Cardiovascular-Risk Indicators Elevated in Overweight & Obese Children

Objectives:

To describe the association and its magnitude between body mass index category, sex, and cardiovascular disease risk parameters in school aged children in highly developed countries.

Design:

Systematic review and meta-analysis. Quality of included studies assessed by an adapted version of the Cochrane Collaboration’s risk of bias assessment tool. Results of included studies in meta-analysis were pooled and analysed by Review Manager version 5.1.

Data sources:

Embase, PubMed, EBSCOHost’s cumulative index to nursing and allied health literature, and the Web of Science databases for papers published between January 2000 and December 2011.

Review methods:

Healthy children aged 5 to 15 in highly developed countries enrolled in studies done after 1990 and using prospective or retrospective cohort, cross sectional, case-control, or randomised clinical trial designs in school, outpatient, or community settings. Included studies had to report an objective measure of weight and at least one prespecified risk parameter for cardiovascular disease.

Results:

We included 63 studies of 49 220 children. Studies reported a worsening of risk parameters for cardiovascular disease in overweight and obese participants. Compared with normal weight children, systolic blood pressure was higher by 4.54 mm Hg (99% confidence interval 2.44 to 6.64; n=12 169, eight studies) in overweight children, and by 7.49 mm Hg (3.36 to 11.62; n=8074, 15 studies) in obese children. We found similar associations between groups in diastolic and 24 h ambulatory systolic blood pressure. Obesity adversely affected concentrations of all blood lipids; total cholesterol and triglycerides were 0.15 mmol/L (0.04 to 0.25, n=5072) and 0.26 mmol/L (0.13 to 0.39, n=5138) higher in obese children, respectively. Fasting insulin and insulin resistance were significantly higher in obese participants but not in overweight participants. Obese children had a significant increase in left ventricular mass of 19.12 g (12.66 to 25.59, n=223), compared with normal weight children.

Conclusion:

Having a body mass index outside the normal range significantly worsens risk parameters for cardiovascular disease in school aged children. This effect, already substantial in overweight children, increases in obesity and could be larger than previously thought. There is a need to establish whether acceptable parameter cut-off levels not considering weight are a valid measure of risk in modern children and whether methods used in their study and reporting should be standardised.

BMJ 2012;345:e4759

Urinary BPA Levels Tied to Obesity in Kids

Context:

Bisphenol A (BPA), a manufactured chemical, is found in canned food, polycarbonate-bottled liquids, and other consumer products. In adults, elevated urinary BPA concentrations are associated with obesity and incident coronary artery disease. BPA exposure is plausibly linked to childhood obesity, but evidence is lacking to date.

Objective:

To examine associations between urinary BPA concentration and body mass outcomes in children.

Design, Setting, and Participants:   

Cross-sectional analysis of a nationally representative subsample of 2838 participants aged 6 through 19 years randomly selected for measurement of urinary BPA concentration in the 2003-2008 National Health and Nutrition Examination Surveys.

Main Outcome Measures:

Body mass index (BMI), converted to sex- and age-standardized z scores and used to classify participants as overweight (BMI ≥85th percentile for age/sex) or obese (BMI ≥95th percentile).

Results:

Median urinary BPA concentration was 2.8 ng/mL (interquartile range, 1.5-5.6). Of the participants, 1047 (34.1% [SE, 1.5%]) were overweight and 590 (17.8% [SE, 1.3%]) were obese. Controlling for race/ethnicity, age, caregiver education, poverty to income ratio, sex, serum cotinine level, caloric intake, television watching, and urinary creatinine level, children in the lowest urinary BPA quartile had a lower estimated prevalence of obesity (10.3% [95% CI, 7.5%-13.1%]) than those in quartiles 2 (20.1% [95% CI, 14.5%-25.6%]), 3 (19.0% [95% CI, 13.7%-24.2%]), and 4 (22.3% [95% CI, 16.6%-27.9%]). Similar patterns of association were found in multivariable analyses examining the association between quartiled urinary BPA concentration and BMI z score and in analyses that examined the logarithm of urinary BPA concentration and the prevalence of obesity. Obesity was not associated with exposure to other environmental phenols commonly used in other consumer products, such as sunscreens and soaps. In stratified analysis, significant associations between urinary BPA concentrations and obesity were found among whites (P < .001) but not among blacks or Hispanics.

Conclusions:

Urinary BPA concentration was significantly associated with obesity in this cross-sectional study of children and adolescents. Explanations of the association cannot rule out the possibility that obese children ingest food with higher BPA content or have greater adipose stores of BPA.

JAMA. 2012;308(11):1113-1121. doi:10.1001/2012.jama.11461

Salt Intake in Kids Associated with Hypertension

OBJECTIVE:

To assess the association between usual dietary sodium intake and blood pressure among US children and adolescents, overall and by weight status.

METHODS:

Children and adolescents aged 8 to 18 years (n = 6235) who participated in NHANES 2003–2008 comprised the sample. Subjects’ usual sodium intake was estimated by using multiple 24-hour dietary recalls. Linear or logistic regression was used to examine association between sodium intake and blood pressure or risk for pre-high blood pressure and high blood pressure (pre-HBP/HPB).

RESULTS:

Study subjects consumed an average of 3387 mg/day of sodium, and 37% were overweight/obese. Each 1000 mg per day sodium intake was associated with an increased SD score of 0.097 (95% confidence interval [CI] 0.006–0.188, ∼1.0 mm Hg) in systolic blood pressure (SBP) among all subjects and 0.141 (95% CI: –0.010 to 0.298, ∼1.5 mm Hg) increase among overweight/obese subjects. Mean adjusted SBP increased progressively with sodium intake quartile, from 106.2 mm Hg (95% CI: 105.1–107.3) to 108.8 mm Hg (95% CI: 107.5–110.1) overall (P = .010) and from 109.0 mm Hg (95% CI: 107.2–110.8) to 112.8 mm Hg (95% CI: 110.7–114.9; P = .037) among those overweight/obese. Adjusted odds ratios comparing risk for pre-HBP/HPB among subjects in the highest versus lowest sodium intake quartile were 2.0 (95% CI: 0.95–4.1, P = .062) overall and 3.5 (95% CI: 1.3–9.2, P = .013) among those overweight/obese. Sodium intake and weight status appeared to have synergistic effects on risk for pre-HBP/HPB (relative excess risk for interaction = 0.29 (95% CI: 0.01–0.90, P < .05).

CONCLUSIONS:

Sodium intake is positively associated with SBP and risk for pre-HBP/HPB among US children and adolescents, and this association may be stronger among those who are overweight/obese.

 Pediatrics 2012;130:611–619

The authors note that on average, these children consumed about as much sodium as adults. They point out that given the observational nature of their study, "a large randomized controlled trial would be needed" to confirm the results.

Bottle-Fed Infants at Increased Risk for Pyloric Stenosis

OBJECTIVES:

Bottle-feeding has been suggested to increase the risk of pyloric stenosis (PS). However, large population based studies are needed. We examined the effect of bottle-feeding during the first 4 months after birth, by using detailed data about the timing of first exposure to bottle-feeding and extensive confounder information.

METHODS:

We performed a large population-based cohort study based on the Danish National Birth Cohort, which provided information on infants and feeding practice. Information about surgery for PS was obtained from the Danish National Patient Register. The association between bottle-feeding and the risk of PS was evaluated by hazard ratios (HRs) estimated in a Cox regression model, adjusting for possible confounders.

RESULTS:

Among 70,148 singleton infants, 65 infants had surgery for PS, of which 29 were bottle-fed before PS diagnosis. The overall HR of PS for bottle-fed infants compared with not bottle-fed infants was 4.62 (95% confidence interval [CI]: 2.78–7.65). Among bottle-fed infants, risk increases were similar for infants both breast and bottle-fed (HR: 3.36 [95% CI: 1.60–7.03]), formerly breastfed (HR: 5.38 [95% CI: 2.88–10.06]), and never breastfed (HR: 6.32 [95% CI: 2.45–16.26]) (P =.76). The increased risk of PS among bottle-fed infants was observed even after 30 days since first exposure to bottle-feeding and did not vary with age at first exposure to bottle-feeding.

CONCLUSIONS:

Bottle-fed infants experienced a 4.6-fold higher risk of PS compared with infants who were not bottle-fed. The result adds to the evidence supporting the advantage of exclusive breastfeeding in the first months after birth.  

Pediatrics 2012;130:1–7

The authors speculate that "infants given formula by bottle ingest a larger volume of milk and retain it for a longer period of time in the stomach. This burden of overfeeding may challenge the pylorus muscle and lead to hypertrophy." They say their results add to the evidence supporting exclusive breast-feeding in an infant's early life.

Omega-3 fatty acids: Benefits for cardio-cerebro-vascular diseases

BACKGROUND AND PURPOSE:

Intracranial artery stenosis (ICAS) is a narrowing of an intracranial artery, which is a common etiology for ischemic stroke. In this commentary, we review key aspects of the discrimination between non-stroke controls and ischemic stroke patients on the background of phospholipid ω3-fatty acid (DHA, EPA) composition. The discussion is embedded in the presentation of general effects of long-chain ω3 polyunsaturated fatty acids (PUFAs) in cardio-cerebro-vascular diseases (CCVDs) and Alzheimer dementia (AD).

SUMMARY OF COMMENTARY:

ICAS is a common stroke subtype and has emerged as a major factor in recurrent stroke and vascular mortality. DHA and EPA are important fatty acids to distinguish between NCAS (no cerebral arteriosclerotic stenosis) and ICAS in stroke. The risk of ICAS is inversely correlated with the DHA content in phospholipids. Furthermore, a mechanistic explanation has been proposed for the beneficial effects of PUFAs in CCVDs and AD.

CONCLUSIONS:

Whereas the beneficial effects of EPA/DHA for cardiovascular diseases and stroke seem to be beyond question, preventive effects in patients with very mild cognitive dysfunction and beginning Alzheimer's disease undoubtedly need confirmation by larger clinical trials. A collaborative international basic science approach is warranted considering cautiously designed studies in order to avoid ethical problems.

Atherosclerosis. 2012 Sep 18. pii: S0021-9150(12)00619-3

Meta-Analysis: Omega-3s Don't Affect Cardiovascular Outcomes

Context: 

Considerable controversy exists regarding the association of omega-3 polyunsaturated fatty acids (PUFAs) and major cardiovascular end points.

Objective: 

To assess the role of omega-3 supplementation on major cardiovascular outcomes.

Data Sources  MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials through August 2012.

Study Selection: 

Randomized clinical trials evaluating the effect of omega-3 on all-cause mortality, cardiac death, sudden death, myocardial infarction, and stroke.

Data Extraction: 

Descriptive and quantitative information was extracted; absolute and relative risk (RR) estimates were synthesized under a random-effects model. Heterogeneity was assessed using the Q statistic and I2. Subgroup analyses were performed for the presence of blinding, the prevention settings, and patients with implantable cardioverter-defibrillators, and meta-regression analyses were performed for the omega-3 dose. A statistical significance threshold of .0063 was assumed after adjustment for multiple comparisons.

Data Synthesis: 

Of the 3635 citations retrieved, 20 studies of 68 680 patients were included, reporting 7044 deaths, 3993 cardiac deaths, 1150 sudden deaths, 1837 myocardial infarctions, and 1490 strokes. No statistically significant association was observed with all-cause mortality (RR, 0.96; 95% CI, 0.91 to 1.02; risk reduction [RD] −0.004, 95% CI, −0.01 to 0.02), cardiac death (RR, 0.91; 95% CI, 0.85 to 0.98; RD, −0.01; 95% CI, −0.02 to 0.00), sudden death (RR, 0.87; 95% CI, 0.75 to 1.01; RD, −0.003; 95% CI, −0.012 to 0.006), myocardial infarction (RR, 0.89; 95% CI, 0.76 to 1.04; RD, −0.002; 95% CI, −0.007 to 0.002), and stroke (RR, 1.05; 95% CI, 0.93 to 1.18; RD, 0.001; 95% CI, −0.002 to 0.004) when all supplement studies were considered.

Conclusion: 

Overall, omega-3 PUFA supplementation was not associated with a lower risk of all-cause mortality, cardiac death, sudden death, myocardial infarction, or stroke based on relative and absolute measures of association.

JAMA. 2012;308(10):1024-1033. doi:10.1001/2012.jama.11374

Ginkgo Biloba: No-Go for Alzheimer's Prevention

Background:

Prevention strategies are urgently needed to tackle the growing burden of Alzheimer's disease. We aimed to assess efficacy of long-term use of standardised ginkgo biloba extract for the reduction of incidence of Alzheimer's disease in elderly adults with memory complaints.

Methods:

In the randomised, parallel-group, double-blind, placebo-controlled GuidAge clinical trial, we enrolled adults aged 70 years or older who spontaneously reported memory complaints to their primary-care physician in France. We randomly allocated participants in a 1:1 ratio according to a computer-generated sequence to a twice per day dose of 120 mg standardised ginkgo biloba extract (EGb761) or matched placebo. Participants and study investigators and personnel were masked to study group assignment. Participants were followed-up for 5 years by primary-care physicians and in expert memory centres. The primary outcome was conversion to probable Alzheimer's disease in participants who received at least one dose of study drug or placebo, compared by use of the log-rank test. This study is registered with ClinicalTrials.gov, number NCT00276510.

Findings:

Between March, 2002, and November, 2004, we enrolled and randomly allocated 2854 participants, of whom 1406 received at least one dose of ginkgo biloba extract and 1414 received at least one dose of placebo. By 5 years, 61 participants in the ginkgo group had been diagnosed with probable Alzheimer's disease (1·2 cases per 100 person-years) compared with 73 participants in the placebo group (1·4 cases per 100 person-years; hazard ratio [HR] 0·84, 95% CI 0·60—1·18; p=0·306), but the risk was not proportional over time. Incidence of adverse events was much the same between groups. 76 participants in the ginkgo group died compared with 82 participants in the placebo group (0·94, 0·69—1·28; p=0·68). 65 participants in the ginkgo group had a stroke compared with 60 participants in the placebo group (risk ratio 1·12, 95% CI 0·77—1·63; p=0·57). Incidence of other haemorrhagic or cardiovascular events also did not differ between groups.

Interpretation:

Long-term use of standardised ginkgo biloba extract in this trial did not reduce the risk of progression to Alzheimer's disease compared with placebo.

The Lancet Neurology, Volume 11, Issue 10, Pages 851 - 859, October 2012