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Biomedical subjects

R Fagard

Publications and source records attributed to R Fagard.

At least 145 records · Page 8Linked to original sources
PubMed1995

Diurnal blood pressure profile in older patients with isolated systolic hypertension. The SYST-EUR Investigators.

This study describes the diurnal blood pressure (BP) profile and identifies its correlates in older patients with isolated systolic hypertension (ISH). The ambulatory BP readings of 408 patients, aged > or = 60 years, with ISH on clinic measurement, enrolled in the placebo run-in phase of the Syst-Eur Trial were examined. The time-weighted 24 h BP, daytime and night-time BP and the cusum-derived crest and trough BP were computed to express the BP level. The daily alteration between the high and low BP span was estimated from the day-night BP difference, the cusum derived circadian alteration magnitude and plot height, as well as the amplitude of the Fourier curve. The 24 h SBP and DBP tended to be higher in men (150 +/- 15/82 +/- 9 mm Hg) than in women (147 +/- 17/79 +/- 10 mm Hg), but the sex difference was only significant for DBP. In multiple regression analysis, the 24 h SBP increased (P < 0.05) by 3 mm Hg for each 10 year increment in age and was also 10 mm Hg higher (P < 0.001) in smokers than in non-smokers; the 24 h DBP was 2 mm Hg higher (P < 0.05) in men than in women and decreased (P < 0.05) by 1.5 mm Hg for each 10 year increment in age. The day-night difference in SBP increased with 2 mm Hg for each 10 mm Hg increase in the conventional pressure, decreased with 5 mm Hg for each 10 year increment in age and was 6 mm Hg higher in smokers than in non-smokers; the day-night difference in diastolic pressure was 2 mm Hg greater in women than in men. We conclude that the main determinants of the diurnal BP variation in older patients with isolated systolic hypertension were sex, age, smoking habits and the level of pressure on conventional measurement.

Age Distribution↗
PubMed1995

Signs of functional efferent reinnervation of the heart in patients after cardiac transplantation.

Short-term heart rate and blood pressure variability were assessed in 62 patients, studied within 1 month, at 1, at 2 or at 3-5 years after cardiac transplantation and in 13 healthy control subjects. Means and total variances were calculated and the powers of the low frequency (LF, 0.07-0.14 EqHz) and of the high frequency (HF, 0.14-0.35 EqHz) components were derived from power spectral analysis. Mean heart period, its total variance and the powers of the LF and HF components were lower in the transplanted patients than in the controls (P < 0.001). The total variance and the LF and HF powers differed significantly among the groups of transplanted patients (P < 0.01) and intergroup comparison showed significantly higher values in patients 3-5 years after transplantation than in those studied within 1 month. The variance of systolic blood pressure and its power spectrum did not differ between patients and controls. The results suggest that partial functional reinnervation of the sinus node occurs after heart transplantation in man.

Blood Pressure↗
PubMed1994

Contribution of tyrosine kinases to the selective orientation of human CD4+ bifunctional cloned T cells toward proliferation or cytolytic function.

We show that T cell activation of human CD4+ cloned T cells through the CD2 molecule can induce either autocrine proliferation or cytolysis, depending on the pair of anti-CD2 mAbs used for stimulation, that is, D66/T11(1) or GT2/T11(1), respectively. As the earliest biochemical event after CD2 stimulation is likely the induction of tyrosine phosphorylation of various proteins, we investigated whether differential activation of protein tyrosine kinases (PTKs) could contribute to the selective induction of each function. Results show that herbimycin A, a potent PTK inhibitor, markedly decreased the induction of both proliferation and cytolysis. This implies a regulatory role for tyrosine phosphorylation in the induction of each function by CD2. However, that PTKs are differentially activated upon induction of proliferation by D66/T11(1) or cytotoxic function by GT2/T11(1) emanated from two different approaches. First, immunoblotting total cellular extracts with an anti-phosphotyrosine mAb showed different patterns of tyrosine phosphorylation depending on the pair of CD2 mAbs used for stimulation. Second, a differential activation of p56lck, a src-related PTK, was observed after stimulation with D66/T11, and GT2/T11(1). Although induction of proliferation by D66/T11(1) was correlated with increased Lck activity, this was not observed when cells were triggered to lyse by GT2/T11(1). Thus, by providing striking correlative evidences linking differences in PTK activation with induction of different functions in bifunctional cloned T cells, our results strongly suggest that PTKs may contribute to the selective orientation of T cell functions at a single-cell level.

Antibodies, Monoclonal↗
PubMed1994

LFA-1-mediated antigen-independent T cell adhesion is regulated by CD4 and p56lck tyrosine kinase.

We examined the role of CD4 and p56lck in the regulation of LFA-1-dependent T cell adhesion to B cells and to fibroblasts expressing ICAM-1 and HLA-DR by using various transfectant constructions. Although CD4 transfection in CD4low HUT78 T cell lines did not significantly modify their maximal binding to B cells and fibroblasts, it made the LFA-1-dependent adhesion sensitive to inhibition by anti-CD4 Ab, HIV-1 (env) gp 160, and a 12-mer peptide encompassing the 35-46 sequence of the beta 1 domain of the MHC class II molecule. CD4low HUT78 T cell adhesion to B cells was stable over 60 min, whereas expression of CD4 led to a transient adhesion. In addition, adhesion of CD4+ T cells to MHC class II- B cells was also stable. The CD4-dependent alteration of adhesion required the association of CD4 with p56lck because expression of mutant forms of CD4 unable to bind p56lck resulted in a lack of CD4-dependent regulation of adhesion. Herbimycin A, an inhibitor of tyrosine kinase activity, reversed the effect of CD4 transfection on adhesion. These results indicate that ligand binding to CD4 delivers a signal-inducing cell dissociation by activating p56lck tyrosine kinase. This regulatory pathway may provide a quick and reliable way for multiple and subsequent Ag-independent adhesion events of CD4+ T cells.

Adult↗
PubMed1994

Ligation of CD4 surface antigen induces rapid tyrosine phosphorylation of the cytoskeletal protein ezrin.

Ezrin is a cytoskeletal protein which is tyrosine phosphorylated in human T lymphocytes upon stimulation through CD3 antigen (Egerton, M., Burgess, W., Chen, D., Druker, B. J., Bretscher, A., and Samelson, L. A., J. Immunol. 149, 1847, 1992). We found that tyrosine phosphorylation of ezrin was markedly enhanced by ligation of either CD3 or CD4 antigen and peaked between 1 and 2 min. Furthermore, stimulations through CD4 and CD3 antigens were additive. Using the cell line HUT 78 T transfected with either normal human CD4 or mutated CD4 molecules unable to associate with p56lck tyrosine kinase, we showed that this kinase plays a major role in the tyrosine phosphorylation of ezrin. Moreover, CD45R ligation studies provided evidence that the membrane-associated tyrosine phosphatase CD45 activity regulates ezrin tyrosine phosphorylation. Subcellular fractionation showed that although ezrin is mainly located in the cytosol of T cells, anti-CD4-induced ezrin phosphorylation involved the membrane fraction, with no concomitant translocation of the protein from the cytosol to the membrane.

Animals↗
PubMed1994

Prognostic significance of peak exercise capacity in patients with coronary artery disease.

OBJECTIVES: The aim of this study was to investigate the prognostic significance of peak oxygen uptake in patients with coronary artery disease who had an exercise test that could be sustained to exhaustion without limiting symptoms. BACKGROUND: Many studies have reported an inverse association between the level of exercise reached during a stress test and mortality or cardiovascular morbidity. These studies have used submaximal or symptom-limited exercise testing in patients with a recent myocardial infarction. METHODS: Peak oxygen uptake was measured in male patients > or = 4 weeks after myocardial infarction (312 patients) or coronary artery surgery (215 patients) by use of a graded uninterrupted exercise test performed to exhaustion. Apart from peak oxygen uptake, several risk factors for cardiovascular disease, patient and exercise characteristics and drug treatment were considered in the Cox proportional hazards model. RESULTS: During the total follow-up period of 3,213 patient-years, 53 patients died. Of these 53 patients, 33 died of cardiovascular causes. All-cause and cardiovascular mortality decreased with increasing peak oxygen uptake, even after adjustment for significant covariates. The relative hazard rates of 0.43 and 0.29 indicate that a hypothetic increase in peak oxygen uptake by 1 liter/min could be associated with decreases in all-cause and cardiovascular mortality of 57% and 71%, respectively. CONCLUSIONS: Exercise capacity is an independent predictor for subsequent all-cause and cardiovascular mortality in patients able to perform an exercise test until exhaustion.

Coronary Artery Bypass↗
PubMed1994

Effect of age on the hemodynamic response to posture in nonelderly hypertensive patients.

The objective of this study was to assess the effects of age on the hemodynamic response to a change in posture in essential hypertension. Invasive hemodynamic measurements were performed in the supine and sitting position in 110 men, aged 16 to 64 years, in whom cardiovascular complications were virtually excluded. The change of systolic and diastolic intraarterial pressure, from 153/83 mm Hg after 30 min of supine rest to 156 (P < .05)/92 (P < .001) mm Hg after sitting for 10 min, was not significantly (P > .10) related to age. Heart rate (+9 beats/min) and systemic vascular resistance (+4.6 mm Hg/L/min) increased (P < .001) on sitting; cardiac output (-1.7 L/min), stroke volume (-31 mL), and pulmonary capillary wedge pressure (-2.1 mm Hg) fell (P < .001). Whereas the postural changes of heart rate (P < .01), cardiac output (P < .001), stroke volume (P < .001), and wedge pressure (P = .06) were less pronounced in older than in younger patients, the increase of systemic vascular resistance was not related to age (P > .10). The slopes of the postural changes of heart rate and of systemic vascular resistance differed significantly (P = .01). The results were not confounded by the level of blood pressure or weight. In conclusion, the smaller postural falls of cardiac output, stroke volume, and wedge pressure in older patients suggest less thoracic blood volume displacement to the lower parts of the body, possibly resulting from a lesser peripheral venous distensibility. The increase of heart rate in response to the upright posture is less pronounced at older age, whereas the reflex control of the peripheral vasculature is preserved and blood pressure maintained.

Adolescent↗
PubMed1994

Life style as a determinant of blood pressure in the general population.

This study investigated which life style factors were correlated with the level and the variability of systolic (SBP) and diastolic (DBP) pressure in a random population sample. Ten blood pressure readings were obtained at home in 405 men and 379 women (20 to 84 years). Each person's average pressure level was computed together with the standard deviation as index of variability. Sodium, potassium, and alcohol intake, smoking habits, social class, psychoemotional stress, and the calories spent at work and in sports were assessed from a questionnaire and from determinations on serum and on a 24-h urine sample. A P10 to P90 (10th and 90th percentile) increase of alcohol intake, as reflected by serum gamma-glutamyltransferase, was associated with a 3.2 +/- 0.9 mm Hg higher DBP in men and with a 3.1 +/- 1.6 mm Hg higher SBP and a 1.5 +/- 0.8 mm Hg higher DBP in women. A P10 to P90 increase in the calories spent in sports was accompanied by a decrease in pressure, averaging 1.5 +/- 0.8 mm Hg for DBP in men and 2.4 +/- 1.2 mm Hg and 1.8 +/- 0.8 mm Hg for SBP and DBP in women. A 2.2 +/- 0.7 mm Hg higher DBP was observed in women living in a working class area. After adjustment for age, the variability of DBP was inversely correlated with self-rated physical activity in men, whereas women living in a working class area showed a decreased SBP variability. In conclusion, in an affluent Western population, alcohol intake, participation in sports, and living in a working class area were identified as the life style factors of importance for the blood pressure level. By contrast, blood pressure variability, as measured in the present study, was only to a minor extent influenced by life style.

Adult↗
PubMed1994

Ambulatory blood pressure and blood pressure measured at home: progress report on a population study.

To determine reference values for ambulatory blood pressure, a population sample of 718 subjects (20 through 88 years old) was investigated. Ambulatory blood pressure was recorded over 24 h, taking measurements at 20-min intervals from 8 a.m. to 10 p.m. and at 45-min intervals from 10 p.m. to 8 a.m. Trained nurses also measured the conventional pressure at each participant's home. The ambulatory blood pressure in the 718 subjects averaged 119/71 mm Hg over 24 h, 125/76 mm Hg during the day (10 a.m.-8 p.m.), and 108/62 mm Hg at night (0 a.m.-6 a.m.). Compared with the daytime pressure, blood pressure at home was on average the same in all 718 subjects but was 3/1 mm Hg lower in 530 normotensive subjects. The 95th percentiles of the 24-h pressures were 134/85 mm Hg in 182 men below age 50, 145/87 mm Hg in 164 men aged > or = 50 years, 127/80 mm Hg in 198 women below age 50, and 141/81 mm Hg in 174 women aged > or = 50 years. In the normotensive subjects of these four strata, these percentiles were 132/82 mm Hg (n = 149), 128/80 mm Hg (n = 103), 125/79 mm Hg (n = 180), and 131/79 mm Hg (n = 98). In comparison with earlier results in a smaller sample (n = 318) from which treated patients were excluded, this analysis demonstrated consistent results in the determination of a reference frame for ambulatory monitoring. Nevertheless, the prognostic significance of such reference values needs to be established in longitudinal studies and clinical trials.

Adult↗
PubMed1994

Is a positive association between lead exposure and blood pressure supported by animal experiments?

The possible association between low-level lead exposure and blood pressure and the causal nature of any such relationship continue to be debated. A recent meta-analysis of the human model data showed that on average a doubling of blood lead was associated with a rise in blood pressure averaging 1 mm Hg systolic and 0.6 mm Hg diastolic. The older animal studies, however, failed to show a significant pressure increase with massive lead exposure. This review therefore attempts to determine whether the more recent animal studies are supportive of a positive association between lead exposure and blood pressure elevation. Of the 21 animal studies published since 1977, one was carried out in dogs, one in pigeons, and the remainder in various rat strains. In the articles in which all the lead doses had been higher than 1 ppm, the association between blood pressure and exposure was found to be positive in seven, inconsistent in three, absent in four, and negative in one. Of the six animal experiments that employed lead doses not exceeding 1 ppm, five reported a small pressor effect. One of these five positive low-dose studies, however, failed to show a dose-effect relationship when exposure was increased from 0.1 to 1 ppm. In conclusion, most, but not all animal studies published since 1977 found a positive association between blood pressure and lead exposure. However, publication bias may have inflated the number of positive studies appearing in the literature.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Respiratory-related blood pressure variability in patients after heart transplantation.

Our objective was to study whether the variations of blood pressure synchronous with respiration depend on the simultaneous changes of heart rate. Power spectral analysis of the heart period or R-R interval, blood pressure, and respiratory activity was performed by fast Fourier transform during 30 min of supine rest in 12 patients between 16 and 23 days after orthotopic heart transplantation and in 12 age- and sex-matched normal control subjects. The components of the variations of the R-R interval and blood pressure associated with respiration [high-frequency (HF) components] were derived from the power spectra. The HF component of the power spectrum of the R-R interval was almost absent in the transplanted patients compared with the control subjects (2.9 vs. 104 ms2; P < 0.001), whereas the HF component of the power spectrum of blood pressure was not significantly different between the two groups (1.72 vs. 1.65 mmHg2 for systolic and 0.35 vs. 0.60 mmHg2 for diastolic blood pressure). Respiratory variations of both systolic and diastolic blood pressure in humans can depend only slightly on the respiratory heart rate variations.

Blood Pressure↗
PubMed1994

Corticosteroids contribute to muscle weakness in chronic airflow obstruction.

Twenty-one patients with chronic obstructive pulmonary disease (COPD) or asthma, admitted to our division because of exacerbation of their conditions and requiring intensified treatment with corticosteroids, underwent pulmonary function tests, tests of respiratory muscle function, measurement of quadricep strength, and a variety of anthropometric and biochemical measurements. All tests were performed the 10th day after admission. As expected, muscle strength and pulmonary function were interrelated. Surprisingly, the average daily dose of steroids taken in the previous 6 mo, which ranged from 1.4 to 21.3 mg (average 4.3 mg), was significantly related to inspiratory muscle strength (PImax) and a similar tendency was present for expiratory muscle strength (PEmax). Multiple regression analysis of the relationship between PImax and quadriceps force (QF) and steroid dose revealed that the average daily dose independently explained 32% of the variance in PImax and up to 51% of the variance in QF. These relationships were independent of the degree of bronchial obstruction estimated by percentage predicted FEV1. Other significant determinants were age, sex, and COPD for PImax and age, sex, and body weight for QF. The present study demonstrates that in patients with COPD or asthma, respiratory and peripheral muscle strength and steroid treatment are interrelated despite the relatively low doses administered. This observation imposes further limitations on the prolonged treatment of chronic airflow obstruction with systemic corticosteroids.

Adrenal Cortex Hormones↗
PubMed1994

Hypertension caused by low-level lead exposure: myth or fact?

BACKGROUND: Several reports on the possible association between low-level lead exposure and blood pressure reflect diverging views. This meta-analysis aimed to find a common denominator in the published literature and to estimate whether a relationship exists between blood pressure and levels of lead in the blood. METHODS: Of the studies reviewed, 23 provided sufficient details to be considered. The meta-analysis included 33 groups with a total of 33 141 subjects, who had been recruited from the general population in 13 surveys and from occupational groups in 10 studies. In all but four studies the results were adjusted for age, and most studies took into account additional confounding factors. RESULTS: The association between blood pressure and blood lead was similar in both men and women. In the combined studies, a twofold increase in blood lead concentration was associated with a 1.0 mmHg rise in systolic pressure (confidence interval 0.4-1.6 mmHg; P = 0.002) and with a 0.6 mmHg increase in diastolic pressure (confidence interval 0.2-1.0 mmHg; P = 0.02). The association with systolic pressure strongly relied on the inclusion of a large study (n = 3851) in which women's blood pressure was measured at the end of pregnancy. The association with diastolic pressure was largely due to a population survey in the USA (n = 6289). There was no relationship across studies between the strength of the blood pressure-blood lead relationship and the mean blood lead concentration. CONCLUSION: The published evidence suggests that there can only be a weak positive association between blood pressure and lead exposure. Any such relationship may not be causal and is unlikely to entail any public-health implication in terms of hypertension-related complications. Nevertheless, these assumptions need to be confirmed in prospective population studies.

Blood Pressure↗
PubMed1994

Efficacy of antihypertensive drugs given once a day: the calcium antagonists revisited.

BACKGROUND: A large number of antihypertensive drugs have been approved for administration once or twice a day, but no standardized evidence is required to demonstrate that the reduction in blood pressure is sustained over 24 h. AIM: To test the validity of claims of a long duration of action for second-generation calcium antagonists. METHOD: Literature search. FLAWS IN REPORTED STUDIES: Most studies relied on ambulatory blood pressure monitoring. However, several reports were difficult to interpret because (1) the study was not blinded or random; (2) the statistical analysis was inappropriate for the study design; (3) analyses were confined to the means of 24-h, daytime and night-time blood pressure; (4) there was no baseline adjustment or formal statistical testing; (5) patients were subdivided into responders and non-responders after treatment; (6) there was no specified time frame linking drug intake to the observed antihypertensive effects. CLAIMS NOT SUBSTANTIATED: The authors of the articles reviewed concluded that amlodipine, nitrendipine and modified (slow-release) formulations of diltiazem, isradipine, nifedipine and verapamil reduced both conventional (clinic) and the 24-h blood pressure levels. In some studies separate results were presented for the daytime (awake) and night-time (sleeping) periods; some investigated the reduction in blood pressure at the end of the dose interval; and some compared the diurnal blood pressure profiles with different drug treatments. However, these reports gave discrepant results, suggesting that at least under certain study conditions the effect of nitrendipine and of slow-release diltiazem, isradipine and nifedipine did not give full 24-h cover with a single daily dose. CONCLUSIONS: We conclude that the interpretation of studies on long-acting antihypertensive agents using ambulatory blood pressure monitoring would be easier if the same standards were applied as required in clinical studies using conventional blood pressure measurements.

Blood Pressure↗
PubMed1994

Why is antihypertensive drug therapy needed in elderly patients with systolodiastolic hypertension?

OBJECTIVE: This paper presents a meta-analysis of eight outcome trials of antihypertensive drug treatment in elderly hypertensive patients, and uses the results of these trials to discuss day-to-day issues in the treatment of elderly hypertensive patients. META-ANALYSIS: In an intention-to-treat analysis, cardiovascular mortality was decreased on average by 22% (95% confidence interval -32% to -10%). This decrease was a result of reductions in both coronary and cerebrovascular mortality, by 26% (-40% to -9%) and 33% (-50% to -9%), respectively. So far, the effectiveness of antihypertensive therapy in reducing cardiovascular mortality has not been established with confidence in trials where the diastolic blood pressure at random allocation to treatment groups was below 95 mmHg or in patients above 75 years of age. IMPLICATIONS FOR DAY-TO-DAY PRACTICE: No blood pressure treatment goal has been definitively established but a reduction in systolic blood pressure to about 150 mmHg may be optimal. Extrapolation of trial results to the elderly population with systolodiastolic hypertension at large seems acceptable for a Western population, but may be premature for elderly Asians and Africans. beta-Blockers and especially diuretics are recommended as first-line drugs in elderly patients with symptomless, uncomplicated hypertension, since the effectiveness of other drugs in reducing morbidity and mortality has not yet been established. Recommendations for the treatment of symptomless patients with isolated systolic hypertension may be premature. Ongoing trials on systolic hypertension in Europe (Syst-Eur) and China (Syst-China) may provide further information.

Aged↗
PubMed1994

Lack of association between the I/D polymorphism of the angiotensin-converting enzyme gene and essential hypertension in a Belgian population.

We tested the insertion/deletion (I/D) polymorphism of the ACE gene in 119 hypertensive patients and in 109 normotensive controls by means of the polymerase chain reaction (PCR). The allele and genotype frequencies of the I/D polymorphism in the ACE gene are essentially identical in both groups, regardless of age or sex. The I/D polymorphism of the ACE gene is thus not implicated in Belgian hypertensive patients.

Base Sequence↗
PubMed1994

Ambulatory pressure decreases on long-term placebo treatment in older patients with isolated systolic hypertension. Syst-Eur Investigators.

OBJECTIVE: This long-term study investigated the widely accepted hypothesis that ambulatory pressure does not decrease in patients given placebo. METHODS: One hundred and twelve older (> or = 60 years) outpatients with isolated systolic hypertension were recruited. Treatment consisted of a placebo during a 3-month baseline period and long-term follow-up. RESULTS: At baseline, on placebo treatment, clinic systolic/diastolic (SBP/DBP) blood pressure (+/- SD) averaged 176 +/- 12/86 +/- 7 mmHg and 24-h SBP/DBP 151 +/- 15/81 +/- 10 mmHg. These pressures were unaltered in 51 patients in whom the baseline measurements were repeated after a further month on placebo. After the 112 patients had received placebo for 1 year (median), clinic SBP/DBP fell by 6.6 +/- 15.9 (P < 0.001)/1.4 +/- 7.4 (P = 0.06)mmHg and 24-h SBP by 2.4 +/- 10.7 mmHg (P < 0.05), whereas 24-h DBP did not change significantly. The 24-h SBP decreased more with higher baseline level and longer follow-up (5-21 months). CONCLUSIONS: These findings in older patients with isolated systolic hypertension suggest that in long-term studies the ambulatory pressure may slightly but significantly decrease on a placebo. Like those using conventional sphygmomanometry, long-term studies using non-invasive ambulatory monitoring require a placebo-controlled design.

Aged↗