consequently, will be of greater value in assessing cardiovascular risk than occasional random measurements.

[Absence of nocturnal decrease in blood pressure in 24-hour blood pressure monitoring: an indication of secondary hypertension]. / Fehlender nächtlicher Blutdruckabfall in der 24-Stunden Blutdruckmessung: Hinweis auf eine sekundäre Hypertonie.

Non invasive 24 hours ambulatory blood pressure monitoring was performed in 81 patients with secondary hypertension (renoparenchymatous nephropathy n = 15, diabetic nephropathy n = 10, Conn's disease n = 4, renal artery stenosis n = 15, pheochromocytoma n = 2, hemodialysis patients n = 15 and patients after kidney transplantation n = 20). The results were compared to 201 patients with essential hypertension. The results showed that 98.5% of patients with essential hypertension have a nightly decline in blood pressure of at least 15 mmHg (systolic + diastolic), whereas 69% of patients with secondary hypertension showed either an attenuated circadian rhythm or no circadian rhythm. Patients with pheochromocytoma who had a night time increase in blood pressure demonstrated the greatest difference to the essential hypertension collective followed by patients with diabetic nephropathy, Conn's disease and the group of patients after kidney transplantation. After successful treatment of the condition leading to hypertension circadian periodicity returned in some patients. In summary these results suggest that the absence of a night time decline in blood pressure during 24-hour-ambulatory monitoring is an indication of secondary hypertension.

[Ambulatory continuous 24-hour blood pressure monitoring in the diagnosis and therapy of arterial hypertension and modification by the antihypertensive agents enalapril, metoprolol, mepindolol and nitrendipine]. / Ambulante kontinuierliche 24 h Blutdruckregistrierung in der Diagnostik and Therapie der arteriellen Hypertonie und die Beeinflussung durch die Antihypertensiva Enalapril, Metoprolol, Mepindolol und Nitrendipin.

After improvement of technical equipment continuous ambulatory blood pressure monitoring is more and more used in the diagnosis of hypertension. New fully automatic systems permit a reliable registration and evaluation of 24-h blood pressure profiles. Typical circadian rhythmics of blood pressure, independent of a variability with different grades of activity, can be demonstrated in normotensive persons and also in patients with essential hypertension. Patients with secondary forms of hypertension show a nivellation or offset of circadian blood pressure rhythmics. A study was performed to examine the antihypertensive efficacy of the calcium antagonist Nitrendipine, the beta 1-adrenoceptor-selective blocker Metoprolol, the beta-blocker with intrinsic activity Mepindolol and the angiotensin converting enzyme inhibitor Enalapril in patients with mild to moderate hypertension over a period of 6 month. Continuous ambulatory blood pressure monitoring was performed before and after 6 month of therapy. 98 of 299 included patients broke off therapy, 47 of those because of side effects. Hydrochlorothiazide was given additionally if the antihypertensive effect of monotherapy was not sufficient after a period of 4 weeks. Morning blood pressure controls at the end of the treatment period showed normotensive values in all groups without significant differences between the groups before and at the end of the treatment period. The number of prescriptions of diuretics necessary to achieve normotension differed between the four treatment groups: Nitrendipine (n = 5), Metoprolol (n = 7), Mepindolol (n = 14), Enalapril (n = 20). In contrast to the morning blood pressure values the continuous 24-h blood pressure monitoring demonstrated significant differences between the therapy groups. Metoprolol turned out as most effective in lowering blood pressure and in reducing the number of systolic blood pressure peaks above 180 mmHg, but on the other hand showed the highest incidence of relative hypotension (less than 100 mmHg systolic, less than 80 mmHg diastolic). Mepindolol demonstrated a significant lower efficacy. In the Nitrendipin group least of all prescriptions of diuretics were necessary and the lowest number of hypotensive systolic blood pressure values occurred. Enalapril showed the most significant reduction of diastolic values above 100 mmHg and the lowest number of diastolic values below 80 mmHg, but the highest number of prescription of diuretics was necessary in the Enalapril group. In none of the four therapy groups a neutralisation of circadian blood pressure rhythmics was demonstrable.

Parameters of the kallikrein-kinin, coagulation and fibrinolytic systems as early indicators of kidney transplant rejection.

In order to find early indicators of kidney transplant rejection before clinical symptoms were noticed, parameters of the coagulation, fibrinolytic and kallikrein-kinin systems were measured. Nineteen patients were followed before and daily after kidney transplantation during the first week and every second day in the following weeks. All patients received immunosuppressive therapy with cyclosporin and corticoids. Ten patients suffered from transplant rejection. The first rejection occurred on the 7th day after transplantation. Of all the parameters measured, kallikrein inhibition, beta-FXIIa inhibition, plasminogen and antithrombin III were early indicators of kidney transplant rejections. A rise in these parameters could be demonstrated 2-3 days before clinical signs were noticed. In the other 9 patients no significant rises in antithrombin III, plasminogen, kallikrein inhibition and beta-FXIIa inhibition could be found.

[Results of a 5-year study with captopril in patients with severe therapy-resistant hypertension]. / Ergebnisse einer 5-Jahres-Studie mit Captopril bei Patienten mit schwerer therapieresistenter Hypertonie.

The angiotensin converting enzyme (ACE) inhibitor captopril proved to be an effective antihypertensive drug during a 5-year follow-up study of patients with severe hypertension who had been resistant to a triple-drug regimen. Of the 42 patients, 41 had to be treated additionally with diuretics. Because of hypokalemia, potassium supplements were necessary in 26 patients, despite the use of "potassium-saving" diuretics in 12 patients. Blood pressure was controlled sufficiently in 3/4 of the patients during the 5 years. Patients with a large elevation in plasma renin activity showed the best response to the treatment. Six patients died during the 5 years. Therapy had to be stopped in 11 patients because of complications. The following complications and adverse effects were observed: cerebral ischemia (n = 10), vertigo and orthostasis (10), exanthema (9), hypogeusia (7), circulatory failure (7), myocardial infarction (6), and scintigraphically demonstrable decrease of renal perfusion (5). One patient with bilateral renal artery stenosis suffered from acute renal failure, which was reversible after withdrawal of captopril. Significant changes of red and white blood cell counts, transaminases, lipids, urine protein excretion, and heart rate were not observed.