Biomedical subjects

F Zannad

Publications and source records attributed to F Zannad.

At least 73 records · Page 4Linked to original sources

PubMed1998

Abnormal transoesophageal Doppler coronary flow reserve in patients with dilated cardiomyopathy: relationship to exercise capacity.

1. In patients with dilated cardiomyopathy, abnormal myocardial blood flow may contribute to poor myocardial function. 2. The aim of this study was to investigate the possible contribution of abnormal myocardial blood flow to the limitation of exercise capacity in patients with dilated cardiomyopathy. 3. Coronary flow reserve was assessed in 16 patients with dilated cardiomyopathy and 9 matched normal control individuals. All participants had angiographically normal coronary arteries. At rest and after dipyridamole infusion (0.56 mg/kg intravenously), peak systolic and diastolic coronary flow velocities were measured in the proximal left anterior descending coronary artery using transoesophageal pulsed Doppler echocardiography, guided by colour flow imaging. Coronary flow reserve was calculated as the ratio of hyperaemic to basal diastolic and systolic peak coronary flow reserve. 4. Baseline diastolic and systolic coronary flow velocities were significantly higher in patients (50 +/- 6 and 30 +/- 4 cm/s respectively) compared with control individuals (37 +/- 3 and 20 +/- 1 cm/s respectively) (mean +/- S.E.M.) (P < 0.05). Diastolic and systolic peak coronary flow reserve were significantly lower in patients (1.60 +/- 0.14 and 1.40 +/- 0.09 respectively) compared with control individuals (2.89 +/- 0.15 and 2.17 +/- 0.17 respectively) (P < 0.001). Although peak VO2 and exercise time were significantly lower in patients compared with control individuals, coronary flow reserve did not correlate to exercise capacity in patients with dilated cardiomyopathy. 5. These results confirm the abnormalities of coronary flow reserve previously observed in patients with dilated cardiomyopathy, but suggest that such abnormalities do not contribute to the limitation of exercise capacity in these patients.

Blood Flow Velocity↗

PubMed1998

Intima-media thickness and diameter of carotid and femoral arteries in children, adolescents and adults from the Stanislas cohort: effect of age, sex, anthropometry and blood pressure.

OBJECTIVES: To study carotid and femoral intima-media thicknesses and diameters in relation to age, sex, morphologic status and blood pressure. PARTICIPANTS: The subjects were 369 men and women (aged 10-54 years) from the Stanislas cohort, with no known cardiovascular disease. METHODS: Intima-media thicknesses and diameters were measured by B-mode ultrasonography. The effects of sex, age, smoking, anthropometric variables, cholesterol and blood pressure were studied using bivariate and regression analysis. RESULTS: Carotid and femoral intima-media thicknesses were not affected by age nor by sex up to 18 years of age. Thereafter, they increased sharply in men and remained higher than in women. Values were correlated with systolic blood pressure only in men, and with fat-free mass in children and young adults only at the femoral site. Smoking, body mass index and fat mass were associated with intima-media thicknesses only in adults. Carotid diameter was little affected by age during childhood and in adults. Femoral diameter increased up to the age of 18 in both sexes and remained unaffected by age thereafter. This increase was more pronounced in boys, and so values became consistently greater in males aged over 14 years. Carotid diameter was correlated with body mass index or fat mass whereas femoral diameter was correlated with weight or fat-free-mass in children and men. The opposite was observed in women. CONCLUSION: Sex differences occur before adolescence for arterial diameter, but only at an adult age for intima-media thickness. In young subjects, carotid geometry seems to be influenced by blood pressure and excess body weight, while femoral artery geometry seems to be related to blood pressure and body growth.

Adolescent↗

PubMed1998

Shear stress abnormalities contribute to endothelial dysfunction in hypertension but not in type II diabetes.

BACKGROUND: The relative contribution of the various hemodynamic and metabolic mechanisms leading to endothelial dysfunction may be different in specific vascular diseases. Since shear stress is one of the main mechanical stimuli of endothelial cells, the aim of this study was to investigate its contribution to endothelial dysfunction in two distinct vascular diseases, hypertension and type II diabetes. SUBJECTS AND METHODS: We measured the radial artery diameter at baseline, after ischemic vasodilation and after nitroglycerin vasodilation in 16 untreated patients with high blood pressure, in 15 type II normotensive diabetic patients and in 17 healthy controls. Wall shear stress was evaluated by simultaneous measurements of whole blood viscosity and blood flow velocity. RESULTS: In diabetic patients, whole blood viscosity was significantly higher whereas wall shear stress was similar compared to controls. In hypertensive patients, whole blood viscosity was higher and wall shear stress was lower than in controls. Endothelium-dependent vasodilation was impaired in both hypertensive and diabetic patients (P < 0.01) after adjustment for age, sex, body mass index and postnitroglycerin vasodilation. When adjustments were made for maximal systolic shear stress, endothelium-dependent vasodilation remained lower in the diabetic patients (P < 0.01), but not in those with high blood pressure compared to controls. CONCLUSIONS: In hypertension, endothelium-dependent vasodilation is mainly due to a chronic decrease in shear stress (the most important physiological stimulus of the endothelial cells) with no major intrinsic endothelial cell dysfunction. In contrast, in diabetics, the lower endothelium-dependent vasodilation was not the result of an altered shear stress.

Adult↗

PubMed1998

Physical activity, skeletal muscle beta-adrenoceptor changes and oxidative metabolism in experimental chronic heart failure.

In chronic heart failure (CHF), changes in sympathetic nervous activity and skeletal muscle metabolism contribute to a limitation in the capacity for exercise. The aim of this study was to investigate the potential relationships between physical deconditioning, skeletal muscle beta-adrenoceptor (beta-AR) characteristics and muscle metabolic changes in rats with coronary ligation-induced experimental CHF. Muscle beta-AR and norepinephrine levels were assessed in rats with CHF that had been treated with propranolol at 28 mg/kg/day and compared with rats with CHF that had not been treated and those that had undergone sham operations. The soleus muscle was investigated because of its predominantly oxidative fibre-type composition. Measurements of spontaneous locomotion activity were carried out using telemetry. After 85 days, muscle energetic phosphate levels were assessed using 31P-magnetic resonance spectroscopy. The phosphocreatine resynthesis rate was decreased in the untreated CHF rats (15 +/- 3 vs 33 +/- 5 mmol L-1 min-1 in the sham-operated rats, p < 0.05), but this had been partially reversed in the rats given propranolol (22 +/- 3 mmol L-1 min-1, non-significant (NS) when compared with the sham-operated rats). Spontaneous activity did not differ among the three groups of animals. Soleus beta-adrenoceptor density was decreased in rats with CHF (8.8 +/- 3.0 fM/mg of protein vs 22.0 +/- 7.0 fM/mg of protein in the sham-operated rats, p < 0.05) and normalized in the propranolol-treated rats (31.9 +/- 7.0 fM/mg of protein, NS vs the sham-operated rats; p < 0.05 vs the untreated rats with CHF). Unchanged spontaneous activity in the rats with CHF suggests that physical deconditioning could not account for the muscle metabolic changes. Changes in skeletal muscle energy metabolism were accompanied by changes in beta-AR density, occurring in typically oxidative beta-AR-rich muscles, reversible after beta-blocker therapy and therefore suggestive of beta-AR downregulation.

Adrenergic beta-Antagonists↗

PubMed1998

Calcium antagonists and thiazide diuretics have opposite effects on blood rheology and radial artery compliance in arterial hypertension: a randomized double-blind study.

In addition to their effects on blood pressure, antihypertensive agents may produce additional effects on blood rheology and arterial compliance abnormalities which may play a role in target-organ damage. However, these effects may depend only on the specific pharmacological properties of certain antihypertensive agents, and may be partly unrelated to blood pressure lowering action. We compared the effects of nitrendipine 20 mg once daily to hydrochlorothiazide 25 mg once daily in 33 mildly to moderately hypertensive and otherwise healthy patients, in a double blind parallel group trial. Blood rheology (blood fibrinogen and protein concentrations, hematocrit, plasma viscosity and whole blood viscosity at shear rates 0.2 to 128 s-1, erythrocyte deformability and aggregation) and radial artery diameter and compliance (Nius I + Finapres) were measured at baseline and after 2 months of treatment. Both drugs produced similar blood pressure lowering. Blood viscosity increased for all shear rates in the hydrochlorothiazide group and decreased in the nitrendipine treated group. Erythrocyte deformability increased in the nitrendipine but not in the thiazide group. Radial artery diameter and compliance were not different between the two groups but there was a trend towards an increase in cross-sectional compliance in the hydrochlorothiazide group and towards a decrease in the nitrendipine group. Our data show that, in mildly hypertensive patients, blood pressure control by nitrendipine produced more favourable effects on relevant rheological variables than hydrochlorothiazide. Radial artery compliance changes tended to be altered also in opposite directions by the two agents. The significance and the clinical relevance of these effects may require further investigations.

Antihypertensive Agents↗

PubMed1997

A randomized controlled trial of epoprostenol therapy for severe congestive heart failure: The Flolan International Randomized Survival Trial (FIRST).

This trial evaluated the effects of epoprostenol on patients with severe left ventricular failure. Patients with class IIIB/IV congestive heart failure and decreased left ventricular ejection fraction were eligible for enrollment if angiography documented severely compromised hemodynamics while the patient was receiving a regimen of digoxin, diuretics, and an angiotensin-converting enzyme inhibitor. We randomly assigned 471 patients to epoprostenol infusion or standard care. The primary end point was survival; secondary end points were clinical events, congestive heart failure symptoms, distance walked in 6 minutes, and quality-of-life measures. The median dose of epoprostenol was 4.0 ng/kg/min, resulting in a significant increase in cardiac index (1.81 to 2.61 L/min/m2), a decrease in pulmonary capillary wedge pressure (24.5 to 20.0 mm Hg), and a decrease in systemic vascular resistance (20.76 to 12.33 units). The trial was terminated early because of a strong trend toward decreased survival in the patients treated with epoprostenol. Chronic intravenous epoprostenol therapy is not associated with improvement in distance walked, quality of life, or morbid events and is associated with an increased risk of death.

Aged↗

PubMed1997

Effects of blood pressure control on radial artery diameter and compliance in hypertensive patients.

The radial artery compliance may be paradoxically increased in untreated arterial hypertension. However, the effect of blood pressure normalization on the radial artery compliance is not well known. We performed a cross-sectional study in order to investigate the effects of blood pressure control on the radial artery diameter and compliance (echotracking and digital photoplethysmography) by comparing these variables in a group of untreated hypertensive patients and in another group of adequately treated hypertensive patients as well as in a group of healthy normotensive subjects. All groups were sex- and age-matched. Radial artery internal diameter was increased in both untreated hypertensive patients and effectively treated hypertensive patients comparatively to controls. Cross-sectional compliance and volumic distensibility were not different between groups. As compared to controls (2.85 +/- 0.39 x 10(-3) mm2 x mm Hg(-1) and 0.42 +/- 0.05 x 10(-3) mm Hg(-1)), isobaric (100 mm Hg) compliance and distensibility were significantly increased in untreated hypertensive patients (4.46 +/- 0.44 and 0.65 +/- 0.07, P < .01) but not significantly different in treated hypertensive patients (3.19 +/- 0.33 and 0.45 +/- 0.04, P = NS). The results of this cross-sectional study suggest that compliance abnormalities of the radial artery, but not internal diameter changes may be reversed by effective therapeutic control of blood pressure in arterial hypertension.

Antihypertensive Agents↗

PubMed1997

Assessment of antihypertensive effect by blood pressure monitoring: applications to bisoprolol and lisinopril in a double-blind study.

The aim of this study was to evaluate the antihypertensive effect of drugs according to the initial ambulatory blood pressure (BP) level. After a 15-day placebo run-in period, 105 patients with moderate essential hypertension (mean age, 52 years) underwent 24-h BP monitoring (spacelabs: 1 measure/15 min). Patients were subdivided into two groups: the "High" group, with 24-h mean values of systolic BP (SBP) > 137 or diastolic BP (DBP) > 87 mm Hg, and the "Low" group, with SBP < or = 137 and DBP < or = 87 mm Hg. All patients received, in a random and double-blind design, either bisoprolol (10 mg q.d.) or lisinopril (20 mg q.d.) for 8 weeks. At the end of this active treatment period, office and ambulatory BP measurements were performed. Casual measurements revealed similar BP decreases in all subgroups receiving bisoprolol and lisinopril; BP monitoring showed that the antihypertensive effect depended on the baseline mean 24-h value; -15/-12 mm Hg for bisoprolol and -18/-13 mm Hg for lisinopril in the High group; -7/-6 mm Hg for bisoprolol and -6/-6 mm Hg for lisinopril in the Low group. This study shows that the antihypertensive effect depended on initial ambulatory BP values, with a lower BP decrease in the Low group. Assessment of the antihypertensive effect on ambulatory BP is useful in clinical trials.

Adrenergic beta-Antagonists↗

PubMed1997

[Measurement of functional inability and quality of life in cardiac failure. Transcultural adaptation and validation of the Goldman, Minnesota and Duke questionnaires].

Cardiac failure has a big impact on the daily life of patients and this can be evaluated using quality of life questionnaires. The aim of this study was to translate and adapt for the French population and test the validity of two quality of life self-administered-questionnaires: the Duke health Profile, the Minnesota Quality of Life Questionnaire in Cardiac Failure and one function capacity questionnaire, the Goldman Specific Activity Scale. The questionnaires were translated and retranslated then submitted to a committee of experts: the final version was presented to 30 patients. The study of the quantitative properties of the three instruments was performed on a sample of 74 patients with cardiac failure to assess their validity and 26 stable patients after cardiac transplantation to test reproducibility. The results of this study show that these three instruments are valid and reproducible and are comparable to the original documents: Cronbach's Alpha ranging from 0.54 to 0.78 for the Duke, except for the social dimension, and from 0.73 to 0.93 for the Minnesota, except for its incapacity dimension, intraclass correlation coefficient > 0.6 in all dimensions. The validity of convergence with LVEF and the NYHA measured during hospitalisation for decompensation was poor, except for the Goldman. The three instruments provided coherent information. The authors conclude that a structured method allows transcultural adaptation of instruments of evaluation of quality of life, the French version having comparable properties to the original documents: they may be used for clinical research.

Activities of Daily Living↗

PubMed1996

Plasma levels of atrial natriuretic peptide and of other vasoconstricting hormones in patients with chronic heart failure: relationship to exercise capacity.

We investigated the relationship between exercise capacity and the level of neurohormonal activation at rest and during exercise in patients with various degrees of severity of chronic heart failure. We performed exercise testing with measurements of peak oxygen consumption (pVo2) and blood sampling at rest and at peak exercise in eight patients with moderate heart failure (pVo2 = 17 +/- 0.4 ml/kg/min) (mean +/- S.E.M.) and eight patients with severe CHF (pVo2 = 9 +/- 1 ml/kg/min). None of the patients was taking angiotensin converting enzyme inhibitors or beta-blockers. Plasma levels of atrial natriuretic peptide, cGMP, arginine-vasopressin, renin, angiotensin II, epinephrine and norepinephrine increased significantly (P < 0.01), from rest to peak exercise, in all patients. Among all the studied neurohormonal factors, only atrial natriuretic peptide levels at rest as well as at peak exercise, in patients with severe heart failure were correlated significantly to pVo2 (r = -0.77, P = 0.04; r = -0.85, P = 0.01, respectively) and to exercise duration (r = -0.72, P = 0.05; r = -0.79; P = 0.03, respectively). The relationship between plasma levels of atrial natriuretic peptide and of cGMP was shifted downward in the more severe patients suggesting the loss of biological activity of atrial natriuretic peptide.

Adult↗

PubMed1996

Investigations of the peripheral vascular mechanisms implicated in congestive heart failure by the non-invasive evaluation of radial artery compliance and reactivity.

The viscoelastic, muscular and endothelial components of the vessel wall may be altered in patients with congestive heart failure (CHF). In order to investigate the relative contribution of each of these components to the peripheral vascular mechanisms of the disease, we have studied post-ischemic (endothelial-dependent) and post-nitroglycerin (endothelial-independent) vasodilatation as well as the response to cold pressure test and the geometry and compliance of the radial artery using a non-invasive echotracking method coupled to digital photoplethysmography. Thirty-nine patients with congestive heart failure (ejection fraction = 28 +/- 2%) were compared to age- and sex-matched healthy controls. Baseline therapy was unchanged during the study. In congestive heart failure patients, cross-sectional compliance and volumic distensibility were greater (P < 0.05) but isobaric compliance which is independent of blood pressure value was unchanged. Post-ischemic and post-nitroglycerin vasodilatation were lower (7 +/- 1 vs. 11 +/- 1%, P < 0.01 and 6 +/- 1 vs. 14 +/- 2%, P < 0.001, respectively) and both of the arterial diameter and pressure responses to cold pressor test were blunted (-5 +/- 1 vs. -8 +/- 1%, P = 0.058 and 6 +/- 3 mmHg vs. 13 +/- 2 mmHg, P < 0.01, respectively) in congestive heart failure. These changes were similar in primary and ischemic congestive heart failure, suggesting that they are more likely related to common neuro-hormonal factors rather than to an atherosclerotic process.

Blood Pressure↗

PubMed1996

Home self blood pressure measurement in general practice. The SMART study. Self-measurement for the Assessment of the Response to Trandolapril.

The SMART study (Self-Measurement for the Assessment of the Response to Trandolapril) was performed in general practice and enrolled 1710 patients in order to assess on a large scale the feasibility and informative value of self-measurement of blood pressure at home (SMBP), define home blood pressure (BP) levels in comparison to office readings, and determine the number of home measurements necessary to provide an accurate and precise BP value. After a 2-week washout period, patients with office diastolic blood pressure within the range 95 to 119 mm Hg received 2 mg trandolapril once daily in the morning for 4 weeks. Four days of SMBP were performed both at the end of the washout period and the end of the treatment period, with an automatic printer-equipped oscillometric device (A&D UA751). The first day values were not analyzed. Thus, the maximum number of BP measurements obtained per patient and per period was 18. Four hundred and twenty-four patients (25%) did not perform any measurements. One thousand one hundred and nine patients (65%) performed at least 4 measurements. Among them, 619 (36%) correctly performed all 18 measurements. A preference for digits 0 and 5 was detected in physicians' measurements (three consecutive values, during a single office visit). This digit preference was not found with the semiautomatic device. When the number of measurements selected for analysis was increased from 1 to 18, in the 604 patients who provided all recordings and fullfilled all protocol criteria, the standard deviation of the mean BP of the cohort was reduced by 17% for SBP and by 23% for DBP. Eighty-five percent of this reduction was already achieved by six home measurements taken at random. BP was significantly lower at home than at the office by 13 +/- 15 mm Hg for systolic BP (SBP), and 8 +/- 10 mm Hg for diastolic BP (DBP). This difference was independent of age, more marked in women (P < .001 for SBP and P < .05 for DBP), and had a Gaussian distribution. Under treatment, office SBP/DBP decreased from 166.4 +/- 14.8/101.4 +/- 5.7 mm Hg to 144.7 +/- 14.2/86.1 +/- 8.3 mm Hg, while SMBP decreased from 153.2 +/- 17.8/93.8 +/- 10.1 mm Hg to 139.4 +/- 16.4/85.1 +/- 9.5 mm Hg (all P < .0001). A major aim in research studies and individual care is to reduce BP measurements variability. This study demonstrates the ability to evaluate baseline SMBP level in two-thirds of patients previously unfamiliar with the method, the ability to evaluate treatment effect in about one-half of the patients, the improvement in the measurement precision obtained with the repetition of measures (at least six home measurements), and the absence of bias of SMBP as compared to office measurements.

Adolescent↗

PubMed1996

Trough/peak ratios of once daily angiotensin converting enzyme inhibitors and calcium antagonists.

Medications given once daily may increase compliance for treatment of hypertension, if the drugs have a prolonged duration of action. The time-effect profiles for antihypertensive drugs may not depend entirely on pharmacokinetic measurements (plasma levels). Thus, trough/peak effects on blood pressure should be measured. It has been suggested that trough/peak ratios be greater than 50% for optimal 24-h control of pressure. Because very little information is available for many angiotensin converting enzyme (ACE) inhibitors and calcium antagonists concerning their trough/peak ratios and awaiting prospective comparative trials with adequate methodology, we have analyzed the duration of action of blood pressure lowering during long-term therapy with commercially available ACE inhibitors and calcium antagonists in published studies that used ambulatory blood pressure monitoring. Published studies were searched in scientific databases using relevant key words. Twenty-four ACE inhibitor and 34 calcium antagonist studies with comparable methodologies were selected. The mean trough/ peak ratios were computed after reconstruction of the curve of the magnitude of blood pressure changes against time. The results showed that once daily administration of ACE inhibitors produced on average ratios higher than 50% with fosinopril (64%), ramipril (50% to 63%), and trandolapril (50% to 100%). Other studied ACE inhibitors produced ratios on average equal to [enalapril (40% to 64%), cilazapril (10% to 80%), lisinopril (30% to 70%)] or significantly lower than 50% [captopril (25%), benazepril (40%), perindopril (35%), quinapril (10% to 40%), and moexipril (0% to 9%)]. As for once daily calcium antagonists, amlodipine (50% to 100%), lacidipine (40% to 100%), nifedipine Coat-Core (50% to 69%), nifedipine gastrointestinal therapeutic system (GITS) (60% to 94%), as well as various "slow release" formulations of diltiazem (20% to 80%) and verapamil (45% to 100%) had on average ratios higher than 50% whereas felodipine ER (30% to 45%), various slow release formulations of isradipine (10% to 80%), and nitrendipine (10% to 80%) had ratios lower than 50%. Although this retrospective literature analysis may have some theoretical limitations, it suggests that not all once daily ACE inhibitors and calcium antagonists cause trough/peak ratio superior to 50%. This may have important clinical implications.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1996

Physical deconditioning may be a mechanism for the skeletal muscle energy phosphate metabolism abnormalities in chronic heart failure.

The aim of our study was to investigate the contribution of physical deconditioning in skeletal muscle metabolic abnormalities in patients with chronic heart failure (CHF). Phosphate metabolism was studied in the leg muscle at rest and during exercise by using phosphate 31 nuclear magnetic resonance spectroscopy in a group of 14 patients with New York Heart Association class II and III CHF and left ventricular ejection fraction <40% and in two groups of age-matched healthy volunteers: one group of 7 sedentary and another of 7 trained subjects. Phosphocreatine depletion rate, intracellular pH, and adenosine diphosphate levels in the muscle during exercise were not statistically different in the CHF patients and in the sedentary healthy subjects, but both groups were statistically different from the trained healthy subjects, who had slower phosphocreatine depletion rates, as well as less intracellular acidosis and lower adenosine diphosphate levels during exercise (p = 0.02; analysis of variance). Our results suggest that metabolic changes occurring in the skeletal muscle of patients with CHF may contribute to the limitation of exercise capacity and are most likely to be a consequence of physical deconditioning because they are very similar to what is observed in sedentary and otherwise healthy subjects as compared with trained subjects.

Adult↗

PubMed1996

Concomitant diseases in elderly hypertensives: the position of nicardipine.

AGE-RELATED CARDIOVASCULAR CHANGES: Age-related changes in vascular structure and function may contribute to isolated systolic hypertension and target-organ damage. These include cardiac hypertrophy, systolic as well as diastolic dysfunction, congestive heart failure, coronary artery disease, cardiac arrhythmias, cerebrovascular diseases, peripheral vascular diseases and renal insufficiency. POTENTIAL ADVANTAGES OF CALCIUM ANTAGONISTS IN THE ELDERLY: Dihydropyridine calcium anatagonists have been advocated as first choice agents for the treatment of hypertension in the elderly on the grounds that (1) they may be more active in lowering blood pressure because of the predominantly low renin status in elderly hypertensives, (2) they may be better tolerated because side effects related to the activation of the sympathetic system may be less frequent because of attenuation of baroflexes during ageing and (3) they may have beneficial effects on a variety of concomitant cardiovascular diseases which are frequently present in the elderly. These assumptions, however are not always proven in clinical practice. ADVANTAGES OF NICARDIPINE: Additional to its potent vasodilatator action, nicardipine has anti-ischemic effects in both the coronary and the cerebral circulation, including antiplatelet and hemorrheological effects, and protection at ther cellular level against calcium overload and ischemia. The results of a large number of studies in cerebrovascular insufficiency suggest that nicardipine, may favourably affect the cerebral circulation and may improve the patient's cognitive function. Nicardipine may decrease left ventricular mass by about 4-12% and may reduce both the frequency and the severity of arrhythmias. The anti-anginal effects of nicardipine are well established. The drug is also able to decrease the progression of new atherosclerotic lesions in coronary arteries and is consequently potentially beneficial in elderly hypertensives with coronary artery disease. Nicardipine has no clinically significant negative inotropic effect. Nevertheless, in congestive heart failure, the use of calcium antagonists is usually not recommended because of the lack of clinical benefit and of possible harmful effects, including sympathetic and renin-angiotensin system stimulation. Although kidney protection may be provided by a strict and long-term control of blood pressure, the effects of nicardipine on long-term protection of renal function are not clear at present. RECENT CONTROVERSY CONCERNING SHORT-ACTING CALCIUM ANTAGONISTS: Much-debated recent case-control studies suggest that hypertensive patients treated with short-acting calcium antagonists may have an increased incidence of myocardial infarction and possibly of cardiovascular and total mortality. However, only well designed prospective comparative trials can answer this question.

Aging↗

PubMed1996

Frequencies of five genetic polymorphisms in coronarographed patients and effects on lipid levels in a supposedly healthy population.

Allele frequencies of genetic polymorphisms were compared between supposedly healthy subjects and angiographically proven coronary artery disease patients. The polymorphic candidate loci investigated were the apolipoprotein (apo) B signal peptide and XbaI polymorphism, the apo E polymorphism and two polymorphism of lipoprotein lipase (LPL) gene: Hind/III and PvuII. Apo B signal peptide and HindIII/LPL polymorphisms showed significant differences in allele partition between cases and controls; the rare alleles of both polymorphisms were less frequent (p < 0.05) in cases. We looked for associations between the polymorphisms and lipid concentration variability in a supposedly healthy population (145 men and 144 women). Apo B signal peptide, apo E and PvuII/LPL polymorphisms seem to influence some lipid metabolism parameters significantly. Apo AI and LpCIII levels were significantly different among apo B signal peptide genotypes: Del homozygotes had the highest concentrations of both variables. The epsilon 4 allele of apo E polymorphism was associated with increased concentrations of total cholesterol, LDL cholesterol and apo B. Increased LpAI:AII levels observed in E3 homozygotes (p < 0.01) have not previously been reported. LpAI:AII concentration was also influenced by PvuII/LPL polymorphisms.

Adult↗

PubMed1996

Skeletal muscle beta-adrenoreceptors and phosphate metabolism abnormalities in heart failure in rats.

To investigate the mechanisms leading to skeletal muscle metabolic abnormalities in chronic heart failure (CHF), we studied phosphate metabolism and skeletal muscle beta-adrenoreceptors (beta-AR) in rats 12-14 wk after coronary ligation (CL). We performed 31P magnetic resonance spectroscopy in the gastrocnemius muscle during motor activity produced by electrical stimulation (5 Hz). The initial slope of phosphocreatine (PCr) depletion was higher in the CL rats compared with sham-operated rats (Pi/PCr/time: 0.211 +/- 0.045 vs. 0.113 +/- 0.029; P < 0.05). During recovery, both PCr resynthesis rate and maximal rate of oxidative ATP synthesis were reduced threefold in the CL rats compared with controls (11 +/- 2 vs. 37 +/- 7 mmol.l-1.min-1, P < 0.04; and 20 +/- 3 vs. 79 +/- 18 mmol.l-1.min-1, P < 0.03, respectively). There were no significant differences either for the skeletal muscle density (13 +/- 6 vs. 15 +/- 3 fM/mg) or for the affinity (0.244 +/- 0.149 vs. 0.246 +/- 0.146 nM) of beta-AR between the two groups. This study showed that, although in moderate CHF skeletal muscle metabolic abnormalities can be demonstrated, these changes could not be explained by skeletal muscle beta-adrenergic receptor alterations in this experimental model.

Animals↗

PubMed1996

Antihypertensive effects of trandolapril and nitrendipine in the elderly: a controlled trial with special emphasis on time effect profiles.

The aim of this double-blind randomized study was to compare the antihypertensive effects of trandolapril and nitrendipine in the elderly. After a 2-week placebo period, patients received either trandolapril 0.5 mg or nitrendipine 10 mg, once daily for 15 days. At the end of this period, according to a forced titration, the dose was increased to 2 mg of trandolapril or 20 mg of nitrendipine once daily for 2 months. Seventy-three hypertensive patients, aged 65 and over, entered the study. Demographic data and initial blood pressure (BP) level were comparable in the two groups. The antihypertensive effect, measured with a mercury sphygmomanometer, was assessed in 64 patients: SBP decreased by 18.6 +/- 12.1 mm Hg in the trandolapril (P < 0.001) and by 21.0 +/- 13.7 mm Hg in the nitrendipine group (P < 0.001); DBP decreased by 13.4 +/- 8.5 mm Hg in the trandolapril group (P < 0.001) and by 15.4 +/-8.2 mm Hg in the nitrendipine group (P < 0.001). No statistically significant difference was seen between the two treatment groups. A sub-group of 42 patients were evaluated by 24 h ambulatory BP monitoring. Mean 24 h ambulatory SBP/DBP decreases were 6.6 +/- 18.0/8.4 +/- 8.5 mm Hg in the trandolapril group (P < 0.001) and 5.7 +/- 11.1/7.2 +/-9.6 mm Hg in the nitrendipine group (P < 0.001). The differences between the two treatment groups were not statistically significant. The antihypertensive action of trandolapril was sustained throughout the 24 h period with a trough-to-peak ratio of 70.2% for SBP and 70.9% for DBP. Nitrendipine exerted its action mainly during the day, with a very modest antihypertensive effect during the night and early morning; its trough/peak ratio was 25.9% for SBP and 28% for DBP. The tolerance of both treatments were good; seven patients were withdrawn from the trial for adverse events (four in the nitrendipine group, three in the trandolapril group).

Aged↗