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Onset and development of puberty is regulated by the neuroendocrine system. Population-based studies worldwide have observed secular trends towards earlier puberty development. These changes are apparently caused by environmental factors such as improved socio-economic status, improved health care and nutrition. However, they may also partly result from endocrine-disrupting chemicals in the environment. Epidemiological studies have investigated the relationship between pubertal development and exposure to endocrine-disrupting chemicals (polychlorinated biphenyls, polybrominated biphenyls, 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane, phthalate esters, furans and the pesticide endosulfan). Associations with both perinatal and postnatal exposure have been reported. Studies in experimental animals support some of these findings and point to differential endocrine regulatory mechanisms linked to pubertal development acting in the perinatal and the pre-pubertal period. Pubertal development is naturally associated with growth and body composition. There is increasing evidence for a link between prenatal development and pubertal onset. In girls born small for gestational age (SGA), pubertal onset and age at menarche often are advanced, especially if there has been an extensive catch-up growth during the first months of life. In utero growth retardation may have multiple causes including exposure to xenobiotic substances as was suggested for some endocrine-disrupting chemicals. An abnormal perinatal environment of children born SGA may alter the endocrine status and the sensitivity of the receptors for endocrine and metabolic signalling that may have effects on maturation of brain and gonads. However, the causal pathways and the molecular mechanisms that may link the pubertal growth pattern of children born SGA, pubertal development and endocrine-disrupting chemicals need further study.

Lipophilic contaminants are present in the environment and bioaccumulate in the food chain. Therefore, their intake via animal fat of various sources was assessed for three age groups of the Flemish population, participating in a large biomonitoring program of the Flemish government. In total, 1636 adolescents (14-15 years), 1186 mothers (18-44 years), and 1586 adults (50-65 years) participated in the study and completed a semi quantitative food frequency questionnaire. Individual consumption data were combined, via a so-called simple distribution approach, with recent data on polychlorinated dibenzo-p-dioxins/furans and dioxin-like polychlorinated biphenyls, measured via the chemical-activated luciferase gene expression (CALUX) bio-assay in food items available on the Flemish market. The median (95th percentile) estimated intakes of dioxin-like contaminants were 2.24 (4.61), 2.09 (4.26), and 1.74 (3.53) pg CALUX-TEQ kg(-1) bw d(-1) for, respectively adolescents, mothers and adults. These data are in the same range as those found in other European studies. The CALUX-TEQ results of respectively 59.8%, 53.7% and 36.2% of the adolescent, mother and adult population exceed the tolerable weekly intake (TWI) of 14 pg WHO-TEQ kg(-1) bw w(-1), as derived by the Scientific Committee on Food [Scientific Committee on Food, 2001. Opinion of the Scientific Committee on Food on the Risk Assessment of Dioxins and Dioxin-like PCBs in Food, CS/CNTM/DIOXIN/20 final Brussels, Belgium]. The main contributors of dioxin-like substances are fish and seafood (25-43% of the total intake), added fats (22-25% of the total intake) and dairy products (17-20% of the total intake).

Aims: Western Europeans have low blood levels of selenium (BSe), an antioxidant trace element. In a Flemish population, we investigated the cross-sectional and longitudinal association of blood pressure (BP) with BSe., Methods and Results: We randomly recruited 710 subjects (mean age 48.8 years; 51.8% women). We measured BP and BSe and kept participants in follow-up for BP. At baseline, systolic/diastolic BP averaged (SD) 130/77 (17.3/9.2) mmHg. BSe was 97.0 (19.0) microg/L. Of 385 participants with normal baseline BP (<130 and <85 mmHg), over 5.2 years (range 3.4-8.4 years), 139 developed high-normal BP (130-139/85-90 mmHg) or hypertension (>or=140/90 mmHg). In multivariate-adjusted cross-sectional analyses of men, a 20 microg/L ( approximately 1 SD) higher BSe was associated with lower BP with effect sizes of 2.2 mmHg systolic (95% CI -0.57 to -5.05; P = 0.009) and 1.5 mmHg diastolic (95% CI -0.56 to -2.44; P = 0.017). In prospective analyses of men, a 20 microg/L higher baseline BSe was associated with a 37% (95% CI -52 to -17; P = 0.001) lower risk of developing high-normal BP or hypertension. None of these associations was significant in women., Conclusion: Deficiency of selenium might be an underestimated risk factor for the development of high BP in European men.

Cadmium exposure and accumulation in the body start at young age. Exposure routes in children are mainly via food, environmental tobacco smoke and house dust. Excretion from the body is limited. Cadmium accumulation in the kidney is responsible for effects such as nephrotoxicity and osteoporosis which are observed at adult age. Cadmium exposure through inhalation is also associated with lung cancer in adulthood. Although transfer to the neonate through the placenta and through breast milk is limited, teratogenic and developmental effects were observed in experimental animals. The database on human studies involving children is limited, yet effects on motoric and perceptual behaviour in children have been associated with elevated in utero cadmium exposure. In school age children urinary cadmium levels were associated with immune suppressive effects. More studies are needed to confirm these results. Experimental data in vitro and in animals refer to effects of cadmium on the hypothalamus-pituitary axis at different levels. This may lead to disorders of the endocrine and/or immune system. Cadmium exposure at early age should be limited as much as possible to prevent direct effects on children and to prevent accumulation of cadmium which may have serious health effects only becoming manifest at older age.

The purpose of this study was to determine if ambulatory blood pressure measurement predicted total and cardiovascular mortality over and beyond clinic blood pressure measurement and other cardiovascular risk factors; 5292 untreated hypertensive patients referred to a single blood pressure clinic who had clinic and ambulatory blood pressure measurement at baseline were followed up in a prospective study of mortality outcome. Multiple Cox regression was used to model time to total and cause-specific mortality for ambulatory blood pressure measurement while adjusting for clinic blood pressure measurement and other risk factors at baseline. There were 646 deaths (of which 389 were cardiovascular) during a median follow-up period of 8.4 years. With adjustment for gender, age, risk indices, and clinic blood pressure, higher mean values of ambulatory blood pressure were independent predictors for cardiovascular mortality. The relative hazard ratio for each 10-mm Hg increase in systolic blood pressure was 1.12 (1.06 to 1.18; P<0.001) for daytime and 1.21 (1.15 to 1.27; P<0.001) for nighttime systolic blood pressure. The hazard ratios for each 5-mm Hg increase in diastolic blood pressure were 1.02 (0.99 to 1.07; P=NS) for daytime and 1.09 (1.04 to 1.13; P<0.01) for nighttime diastolic pressures. The hazard ratios for nighttime ambulatory blood pressure remained significant after adjustment for daytime ambulatory blood pressure. These results have 2 important clinical messages: ambulatory measurement of blood pressure is superior to clinic measurement in predicting cardiovascular mortality, and nighttime blood pressure is the most potent predictor of outcome.

To be suitable for the management of hypertension, self-measurement of blood pressure (BP) at home should follow international recommendations. The use of accurate and validated measuring devices is an important prerequisite. Upper arm BP monitors are the first choice, while wrist and finger devices cannot be recommended. Measurements should, preferentially, be downloaded from the memory of a device or printed. Reference values have been proposed, but were mostly based on cross-sectional observations and have not yet been widely validated by prospective outcome studies. Currently, levels of home BP of <135 mm Hg systolic and 85 mm Hg diastolic are usually considered normal. Home BP measurement is sometimes recommended as an alternative to ambulatory BP monitoring to diagnose white-coat hypertension.However, home BP measurement cannot replace ambulatory BP monitoring in the diagnosis of hypertension (white-coat), but both techniques have complementary roles. The appropriateness of home BP measurement to guide antihypertensive treatment has only been tested in one large-scale randomized trial: the THOP (Treatment of Hypertension Based on Home or Office Blood Pressure) trial. The THOP trial showed that antihypertensive treatment based on home instead of office BP led to less intensive drug treatment, but also to less BP control with no differences in general wellbeing and left ventricular mass. Home BP monitoring also contributed to the identification of patients with white-coat hypertension. On balance, most evidence supports the view that office BP measurement remains the key in the diagnosis and treatment of hypertension. Treatment can be started without confirmation of elevated office BP in patients with high office BP and target organ damage, or a high cardiovascular risk profile. In patients with raised office BP but without target organ damage (white-coat hypertension), or with normal office BP but unexplained target organ damage (masked hypertension), ambulatory or home BP monitoring or both must be used to confirm the diagnosis. Few longitudinal studies have addressed the long-term prognostic meaning of home BP measurement. Until more prospective data become available, management of hypertension exclusively based on self-measurement of BP at home cannot be recommended.

Background: Risk factors in young adulthood may persist into later life and eventually lead to cardiovascular (CV) disease. The purpose of this study was to describe the prevalence of hypertension and other established CV risk factors in older adolescents., Methods: Study nurses examined 120 girls and 80 boys with a mean age of 17.4 (SD, 0.8; range 15.8-19.6 years). After 5 minutes of sitting rest, resting blood pressure (BP) of the participants was measured in triplicate by sphygmomanometry. Body height and weight were measured and body mass index (BMI) was calculated. Serum lipids, smoking and drinking status were assessed. Hypertension was diagnosed according to the criteria specified in the 1996 update of the Task Force on BP treatment in Children and Adolescents (Pediatrics 1996;98:649-58)., Results: Almost 25% of the subjects currently smoked with a median daily consumption of 6 (Interquartile 4-9) and 11 (6-16) cigarettes in girls and boys, respectively. Fourty-nine (41%) girls used oral contraceptives. Systolic (118 versus 109 mm Hg, p<0.001) and diastolic BPs (70.5 versus 68.0 mm Hg, p=0.033) were significantly higher in boys than in girls. Two (2%) girls and four (5%) boys had systolic hypertension; diastolic hypertension was found in six (5%) girls and one (1%) boy. Twelve (10%) girls and six (8%) boys were overweight (>25.0 kg/m2). Twenty (17%) girls and seven (9%) boys had hypercholesterolemia (total serum cholesterol > or =5.2 mmol/L). Overall, 50 (42%) girls and 31 (39%) boys had at least one CV risk factor, 12 (10%) girls and four (5%) boys had two risk factors, and three (3%) girls and one (1%) boy had more than two risk factors., Conclusions: In 17-year-olds living in an affluent society the prevalence of CV risk factors was high. These findings underscore the importance of health education and prevention at this age.

Objective and Methods: In this randomized clinical trial, conducted in 400 hypertensive patients [sitting diastolic blood pressure (DBP) >95 mmHg], 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 doctor's office., Results: Therapy 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., Conclusions: The 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.

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.

Context: Self-measurement of blood pressure is increasingly used in clinical practice, but how it affects the treatment of hypertension requires further study., Objective: To compare use of blood pressure (BP) measurements taken in physicians' offices and at home in the treatment of patients with hypertension., Design, Setting, and Participants: Blinded randomized controlled trial conducted from March 1997 to April 2002 at 56 primary care practices and 3 hospital-based outpatient clinics in Belgium and 1 specialized hypertension clinic in Dublin, Ireland. Four hundred participants with a diastolic BP (DBP) of 95 mm Hg or more as measured at physicians' offices were enrolled and followed up for 1 year., Interventions: Antihypertensive drug treatment was adjusted in a stepwise fashion based on either the self-measured DBP at home (average of 6 measurements per day during 1 week; n = 203) or the average of 3 sitting DBP readings at the physician's office (n = 197). If the DBP guiding treatment was above (>89 mm Hg), at (80-89 mm Hg), or below (<80 mm Hg) target, a physician blinded to randomization intensified antihypertensive treatment, left it unchanged, or reduced it, respectively., Mean Outcome Measures: Office and home BP levels, 24-hour ambulatory BP, intensity of drug treatment, electrocardiographic and echocardiographic left ventricular mass, symptoms reported by questionnaire, and costs of treatment., Results: At the end of the study (median follow-up, 350 days; interquartile range, 326-409 days), more home BP than office BP patients had stopped antihypertensive drug treatment (25.6% vs 11.3%; P<.001) with no significant difference in the proportions of patients progressing to multiple-drug treatment (38.7% vs 45.1%; P =.14). The final office, home, and 24-hour ambulatory BP measurements were higher (P<.001) in the home BP group than in the office BP group. The mean baseline-adjusted systolic/diastolic differences between the home and office BP groups averaged 6.8/3.5 mm Hg, 4.9/2.9 mm Hg, and 4.9/2.9 mm Hg, respectively. Left ventricular mass and reported symptoms were similar in the 2 groups. Costs per 100 patients followed up for 1 month were only slightly lower in the home BP group (3875 vs 3522 [4921 dollars vs 4473 dollars]; P =.04)., Conclusions: Adjustment of antihypertensive treatment based on home BP instead of office BP led to less intensive drug treatment and marginally lower costs but also to less BP control, with no differences in general well-being or left ventricular mass. Self-measurement allowed identification of patients with white-coat hypertension. Our findings support a stepwise strategy for the evaluation of BP in which self-measurement and ambulatory monitoring are complementary to conventional office measurement and highlight the need for prospective outcome studies to establish the normal range of home-measured BP.

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 microg) and a progestogen, four (8%) on anti-androgens (35 microg) 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 is present in 60% to 70% of the population over 60 years of age and may result in 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 hypertension is discussed extensively. Antihypertensive drug treatment may control high blood pressure and prevent complications. This review summarizes the results of several placebo-controlled and comparative clinical trials that have studied the efficacy of different classes of antihypertensive drugs.

Background: The relationship between LV mass and systolic blood pressure at baseline was studied in the pooled database of the APTH (n = 408) and THOP (n = 376) trials., Methods: Partial correlation coefficients were calculated between electrocardiographic and echocardiographic LV mass at baseline and different types of blood pressure, that is, office blood pressure (OBP), 24-h ambulatory blood pressure (ABP), daytime ABP and night-time ABP., Results: Electrocardiographic LV mass correlated equally well (P < or = 0.001) with all types of systolic blood pressure (partial r = 0.19 to 0.22 for the Sokolow-Lyon index, 0.20 to 0.22 for the sum of the Sokolow-Lyon index plus the R-wave in aVl, and 0.12 to 0.19 for the Cornell voltage). The findings were similar for echocardiographic LV mass index (partial r = 0.15 to 0.22). However, for echocardiographic mean wall thickness, there was a stronger association with ABP than with OBP (partial r = 0.30 for 24-h ABP, 0.29 for daytime ABP, 0.26 for night-time ABP versus 0.15 for OBP (P < or = 0.05)). CONCLUSIONS In the combined dataset of the APTH and THOP trials, electrocardiographic and echocardiographic LV mass at baseline correlated significantly with all types of systolic blood pressure. For mean wall thickness, the relationship was stronger for ABP than OBP.

Cardiovascular disease (CVD) has a multifactorial aetiology and many potential risk markers are known. As it was not feasible to discuss all markers and their possible interactions in relation to all aspects of CVD, selections had to be made in this paper. In the context of claims and functional foods, emphasis was placed on those aetiological processes and risk markers that have been shown previously to be modified by diet: lipid and lipoprotein metabolism, haemostatic function, oxidative damage, homocysteine metabolism, and blood pressure. Except for methodological and biological characteristics of these biomarkers, their relationships with the risk of CVD are discussed. For LDL and HDL cholesterol, fasting triacylglycerol, homocysteine, and blood pressure well-validated, easy applicable, and generally accepted biomarkers exist. For haemostatic function and oxidative damage validation of markers with respect to CVD or intermediate clinical markers is recommended. For diet-related CVD, however, the ultimate question is whether changes in the biomarker are truly related to changes in risk. Only for LDL cholesterol and blood pressure does consensus exist among scientists for a possible application as enhanced function claims. For HDL, triacylglycerol, and homocysteine, and in particular for haemostatic function and oxidative damage, however, formal proof is lacking that diet-induced changes in these biomarkers alter the risk of CVD. At the same time, it should be emphasised that CVD is multifactorial. Therefore it does not seem justified that a change in one particular biomarker is enough evidence to substantiate a claim. There are examples of food components or drugs that one biomarker is changed in a favourable way, but at the same time another biomarker is changed in an unfavourable way. Therefore, studies to further validate generic predictors for the CVD risk should be initiated.

Background: Gender, age, smoking, race, and body mass index have been reported to determine the ambulatory white-coat effect (WCE) and white-coat hypertension (WCH)., Methods: Baseline conventional, day-time ambulatory and self-measured home blood pressure measurements from the THOP trial were used to study the effect of gender, age, body mass index, smoking habits and treatment status on the white-coat syndrome as assessed by ambulatory monitoring or self-measurement., Results: The mean systolic/diastolic WCE was 9.1/6.7 mmHg if based on ambulatory blood pressure and 12.2/8.7 mmHg if based on self-measured blood pressure. The ambulatory WCE was significantly higher in women, in older subjects (65+), in obese subjects, in non-smokers and in patients on antihypertensive drug treatment. The self-measured WCE was significantly higher in women and in non-smokers. Ambulatory WCH was present in 6.6% of the untreated patients and 14.2% had self-measured WCH. The proportion of ambulatory WCH was significantly higher in obese subjects; the proportion of self-measured WCH did not differ by gender, age, body mass index, or smoking habits., Conclusions: The ambulatory white-coat syndrome was determined by gender, age, body mass index, smoking habits, and treatment status. The self-measured white-coat syndrome was greater than the ambulatory white-coat syndrome but depended less on the determinants under study.

Background: In a Caucasian population, the prevalence and incidence of hypertension, renal function and large artery stiffness were significantly correlated with polymorphisms in the genes encoding the angiotensin-converting enzyme (ACE I/D), aldosterone synthase (-C344T) and the cytoskeleton protein alpha-adducin (Gly460Trp)., Objective: This study investigated intima-media thickening, a precursor of atherosclerosis, in relation to these genetic polymorphisms., Methods: Carotid and femoral intima-media thickness were assessed with a wall-track system in 380 subjects enrolled in a population study. Subjects were genotyped for the presence of the ACE D, aldosterone synthase -344T and alpha-adducin 460Trp alleles. The statistical analysis allowed for confounders, interactions among genes, and the non-independence of the phenotypes within families., Results: The sample included 188 men (49.5%). Mean age was 39.8 years. Intima-media thickness of the carotid and femoral arteries averaged 575 and 719 microm, respectively. Intima-media thickness of the femoral-but not carotid-artery increased with the number of ACE D alleles. The effect of ACE genotype on femoral intima-media thickness was confined to carriers of the 460Trp allele and the -344T allele. Expressed as a percentage of the population mean, the mean differences between II and DD homozygotes averaged 13.4% (95% CI 5.6-21.2%) in all subjects, 21.2% (8.0-34.5%) in carriers of the 460Trp allele, 15.4% (4.1-26.8%) in carriers of the -344T allele, and 25.2% (10.7-39.7%) if the 460Trp and -344T alleles were both present., Conclusion: This study shows that a relationship exists between the intima-media thickness of the large muscular femoral artery and the ACE gene. This relationship is only apparent in the presence of either the alpha-adducin 460Trp or the aldosterone synthase -344T allele. These findings may have clinical implications for the assessment of genetic cardiovascular risk.

Polychlorinated aromatic hydrocarbons (PCAHs) have been described as endocrine disruptors in animals and in accidentally or occupationally exposed humans. In the present study we examined the effect of moderate exposure to PCAHs on sexual maturation. Two hundred adolescents (mean age, 17.4 years) who resided in two polluted suburbs and a rural control area in Flanders (Belgium) participated. We measured the serum concentration of polychlorinated biphenyl (PCB) congeners 138, 153, and 180 and dioxin-like compounds [chemically activated luciferase expression (CALUX) assay] as biomarkers of exposure. School physicians assessed the pubertal development of boys and girls and measured testicular volume. In one suburb near two waste incinerators, compared with the other suburb and the control area, fewer boys (p < 0.001) had reached the adult stages of genital development (62% vs. 92% and 100%, respectively) and pubic hair growth (48% vs. 77% and 100%). Also, in the same suburb, fewer girls (p = 0.04) had reached the adult stage of breast development (67% vs. 90% and 79%). In individual boys, a doubling of the serum concentration of PCB congener 138 increased the odds of not having matured into the adult stage of genital development by 3.5 (p = 0.04); similarly for PCB congener 153 in relation to male pubic hair growth, the odds ratio was 3.5 (p = 0.04). In girls, a doubling of the serum dioxin concentration increased the odds of not having reached the adult stage of breast development by 2.3 (p = 0.02). Left plus right testicular volume was lower in both polluted areas than in the control area (42.4 mL vs. 47.3 mL, p = 0.005) but was not related to the current exposure of the adolescents to PCAHs. Through endocrine disruption, environmental exposure to PCAHs may interfere with sexual maturation and in the long-run adversely affect human reproduction.

We compared cardiovascular outcome between patients with white-coat and sustained hypertension who had previously participated in the Ambulatory Blood Pressure Monitoring and Treatment of Hypertension (APTH) trial. Baseline characteristics, including office and ambulatory blood pressure (BP), were measured during the 2-month run-in period of the APTH trial. During follow-up, information on the occurrence of major cardiovascular events (death, myocardial infarction, stroke and heart failure), achieved office BP and treatment status was obtained. At entry, 326 patients had sustained hypertension (daytime ambulatory BP > or = 140 mmHg systolic and/or > or = 90 mmHg diastolic) and 93 had daytime ambulatory BP below these limits and were classified as white-coat hypertensives. During 2088 patient-years of follow-up (median follow-up 5.3 years), all major cardiovascular events (n = 22) occurred in the patients with sustained hypertension (rate 12.7 per 1000 patient-years, p = 0.02 for between-group difference). Furthermore, multiple Cox regression confirmed that after adjustment for important covariables, daytime ambulatory BP--but not office BP at entry--significantly and independently predicted cardiovascular outcome. After additional adjustment for office BP, daytime ambulatory BP still predicted the occurrence of major cardiovascular events. Although white-coat hypertension was less frequently associated with antihypertensive drug treatment during follow-up, it carried a significantly better prognosis than sustained hypertension.

Background: Serologic 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., Aims: To 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., Methods: We 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., Results: ASCA was associated with sporadic Crohn's disease (CD) (63%), with Crohn's 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., Conclusion: ASCA 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.

Background: Glutamine 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 Crohn's 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 Crohn's disease., Methods: The inclusion criteria for the study were Crohn's 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., Results: Baseline 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, Crohn's disease activity index, C-reactive protein, or nutritional status., Conclusions: Oral glutamine supplements, in the dose administered, do not seem to restore impaired permeability in patients with Crohn's disease.

Background & Aims: Impaired short-chain fatty acid metabolism by the colonocyte has been suggested as a pathogenic factor in ulcerative colitis (UC). The aim of this study was to measure in vivo butyrate metabolism in UC and to correlate butyrate oxidation with colonic permeability., Methods: Butyrate oxidation was measured by means of a 14CO2-breath test after rectal instillation of 14C-butyrate. 51Cr-ethylenediaminetetraacetic acid (EDTA) was added to the enema, and the urinary % dose excretion of 51Cr-EDTA after 6 hours was a measure for permeability., Results: Patients with active extensive UC showed a significantly lower butyrate oxidation and increased colonic permeability in comparison to healthy controls. Butyrate oxidation correlated significantly negative with clinical activity. Oxidation of butyrate was not decreased in most patients with inactive extensive UC. In 3 patients with inactive disease and decreased oxidation, a relapse occurred within a few weeks after the test, whereas all patients with normal oxidation maintained their remission for at least 3 months. A significantly negative correlation existed between butyrate oxidation and colonic permeability., Conclusions: Patients with active extensive UC have a decreased colonic butyrate oxidation. However, the fact that remission is associated with normal oxidation suggests that UC mucosa is not intrinsically altered in butyrate oxidation, making this unlikely to be a primary defect in UC.