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Biomedical subjects

L Thijs

Publications and source records attributed to L Thijs.

At least 109 records · Page 6Linked to original sources

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↗

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↗

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↗

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↗

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↗

Efficacy and safety of pravastatin in hypertensive hypercholesterolaemic patients on antihypertensive drug therapy.

This double-blind, placebo-controlled, six month trial evaluated the efficacy and safety of pravastatin in hypercholesterolaemic, hypertensive patients on antihypertensive treatment, who on a standard lipid-lowering diet maintained a plasma total cholesterol level of at least 250 mg%. Fifty hypertensive patients were randomised to placebo or pravastatin treatment. Once daily dosing consisted of 10 mg pravastatin during the first month, 20 mg during the second month and 40 mg during an additional 4 months or matching placebos. Compared with placebo, pravastatin reduced (P < 0.001) the plasma level of total cholesterol, LDL-cholesterol and phospholipids during the six month study period whereas plasma HDL-cholesterol and triglycerides did not change significantly. These changes in plasma lipids were independent of age and of the nature of the concomitant antihypertensive treatment. No serious side-effects were observed and pravastatin was generally well tolerated. In conclusion, pravastatin 10-40 mg once daily reduced plasma total and LDL-cholesterol in hypercholesterolaemic, hypertensive patients, independent of age and concurrent antihypertensive drug therapy.

Adolescent↗

Number of measurements required for the analysis of diurnal blood pressure profile.

The aim of this study was to investigate how frequent blood pressure (BP) readings need to be obtained to reproduce the diurnal BP profile without loss or distortion of information. The subjects were 97 normotensives aged 23-84 years. Noninvasive ambulatory BP readings were programmed with an interval of 7.5 minutes during the day (from 8 am to 8 pm) and at 15 minutes intervals at night. Readings were stepwise omitted from the original recordings. For each step the diurnal BP profile was modelled with five different techniques. The concordance between original and reduced recordings was quantified using the repeatability coefficient, i.e. twice the standard deviation of the differences between these recordings (expressed as a percentage of the 5th to 95th percentile range of the parameter under investigation). The concordance between original and reduced recordings tended to be better for the level of pressure than for the parameters of the diurnal profile. If the sampling frequency was two readings per hour, concordance for SBP was < 10% for the BP level, 19% for the 24h standard deviation, 12% for the nocturnal fall in BP, 23% for the amplitude of the Fourier curve and 17% for the cusum derived circadian alteration magnitude. Concordance worsened to > 25% for most parameters of the diurnal BP curve when the interval between consecutive measurements exceeded 30 minutes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Mechanical and other factors relating to left ventricular hypertrophy.

Although the development of left ventricular hypertrophy in hypertension is explained as a response to increases in pressure load and wall tension, the relationship between left ventricular mass and conventional blood pressure is usually weak. This may be due to the lack of standardization and the small number of blood pressure measurements in some studies. However, even 24-h blood pressure monitoring can explain only around 25% of the variation in left ventricular mass, and repeated blood pressure measurements over 30 years have not proved better in this respect. Therefore, other factors have been considered, including anthropometric and demographic characteristics; genetic influences; differences in salt intake, physical activity and alcohol consumption; neurohumoral factors; duration of hypertension; and previous antihypertensive treatment. Antihypertensive treatment may reduce left ventricular mass and a number of prospective, randomized, comparative studies have assessed whether some (classes of) drugs are more effective than others. A meta-analysis of such studies, comparing diuretics, beta-blockers, calcium antagonists and/or angiotensin-converting enzyme (ACE) inhibitors, suggests that the reduction of left ventricular mass with each of these classes is similar to the reduction obtained with the other three classes statistically combined. Of particular interest is the observation that the four studies which specifically compared an ACE inhibitor and a calcium antagonist concluded that their effects on left ventricular mass did not significantly differ. Furthermore, that agents such as minoxidil and hydralazine do not reduce left ventricular mass.

Antihypertensive Agents↗

Implications for trials in progress of publication of positive results.

It is not easy to decide, when results from similar trials appear, whether a trial still underway should be stopped or not. The weight of the other evidence has to be taken into account--as indeed it has to be for decisions by clinicians and by health service managers outside the settings of a trial. Taking the Systolic Hypertension in the Elderly Trial (SHEP) as an example, we show how its results are not unequivocal (ie, there is no proof beyond reasonable doubt). This verdict justifies the continuation of similar trials in progress. More generally--but again for individual clinicians and for trial organisers and again with SHEP as the example--we illustrate a bayesian approach to trial-termination decisions.

Aged↗

Fourier analysis of blood pressure profiles.

This short review deals with the use of the Fourier technique to analyze diurnal blood pressure (BP) profiles obtained by noninvasive ambulatory monitoring. A Fourier series with four harmonics strikes an acceptable balance between the accuracy and complexity required to model the diurnal profile accurately in most subjects. A weighting procedure makes it possible to allow for the varying time intervals between consecutive pressure readings. Studies based on a single recording are insufficient to characterize an individual with respect to the statistical parameters describing the diurnal BP profile, regardless of whether they are obtained by Fourier analysis or by other methods. The Fourier approach provides the means to translate 24 h BP profiles into interpretable statistical parameters, such as the amplitude and acrophase of the overall model and the harmonics. These parameters can subsequently be used in further statistical analyses. In conclusion, the Fourier approach makes the description of complex, asymmetrical, and multiphasic BP profiles possible. By using the procedures of linear multiple regression, commonly provided by software packages, the calculations can be readily implemented on microcomputers without requiring advanced skills in mathematics or programming techniques.

Blood Pressure↗

Response of ambulatory blood pressure to antihypertensive therapy guided by clinic pressure.

The objective of this prospective study was to define the limits below which ambulatory blood pressure (BP) does not decrease in patients with essential hypertension, when the decision to institute and intensify drug treatment is based on conventional blood pressure measurements. After a 1 month placebo run-in period, 30 patients were treated for 1 year with the converting enzyme inhibitor lisinopril or the calcium antagonist isradipine; dose adjustments and the decision to add hydrochlorothiazide were based on conventional blood pressure measurements in the clinic. Ambulatory blood pressure was recorded during 24 h in the run-in period and after 16, 24, and 52 weeks of active therapy. The baseline ambulatory blood pressure below which pressure does, on average, not decrease during active treatment was defined as the pressure at which the regression line between the on-treatment pressure and blood pressure in the run-in period intersects the line of identity. The systolic/diastolic blood pressure limits were similar for the three assessments during active treatment and averaged 128/88 mm Hg for daytime, 106/73 mm Hg for nighttime pressure, and 119/81 mm Hg for the whole 24 h, with upper 95% confidence limits of 137/93, 115/78, and 127/86 mm Hg, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The relationship between blood pressure and sodium and potassium excretion during the day and at night.

OBJECTIVE: The relationships between blood pressure and the urinary excretion rates of sodium and potassium during the day and at night were investigated. METHODS: A total of 160 participants (135 normotensive subjects and 25 untreated patients with essential hypertension) were examined using ambulatory blood pressure monitoring and timed urine collections during waking and sleeping hours. RESULTS: Blood pressure averaged 126/79 mmHg during waking hours and 107/62 mmHg during sleep. More sodium, potassium and aldosterone were excreted during the daytime, but the natriuretic substance kallikrein was excreted at a fixed rate throughout the 24 h. During waking hours there was poor correlation between blood pressure and urinary sodium and potassium excretion. By contrast, at night when the aldosterone: kallikrein ratio fell, the sodium and potassium excretion rates were positively correlated with blood pressure. CONCLUSIONS: Pressure natriuresis, not apparent during waking hours, may be unmasked at night when the balance between sodium-retaining and sodium-losing mechanisms favours natriuresis. Thus, the relationship between blood pressure and 24-h sodium excretion, usually considered to show the influence of salt intake on blood pressure, may also reflect pressure-induced natriuresis, if urine is more completely collected at night than during the day, and in circumstances favouring sodium retention during the day and sodium loss during sleep.

Adult↗

Does isradipine modified release 5 mg once daily reduce blood pressure for 24 hours?

Twelve patients with essential hypertension were randomized in a double-blind cross-over study to investigate the blood pressure BP-lowering activity of isradipine regular formulation (RF) 2.5 mg twice daily (between 7 and 8 a.m. and at approximately 6 p.m.), and isradipine modified release (MR), 5 mg once daily (between 7 and 8 a.m.). The two randomized treatment periods were separated by a placebo period. Patient compliance was similar between placebo and isradipine RF and MR treatment. As compared with placebo, isradipine RF decreased daytime BP by 10 mm Hg systolic (SBP, p < 0.001) and by 6 mm Hg diastolic (DBP, p < 0.01), and night SBP and DBP by 7 (p < 0.05) and 3 mm Hg (P = NS), respectively. Isradipine MR reduced the daytime SBP 8 mm Hg (p < 0.05) and DBP by 3 mm Hg (p = NS), and the night SBP by 1 mm Hg (p = NS) and DBP by < 1 mm Hg (P = NS). Analysis of variance showed that the interaction terms between the effects of treatment and time of day were not significant for SBP (F = 1.56, p = 0.24) or DBP (F = 1.40, p = 0.26) with isradipine RF treatment, but they were significant for SBP (F = 6.33, p = 0.03) and DBP (F = 5.12, p = 0.04) with isradipine MR treatment. Therefore, the BP-lowering effect of isradipine MR 5 mg once daily appears to weaken as the day progresses.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Influence of antihypertensive drugs on exercise capacity.

Both single dose and short term diuretic treatment adversely affect maximal exercise capacity and the duration of prolonged submaximal exercise. However, insufficient data are available to establish the effect of long term diuretic treatment on exercise capacity. beta-Blockade reduces maximal aerobic power by approximately 7%. In addition, the capacity for prolonged submaximal exercise appears to be markedly impaired in normotensive and hypertensive patients, particularly when nonselective beta-blockers are prescribed. Fewer data are available for other drugs, but, whatever the mechanism of vasodilation, drugs that reduce systemic vascular resistance do not seem to have any effect on exercise capacity.

Antihypertensive Agents↗

Antihypertensive therapy in elderly patients with isolated systolic hypertension: third progress report of the Syst-Eur trial.

The Syst-Eur trial is a randomised, double-blind, placebo-controlled trial that examines the hypothesis that antihypertensive treatment can prevent or delay cardiovascular complications in elderly patients (> 60 years) with isolated systolic hypertension. On March, 1st 1993 a total of 1395 patients with a sitting systolic blood pressure on placebo averaging 160-219 mmHg and a diastolic blood pressure < 95 mmHg were randomised into this trial. The placebo and active treatment groups were similar at randomisation with respect to age (72 +/- 7 years, mean +/- SD), percentage of women (68%), percentage of patients with cardiovascular complications (30%) and sitting blood pressures (175 +/- 12/85 +/- 6 mmHg). The fall in sitting systolic and diastolic blood pressures from baseline to 2 years was significantly more pronounced (p < 0.001) in the actively treated (-22 +/- 18/-6 +/- 9 mmHg) as compared with the placebo treated Syst-Eur patients (-10 +/- 20/-1 +/- 9 mmHg). Active treatment consists of nitrendipine if necessary associated with a converting-enzyme inhibitor and a thiazide. Whether treatment with these antihypertensive agents results in a clinically meaningful reduction of cardiovascular morbidity and mortality is the subject of investigation in this trial.

Aged↗

The older hypertensive. Assessment and treatment.

A meta-analysis is presented of 8 therapeutic trials in elderly hypertensive patients. In an intention-to-treat analysis, cardiovascular mortality was decreased on average by 22% (95% confidence interval ranging from -32% to -10%). This decrease was explained by both a reduction in coronary mortality by 26% (-40% to -9%) and in cerebrovascular mortality by 33% (-50% to -9%). The effectiveness of therapy in terms of reducing cardiovascular mortality is not established with confidence in those trials where the diastolic blood pressure at randomization is below 95 mmHg or in the patients above 75 years of age. A goal blood pressure is not definitively established, but a reduction of the systolic blood pressure to about 150 mmHg may be optimal. Extrapolation of the trial results to the elderly population with systolo-diastolic hypertension at large seems acceptable for the western population, but may be premature for the Asian and African elderly. 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 is not yet established. Recommendation for treatment of symptomless patients with isolated systolic hypertension may be premature. The ongoing Syst-Eur and Syst-Chin trials may provide further information.

Aged↗

The increase in blood pressure with age and body mass index is overestimated by conventional sphygmomanometry.

This cross-sectional study investigated whether the technique of blood pressure measurement used (conventional sphygmomanometry vs. ambulatory monitoring) affects the relation between blood pressure and both age and body mass index. Two independent data sets were analyzed. The first comprised 328 subjects (48% men) drawn from the population of a small Belgian town, and the second comprised 776 Irish bank employees (51% men). Age ranged from 17 years to 81 years, and body mass index (weight (kg)/height (m)2) ranged from 16.6 to 40.2. Twenty-four-hour ambulatory blood pressure was lower than blood pressure measured by a nurse in both the Belgian population sample (118/71 mmHg vs. 122/73 mmHg) and the Irish employees (118/72 mmHg vs. 119/76 mmHg). When blood pressure was measured by an observer, the well-established relations between systolic and diastolic blood pressure and both age and body mass index were evident. When the analyses were repeated using 24-hour measurements, the increment (cross-sectionally assessed) in blood pressure with age was weaker, especially in young and middle-aged subjects (20-60 years), while the increase in blood pressure with body mass index was also reduced. The within-subject differences between the conventional and ambulatory blood pressure measurements increased with older age and greater body mass index. Several other relations with blood pressure as the response variable may require revision in light of the present findings.

Adult↗