Terminal digit preference and single-number preference in the Syst-Eur trial: influence of quality control.

Background: Terminal digit and single-number preference may produce inaccuracy and biased results when measuring blood pressure. We describe these preferences in the Syst-Eur randomized placebo-controlled trial of the treatment of isolated systolic hypertension and describe how we sought to eliminate these problems.

Methods: The Data Monitoring Committee of the trial conducted yearly quality control meetings in Belgium and visited the participating centres to check their adherence to the protocol.

Resistance to fludarabine-induced apoptosis in Epstein-Barr virus infected B cells.

The Epstein-Barr virus (EBV) transforms B cells in part by inhibiting the cellular apoptotic programme. This is also observed when Burkitt lymphoma cell lines are infected with EBV. Induction of apoptosis is one of the mechanisms by which fludarabine inhibits the growth of cells with low proliferative capacity.

Host and environmental determinants of polychlorinated aromatic hydrocarbons in serum of adolescents.

This study investigated host factors and environmental factors as potential determinants of polychlorinated aromatic hydrocarbons (PCAHs) in serum of adolescents. We recruited 200 participants (80 boys and 120 girls), with a mean age of 17.4 years (SD, 0.

Characteristics of conventional blood pressure in studies on the predictive power of ambulatory blood pressure.

Background: It is commonly believed that the associations of left ventricular mass and cardiovascular morbidity/mortality with blood pressure are stronger for 24-h ambulatory pressure than for conventional clinic or casual pressure.

Methods: The investigation comprised a review of relevant studies, with particular emphasis on the characteristics of the conventional blood pressure measurement.

Results: A review of 21 studies on left ventricular mass, published between 1982 and 1993, showed that the relationship between mass and blood pressure was stronger for ambulatory blood pressure than for clinic blood pressure but that the methodology and conditions of the conventional blood pressure measurements were poorly described or standardized in several reports.

Heritability of plasma renin activity and plasma concentration of angiotensinogen and angiotensin-converting enzyme.

The purpose of the present investigation was to describe the relative impact of genes and environment on the variance of the plasma constituents of the renin angiotensin system. We ascertained 56 male and 80 female adult same-sex twin pairs from the Flemish population. Plasma renin activity (PRA), the concentration of angiotensinogen (AGT) and angiotensin-converting enzyme (ACE) were measured, and path analysis was applied, after transformation toward normality.

Transforming growth factor-beta(1) induces angiotensin-converting enzyme synthesis in rat cardiac fibroblasts during their differentiation to myofibroblasts.

Objectives: Appearance of angiotensin-converting enzyme (ACE) in fibrotic tissue can be the result of the action either of one particular growth factor or of cross-talk between multiple factors. Transforming growth factor-beta1 (TGF-beta(1)) is an effective inducor of the differentiation of cultured fibroblasts to myofibroblasts, which are heterogeneous cells with different phenotypes. The present study investigated whether TGF-beta(1) is able to induce, in vitro, the differentiation of cultured fibroblasts to myofibroblasts with a phenotype containing ACE.

Birth weight and body composition in young women: a prospective twin study.

Background: The intrauterine environment may be critical for the development of obesity. Alternatively, the same genetic factors may influence both birth weight and adult body composition.

Objective: We evaluated the association between birth weight and adult body composition in female twins, which allowed us to control for maternal and genetic influences.

J-shaped relationship between blood pressure and mortality in hypertensive patients: new insights from a meta-analysis of individual-patient data.

Background: Population-based longitudinal studies of hypertension have usually shown a continuous and positive relationship between blood pressure and mortality. However, several studies in hypertensive patients receiving treatment have described this relationship as J-shaped, with an increased risk for events in patients with low blood pressure.

Objective: To assess the evidence for a J-shaped relationship between blood pressure and mortality and its relation to treatment.

Angiotensin II-induced stimulation of collagen secretion and production in cardiac fibroblasts is mediated via angiotensin II subtype 1 receptors.

The possible contributions of the angiotensin receptor subtypes 1 (AT1) and 2 (AT2) to angiotensin II (Ang II)-induced changes in collagen secretion and production were studied using the specific angiotensin AT1- and AT2-receptor antagonists telmisartan and P-186, respectively. Cardiac fibroblasts (from normal male adult rats) from passage 2 were cultured to confluency and incubated in the presence of 10(-10) to 10(-6) M Ang II in serum-free Dulbecco's MEM medium for 24 hours. Collagen production and secretion were assayed by'H-Proline incorporation; non-collagen production and secretion were also calculated.

The influence of zygosity and chorion type on fat distribution in young adult twins consequences for twin studies.

An adverse intra-uterine environment has been associated with abdominal fat distribution in singletons. Twins often have a low birth weight and a short gestation. Therefore, they may have an increased risk to develop abdominal obesity.

Stimulation of collagen production by transforming growth factor-beta1 during differentiation of cardiac fibroblasts to myofibroblasts.

The aim of the present study was to elucidate how transforming growth factor-beta(1) (TGF-beta(1)) can stimulate collagen deposition in cardiac tissue by interstitial cells via stimulation of fibroblasts, via myofibroblasts, or via differentiation of fibroblasts to myofibroblasts. The dose- and time-dependent stimulation of collagen production and of expression of alpha-smooth muscle actin (alpha-SMA), a marker of myofibroblasts, was studied in cultures of second-passage adult rat cardiac fibroblasts. The TGF-beta(1)-stimulated collagen production is positively correlated (r=0.

Dihydropyridine calcium-channel blockers for antihypertensive treatment in older patients--evidence from the Systolic Hypertension in Europe Trial.

Objective: The Syst-Eur study investigated whether active antihypertensive treatment could reduce cardiovascular complications in elderly patients with isolated systolic hypertension.

Design: Randomised, placebo-controlled, double-blind outcome trial.

Setting: Hypertension clinics or general practitioners' surgeries in 198 centres in 23 Western and Eastern European countries.

Withdrawal from treatment in the Syst-Eur Trial.

Objective: To investigate the reasons for withdrawal from double-blind randomized trials, and the reasons for changing treatment within a randomized therapeutic group.

Design: The Syst-Eur trial, in which 4695 older patients with systolic hypertension were randomized to active or placebo treatment.

Methods: The reasons for withdrawal from the trial were examined, both for patient-initiated and investigator-initiated withdrawals.

How well can blood pressure be controlled? Progress report on the Systolic Hypertension in Europe Follow-Up Study (Syst-Eur 2).

BACKGROUND: The randomised, double-blind, placebo-controlled Systolic Hypertension in Europe trial (Syst-Eur 1) proved that blood pressure (BP) lowering therapy starting with nitrendipine reduces the risk of cardiovascular complications in elderly patients with isolated systolic hypertension. In an attempt to confirm the safety of long-term antihypertensive therapy based on a dihydropyridine, the Syst-Eur patients remained in open follow-up after the end of Syst-Eur 1. This paper presents the second progress report of this follow-up study (Syst-Eur 2).

Pulsatile blood pressure component as predictor of mortality in hypertension: a meta-analysis of clinical trial control groups.

Objective: Although current guidelines rest exclusively on the measurement of systolic and diastolic blood pressures, the arterial pressure wave is more precisely described as consisting of a pulsatile (pulse pressure) and a steady (mean pressure) component. This study explored the independent roles of pulse pressure and mean pressure as predictors of mortality in a wide range of patients with hypertension.

Design And Methods: This meta-analysis, based on individual patient data, has combined results from the control groups of seven randomized clinical trials conducted in patients with systolo-diastolic or isolated systolic hypertension.

Epidemiology of hypertension in the elderly.

In Western populations, mean systolic and diastolic blood pressures rise with advancing age up to the sixth decade of life, whereupon systolic blood pressure continues to increase and diastolic pressure starts to decline. The ensuing widening of pulse pressure is mainly ascribed to stiffening of the arterial vasculature. When hypertension is defined as systolic blood pressure of at least 140 mm Hg and/or diastolic pressure of at least 90 mm Hg, its prevalence amounts to 60%-70% of the population above 60 years of age.

In vitro assay of collagen gel contraction by cardiac fibroblasts in serum-free conditions.

The aim of the present study was to investigate whether collagen gel contraction can be induced by cardiac fibroblasts in serum-free conditions. Cardiac fibroblasts (from normal male adult rats) from passage 2 were cultured to confluency and added to a hydrated collagen gel in Dulbecco's Modified Eagle's Medium with or without fetal bovine serum for 1, 2, 3 or 7 days. Control gels containing adult rat cardiac fibroblasts showed a significant amount of contraction after 2 days of incubation in a serum-free medium, causing a contraction to 47% of the area at the start of the incubation.

Renal function in relation to three candidate genes.

We recently found that femoral intima media thickness, as well as the incidence of hypertension, is influenced by genes encoding the angiotensin-converting enzyme (ACE; insertion/deletion [I/D]) polymorphism, alpha-adducin (Gly460Trp), and aldosterone synthase (-344C/T). By interfering with blood pressure or sodium homeostasis, these genetic polymorphisms also may change renal function. We therefore investigated serum creatinine level, calculated and measured creatinine clearances, and 24-hour urinary protein excretion in subjects previously genotyped for these three polymorphisms.

Risk and benefit of treatment of isolated systolic hypertension in the elderly: evidence from the Systolic Hypertension in Europe Trial.

The Syst-Eur trial investigated whether active treatment starting with the dihydropyridine calcium channel blocker (CCB) nitrendipine, could reduce the cardiovascular complications of isolated systolic hypertension (ISH) in the elderly. The intention-to-treat analysis showed that active treatment improved outcome. The per-protocol analysis largely confirmed these results.

Birth weight and body composition in young adult men--a prospective twin study.

Objectives: To evaluate the association between birth weight and adult body composition in twins, controlling for maternal and genetic influences.

Design: Twins were randomly selected from the East Flanders Prospective Twin Survey, a population-based historic twin cohort.

Subjects: Male members of 229 twin pairs between 18 and 34 y of age who participated in the Prenatal Programming Twin Study.

T-lymphocyte and plasma angiotensin-converting enzyme activity during enalapril and losartan administration in humans.

This study evaluated the long-term effects of the angiotensin-converting enzyme inhibitor enalapril and the angiotensin II type 1 receptor antagonist losartan on the angiotensin-converting enzyme activity in T lymphocytes and plasma in patients with essential hypertension. The study was a randomized, placebo-controlled, double-blind, crossover design. Nine patients with sitting blood pressure > or = 95 mm Hg and < or = 105 mm Hg at the end of a 4-week placebo run-in period entered the double-blind phase of the study, which consisted of three 6-week periods during which patients were treated with placebo, enalapril (20 mg, once daily), or losartan (50 mg, once daily) The angiotensin-converting enzyme activity in T lymphocytes was measured as the activity of the degradation of the substrate Hippuryl-His-Leu and as the appearance of the dipeptide His-Leu, which was quantified spectrofluorometrically.