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Biomedical subjects

B Waeber

Publications and source records attributed to B Waeber.

At least 55 records · Page 3Linked to original sources

[Nebivolol: a beta blocker with vasodilator properties].

Nebivolol is a new cardioselective beta-blocking agent possessing vasodilatory properties involving the endothelium. This compound is a dl-racemic mixture. The d-enantiomer is responsible for the beta-blocking properties whereas the l-enantiomer induces a vasodilation via a nitric oxide (NO) mechanism. Nebivolol is an unique agent that appears promising for the management of patients with hypertension, coronary heart disease or congestive heart failure.

Adrenergic beta-Antagonists↗

Reproducibility of laser Doppler imaging of skin blood flow as a tool to assess endothelial function.

Endothelial dysfunction might be an important and early event in the pathogenesis of major cardiovascular diseases. Therefore, the evaluation of endothelial function in humans may be of great clinical relevance. Usual methods for that purpose are either invasive and/or technically demanding. In the dermal microcirculation, endothelial function may be assessed noninvasively from the laser Doppler measurement of increases in blood flow after either the transdermal application of acetylcholine by iontophoresis, or the release of transient arterial occlusion (reactive hyperemia). An endothelium-independent response may be provided by the iontophoresis of sodium nitroprusside. This approach is notable for technical simplicity, but of uncertain reproducibility. Sixteen young, healthy, nonsmoking males were examined in the fasting state. Changes in skin blood flow were measured with a laser Doppler imager during the iontophoresis of acetylcholine and sodium nitroprusside, as well as during reactive hyperemia, on two different days, at each of two different sites on the volar face of the forearm. Nonspecific effects related to the stimulation of terminal nerve fibers by the iontophoretic current were suppressed by prior surface anesthesia. The iontophoresis of acetylcholine and sodium nitroprusside induced a seven- to eightfold increase in dermal blood flow. The corresponding figure for peak reactive hyperemia was approximately fourfold. The mean coefficients of variation of responses recorded on different days, on the same site, in the same individual were <10% for iontophoresis of acetylcholine and for peak reactive hyperemia, and between 10 and 20% for iontophoresis of sodium nitroprusside. This day-to-day variation was significantly smaller than the site-to-site variation (p < 0.01 for all three responses). Endothelium-dependent and -independent responses of dermal blood flow evaluated with laser Doppler imaging are highly reproducible from day to day, at least in healthy nonsmoking young male subjects, and provided some simple precautions are observed, foremost among which is the strict standardization of the recording site. These observations may have implications for the testing of endothelial function in clinical studies.

Acetylcholine↗

How to improve adherence with prescribed treatment in hypertensive patients?

Low adherence of hypertensive patients to prescribed antihypertensive medications is a major cause of unsatisfactory blood pressure control. Several factors might have a negative influence on long-term adherence with treatment, for example a poor patient-doctor relationship and the presence of drug-induced side-effects. Various strategies are recommended in order to improve patient compliance, including educational programmes, self-measurement of blood pressure and monitoring of compliance. All methods may be helpful to encourage the patient to take the prescribed medication(s) regularly. It is also important to find a drug regimen which is at the same time simple, efficacious and well tolerated. Finally it should be pointed out that the motivation of the patient to follow the treatment requires the doctor to be equally motivated.

Antihypertensive Agents↗

Self-measurement of blood pressure in clinical trials and therapeutic applications.

Self-measurement of blood pressure (SMBP) is increasingly used to assess blood pressure outside the medical setting. A prerequisite for the wide use of SMBP is the availability of validated devices providing reliable readings when they are handled by patients. This is the case today with a number of fully automated oscillometric apparatuses. A major advantage of SMBP is the great number of readings, which is linked with high reproducibility. Given these advantages, one of the major indications for SMBP is the need for evaluation of antihypertensive treatment, either for individual patients in everyday practice or in clinical trials intended to characterize the effects of blood-pressure-lowering medications. In fact, SMBP is particularly helpful for evaluating resistant hypertension and detecting white-coat effect in patients exhibiting high office blood pressure under antihypertensive therapy. SMBP might also motivate the patient and improve his or her adherence to long-term treatment. Moreover, SMBP can be used as a sensitive technique for evaluating the effect of antihypertensive drugs in clinical trials; it increases the power of comparative trials, allowing one to study fewer patients or to detect smaller differences in blood pressure than would be possible with the office measurement. Therefore, SMBP can be regarded as a valuable technique for the follow-up of treated patients as well as for the assessment of antihypertensive drugs in clinical trials.

Antihypertensive Agents↗

Cellular localization, expression and regulation of neuropeptide Y in kidneys of hypertensive rats.

Neuropeptide Y (NPY) is a key modulator of the autonomic nervous system playing pivotal roles in cardiovascular and neuronal functions. In this study, we assessed the cellular localization and gene expression of NPY in rat kidneys. We also examined the relationship between NPY gene expression and renin in two rat models of hypertension (two-kidney, one-clip renal hypertension (2K1C), and deoxycorticosterone-salt-induced hypertension (DOCA-salt)) characterized by a similar blood pressure elevation. In situ hybridization and immunohistochemistry, using anti-NPY or anti-C-flanking peptide of NPY (CPON) antibodies, showed that NPY transcript and protein were colocalized in the tubules of rat kidneys. During experimental hypertension, NPY mRNA was decreased in both kidneys of the 2K1C animals, but not in the kidney of DOCA-salt rats. In 2K1C rats, renal NPY content was also decreased. The difference in NPY gene expression between 2K1C rats (a high renin model of hypertension) and DOCA-salt rats (a low renin model of hypertension) suggests that circulating angiotensin II plays a role in local renal NPY gene expression and that the elevated blood pressure per se is not the primary factor responsible for the control of NPY gene expression in the kidney.

Animals↗

[Treatment strategies in essential arterial hypertension].

Essential hypertension is a very heterogeneous disease. The availability of antihypertensive drugs lowering blood pressure by various mechanisms allows most often to tailor the treatment, i.e. to find for each patient a drug regimen that is both efficient and well tolerated. Frequently medications given as monotherapy are not effective enough so that the use of drug combinations is required. When combined, low doses of antihypertensive agents are generally sufficient, so that tolerability is optimally preserved. Unfortunately many patients do not have their blood pressure controlled during antihypertensive therapy. These patients therefore do not benefit maximally from the cardiovascular protection afforded by blood pressure lowering. It is also imperative to correct all cardiovascular risk factors in each hypertensive patient. Such a multifactorial approach is known to improve effectively the prevention of cardiovascular diseases.

Antihypertensive Agents↗

Felodipine-metoprolol combination tablet: a valuable option to initiate antihypertensive therapy?

The aim of the present study was to assess the efficacy and tolerability of a calcium antagonist/beta-blocker fixed combination tablet used as first-line antihypertesnive therapy in comparison with an angiotensin converting enzyme inhibitor and placebo. Patients with uncomplicated essential hypertension (diastolic blood pressure between 95 and 110 mm Hg at the end of a 4-week run-in period) were randomly allocated to a double-blind, 12-week treatment with either a combination tablet of felodipine and metoprolol (Logimax), 5/50 mg daily (n = 321), enalapril, 10 mg daily (n = 321), or placebo (n = 304), with the possibility of doubling the dose after 4 or 8 weeks of treatment if needed (diastolic blood pressure remaining >90 mm Hg). The combined felodipine-metoprolol treatment controlled blood pressure (diastolic < or =90 mm Hg 24 h after dose) in 72% of patients after 12 weeks, as compared with 49% for enalapril and 30% for placebo. A dose adjustment was required in 38% of patients receiving the combination, in 63% of patients allocated to placebo, and 61% of enalapril-treated patients. The overall incidence of adverse events was 54.5% during felodipine-metoprolol treatment; the corresponding values for enalapril and placebo were 51.7% and 47.4%, respectively. Withdrawal of treatment due to adverse events occurred in 18 patients treated with the combination, in 10 patients on enalapril, and 12 patients on placebo. No significant change in patients' well-being was observed in either of the three study groups. These results show that a fixed combination tablet of felodipine and metoprolol allows to normalize blood pressure in a substantially larger fraction of patients than enalapril given alone. This improved efficacy is obtained without impairing the tolerability. The fixed-dose combination of felodipine and metoprolol, therefore, may become a valuable option to initiate antihypertensive treatment.

Administration, Oral↗

[Fixed antihypertensive drug combinations].

Arterial hypertension is a highly heterogeneous condition. It is therefore not surprising that blood pressure lowering agents acting via a given mechanism allow a normalization of blood pressure in a fraction of hypertensive subjects only. The combination of drugs with different mechanisms of action on the cardiovascular system results in a considerably higher antihypertensive efficacy, not only with regard to the absolute blood pressure reduction but also in the number of responders. This effect is not achieved at the expenses of tolerance, because usually lower doses of the combined agents are sufficient to achieve the target blood pressure. The administration of antihypertensive agents in fixed combination has the advantage of its simplicity for both the physician as well as the patient. This aspect also explains the increasing popularity of fixed combinations as a valuable option in the initial treatment of the hypertensive patient.

Antihypertensive Agents↗

Compliance with aspirin or placebo in the Hypertension Optimal Treatment (HOT) study.

OBJECTIVE: The Hypertension Optimal Treatment (HOT) study is a large, prospective trial aimed at defining the level of diastolic blood pressure required during anti-hypertensive therapy in order to achieve maximal protection against cardiovascular complications. A further aim is to assess the effects on morbidity and mortality of a 75 mg daily dose of aspirin compared with placebo. SUBJECTS AND METHODS: Compliance with double-blind administration of aspirin or placebo added to anti-hypertensive treatment was evaluated for 1 year in a subset (n = 530) of the study population (n = 18 790) by placing the medication in a container closed with an electronic cap that records precisely the time of each opening. RESULTS: The 1-year compliance rate (percentage of days with one opening per day) could be assessed in 501 patients. It averaged 78.3 +/- 25% in aspirin-treated patients (n = 236, mean +/- SD), compared with 78.5 +/- 25% in patients having received placebo (n = 265), and was not influenced by age, sex or country (Germany, Italy, Switzerland, UK). The compliance rate was also similar irrespective of whether the patients had reached their target blood pressure, but was significantly better during the first than the second 6-month monitoring period (84.1 +/- 22% versus 72.3 +/- 32%, n = 501). CONCLUSIONS: The high rate of compliance with aspirin or placebo observed in the HOT study suggests that the patients were highly motivated and may account for the unusually good blood pressure control achieved in this trial during long-term anti-hypertensive treatment.

Aged↗

Task force IV: Clinical use of ambulatory blood pressure monitoring. Participants of the 1999 Consensus Conference on Ambulatory Blood Pressure Monitoring.

OBJECTIVE: To reach a consensus on the clinical use of ambulatory blood pressure monitoring (ABPM). METHODS: A task force on the clinical use of ABPM wrote this overview in preparation for the Seventh International Consensus Conference (23-25 September 1999, Leuven, Belgium). This article was amended to account for opinions aired at the conference and to reflect the common ground reached in the discussions. POINTS OF CONSENSUS: The Riva Rocci/Korotkoff technique, although it is prone to error, is easy and cheap to perform and remains worldwide the standard procedure for measuring blood pressure. ABPM should be performed only with properly validated devices as an accessory to conventional measurement of blood pressure. Ambulatory recording of blood pressure requires considerable investment in equipment and training and its use for screening purposes cannot be recommended. ABPM is most useful for identifying patients with white-coat hypertension (WCH), also known as isolated clinic hypertension, which is arbitrarily defined as a clinic blood pressure of more than 140 mmHg systolic or 90 mmHg diastolic in a patient with daytime ambulatory blood pressure below 135 mmHg systolic and 85 mmHg diastolic. Some experts consider a daytime blood pressure below 130 mmHg systolic and 80 mmHg diastolic optimal. Whether WCH predisposes subjects to sustained hypertension remains debated. However, outcome is better correlated to the ambulatory blood pressure than it is to the conventional blood pressure. Antihypertensive drugs lower the clinic blood pressure in patients with WCH but not the ambulatory blood pressure, and also do not improve prognosis. Nevertheless, WCH should not be left unattended. If no previous cardiovascular complications are present, treatment could be limited to follow-up and hygienic measures, which should also account for risk factors other than hypertension. ABPM is superior to conventional measurement of blood pressure not only for selecting patients for antihypertensive drug treatment but also for assessing the effects both of non-pharmacological and of pharmacological therapy. The ambulatory blood pressure should be reduced by treatment to below the thresholds applied for diagnosing sustained hypertension. ABPM makes the diagnosis and treatment of nocturnal hypertension possible and is especially indicated for patients with borderline hypertension, the elderly, pregnant women, patients with treatment-resistant hypertension and patients with symptoms suggestive of hypotension. In centres with sufficient financial resources, ABPM could become part of the routine assessment of patients with clinic hypertension. For patients with WCH, it should be repeated at annual or 6-monthly intervals. Variation of blood pressure throughout the day can be monitored only by ABPM, but several advantages of the latter technique can also be obtained by self-measurement of blood pressure, a less expensive method that is probably better suited to primary practice and use in developing countries. CONCLUSIONS: ABPM or equivalent methods for tracing the white-coat effect should become part of the routine diagnostic and therapeutic procedures applied to treated and untreated patients with elevated clinic blood pressures. Results of long-term outcome trials should better establish the advantage of further integrating ABPM as an accessory to conventional sphygmomanometry into the routine care of hypertensive patients and should provide more definite information on the long-term cost-effectiveness. Because such trials are not likely to be funded by the pharmaceutical industry, governments and health insurance companies should take responsibility in this regard.

Antihypertensive Agents↗

Task force VI: Self-monitoring of the blood pressure.

BACKGROUND: Self-monitoring of the blood pressure by patients at home or in other nonclinical settings has become increasingly common in recent years. This phenomenon has been fueled in part by the increase in availability of automatic sphygmomanometers, which are now both affordable and easy for patients to use. BENEFITS OF SELF-MONITORING: Self-monitoring of the blood pressure can be an important adjunct to management of hypertension. The technique allows patients to participate more in their care. Self-measured values of blood pressure are more likely to be representative of the average daily blood pressure than is a clinic measurement and may be better related to hypertensive involvement of target organs and cardiovascular morbidity than is the clinic blood pressure. Finally, the self-monitoring of blood pressure has the potential to reduce the costs of hypertension-related care. LIMITATIONS OF SELF-MONITORING: There are several issues that prevent the more widespread use of self-monitoring of the blood pressure in clinical practice. First, devices marketed for use by patients have advanced technically during the 1990s, but many have not been subjected to rigorous clinical validation for precision and reliability (e.g. in terms of Association for the Advancement of Medical Instrumentation and British Hypertension Society guidelines). It is recommended that devices for measuring blood pressure used by patients at home be subjected to the same validation processes as those that are applied to ambulatory recordings. Second, although the upper limits of normal for self-monitored blood pressure of a general population can be defined statistically (it is approximately 135/85 mmHg), it is not yet possible to determine the normal self-monitored blood pressure because these values must be linked to classical clinical cardiovascular endpoints or outcomes. Third, the relationships among self-monitored, clinic, and ambulatory blood pressures are defined for some populations but their behaviors according to age, sex, ethnicity, and treatment status require further study. Fourth, several different schedules for self-monitoring of the blood pressure by patients have been used in clinical research and practice. It will be necessary to determine the optimal schedule and number of recordings required when patients perform self-monitoring of the blood pressure. Fifth, self-monitoring of the blood pressure in clinical trials of antihypertensive therapies is certainly feasible but has typically not been included in their design, either by investigators or by the pharmaceutical sponsors. Sixth, there have been data suggesting that self-monitoring of the blood pressure reduces the comprehensive costs associated with hypertension care on an annual basis. However, since most work on the economic impact of self-monitoring of the blood pressure has been performed in managed-care environments in the USA, it is not known whether this reduction in health-care costs would be applicable to other types of practice environments on a worldwide basis. CONCLUSIONS: Self-monitoring of the blood pressure is at present useful as an adjunct measurement for the management of hypertensive patients and might provide benefits in clinical trials of antihypertensive therapy. Nevertheless, the available data on self-monitoring of the blood pressure are inadequate as grounds for clinicians to make primary diagnostic or therapeutic decisions and should not override the blood pressure obtained by clinical measurement or via ambulatory monitoring.

Blood Pressure↗

Electronic monitoring of compliance to lipid-lowering therapy in clinical practice.

Nonadherence to treatment is a common problem in the clinical management of hypercholesterolemic patients. This study was carried out with the aim of monitoring the daily compliance to a 6-month course of lipid-lowering therapy, using a microelectronic device, the Medication Event Monitoring System (MEMS), versus pill count. Forty men with primary hypercholesterolemia were prescribed fluvastatin 1 x 40 mg daily, provided in a MEMS package to record the date and time of each opening of the pillbox. Thirty-nine of 40 patients (98%) completed the study. Total cholesterol and LDL cholesterol levels decreased significantly (18% and 25%, p < 0.001) during the 6-month therapy period. A high mean rate of compliance was achieved by MEMS using the following three indexes--compliance to total prescribed dose (88.8% +/- 13.5%), compliance to prescribed days (82.4% +/- 19.5%), and compliance to prescribed time of day (81.86% +/- 19.5%)--and by pill count (93.4% +/- 9.5%). In addition, the MEMS provided some patterns of nonadherence to medication, undetectable by pill count alone, such as a drug holiday in 38% of cases, a drug omission for more than 7 consecutive days in 9% of cases, and, conversely, use of more than the one prescribed daily dose in 47% of cases. A significant correlation between the rate of compliance and the decrease in LDL cholesterol was observed only when the compliance was assessed by MEMS. The results indicate that MEMS is a useful tool for monitoring compliance in clinical practice and may possibly increase adherence to long-term lipid-lowering therapy.

Adult↗

Clinical value of ambulatory blood pressure monitoring in the assessment of antihypertensive therapy.

Non-invasive ambulatory blood pressure monitoring (ABPM) is particularly useful for assessing the efficacy of antihypertensive drugs. It provides a large number of blood pressure readings during daytime as well as night-time, which results in a more precise assessment of prevailing blood pressure than can be obtained from sporadic measurements taken by a doctor. Because of this greater precision ABPM reduces the number of patients required in clinical trials to demonstrate differences. It also allows one to define precisely the profile of the blood-pressure-lowering effect of a given drug. Placebo has little effect on ABPM. Thus, a placebo phase is not absolutely necessary. ABPM makes it possible to evaluate the efficacy of an antihypertensive medication by analysing data for patients with a placebo effect separately from data for true responders to the medication. In everyday practice ABPM helps one to detect among patients with hypertension refractory to treatment those who exhibit controlled blood pressures outside the medical environment, thus permitting one to avoid an unnecessary step-up of treatment. In addition ABPM can also help one to identify symptoms occurring during antihypertensive treatment that are related to excessive drug-induced changes in blood pressure.

Antihypertensive Agents↗