Reversal of cardiac and large artery structural abnormalities induced by long-term antihypertensive treatment with trandolapril.

In 15 patients with untreated mild to moderate essential hypertension and left ventricular hypertrophy, we assessed blood pressure, echocardiographic left ventricular mass index, brachial artery compliance (pulsed doppler flowmetry), and calculated forearm vascular resistance (strain gauge plethysmography) before, during (6 and 12 months) and after (1 month washout period) 1 year of satisfactory (blood pressure < or = 140/90 mm Hg) antihypertensive therapy with the angiotensin-converting enzyme inhibitor trandolapril (2.0 mg orally once daily). During the antihypertensive effective treatment, we observed a significant reduction of systolic and diastolic blood pressures, left ventricular mass index, and forearm vascular resistance at both 6 and 12 months. In addition, brachial artery compliance was significantly increased. After washout, systolic (156 +/- 3 mm Hg) and diastolic (102 +/- 1 mm Hg) blood pressures returned to levels comparable to baseline. However, left ventricular mass index (132 +/- 4; p < 0.01) and brachial artery compliance (1.53 +/- 0.01; p < 0.01) were still different from baseline. These results demonstrate that chronic antihypertensive treatment with trandolapril is associated with a stable regression of cardiac and vascular abnormalities, which is partially unrelated to the blood pressure lowering effect.

Effects of long-term antihypertensive treatment with tertatolol on diastolic function in hypertensive patients with and without left ventricular hypertrophy.

UNLABELLED: We assessed the effects of long-term antihypertensive treatment with 5 mg tertatolol, a noncardioselective beta-blocker, on left ventricular hypertrophy (LVH) and diastolic function. Fifteen hypertensive patients were selected as good responders to previous treatment with tertatolol (supine blood pressure less than 140/90 mm Hg). They were divided into 2 groups: group 1 with LVH (n = 6) and group 2 without LVH (n = 9). After a one month wash-out period, all patients received 5 mg tertatolol once daily. In case of uncontrolled blood pressure (BP), the dose was doubled after 2 weeks in 10 patients. BP control was obtained in all patients. M-mode echocardiography and Doppler-echocardiography were performed under controlled conditions after BP normalization and after 6 months of treatment. Long-term BP normalization significantly reduced left ventricular mass index (LVMI) in group 1 (from 137 +/- 3 to 121 +/- 3 g/m2, P less than .01), but not in group 2 (from 120 +/- 3 to 114 +/- 4 g/m2, P = NS). After 2 weeks of effective therapy, the ratio between early and late diastolic peak flow velocity across the mitral valve (E/A ratio), significantly increased in both groups (from 0.72 +/- 0.04 to 0.87 +/- 0.06 in group 1, P less than .05; and from 1.13 +/- 0.06 to 1.26 +/- 0.07 in group 2, P less than .05). After 6 months, together with the reduction of LVMI, a further increase of E/A ratio was only observed in group 1 (to 1.30 +/- 0.12, P less than .05). IN CONCLUSION: (1) LVH contributes to left ventricular diastolic dysfunction in hypertensive patients since its reversal is able to improve diastolic filling, and (2) effective antihypertensive treatment with tertatolol improves diastolic function independently from its effect on LV mass.

[The effects of plasma cholesterol reduction on vasoconstriction due to sympathetic activation in patients with moderate primary hypercholesterolemia]. / Effetti della riduzione del colesterolo plasmatico sulla vasoconstrizione da attivazione simpatica in pazienti con ipercolesterolemia primaria moderata.

Recent studies have demonstrated that hypercholesterolemia is one of the major factor involved in the progression of coronary heart disease and that the reduction in plasma cholesterol reduces mortality for cardiovascular events. Indeed, recent experimental studies have demonstrated alterations in vascular reactivity in atherosclerosis. The aim of this study was to evaluate in patients with primary hypercholesterolemia the consequences of an effective of chronic treatment with inhibitor of HMG-CoA reductase on vascular responsiveness to cold pressure test. We observed a significant reduction in total plasma cholesterol during the study that was accompanied by a significant decrease in the response of peripheral vascular resistances to cold pressure test (55 +/- 4% vs 73 +/- 5% p < 0.01). There was also a significant relationship between the reduction of total cholesterol and the response of vascular resistance to the cold pressure test (r = 0.853, p < 0.05). Our results demonstrate that the reduction in total plasma cholesterol may influence the haemodynamic response induced by the activation of the sympathetic system.

[Coronary effects of left ventricular hypertrophy associated with hypertension]. / Effets coronariens de l'hypertrophie ventriculaire gauche associée à l'hypertension.

Left ventricular hypertrophy secondary to hypertension has been associated with a reduction of maximum coronary flow per unit mass as shown by the increase in the minimal threshold of coronary vascular resistance per gramme. This phenomenon has usually been attributed to an increase in muscle mass with absent or inadequate vascular compensation. However, chronic hypertension may induce a function reduction in coronary flow. In particular, it has been recently shown that coronary vascular resistances are influenced by a cardio-cardiac reflex involving the baroreceptor response. Left ventricular hypertrophy could alter the function of the ventricular receptors and favourise myocardial ischemia by preventing the adaptation of coronary flow to myocardial metabolic demands.

[Dose-response study of bunazosin in the treatment of light-to-moderate arterial hypertension]. / Studio dose-risposta sulla bunazosina nel trattamento dell'ipertensione arteriosa lieve-moderata.

INTRODUCTION: The antagonists of alpha-adrenergic receptors were introduced in the therapy of arterial hypertension in 1950, but have had limited use due to the poor efficacy and safety of some drugs belonging to this pharmacological class. A recent molecule from this class, bunazosin, is a highly selective alpha 1-antagonist, whose long half-life allows a single daily administration. The aim of this study was to identify the minimum effective dose of bunazosin in the treatment of mild-moderate arterial hypertension. MATERIALS AND METHODS: Patients of both sexes, aged over eighteen years, suffering from mild/moderate essential arterial hypertension were admitted to the study. The experimental design was controlled between patients; and the study was carried out in accordance with the principles of Helsinki anf Tokyo. Dosage was of 3 and 6 mg/day per os; after 2 weeks' treatment, if DBP in clinostatism > or = 95 mmHg, the dose was doubled. Treatment lasted four weeks. RESULTS: At the end of treatment, in the group of patients initially treated with 3 mg/day, SBP, in clinostatism fell by 10.0% and DBP by 8.4% (p < 0.01 between times); in the group of patients initially treated with 6 mg/day, the reductions were of 9.2% and 6.5% respectively (p < 0.01 between times). Heart rate, electrocardiograph traces and laboratory parameters showed no clinically significant modifications. The safety profile of the treatment was excellent in 80% of the patients treated overall. DISCUSSION: This study allowed the minimum effective dose of bunazosin, equal to 3-6 mg/day, to be identified, as well as confirming the antihypertensive efficacy of the drug and its ample safety margin. In fact, this range of daily dosage led to a fall in pressure values, without causing clinically significant alterations of heart rate, electrocardiograph traces and laboratory parameters. CONCLUSIONS: In conclusions, in mild/moderate arterial hypertension, bunazosin in monotherapy at the dosage of 3-6 mg/day, is an effective and safe treatment.

[Carotid vascular structural changes and left ventricular hypertrophy]. / Alterazioni strutturali vascolari carotidee ed ipertrofia ventricolare sinistra.

In the literature there are few studies evaluating carotid vascular atherosclerotic involvement in patients with essential arterial hypertension. Nowadays with new non-invasive methodological methods, such as Doppler-echotomography, it is possible to evaluate accurately structural vascular and cardiac changes. In this study we evaluated the relationship between carotid vascular structural changes and cardiac left ventricular mass index in 15 normotensive subjects and in 15 patients with essential hypertension. We performed a B-mode echotomography (7.5 MHz) of a common carotid in order to measure the diameter of the vessel and intima-media wall thickness. In the same subjects we determined echocardiographic left ventricular mass index and we measured arterial pressure by sphygmomanometric method. There was no statistical significant difference in the two groups except that in systolic, diastolic and mean arterial pressure (96 +/- 2 vs 123 +/- 2 mmHg, p < 0.01), left ventricular mass index (102 +/- 3 vs 118 +/- 3 g/m2, p < 0.01) and in the common carotid intima media wall thickness (0.91 +/- 0.01 vs 2.23 +/- 0.02 mm). In the normotensive subject mean arterial pressure correlated significantly with age (r = 0.699) and with common carotid arterial diameter (r = 0.523) (both p < 0.05). In hypertensive patients, on the contrary, mean arterial pressure correlated with left ventricular mass index (r = 0.523), carotid arterial diameter (r = 0.627) and common carotid intima media wall thickness (r = 0.847). These results demonstrate that in hypertensive patients cardiac abnormalities accompanied vascular structural changes.

[Effects of antihypertensive treatment on carotid vascular changes]. / Effetti del trattamento antipertensivo sulle alterazioni vascolari del distretto carotideo.

The carotid artery is one of the most important sites in the progression of atherosclerotic lesions. Atherosclerosis is known to be determined by a variety of factors, among which arterial hypertension is one of the most important. Blood pressure control by antihypertensive treatment is thus of great benefit in management of atherosclerosis, particularly in view of the direct action of some classes of antihypertensive agents on atheromatous lesions. Today, modern diagnostic technique allow a non-invasive examination of the artery wall (B-mode ultrasound and pulsed-Doppler), so that early detection of structural and functional alterations is possible. In order to evaluate the efficacy of the long term blood pressure reduction in the progression and/or in the regression of cardiovascular structural abnormalities, we studied intima-media thickness and arterial compliance during one-year antihypertensive treatment with a new calcium-antagonist, lacidipine, or a diuretic hydrochlorothiazide. In both groups we observed a comparable blood pressure reduction (lacidipine: from 166 +/- 5/100 +/- 1 to 142 +/- 4/88 +/- 2 mmHg; hydrochlorothiazide: from 154 +/- 5/102 +/- 2 to 140 +/- 4/88 +/- mmHg; both p < 0.01). On the contrary, only in patients treated with lacidipine did we obtain a significant improvement in carotid blood flow (383 +/- 16 vs 411 +/- 16 ml/min p <) and in arterial compliance (0.8 +/- 0.1 vs 1.2 +/- 0.2 cm/dyne p < 0.01). Indeed, we observed a different behaviour of the intima-media thickness in the two groups (lacidipine: 1.11 +/- 1.4 vs 1.13 +/- 1.5 mm n.s.; hydrochlorothiazide: 1.15 +/- 0.15 vs 1.21 +/- 0.17 mm p < 0.06). Our results demonstrate that an effective antihypertensive treatment with calcium antagonists may influence the progression of carotid vascular abnormalities.

Recovery systolic blood pressure response after treadmill exercise procedures. Evidence against its usefulness in detecting coronary artery disease.

We compared the response of the systolic blood pressure (SBP) recovery ratio (obtained by dividing the SBP recovery values by the peak exercise values) during a treadmill exercise test in patients with chest pain and an angiographically normal coronary tree (n = 18) (C group), one or more greater than or equal to 70% stenosed major coronary vessel and normal resting ejection fraction (n = 26) (CAD group) or depressed left ventricular function (ejection fraction less than 40%) (n = 15) (CAD DYS group). The mean values of SBP recovery ratios were, in the three groups: 0.93 +/- 0.07, 0.97 +/- 0.07, 0.95 +/- 0.09, respectively, at the 1st min and 0.83 +/- 0.08, 0.88 +/- 0.09, 0.86 +/- 0.08, at the 3rd min. There are no significant differences in the CAD or CAD DYS group versus the C group, because of large overlapping of points in the plot. The post-exercise SBP response during treadmill procedures cannot provide the opportunity for differentiation of CAD patients with or without left ventricular dysfunction at rest from subjects with chest pain and normal coronary tree, while upright bicycle exercise, as we previously observed, can.

Trandolapril in patients with essential hypertension: effects on vascular and cardiac structural changes.

Elevated arterial pressure levels increase the hemodynamic load on heart and vessels, thus leading to functional and structural abnormalities. Because cardiac and vascular changes increase the risk of cardiovascular disease, their reversal is an important target of antihypertensive therapy, even though the prognostic value of this regression has not been fully established. In patients with untreated mild-to-moderate essential hypertension and left ventricular hypertrophy, trandolapril, a new angiotensin-converting enzyme inhibitor, reduces blood pressure by decreasing total peripheral resistance and improves both systolic and diastolic ventricular function. The latter effect is not only functional in nature because, after long-term antihypertensive treatment, the improvement in diastolic ventricular function is detectable also after 1-month withdrawal of trandolapril. The concurrent reversal of left ventricular hypertrophy may contribute to the improved left ventricular diastolic function. However, plethysmographic studies suggest that long-term antihypertensive treatment with trandolapril is also able to reverse structural vascular changes in the forearm vascular bed, because after 1-month washout forearm peripheral resistance also is lower than in control conditions. Finally, in hypertensive patients, trandolapril induces significant increases in brachial artery compliance and diameter that persist after 1 month of withdrawal from treatment. The latter observation suggests that trandolapril also is able to reverse the structural changes of the large artery wall.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of the single and repeated administration of benazepril on systemic and forearm circulation and cardiac function in hypertensive patients.

The hemodynamic and cardiac effects of the new angiotensin-converting enzyme inhibitor, benazepril, were studied in 28 hypertensives in a double blind, placebo-controlled, between-patient study. Hemodynamic studies were performed noninvasively by means of M-mode echo (central hemodynamics and left ventricular systolic function), 2-D echo-Doppler (left ventricular diastolic function), and pulsed Doppler flowmetry (forearm circulation). Examinations were done at the end of a placebo run-in period and 3 hours after benazepril administration, both on the first day and after 6 weeks of treatment (10 or 20 mg once daily, according to patient response). In comparison with placebo, benazepril reduced systolic (p = 0.04) and diastolic (p = 0.003) blood pressure, because of a significant reduction in systemic vascular resistance (p = 0.03), while cardiac output was unchanged. Forearm vascular resistance was reduced and brachial artery compliance increased, although not to a statistically significant level (both p = 0.07). Both systolic and diastolic left ventricular function were positively influenced by the afterload reduction: End-systolic stress was reduced by 12% (p = 0.07), as was the late diastolic peak flow velocity (p = 0.02). All hemodynamic changes were evident after acute benazepril administration, and no differences was observed between acute and repeated treatment. We conclude that, similar to other ACE-inhibitors, benazepril reduces blood pressure through a reduction in vascular resistance, while cardiac output and heart rate are unaffected. These hemodynamic effects occur as early as after the first administration and exert a favorable influence on left ventricular dynamics.

[The early hemodynamic and hormonal changes in patients with left ventricular dysfunction]. / Alterazioni emodinamiche ed ormonali precoci in pazienti con disfunzione ventricolare sinistra.

The aim of this study was to highlight a different hormonal and hemodynamic pattern in patients with mild cardiomyopathy. For this purpose, we studied subjects with mild heart failure (CHF; NYHA class I and II; post-ischemic and idiopathic) who underwent an isotonic saline load (SL) (0.22 ml/kg/min of 0.9% NaCl for 120 min). A second group of age- and sex-matched normal subjects (C) was studied as a control. Basal hormonal and hemodynamic values of the 2 groups differed only in atrial natriuretic factor (ANF), left ventricular end-diastolic diameter and ejection fraction (EF). There were, on the contrary, no differences in basal plasma renin activity (PRA) and plasma aldosterone (PA) values. After SL, in C, percent changes in EF, cardiac output and ANF values were significantly higher than in CHF while total peripheral resistances increased only in CHF but not in C. In both groups there were decrements of PRA and PA, but these responses were significantly higher in C than in CHF. In conclusion, our results show that hormonal, renal and hemodynamic responses to salt/volume load are compromised in the early asymptomatic phase of heart failure. These abnormalities may predict the progressive deterioration of cardiac function, and may indicate appropriate therapeutic interventions since the early phases of the disease.

Effects of nisoldipine and/or enalapril on left ventricular function and exercise capacity in patients with recent anterior myocardial infarction and mild cardiac dysfunction.

Treatment of abnormal remodeling and dysfunction of left ventricle after myocardial infarction is one of the major goals of recent therapeutic interventions. The current study, the Nisoldipine Enalapril Anterior Myocardial infarction Study pilot investigation, was designed to investigate the effects of 12 weeks of treatment with enalapril or nisoldipine or their combination on left ventricular (LV) function and exercise capacity in patients with recent (< 1 month) anterior myocardial infarction and mild LV dysfunction (LV ejection fraction [EF] 38% to 48%). Forty-six patients were studied and received, by random assignment, enalapril (5 mg once per day) plus placebo (n = 14) or nisoldipine (10 mg two times per day) plus placebo (n = 18) or enalapril (5 mg once per day) plus nisoldipine (10 mg two times per day) (n = 14). All patients received aspirin (325 mg) throughout the study. Data on LV EF and peak filling rate at rest and LV EF during exercise were collected during radionuclide ventriculography. In addition, the product of heart rate and systolic blood pressure (rate-pressure product) and exercise time were determined during exercise stress testing. The analyzed parameters were not significantly modified after treatment with enalapril or with nisoldipine. In contrast, the combination of enalapril and nisoldipine significantly raised LV EF at rest (from 43% +/- 3% to 48% +/- 6%, p < 0.01) and during exercise (from 45% +/- 8% to 50% +/- 9%, p < 0.01) and raised peak filling rate at rest (fraction of end-diastolic volume per second) from 1.57 +/- 0.3 to 1.67 +/- 0.3 (p < 0.05). In addition, the combined administration of the two drugs increased the rate-pressure product (values x 10(3)) (from 20.7 +/- 5 to 22.7 +/- 4, p < 0.05) and increased exercise time (from 573 +/- 173 seconds to 668 +/- 178 seconds, p < 0.05). These results show that in patients with recent anterior myocardial infarction and mild LV dysfunction, the combination of the angiotensin-converting enzyme inhibitor enalapril and the dihydropyridine nisoldipine improves resting LV systolic and diastolic function and exercise LV systolic function and exercise capacity.

Indapamide reduces hypertensive left ventricular hypertrophy: an international multicenter study.

The effect of 6 months of treatment with indapamide (IND, 2.5 mg/day) on regression of left ventricular hypertrophy (LVH), an independent predictor of poor prognosis in hypertension, was compared by echocardiography to that of nifedipine (NFD, 40 mg/day), enalapril (ENL, 20 mg/day), atenolol (ATL, 100 mg/day), and hydrochlorothiazide (HCTZ, 25 mg/day) in four parallel double-blind studies in 151 hypertensive patients with a diastolic blood pressure between 95 and 120 mm Hg and a raised left ventricular mass index (LVMI) (mg/m2) (Devereux). Patients were randomized to IND or comparator following a 2-week washout (1 month in the IND vs. ATL study). Respective baseline and 6-month LVMI values (mg/m2) were: IND (n = 20) vs. HCTZ (n = 20): 151.4 +/- 6.3 and 125.70 +/- 4.6 (p < 0.001) vs. 141.3 +/- 6.6 and 135.6 +/- 8.3 (p = N.S.); IND (n = 22) vs NFD (n = 19): 144.1 +/- 5.3 and 125.1 +/- 4.3 (p < 0.001) vs. 170.4 +/- 6.6 and 148.2 +/- 6.2 (p < 0.001); IND (n = 9) vs. ENL (n = 9): 155.1 +/- 6.3 and 143.4 +/- 5.2 (p < 0.001) vs. 142.0 +/- 6.7 and 130.0 +/- 5.9 (p < 0.001); IND (n = 17) vs. ATL (n = 12): 146.2 +/- 5.1 and 130.8 +/- 6.5 (p < 0.001) vs. 156.7 +/- 8.4 and 142.9 +/- 10.3 (p < 0.01). All drugs significantly reduced diastolic blood pressure, and all except HCTZ induced a significant and similar reduction in left ventricular mass.