Prehypertension is considered a precursor of stage 1 hypertension and a predictor of excessive cardiovascular risk. We investigated whether pharmacologic treatment of prehypertension prevents or postpones stage 1 hypertension. Participants with repeated measurements of systolic pressure of 130 to 139 mm Hg and diastolic pressure of 89 mm Hg or lower, or systolic pressure of 139 mm Hg or lower and diastolic pressure of 85 to 89 mm Hg, were randomly assigned to receive two years of candesartan (Atacand, AstraZeneca) or placebo, followed by two years of placebo for all. When a participant reached the study end point of stage 1 hypertension, treatment with antihypertensive agents was initiated. Both the candesartan group and the placebo group were instructed to make changes in lifestyle to reduce blood pressure throughout the trial. A total of 409 participants were randomly assigned to candesartan, and 400 to placebo. Data on 772 participants (391 in the candesartan group and 381 in the placebo group; mean age, 48.5 years; 59.6 percent men) were available for analysis. During the first two years, hypertension developed in 154 participants in the placebo group and 53 of those in the candesartan group (relative risk reduction, 66.3 percent; P<0.001). After four years, hypertension had developed in 240 participants in the placebo group and 208 of those in the candesartan group (relative risk reduction, 15.6 percent; P<0.007). Serious adverse events occurred in 3.5 percent of the participants assigned to candesartan and 5.9 percent of those receiving placebo. Over a period of four years, stage 1 hypertension developed in nearly two thirds of patients with untreated prehypertension (the placebo group). Treatment of prehypertension with candesartan appeared to be well tolerated and reduced the risk of incident hypertension during the study period. Thus, treatment of prehypertension appears to be feasible. (ClinicalTrials.gov number, NCT00227318.)

Fine particulate matter air pollution plus ozone impairs vascular function and raises diastolic blood pressure. We aimed to determine the mechanism and air pollutant responsible. The effects of pollution on heart rate variability, blood pressure, biomarkers, and brachial flow-mediated dilatation were determined in 2 randomized, double-blind, crossover studies. In Ann Arbor, 50 subjects were exposed to fine particles (150 μg/m ³ ) plus ozone (120 parts per billion) for 2 hours on 3 occasions with pretreatments of an endothelin antagonist (Bosentan, 250 mg), antioxidant (Vitamin C, 2 g), or placebo. In Toronto, 31 subjects were exposed to 4 different conditions (particles plus ozone, particles, ozone, and filtered air). In Toronto, diastolic blood pressure significantly increased (2.9 and 3.6 mm Hg) only during particle-containing exposures in association with particulate matter concentration and reductions in heart rate variability. Flow-mediated dilatation significantly decreased (2.0% and 2.9%) only 24 hours after particle-containing exposures in association with particulate matter concentration and increases in blood tumor necrosis factor α. In Ann Arbor, diastolic blood pressure significantly similarly increased during all of the exposures (2.5 to 4.0 mm Hg), a response not mitigated by pretreatments. Flow-mediated dilatation remained unaltered. Particulate matter, not ozone, was responsible for increasing diastolic blood pressure during air pollution inhalation, most plausibly by instigating acute autonomic imbalance. Only particles from urban Toronto additionally impaired endothelial function, likely via slower proinflammatory pathways. Our findings demonstrate credible mechanisms whereby fine particulate matter could trigger acute cardiovascular events and that aspects of exposure location may be an important determinant of the health consequences.

OBJECTIVE. The goal was to determine the relationship between the 4 parenting styles (authoritative, authoritarian, permissive, and neglectful) and overweight status in first grade. METHODS. Data from the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development were analyzed. Children with complete data for parenting parameters at 54 months and measured weight and height in first grade were included in the analysis. Overweight was defined as BMI of ≥95th percentile. The 4 parenting styles were constructed with 2 scales, namely, maternal sensitivity and maternal expectations for child self-control. Multivariate logistic regression analysis was used to evaluate the relationship between parenting style and overweight in first grade, controlling for gender, race, maternal education, income/needs ratio, marital status, and child behavior problems. RESULTS. A total of 872 children, 11.1% overweight and 82.8% white, were included in the analysis. Children of authoritarian mothers (n = 298) had an increased risk of being overweight, compared with children of authoritative mothers (n = 179). Children of permissive (n = 132) and neglectful (n = 263) mothers were twice as likely to be overweight, compared with children of authoritative mothers. Of the covariates, only income/needs ratio was significant and did not alter the relationship between parenting style and overweight risk. CONCLUSIONS. Among the 4 parenting styles, authoritarian parenting was associated with the highest risk of overweight among young children. Understanding the mechanisms through which parenting styles are associated with overweight risk may lead to the development of more-comprehensive and better-targeted interventions.

Objective: The relationship between adipose tissue fibrosis, adipocyte hypertrophy, and preadipocyte hyperplasia in the context of obesity and the correlation of these tissue‐based phenomena with systemic metabolic disease are poorly defined. The goal of this study was to clarify the relationship between adipose tissue fibrosis, adipocyte hypertrophy, and preadipocyte hyperplasia in human obesity and determine the correlation of these adipose‐tissue based phenomena with diabetes.Methods: Visceral and subcutaneous adipose tissues from humans with obesity collected during bariatric surgery were studied with QRTPCR, immunohistochemistry, and flow cytometry for expression of collagens and fibrosis‐related proteins, adipocyte size, and preadipocyte frequency. Results were correlated with clinical characteristics including diabetes status.Results: Fibrosis was decreased, hypertrophy was increased, and preadipocyte frequency and fibrotic gene expression were decreased in adipose tissues from diabetic subjects compared to non‐diabetic subjects. These differences were greater in visceral compared to subcutaneous adipose tissue.Conclusions: These data are consistent with the hypothesis that adipose tissue fibrosis in the context of human obesity limits adipocyte hypertrophy and is associated with a reciprocal increase in adipocyte hyperplasia, with beneficial effects on systemic metabolism. These findings suggest adipose tissue fibrosis as a potential target for manipulation of adipocyte metabolism.

OBJECTIVE. We sought to examine the association between weight status in early childhood and onset of puberty. PATIENTS AND METHODS. The study included 354 girls from the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development. Girls were followed longitudinally with height and weight measurements at 36 and 54 months and grades 1, 4, 5, and 6 and with assessment of pubertal stage by physical examination and maternal report in grades 4 through 6. The main outcome was the presence of early puberty, indexed as follows: (a) breast development at or more than Tanner stage 2 by physical examination at grade 4; (b) breast development at or more than Tanner stage 3 by physical examination at grade 5; (c) maternal report of breast development at or more than Tanner stage 3 at grade 5; and (d) maternal report of menarche having already occurred (yes versus no) at grade 6. Multiple logistic regression models predicting early versus late puberty were constructed by using the covariate BMI z score at 36 months, rate of change of BMI and accelerated BMI between 36 months and grade 1, race, maternal education, and maternal age of menarche. RESULTS. BMI z score at 36 months, rate of change of BMI between 36 months and grade 1, an earlier age of maternal menarche, and nonwhite race were each consistently and positively associated with an earlier onset of puberty across the various measures of puberty. CONCLUSIONS. Higher BMI z score in girls as young as 36 months of age and higher rate of change of BMI between 36 months old and grade 1, a period well before the onset of puberty, are associated with earlier puberty, which suggests that increasing rates of obesity in the United States may result in an earlier average age of onset of puberty for US girls.

Iron deficiency in infancy negatively impacts a variety of neurodevelopmental processes at the time of nutrient insufficiency, with persistent central nervous system alterations and deficits in behavioral functioning, despite iron therapy. In rodent models, early iron deficiency impairs the hippocampus and the dopamine system. We examined the possibility that young adults who had experienced chronic, severe, iron deficiency as infants would exhibit deficits on neurocognitive tests with documented frontostriatal (Trail Making Test, Intra-/Extra-dimensional Shift, Stockings of Cambridge, Spatial Working Memory, Rapid Visual Information Processing) and hippocampal specificity (Pattern Recognition Memory, Spatial Recognition Memory). Participants with chronic, severe iron deficiency in infancy performed less well on frontostriatal-mediated executive functions, including inhibitory control, set-shifting, and planning. Participants also exhibited impairment on a hippocampus-based recognition memory task. We suggest that these deficits may result from the long-term effects of early iron deficiency on the dopamine system, the hippocampus, and their interaction.