Showing papers by "Robert Fagard published in 1998"

Reference values for self-recorded blood pressure: a meta-analysis of summary data

Abstract: Background: The widespread clinical use of selfrecorded blood pressure measurement is limited by the lack of generally accepted reference values. The purpose of this study was therefore to perform a metaanalysis of summary data in an attempt to determine an operational threshold for self-recorded blood pressures. Studies and Methods: Seventeen studies, including a total of 5422 subjects, were reviewed. Eight of these 17 studies included both normotensive and untreated hypertensive subjects, while the other 9 reports included normotensive subjects only. Within each study an operational cutoff point between normotension and hypertension was derived by means of the mean+2 SDs and the 95th percentiles of the self-recorded blood pressure in normotensive subjects. These 2 methods were contrasted with 2 other techniques that have been applied in the literature to calculate (1) the self-recorded pressures equivalent to a conventional pressure of 140 mm Hg systolic and 90 mm Hg diastolic by means of regression analysis and (2) the self-recorded blood pressures at the percentiles corresponding to a conventional pressure of 140/90 mm Hg. The latter 2 methods were applied in untreated subjects not selected on the basis of their blood pressure.

Subgroup and Per-Protocol Analysis of the Randomized European Trial on Isolated Systolic Hypertension in the Elderly

Abstract: Background In 1989, the European Working Party on High Blood Pressure in the Elderly started the double-blind, placebo-controlled, Systolic Hypertension in Europe Trial to test the hypothesis that antihypertensive drug treatment would reduce the incidence of fatal and nonfatal stroke in older patients with isolated systolic hypertension. This report addresses whether the benefit of antihypertensive treatment varied according to sex, previous cardiovascular complications, age, initial blood pressure (BP), and smoking or drinking habits in an intention-to-treat analysis and explores whether the morbidity and mortality results were consistent in a per-protocol analysis. Methods After stratification for center, sex, and cardiovascular complications, 4695 patients 60 years of age or older with a systolic BP of 160 to 219 mm Hg and diastolic BP less than 95 mm Hg were randomized. Active treatment consisted of nitrendipine (10-40 mg/d), with the possible addition of enalapril maleate (5-20 mg/d) and/or hydrochlorothiazide (12.5-25 mg/d), titrated or combined to reduce the sitting systolic BP by at least 20 mm Hg, to below 150 mm Hg. In the control group, matching placebo tablets were employed similarly. Results In the intention-to-treat analysis, male sex, previous cardiovascular complications, older age, higher systolic BP, and smoking at randomization were positively and independently correlated with cardiovascular risk. Furthermore, for total (P=.009) and cardiovascular (P=.09) mortality, the benefit of antihypertensive drug treatment weakened with advancing age; for total mortality (P=.05), the benefit increased with higher systolic BP at entry, while for fatal and nonfatal stroke (P=.01), it was most evident in nonsmokers (92.5% of all patients). In the per-protocol analysis, active treatment reduced total mortality by 24% (P=.05), reduced all fatal and nonfatal cardiovascular end points by 32% (P Conclusions In elderly patients with isolated systolic hypertension, stepwise antihypertensive drug treatment, starting with the dihydropyridine calcium channel blocker nitrendipine, improves prognosis. The per-protocol analysis suggested that treating 1000 patients for 5 years would prevent 24 deaths, 54 major cardiovascular end points, 29 strokes, or 25 cardiac end points. The effects of antihypertensive drug treatment on total and cardiovascular mortality may be attenuated in very old patients.

The epidemiology of the association between hypertension and menopause

Abstract: Menopause is a normal aging phenomenon in women and consists of the gradual transition from the reproductive to the non-reproductive phase of life. The median age at the menopause is currently around 50 years. As a result of the increasing life expectancy in the first and second worlds, many women will be postmenopausal for over one-third of their lives. The influence of menopause per se on blood pressure remains uncertain. Recent experimental and epidemiological evidence supports the hypothesis that oestrogen deficiency may induce endothelial and vascular dysfunction and potentiate the age-related increase in systolic pressure, possibly as a consequence of a reduced compliance of the large arteries. However, the latter hypothesis requires further investigation.

Limitations of the difference between clinic and daytime blood pressure as a surrogate measure of the 'white-coat' effect. Syst-Eur investigators

Abstract: BackgroundThe difference between clinic and ambulatory average daytime blood pressures is frequently taken as a surrogate measure of the ‘white-coat effect’ (i.e. the pressor reaction triggered in the patient by the physician's visit).ObjectiveTo assess the reproducibility of this difference and its

Calcium channel blockade and cardiovascular prognosis in the European trial on isolated systolic hypertension

Abstract: —In the double-blind Systolic Hypertension in Europe (Syst-Eur) Trial, active treatment was initiated with nitrendipine (10 to 40 mg/d) with the possible addition of enalapril (5 to 20 mg/d) and/or hydrochlorothiazide (125 to 25 mg/d) titrated or combined to reduce sitting systolic blood pressure by at least 20 mm Hg to <150 mm Hg In the control group, matching placebos were used similarly In view of persistent concerns about the use of calcium channel blockers as first-line antihypertensive drugs, this report explored to what extent nitrendipine, administered alone, prevented cardiovascular complications Age at randomization averaged 702 years and systolic/diastolic blood pressure 1738/855 mm Hg Of 2398 actively treated patients, 1327 took only nitrendipine (average dose, 234 mg/d), and 1042 progressed to other treatments including nitrendipine (n=757; 357 mg/d), enalapril (n=783; 134 mg/d), and/or hydrochlorothiazide (n=294; 210 mg/d) Compared with the whole placebo group (n=2297), patients receiving monotherapy with nitrendipine had 25% ( P =005) fewer cardiovascular end points, and those progressing to other active treatments showed decreases ( P ≤001) in total mortality (40%), stroke (59%), and all cardiovascular end points (39%) Among the control patients, 863 used only the first-line placebo Compared with this subgroup, patients receiving monotherapy with nitrendipine showed a nearly 50% ( P ≤0004) reduction of all types of end points, including total and cardiovascular mortality The full relative benefit from nitrendipine was seen as early as 6 months after randomization To ascertain that the benefit conferred by the dihydropyridine was not due to selection bias, the 1327 patients remaining on monotherapy with nitrendipine were matched by gender, age, previous cardiovascular complications, and systolic blood pressure at entry with an equal number of placebo patients In this analysis, nitrendipine reduced ( P ≤005) cardiovascular mortality by 41%, all cardiovascular end points by 33%, and fatal and nonfatal cardiac end points by 33% Despite the limitations inherent in post hoc analyses, the present findings suggest that the calcium channel blocker nitrendipine, given as a single antihypertensive medication, prevents cardiovascular complications in older patients with isolated systolic hypertension

Treatment of isolated systolic hypertension in the elderly: further evidence from the Systolic Hypertension in Europe (Syst-Eur) trial

Abstract: The Systolic Hypertension in Europe (Syst-Eur) study investigated whether antihypertensive treatment could decrease the risk of cardiovascular complications in elderly patients with isolated systolic hypertension. Patients > or = 60 years were randomly assigned to treatment with the dihydropyridine calcium antagonist nitrendipine (n = 2,398), with the addition of enalapril and hydrochlorothiazide if needed, or to matching placebo (n = 2,297). In the intent-to-treat analysis, the between-group difference in blood pressure was 10.1/4.5 mm Hg (p < 0.001). Active treatment decreased the total incidence of stroke (the primary endpoint) by 42% (p = 0.003), of all cardiac endpoints by 26% (p = 0.03), and of all cardiovascular endpoints combined by 31% (p < 0.001). Cardiovascular mortality was somewhat lower with active treatment (-27%, p = 0.07); all-cause mortality was not significantly different (-14%; p = 0.22). For total (p = 0.009) and cardiovascular (p = 0.09) mortality, the benefit of antihypertensive treatment weakened with advancing age and for total mortality it decreased with lower systolic blood pressure at entry (p = 0.05). The benefits of active treatment were not independently related to gender or to the presence of cardiovascular complications at entry. Antihypertensive therapy was at least as effective in patients with diabetes as in those without diabetes at entry. Further analyses suggested benefit in patients who were taking nitrendipine as monotherapy. Per-protocol analysis largely confirmed the intent-to-treat results. Active treatment decreased all strokes by 44% (p = 0.004), all cardiac endpoints by 26% (p = 0.05), and all cardiovascular endpoints by 32% (p < 0.001). Total mortality was decreased by 26% (p = 0.05), but the similar reduction in cardiovascular mortality did not reach significance in this analysis. It is concluded that stepwise antihypertensive drug treatment starting with nitrendipine improves prognosis in elderly patients with isolated systolic hypertension.

Ambulatory blood pressure monitoring and postprandial hypotension in elderly patients with isolated systolic hypertension

Abstract: The present analysis was undertaken to evaluate postprandial (PP) changes in blood pressure (BP) assessed with ambulatory BP monitoring (ABPM) in elderly subjects with isolated systolic hypertension (ISH) on conventional measurement. A total of 530 patients (335 women and 195 men, aged 60–100 years, median 70 years) who performed an ABPM during the placebo run-in period of the Syst-Eur trial were included into the analysis. The PP changes in BP and heart rate (HR) were calculated by subtracting the mean systolic BP (SBP), diastolic BP (DBP) and HR in the 2 h preceding the main meal from the corresponding means covering the 2 h after the meal. The reproducibility of the postprandial fall in BP and heart rate (PPH) was assessed by contrasting the first and second ABPM in a subgroup of 147 patients who performed two ABPM’s during the placebo run-in period. The mean SBP and DBP decreased and reached the nadir 2 h after the main meal while HR did not change. When PPH was assessed by comparing BP in the 2 h before and after the meal, both SBP and DBP decreased significantly (respectively −6.6 mm Hg, −5.4 mm Hg; P < 0.001). in 67.6% of all patients a decrease in sbp was observed and in 24.1% it exceeded 16 mm hg. the corresponding values for dbp were 71.3% and 24.5% (dbp decreased more than 12 mm hg). a greater fall in dbp was associated with a greater decrease in hr (r = 0.20, P < 0.001), while changes in sbp and hr were not interrelated. regression analysis did not identify any significant covariate of pph. group means of pph could be reproduced without significant changes in their values, but the within-subject reproducibility of the pp changes was low. there were no differences in pph according to the place of residence of the patients. in conclusion, the descriptive analysis of the meal-induced changes in abpm in elderly subjects with ish showed that in every day circumstances most of them experience falls in both sbp and dbp within 2 h after the meal.

Power spectral analysis of heart rate variability by autoregressive modelling and fast Fourier transform: a comparative study.

Abstract: OBJECTIVE To compare the results from autoregressive modelling (ARM) and from fast Fourier transform (FFT), the most commonly used methods for the analysis of short-term heart rate variability in the frequency domain. METHODS & RESULTS RR interval and respiratory activity were recorded in the supine and standing positions under standardized laboratory conditions in a population-based sample of 614 subjects. The low-(LF) and high-frequency (HF) components of heart rate variability were identified by power spectral analysis, by use of FFT, with application of two sets of frequency ranges, and by ARM; LF and HF power were expressed in both normalized (%) and absolute units (ms2). The RR interval, its variance and the HF power decreased from the supine to the standing position (P < 0.001). The LF power increased on standing when expressed in normalized units, but decreased in absolute units, whereas the LF-to-HF ratio increased (P < 0.001). On the low side of the spectrum, FFT slightly overestimated the LF component obtained with ARM, when the predefined frequency range was 0.05-0.15 Hz (P < 0.001); the underestimation of LF in the frequency range 0.07-0.14 Hz was more pronounced, particularly in the erect position (P < 0.001). Both FFT methods overestimated (P < 0.001) the ARM HF component, more so for the 0.15-0.50 Hz range than for the 0.14-0.35 Hz range. Finally, we observed considerable within-subject differences between methods, which were estimated by calculation of the limits of agreement. CONCLUSIONS Different methods for spectral decomposition of short-term heart rate variability yield similar qualitative results, but the quantitative results differ between ARM and FFT, and within the FFT method according to the selected frequency range.

Conventional and ambulatory measurements of blood pressure in old patients with isolated systolic hypertension: baseline observations in the Syst-Eur trial.

Abstract: OBJECTIVES: To compare clinic and am measurements of blood pressure in old patients with isolated systolic hypertension and their reproducibilities. PATIENTS: In total 610 patients aged >/= 60 years with isolated systolic hypertension detected by clinic measurement were monitored during the placebo run-in phase of the Syst-Eur trial. METHODS: The time-weighted 24 h blood pressure, clock-time day and night blood pressures, the cumulative-sum-derived crest and trough blood pressures and the high and low blood pressure levels according to the square-wave model were computed. The daily alteration between the high and low spans of blood pressure was quantified using the day-night difference, the cumulative-sum-derived magnitude of circadian alteration, the Fourier amplitude and the difference between the high and low blood pressure levels of the square-wave model. RESULTS: The daytime am systolic blood pressure was, on average, 21 mmHg lower than the clinic systolic blood pressure, whereas diastolic pressure was, on average, similar with both techniques of measurement. Clinic levels of blood pressure in the 141 patients who underwent repeat measurements and the parameters describing the difference between the daily high and low spans of blood pressure were equally reproducible. However, both were less reproducible than the ambulatory blood pressure levels. The reproducibility coefficients, expressed as percentages of near maximum variation, were 49 and 50% for the clinic systolic and diastolic blood pressures, 30 and 32% for the mean 24 h systolic and diastolic blood pressures and 45-55% for the parameters describing the daily alteration between the high and low spans of blood pressure. CONCLUSION: Values of blood pressure in old patients with isolated systolic hypertension were more reproducible for ambulatory than they were for clinic measurements. Levels in patients selected because they have a high clinic blood pressure may be substantially higher with conventional than they are with daytime ambulatory measurement. The prognostic significance of this difference for the present patients is currently under investigation.

Human erythrocytes contain Ca2+, calmodulin-dependent cyclic nucleotide phosphodiesterase which is involved in the hydrolysis of cGMP.

Abstract: To determine whether phosphodiesterase (PDE) is involved in the degradation of cGMP in human erythrocytes, we studied the cell cGMP content in the presence of different PDE inhibitors: zaprinast and dipyridamole, specific inhibitors of cGMP-binding, cGMP-specific PDE (cG-BPDE); vinpocetine, a specific inhibitor of Ca2+, calmodulin-dependent phosphodiesterase (CaM-PDE); an unspecific inhibitor, 3-isobutyl-1-methylxanthine (IBMX). IBMX, zaprinast, and dipyridamole at 30 microM did not affect the intracellular cGMP content. However, vinpocetine at this concentration increased the cGMP content by 102 +/- 14% (p < 0.05). The effect of vinpocetine was dose-dependent, reached the maximal level after 1 min of incubation and flattened at the same level. Ca2+ (10 microM) in the presence of the Ca(2+)-ionophore, A23187 (5 microM), decreased the cGMP content (-23% +/- 4; p < 0.05), which can be explained by the CaM-PDE activation. The Ca(2+)-induced decrease in cGMP was completely inhibited by the CaM antagonist, W-7 (100 microM). These data suggest that erythrocytes contain Ca2+, CaM-PDE.

Opposite associations of circulating aldosterone and atrial natriuretic peptide with left ventricular diastolic function in essential hypertension.

Abstract: Opposite associations of circulating aldosterone and atrial natriuretic peptide with left ventricular diastolic function in essential hypertension

Activation by calcium of erythrocyte Na+/H+ exchange in men.

Abstract: Objective To determine whether protein kinase C is necessary for the calcium activation of the Na + /H + exchange in human erythrocytes by studying activation by calcium of erythrocyte Na + /H + exchange in control cells, in protein kinase C-depleted cells after downregulation of protein kinase C with phorbol-12-myristate-1 3-acetate and in cells that had been treated beforehand with phorbol-12-myristate-13-acetate with and without the calpain inhibitor E-64d. Methods Erythrocyte Na + /H + exchange was measured by determining the initial rates of the influx of Na + into Na + -depleted, acid loaded cells. The effects of various concentrations (0-1 mmol/l) of CaCl 2 and the effects of 1 mmol/l CaCl 2 on activation of the intracellular pH and on the external Na + activation of Na + /H + exchange were studied. The effects of 1 mmol/l CaCl 2 on Na + /H + exchange in control cells and cells that had been incubated beforehand with and without 1 μmol/l phorbol-12-myristate-13-acetate and with E-64d and 1 μmol/l phorbol-12-myristate-13-acetate for 1, 2, 3 and 24 h were also investigated. Results Addition of Ca 2+ to a concentration in the range 0-1 mmol/l in the presence of calcimycin resulted in stimulation of Na + /H + exchange: 1 mmol/l CaCl 2 increased (P < 0.001) the erythrocyte Na + /H + exchange by 74%. Calcium increased the maximum rate for activations by intracellular pH and by external Na + of Na + /H + exchange, whereas it did not affect the Michaelis-Menten constants for activation by intracellular H + and external Na + . However, calcium did not activate the Na + /H + exchange in protein kinase C downregulated erythrocytes and administration of the calpain inhibitor E-64d could not prevent this inactivation. Conclusion Our data indicate that protein kinase C is necessary for the activation by calcium of the erythrocyte Na + /H + exchange.

Antihypertensive drugs and cognitive function in older people.

Abstract: To the Editor: We have read with interest the recent report by Heckbert and colleagues.' However, we feel the suggestion that treatment with calcium channel blockers or loop diuretics would be associated with worse cognitive function in older hypertensive patients is not substantiated by the evidence presented. First, the analysis included only 1268 of 2815 potentially eligible hypertensive patients (45%). The 2815 hypertensive patients represented are already a selected group as the overall response rate was 58%. In addition, the authors did not state explicitly that all study participants underwent a magnetic resonance imaging (MRI) scan. Consenting patients are self-selected to a large extent. Furthermore, the authors included the 3073 normotensive subjects in only part of their analyses although a substantial proportion of them must have been taking cardiovascular drugs for reasons other than hypertension, e.g., angina pectoris. Why Heckbert and colleagues' chose patients taking p-blockers as the reference group (104 patients receiving monotherapy) rather than those taking thiazides remains unclear. Indeed, a total of 479 patients were taking thiazide diuretics either alone (n = 254) or in combination with other agents (n = 225). Thiazide diuretics, according to the national guidelines in the United States; remain the drug of choice to treat older hypertensive patients. Moreover, the results on dementia observed in the Systolic Hypertension in the Elderly Program (SHEP) trial3 are not referenced. In this prospective trial, diuretic-based antihypertensive treatment, compared with placebo, did not significantly change the incidence of dementia. This null result in a long-term trial with a double-blind, placebo-controlled design is another reason why selecting patients prescribed diuretics as the reference group would have been more appropriate. As in other observational studies on the adverse effects of medications, confounding by indication is a potential source of bias in Heckbert's study.' Hypertensive patients treated with calcium channel blockers and loop diuretics could have differed in some way from those treated with p-blockers. Also, the suggestion that a higher white matter grade on an MRI scan correlated with a higher dose of the calcium channel blocker is questionable. A test statistic with a P value of .163 is nonsignificant, even in evaluating a one-sided hypothesis. Furthermore, the authors' only considered the antihypertensive medications at the annual visit just preceding the date of the MRI scan and did not attcmpt to account for the duration of drug usage or the total number of patient-years on specific antihypertensive agents. On the other hand, Heckbert and colleagues' are right in stating that randomized trials of the long-term use of antihypertensive agents are needed to assess possible causal associations between brain abnormalities and the intake of these drugs. The Vascular Dementia substudy4 to the placebocontrolled, double-blind Syst-Eur trial' aims to provide information about the effects of antihypertensive treatment on the incidence of dementia and on the change in the Mini-Mental State score in older patients with isolated systolic hypertension4 Active treatment consists of the dihydropyridine calcium channel blocker nitrendipine (10-40 mg/day) with the possible addition in treatment-resistant patients of enalapril (5-20 mg/day) and/or hydrochlorothiazide (12.5-25 mg/ day).' A total of 3110 patients have been enrolled in this substudy. The principal results will become available in the course of 1998.