Underestimation of 24-hour hypotensive efficacy of nifedipine GITS versus enalapril: ambulatory recording as an adjunct to clinical blood pressure measurement.

AIMS: Short-acting calcium entry blockers should be used primarily in slow-release form. Furthermore, studies of the antihypertensive efficacy of drugs can be negatively influenced by between 15% and 30% of the enrolled patients not being hypertensive according to ambulatory blood pressure (BP) measurement. Thus, a randomized double-blind multicenter parallel-group study was conducted to compare the effect of nifedipine GITS (gastrointestinal therapeutic system) with enalapril. METHODS AND RESULTS: After a 2-week placebo run-in period, 186 patients with a sitting diastolic BP > or = 95 mmHg were enrolled for an 8-week treatment period. They received 30-60 mg nifedipine GITS or 5-10 mg enalapril. Diastolic BP fell comparably from 99 to 87 mmHg (p < 0.01) in the nifedipine GITS group, and from 100 to 88 mmHg (p < 0.01) in the enalapril group. The increase in BP 2 h before waking, however, was suppressed significantly more by nifedipine. Furthermore, this study highlighted the existence of "whitecoat" hypertension in a number of patients, especially when clinical BP was used to identify hypertension. Of the patients who had been identified as hypertensive before randomization by standardized BP measurement, 53 (28.5%) were identified as non-hypertensives by 24-h BP monitoring. This led to an underestimation of the efficacy of the antihypertensive therapy. CONCLUSION: Nifedipine GITS as well as enalapril are comparably effective antihypertensive drugs.

Hypertensive heart disease: quantitative evaluation of response to therapy with cine MR imaging.

RATIONALE AND OBJECTIVES: To assess the ability of cine magnetic resonance (MR) imaging to help detect and quantity changes in left ventricular parameters in patients receiving antihypertensive therapy. MATERIALS AND METHODS: After undergoing baseline cine MR imaging of the heart, 16 (12 men, four women) hypertensive patients participating in a prospective drug trial began isradipine therapy. Follow-up serial cine MR imaging was performed at 3 months and 6 months. Myocardial mass, end-systolic volume, end-diastolic volume, stroke volume, and ejection fraction were measured. Results from transaxially acquired three-dimensional data sets and monoplanar imaging were compared. RESULTS: Three dimensional data showed reductions of 11% in end-systolic volume (P = .0051) and 17% in end-diastolic volume (P = .0023). These changes were not detected with monoplanar imaging. Changes in myocardial mass, stroke volume, and ejection fraction were not statistically significant. CONCLUSION: Three-dimensional cine MR imaging can depict small yet statistically significant reductions in left ventricular volumes in response to antihypertensive therapy.

[Screening and diagnosis for eliminating renovascular hypertension. Value of 24-hour blood pressure monitoring and color-coded duplex ultrasound diagnosis]. / Screening and Diagnostik zum Ausschluss einer renovaskulären Hypertonie. Stellenwert der 24-Stunden-Blutdruckmessung und der farbkodierten Duplexsonographie.

BACKGROUND: Direct renal angiography is still the method of choice for identification of renal artery stenosis. Newer non-invasive diagnostic methods include color coded duplex sonography and also ambulatory 24-h blood pressure monitoring, since in a large proportion of patients with secondary forms of hypertension the usual blood pressure fall during nighttime disappears. PATIENTS AND METHODS: In a prospective in-hospital study we investigated 86 patients with suspected renovascular hypertension. Circadian blood pressure was measured oscillometrically and color coded duplex sonography was performed immediately before direct renal angiography. RESULTS: Angiography revealed renal artery stenosis (> or = 50%) in 42 patients. This compared to a sensitivity of 92.9% and specificity of 91.7% for the use of sonography in those patients (70.4%) who could be adequately examined. Mean 24-h pressure values as well as standard deviations of blood pressure means as an indicator for blood pressure variability were not different in the 2 groups of patients, when all the data were analysed together and also when the data for nighttime and daytime were examined separately. The percent of blood pressure fall during nighttime was also not different in the 2 groups. In both groups 4 hypertensive patients had a blood pressure increase during nighttime. In 11 patients without renal artery stenosis a blood pressure fall of < 10% was observed, compared to 12 patients with renal artery stenosis. The circadian pattern of pulse rate was similar in both groups. CONCLUSION: We conclude that ambulatory blood pressure monitoring has a considerably lower diagnostic value for renal artery stenosis compared to angiography and also to color duplex sonography. This method therefore does not appear to be an appropriate screening approach for this kind of secondary hypertension. The color coded duplex sonography, however, seems to be the best non-invasive diagnostic method in those patients, who can be adequately examined.

Clinical correlation of anticentromere antibodies.

A retrospective survey of all patients with a positive anticentromere antibody (ACA) determination was undertaken over a 3-years period of time in a university hospital. Forty-five patients were positive for anticentromere antibodies. The analysis of the clinical characteristics and diagnoses of the patients with anticentromere antibodies were correlated and showed a diverse array of symptoms. Only 4.4% had CREST syndrome, 6.7% had limited scleroderma, 17.8% had diffuse scleroderma, 20% had other connective tissue diseases, 20% had other miscellaneous rheumatic conditions, 11.1% had tumours and 20% other nonrheumatic diseases. The study shows that the presence of ACA, as detected during routine ANA-testing, does not strongly suggest a diagnosis of CREST at that time. The presence of a scleroderma-variant in almost 50% of the patients and the occurrence of Raynaud's phenomenon in 62% underscores, however, an association of ACA with (early) scleroderma-like disorders.

Quinapril, hydrochlorothiazide, and combination in patients with moderate to severe hypertension.

This 8-week, double-blind, multicentre study compared the efficacy and safety of the combination of quinapril and hydrochlorothiazide (HCTZ) with each drug as monotherapy. Outpatients with moderate to severe hypertension defined as supine diastolic blood pressure (DBP) > or = 105 mmHg and < or = 120 mmHg at the end of a 2 to 4-week placebo-baseline period were randomly assigned to one of the three treatments: once-daily 10 mg quinapril plus 12.5 mg HCTZ or monotherapy with these doses. After 4 weeks, the doses were to be doubled for the remaining 4 weeks. Three hundred and sixty-eight patients were randomized to double-blind medication; 346 completed the study. Seven patients withdrew due to lack of efficacy. Four patients withdrew due to side effects. In all three treatment groups, clinically significant reductions in DBP were achieved. Combination therapy was statistically more effective than each component taken as monotherapy. Adverse events were infrequent in all treatment groups. No patients experienced symptomatic hypotension or orthostatic hypotension.

Relationships between ambulatory blood pressure, forearm vascular resistance, and left ventricular mass in hypertensive and normotensive subjects.

Ambulant 24 h blood pressure was recorded in 97 untreated hypertensive subjects (50 with, 47 without echocardiographic signs of left ventricular hypertrophy) and 45 matched normotensive subjects. Forearm vascular resistance was calculated from mean blood pressure and blood flow, which was measured by venous plethysmography during reactive hyperemia. Blood pressure variability was calculated by standard deviations of pressure values. Systolic 24 h blood pressure exhibited the closest correlation with left ventricular mass index in hypertensives (4 = 0.48; P < .001). No relation could be found between blood pressure fall during the night and left ventricular mass index. Furthermore, body weight was a significant correlate of left ventricular mass (r = 0.53; P < .001). Regression analysis indicated that body weight and 24 h blood pressure were the principal determinants of left ventricular mass. Blood pressure variability was significantly higher in hypertensive than in normotensive subjects (P < .05). The highest vascular resistance was found in hypertensive patients with left ventricular hypertrophy compared with the other groups (P < .05). A significant close correlation between systolic resting as well as 24 h blood pressure and vascular resistance was identified for the group of hypertensives and all subjects investigated. Furthermore, left ventricular mass index and vascular resistance were correlated (in hypertensives: r = 0.32; P < .01). The extent of left ventricular mass index and forearm vascular resistance are proportional to the severity of hypertension. As vascular resistance and left ventricular mass are also related, these findings could speak for a parallel development of total peripheral resistance and left ventricular hypertrophy in essential hypertension.

Relation of regression of left ventricular hypertrophy to changes in ambulatory blood pressure after long-term therapy with perindopril versus nifedipine.

Casual as well as ambulatory 24-hour blood pressure (BP) and echocardiographic parameters were studied in 40 patients with untreated or insufficiently treated mild to moderate essential hypertension. Left ventricular (LV) hypertrophy was assessed before and after 24 weeks of therapy with either the converting enzyme inhibitor perindopril or the calcium antagonist nifedipine. The design was a double-blind parallel study with a placebo run-in period. Patients received a daily oral dosage of either 4 to 8 mg of perindopril or 40 to 80 mg of nifedipine in slow-release form. A diuretic (25 mg/day of hydrochlorothiazide) was added in nonresponders (greater than 90 mm Hg casual diastolic BP). Once-daily perindopril and twice-daily nifedipine comparably reduced both casual and ambulatory BP throughout 24 hours (p less than 0.01) without affecting 24-hour heart rate. Six subjects withdrew from the nifedipine group and 4 from the perindopril group. After 12 and 24 weeks of therapy, LV hypertrophy was significantly reduced by both agents. Before active treatment was begun, LV mass index was more closely correlated to 24-hour (p less than 0.001) than to casual BP. This correlation disappeared after treatment with both agents. The correlation between ambulatory systolic day-time BP and LV mass was only still present (r = 0.54; p less than 0.05) after 24 weeks of treatment with nifedipine. It is concluded that regression of LV hypertrophy during converting enzyme inhibition or calcium antagonism may be partly independent of dosage and magnitude of 24-hour BP decrease.

[Value of 24-hour blood pressure measurement in patients with arterial hypertension, left heart enlargement and increased cardiac risk]. / Stellenwert der 24-Stunden-Blutdruckmessung bei Patienten mit arterieller Hypertonie, Linksherzhypertrophie und erhöhtem kardialem Risiko.

Non-invasive 24-h blood pressure and a 24-h electrocardiogram were recorded in 45 normotensive and 97 matched, untreated, hypertensive subjects, with and without echocardiographic signs of left-ventricular hypertrophy and without signs of coronary artery disease. Forearm vascular resistance was calculated from mean blood pressure and postischemic blood flow, which was measured by venous plethysmography. Systolic ambulant 24-h blood pressure exhibited the closest correlation with left-ventricular mass index in hypertensives (r = 0.48; p less than 0.001). No relation could be found between blood-pressure fall overnight and left-ventricular hypertrophy. Blood-pressure variability was significantly higher in hypertensive subjects. Furthermore, systolic 24-h blood pressure significantly correlated with the rate of ventricular arrhythmias in hypertensives. Casual blood pressure exhibited no comparable correlations. A significant close correlation between 24-h blood pressure and vascular resistance was identified in hypertensives. Furthermore, left-ventricular mass index and vascular resistance were correlated (in hypertensives: r = 0.32; p less than 0.01). This finding speaks for a parallel development of total peripheral resistance and left-ventricular hypertrophy in essential hypertension. The close relationships between ambulatory 24-h blood pressure, left-ventricular hypertrophy, ventricular arrhythmias, and vascular resistance demonstrates the high diagnostic and, possibly, the prognostic value of long-term blood-pressure measurement.

[Diagnosis of deep leg vein thrombosis with color-coded duplex sonography and sonographic determination of the duration of the thrombosis]. / Diagnostik tiefer Beinvenenthrombosen mit der farbcodierten Duplexsonographie und sonographische Altersbestimmung der Thrombose.

In a prospective study, 188 patients with suspected deep venous thrombosis were examined by color-coded duplex sonography. In 114 patients the diagnosis of deep venous thrombosis was based on the criteria of 1) compressibility, 2) blood flow changes during compression, and 3) pelvic level during Valsalva maneuver. In all patients the results were compared with data from contrast venography. Venography was performed by an investigator, who was blinded to the prior findings. Sensitivity and specificity of the color-coded duplex sonography in diagnosing deep vein thrombosis were 96% and 97%, respectively. In the other 74 patients, in which the diagnosis of deep vein thrombosis was made by phlebography and/or ultrasound, a follow-up by color-coded duplex sonography was performed to determine the age of thrombosis. Criteria considered to determine the thrombus age included 1) margin of the vessel, 2) echogenicity; and 3) venous diameter. In 20 patients the results were compared to the age of thrombus that had been determined by histologic criteria (group I). In 54 patients the results were compared with the age that had been determined by patient history and symptoms (group II). A significant correlation was found between the age of thrombosis and the venous diameter (p less than 0.001). When thrombosis was less than 10 days old, the venous diameter was at least twice that of the diameter of the accompanying artery. The two other criteria, echogenicity and margin of the venous wall, however, did not prove to be accurate criteria to determine the age of deep venous thrombosis.

[Technical possibilities and limits of ambulatory 24-hour blood pressure measurement]. / Technische Möglichkeiten und Grenzen der ambulanten 24-h-Blutdruckmessung (ABDM).

Noninvasive automatic 24-h indirect ambulatory monitoring of blood pressure (ABPM) and heart rate has been performed in more than 2000 subjects from 1983-1990 using 12 different devices. According to the requirements of national validation authorities (e.g. AAMI, PTB and BHS) only four devices have passed at least two protocols. These monitors were equipped with auscultatory and/or oscillometric devices; they provided accurate readings and were repeatedly used up to eight times in some patients. Up to 100 data points per 24-h provided diurnal blood pressure profiles for over 91% of the patients in clinical and non-clinical situations. Early identification of borderline hypertensives at risk and detailed information on the efficacy of different anti-hypertensive regimes may in part justify the high costs of the monitors. Although sleep disturbance continued in more than 20% of investigated patients, the new lighter, quieter monitors (e.g., SL 90207, 380 g) were well received by patients and nurses. In the future, simultaneous registration with 24-h ECG may help in identifying the effects of different antihypertensive therapies on blood pressure variabilities and rhythmicity of the heart rate. The cost-benefit-ratio and the prognostic importance have yet to be defined.

A double-blind comparison of perindopril and hydrochlorothiazide-amiloride in mild to moderate essential hypertension.

The aim of this 3-month double-blind multicenter trial was to compare the antihypertensive efficacy and tolerability of the ACE inhibitor perindopril with those of a diuretic combination. After 1 month of receiving placebo, 165 patients with essential hypertension were randomised to perindopril 4 mg (n = 82) or to 50 mg hydrochlorothiazide + 5 mg amiloride (n = 83). The patients were treated for 3 months with monthly assessments, "uncontrolled" patients (DBP greater than 90 mm Hg) had their dosage doubled and then, if necessary, atenolol 50 mg was added. At the end of the 3-month study, mean decreases in supine and standing systolic and diastolic blood pressures were similar in both groups. In the perindopril group, BP control was obtained in 56% of the patients with the 4 mg dosage and required an increase to 8 mg alone in 16% and with atenolol in 5%. The corresponding percentages in the diuretic group were 48, 23 and 13%. The overall percentage of "controlled" patients was similar in the 2 groups, respectively 78 and 84%. The nature and incidence of complaints were comparable in the 2 groups. Adverse laboratory changes were more frequent in the diuretic group: decrease in blood sodium (140.5 vs 139.1 mmol/l; P less than 0.01), potassium (4.2 vs 3.9 mmol/l; P less than 0.01) with 10 patients having significant hypokalemia, increase in blood urea, triglycerides and uric acid. By contrast, a transient increase in blood potassium with a decrease in triglycerides was observed in the perindopril group.

[Detection of cardiac risk in hypertensive patients with left heart hypertrophy]. / Erkennung des kardialen Risikos bei Hypertonikern mit Linksherzhypertrophie.

Arterial hypertension is a consistent and modifiable cause of cardiovascular disease. The risk is further increased by left ventricular hypertrophy as an independent contributor to these cardiovascular events. However, the incidence of coronary mortality and sudden death could not be reduced by antihypertensive drug therapy. It seems possible that there is a subgroup of patients with arterial hypertension with excess risk associated with increased left ventricular mass, ventricular arrhythmias, and silent myocardial ischemia. These patients could be detected by a more developed diagnostic approach using echocardiography, 24-h ECG, and noninvasive 24-h blood-pressure measurement.

Non-invasive ambulatory blood pressure monitoring: technical possibilities and problems.

Non-invasive automatic 24-h indirect ambulatory monitoring of blood pressure and the heart rate was performed in 2010 subjects at the Department of Internal Medicine, Klinikum Steglitz, Free University of Berlin, Germany, from 1983 to 1990. Blood pressure profiles were obtained using seven different monitors, Pressurometer III (Del Mar Avionics), Physioport (Natic), Accutracker (Oxford), Blutdrucksystem (Medizintechnik), SL 5200, SL 90202 and SL 90207 (SpaceLabs). The monitors were equipped with auscultatory and/or oscillometric devices, provided accurate readings and were repeatedly used up to eight times in some patients. Up to 100 data points per 24 h provided diurnal blood pressure profiles for over 91% of the patients in clinical and non-clinical situations. Early identification of borderline hypertensives at risk of cardiovascular disease and detailed information on the efficacy of different antihypertensive regimens may in part justify the high costs of the monitors. Although disturbance to sleep remained a problem in more than 20% of the patients investigated, the new, lighter, quieter monitors (e.g. SpaceLabs 90207 at 380 g) were well received by patients and nurses. In the future, simultaneous registration with 24-h ECG may help in identifying the effects of different antihypertensive therapies on blood pressure variability and the periodicity of the heart rate.

Blood pressure profile and cardiac risk in hypertensive patients with left ventricular hypertrophy.

A study of normotensive volunteers and patients with primary hypertension demonstrated the superiority of a single 24-h mean systolic and diastolic ambulatory blood pressure monitoring (SpaceLabs 90207 ABPM) over standardized sphygmomanometric casual readings. In contrast to the casual blood pressure measurement there was a significant correlation between both 24-h mean systolic and diastolic blood pressures and left ventricular hypertrophy as assessed by two-dimensional M-mode echocardiography. Although no significant differences between daytime and night-time blood pressure were demonstrated in normotensive or hypertensive subjects with or without target organ damage, larger prospective trials are required to confirm this finding.

Technical possibilities and limits of indirect automatic twenty-four-hour blood pressure devices.

Automatic 24-h indirect ambulatory monitoring of blood pressure and heart rate was performed in 758 patients. The blood pressure profiles of 1105 subjects were evaluated for 5 years using seven different monitors: Pill (Del Mar Avionics), PHYSIOPORT (Natic), Accutracker (Oxford), BDS (Medizintechnik), SL 5200, SL 90202 and SL 90207 (Spacelabs). The monitors were equipped with auscultatory and/or oscillometric devices, provided accurate readings and were repeatedly used up to eight times in some patients. Up to 100 data points per 24 h provided circadian blood pressure profiles for over 91% of the patients in clinical and non-clinical situations. Early identification of borderline hypertensives at risk and detailed information on the efficacy of different antihypertensive regimens may in part justify the high costs of the monitors. Although sleep disturbance continued in more than 24% of investigated patients, the new lighter, quieter monitors (e.g. SL 90207, 380 g) were well received by patients and nurses. In the future, simultaneous registration with 24-h ECG may help in identifying the effects of different antihypertensive therapies on blood pressure variability and rhythmicity of the heart rate.

Combined beta 1-adrenoceptor blockade and/or beta 2- or beta 1/2 adrenoceptor stimulation as treatment of essential hypertension.

Single and combined therapy with terbutaline (10 mg/day) and metoprolol (200 mg/day) and single therapy with orciprenaline (30 mg/day) were assessed over 8 weeks in a total of 45 patients with essential hypertension. Blood pressure at rest was comparably reduced by metoprolol + terbutaline and metoprolol alone, but with terbutaline and orciprenaline only after 4 weeks. The responder rates (greater than or equal to 10% reduction in diastolic blood pressure) at rest were 58% (metoprolol + terbutaline), 63% (metoprolol) and significantly lower with terbutaline alone at 42% and orciprenaline alone at 45%. The heart rate was affected only by metoprolol monotherapy, which caused a significant decrease. The beta-adrenoceptor stimulators terbutaline and orciprenaline in the chosen doses slightly decreased blood pressure and did not increase the heart rate. Metoprolol was an effective antihypertensive agent but decreased the heart rate. Under combined therapy with terbutaline, there was no additional blood pressure decrease, but the heart rate remained unaffected.

Functional versus structural changes of forearm vascular resistance in hypertension.

Structural changes in resistance vessels have been considered an important factor in triggering and maintaining chronic hypertension in humans and in experimental animals. To determine whether the increased forearm vascular resistance observed following vasodilator maneuvers in hypertensive patients is predominantly due to structural or to functional changes, we examined the influence of different vasodilator stimuli on forearm blood flow and blood pressure in 22 male patients with established essential hypertension and in 22 age-matched normotensive men (age range, 28-52 years). Blood pressure was measured directly, and blood flow was measured by venous occlusion plethysmography. The maneuvers applied were 1) arterial occlusion combined with handgrip exercise and local heating, 2) intra-arterial infusion of the calcium entry blocker nifedipine, 3) intra-arterial infusion of the nonspecific vasodilator sodium nitroprusside, 4) arterial occlusion initiated after intra-arterial infusion of nifedipine. Vascular resistance during vasodilation induced by arterial occlusion or infusion of nifedipine or sodium nitroprusside remained significantly higher in the hypertensive than in the normotensive subjects. However, the maximal vasodilation achieved by the combination of arterial occlusion and nifedipine resulted in a similar resistance in both groups (1.6 +/- 0.2 in the hypertensive vs 1.4 +/- 0.2 mm Hg/ml/min/100 ml tissue in the normotensive subjects. These data suggest that there is an important functional component of the elevated resistance in patients with essential hypertension.

24-hour noninvasive oscillometric blood pressure monitoring: evaluation of the antihypertensive circadian profile of nitrendipine.

The understanding of blood pressure (BP) and heart rate (HR) variation, circadian changes, and the responses to nonclinical situations has been improved by automated ambulatory recordings. The antihypertensive efficacy of a once-daily regimen (10/20 mg) of nitrendipine was evaluated in detail using the lightest available portable device equipped with an oscillometric blood pressure (BP) recorder (SpaceLabs 90202, weight 480 g) devoid of any electrode. A good antihypertensive effect throughout the day in 20 outpatients could be demonstrated. No significant change of BP could be found in early morning and wake-up period; HR was not significantly affected after 6 weeks of oral therapy.

Ouabain-induced elevation in forearm vascular resistance, calcium entry and alpha-adrenoceptor blockade, and release and removal of noradrenaline.

The activity of the ouabain-sensitive Na+K+-ATPase may be reduced in primary hypertension by an ouabain-like humoral factor with resultant increase in intracellular Na+ and Ca2+ and peripheral vasoconstriction. To test this, we studied the forearm blood flow in 18 normotensive subjects. First, nifedipine, phentolamine, prazosin, sodium nitroprusside and ouabain were infused into the brachial artery. Secondly, each vasodilator was given in combination with ouabain. Blood pressure was measured directly, and blood flow by venous occlusion plethysmography. When nifedipine was combined with ouabain the elevation of vascular resistance was completely abolished. We detected no effect on the forearm veno-arterial difference for noradrenaline following intra-arterial infusion of drugs. If an ouabain-like factor plays a role in producing the elevated resistance of chronic hypertension, calcium entry blockers will act close to the site of this primary abnormality.

Effects of diltiazem alone and combined with mefruside on cardiovascular response at rest and during exercise, carbohydrate metabolism and serum lipoproteins in patients with systemic hypertension.

The antihypertensive effects of the calcium antagonist diltiazem, both alone and combined with the diuretic mefruside, were assessed over 14 months in 36 patients with essential hypertension. Patients received 180 or 270 mg/day; those with inadequate response were given 270 mg/day plus mefruside, 20 mg/day. Both monotherapy and combination therapy significantly reduced blood pressure (BP) at rest and during exercise. However, adding mefruside did not significantly decrease BP below that achieved with diltiazem alone. After 14 months of therapy, the percentage of responders (patients with at least 10% reduction in diastolic BP at rest) was 64% for all patients, 100% (by definition) for those receiving diltiazem alone and 47% for those receiving the combination. Diltiazem decreased heart rate by 6% (4 beats/min at rest) (p less than 0.05). Combined therapy with mefruside did not further reduce heart rate. There were few adverse effects and no undesirable metabolic effects with either monotherapy or combined therapy. Plasma renin activity, aldosterone levels, carbohydrate metabolism, serum lipoprotein levels and routine laboratory test results were unchanged in both groups at the end of the study. Thus, diltiazem is an effective antihypertensive agent and apparently the combination of diltiazem and mefruside does not potentiate the antihypertensive effect of diltiazem alone during long-term therapy.