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F Zannad

Publications and source records attributed to F Zannad.

At least 55 records · Page 3Linked to original sources

Familial studies on the genetics of cardiovascular diseases: the Stanislas cohort.

In a given individual, the level of cardiovascular risk results from the combination of and interactions between genetic and environmental components. We choose to investigate segregation analysis of intermediate phenotypes in healthy nuclear families, belonging to the Stanislas cohort, a large familial cohort composed of 1006 families, which will be followed for 10 years. We developed a panel of 35 genetic markers including genes involved in lipid metabolism, regulation of blood pressure, thrombosis, platelet function, and endothelial cell adhesion. The allele frequencies of the studied polymorphisms were in agreement with those reported in other Caucasian populations. As an example of segregation analysis, we investigated carotid intima-media thickness (CIMT) variability in a subset sample of the Stanislas cohort. We found that about 30% of CIMT variability was attributable to genetic factors. Associations between CIMT and polymorphisms in apo CIII, cholesteryl ester transfer protein, methylene tetrahydrofolate reductase, and fibrinogen genes were observed and explained about 20% of CIMT variability in men. Furthermore, as another example of association studies, we investigated the relations between E-selectin polymorphisms and blood pressure interindividual variability and longitudinal changes in unrelated adults of this familial population. The E-selectin Phe554 allele was found associated with lower systolic blood pressure and diastolic blood pressure.

Adult↗

[Effects of calcium antagonists on atherosclerosis progression and intima media thickness].

Calcium antagonists are currently considered first-choice agents for treating hypertension. They are also active antianginal drugs. Their protective effects against ischaemia and their antiatherogenic potential, which have been demonstrated in various experimental models, may contribute to their preventive effect against the early atherosclerotic processes. However, their effects on survival and cardiovascular events have been inconsistent and controversial. Recent studies have suggested that mortality may be increased by short-acting agents. The effects of certain long-acting calcium antagonists may be different. In early clinical trials, nifedipine and nicardipine did not alter the progression of significant coronary artery narrowing, but did reduce the development of new atherosclerotic lesions. Nevertheless, the number of cardiovascular events was not decreased. The Multicenter Isradipine Diuretic Atherosclerosis Study (MIDAS) showed a higher incidence of angina and more frequent cardiovascular events in patients treated with isradipine. In the Prospective Randomized Evaluation of the Vascular Effects of Norvasc Trial (PREVENT), after 3 years' follow-up, progression of significant atherosclerotic lesions and the development of new lesions were not significantly altered by treatment with amlodipine. However, it would appear that quantitative angiography may not be appropriate for monitoring the progression of atherosclerosis. Because of arterial remodelling, angiographic images may not show changes in the arterial lumen, in arteries where intravascular ultrasound may detect important atherosclerotic plaques. High resolution B-mode ultrasonography of the carotid artery may be more informative, since carotid intima media thickness is strongly correlated with cardiovascular risk factors, the prevalence of cardiovascular disease, and the presence of atherosclerotic lesions at other arterial sites. In the PREVENT trial, carotid ultrasonography showed that intima media thickness was stabilised in the amlodipine group, while progression was uninterrupted in the placebo group. The mechanism of amlodipine in slowing the progression of intima media thickness may be related to its antiatherogenic effect, as well as to its effect on cellular growth and hyperplasia of the arterial wall. It is interesting to note that, as a secondary objective of the PREVENT trial, patients treated with amlodipine had fewer ischaemic events than those treated with placebo. The beneficial effects of amlodipine on arterial thickening and on the prevention of ischaemic events suggest that amlodipine may be recommended for the management of all patients with stable angina. A larger trial with a longer follow-up period should be performed in order to confirm the promising results of PREVENT.

Amlodipine↗

Preserving target-organ function with candesartan cilexetil in patients with hypertension.

Epidemiological evidence suggests that reducing blood pressure alone in hypertensive patients delays the onset of cardiovascular events without necessarily preventing the progression of chronic target-organ disease, such as end-stage renal failure and heart failure. Successful clinical management of hypertensive patients will therefore not be possible unless therapies are aimed both at the effective control of blood pressure and at the preservation of target-organ function. The new angiotensin II type I (AT1) receptor blocker candesartan cilexetil has been shown to be effective in reducing target-organ damage in animal models of hypertension, even at doses that do not produce significant reductions in blood pressure. Protective effects of candesartan cilexetil towards the heart and kidney have also been demonstrated in the clinical studies that have been conducted to date. Thus, candesartan cilexetil has been shown to induce regression of left ventricular hypertrophy within 8-12 weeks of treatment and to improve renal haemodynamics, both acutely and after 6 weeks of treatment in hypertensive patients. Furthermore, in hypertensive patients with co-existent non-insulin-dependent diabetes mellitus and microalbuminuria, 12 weeks of treatment with candesartan cilexetil, 8-16 mg, significantly reduced urinary albumin excretion. Clinical evidence is therefore accumulating that the antihypertensive efficacy and tolerability profile already established for candesartan cilexetil is combined with the renal and cardioprotective effects necessary for optimal management of hypertension.

Angiotensin Receptor Antagonists↗

Consequences of labetalol administration on myocardial beta adrenergic receptors in the brain dead pig.

OBJECTIVES: Cardiac dysfunction following brain death is associated with highly increased myocardial norepinephrine, lactate and adenosine concentrations. Administration of labetalol, a mixed alpha-, beta-adrenergic receptor antagonist, attenuates metabolic disturbances and improves myocardial function. The purpose of this study was to investigate beta-adrenergic receptor (beta AR) density and affinity in the presence or absence of labetalol administration, as a possible mechanism of the protective effects of this drug. METHODS: Experimental animals were divided into three groups: sham-operated, brain-dead pigs, and brain-dead pigs treated with labetalol (10 +/- 3 mg/kg). The maximum number of binding sites (Bmax) and the dissociation constant (Kd) of beta AR were determined with (-)-[125I]cyanopindolol on myocardial samples harvested 3 hours after brain death. RESULTS: Left ventricular beta AR density and affinity were identical in brain-dead and sham-operated animals. Labetalol-treated pigs exhibited a significant decrease of Bmax and an increase of Kd as compared with brain-dead pigs. Bmax decrease was due to the persistence of labetalol in the membrane preparations. Increased Kd was too low to be biologically significant. Therefore, beta AR number and affinity can be considered as unchanged after adrenergic blockade with labetalol. CONCLUSIONS: The protective mechanism of labetalol on brain death-induced myocardial dysfunction cannot be explained by changes in beta AR density and affinity but is probably related to a preservation of the oxygen consumption/oxygen delivery balance during the autonomic storm.

Adrenergic alpha-Antagonists↗

The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators.

BACKGROUND AND METHODS: Aldosterone is important in the pathophysiology of heart failure. In a doubleblind study, we enrolled 1663 patients who had severe heart failure and a left ventricular ejection fraction of no more than 35 percent and who were being treated with an angiotensin-converting-enzyme inhibitor, a loop diuretic, and in most cases digoxin. A total of 822 patients were randomly assigned to receive 25 mg of spironolactone daily, and 841 to receive placebo. The primary end point was death from all causes. RESULTS: The trial was discontinued early, after a mean follow-up period of 24 months, because an interim analysis determined that spironolactone was efficacious. There were 386 deaths in the placebo group (46 percent) and 284 in the spironolactone group (35 percent; relative risk of death, 0.70; 95 percent confidence interval, 0.60 to 0.82; P<0.001). This 30 percent reduction in the risk of death among patients in the spironolactone group was attributed to a lower risk of both death from progressive heart failure and sudden death from cardiac causes. The frequency of hospitalization for worsening heart failure was 35 percent lower in the spironolactone group than in the placebo group (relative risk of hospitalization, 0.65; 95 percent confidence interval, 0.54 to 0.77; P<0.001). In addition, patients who received spironolactone had a significant improvement in the symptoms of heart failure, as assessed on the basis of the New York Heart Association functional class (P<0.001). Gynecomastia or breast pain was reported in 10 percent of men who were treated with spironolactone, as compared with 1 percent of men in the placebo group (P<0.001). The incidence of serious hyperkalemia was minimal in both groups of patients. CONCLUSIONS: Blockade of aldosterone receptors by spironolactone, in addition to standard therapy, substantially reduces the risk of both morbidity and death among patients with severe heart failure.

Aged↗

Continuous intravenous dobutamine is associated with an increased risk of death in patients with advanced heart failure: insights from the Flolan International Randomized Survival Trial (FIRST).

OBJECTIVE: To evaluate clinical characteristics and outcomes of patients with advanced heart failure receiving intravenous continuous dobutamine in the FIRST Trial (Flolan International Randomized Survival Trial). METHODS: Four hundred seventy-one patients with class IIIb to IV heart failure who were enrolled in the FIRST trial were included. Eighty patients treated with dobutamine at FIRST randomization were compared with 391 patients not treated with dobutamine at randomization. The occurrence of worsening heart failure, need for vasoactive medications, resuscitated cardiac arrest, myocardial infarction, and total mortality were compared between the 2 groups. RESULTS: The dobutamine group had a higher occurrence of first event (85.3% vs 64. 5%; P =.0006) and a higher mortality rate (70.5% vs 37.1%; P =.0001) compared with the no dobutamine group. Intravenous continuous dobutamine was an independent risk factor for death after adjusting for baseline differences. CONCLUSIONS: Dobutamine use at the time of randomization was associated with a higher 6-month mortality rate. This effect persisted after adjustment for baseline differences. This analysis challenges the concept that continuous intravenous dobutamine is beneficial to advanced heart failure patients with respect to survival.

Aged↗

Incidence, clinical and etiologic features, and outcomes of advanced chronic heart failure: the EPICAL Study. Epidémiologie de l'Insuffisance Cardiaque Avancée en Lorraine.

OBJECTIVES: Characterize the incidence, clinical and etiologic features and outcomes of advanced congestive heart failure. BACKGROUND: This condition is frequent, severe and costly, yet no population-based epidemiological data are available that take into account modern advances in diagnosis and therapy. METHODS: The EPICAL (Epidémiologie de l'Insuffisance Cardiaque Avancée en Lorraine) study was based on a comprehensive registration of patients with ACHF (defined as hospital admission for presence of NYHA class III or IV symptoms, radiological and/or clinical signs of pulmonary congestion and/or signs of peripheral edema, left ventricular ejection fraction <30% or a cardiothoracic ratio >60%) in patients aged 20-80 years during year 1994, in the community of the Lorraine region in France (n = 1,592,263). Average follow-up for readmission to hospital and mortality was 18 months (12-24 months). RESULTS: From 2,576 registered patients, 499 were enrolled into the study among which, 358 were new presentations. This represents a crude incidence rate of 225 per million. 46.3% had a coronary heart disease. One-year mortality rate was 35.4% and the rate of mortality and/or readmission to hospital was 81%. Patients were admitted to hospital 2.05 times per year (64% of these for worsening heart failure), spending 27.6 days per year in hospital. Twenty received a heart transplant (4%). On discharge, 74.8% were using ACE inhibitors and 49.6% digitalis. CONCLUSIONS: Mortality and hospitalization rate of advanced CHF remain very high despite recent therapeutic progress. Major therapeutic and managed-care research is required.

Adult↗

Effects of medical therapy on outcome assessment using exercise thallium-201 single photon emission computed tomography imaging: evidence of a protective effect of beta-blocking antianginal medications.

OBJECTIVES: The purpose of this study was to determine whether antianginal medications modify the prognostic significance of exercise single photon emission computed tomography (SPECT) ischemia. BACKGROUND: Antianginal medications (especially beta-adrenergic blocking agents) limit exercise SPECT ischemia, but it is not known whether such medications also modify the prognostic effect of exercise SPECT ischemia. METHODS: We included 352 patients with coronary heart disease, who had exercise Tl-201 SPECT and coronary angiography, and who were initially treated medically. Survival Cox models were applied in patients for whom classes of antianginal medications taken at exercise SPECT were the same as those prescribed for follow-up (GI; n = 136), and in patients for whom new classes of antianginal medications, including beta-blockers (GII; n = 79) or not including beta-blockers (GIII; n = 113), were added for follow-up. RESULTS: During a mean 5.3+/-1.6 years of follow-up, 45 patients had cardiac death or myocardial infarction. Variables reflecting necrosis (irreversible defect extent, left ventricular ejection fraction) and those from coronary angiography provided equivalent prognostic information in the three groups. In contrast, the SPECT variable reflecting ischemia (reversible defect extent), which provided comparable prognostic information in GI (p = 0.005) and GIII (p = 0.004), lost its prognostic significance (p = 0.54) in GII, and was associated with a lower relative risk in GII than in GI or GIII (both p < 0.05). CONCLUSIONS: In patients with coronary heart disease, the introduction of antianginal medications, when including beta-blockers, appears to have a favorable effect on the deleterious prognostic effect of exercise ischemia.

Adrenergic beta-Antagonists↗

Beta-blocker therapy in advanced heart failure: clinical characteristics and long-term outcomes.

AIMS: To evaluate the clinical characteristics and long-term outcomes of advanced heart failure patients (NYHA Class IIIb-IV) receiving beta-blocker therapy vs. those patients not receiving beta-blockers at randomization in the FIRST trial, a randomized, double-blind, placebo-controlled trial of epoprostenol vs. usual care in advanced heart failure. METHODS AND RESULTS: The patient population consisted of 471 patients enrolled in FIRST with Class IIIb-IV heart failure, left ventricular ejection fraction (LVEF) of <30%, advanced hemodynamic abnormalities, and standard pharmacologic treatment of ACE-inhibitor, diuretics, and/or digoxin. The study cohort consisted of 448 patients not receiving beta-blockers and 23 patients receiving beta-blockers at randomization for the FIRST trial. Patients in the beta-blocker group had decreased rates of any clinical event (P = 0.03), worsening heart failure (P = 0.001), and death or worsening heart failure (P = 0.0008) than patients not receiving beta-blockers. After adjusting for prognostically important variables, the favorable effect of beta-blockers on worsening heart failure (P = 0.02) and death or worsening heart failure (P = 0.02) persisted. CONCLUSION: Patients with advanced heart failure who receive beta-blocker therapy have a lower rate of hospitalization and are less likely to experience worsening heart failure or death at 6 months than patients who are not treated with beta-blockers. These observational data contribute to the growing body of data demonstrating a favorable effect of beta-blockers on clinical outcomes in heart failure.

Adrenergic beta-Antagonists↗

Differential effects of aging on heart rate variability and blood pressure variability.

Previous studies investigating autonomic cardiovascular control in elderly persons usually included analysis of R-R interval but not of blood pressure variability. "Physiological" blood pressure rise during the aging process was not accounted for as a possible confounding factor. This study was designed to characterize the relationship between age and short-term heart rate (HR) and blood pressure (BP) variability, independently of the "physiological" rise in BP associated to aging. The study was carried out in 65 "normotensive" (BP< or =140/80 mm Hg) healthy subjects, ranging in age from 18 to 80 years. BP and HR were recorded at rest with a Finapres device. Low-frequency (LF = 0.066 to 0.129 Hz) and high-frequency (HF = respiratory peak +/-0.05 Hz) components of HR and BP variability were assessed using fast-Fourier spectral analysis. Transfer-function analysis between systolic BP and HR variability permitted the calculation of the gain of baroreflex sensitivity. Significant results of this study include a continuous and linear decline with age of normalized LF spectral power of HR in the standing position and of normalized HF spectral power of HR during paced breathing. No correlation was found between age and BP variability, except for LF diastolic BP spectral power in the standing position. The baroreflex gain was negatively correlated with age. The effect of aging on autonomic nervous system cardiac control is progressive and continuous throughout an 18-80 years age range. Although the aging process diminished HR variability and diastolic BP variability, it had no influence on systolic BP variability.

Adolescent↗

Double-blind, randomized, multicentre comparison of the effects of amlodipine and perindopril on 24 h therapeutic coverage and beyond in patients with mild to moderate hypertension. General Physicians Investigators' Group.

OBJECTIVE: To compare the therapeutic coverage and safety of amlodipine and perindopril in patients with mild to moderate hypertension (diastolic blood pressure > or = 90 mmHg and < or = 109 mmHg). DESIGN: A double-blind, randomized, parallel-group, multicentre study. METHODS: Following a 2-week placebo wash-out period, the patients were randomly allocated to treatment with either amlodipine at 5-10 mg once a day or perindopril at 4-8 mg once a day, for 60 days. Trough: peak ratios were calculated by two different methods (global and individualized approaches) from 24 h ambulatory blood pressure recordings made after the placebo period and after the active treatment period. Residual lowering of blood pressure after single-blind, single-dose omission was also investigated with further 24 h ambulatory blood pressure monitoring. Safety assessments were made throughout the study. RESULTS: The placebo-adjusted, global, diastolic blood pressure trough: peak ratio was 0.80 in the amlodipine group (n = 47) and 0.81 in the perindopril group (n = 49) in an intent-to-treat analysis. The corresponding global systolic blood pressure trough: peak ratio was 0.83 for amlodipine and 0.68 for perindopril. Individual trough: peak ratios were non-normally distributed. Mean (+/- SD) individual trough: peak ratios (intent-to-treat analysis) for diatolic blood pressure were 0.50 +/- 0.69 for amlodipine (median 0.42) and 0.15 +/- 3.27 for perindopril (median 0.33). In the per protocol analysis, the corresponding values were 0.50 +/- 0.72 (median 0.34) for amlodipine and 0.01 +/- 3.90 for perindopril (median 0.21). Both treatments produced comparable decreases in clinic systolic and diastolic blood pressure between days 0 and 60. Forty-eight hours after the last dose, both systolic and diastolic blood pressure were lower in amlodipine-treated patients than perindopril-treated patients. Amlodipine and perindopril were generally well tolerated. The most frequently reported adverse event was leg oedema in amlodipine-treated patients (19.1%), and coughing in perindopril-treated patients (14.3%). CONCLUSIONS: These results showed no statistically significant difference in trough: peak ratios between amlodipine and perindopril. However, the ambulatory blood pressure trough: peak ratios showed very large variations. Determination of trough: peak ratios by the conventional approach or by an individual approach can yield disparate values. After omitting one dose, a condition imitating noncompliance, blood pressure was more effectively controlled with amlodipine than with perindopril.

Adolescent↗

Ambulatory 24-h blood pressure assessment of the felodipine-metoprolol combination versus amlodipine in mild to moderate hypertension. Lorraine General Physician Investigators Group.

OBJECTIVE: To measure the time effect profiles of a once daily administered combination tablet felodipine-metoprolol 5/50 mg (Logimax, Astra) and amlodipine 5 mg (Norvasc, Pfizer) on blood pressure and heart rate using 24-h ambulatory blood pressure monitoring. DESIGN: Randomized multicentre parallel-group study with a single-blind placebo run-in period of 4 weeks duration and a 6-week double-blind active treatment period. PATIENTS AND METHODS: Out of 245 randomized outpatients (90 men, 155 women) with uncomplicated mild-to-moderate primary hypertension and mean sitting diastolic blood pressure (DBP) 95-115 mmHg inclusive, 212 (102 on felodipine-metoprolol, 110 on amlodipine) were eligible for analysis. 24-h ambulatory blood pressure monitoring was performed at the end of the placebo run-in (baseline) and after 6 weeks active treatment (posttreatment). RESULTS: Both felodipine-metoprolol and amlodipine induced smooth and consistent reduction in DBP and systolic blood pressure throughout the 24-h period, hence not altering the diurnal rhythm. However, felodipine-metoprolol reduced all average blood pressures (24-h, day- and night-time) more than amlodipine (for 24-h average blood pressure 14.4/9.5 mmHg and 8.9/5.5 mmHg, respectively). Medians of individual diastolic trough-to-peak (T/P) ratios were similar for felodipine-metoprolol and amlodipine (54 and 50%, respectively), while for the systolic T/P ratios, the corresponding values were 74 and 35%, repectively; no significant difference between treatments was seen. As distinguished from amlodipine, both heart rate and rate pressure product were markedly decreased on felodipine-metoprolol throughout the 24-h period and even during the early morning hours. In general, both treatments were well tolerated. CONCLUSIONS: Both felodipine-metoprolol and amlodipine achieved optimal control of blood pressure during the inter-dosing interval in line with their pharmokinetic profiles. The vasodilatory adverse events were slightly more reported with felodipine-metoprolol combination, but due to more pronounced lowering of the average blood pressures and the potent additional effect on heart rate and rate pressure product, the efficacy/tolerability balance seems to be equal to or better than that obtained with monotherapy such as amlodipine.

Amlodipine↗

Influence of a calcium antagonist on blood rheology and arterial compliance in hypertension: comparison with a thiazide diuretic.

Beyond their effects on blood pressure, antihypertensive agents may produce additional effects on blood rheology and arterial compliance abnormalities which may play a role in the target organ damage. These effects may depend only on their specific pharmacological properties. We compared the effects of nitrendipine to hydrochlorothiazide in 33 mild to moderate hypertensives in a double blind parallel group trial. Blood rheology and radial artery diameter and compliance were measured at t=0 and t=2 months. Both drugs produced blood pressure lowering. Blood viscosity decreased in the nitrendipine group and increased in the hydrochlorothiazide patients. Red blood cells deformability increased only in the nitrendipine group. Radial artery diameter and compliance were not different between the two groups but there was a trend to an increase of the cross-sectional compliance in hydrochlorothiazide group and to a decrease in nitrendipine group. Our data show that a calcium antagonist (Nitrendipine) could improve rheological parameters.

Antihypertensive Agents↗

Genetics strongly determines the wall thickness of the left and right carotid arteries.

In 76 supposedly healthy families, we investigated the familial resemblance of left and right carotid intima-media thickness (IMT) measured by B-mode ultrasonography and the impact of the common apolipoprotein E (apo E) polymorphism and the insertion/deletion polymorphism of the angiotensin-converting enzyme (ACE). Genetic factors accounted for about 30% of IMT variation. The insertion/deletion ACE polymorphism did not influence carotid IMT, whereas apoE polymorphism explained about 1.5% of only right carotid IMT variability independently of cholesterol levels. The apo epsilon2 and apo epsilon4 alleles were associated with lower right carotid IMT than was the apo epsilon3 allele. We conclude that genetic factors strongly contribute to IMT variability in healthy people and that the apo E polymorphism may be one of these factors.

Analysis of Variance↗

Differential effects of fosinopril and enalapril in patients with mild to moderate chronic heart failure. Fosinopril in Heart Failure Study Investigators.

OBJECTIVES: To investigate the efficacy and safety of fosinopril in the treatment of chronic heart failure (CHF), patients with mild to moderate CHF and left ventricular ejection fractions <40% were randomly assigned in a double-blind manner to receive fosinopril 5 to 20 mg every day (n = 122) or enalapril 5 to 20 mg every day (n = 132) for 1 year. RESULTS: The event-free survival time was longer (1.6 vs 1.0 months, P= .032) and the total rate of hospitalizations plus deaths was smaller with fosinopril than with enalapril (19.7% vs 25.0%, P= .028). There was consistently better symptom improvement with fosinopril (P< .05). The incidence of orthostatic hypotension was lower in the fosinopril group (1.6% vs 7.6%, P< .05). CONCLUSIONS: Fosinopril 5 to 20 mg every day was more effective in improving symptoms and delaying events related to worsening of CHF and produced less orthostatic hypotension than enalapril 5 to 20 mg every day.

Adult↗

Apolipoprotein E4, lipoprotein lipase C447 and angiotensin-I converting enzyme deletion alleles were not associated with increased wall thickness of carotid and femoral arteries in healthy subjects from the Stanislas cohort.

Studies have shown contrasting results concerning the relation between carotid intima-media thickness (IMT) and apolipoprotein E (apo E) and angiotensin-converting enzyme (ACE) polymorphisms. Subjects, 76 men and 74 women, between 33 and 50 years, without any history of cardiovascular disease and without any anti-hypertensive or lipid lowering medication were selected from the Stanislas cohort. The IMT of carotid and femoral arteries were investigated by B-mode ultrasonography. The common apo E, (C/G)447 lipoprotein lipase (LPL) and I/D ACE gene polymorphisms and serum ACE activity were determined. In the overall sample, male sex, age, systolic blood pressure, BMI, serum apo B level and tobacco consumption were positively correlated with carotid and femoral IMT. The common apo E polymorphism, the (C/G)LPL447 polymorphism and ACE activity were not related to carotid and femoral IMT variability in either men or women. Unexpectedly, the I allele of the ACE gene was related to higher femoral IMT than the D allele in non-smokers only. Similar results were observed after adjustment for the main covariates of IMT variability. In conclusion, amongst our young adult sample the candidate risk factors for cardiovascular disease, apo epsilon4, C447-LPL and D-ACE alleles and ACE activity were not associated with increased carotid and femoral IMT.

Adult↗