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Biomedical subjects

R Fagard

Publications and source records attributed to R Fagard.

At least 127 records · Page 7Linked to original sources

Public health implications of environmental exposure to cadmium and lead: an overview of epidemiological studies in Belgium. Working Groups.

The CadmiBel Study was a cross-sectional population study that investigated the health effects of environmental exposure to cadmium and lead. The 2327 participants constituted a random sample of the population of four Belgian districts, chosen in order to provide a wide range of environmental exposure to cadmium. After adjustment for confounding factors, such as smoking and occupational exposure, the urinary cadmium excretion, a measure of lifetime exposure, was nearly 30% higher in the polluted areas. The CadmiBel Study produced evidence inconsistent with the hypothesis that environmental exposure to cadmium and lead would lead to an increase in blood pressure and to a higher prevalence of hypertension and other cardiovascular diseases. On the other hand, the serum alkaline phosphatase activity and the urinary excretion of calcium were significantly and positively correlated with urinary cadmium in both sexes. These findings suggested that the homeostasis of calcium was gradually affected as cadmium accumulated in the body. Furthermore, several markers of renal tubular dysfunction (urinary excretion of retinol-binding-protein, N-acetyl-beta-glucosaminidase, beta 2-microglobulin and amino acids) were significantly and positively associated with urinary cadmium. Across 10 small areas of which six were polluted with cadmium, an inverse association existed between the creatinine clearance and several indexes of environmental exposure to cadmium (cadmium concentration in the soil, cadmium content of locally grown vegetables, the inhabitants' 24 h urinary cadmium excretion). In the CadmiBel Study, the creatinine clearance was also inversely correlated with the concentrations of lead and zinc protoporphyrin in the blood. Thus, environmental exposure to cadmium and lead was associated with alterations in renal function. The significance in terms of morbidity and mortality of the functional disturbances observed in the CadmiBel Study, and the possible strategies to prevent the transfer of cadmium from the environment to man are under investigation in the prospective PheeCad Study in which half of the Cadmibel participants have been enrolled (participation rate 80%).

Adult↗

Treatment of hypertensive patients according to the conventional or ambulatory pressure: a progress report on the APTH trial. APTH Investigators. Ambulatory Blood Pressure and Treatment of Hypertension.

The main objective of the Ambulatory Blood Pressure and Treatment of Hypertension (APTH) trial is to test the hypothesis that antihypertensive treatment based on ambulatory monitoring may be more beneficial than treatment guided by conventional sphygmomanometry. After a 2-month run-in period on single-blind placebo, hypertensive patients were randomized to two groups, one in which the target pressure was a sitting diastolic pressure from 80 through 89 mm Hg on conventional sphygmomanometry (conventional blood pressure [CBP] group), and one in which a daytime (from 10 to 20 h) diastolic pressure from 80 through 89 mm Hg had to be achieved (ambulatory blood pressure [ABP] group). After randomization all patients were started on lisinopril 10 mg/day. One month later lisinopril could be continued at 10 or 20 mg/day or discontinued depending on the attained blood pressure level. This article is an interim report on 207 patients followed for two months into the trial. At one month lisinopril was discontinued more frequently in the ABP than the CBP group (24 vs 9 patients, p = 0.004). Nevertheless at two months, blood pressure control was not significantly different in the two treatment groups. The baseline-adjusted differences in systolic pressure between the two treatment arms of the trial (ABP-CBP group) were +2.7 mm Hg (95% confidence interval [CI]): -2.9, +8.3) for the conventional pressure, +0.4 mm Hg (CI: -4.3, +5.1) for the 24 h pressure, -0.1 mm Hg (CI: -5.1, +4.8) for the daytime pressure and -0.7 mm Hg (CI: -6.7, +5.4) for the night-time pressure. The corresponding differences in diastolic pressure were -1.3 mm Hg (CI: -4, +1.4), +0.1 mm Hg (CI: -3, +3.1), -1.1 mmgH (CI: -4.4, +2.1) and +0.3 mm Hg (CI: -3.7, +4.3), respectively. Thus, the present findings do not refute the APTH research hypothesis. In terms of blood pressure control and the number of patients remaining on antihypertensive drugs, treatment based on ambulatory recordings may be preferable to treatment guided by conventional sphygmomanometry.

Antihypertensive Agents↗

Associations of orthostatic blood pressure fall in older patients with isolated systolic hypertension. Syst-Eur Investigators.

OBJECTIVES: To investigate the associations of the orthostatic blood pressure changes in older patients with isolated systolic hypertension. METHODS: A total of 2716 patients, 917 men and 1799 women, aged > or = 60 years, were examined at three separate outpatient visits whilst receiving placebo during the single-blind run-in phase of the Syst-Eur trial. The orthostatic blood pressure changes were calculated by subtracting the average of two blood pressure readings with the patient in the supine position from the mean of two readings obtained after the patient had stood for 2 min. An orthostatic blood pressure drop by at least 20 mmHg systolic or 10 mmHg diastolic was considered exaggerated. RESULTS: For the three run-in visits combined, the supine blood pressure was 175 +/- 13 mmHg systolic and 86 +/- 6 mmHg diastolic (means +/- SD). With the patients standing the systolic blood pressure was 5 +/- 12 mmHg lower, whereas the diastolic blood pressure was 2 +/- 7 mmHg higher. An exaggerated fall in systolic blood pressure was observed on at least 1 visit in 21.0% of the patients and on all three visits in 2.5%. The corresponding values for diastolic blood pressure were 9.7 and 0.4%. The orthostatic fall in systolic blood pressure increased with previous antihypertensive treatment, age and smoking, but decreased with a higher sitting pulse rate and usual alcohol consumption versus none. The rise in diastolic blood pressure upon standing was higher in women than in men, was curvilinearly associated with age and increased with the sitting diastolic blood pressure. By multiple logistic regression analysis, the odds of having a persistent or occasional exaggerated orthostatic fall in systolic blood pressure were 22% higher in women than in men. The odds increased with previous antihypertensive treatment (by 42%), age (by 1.4%/year), electrocardiographic left ventricular mass (by 15%/mV) and sitting systolic blood pressure (by 0.9%/mmHg), but decreased with sitting pulse rate (by 1.9%/beat per min). An exaggerated orthostatic fall in diastolic blood pressure was 30% more likely in men; the likelihood increased with age (by 6.4%/year) and decreased with sitting diastolic blood pressure (by 6.6%/mmHg). CONCLUSION: An exaggerated orthostatic blood pressure fall in older patients with isolated systolic hypertension is associated mainly with gender, age and blood pressure level. Previous antihypertensive treatment, a lower pulse rate and a lower electrocardiographic left ventricular mass were also associated with an exaggerated orthostatic fall in systolic blood pressure.

Age Factors↗

Long-term blood pressure control in older Chinese patients with isolated systolic hypertension: a progress report on the Syst-China trial.

This report on the ongoing double-blind placebo-controlled Syst-China trial investigated whether antihypertensive drug treatment based mainly on a calcium entry blocker and a converting enzyme inhibitor, would be suitable for maintaining long-term blood pressure (BP) control in older Chinese patients (average age: 67 years) with isolated systolic hypertension (systolic pressure 160-219 mm Hg and diastolic pressure < 95 mm Hg). Active treatment consisted of nitrendipine (10- 40 mg/day) with the possible addition of captopril (12.5- 50 mg/day) and hydrochlorothiazide (12.5-50 mg/day), as necessary to reduce systolic pressure to a level of 150 mm Hg or lower and by at least 20 mm Hg. Matching placebos were used in the control group. This progress analysis was restricted to BP control up to 3 years of follow-up. The placebo (n = 1134) and active treatment n = 1245) groups had similar characteristics at enrolment. The sitting BP averaged 170/86 mm Hg. Systolic pressure fell (P < 0.001) on average 8 mm Hg more on active treatment than on placebo and diastolic pressure 3 mm Hg more. Fewer patients remained on monotherapy in the placebo than in the active treatment group (P < 0.001); on placebo the second and third line medications were started more frequently (P < 0.001). This progress report showed that significant BP reduction can be achieved and maintained in older Chinese patients treated with a calcium antagonist, associated with a converting-enzyme inhibitor and a thiazide, as necessary. Whether this BP reduction would result in a clinically meaningful decrease of cardiovascular complications is still under investigation.

Aged↗

Prognostic value of training-induced change in peak exercise capacity in patients with myocardial infarcts and patients with coronary bypass surgery.

An inverse association between mortality and exercise capacity has been demonstrated previously in patients with coronary artery disease. Physical training generally increases exercise capacity. Only 1 study investigated the prognostic value of exercise capacity after training, but only in a limited number of patients. No data are available on the relation between mortality and the change in exercise performance with training. Peak oxygen uptake (VO2) was measured before and after a 3-month, predominantly dynamic training period in 417 patients with coronary artery disease. Apart from peak VO2, several patient characteristics, risk factors for cardiovascular disease, and exercise data were considered in a Cox proportional-hazards model. Peak VO2 had increased by 33% after the training period. During the total follow-up of 2,583 patient-years, 37 patients died. The cause of death was cardiovascular in 21. The prognostic value of peak VO2 was higher after training than before training, even after adjustment for age and other significant covariates. Cardiovascular mortality decreased more with greater increases in peak VO2 after training. The relative hazard rate of 0.98 indicates that a 1% greater increase in peak VO2 after training would be associated with a decrease in cardiovascular mortality of 2%. No differences in prognostic value and in training effects were observed between patients with myocardial infarcts and patients after coronary bypass grafting. Peak VO2, evaluated after a physical training program, and its change in response to training are independent predictors for cardiovascular mortality in patients with coronary artery disease.

Adult↗

Relation of left ventricular mass and filling to exercise blood pressure and rest blood pressure.

Ninety-two young men with normal blood pressure (BP) or borderline elevated BP underwent echocardiography and maximal exercise testing to study whether left ventricular (LV) mass and the mitral inflow velocity pattern are more closely related to BP measured during dynamic exercise than to pressure measured at rest. LV mass was significantly related (p < 0.05) to systolic BP measured at rest and at various workloads; however, the variance of LV mass that could be explained by exercise pressures, in addition to preexercise pressure, age, body size, resting heart rate, and peak oxygen uptake, was not significant. The ratio of the late to early mitral inflow velocity was significantly related to systolic BP at rest but not to the pressures during exercise, and there was no independent contribution of exercise BP to its variance. Thus, systolic BP at various levels of dynamic exercise does not contribute independently to the interindividual variance of LV mass and mitral inflow pattern in young men with normal or borderline elevated BP.

Adolescent↗

Contribution of p56lck to the upregulation of cytokine production and T cell proliferation by IL-2 in human CD3-stimulated T cell clones.

Interaction of the interleukin 2 receptor (IL-2R) beta chain with the lymphocyte-specific protein tyrosine kinase (PTK), p56lck, has led to the speculation that p56lck participates in growth signal transduction. Although activation of T cells with interleukin 2 (IL-2) results in the activation of p56lck, accumulating data support the notion that Lck does not play an essential role in mitogenic signal delivery from the IL-2R. Since this src-related PTK has been shown to enhance TCR/CD3-mediated T cell responsiveness, here we investigated whether activation of Lck by IL-2 could contribute to enhance TCR/CD3-mediated T cell functions. This was achieved by using human CD4(+)-cloned T cells and comparing the effects of IL-2 on p56lck kinase activation and cytokine production. Results show that p56lck kinase activity increased as early as 1 min, reached a maximum within 5 min and decreased within 60 min after IL-2 stimulation. Such treatment with IL-2 also resulted in enhancing T cell responsiveness to CD3+PMA stimulation, as assessed by IL-2 and IFN-gamma secretion and by T cell proliferation. This increase of T cell functions was correlated with IL-2-induced p56lck activation in both dose-response and time-course experiments. Taken together these results strongly suggest that activation of Lck by IL-2 may play a role in regulating CD3-mediated T cell functions.

CD3 Complex↗

Once-daily antihypertensive treatment with calcium antagonists: utopia or reality?

Although a large number of antihypertensive drugs have been approved for once- or twice-daily dosing, no standardized set of evidence is required to demonstrate that the blood pressure reduction is sustained for 24 h. The recent literature on calcium antagonists was therefore searched for the arguments usually put forward to objectify a long duration of action. Most studies relied on ambulatory blood pressure monitoring. However, several published reports were difficult to interpret for a variety of reasons, such as: (1) a non-blinded non-randomized study design; (2) a statistical analysis, which was discordant with the study design; (3) analyses confined to the 24 h, day-time and night-time pressure means; (4) the absence of a baseline adjustment and/or formal statistical testing; (5) the "post hoc" subdivision of patients into responders and non-responders; and (6) the absence of a well-specified time-frame linking drug intake to the observed antihypertensive effects. According to the authors' interpretation, amlodipine, diltiazem SR (modified release), felodipine SR, isradipine SR, nifedipine SR, nitrendipine and verapamil SR have all been confirmed to reduce both the conventional and the 24 h blood pressure. Some studies went beyond the 24 h blood pressure means and also presented separate results for the day-time (or awake) and night-time (or sleeping) periods, or investigated the blood pressure reduction at the end of the dosing interval, or compared the diurnal blood pressure profiles on different treatments.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure Monitoring, Ambulatory↗

Multiple standardized clinic blood pressures may predict left ventricular mass as well as ambulatory monitoring. A metaanalysis of comparative studies.

It is generally recognized that the relation between left ventricular mass (index) and blood pressure measured in the clinic is weak. Several investigators have studied whether ambulatory blood pressure outside the hospital environment can explain more of the variance of left ventricular mass than does clinic pressure. In a metaanalysis of such comparative studies, the weighted correlation coefficient averaged 0.35 (95% confidence limits: 0.30 to 0.40) for systolic clinic pressure and was significantly (P < .001) higher for the 24-h pressure (r = 0.50; range 0.45 to 0.54). In several studies, however, the methodology and conditions of the clinic pressure measurements were poorly described or standardized, whereas multiple meticulously obtained measurements were present in other reports. The ambulatory pressure monitoring was usually performed with great care and reported in detail. In some studies in which clinic blood pressure consisted of multiple readings in well-standardized conditions in the resting subject, clinic pressure seemed to predict left ventricular mass as well as ambulatory monitoring. We suggest that the strength of the relationship of left ventricular mass with ambulatory pressure may not differ from that with clinic pressure when an adequate number of blood pressures are measured in well-standardized conditions in the clinic.

Adult↗

The relationships between left ventricular mass and daytime and night-time blood pressures: a meta-analysis of comparative studies.

OBJECTIVE: To review the literature to examine critically the assertion that night-time blood pressure is a better predictor of echocardiographic left ventricular mass than daytime blood pressure, and that left ventricular mass is inversely related to the day-night blood pressure difference. STUDY SELECTION: Published studies in which left ventricular mass (index) of normotensive or hypertensive individuals, or both, was related to automated blood pressure measurement during the day and night, or their difference, or both. RESULTS OF DATA ANALYSIS: The meta-analysis of 19 comparative studies, involving 1223 participants, indicates that the weighted correlation coefficient for the relationship between left ventricular mass (index) and systolic night-time blood pressure (0.44; 95% confidence limit 0.39-0.48) is not significantly different from the correlation with systolic daytime blood pressure (0.48; 95% confidence limit 0.44-0.52; P > 0.2). The corresponding correlation coefficients for diastolic blood pressure both average 0.37. In half of the eight studies in which the association between left ventricular mass (index) and the day-night difference in blood pressure was analysed, investigators found no significant relationship between those variables; in the others, the variance of the mass (index) that can be explained by the blood pressure difference is 15% at the most. CONCLUSION: The overall analysis suggests that night-time blood pressure is not a significantly better predictor of left ventricular mass than daytime blood pressure is, and that the relationship to the day-night blood pressure difference is not a unanimous finding and is only ever weakly significant.

Blood Pressure↗

A consensus view on the technique of ambulatory blood pressure monitoring. The Fourth International Consensus Conference on 24-Hour Ambulatory Blood Pressure Monitoring.

This review, based on the Fourth International Consensus Conference on Ambulatory Blood Pressure Monitoring (Leuven, Belgium, 1994), deals with the technical aspects of ambulatory blood pressure monitoring. Ambulatory blood pressure monitoring by noninvasive intermittent techniques is widely used despite artifacts due to cuff size, movement, body position, short-term blood pressure variability, and interference with sleep. The performance of the currently available monitors under truly ambulatory conditions and during exercise remains a matter of debate, as are the procedures required to validate portable monitors under these circumstances. There is general agreement that whenever a monitor is to be used in special populations, such as older subjects or pregnant women, or in special conditions, such as exercise, a specific demonstration of its accuracy in these defined subgroups or conditions is warranted. Whether the auscultatory or oscillometric method is preferred remains controversial because each technique has specific advantages and disadvantages and because both can provide accurate results. Most experts in the field strongly believe that manufacturers should disclose the algorithms of their devices and that they should specify all changes made to the hardware and software of a previously validated monitor. Finally, the development of the volume-clamp method, which makes continuous noninvasive registration of blood pressure at the finger possible in both stationary and ambulatory conditions, opens new perspectives in research, in particular in relation to short-term blood pressure variability.

Adult↗

Heritability of conventional and ambulatory blood pressures. A study in twins.

Conventional and 24-hour ambulatory blood pressures were measured in 26 pairs of monozygotic twins and 27 pairs of dizygotic twins, all male, ages 18 to 38 years, to determine the heritability of blood pressure measured under various conditions. Conventional pressure was the average of three well-standardized measurements in the supine position, and ambulatory pressure was recorded during the subjects' normal activities by use of the SpaceLabs 90202 device. Heritability was assessed by classic methods and by model fitting and path analysis. In the latter approach, the percent genetic variance was 70% for mean 24-hour systolic pressure and 73% for diastolic pressure, which was similar to the results for the conventional pressures (64% and 73%, respectively). During the night, these estimates were 72% and 51% for systolic and diastolic pressures, respectively, and also the average pressures of the total awake daytime period were under partial genetic control (63% and 55%, respectively). The remaining variances could be attributed primarily to unique environmental influences. However, shared and nonshared environmental factors were predominant for the pressures during a fixed 6-hour afternoon period. We conclude that the heritability of blood pressure is relatively high in young adult healthy men, for standardized conventional pressure and the average 24-hour pressure. Genetic variance is somewhat higher for the asleep pressure than for the awake systolic pressure.

Adolescent↗

The trough-to-peak ratio as an instrument to evaluate antihypertensive drugs. The APTH Investigators. Ambulatory Blood Pressure and Treatment of Hypertension Trial.

The U.S. Food and Drug Administration designed the trough-to-peak ratio as an instrument for the evaluation of long-acting antihypertensive drugs, but the ratios are usually reported without accounting for interindividual variability. This study investigated how the trough-to-peak ratio would be affected by interindividual and intraindividual variability and by smoothing of the diurnal blood pressure profiles. The ambulatory blood pressure was recorded on placebo in 143 hypertensive patients (diastolic pressure on conventional measurement > 95 mm Hg). After 2 months, the recordings were repeated on 10 mg (n = 66) or 20 mg (n = 77) lisinopril given once daily between 7 and 11 PM. The baseline-adjusted trough-to-peak ratios were determined from diurnal blood pressure profiles with 1-hour precision. Lisinopril reduced (+/- SD) the 24-hour pressure by 16 +/- 17 mm Hg for systolic and 10 +/- 10 mm Hg for diastolic (P < .001). According to the usual approach, disregarding interindividual variability, the trough-to-peak ratio was 0.72 for systolic pressure and 0.67 for diastolic pressure. In the 143 patients the ratios were not normally distributed. They were the same on both lisinopril doses. When interindividual variability was accounted for, the median trough-to-peak ratio was 0.34 (P5 to P95 interval, -0.46 to 0.87) for systolic pressure and 0.26 (-0.44 to 0.84) for diastolic pressure. In 66 patients examined twice on 10 mg lisinopril at a median interval of 32 days, the trough-to-peak ratios were characterized by large intraindividual variability.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Trough-to-peak versus surface ratio in the assessment of antihypertensive agents. APTH Investigators. Ambulatory Blood Pressure and Treatment of Hypertension.

This study investigated whether the 'surface ratio', a novel index to characterize long-acting antihypertensive agents, would provide a more reproducible estimate of the duration of the antihypertensive effect than the more commonly used trough-to-peak ratio. In 66 hypertensive patients (diastolic pressure on conventional measurement > 95 mmHg), the ambulatory blood pressure was measured on a placebo at baseline and 2 months later, while the patients took 10 mg lisinopril once a day between 7 p.m. and 11 p.m. Diurnal treatment effect curves were obtained by subtracting the blood pressure at baseline from the corresponding value at 2 months for all time intervals considered in the analysis. In order to calculate the surface ratio, the area under the treatment effect curve was divided by the product of the maximal blood pressure lowering effect and the dosing interval (24 h). Reproducibility of the trough-to-peak and surface ratios was investigated by the Bland and Altman techniques. At 2 months, lisinopril reduced (+/- standard deviation) the 24 h pressure by 13 +/- 16 mmHg systolic and by 8 +/- 8 mmHg diastolic (p < 0.001). According to the usual approach, disregarding inter-individual variability, the trough-to-peak ratio was 0.7 for systolic and diastolic pressure. When in individual patients diurnal treatment effects curves with a 1 h resolution were investigated, the median trough-to-peak ratio was 0.30 for systolic pressure (5th-95th percentile interval [PI]: -0.51, 0.82) and 0.28 for diastolic pressure (PI: -0.37, 0.78); the corresponding values for the surface ratio were 0.33 (PI: 0.03, 0.58) and 0.30 (PI: -0.01, 0.55). In the same manner, the trough-to-peak ratios and surface ratios became larger when the individual blood pressure profiles were progressively smoothed by substituting 1 h averages by 2 h moving averages, 2 h averages, 3 h moving averages or by 3 h averages. The distributions of the trough-to-peak ratios and surface ratios were non-normal in 37 of 40 instances (p < 0.001, Shapiro-Wilk's test). Consistency was higher (p < 0.001) for the surface than for the trough-to-peak ratios. The within-subject reproducibility of the surface ratios tended to be superior to that of the corresponding trough-to-peak ratios. In conclusion, the surface ratio provides an index of the duration of action of antihypertensive agents. Moreover, in the present patients, the surface ratio tended to be characterized by a higher within-subject reproducibility than the trough-to-peak ratio.

Adult↗

Lack of association between HLA class II polymorphisms and essential hypertension in a Belgian population.

The aim of the present study was to investigate whether the HLA class II polymorphisms contributes to the susceptibility to essential hypertension in the Belgian population. For this purpose we studied 120 hypertensive patients and 168 normotensive controls by means of a PCR-SSO assay. No significant difference in allele and genotype frequencies of the DRB and DPB1 loci could be found between the two groups. We concluded that essential hypertension as a multifactorial and heterogeneous disease cannot be associated with one of the HLA class II DRB and DPB1 alleles in Belgian patients.

Adult↗

Changes in plasma lipids, lipoproteins and apolipoproteins in hypercholesterolaemic patients treated with pravastatin.

Plasma lipids, lipoproteins and apolipoproteins were studied before and during 6 months of pravastatin administration in patients with hypecholesterolaemia. After a 1 month placebo run-in period, the patients were treated double-blind either with placebo (n = 25) or with pravastatin (n = 25) for 6 months. Placebo or pravastatin 10 mg during the first month, 20 mg during the second month and 40 mg during the additional 4 months was administered once daily in the evening. Compared with the placebo group the plasma concentration of total cholesterol and phospholipids, free cholesterol and cholesterol esters as well as the plasma LDL-cholesterol and LDL-phospholipids were decreased during 6 months of pravastation therapy. No changes in plasma VLDL-, HDL-, HDL2-, or HDL3-cholesterol, -phospholipids or -triglycerides were observed in the pravastatin-treated patients. A decrease in the plasma level of apolipoprotein B and of LDL-apo B, but not of VLDL-apo B, was observed during pravastatin therapy; the plasma apolipoprotein AI and AII levels as well as HDL2- and HDL3-apo AI and apo AII levels remained, however, unchanged. Plasma lipoprotein Lp(a) did not change during pravastatin therapy whereas the plasma lecithin cholesterol acyltransferase activity (LCAT) increased. In conclusion, treatment of hypercholesterolaemic patients with pravastatin results in a decrease in the plasma concentration of total and free cholesterol, LDL-cholesterol, apolipoprotein B, LDL-apo B, phospholipids and cholesterol esters and in an increase in plasma LCAT activity. Plasma Lp(a), HDL-cholesterol and triglyceride levels remained, however, unchanged.

Apolipoproteins↗