Elly Den Hond

Risks of untreated and treated isolated systolic hypertension in the elderly: meta-analysis of outcome trials

BACKGROUNDnPrevious meta-analysis of outcome trials in hypertension have not specifically focused on isolated systolic hypertension or they have explained treatment benefit mainly in function of the achieved diastolic blood pressure reduction. We therefore undertook a quantitative overview of the trials to further evaluate the risks associated with systolic blood pressure in treated and untreated older patients with isolated systolic hypertensionnnnMETHODSnPatients were 60 years old or more. Systolic blood pressure was 160 mm Hg or greater and diastolic blood pressure was less than 95 mm Hg. We used non-parametric methods and Cox regression to model the risks associated with blood pressure and to correct for regression dilution bias. We calculated pooled effects of treatment from stratified 2 x 2 contingency tables after application of Zelens test of heterogeneity.nnnFINDINGSnIn eight trials 15 693 patients with isolated systolic hypertension were followed up for 3.8 years (median). After correction for regression dilution bias, sex, age, and diastolic blood pressure, the relative hazard rates associated with a 10 mm Hg higher initial systolic blood pressure were 1.26 (p=0.0001) for total mortality, 1.22 (p=0.02) for stroke, but only 1.07 (p=0.37) for coronary events. Independent of systolic blood pressure, diastolic blood pressure was inversely correlated with total mortality, highlighting the role of pulse pressure as risk factor. Active treatment reduced total mortality by 13% (95% CI 2-22, p=0.02), cardiovascular mortality by 18%, all cardiovascular complications by 26%, stroke by 30%, and coronary events by 23%. The number of patients to treat for 5 years to prevent one major cardiovascular event was lower in men (18 vs 38), at or above age 70 (19 vs 39), and in patients with previous cardiovascular complications (16 vs 37).nnnINTERPRETATIONnDrug treatment is justified in older patients with isolated systolic hypertension whose systolic blood pressure is 160 mm Hg or higher. Absolute benefit is larger in men, in patients aged 70 or more and in those with previous cardiovascular complications or wider pulse pressure. Treatment prevented stroke more effectively than coronary events. However, the absence of a relation between coronary events and systolic blood pressure in untreated patients suggests that the coronary protection may have been underestimated.

Renal function, cytogenetic measurements, and sexual development in adolescents in relation to environmental pollutants: a feasibility study of biomarkers

BACKGROUNDnHuman exposure to chemicals is normally monitored by measurement of environmental pollutants in external media. We investigated whether biomarkers in adolescents can show exposure to, and health effects of, common environmental pollutants.nnnMETHODSnWe recruited 200 17-year-old adolescents (120 girls) from a rural control area and from two suburbs polluted by a lead smelter and two waste incinerators. We measured biomarkers of exposure and of effect in blood and urine samples, and obtained questionnaire data. School doctors measured testicular volume and staged sexual maturation.nnnFINDINGSnInternal exposure was mostly within current standards. Concentrations of lead and cadmium in blood, PCBs (polychlorinated biphenyls) and dioxin-like compounds in serum samples, and metabolites of VOCs (volatile organic compounds) in urine were higher in one or both suburbs than in the control area. Children who lived near the waste incinerators matured sexually at an older age than others, and testicular volume was smaller in boys from the suburbs than in controls. Biomarkers of glomerular or tubular renal dysfunction in individuals were positively correlated with blood lead. Biomarkers of DNA damage were positively correlated with urinary metabolites of PAHs (polycyclic aromatic hydrocarbons) and VOCs. Interpretation Biomarkers can be used to detect environmental exposure to pollutants and measure their biological effects before overt disease develops. Our findings suggest that current environmental standards are insufficient to avoid measurable biological effects.

Anti‐Saccharomyces Cerevisiae antibodies (ASCA), phenotypes of IBD, and intestinal permeability: A study in IBD families

BackgroundSerologic markers anti-Saccharomyces cerevisiae antibodies (ASCA) and antineutrophil cytoplasmic antibodies with perinuclear staining (pANCA) have been proposed to study the immunopathogenesis of IBD. Their measurement may allow better phenotyping of the disease and the detection of subclinical disease. AimsTo test the hypothesis that serological markers identify an immunologic trait related to disease susceptibility. We also wanted to test the hypothesis that ASCA is a marker related to abnormal tissue permeation by common antigens. MethodsWe studied the prevalence of pANCA and ASCA in a large cohort of sporadic and familial inflammatory bowel diseases and their unaffected relatives and spouses. Kinetics of ASCA was studied and the relationship between ASCA and 51Cr-EDTA intestinal permeation was investigated. ResultsASCA was associated with sporadic Crohns disease (CD) (63%), with Crohns patients belonging to pure CD families (62%) and also with their unaffected family members (21%). pANCA was associated with UC (58%). The prevalence of ASCA in CD patients belonging to mixed families was strikingly low (33%). ASCA was a stable marker throughout the disease and was not related to an increased small intestinal permeability. ConclusionASCA is strongly associated with familial CD in Belgium, and 21% of healthy family members also display the marker. The association is much weaker in patients belonging to mixed families. ASCA is a stable marker and is not a secondary phenomenon due to increased intestinal permeability.

Effect of high performance chicory inulin on constipation

Abstract It is known that chicory inulin (average degree of polymerisation DP=10) and oligofructose (DP=4) affect bowel function. Whereas transit time is not affected with daily doses ranging between 4 and 15g, such doses increase stool frequency and have a faecal bulking effect in healthy volunteers. Recently a new type of chicory inulin with higher average chain length (DP=25) has become commercially available. From a nutritional point of view this is an interesting carbohydrate, as it is fermented more slowly than the native product, giving it the opportunity to arrive in more distal parts of the colon. In this placebo controlled study, we investigated the effect of this high performance inulin on bowel function in healthy volunteers with low stool frequency (1 stool every 2 to 3 days). Subjects were administered 15g of the product/day for 2 weeks. Besides macroscopic observations (stool frequency, faecal bulking, etc.), or-caecal transit time, effect on intestinal permeability, amount of faecal fat, bile acids, dry solids, etc. were monitored. There was a significant increase in stool frequency with the high performance inulin ( p =0.02). The earlier observed trend to increase faecal bulk with 1.5 to 2g per g inulin ingested was observed in present study as well. There were no effects on the other measured parameters.

Effect of Long-Term Oral Glutamine Supplements on Small Intestinal Permeability in Patients With Crohn's Disease

BACKGROUNDnGlutamine is a major fuel and an important nitrogen source for the small intestinal cell. It plays a key role in maintaining mucosal cell integrity and gut barrier function. Increased permeability may be a factor in the pathogenesis of Crohns disease and may be an interesting parameter in the follow-up of the disease. Therefore, the aim of this study was to examine whether oral glutamine supplements are able to restore an increased intestinal permeability in patients with Crohns disease.nnnMETHODSnThe inclusion criteria for the study were Crohns disease and a disturbed small intestinal permeability for 51Cr-EDTA. Of 38 patients screened, 18 had an increased permeability (6 hours urinary excretion >1.1% of label recovered in urine). Fourteen patients were included in the study and were randomized to receive either oral glutamine (7 g three times per day; n = 7) or placebo (7 g glycine three times per day; n = 7) in addition to their normal treatment during a 4-week period. The study was performed in a double-blind manner.nnnRESULTSnBaseline permeability (mean +/- SD) was 2.32%+/-0.77% dose in the glutamine group and 2.29%+/-0.67% dose in the placebo group. Permeability did not change significantly after glutamine (3.26%+/-2.15% dose) or after placebo (2.27%+/-1.32% dose). There was no significant effect on plasma glutamine, plasma glutamate, plasma ammonium, Crohns disease activity index, C-reactive protein, or nutritional status.nnnCONCLUSIONSnOral glutamine supplements, in the dose administered, do not seem to restore impaired permeability in patients with Crohns disease.

Chapter 2F:The Flemish Environment and Health Study (FLEHS) – Second Survey (2007–2011): Establishing Reference Values for Biomarkers of Exposure in the Flemish Population

The second Flemish human biomonitoring survey (2007–2011) generated information on the distribution of biomarker values for a large number of environmental pollutants in a representative sample of the Flemish population. The study was implemented by the Flemish Centre of Expertise for Environment and Health, which was funded and steered by the Flemish government. From May 2008 to July 2009, 255 newborns and their mothers, 210 adolescents (14–15 years old) and 204 adults (20–40 years old) were recruited as a representative sample of the Flemish population. In all age groups, invitation letters, information brochures, letter of informed consent and self-administered questionnaires were distributed. The collected samples consisted of cord blood from the newborns, blood from the mothers, the adolescents and the adults, urine from the adolescents and the adults, and hair from the mothers. In addition to historical compounds (i.e. heavy metals, persistent chlorinated compounds, 1-hydroxy pyrene and t,t-muconic acid), new emerging pollutants were analyzed for the first time in individual samples from the Flemish population. Perfluorinated compounds and polycyclic musk compounds could be detected in all analyzed blood samples. Levels of brominated flame retardants were under the limit of quantification in most individual blood samples. Bisphenol A, metabolites of phthalates and para-hydroxybenzoic acid, a metabolite of parabens, could be detected in 90% or more of the urine samples. For metabolites of organophosphate pesticides, the highest detection frequency was observed for DMTP, detected in 90–95% of the individual urine samples. In addition, 2,5-DCP, a metabolite of para-dichlorobenzene, could be detected in over 80% of the individual urine samples. Margins of safety (MOS) were calculated by dividing the P90 obtained in FLEHSII by the available health based biomonitoring equivalants (BEs). MOS below 10 were found for toxicologically relevant arsenic, cadmium, lead, MeHg, HCB and phthalates.

Antihypertensive treatment based on home or office blood pressure—the THOP trial

Objective and methodsIn this randomized clinical trial, conducted in 400 hypertensive patients [sitting diastolic blood pressure (DBP) >95u2009mmHg], blood pressure-lowering therapy was adjusted in a stepwise manner, either on the basis of the self-measured DBP at home or on the basis of conventional DBP measured at the doctors office. ResultsTherapy guided by home blood pressure instead of office blood pressure led to less intensive drug treatment and marginally lower costs, but also to less blood pressure control with no differences in left ventricular mass. Self-measurement helped to identify patients with white-coat hypertension. ConclusionsThe present findings support a stepwise strategy for the evaluation of blood pressure, in which self-measurement and ambulatory monitoring are complementary to conventional office blood pressure measurement.

Prevalence, pathophysiology and treatment of isolated systolic hypertension in the elderly

Isolated systolic hypertension is the predominant type of hypertension in the elderly and is associated with cardiovascular complications such as stroke, coronary heart disease and heart failure. In this review, the role of arterial stiffness, endothelial function, atherosclerosis and oxidative stress in the pathogenesis of isolated systolic hypertension is extensively discussed. Placebo-controlled intervention trials such as the Systolic Hypertension in Europe Trial and the Systolic Hypertension in the Elderly Program have clearly shown that pharmacological treatment of isolated systolic hypertension improves outcome in the elderly. Nevertheless, isolated systolic hypertension remains the major subtype of untreated and uncontrolled hypertension.

Blood pressure, serum total cholesterol and contraceptive pill use in 17-year-old girls

Background Many studies have analysed the relation between cardiovascular risk factors and oral contraceptive use in adult women, whereas information on the possible health effects of oral contraceptive use during adolescence is lacking. Design The effect of current contraceptive pill use on blood pressure and serum total cholesterol concentration was studied in a cross-sectional sample of 120 adolescent girls with a mean age of 17.4 years. Methods After the girls had rested for 5 minutes in the sitting position, trained study nurses measured blood pressure three times consecutively using a mercury sphygmomanometer. The nurses also administered a questionnaire gathering information on the use of oral contraceptives, smoking and parental social class. In the morning blood samples were taken for the measurement of serum total cholesterol. Results Mean age (± SD) was 17.4 ± 0.8 years. Blood pressure averaged (± SD) 108.7 ± 9.9 systolic and 68.0 ± 8.2 mmHg diastolic. Serum total cholesterol was 4.5 ± 0.7 mmol/l. Forty-nine girls (41%) were taking the contraceptive pill. Of these, 44 (90%) were on a combination of ethinyloestradiol (20-35 μg) and a progestogen, four (8%) on anti-androgens (35 μg) and one (2%) only on a progestogen. After adjustment for age, body mass index, smoking and alcohol status systolic blood pressure was 4.6 mmHg higher (95% CI 1.2-8.1; P<0.001) in current pill users than in girls not currently on the pill (111.4 versus 106.8 mmHg). Adjusted for the aforementioned covariates, diastolic blood pressure was not related to pill use (68.2 versus 67.8 mmHg; P = 0.7). Serum total cholesterol was 0.43 mmol/l (95% CI 0.18-0.60; P = 0.001) higher among girls using oral contraceptives (4.7 versus 4.3 mmol/l), irrespective of whether or not the model was adjusted for age, body mass index, smoking and alcohol status. Conclusions In 17-year-old girls, the use of oral contraceptives was associated with a nearly 5 mmHg higher systolic blood pressure and a 0.4 mmol/l higher level of serum total cholesterol. The long-term prognostic implications of our findings remain to be elucidated.

Hypertension and Low-Level Lead Exposure: A Scientific Issue or a Matter of Faith?

To the Editor:nnVupputuri et al1 analyzed the NHANES III data. They reported that among blacks, a 3.3 μg/dL increment in the blood lead concentration was associated with an increase in systolic pressure averaging 0.82 mm Hg in men and 1.55 mm Hg in women. In contrast, blood pressure was not associated with the blood lead level among white men and women.nnWe analyzed the same NHANES III database.2 In line with Vupputuri’s article, we also found a significant and positive relationship between systolic blood pressure and the blood lead concentration in blacks. On the other hand, our analyses revealed significant and negative associations between diastolic pressure and blood lead in whites. We concluded that, across the NHANES III race and sex strata, the relationship between blood pressure and lead exposure was not consistent and should probably be attributed to residual confounding rather than to causation. Vupputuri et al emphasized the …