Endothelium-dependent responses in patients with hypercholesterolemic coronary artery disease under the effects of simvastatin and enalapril, either separately or combined.

BACKGROUND: Endothelial dysfunction is an early event in atherosclerotic disease that precedes clinical manifestations and complications. The noninvasive assessment of endothelial function in patients with risk factors undergoing clinical treatment is an important medical advance. In this setting, altered endothelial function in patients with coronary hypercholesterolemia and its modifications by treatment with enalapril and simvastatin, either separately or in combination, was assessed in the brachial artery in a randomized, double-blind, 2-period crossover study. METHODS: Thirty-eight patients were separated in 2 groups. Group 1 (18 patients, 3 female, mean age 63 +/- 6.0 years) received simvastatin 10 mg/d for 8 weeks and simvastatin plus enalapril 5 mg/d for another 8 weeks. Group 2 (20 patients, 3 female, mean age 64 +/- 5.8 years) received enalapril 5 mg/d for 8 weeks and enalapril plus simvastatin 10 mg/d for another 8 weeks. All subjects underwent measurements of brachial artery diameter before and after postischemic hyperemia with high-resolution ultrasound at basal conditions (control) and under the effects of the drugs at the end of 8 and 16 weeks. RESULTS: Cholesterol and LDL cholesterol levels significantly decreased with simvastatin treatment alone or with enalapril. Mean baseline arterial diameter was 5.24 +/- 1.25 mm in group 1 and 4.83 +/- 0.99 mm in group 2 (not significant). In group 1 after the first 8 weeks, endothelium-dependent vasodilation significantly increased with simvastatin treatment (control, 4.4%; 8 weeks, 7.6%; P <.001). After 16 weeks with the addition of enalapril, a further increase in vasodilation was seen (8.6%, P <.05 vs 8 weeks). In group 2, with enalapril treatment an increase in vasodilation versus control was seen (control, 4.3%; 8 weeks, 5.8%; P <.01). After 16 weeks, with the addition of simvastatin an additional increase in vasodilation was observed (9.1%, P <.001 vs 8 weeks). After nitroglycerin, vasodilation in group 1 at control, 8, and 16 weeks was 17%, 17.5%, and 18%, respectively. In group 2, nitroglycerin vasodilation at control, 8, and 16 weeks was 21%, 21%, and 22%, respectively. CONCLUSIONS: Simvastatin significantly increased the postischemic vasodilator response in patients with coronary hypercholesterolemia, either as single treatment or added to enalapril. Similarly, the response was increased by enalapril, either alone or while simvastatin was being administered. Both drugs improve vasodilation and additive effects appear to be present.

Impaired endothelial function in patients with rapidly stabilized unstable angina: assessment by noninvasive brachial artery ultrasonography.

BACKGROUND: Endothelial dysfunction may contribute to symptoms of instability in patients with acute coronary syndromes. High-resolution external ultrasound assessment of the brachial artery responses allows noninvasive determination of endothelial function. HYPOTHESIS: This study was conducted to assess endothelial function in patients with unstable angina using a noninvasive technique. METHODS: We studied 189 patients who were subdivided into three groups. Group 1: 60 apparently healthy subjects with no cardiovascular risk factors or symptoms of coronary artery disease; Group 2: 105 subjects with cardiovascular risk factors--arterial hypertension, hypercholesterolemia, cigarette smoking, diabetes, and obesity, but no evidence of coronary artery disease; and Group 3: 24 patients with unstable angina (chest pain at rest within the 24 h preceding study entry). All patients underwent pre- and postischemic brachial artery test evaluation with measurements of internal arterial diameters and blood flow. RESULTS: Results are expressed as percentage change from basal values. Subjects in Groups 1 and 2 showed a diameter increase of 19.1 and 11.9%, respectively, whereas patients in Group 3 showed a diameter change of 1.2% (p < 0.002 and < 0.0001, respectively). Calculated blood flow did not differ significantly in Groups 1 or 2 (74.4 and 56.4%), but was notably lower in Group 3 (18.4%, p < 0.005 vs. Groups 1 and 2). In nine patients of Group 3, the brachial studies were repeated 4 weeks after symptom stabilization and showed values comparable with those in Group 2. CONCLUSIONS: Patients with unstable angina showed endothelial dysfunction compared with control individuals. It is of interest that in patients whose symptoms were stabilized by medical therapy, endothelial function was restored 4 weeks after hospital discharge.

The role of lipid-lowering therapy in multiple risk factor management.

Epidemiological studies have demonstrated that the risk of death from coronary heart disease (CHD) increases in parallel with increasing serum cholesterol levels. The risk is highest in patients with severely elevated cholesterol levels [i.e. > 6.2 mmol/L(240 mg/dl)]. However, even in patients with serum cholesterol levels of 4.7 to 5.7 mmol/L (180 to 220 mg/dl), mortality from CHD is 30 to 70% higher than in patients with cholesterol levels < 4.7 mmol/L (180 mg/dl). A number of factors other than serum total cholesterol levels affect CHD risk. It is increasingly accepted that dysfunction of the vascular endothelium contributes to the pathogenesis of atherosclerosis. Experimental evidence and clinical studies suggest that endothelium-derived nitric oxide (NO) plays an important role as an endogenous antiatherogenic molecule, and that reduced levels of NO may promote progression of atherosclerosis. Hypercholesterolaemia can hasten atherogenesis in part by reducing levels of NO. In humans, it is possible to evaluate the effects of hypercholesterolaemia by measuring the vasodilator response to pharmacological or physical stimuli that increase the synthesis and release of endothelium-derived NO. The use of high resolution external ultrasound to assess post-ischaemic brachial artery vasodilation in patients with cardiovascular risk factors has demonstrated that endothelial dysfunction exists, even in the absence of overt atherosclerotic plaques. Impaired endothelium-dependent vasodilation has been observed in asymptomatic individuals with hypercholesterolaemia, as well as in patients with other recognised risk factors. Dietary and pharmacological lipid lowering has been shown to produce improvements in endothelial-dependent vasodilation. Among normocholesterolaemic healthy young individuals without cardiac risk factors, endothelium-dependent vasodilation was more likely to be impaired in those with relatively higher total and low density lipoprotein-cholesterol levels (i.e. above versus below the 25th percentile). This suggests that an inverse and continuous relationship exists between the prevailing cholesterol level and endothelial function. The implication of these findings is that the treatment of hypercholesterolaemia remains, at present, an underutilised means of reducing CHD.

Left ventricular mass regression and diastolic function improvement in mild and moderate hypertensive patients treated with lisinopril.

Thirty patients (18 male), mean age 49.5 +/- 6.3 years, were treated with lisinopril 10-40 mg once daily for 16 weeks. The effect of treatment on left ventricular mass and improvement in left ventricular diastolic function (measured by echo-Doppler) was assessed. Blood pressure changes were measured conventionally in the clinic and by ambulatory blood pressure monitoring. Clinic blood pressure decreased from 168.3 +/- 13.8/105.5 +/- 5.4 mm Hg to 137.5 +/- 4.1/88.8 +/- 4.1 mm Hg (p < 0.005 for both systolic and diastolic blood pressures), and the heart rate from 75.2 +/- 3.7 to 74.4 +/- 7.6 beats per minute (NS). The frequency of ambulatory systolic blood pressure values > 140 mm Hg decreased in percentage from 63.3 +/- 12.8 to 29.9 +/- 9.1% (p < 0.005) and the frequency of ambulatory diastolic blood pressure values > 90 mm Hg decreased in percentage from 61.1 +/- 12.8 to 28.6 +/- 7.5% (p < 0.005). Septal and left ventricular posterior wall thickness decreased from 11.2 +/- 0.9 to 10.3 +/- 0.6 mm and from 10.9 +/- 0.9 to 10.1 +/- 0.6 mm, respectively (both p < 0.005). Left ventricular diastolic diameter and the shortening fraction did not change significantly. Left ventricular mass, calculated from left ventricular wall thickness and diastolic diameter, decreased from 132.6 +/- 11.5 to 119.9 +/- 6.3 g/m2 (p < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Effectiveness of atenolol in the treatment of hypertension during pregnancy.

This study assessed the effectiveness of atenolol in the treatment of moderate and severe hypertension during pregnancy. Seventy patients (mean age, 30.3 +/- 6.0 years), 35.7% primiparous, were included. Three groups were formed according to Davey and MacGillivray's classification: 1) chronic hypertension without proteinuria (12 patients), 2) gestational hypertension without proteinuria (52 patients), and 3) preeclampsia (six patients). Treatment with atenolol was started when blood pressure was 150/100 mm Hg or higher after 48 hours' rest. The treatment lasted at least 1 week; follow-up was every 2 weeks up to week 36, and from then on, weekly up to delivery. If blood pressure exceeded 160/110 mm Hg and the fetus was not yet mature, a second drug was added. A significant decrease in blood pressure was observed in the three groups (group 1: 155.8 +/- 15.0/100.8 +/- 7.6 versus 135.0 +/- 12.9/85.0 +/- 6.7 mm Hg; group 2: 154.2 +/- 13.6/104.9 +/- 9.3 versus 129.6 +/- 10.2/83.7 +/- 9.1 mm Hg; group 3: 158.3 +/- 27.1/104.1 +/- 8.0 versus 129.1 +/- 6.6/87.5 +/- 6.1 mm Hg). The doses of atenolol were 62.5 +/- 23.0 mg/day in group 1, 70.0 +/- 30.0 mg/day in group 2, and 100.0 +/- 41.0 mg/day in group 3. There was no fetal mortality. No significant difference occurred in newborn body weights. Four babies from group 2 mothers had an Apgar score of less than 7 at 1 minute, but only one remained abnormal after 5 minutes. In the same group, three cases of respiratory distress were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of moderate physical training on left ventricular mass in mild hypertensive persons.

Exercise might reduce blood pressure in mild essential hypertensive individuals, but it could raise left ventricular mass, counteracting the beneficial effects induced by a decrease in blood pressure. Seventeen (group 1) of 25 mild hypertensive patients, nonresponders to a 3-month low sodium diet (2 g/day), were admitted into a physical training program consisting of three weekly sessions of aerobics (20 minutes), bicycling at prefixed loads (20 minutes), and induced muscular relaxation (10 minutes). They were compared with 15 mild hypertensive patients (group 2), nonresponders to the low sodium diet who remained untrained. The follow-up lasted 15.7 +/- 5.8 months. There were significant blood pressure decreases in group 1 at rest (155 +/- 9.8/101 +/- 3.3 vs. 136 +/- 8.1/86 +/- 6.6 mm Hg, p less than 0.001) and at maximal effort (219 +/- 27.4/119 +/- 14.4 vs. 196 +/- 21.8/101 +/- 10.5 mm Hg, p less than 0.001). Maximal work capacity increased from 758.8 +/- 256.7 to 944.1 +/- 203.8 kpm (p less than 0.001). Echocardiographic left ventricular mass index tended to decrease (137.8 +/- 36.3 vs. 125.4 +/- 29.9 g/m2, p = NS), without any significant modification of either left ventricular volume index or left ventricular shortening fraction. No significant changes occurred in group 2. There was no correlation between blood pressure and left ventricular mass changes and left ventricular shortening fraction and left ventricular mass index changes. According to these results, it seems prudent to prescribe physical training to mild hypertensive patients because it does not induce left ventricular mass increases.(ABSTRACT TRUNCATED AT 250 WORDS)

[Reduction of the left ventricular mass in essential hypertension patients chronically treated with monotherapy]. / Reducción de la masa ventricular izquierda en hipertensos esenciales tratados crónicamente con monoterapia.

Changes in left ventricular mass (LVM) were measured by echocardiography in 104 mild and moderate essential hypertensives treated with only one drug for at least 12 months. They were classified into 4 groups. G1: 40 patients (p) treated with atenolol (73.6 +/- 31.8 mg daily), G2: 32 p treated with enalapril maleate (17.7 +/- 8.7 mg daily), G3: 22 p treated with nifedipine (44.0 +/- 10.8 mg daily), G4: control group, 10 mild hypertensives without medication. At the end of the treatment blood pressure (BP) fell significantly in the first 3 groups (G1: 155 +/- 19/.98 +/- 11 vs. 136 +/- 11/86 +/- 15 mm Hg, G2: 163 +/- 19/104 +/- 10 vs. 139 +/- 12/90 +/- 8 mm Hg, G3: 166 +/- 17/103 +/- 7 vs. 142 +/- 7/85 +/- 7 mm Hg, p less than 0.001), but remained unchanged in G4. Heart rate was reduced significantly only in G1. Body weight did not change (71 +/- 7 vs. 67 +/- 7, p greater than .05). Patients were subclassified according to wether they had normal (N, LVM less than 120 g/m2 in females, LVm less than 135 g/m2 in males) or increased (H) LVM. There was a significant reduction in LVM in all H subgroups (G1 163 +/- 37 vs. 131 +/- 27 g/m2, G2: 155 +/- 19 vs. 126 +/- 21 g/m2, G3: 158 +/- 2 vs. 138 +/- 38 g/m2, p less than .005). The LVM/left ventricular end-diastolic volume ratio (M/V) fell in all H subgroups.(ABSTRACT TRUNCATED AT 250 WORDS)

Reducción de la masa ventricular izquierda en hipertensos esenciales tratados crónicamente con monoterapia. / [Reduction of the left ventricular mass in essential hypertension patients chronically treated with monotherapy]

Changes in left ventricular mass (LVM) were measured by echocardiography in 104 mild and moderate essential hypertensives treated with only one drug for at least 12 months. They were classified into 4 groups. G1: 40 patients (p) treated with atenolol (73.6 +/- 31.8 mg daily), G2: 32 p treated with enalapril maleate (17.7 +/- 8.7 mg daily), G3: 22 p treated with nifedipine (44.0 +/- 10.8 mg daily), G4: control group, 10 mild hypertensives without medication. At the end of the treatment blood pressure (BP) fell significantly in the first 3 groups (G1: 155 +/- 19/.98 +/- 11 vs. 136 +/- 11/86 +/- 15 mm Hg, G2: 163 +/- 19/104 +/- 10 vs. 139 +/- 12/90 +/- 8 mm Hg, G3: 166 +/- 17/103 +/- 7 vs. 142 +/- 7/85 +/- 7 mm Hg, p less than 0.001), but remained unchanged in G4. Heart rate was reduced significantly only in G1. Body weight did not change (71 +/- 7 vs. 67 +/- 7, p greater than .05). Patients were subclassified according to wether they had normal (N, LVM less than 120 g/m2 in females, LVm less than 135 g/m2 in males) or increased (H) LVM. There was a significant reduction in LVM in all H subgroups (G1 163 +/- 37 vs. 131 +/- 27 g/m2, G2: 155 +/- 19 vs. 126 +/- 21 g/m2, G3: 158 +/- 2 vs. 138 +/- 38 g/m2, p less than .005). The LVM/left ventricular end-diastolic volume ratio (M/V) fell in all H subgroups.(ABSTRACT TRUNCATED AT 250 WORDS)

Reduccion de la masa ventricular izquierda en hipertensos esenciales tratados cronicamente con monoterapia / Reduction of the left ventricular mass in essential hypertension patients treated chronically with monotherapy

En 104 hipertensos esenciales leves y moderados se midieron mediante ecocardiografía los cambios inducidos en la masa ventricular izquierda (MV) por el tratamiento con monodrogas durante por lo menos 12 meses. Los pacientes (p) fueron clasificados en 4 grupos (G). G1: 40p tratados con atenolol, G2: 32p tratados con maleato de enalapril, G3: 22p tratados cocn nifedipina, G4: grupo control, 10 en los primeros 3 grupos, pero no se modificó en el G4. La frecuencia cardíaca se redujo significativamente solo en el G1. El peso corporal no varió. Los pacientes fueron subclasificados de acuerdo a que su MV fuese normal (N, MV, < 120 g/m2 en hombres) o aumentada (H). Hubo una reducción significativa de la MV en todos los grupos H. La relación MV/volumen de fin de diastole del ventrículo izquierdo (M/V) cayó en todos los grupos H. Hubo una correlación pequeña, aunque significativa entre la PA vbasal y la MV. La regresión de la MV fue mayor en los ventrículos hipertróficos, sin que se produjesen cambios significativos en a fracción de acortamiento. En base a estos resultados parecería razonable elegir para el tratamiento las drogas antihipertensivas que reduzcan la MV (AU)

Reduccion de la masa ventricular izquierda en hipertensos esenciales tratados cronicamente con monoterapia / Reduction of the left ventricular mass in essential hypertension patients treated chronically with monotherapy

En 104 hipertensos esenciales leves y moderados se midieron mediante ecocardiografía los cambios inducidos en la masa ventricular izquierda (MV) por el tratamiento con monodrogas durante por lo menos 12 meses. Los pacientes (p) fueron clasificados en 4 grupos (G). G1: 40p tratados con atenolol, G2: 32p tratados con maleato de enalapril, G3: 22p tratados cocn nifedipina, G4: grupo control, 10 en los primeros 3 grupos, pero no se modificó en el G4. La frecuencia cardíaca se redujo significativamente solo en el G1. El peso corporal no varió. Los pacientes fueron subclasificados de acuerdo a que su MV fuese normal (N, MV, < 120 g/m2 en hombres) o aumentada (H). Hubo una reducción significativa de la MV en todos los grupos H. La relación MV/volumen de fin de diastole del ventrículo izquierdo (M/V) cayó en todos los grupos H. Hubo una correlación pequeña, aunque significativa entre la PA vbasal y la MV. La regresión de la MV fue mayor en los ventrículos hipertróficos, sin que se produjesen cambios significativos en a fracción de acortamiento. En base a estos resultados parecería razonable elegir para el tratamiento las drogas antihipertensivas que reduzcan la MV

Loud systolic and diastolic murmurs originating on a right atrial metastatic tumor.

A 36-year-old asymptomatic man, who two months before had a normal clinical examination, developed two loud, grade 5/6 harsh systolic and diastolic murmurs, audible over the entire precordium. Two-dimensional echocardiography revealed a huge tumoral mass, attached to the right atrium near the tricuspid valve, pedicellated and of great mobility, reaching the right ventricular outflow tract during diastole, and coming back to the atrium in systole. Right-sided angiography confirmed the diagnosis, and after ablation of the tumor, the auscultation was normal again. Two loud murmurs constitute a quite uncommon manifestation of an intracavitary mass, and this unusual finding has not previously reported in the medical literature available to the authors.

QT prolongation and torsade de pointes ventricular tachycardia produced by Ketanserin.

A 65-year-old man with arterial hypertension received oral treatment with Ketanserin, a new drug, during a period of five months. He developed marked QT interval prolongation and have several Stokes-Adams attacks. A Holter recording obtained during one of these episodes showed torsade de pointes ventricular tachycardia. The arrhythmias occurred during maximum QT interval prolongation. The correlation between Ketanserin and QT interval prolongation was evaluated by using several Holter studies during administration and withdrawal of the drug. The effect of Ketanserin on the QTc interval was analyzed retrospectively in six patients who had been taking the drug orally. Following a period of four to eight months, the QTc interval was prolonged by the drug (5 to 31%, mean 17%) in five patients. We conclude that torsade de pointes is a potential hazard of long-term treatment with Ketanserin.

Noninvasive assessment of left ventricular performance after administration of bisoprolol.

The effects of single doses of 10, 20, and 40 mg of bisoprolol on left ventricular performance were assessed by left ventricular systolic time interval measurements, echocardiographic measurements, and exercise stress tests in patients with mild to moderate arterial hypertension. Bisoprolol caused a significant, dose-dependent fall in systolic and diastolic blood pressure and heart rate, at rest and under exercise stress test. Left ventricular systolic time intervals were prolonged at the higher doses, but pre-ejection period/left ventricular ejection time (PEP/LVET) ratio, as an indicator for left ventricular performance, remained unchanged. Left ventricular echocardiographic dimensions increased significantly, but shortening fraction was not altered. We conclude that 10-40 mg bisoprolol, apart from the blockade of beta 1-adrenoceptors, does not affect left ventricular cardiac function.

Dose finding study in chronic congestive heart failure patients. Results of a short- and long-term study.

A multi-center open trial was carried out with 103 patients with chronic congestive heart failure (CHF) of diverse etiologies with oedemas, 25 with hepatomegalia, placed in classes II or III of NYHA functional capacity, with increasing doses of 30, 60 and 90 mg of muzolimine qd to ascertain (1) the effective dose for the elimination of oedemas and hepatomegalia and (2) whether such a dose keeps its efficacy throughout a long administration period. After a wash-out period of 3-7 days, heart rate (HR), systolic (SBP) and diastolic blood pressure (DBP) in supine and standing positions, body weight (BW) and 24 hour diuresis were controlled and laboratory tests were performed. Muzolimine was administered and an assessment of the therapeutic effect was carried out every week. When the clinical results were ineffective, the dose was increased weekly up to 90 mg. When the results were partial, the same dose was given for another week and when it was effective the search for the dose was concluded. Out of the 103 patients, 67 needed only 30 mg of muzolimine for an effective elimination of oedemas and hepatomegalia, 32 needed 60 mg and only 4 had to have the dose increased to 90 mg to obtain efficacy. The SBP and DBP diminished by 6.3% and 7.2% respectively, and HR was reduced, though not significantly. BW diminished an average of 2.4 Kg and the diuresis increased significantly from a mean value of 1.043 ml/24 h to 1.714 ml/24 h. Sixty-two patients with effective results agreed to undergo chronic treatment for 24 weeks and be controlled every 2 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term effectiveness of BAY e 5009-nitrendipine in the treatment of mild and moderate arterial hypertension.

Thirty-seven white patients of both sexes were studied to determine the efficacy and tolerance of nitrendipine for long ambulatory treatment in patients suffering from mild to moderate essential arterial hypertension whose response to the drug had been effective in a previous study. They all suffered from mild essential arterial hypertension, with diastolic arterial blood pressure (DBP) of 95-104 mm Hg, and moderate arterial hypertension with DBP of 105-114 mm Hg, in WHO Stage I or II, according to the clinical, radiological, electrocardiographic, and ophthalmoscopic examinations. In a previous study, all of them had been subjected to tensional controls, performed hourly during an 8-h period to assess their hypertension. Later, they were treated with increasing doses of nitrendipine, administered once or twice daily, until DBP figures under 90 mm Hg were obtained in at least five of the eight controls of each daily profile. All of them agreed to take part in the present research and underwent heart rate and arterial blood pressure controls in supine and standing position every 14 days during 24 periods. Simultaneous clinical and weight controls were performed. Moreover, an electrocardiogram was made every 28 days, and blood and urine tests were performed every 3 months. Of the 37 patients, 31 completed the 24 periods of 2 weeks each. Therefore, of 888 possible controls only 837 controls were made and submitted for assessment. Eighteen patients (48.6%) went on with the initial dose throughout the study or were able to reduce it. Eleven (29.7%) had to increase it, and in eight cases (21.6%) it was either increased or reduced.(ABSTRACT TRUNCATED AT 250 WORDS)

Detection of mild aortic regurgitation by range-gated pulsed Doppler echocardiograhy.

In order to assess the sensitivity and specificity of the range-gated pulsed Doppler echocardiogram for the detection of aortic regurgitation, a study with use of this technique was carried out in 46 patients. They were classified into 3 groups: Group I was composed of 19 patients with a variety of heart diseases but with a competent aortic valve. Cardiac catheterization revealed no aortic regurgitation in any of the 19 patients, and the Doppler echocardiogram detected no turbulent diastolic flow in the left ventricular outflow tract. Group II was composed of 17 patients who clinically and by auscultation had aortic regurgitation, which was confirmed by cardiac catheterization in 6. In all 17 patients the Doppler echocardiogram detected several grades of turbulent diastolic flow compatible with aortic regurgitation in the left ventricular outflow tract. Group III was composed of 10 patients with aortic regurgitation but without the expected clinical or auscultatory evidence. The echocardiogram detected mitral valve flutter in only 1 patient. Cardiac catheterization revealed aortic regurgitation graded 1/4 and 2/4 in 9 patients, and the patient who did not undergo catheterization had a murmur of aortic insufficiency 6 months later. In all 10 patients the Doppler echocardiogram detected a regurgitating turbulent flow compatible with aortic regurgitation in the left ventricular outflow tract. It is concluded that the Doppler echocardiogram was more useful than auscultation and echocardiography for the detection of mild aortic regurgitation. In this study the range-gated pulsed Doppler echocardiogram proved 100% sensitive and specific. However, it will be necessary to study larger groups in order to assess its utility in more complicated conditions (obesity, emphysema, and heart failure) and the differential diagnosis with other diastolic murmurs.