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Biomedical subjects

R Asmar

Publications and source records attributed to R Asmar.

At least 73 records · Page 4Linked to original sources
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↗
PubMed1996

Placebo-controlled, randomized, double-blind study of intravenous enalaprilat efficacy and safety in acute cardiogenic pulmonary edema.

BACKGROUND: Converting enzyme inhibitors meet most of the criteria required to be used in acute pulmonary edema. However, they could also induce deleterious effects on renal function and electrolytes. The purpose of this study was to evaluate the efficacy and safety of a single intravenous 2-hour infusion of enalaprilat (1 mg) after an acute pulmonary edema. METHODS AND RESULTS: This was a placebo-controlled, randomized, double-blind study performed in 20 congestive heart failure patients (New York Heart Association class III or IV). Systemic and regional hemodynamic parameters, biological parameters, and blood gases were measured before and repeatedly after the onset of infusion. Compared with placebo, enalaprilat decreased pulmonary capillary wedge pressure (-37% versus -10%, P = .001), diastolic and mean systemic blood pressures (-21% versus 0%, P = .009, and -18% versus -1%, P = .026, respectively), diastolic and mean pulmonary blood pressures (-21% versus -8%, P = .040; -18% versus -9%, P = .046), and brachial and renal resistances (-44% versus -14%, P = .017, and -22% versus -2%, P = .014, respectively); increased brachial and renal blood flows (+77% versus +8%, P = .036, and +12% versus 0%, P = .043, respectively), arterial oxygen tension (+2% versus -16%, P = .041), and arterial oxygen saturation (+1% versus -2%, P = .045); and tended to decrease rate-pressure product (-19% versus -7%, P = .076), increase brachial artery diameter (+13% versus 0%, P = .081), and improve intrapulmonary shunt (-18% versus +16%, P = .080). Enalaprilat did not affect cardiac output or carotid or hepatosplanchnic hemodynamics. CONCLUSIONS: Early administration of enalaprilat is effective and well tolerated in acute pulmonary edema.

Acute Disease↗
PubMed1996

Influence of angiotensin-converting enzyme and angiotensin II type 1 receptor gene polymorphisms on aortic stiffness in normotensive and hypertensive patients.

BACKGROUND: Clinical and experimental studies have demonstrated a major role of the renin-angiotensin system in the functional and structural changes of the large arteries in hypertension. Because genetic studies may help us to understand the mechanisms underlying the involvement of this system in arterial regulation, the present study was designed to assess the contribution of polymorphisms of the ACE insertion/deletion (I/D) and angiotensin II type 1 receptor (AGTR1 A 1166C) genes on aortic stiffness regulation. METHODS AND RESULTS: This study included 311 untreated hypertensive and 128 normotensive subjects. Aortic stiffness was evaluated by measurement of the carotid-femoral pulse-wave velocity (PWV). In normotensive subjects, the two polymorphisms did not influence any of the studied parameters. In hypertensive subjects, there was a decreasing trend of mean PWV with the number of ACE D alleles, but this association became significant only after adjustment for blood pressure (P < .05). Conversely, the AGTR1 A 1166C polymorphism was independently associated with aortic stiffness. Mean values of PWV were 11.6 +/- 2.7 m/s in AGTR1 AA homozygotes, 13.3 +/- 3.3 m/s in AC heterozygotes, and 15.3 +/- 4.3 m/s in CC homozygotes (P < .0001 and P < .00001 after adjustment for age and mean blood pressure, respectively). The percentage of variance of PWV explained by AGTR1 A 1166C polymorphism (11.6%) was much larger than that of ACE I/D polymorphism (1.7%). CONCLUSIONS: These results suggest that in hypertensive but not normotensive subjects, the AGTR1 and ACE genotypes are involved in the regulation of aortic rigidity. The presence of the AGTR1 C allele is a strong independent determinant of aortic stiffness, whereas presence of the ACE 1 allele is weakly associated with increased stiffness.

Adolescent↗
PubMed1996

Prevalence and circadian variations of ST-segment depression and its concomitant blood pressure changes in asymptomatic systemic hypertension.

Coronary artery disease is a major complication of hypertension; one of its manifestations is silent ischemia. The aim of this study was to assess the prevalence and circadian distribution of ST-segment depression together with concomitant blood pressure (BP) and heart rate variations. One hundred patients (male:female ratio 1:1) with a mean age (+/- SD) of 51 +/- 8 years underwent ambulatory monitoring using the combined AMP 5600 monitor which simultaneously records a continuous Holter electrocardiogram and intermittent noninvasive BP measurements at 15-minute intervals, with extra measurements triggered by detection of a horizontal or downsloping ST depression (> 1 mm and >60 seconds). Cardiovascular risk factors were fully evaluated in all patients; accurate and reliable echocardiogram enabled left ventricular mass index to be calculated in 52 patients. Twenty-three patients (15 men and 8 women) experienced a total of 72 episodes of ST depression. Duration of such episodes (mean +/- SD) was 132 +/- 65 seconds and amplitude was 1.51 +/- 0.55 mm. Circadian distribution showed 2 peaks: on awakening and in the late afternoon periods. The mean ambulatory BP load was greater in the patients with than without ST-segment depression for both systolic and diastolic BP (135 +/- 14 vs 129 +/- 15 and 84 +/- 8 vs 79 +/- 10 mm Hg, respectively; p < 0.01). Plasma glucose (5.83 +/- 0.70 vs 5.46 +/- 0.71 mmol/L; p = 0.04) and self-related work-related stress levels (22% vs 13%; p = 0.03) were also higher in patients with ST-segment depression. There were no significant differences between groups for clinical parameters, left ventricular mass index, and other cardiovascular risk factors. During ST depression episodes, systolic BP increased by 9 +/- 15 mm Hg, diastolic BP by 7 +/- 11 mm Hg, and heart rate by 5 +/- 17 beats/min. Thus, 24-hour Holter electrocardiographic monitoring showed ST depression episodes in 23 of 100 hypertensive patients (23%); ambulatory BP load was greater in these patients. BP variations, and mainly its elevation, may trigger such episodes of ST-segment depression.

Adult↗
PubMed1996

Influence of the angiotensin II type 1 receptor gene polymorphism on the effects of perindopril and nitrendipine on arterial stiffness in hypertensive individuals.

Angiotensin-converting enzyme inhibitors improve arterial stiffness independently of blood pressure reduction. Since we have recently shown that in hypertensive individuals the A1166C polymorphism of the angiotensin II type 1 receptor (AT1-R) is an independent determinant of aortic stiffness, we designed the present study to assess the influence of this polymorphism on the changes of aortic stiffness after chronic treatment with the angiotensin-converting enzyme inhibitor perindopril and the calcium channel blocker nitrendipine. Forty perindopril- and 42 nitrendipine-treated hypertensive individuals were studied. We evaluated aortic stiffness by measuring the carotid-femoral pulse wave velocity. Carriers of the AT1-RC allele showed higher baseline values of pulse wave velocity than AA homozygotes (P < .05). In the perindopril group, a threefold greater reduction in pulse wave velocity was observed in carriers of the C allele than in AA homozygotes (-2.85 +/- 0.62 versus -0.94 +/- 0.32 m/s, respectively; P < .001), whereas in the nitrendipine group, pulse wave velocity decreased only in AA homozygotes and not in AT1-R C carriers (-1.38 +/- 0.35 versus +0.04 +/- 0.60 m/s, respectively; P < .01). These results indicate that according to the AT1-R A1166C genotype, an angiotensin-converting enzyme inhibitor and a calcium channel blocker affect pulse wave velocity in opposite ways. Since some evidence shows that increased pulse wave velocity may enhance cardiovascular risk, it might be useful for physicians to consider the AT1-R genotype when prescribing an angiotensin-converting enzyme inhibitor or calcium channel blocker to a hypertensive individual.

Adult↗
PubMed1996

Repeated measurements of non-invasive ambulatory blood pressure: distinction between reproducibility and the proper effect of placebo.

OBJECTIVE: To determine whether non-invasive ambulatory blood pressure is more reproducible and less affected by the placebo treatment than are clinic blood pressure measurements. METHOD: Thirty-four essential hypertensive outpatients were randomly allocated after a 4-week preselection period in two groups in a cross-over study design. One group received placebo for 4 weeks while the other formed the control group (reproducibility), then the treatments were exchanged for another 4 weeks. Clinic and ambulatory blood pressures were measured at three different times for each patient, namely bnefore the random allocation to groups and at the end of each period, using a mercury sphygmomanometer and 24 h non-invasive ambulatory blood pressure monitoring. RESULTS: Administration of placebo was accompanied by a significant reduction in systolic and diastolic clinic blood pressures (by 3.4+/-13 and 3.6+/-8 mmHg, respectively), but not in 24 h, daytime and night-time blood pressures. Circadian hourly blood pressure and heart rate curves were virtually superimposable. In the 13 placebo responder patients selected on the basis of clinic blood pressure, placebo decreased the clinic blood pressure and also reduced systolic and diastolic ambulatory blood pressures, mainly during the day period (by 5.2+/-6.2 and 4.89+/-7.8 mmHg, respectively). This effect is specific and related to the placebo administration because repetition of the measurements without any treatment showed no significant difference. To characterize at baseline the placebo responder patients, comparison with the non-placebo responders showed lower baseline values of ambulatory systolic blood pressure recorded during 24 h daytime and night-time in the placebo responder group. CONCLUSION: The 24 h ambulatory blood pressure average is not affected by placebo in the present group of patients but that a placebo effect occurs mainly during the daytime in patients who decreased their clinic blood pressure under placebo (placebo responders); the placebo-induced reduction in blood pressure is related to a specific effect of placebo and is independent from any alerting reaction or reproducibility hypothesis. This study clearly indicates the necessity of including placebo and ambulatory blood pressure monitoring in the therapeutic and pharmacological trials of antihypertensive drugs.

Journal Article↗
PubMed1996

Therapeutic efficacy.

This session was devoted to the application of ambulatory blood pressure monitoring (ABPM) to evaluate the therapeutic efficacy of antihypertensive treatment. Several aspects of this large field have been discussed, but others, no less important, need to be treated and clarified in the future.

Journal Article↗
PubMed1996

Assessment of antihypertensive efficacy by non-invasive ambulatory blood pressure monitoring.

The session devoted to the usefulness of non-invasive ambulatory blood pressure monitoring (ABPM) in the evaluation of antihypertensive therapy allowed us to discuss a number of important issues. ABPM emerged as a widely accepted technique to measure blood pressure in clinical trials. Actually, it was generally considered to provide more valuable information than do conventional blood pressure readings obtained sporadically by a doctor. However, still debated was the way of analysing ABPM recordings. This was particularly true with respect to the proposal of considering separately responders and non-responders when assessing the quality of blood pressure control achieved during treatment.

Journal Article↗
PubMed1996

Arterial stiffness, hydrochlorothiazide and converting enzyme inhibition in essential hypertension.

In a randomized double blind study, the arterial changes produced either by hydrochlorothiazide plus amiloride (Group I), or by hydrochlorothiazide plus captopril (Group II) were investigated in two territories of the arterial tree, the common carotid artery and the terminal aorta. Arterial echo-tracking techniques of high resolution and applanation tonometry were used to evaluate non-invasively the indices of arterial stiffness and carotid wave reflections. In Group I and II, there was a similar significant decrease in brachial blood pressure (BP) and carotid diastolic diameter and an increase in aortic compliance and distensibility. Groups I and II differed significantly in aortic diastolic diameter which decreased in Group I but not in Group II, and in carotid wave reflections which were modified in Group II but not in Group I. Thus, captopril associated with hydrochlorothiazide resulted in a shift in the carotid arterial reflection wave from systole to diastole with no reduction in the aortic diastolic dimension. For similar BP reduction, the combination of hydrochlorothiazide and amiloride had no significant effect on the carotid reflection wave, but caused a significant reduction in the aortic diastolic diameter. These intergroup differences were related to the presence or absence of converting enzyme inhibition.

Adult↗
PubMed1996

[Family physicians and scientific information. Survey on hypertension and diuretics].

In order to analyse the quality of scientific communication in the field of hypertension, we have conducted a survey among French physicians. The topics of the questions were partly related to hypertension and partly to diuretics; 3,600 questions forms have been mailed: 610 answers were returned (17%). The results show that most of physicians are unsufficiently informed about primary prevention therapeutical trials and recommendations. Moreover, whereas all physicians questionned (97%) consider that diuretics constitute a current therapeutic approach, this class remains largely unknown concerning its mechanisms, efficacy and tolerance dose relationships. As 80% of general practitioners having participated to this survey wish to be more informed on recent data in this field, these results emphasize the necessity of adapting information to the need of practitioners, raise questions concerning the information supports, the role of scientific committees in the medical information and the necessity to complete clinical research by studies which results may be rapidly applicable in clinical practice.

Adult↗
PubMed1996

[Evaluation of trough/peak ratio of indapamide 1.5 mg sustained-release form assessed by ambulatory blood pressure monitoring].

Because of the high variability of casual blood pressure measurements. ABPM has become a complementary clinical tool for evaluating antihypertensive treatment. Nevertheless, there is still a lack of practical guidelines to interpret the data. A review of the literature shows that ABPM efficacy data are analyzed differently, especially the trough-to-peak ratio proposed by the Food and Drug Administration. Published trough-to-peak ratios are widely disparate due to the diversity of the calculation methods which are most often not justified. Thus inappropriate comparisons of these results can easily produce incorrect conclusions. The aim of this review is to select, through the literature, basic methodological requirements commonly agreed on for accurate assessment of trough-to-peak ratio, and to apply them to the ABPM data on indapamide, a diuretic related to the thiazides. Six methodological requirements commonly agreed on at this time are the following: 1. study design: placebo-controlled study with a placebo run-in period; 2. patients selection: compliance with the study protocol, record obtained before and after treatment for each patient; 3. population analysis: whole and responder population: 4. quality control of the records: 5. placebo effect subtraction; 6. global and individual calculation with the indication of median values. Given that, no T/P ratio, especially for a diuretic, has yet been calculated according to these requirements, the above methodological points were taken into account for the T/P calculation of indapamide, from a placebo-controlled dose-finding study involving 285 patients.

Adult↗
PubMed1995

Influence of angiotensin II type 1 receptor polymorphism on aortic stiffness in never-treated hypertensive patients.

Several clinical and experimental studies have suggested a significant role of angiotensin II in the development of alterations of small and large arteries. The present study was designed to assess the contribution of polymorphism (corresponding to an A1166-->C transversion) of the angiotensin II type 1 receptor (AT1) gene to aortic stiffness. One hundred thirty-four never-treated hypertensive patients were included in the study. Aortic distensibility was evaluated by measuring carotid-femoral pulse wave velocity. Age, systolic and diastolic pressure, and metabolic parameters were similar in the three genotypes. Pulse wave velocity was 11.4 +/- 2.5 m/s in AT1 AA homozygotes, 12.5 +/- 3.2 m/s in AC heterozygotes, and 14.7 +/- 4.0 m/s in CC homozygotes (P = .003, P < .001 after adjustment for age, blood pressure, and body mass index). Moreover, an interaction was found between AT1 genotype and the ratio of total to high-density lipoprotein cholesterol in terms of the development of aortic stiffness. Thus, a positive correlation was observed between the ratio of total to high-density lipoprotein cholesterol and pulse wave velocity in AC and CC (r = .42, P < .001) but not AA patients. These results suggest that the AT1 gene is involved in the development of aortic stiffness in hypertensive patients and could modulate the effects of lipids on large arteries.

Adult↗
PubMed1995

Assessment of arterial distensibility by automatic pulse wave velocity measurement. Validation and clinical application studies.

Pulse wave velocity is widely used as an index of arterial distensibility. The aim of this study was to evaluate the accuracy of a new automatic device to measure it and then to analyze the major determinants of pulse wave velocity by application of this device in a large population. We evaluated the accuracy of on-line and computerized measurement of pulse wave velocity using an algorithm based on the time-shifted and repeated linear correlation calculation between the initial rise in pressure waveforms compared with the reference method (manual calculation) in 56 subjects. The results, analyzed according to the recommendations of Bland and Altman, showed a mean difference of -0.20 +/- 0.45 m/s for the mean carotid-femoral pulse wave velocity values (reference method, 11.05 +/- 2.58 m/s; automatic device, 10.85 +/- 2.44 m/s). The interreproducibility and intrareproducibility of measurements by each method were analyzed with the use of the repeatability coefficient according to the British Standards Institution. The interobserver repeatability coefficient was 0.947 for the manual method and 0.890 for the automatic, and intraobserver repeatability coefficients were 0.938 and 0.935, respectively. We evaluated the major determinants of the carotid-femoral pulse wave velocity measured by the automatic method in a separate study performed in 418 subjects of both sexes without any cardiovascular treatment or complication (18 to 77 years of age; 98 to 222 mm Hg systolic and 62 to 130 mm Hg diastolic pressure).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Aortic distensibility in normotensive, untreated and treated hypertensive patients.

BACKGROUND: Compared with normotensive subjects, untreated hypertensive patients show a decrease of their aortic distensibility. Whether antihypertensive treatment, by reducing blood pressure and changing functional and/or structural abnormalities of the arterial wall, may prevent or reverse the arterial damage due to the accelerated ageing process remains unclear. The objective of the present study was to determine, using a cross-sectional approach, whether aortic distensibility as measured by pulse wave velocity, in treated hypertensive patients whose diastolic blood pressure had been normalised for several months, was significantly improved over that of untreated hypertensive patients. METHODS: Carotid femoral pulse wave velocity was measured in 124 normotensive subjects and 388 hypertensive patients. The latter group included 164 treated patients with well controlled diastolic blood pressure and 224 untreated hypertensive subjects. The three groups did not differ in other cardiovascular risk factors. RESULTS: In each group there was a significant relationship between age and pulse wave velocity. When compared with untreated hypertensives, treated hypertensives with well controlled diastolic blood pressure had significantly lower blood pressure and pulse wave velocity according to age. However, although diastolic blood pressure of well controlled hypertensives was not significantly different from that of normotensive subjects, the aortic distensibility of the controlled hypertensives remained reduced showing two characteristics: a faster increase in pulse wave velocity with age and a negative relationship with HDL-cholesterol. CONCLUSION: These results suggest that long-term antihypertensive treatment and control of blood pressure using only diastolic blood pressure criteria may not fully reverse arterial alteration associated with hypertensive vascular disease.

Adolescent↗
PubMed1995

[Therapeutic benefit of a low dose of indapamide: results of a double-blind against placebo European controlled study].

Indapamide is a diuretic prescribed in the treatment of hypertension at the dosage of 2.5 mg per day. In accordance with international recommendations concerning the need to use low doses of antihypertensives, a new lower-dose form of indapamide has been developed to achieve the best safety/efficacy ratio by decreasing the incidence of hypokalemia. A new pharmaceutical sustained-release (SR) form was developed to give a smooth pharmacokinetic profile in comparison with the indapamide instant release (IR) form. The aim of this study was to determine the lowest new dosage of the SR form producing similar hypertensive efficacy as the LR form, and decreasing the percentage of patients with a serum potassium concentration below 3.4 mmol/l. This multicenter study was designed as a single-blind, run-in, placebo period of 1 month, followed by a double-blind, active treatment period of 2 months, using parallel groups: 285 patients with essential uncomplicated mild-to-moderate hypertension (95 mmHg < or = supine diastolic blood pressure (sDBP) < or = 114 mmHg) were included and randomly treated by either IR indapamide (2.5 mg) or SR indapamide (1.5, 2.0, 2.5 mg). After 2 months of active treatment, the one-way analysis of variance on the principal criterion (difference in sDBP between M2 and M0) revealed a significant treatment effect (p = 0.016). The mean drop in sDBP (+/- standard deviation) was 5.8 mmHg (+/- 8.6) after 2 months of placebo; 10.1 mmHg (+/- 7.0) after indapamide IR 2.5 mg; and 11.0 mmHg (+/- 9.4), 8.9 mmHg (+/- 9.4), and 10.5 mmHg (+/- 8.5) after indapamide SR 1.5 mg, 2 mg, and 2.5 mg, respectively. The difference between the placebo and indapamide treatment was significant (p < or = 0.05). No significant difference was detected between the various indapamide treatments, i.e., no difference between the IR and SR formulations, no difference between the various dosages of the SR form, and therefore no dose/effect relationship in the dose interval tested (SR 1.5, 2, and 2.5 mg). The incidence of patients with a serum potassium concentration less than 3.4 mmol/l was lower with indapamide SR 1.5 mg (11%) than with indapamide 2.5 mg, SR 2 mg, and SR 2.5 mg, respectively: 29%, 18% and 14%. These results show the interest of a low dose of indapamide in improving the safety while producing the same antihypertensive efficacy.

Adolescent↗
PubMed1995

[Ambulatory blood pressure monitoring and clinical trials].

Ambulatory blood pressure monitoring (ABPM) is now widely used for the assessment of antihypertensive drugs. This procedure may be used in phase II studies in dose-ranging evaluations as well as in phase III in order to assess the drug efficacy in the patient's natural environment. The increase in the reproducibility related to the repetition of blood pressure measurements by ambulatory monitoring may improve the accuracy of the trial and minimize the numbers of subjects required. Placebo fails to lower ambulatory blood pressure in almost all studies. Nevertheless, placebo is always necessary in clinical studies with ABPM at least for the pre-inclusion phase and in order to study the peak-trough ratio. This ratio may be accurately assessed by ABPM. Finally, ABPM may be useful to rule out "white coat" responders, who are not really hypertensive patients.

Antihypertensive Agents↗
PubMed1994

[Hemodynamic effects of chronic treatment by cilazapril in normotensive patients with obliterative arterial diseases of the lower limbs].

OBJECTIVE: To determine whether long-term treatment with cilazapril (CIL) may improve pulse pressure (PP), arterial compliance and ankle-arm systolic index (AAI) in patients with lower-extremity arterial disease (LEAD). Indeed, in both systolic hypertension and LEAD, the increase in pulse pressure has been attributed to a reduced compliance. DESIGN AND METHODS: Thirteen patients (age: 65 +/- 5 yrs; AAI: 0.78 +/- 0.15; m +/- SD) were included in a double-blind randomized parallel study to compare the effects of a 6 month treatment with CIL (10 mg per day; n = 6) to those of placebo (PL; n = 7) Blood pressure, AAI and arterial compliance were determined at baseline (MO) and after 3 (M3) and 6 months (M6). Common carotid (CC) and common femoral (CF) artery compliances were noninvasively determined from pulsatile changes in arterial diameter (Wall Track System, Hoeks et al., 1990) and pressure (PP). RESULTS: Both groups were comparable at MO. Compared to PL, CIL significantly reduced PP (-22 +/- 4 vs -2 +/- 9 mmHg) and MAP (-16 +/- 11 vs -4 +/- 7 mmHg) and improved CC (+54 +/- 34 vs +5 +/- 21 mm2.mmHg-1.10(-3)) at M6. Weaker effects were observed at M3. No significant changes in AAI and CF compliance were observed. CONCLUSIONS: A direct effect of CIL on the large artery wall was suggested by 1) a greater reduction in PP than in MAP and 2) a disproportionately greater improvement in CC compliance compared with the reduction in distending pressure (MAP). These results indicate that long-term treatment with CIL may improve large artery function in patients with LEAD.

Adult↗