Childhood Infections, Socioeconomic Status, and Adult Cardiometabolic Risk

BACKGROUND AND OBJECTIVES: Socioeconomic disadvantage throughout the life course is associated with increased risk of cardiometabolic diseases, but traditional risk factors do not fully account for the social gradient. We investigated the interactions between low socioeconomic status (SES) and infection in childhood and adverse cardiometabolic parameters in adulthood. METHODS: Participants from the Cardiovascular Risk in Young Finns Study, a cohort well phenotyped for childhood and adulthood cardiometabolic risk factors and socioeconomic parameters, were linked to lifetime hospitalization data from birth onward available from the Finnish National Hospital Registry. In those with complete data, we investigated relationships between infection-related hospitalization in childhood, SES, and childhood and adult cardiometabolic parameters. RESULTS: The study cohort consisted of 1015 participants (age range 3–18 years at baseline and 30–45 years at follow-up). In adults who were raised in below-median income families, childhood infection-related hospitalizations (at age 0–5 years) were significantly associated with higher adult BMI (β ± SE comparing those with 0 vs ≥1 hospitalizations 2.4 ± 0.8 kg/m2, P = .008), waist circumference (7.4 ± 2.3 cm, P = .004), and reduced brachial flow–mediated dilatation (−2.7 ± 0.9%, P = .002). No equivalent associations were observed in participants from higher-SES families. CONCLUSIONS: Infection was associated with worse cardiovascular risk factor profiles only in those from lower-SES families. Childhood infection may contribute to social gradients observed in adult cardiometabolic disease risk factors. These findings suggest reducing childhood infections, especially in socioeconomic disadvantaged children, may reduce the cardiometabolic disease burden in adults

A Cross-Cohort Study Examining the Associations of Metabolomic Profile and Subclinical Atherosclerosis in Children and Their Parents: The Child Health CheckPoint Study and Avon Longitudinal Study of Parents and Children

Background-High-throughput nuclear magnetic resonance profiling of circulating metabolites is suggested as an adjunct for cardiovascular risk evaluation. The relationship between metabolites and subclinical atherosclerosis remains unclear, particularly among children. Therefore, we examined the associations of metabolites with carotid intima-media thickness (cIMT) and arterial pulse wave velocity (PWV).Methods and Results-Data from two independent population-based studies was examined; (1) cross-sectional associations with cIMT and PWV in 1178 children (age 11-12 years, 51% female) and 1316 parents (mean age 45 years, 87% female) from the CheckPoint study (Australia); and (2) longitudinal associations in 4249 children (metabolites at 7-8 years, PWV at 10-11 years, 52% female), and cross-sectional associations in 4171 of their mothers (mean age 48 years, cIMT data) from ALSPAC (The Avon Longitudinal Study of Parents and Children; UK). Metabolites were measured by the same nuclear magnetic resonance platform in both studies, comprising of 69 biomarkers. Biophysical assessments included body mass index, blood pressure, cIMT and PWV. In linear regression analyses adjusted for age, sex, body mass index, and blood pressure, there was no evidence of metabolite associations in either children or adults for cIMT at a 10% false discovery threshold. In CheckPoint adults, glucose was positively, and some high-density lipoprotein-cholesterol derived measures and amino acids (glutamine, histidine, tyrosine) inversely associated with PWV.Conclusions-These data suggest that in children circulating metabolites have no consistent association with cIMT and PWV once adjusted for body mass index and blood pressure. In their middle-aged parents, some evidence of metabolite associations with PWV were identified that warrant further investigation

Bayesian hierarchical piecewise regression models: a tool to detect trajectory divergence between groups in long-term observational studies

Background: Bayesian hierarchical piecewise regression (BHPR) modeling has not been previously formulated to detect and characterise the mechanism of trajectory divergence between groups of participants that have longitudinal responses with distinct developmental phases. These models are useful when participants in a prospective cohort study are grouped according to a distal dichotomous health outcome. Indeed, a refined understanding of how deleterious risk factor profiles develop across the life-course may help inform early-life interventions. Previous techniques to determine between-group differences in risk factors at each age may result in biased estimate of the age at divergence.Methods: We demonstrate the use of Bayesian hierarchical piecewise regression (BHPR) to generate a point estimate and credible interval for the age at which trajectories diverge between groups for continuous outcome measures that exhibit non-linear within-person response profiles over time. We illustrate our approach by modeling the divergence in childhood-to-adulthood body mass index (BMI) trajectories between two groups of adults with/without type 2 diabetes mellitus (T2DM) in the Cardiovascular Risk in Young Finns Study (YFS).Results: Using the proposed BHPR approach, we estimated the BMI profiles of participants with T2DM diverged from healthy participants at age 16 years for males (95% credible interval (CI): 13.5-18 years) and 21 years for females (95% CI: 19.5-23 years). These data suggest that a critical window for weight management intervention in preventing T2DM might exist before the age when BMI growth rate is naturally expected to decrease. Simulation showed that when using pairwise comparison of least-square means from categorical mixed models, smaller sample sizes tended to conclude a later age of divergence. In contrast, the point estimate of the divergence time is not biased by sample size when using the proposed BHPR method.Conclusions: BHPR is a powerful analytic tool to model long-term non-linear longitudinal outcomes, enabling the identification of the age at which risk factor trajectories diverge between groups of participants. The method is suitable for the analysis of unbalanced longitudinal data, with only a limited number of repeated measures per participants and where the time-related outcome is typically marked by transitional changes or by distinct phases of change over time

Socioeconomic Position Is Associated With Carotid Intima-Media Thickness in Mid-Childhood: The Longitudinal Study of Australian Children

Background Lower socioeconomic position (SEP) predicts higher cardiovascular risk in adults. Few studies differentiate between neighborhood and family SEP or have repeated measures through childhood, which would inform understanding of potential mechanisms and the timing of interventions. We investigated whether neighborhood and family SEP, measured biennially from ages 0 to 1 year onward, was associated with carotid intima–media thickness (IMT) at ages 11 to 12 years.Methods and Results Data were obtained from 1477 families participating in the Child Health CheckPoint study, nested within the Longitudinal Study of Australian Children. Disadvantaged family and neighborhood SEP was cross‐sectionally associated with thicker maximum carotid IMT in separate univariable linear regression models. Associations with family SEP were not attenuated in multivariable analyses, and associations with neighborhood SEP were attenuated only in models adjusted for family SEP. The difference in maximum carotid IMT between the highest and lowest family SEP quartile measured at ages 10 to 11 years was 10.7 μm (95% CI, 3.4–18.0; P=0.004), adjusted for age, sex, pubertal status, passive smoking exposure, body mass index, blood pressure, and arterial lumen diameter. In longitudinal analyses, family SEP measured as early as age 2 to 3 years was associated with maximum carotid IMT at ages 11 to 12 years (difference between highest and lowest quartile: 8.5 μm; 95% CI, 1.3–15.8; P=0.02). No associations were observed between SEP and mean carotid IMT.Conclusions We report a robust association between lower SEP in early childhood and carotid IMT in mid‐childhood. Further investigation of mechanisms may inform pediatric cardiovascular risk assessment and prevention strategies.</ul

Socioeconomic position Is associated with carotid intima-media thickness in mid-childhood: The longitudinal study of Australian children

Background: Lower socioeconomic position (SEP) predicts higher cardiovascular risk in adults. Few studies differentiate between neighborhood and family SEP or have repeated measures through childhood, which would inform understanding of potential mechanisms and the timing of interventions. We investigated whether neighborhood and family SEP, measured biennially from ages 0 to 1 year onward, was associated with carotid intima-media thickness (IMT) at ages 11 to 12 years.Methods and Results: Data were obtained from 1477 families participating in the Child Health CheckPoint study, nested within the Longitudinal Study of Australian Children. Disadvantaged family and neighborhood SEP was cross-sectionally associated with thicker maximum carotid IMT in separate univariable linear regression models. Associations with family SEP were not attenuated in multivariable analyses, and associations with neighborhood SEP were attenuated only in models adjusted for family SEP. The difference in maximum carotid IMT between the highest and lowest family SEP quartile measured at ages 10 to 11 years was 10.7 μm (95% CI, 3.4-18.0; P=0.004), adjusted for age, sex, pubertal status, passive smoking exposure, body mass index, blood pressure, and arterial lumen diameter. In longitudinal analyses, family SEP measured as early as age 2 to 3 years was associated with maximum carotid IMT at ages 11 to 12 years (difference between highest and lowest quartile: 8.5 μm; 95% CI, 1.3-15.8; P=0.02). No associations were observed between SEP and mean carotid IMT.Conclusions: We report a robust association between lower SEP in early childhood and carotid IMT in mid-childhood. Further investigation of mechanisms may inform pediatric cardiovascular risk assessment and prevention strategies

The potential of intervening on childhood adversity to reduce socioeconomic inequities in body mass index and inflammation among Australian and UK children: A causal mediation analysis.

BACKGROUND: Lower maternal education is associated with higher body mass index (BMI) and higher chronic inflammation in offspring. Childhood adversity potentially mediates these associations. We examined the extent to which addressing childhood adversity could reduce socioeconomic inequities in these outcomes. METHODS: We analysed data from two early-life longitudinal cohorts: the Longitudinal Study of Australian Children (LSAC; n=1873) and the UK Avon Longitudinal Study of Parents and Children (ALSPAC; n=7085). EXPOSURE: low/medium (below university degree) versus high maternal education, as a key indicator of family socioeconomic position (0-1 year). OUTCOMES: BMI and log-transformed glycoprotein acetyls (GlycA) (LSAC: 11-12 years; ALSPAC: 15.5 years). Mediator: multiple adversities (≥2/<2) indicated by family violence, mental illness, substance abuse and harsh parenting (LSAC: 2-11 years; ALSPAC: 1-12 years). A causal mediation analysis was conducted. RESULTS: Low/medium maternal education was associated with up to 1.03 kg/m2 higher BMI (95% CI: 0.95 to 1.10) and up to 1.69% higher GlycA (95% CI: 1.68 to 1.71) compared with high maternal education, adjusting for confounders. Causal mediation analysis estimated that decreasing the levels of multiple adversities in children with low/medium maternal education to be like their high maternal education peers could reduce BMI inequalities by up to 1.8% and up to 3.3% in GlycA. CONCLUSIONS: Our findings in both cohorts suggest that slight reductions in socioeconomic inequities in children's BMI and inflammation could be achieved by addressing childhood adversities. Public health and social policy efforts should help those affected by childhood adversity, but also consider underlying socioeconomic conditions that drive health inequities

Household Tobacco Smoke and Admission Weight Predict Severe Bronchiolitis in Infants Independent of Deprivation: Prospective Cohort Study

To examine demographic, environmental and clinical factors associated with severe bronchiolitis in infants admitted to hospital and quantify the independent effects of these factors

Exposure to parental smoking and cardiac structure and function in adulthood: the Cardiovascular Risk in Young Finns Study

Background and aims: The relationship between childhood tobacco smoke exposure and cardiac structure and function in midlife is unclear. We investigated the association between parental smoking with cardiac structure and function in adulthood.Methods: 1250 participants (56.5% female) from the Cardiovascular Risk in Young Finns Study who had data on parental smoking and/or serum cotinine, a biomarker of exposure to tobacco smoke, at baseline 1980 (age 3-18 years) and echocardiography performed in 2011. Parental smoking hygiene (i.e., smoking in the vicinity of children) was categorized by parental smoking and serum cotinine levels in offspring. Dimensions of the left ventricle, diastolic and systolic function, and cardiac remodeling were used as outcomes. Analyses were adjusted for sex, age, and covariates (blood pressure (BP), serum lipids, body mass index, socioeconomic status, smoking (only in adulthood)) in childhood and adulthood.Results: Parental smoking was not associated with systolic or diastolic function in adulthood. Participants exposed to parental smoking (odds ratio (OR) 1.90, 95%CI 1.23-2.92), hygienic parental smoking (OR 1.74, 95%CI 1.12-2.71), and non-hygienic parental smoking (OR 1.88, 95%CI 1.02-3.45) had higher odds of concentric remodeling (relative wall thickness >85th sex-specific percentile without left ventricular hypertrophy). These associations were attenuated after adjustment for child and adult covariates in the non-hygienic parental smoking group.Conclusions: Exposure to parental smoking in childhood was associated with a higher likelihood of concentric remodeling and thicker left ventricular and interventricular septal walls in midlife, which was not improved by parents who smoked hygienically. Parental smoking was not related to systolic or diastolic function in this relatively young population.</p