Childhood Bradycardia Associates With Atrioventricular Conduction Defects in Older Age: A Longitudinal Birth Cohort Study

Background: This study explored the association between childhood bradycardia and later‐life cardiac phenotype using longitudinal data from the 1946 National Survey of Health and Development (NSHD) birth cohort. // Methods and Results: Resting heart rate was recorded at 6 and 7 years of age to provide the bradycardia exposure defined as a childhood resting heart rate <75 bpm. Three outcomes were studied: (1) echocardiographic data at 60 to 64 years of age, consisting of ejection fraction, left ventricular mass index, myocardial contraction fraction index, and E/e′; (2) electrocardiographic evidence of atrioventricular or ventricular conduction defects by 60 to 64 years of age; and (3) all‐cause and cardiovascular mortality. Generalized linear models or Cox regression models were used, and adjustment was made for relevant demographic and health‐related covariates, and for multiple testing. Mixed generalized linear models and fractional polynomials were used as sensitivity analyses. One in 3 older adults with atrioventricular conduction defects had been bradycardic in childhood, with defects being serious (Mobitz type II second‐degree atrioventricular block or higher) in 12%. In fully adjusted models, childhood bradycardia was associated with 2.91 higher odds of atrioventricular conduction defects (95% CI, 1.59–5.31; P=0.0005). Associations persisted in random coefficients mixed generalized linear models (odds ratio, 2.50; 95% CI, 1.01–4.31). Fractional polynomials confirmed a linear association between the log odds of atrioventricular conduction defects at 60 to 64 years of age and resting heart rate at 7 years of age. There was no association between bradycardia in childhood and mortality outcomes or with echocardiographic parameters and ventricular conduction defects in older age. // Conclusions: Longitudinal birth cohort data indicate that childhood bradycardia trebles the odds of having atrioventricular conduction defects in older age, 88% of which are benign. In addition, it does not influence mortality or heart size and function. Future research should concentrate on identifying children at risk

Body mass index, waist circumference, and chronic disease risk factors in australian adolescents

Objective: To determine the association between measures of adiposity (body mass index and waist circumference) and risk factors for heart disease, type 2 diabetes, fatty liver disease, and the clustering of risk factors in middle adolescence. Design: Cross-sectional study. Setting: Secondary schools in Sydney. Participants: Grade 10 students (N = 496; 58.4% boys; mean [SD] age, 15.4 [0.4] years). Main Exposures: Height, weight, waist circumference, blood pressure, and fasting blood samples. Outcome Measures: Participants were categorized as overweight or obese using the International Obesity Task Force cut points and the UK waist circumference cut points. Blood was analyzed for high- and low-density lipoprotein cholesterol, triglycerides, insulin, glucose, alanine aminotransferase, γ-glutamyltransferase, and high-sensitivity C-reactive protein levels, and the results were categorized as normal or abnormal according to published guidelines where possible. Associations between overweight and obesity and risk factors were explored using logistic regression. Clustering of risk factors within individuals was also explored. Results: Insulin (P < .001), alanine aminotransferase (P < .001), γ-glutamyltransferase (P = .005), high-density lipoprotein cholesterol (P < .001), highsensitivity C-reactive protein (P < .001), and blood pressure (P < .001) were significantly associated with overweight and obesity in adolescent boys. In adolescent girls, insulin, high-density lipoprotein cholesterol (P < .001), and high-sensitivity C-reactive protein (P < .001) were significantly associated with overweight and obesity. Obese adolescent boys and girls were significantly more likely to have 2 or more risk factors (boys: 73.5% vs 7.6%; girls: 44.4% vs 5.4%; P < .001 for both) than nonoverweight adolescents. Conclusions: Overweight and obese adolescents, especially boys, are at substantial risk for chronic conditions. Waist circumference is not a better predictor of metabolic risk factors than is body mass index. ©2008 American Medical Association. All rights reserved

The Duffin-Schaeffer Conjecture with extra divergence II

This paper takes a new step in the direction of proving the Duffin-Schaeffer Conjecture for measures arbitrarily close to Lebesgue. The main result is that under a mild `extra divergence' hypothesis, the conjecture is true.Comment: 7 page

Association between resting heart rate across the life course and all-cause mortality: longitudinal findings from the Medical Research Council (MRC) National Survey of Health and Development (NSHD)

Background: Resting heart rate (RHR) is an independent risk factor for mortality. Nevertheless, it is unclear whether elevations in childhood and mid-adulthood RHR, including changes over time, are associated with mortality later in life. We sought to evaluate the association between RHR across the life course, along with its changes and all-cause mortality. / Methods: We studied 4638 men and women from the Medical Research Council (MRC) National Survey of Health and Development (NSHD) cohort born during 1 week in 1946. RHR was obtained during childhood at ages 6, 7 and 11, and in mid-adulthood at ages 36 and 43. Using multivariable Cox regression, we calculated the HR for incident mortality according to RHR measured at each time point, along with changes in mid-adulthood RHR. / Results: At age 11, those in the top fifth of the RHR distribution (≥97 bpm) had an increased adjusted hazard of 1.42 (95% CI 1.04 to 1.93) for all-cause mortality. A higher adjusted risk (HR, 95% CI 2.17, 1.40 to 3.36) of death was also observed for those in the highest fifth (≥81 bpm) at age 43. For a >25 bpm increased change in the RHR over the course of 7 years (age 36–43), the adjusted hazard was elevated more than threefold (HR, 95% CI 3.26, 1.54 to 6.90). After adjustment, RHR at ages 6, 7 and 36 were not associated with all-cause mortality. / Conclusions: Elevated RHR during childhood and midlife, along with greater changes in mid-adulthood RHR, are associated with an increased risk of all-cause mortality

Cardiovascular Risk Factors from Early Life Predict Future Adult Cardiac Structural and Functional Abnormalities: A Systematic Review of the Published Literature

Background: Clinical practice evaluates cardiovascular risk based on current risk factor (RF) levels [Blood pressure (BP), body mass index (BMI) and glycaemic control] largely disregarding previous risk-factor history over the totality of the life course. RFs are related to contemporaneous echocardiographic measures of cardiac structure and function which in turn are independently related to cardiovascular morbidity and mortality in cross-sectional studies. However, the effect of lifetime or earlier RF history on future echocardiographic changes has never been systematically examined. Methods: A systematic review of the published literature identified 24 studies relating either earlier BP, BMI, glycaemic control or a combination to future cardiac structure and/or function. Results: The majority of studies showed that elevated BP and BMI in earlier life and greater cumulative burden of these factors resulted in worse cardiac structure up to 24 years later. Studies examining glycaemic control as a RF were few, but poorer glycaemic control in young adults was associated with increased future left ventricular mass. While only 5 papers related RFs to future cardiac function, all RFs were positively associated with worse future diastolic function. Conclusions: BP, BMI and glycaemic control measures in childhood, adolescence and early adulthood and subsequent longitudinal trajectories of BP and BMI are predictive of future abnormalities in cardiac structure and function. Lifetime RF history should be used to inform clinical practice. Further research is required to enable the identification of any sensitive periods in the life course to enable prevention when it is most likely to be effective

The relationship between pubertal timing and markers of vascular and cardiac structure and function in men and women aged 60-64 years

Earlier age at menarche has been associated with higher risk of coronary heart disease, but the mechanisms underlying the association remain unclear. We assessed the relationship of pubertal timing, in both men (n = 672) and women (n = 713), with vascular (carotid intima-media thickness (cIMT), pulse wave velocity (PWV)) and cardiac (left ventricular (LV) structure and function) measures recorded at age 60-64 yrs in a British birth cohort study. Regression models found that earlier menarche was associated with higher (more adverse) LV mass, LV end diastolic volume and left atrial volume, but not with other cardiac measures, cIMT or PWV. Associations were attenuated after adjustment for either adult or childhood BMI (e.g. mean difference in LV mass per year later menarche: -4.2 g (95% CI:-7.0,-1.4) reducing to -2.2 g (95% CI:-4.7,0.4) after adjustment for adult BMI). There were no associations among men, despite those fully mature at 15 yrs having higher blood pressure than the least mature group by 10.21 mmHg (95% CI:19.45,0.98). Any effect of pubertal timing on vascular and cardiac structure and function is likely to be small and primarily confounded by pre-pubertal BMI and/or mediated through adult adiposity

A phase I, randomized study of combined IL-2 and therapeutic immunisation with antiretroviral therapy

BACKGROUND: Fully functional HIV-1-specific CD8 and CD4 effector T-cell responses are vital to the containment of viral activity and disease progression. These responses are lacking in HIV-1-infected patients with progressive disease. We attempted to augment fully functional HIV-1-specific CD8 and CD4 effector T-cell responses in patients with advanced chronic HIV-1 infection. DESIGN: Chronically infected patients with low CD4 counts T-cell counts who commenced antiretroviral therapy (ART) were subsequently treated with combined interleukin-2 and therapeutic vaccination. METHODS: Thirty six anti-retroviral naive patients were recruited and initiated on combination ART for 17 weeks before randomization to: A) ongoing ART alone; B) ART with IL-2 twice daily for 5 days every four weeks starting at week 17 for 3 cycles; C) ART with IL-2 as in group B and Remune HIV-1 vaccine administered once every 3 months, starting at week 17; and D) ART with Remune vaccine as in group C. Patients were studied for 65 weeks following commencement of ART, with an additional prior 6 week lead-in observation period. CD4 and CD8 T-cell counts, evaluations of HIV-1 RNA levels and proliferative responses to recall and HIV-1 antigens were complemented with assessment of IL-4-secretion alongside quantification of anti-HIV-1 CD8 T-cell responses and neutralizing antibody titres. RESULTS: Neither IL-2 nor Remune™ vaccination induced sustained HIV-1-specific T-cell responses. However, we report an inverse relationship between HIV-1-specific proliferative responses and IL-4 production which continuously increased in patients receiving immunotherapy, but not patients receiving ART alone. CONCLUSION: Induction of HIV-1-specific cell-mediated responses is a major challenge in chronically HIV-1-infected patients even when combining immunisation with IL-2 therapy. An antigen-specific IL-4-associated suppressive response may play a role in attenuating HIV-specific responses

Midlife blood pressure predicts future diastolic dysfunction independently of blood pressure

OBJECTIVES: High blood pressure (BP) is associated with diastolic dysfunction, but the consequence of elevated BP over the adult life course on diastolic function is unknown. We hypothesised that high BP in earlier adulthood would be associated with impaired diastolic function independent of current BP. METHODS: Participants in the Medical Research Council National Survey of Health and Development birth cohort (n=1653) underwent investigations including echocardiography at age 60-64 years. The relationships between adult BP, antihypertensive treatment (HTT) and echocardiographic measures of diastolic function were assessed using adjusted regression models. RESULTS: Increased systolic BP (SBP) at ages 36, 43 and 53 years was predictive of increased E/e' and increased left atrial volume. These effects were only partially explained by SBP at 60-64 years and increased left ventricular mass. HTT was also associated with poorer diastolic function after adjustment for SBP at 60-64 years. Faster rates of increase in SBP in midlife were also associated with increased poorer diastolic function. CONCLUSIONS: High SBP in midlife is associated with poorer diastolic function at age 60-64 years. Early identification of individuals with high BP or rapid rises in BP may be important for prevention of impaired cardiac function in later life

Fundamental movement skills are more than run, throw and catch: The role of stability skills.

Introduction In motor development literature fundamental movement skills are divided into three constructs: locomotive, object control and stability skills. Most fundamental movement skills research has focused on children's competency in locomotor and object control skills. The first aim of this study was to validate a test battery to assess the construct of stability skills, in children aged 6 to 10 (M age = 8.2, SD = 1.2). Secondly we assessed how the stability skills construct fitted into a model of fundamental movement skill. Method The Delphi method was used to select the stability skill battery. Confirmatory factor analysis (CFA) was used to assess if the skills loaded onto the same construct and a new model of FMS was developed using structural equation modelling. Results Three postural control tasks were selected (the log roll, rock and back support) because they had good face and content validity. These skills also demonstrated good predictive validity with gymnasts scoring significantly better than children without gymnastic training and children from a high SES school performing better than those from a mid and low SES schools and the mid SES children scored better than the low SES children (all p < .05). Inter rater reliability tests were excellent for all three skills (ICC = 0.81, 0.87, 0.87) as was test retest reliability (ICC 0.87-0.95). CFA provided good construct validity, and structural equation modelling revealed stability skills to be an independent factor in an overall FMS model which included locomotor (r = .88), object control (r = .76) and stability skills (r = .81). Discussion This study provides a rationale for the inclusion of stability skills in FMS assessment. The stability skills could be used alongside other FMS assessment tools to provide a holistic assessment of children's fundamental movement skills. Copyright