Luigi Argenziano

Haemodynamic and metabolic effects of rilmenidine in hypertensive patients with metabolic syndrome X. A double-blind parallel study versus amlodipine

Objective To compare the effects of rilmenidine with those of amlodipine on blood pressure, glucose metabolism, plasma lipid concentration and fibrinolysis parameters. Design A four-month randomized double-blind, parallel group study. Patients and methods Obese hypertensive patients with hypertriglyceridaemia (≥ 2.3 mmol/l) and impaired glucose tolerance (OMS-ADA) were included (n = 52). A placebo run-in period of 2 weeks was followed by 4 months of double-blind treatment with either rilmenidine or amlodipine. Blood pressure was recorded using a mercury sphygmomanometer. Glucose metabolism was evaluated by an oral glucose tolerance test. Results Of the 52 patients recruited, 47 (21 rilmenidine and 26 amlodipine) completed the 4-month treatment period. The intention-to-treat analysis showed a comparable reduction in systolic and diastolic blood pressure (SBP, DBP) with the two anti-hypertensive treatments (rilmenidine –13.9/–13.5 mmHg; amlodipine —17.6/–15.0 mmHg). Insulin concentrations under basal conditions and 2 h after a standard oral glucose load did not change significantly after treatment in both groups. Plasma glucose under basal conditions and 2 h after a standard oral glucose load as well as the area under the plasma glucose concentration curve tended to decrease in the rilmenidine group and to increase in the amlodipine group so that the changes in these parameters were significantly different between the two study groups (P = 0.041, P = 0.042 and P = 0.015, respectively). Plasminogen activator inhibitor type 1 (PAI-1) antigen and PAI-1 activity were only decreased in the rilmenidine group (not statistically significant). Conclusion Our results demonstrate that rilmenidine and amlodipine have a comparable anti-hypertensive effect but only rilmenidine is able to improve glucose metabolism.

Technetium 99m-labeled tetrofosmin myocardial tomography in patients with coronary artery disease: Comparison between adenosine and dynamic exercise stress testing

BackgroundPharmacologic coronary vasodilation with adenosine, combined with myocardial scintigraphy, is a useful test for the diagnosis of coronary artery disease (CAD) in patients unable to exercise. It has been demonstrated recently that exercise 99mTc-labeled tetrofosmin cardiac imaging can be used for the detection of CAD. However, no data are available comparing 99mTc-labeled tetrofosmin adenosine and exercise tests in the same patients.Methods and ResultsThe results of adenosine and exercise 99mTc-labeled tetrofosmin myocardial tomography were compared in 41 patients (37 men and four women; mean age 53±8 years) with suspected or known CAD who underwent coronary angiography. All patients were submitted, on separate days, to three injections of 99mTc-labeled tetrofosmin (740 MBq intravenously): one at rest, one during bicycle exercise, and one during adenosine infusion (140 μg/kg/min for 6 minutes with injection of 99mTc-labeled tetrofosmin at 4 minutes). A total of 902 myocardial segments were analyzed quantitatively. One patient had normal coronary vessels, 19 patients had single-vessel CAD, 12 patients had two-vessel CAD, and nine patients had three-vessel CAD (>50% coronary stenosis) on coronary angiography. Adenosine induced a significant increase in heart rate (88±16 beats/min at peak vs 72±11 beats/min at rest; p<0.01). Systolic and diastolic blood pressure was not significantly different after adenosine infusion compared with rest. Double product was 22931 ± 7039 at peak exercise and 11229±3413 after adenosine (p<0.01). Agreement on the presence of abnormal single-photon emission computed tomography by adenosine and exercise was 100% by quantitative analysis. In all segments a significant relationship between exercise and adenosine 99mTc-99m-labeled tetrofosmin uptake was observed (r=0.90; p<0.001). Segmental agreement for regional 99mTc-labeled tetrofosmin uptake score between exercise and adenosine was observed in 737 (82%) of the 902 segments (kappa value of 0.66). Concordance between the two studies for identification of perfusion status was observed in 809 (90%) of the segments (kappa value of 0.80). Sensitivity and specificity for detection of stenosed vessels were not different for dynamic exercise stress testing and adenosine 99mTc-labeled tetrofosmin cardiac tomography.ConclusionsDespite different hemodynamic effects, adenosine and dynamic exercise 99mTc-labeled tetrofosmin single-photon emission computed tomographic imaging provides similar information in the diagnosis and localization of CAD.

Adenosine coronary vasodilation quantitative technetium 99m methoxy isobutyl isonitrile myocardial tomography in the identification and localization of coronary artery disease

BackgroundExercise and dipyridamole 99mTc-labeled methoxy isobutyl isonitrile (MIBI) myocardial scintigraphy have been widely used for the diagnosis of coronary artery disease (CAD). However, only limited data on adenosine 99mTc-labeled MIBI cardiac imaging are currently available. This study was designed to assess the accuracy of quantitative adenosinerest 99mTc-labeled MIBI tomography in the diagnosis and localization of CAD.Methods and ResultsFifty-seven consecutive patients with suspected CAD who underwent coronary angiography and 22 normal volunteers were studied. All patients underwent 99mTc-labeled MIBI tomography after administration of adenosine (140 μg/kg intravenously for 6 minutes) and at rest. A total of 171 vascular coronary territories were analyzed quantitatively. All patients with CAD (≥50% luminal stenosis) (n=55) had abnormal 99mTc-labeled MIBI tomograms. The normalcy rate was 86% by quantitative analysis. Overall sensitivity, specificity, and diagnostic accuracy for detection of individual stenosed vessels were 84%, 87%, and 85%, respectively. In patients with one-vessel CAD (n=24), sensitivity and diagnostic accuracy in the detection of individual stenosed vessels were significantly (p<0.05) higher compared with patients with multivessel CAD (n=31). Moreover, 75% of patients with one-vessel disease showed a scintigraphic pattern characterized by the presence of perfusion defects in only one coronary artery territory, and 74% of patients with multivessel disease showed a scintigraphic pattern characterized by the presence of perfusion defects in two or more coronary artery territories. Sensitivity, specificity, and diagnostic accuracy for detecting individual diseased vessels were similar in patients without previous myocardial infarction (n=18) compared with those with previous myocardial infarction (n=39). In myocardial territories related to noninfarcted areas (n=124), sensitivity and specificity in the detection of stenosed vessels were 75% and 88%. In infarcted areas (n=47), sensitivity and specificity in the detection of stenosed vessels were 98% and 80% (differences not significant vs noninfarcted areas).ConclusionsAdenosine-controlled coronary vasodilation combined with quantitative 99mTc-labeled MIBI tomography is accurate for identifying patients with CAD and localizing individual stenosed coronary arteries.

Distinct Vasodilation, without Reflex Neurohormonal Activation, Induced by Barnidipine in Hypertensive Patients

Barnidipine is a new 1,4-dihydropyridine calcium antagonist with a strong and long-lasting vasodilatory effect. In order to assess the haemodynamic profile of the antihypertensive effect of barnidipine, a randomized, double-blind study of barnidipine vs nitrendipine was performed in 24 patients with mild to moderate essential hypertension. Following an initial 4-week placebo period, patients whose sitting diastolic blood pressure (SiDBP) was between 95 and 114 mm Hg, and whose sitting systolic blood pressure was between 150 and 219 mm Hg, were randomized (2:1 ratio) to receive either barnidipine (10 mg) or nitrendipine (10 mg) once daily, for a 6-week double-blind period. Subsequently, patients with an SiDBP of less than 90 mm Hg continued for a second 6-week period with the same monotherapy, while patients with an SiDBP of 90 mm Hg or above received double the dose of antihypertensive treatment for the next 6 weeks. Two-dimensional M- and B-mode echocardiography with Doppler flowmetry was performed at the end of both the placebo and active treatment phases. Barnidipine and nitrendipine reduced blood pressure by the same degree (barnidipine: from 165 +/- 2/100 +/- 1 to 145 +/- 2/89 +/- 1 mm Hg, p < 0.01; nitrendipine: from 163 +/- 3/100 +/- 2 to 143 +/- 7/90 +/- 3 mm Hg, p < 0.01) as a result of peripheral vasodilation. This was not accompanied by reflex neurohormonal activation. Moreover, only in the group receiving barnidipine was a significant decrease in plasma noradrenaline observed, both when the patients were in the supine position (from 298 +/- 27 to 214 +/- 21 pg/ml, p < 0.05) and when they were upright (from 472 +/- 37 to 348 +/- 38 pg/ml, p < 0.05).

Lisinopril in the Treatment of Congestive Heart Failure in Elderly Patients: Comparison versus Captopril

The present study was performed in order to compare the efficacy, safety, and tolerability of lisinopril, a long-acting angiotensin-converting enzyme (ACE) inhibitor, with captopril, the shorter acting ACE inhibitor available, in the treatment of elderly patients (mean age 70 ± 0.5 years) with congestive heart failure (mean left ventricular ejection fraction 33.5 ± 1%). The study was organized according to a double-blind, parallel-group, randomized multicenter protocol. After a 14-day placebo run-in period, patients were randomized to receive either lisinopril 5 mg orally once per day or captopril 12.5 mg orally once per day. The dose of the study drug could be doubled at 2-week intervals for 6 weeks. The maximal dose was lisinopril 20 mg once per day or captopril 25 mg twice per day. The addition of either captopril or lisinopril to a regimen of diuretics caused a significant increase in exercise tolerance assessed by bicycle ergometry after 12 weeks of treatment (530 ± 21 seconds vs. 431 ± 13 seconds, p < 0.01; 555 ± 19 seconds vs. 463 ± 12 seconds, p < 0.01, respectively). Both drugs significantly increased left ventricular ejection fraction and stroke volume, were equally effective in improving NYHA class, and were well tolerated, with no differences detectable between treatments. The results of this study indicate that lisinopril 5–20 mg once daily is at least as effective and well tolerated as captopril 12.5–50 mg daily in the treatment of elderly patients with congestive heart failure.

Assessment of systolic wall thickening using technetium-99m methoxyisobutylisonitrile in patients with coronary artery disease: relation to thallium-201 scintigraphy with re-injection

The results of resting planar ECG-gated technetium-99m methoxyisobutylisonitrile (99mTc-MIBI) imaging were compared with those of thallium-201 (TI) reinjection after exercise-redistribution scintigraphy in 20 patients (19 men, 1 woman, mean age 53±10 years) with angiographically proven coronary artery disease. Eight normal subjects (seven men, one woman, mean age 50±8 years) constituted the control group. In these subjects, only resting99mTc-MIBI imaging was performed. The standardized percent count increase from end-diastole to end-systole was calculated as an index of wall thickening in 13 segments for each study. Regional wall thickening index (WTI) and99mTc-MIBI uptake were significantly different (P<0.05) among segments classified as normal, reversible defects, irreversible defects with increased tracer uptake after re-injection (Re+) or irreversible defects with unchanged tracer uptake after re-injection (Re-) on TI imaging. Furthermore, WTI and99mTc-MIBI uptake were significantly higher (P<0.05) in Resegments with moderate reduction of T1 uptake (≥50% of peak activity) than in Re- segments with severe reduction of TI uptake (<50% of peak activity). A significant relationship between WTI and the results of TI scintigraphy was observed (rho=0.71,P<0.0001). The percentage of Re- segments with severe reduction of WTI was significantly higher compared to Re+ segments (64% vs 3%,P<0.01). Furthermore, compared with moderate Re- segments, a significantly higher percentage of severe Re- segments showed a severe reduction of WTI (86% vs 48%,P<0.01). Our data document a close relationship between99mTc-MIBI regional wall thickening, myocardial perfusion and TI uptake after reinjection. The results of this study suggest that regional WTI decreased significantly as myocardial perfusion decreased. In addition, regional wall thickening was preserved in segments with exercise-induced ischaemia and enhanced TI uptake after re-injection.

Rilmenidine in patients with left ventricular hypertrophy : Beyond the reduction of left ventricular mass

It is generally accepted that the development of left ventricular hypertrophy (LVH) represents a multifactorial phenomenon that also involves neurohormonal mechanisms. This finding may account for the ability of angiotensin-converting enzyme inhibitors to induce faster and more complete reversal of LVH than that observed with other antihypertensive treatments. The sympathetic system is also involved in the genesis of hypertension-induced LVH. We assessed the effects of satisfactory long-term treatment with rilmenidine, a new oxazoline with a potent antihypertensive action, on cardiovascular structural abnormalities and cardiac endocrine function in hypertensive patients with left ventricular hypertrophy. Eleven patients underwent M-mode and two-dimensional Doppler echocardiography, peripheral pulsed Doppler flowmetry, determination of plasma atrial natriuretic factor [(ANF) pg/ml] and renin activity, and 24-h urine electrolyte excretion under control conditions, after 4 weeks of blood pressure normalization, after 1 year of satisfactory antihypertensive treatment and, finally, 4 weeks after therapy withdrawal. I.VH (g/m2 body surface area) was reversed after 1-year treatment (from 152 +/- 5 to 131 +/- 4, p < 0.05). One-year treatment induced an improvement in brachial artery compliance (cm4/dyne.10(7)) (from 0.92 +/- 0.06 to 1.16 +/- 0.08, p < 0.05) that persisted after withdrawal of treatment (1.17 +/- 0.06, p < 0.05). Plasma renin activity and urinary electrolyte excretion did not change throughout the study, whereas ANF remained unchanged after blood pressure normalization (48.4 +/- 6.2 versus 44.7 +/- 2.9, NS), fell after reversal of LVH (28.6 +/- 3.4, p < 0.05), and remained significantly lower than under control conditions after therapy withdrawal (27.5 +/- 2.9, p < 0.05). These results demonstrate that a satisfactory long-term antihypertensive treatment with rilmenidine is able to reverse cardiovascular structural changes and to restore cardiac endocrine function.

Benefits of combination therapy in hypertensive patients with associated Coronary Artery Disease: A subgroup with specific demands

Although prevention of coronary artery disease (CAD) is one of the main goals of antihypertensive therapy, when first seen hypertensive patients often have associated CAD. These patients need a therapy that can exert an acute anti-ischemic action, such as ad hoc relief of angina pectoris, and can also reduce the incidence of myocardial infarction (MI) or reinfarction. Reduction in blood pressure (BP) alone does not appear to be adequate because in hypertensive patients CAD is a complex and multifactorial process involving not only hemodynamic, neurohormonal, and metabolic factors but also hypertension-induced myocardial and vascular structural changes, which appear independently to contribute to risk for CAD. In theory, antihypertensive combination therapy, by summing the different effects of various drugs, appears to have a greater capacity for comprehensive management of hypertensive patients with CAD. Simultaneous administration of angiotensin-converting enzyme (ACE) inhibitors and calcium-channel blockers appears to be particularly effective. In several clinical trials with long-term follow-up, ACE inhibitor therapy has been associated with a substantial reduction in the risk for major ischemic events. The antiproliferative action of ACE inhibitors on myocardium and the vascular wall, their hemodynamic effects, antiatherogenic actions, neurohormonal attenuation, and certain genetic issues may account for the ability of this class of drugs to reduce the risk for CAD-related events. Although ACE inhibitors can be expected to increase coronary blood flow when the renin-angiotensin system is activated and to reduce BP, ventricular filling pressure, and sympathetic drive, thus far an acute anti-ischemic action of these drugs has not been demonstrated. Unlike ACE inhibitors, which usually have class-specific effects, there are important differences in the clinical effects of various calcium antagonists. The first generation of dihydropyridine calcium-entry blockers has failed to demonstrate efficacy in secondary prevention of coronary artery events. However, verapamil reduces mortality in patients with normal left ventricular function. The antihypertensive efficacy of verapamil, its antiatherogenic action, and its ability to reverse left ventricular hypertrophy, to improve diastolic function, and to interfere with endothelium-derived contracting factors may also account for the improved survival of patients with CAD treated with this drug. Moreover, verapamil is also effective in the treatment of all types of angina because it reduces myocardial oxygen consumption as a result of its hypotensive effect and its ability to reduce heart rate, and it may also improve oxygen delivery to the myocardium because of its action on coronary vasodilatation. It is also important to consider that ACE inhibitors and calcium antagonists often induce the same beneficial effects through different mechanisms, thus allowing a synergistic action when the two classes of drugs are administered together.

Effects of nitrendipine on plasma levels of insulin and glucose in patients with essential hypertension

Abstract In this randomized, double-masked, parallel-group study we assessed the effects of the calcium-channel blocker nitrendipine (10 or 20 mg) and placebo on blood pressure, glucose tolerance, and plasma insulin and cholesterol levels in 24 patients (17 men and 7 women; mean age, 44 ± 6 years) with mild-to-moderate essential hypertension. The basal insulin plasma level and the level after administration of an oral glucose load of 75 g were determined before and after the 16-week study. Patients in the nitrendipine group showed a significant decrease in sitting and standing blood pressures (from 165 ± 9.6/103 ± 6 mm Hg to 144 ± 19/91 ± 7 mm Hg and from 163 ± 7/103 ± 4 mm Hg to 144 ± 15/95 ± 7 mm Hg, respectively). Plasma glucose concentration in the nitrendipine group decreased significantly at 90 (140 ± 13 vs 183 ± 9 mg/dL, P P P

Effects of angiotensin converting enzyme inhibitors on left ventricular hypertrophy

SummaryIt is well known that, in patients with essential hypertension, left ventricular hypertrophy (LVH) is an independent risk factor for cardiovascular disease. However, it has been demonstrated that normalisation of arterial pressure, by therapy with antihypertensive drugs, is associated with regression of LVH, although the extent and time-course of this phenomenon depend on the antihypertensive drug used. In particular, angiotensin converting enzyme (ACE) inhibitors seem capable of inducing a faster and more complete reversal of LVH in patients with essential hypertension than other antihypertensive drugs.The mechanisms underlying this property of ACE inhibitors remain unclear, although 2 features of ACE inhibitors may be particularly relevant. The first is their ability to improve large artery compliance, this being a major determinant of LVH. Arterial compliance is reduced in essential hypertension, resulting in increased left ventricular end-systolic stress, which then contributes to the development of LVH. The second possible mechanism by which ACE inhibitors reverse LVH to a greater degree than other antihypertensive drugs may relate to their ability to interfere with the cardiopulmonary receptor control of the circulation.Thus, ACE inhibitors may counteract the neural and hormonal abnormalities that contribute to the maintenance of LVH in hypertensive patients.