The antihypertensive efficacy and tolerability profiles of the selective AT1 receptor antagonists telmisartan and losartan were compared with placebo in a 6-week, multinational, multicentre, ...randomised, double-blind, double-dummy, parallel-group study of 223 patients with mild-to-moderate hypertension, defined as clinic diastolic blood pressure (DBP) >/=95 and </=114 mm Hg, clinic systolic blood pressure (SBP) >/=140 and </=200 mm Hg, and 24-h ambulatory DBP >/=85 mm Hg. After a 4-week single-blind placebo run-in, eligible patients were randomised to receive telmisartan 40 mg, telmisartan 80 mg, losartan 50 mg, or placebo. Ambulatory blood pressure monitoring (ABPM) after 6 weeks of double-blind therapy showed that all active treatments produced significant (P < 0.01) reductions from baseline in 24-h mean SBP and DBP compared with placebo. During the 18-to-24 h period after dosing, the reductions in SBP/DBP with telmisartan 40 mg (10.7/6.8 mm Hg) and 80 mg (12.2/7. 1 mm Hg) were each significantly (P <0.05) greater than those observed for losartan 50 mg (6.0/3.7 mm Hg), and losartan was no better than placebo. Also for the 24-h mean blood pressure, telmisartan 40 mg and 80 mg were significantly (P< 0.05) better than losartan 50 mg. Compared with losartan, telmisartan 80 mg produced significantly (P < 0.05) greater reductions in both SBP and DBP during all monitored periods of the 24-h period, while telmisartan 40 mg produced significantly greater reductions in SBP and DBP in the night-time period (10.01 pm to 5.59 am) (P < 0.05) and in DBP in the morning period (6.00 am to 11.59 am) (P < 0.05). All treatments were comparably well tolerated. Telmisartan 40 mg and 80 mg once daily were effective and well tolerated in the treatment of mild-to-moderate hypertension, producing sustained 24-h blood pressure control which compared favourably with losartan.
Systolic and diastolic blood pressures are the exclusive mechanical factors considered as predictors of cardiovascular risk for members of populations of normotensive and hypertensive subjects. ...However, if hypertension is considered as a mechanical factor acting on the arterial wall with deleterious consequences, the totality of the blood pressure curve should be considered in order to investigate the risk. The purpose of this review is to show that in addition to systolic and diastolic blood pressures, other hemodynamic indexes with particular relevance for cardiac complications and that originate from pulsatile pressure should be taken into account, namely brachial pulse pressure, pulse pressure amplification, early wave reflections, and pulse wave velocity.
Recent studies have shown that F2-isoprostane levels-a marker for lipid peroxidation-are increased in human renovascular hypertension but not in essential hypertension. Angiotensin II specifically ...stimulates F2-isoprostane production through activation of the AT1 receptor. The objective was to determine whether there is a relationship between the level of oxidative stress evaluated by measuring urinary F2-isoprostanes levels and polymorphisms of genes involved in the renine angiotensin aldosterone system (RAAS) regulation. The population studied included 100 subjects, 65 of whom were healthy normotensives; the other 35 were suffering from untreated, essential hypertension. The polymorphisms studied concern the genes encoding angiotensin I-converting enzyme (ACE/in16del/ins), angiotensin II receptor type I (AGTR1/A+39CA+1166C and AGTR1/A-153G), angiotensinogen (AGT/M235T), and aldosterone synthase (CYP11B2/T344C). Oxidative stress was evaluated by measuring urinary F2-isoprostanes levels. The characteristics of the population were as follows: men/women = 46/56; age = 50 +/- 10 years; BMI = 24 +/- 3 kg/m2; SBP = 131.7 +/- 17.2 mm Hg; DBP = 84.6 +/- 10.4 mm Hg. In univariate analysis, urinary F2-isoprostane levels were significantly lower in the presence of the G allele of AGTR1/A-153G (56 +/- 17 vs 76 +/- 39 pmol/mmol creatinine; P < 0.001, and P < 0.01 after Bonferroni correction for 10 tests). In multivariate analysis, taking into account BP, age, gender, BMI, plasma glucose, and total cholesterol, the G allele of AGTR1/A-153G is linked independently to urinary F2-isoprostanes level (P < 0.01). Our data suggest that F2-isoprostane level depends at least in part on the A-153G polymorphism of the angiotensin II AT1 receptor gene. The clinical and prognostic relevance of this polymorphism requires further investigation.
Subjects with white-coat normotension (WCNT) or masked hypertension, i. e. a normal office blood pressure (BP) reading but elevated ambulatory blood pressure monitoring (ABPM) results, have not been ...extensively studied. The aim of this work was to compare true normotensive subjects (NT), WCNT and nevertreated hypertensive subjects (HT, with elevated BP according to both office and ABPM readings). One hundred and fifty subjects were recruited to analyze cardiovascular characteristics. Office BP readings coupled with ABPM results were used to break this population down into 51 NT, 18 WCNT and 81 HT. Office BP readings were higher in WCNT than in NT. In WCNT, carotid-femoral pulse wave velocity (PWV) was higher than in NT (with a borderline significance p = 0.05) and the standing baroreflex sensitivity (BRS) was lower (p = 0.04). Left ventricular mass index (LVMI) and carotid intima-media thickness (IMT) tended to increase and BRS measurements tended to decrease from NT through WCNT to HT. However, the difference across the board is only significant (p < 0.05) between NT and HT. If only the subset of NT subjects with SBP readings comparable to those of the WCNT subjects (i. e. SBP > 120 mmHg) is considered, no significant difference is detected in PWV and the only difference is detected in BRS (respectively for standing PS+/RR+: 5.7 +/- 1.4 ms/mmHg vs 4.9 +/- 1.2 ms/mmHg, p = 0.04). In conclusion, the principal cardiovascular differences measured between the NT and the WCNT can probably be explained by their difference in clinical level of pressure at rest. Only the BRS remains different between NT and WCNT when the real level of clinical pressure is taken into account.
Objective: This double-blind parallel-group randomized trial compared the efficacy and safety of fixed combination valsartan 160 mg/hydrochlorothiazide 12.5 mg (Val 160/HCTZ 12.5) once daily (o.d.) ...and Val 160/hydrochlorothiazide 25 mg (Val 160/HCTZ 25) o.d. vs Val 160 o.d. monotherapy in patients with mild-to-moderate essential hypertension not adequately controlled with valsartan monotherapy. Method: A total of 2002 patients whose BP was inadequately controlled with 4 weeks of Val 160 mg o.d. monotherapy were randomized to treatment for 8 weeks with Val 160 (n = 666), Val 160/HCTZ 12.5 (n = 670) or Val 160/HCTZ 25 (n = 666). Results: Active treatment significantly reduced BP in all groups over the 12 weeks of the study (p < 0.001). The greatest reductions were achieved with Val 160/HCTZ 25. Reductions were 10.8, 12.8 and 14.2 mmHg (sitting diastolic blood pressure) and 15.7, 19.4 and 21.8 mmHg (sitting systolic blood pressure), for the Val 160, Val 160/HCTZ 12.5 and Val 160/HCTZ 25 groups, respectively. Responder rates were high in all groups (49%, 62% and 68%). In elderly patients (≥65 years) responder rates of 70% were achieved with Val 160/HCTZ 25. All treatments were well tolerated, in all patient groups. Conclusions: The combination of Val 160 plus HCTZ 12.5 or HCTZ 25 provides effective and well-tolerated treatment in patients inadequately controlled after 4 weeks of monotherapy. In elderly patients a responder rate of 70% was achieved with Val 160/HCTZ 25.
The antihypertensive efficacy of a 1.5-mg sustained-release formulation (SR 1.5) of indapamide, a diuretic related to thiazide, has been pointed out by using conventional sphygmomanometric ...measurement 24 h after dosing in clinic, in two large European randomized, double-blind, controlled studies (2 and 3 months). One of these studies was then extended to 12 months, as a complementary open study. Quality-controlled ambulatory blood pressure monitoring (ABPM) data for a total of 216 patients from these studies are presented, including subgroups of hypertensives and responders. Indapamide SR 1.5 achieves an adequate 24-h blood pressure control by significantly reducing the 24-h, diurnal, and nocturnal blood pressures versus baseline, confirming the sphygmomanometric data. The benefit at 2 and 3 months is maintained at 1 year, which confirms the long-term efficacy of SR 1.5 mg. The trough-to-peak ratio--not previously calculated for a diuretic according to international guidelines--meets Food and Drug Administration requirements and confirms the 24-h efficacy of indapamide SR 1.5.
The number of studies of the efficacy of drugs in hypertension and of their effects on morbidity and mortality continues to be large. Traditionally such studies were carried out by measuring the ...blood pressure (BP) in the office. Recently, there has been an increasing use of other approaches, such as self-measurement. The advantages of this technique may be the achievement of greater precision of measurement, explained by elimination of the white-coat effect, reduction in placebo effect and reduction in variability of BP. Some have even noted a greater reproducibility than using ambulatory BP monitoring. We now have available reference values and normal ranges for self-BP monitoring. The feasibility and the limitations of self-BP measurement are also known. Self-measurement allows multiple recordings of BP over the short term as well as over the long term. Moreover, the compliance of this technique is satisfying. The analysis of the data requires precise recommendations. One cannot refer to trough : peak ratio, which is used in ambulatory recordings. However, other methods of analysis such as evening BP : morning BP ratio or measures taken after taking treatment are useful. The number of subjects needed for a study is much smaller than in a study performed using office measurements for a similar or better statistical power. Such a method has a higher predictive value than clinic measurement both for study of end organ damage and for morbidity and mortality. Finally home measurement is much less costly. In conclusion, provided one uses validated equipment and if one follows recommendations for each measurement and for the succession of measurements, then self-measurement of BP at home seems a useful and practical tool for therapeutic trials.
Patent foramen ovale is frequently associated with embolic cerebrovascular accidents. The diagnosis of patent foramen ovale is easier since the advent of transesophageal echocardiography. However, ...this method is semi-invasive and is not readily available in all units. Contrast transcranial Doppler ultrasound enables the detection of the passage of a contrast material injected into a peripheral vein to the cerebral circulation across an orifice which is most often a patent foramen ovale. Contrast transcranial Doppler ultrasound may facilitate, with a high sensitivity and specificity, the diagnosis of a patent foramen ovale when a transesophageal echo is not possible. However, transesophageal echocardiography remains the preferred test especially in the young since other potentially embolic sources, such as a thrombus in the left atrium, may be demonstrable.
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