Search

Purpose: Recent evidence suggests that plant-based diets may reduce the risk of breast cancer (BC). However, the macronutrient composition of plant-based diets and its potential impact on BC risk has not been well explored. This analysis investigated the association of macronutrient composition with BC risk across a spectrum of plant-based diet indexes using a multidimensional approach., Design: This study followed 64,655 participants from the Etude Epidémiologique auprès de femmes de la Mutuelle Générale de l'Education Nationale (E3N) cohort from 1993 to 2014. Diets were evaluated using validated 208-item diet history questionnaires at baseline (1993) and follow-up (2005), to calculate adherence to the overall plant-based diet (PDI), healthful plant-based diet (hPDI), and unhealthful plant-based diet (uPDI). The association of macronutrient composition with BC risk was assessed via generalized additive time-dependent Cox models across different levels of these indexes. Response surfaces were generated to visualize compositional associations at the 25th, 50th, and 75th percentile of each index (low, moderate, and high)., Results: A total of 3,932 incident BC cases were identified during the 21-year follow-up. There was a significant association between macronutrient composition and BC risk for hPDI, uPDI, and PDI (all P < 0.001). Akaike information criterion favored the hPDI model for characterizing the association between macronutrients and BC. BC risk was highest for individuals with a lower hPDI score who also consumed a diet containing lower protein (10%), lower carbohydrate (35%), and higher fat (55%). The lowest risk of BC was observed in those with higher hPDI scores with the lowest intake of protein (10%). At higher PDI and uPDI, diets containing higher protein (30%) and fat (45%) had the highest BC risk., Conclusion: These results demonstrate a complex relationship between macronutrient composition, plant-based diet quality, and BC risk. Further research is needed to examine specific foods that may be driving these associations., Registry: The protocol is registered at clinicaltrials.gov as NCT03285230., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

The role of dietary macronutrients and energy intake in the aging process has been well-established. However, previous research has mainly focused on the association between leukocyte telomere length (LTL) and individual macronutrients, while the effects of macronutrient composition on LTL remain unclear. This cross-sectional analysis involved 4130 US adults (44.8 ± 17.0 years; 51% female) from the National Health and Nutrition Examination Survey during 1999-2002. A single 24-h dietary recall is used to collect dietary data. The relationship between dietary macronutrient composition and LTL is examined using three-dimensional generalized additive models. After adjustment for age, sex, ethnicity, education, physical activity, BMI, and dietary quality, a three-dimensional association of macronutrient composition with LTL (P = 0.02) is revealed. Diets lower in protein (5-10%), higher in carbohydrates (75%), and lower in fat (15-20%) are associated with the longest LTL corresponding to 7.7 years of slower biological aging. Diets lowest in protein (5%) and carbohydrate (40%), while highest in dietary fat (55%) are associated with the shortest LTL, corresponding to accelerated biological aging of 4.4 years. The associations appeared magnified with higher energy intake. These findings support a complex relationship between dietary macronutrients and biological aging independent of diet quality., (© 2024 The Authors. Advanced Biology published by Wiley‐VCH GmbH.)

Blood pressure (BP) rises rapidly at puberty. While this is partly due to normal development, factors like excess adiposity and a high intake of dietary sodium relative to potassium may contribute to a true increase in hypertension risk. This study aimed to assess the relative impact of growth, gonadal hormones, adiposity and the sodium-to-potassium ratio (Na:K) on longitudinal BP measures at puberty. This study analysed data from a three-year longitudinal cohort study of pubertal adolescents. Anthropometry, body composition (bio-electrical impedance), serum testosterone and oestradiol (mass spectrometry) were measured annually. Na:K was measured from three-monthly urine samples. These variables were used to predict annual BP measures using mixed modelling and ordinal regression. Data from 325 adolescents (11.7 ± 1.0 y; 55% male) were analysed, showing typical growth patterns at puberty. Systolic BP increased over time in both sexes (p < 0.01), with boys exhibiting a significantly steeper rise compared to girls. Adiposity variables (BMI z-score, percent body fat, fat mass, waist-to-height ratio) strongly and consistently predicted systolic and diastolic BP in both sexes (all p < 0.05). Systolic BP was also significantly and positively related to height (p < 0.05). No associations with BP were identified in either sex for gonadal hormones or Na:K. Similar results were obtained when BP was classified into hypertension categories. Relative to other developmental and diet-related variables tested, adiposity was found to be the strongest most consistent predictor of BP in pubertal adolescents. Findings highlight the importance of dedicated youth obesity management interventions and policy measures for reducing long-term hypertension and cardiovascular disease risks.Australian New Zealand Clinical Trials Registry ACTRN12617000964314., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

The gut microbiome has been shown to play a role in the relationship between diet and cardiometabolic health. We sought to examine the degree to which key microbial lignan metabolites are involved in the relationship between diet quality and cardiometabolic health using a multidimensional framework. This analysis was undertaken using cross-sectional data from 4685 US adults (age 43.6 ± 16.5 years; 50.4% female) participating in the National Health and Nutrition Examination Survey for 1999-2010. Dietary data were collected from one to two separate 24-hour dietary recalls and diet quality was characterized using the 2015 Healthy Eating Index. Cardiometabolic health markers included blood lipid profile, glycemic control, adiposity, and blood pressure. Microbial lignan metabolites considered were urinary concentrations of enterolignans, including enterolactone and enterodiol, with higher levels indicating a healthier gut microbial environment. Models were visually examined using a multidimensional approach and statistically analyzed using three-dimensional generalized additive models. There was a significant interactive association between diet quality and microbial lignan metabolites for triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, insulin, oral glucose tolerance, adiposity, systolic blood pressure, and diastolic blood pressure (all p < 0.05). Each of these cardiometabolic health markers displayed an association such that optimal cardiometabolic health was only observed in individuals with both high diet quality and elevated urinary enterolignans. When comparing effect sizes on the multidimensional response surfaces and model selection criteria, the strongest support for a potential moderating relationship of the gut microbiome was observed for fasting triglycerides and oral glucose tolerance. In this study, we revealed interactive associations of diet quality and microbial lignan metabolites with cardiometabolic health markers. These findings suggest that the overall association of diet quality on cardiometabolic health may be affected by the gut microbiome.

Macronutrients are a major component of the human diet. However, few studies have assessed their collective association with mortality. We sought to evaluate the associations of macronutrient intake with all-cause, cardiovascular, and cancer mortality in US adults using a multi-nutrient approach. This prospective cohort analysis used data from the National Health and Nutrition Examination Survey from the years 1999 to 2014. The participants included 33,681 US adults aged 20−85 years (52.5% female). The maximum follow-up time was 16.8 years, with a total of 4398 total deaths, including 772 cardiovascular deaths and 952 cancer deaths. The associations between mortality and dietary macronutrients were explored using three-dimensional generalized additive models, allowing for visual and statistical inference of complex nonlinear associations. Absolute macronutrient intake demonstrated a three-way interactive association with all-cause mortality (p < 0.001), cardiovascular mortality (p = 0.02), and cancer mortality (p = 0.05), adjusted for age, sex, ethnicity, socioeconomic status, dietary quality, and lifestyle. Compositionally, a high caloric diet composed of moderately high protein (20%), moderate fat (30%), and moderate carbohydrate (50%) levels was associated with the highest mortality risk. Across the total energy intake levels, lower mortality risk was observed in two separate regions consisting of higher protein (30%), higher carbohydrate (60%), and lower fat levels (10%) or lower protein (10%), moderate carbohydrate (45%), and higher fat levels (45%). These findings highlight a complex nonlinear and interactive association between macronutrients and all-cause mortality such that several distinct dietary compositions are associated with similarly high or low risk. Future research is needed to explore the drivers of these associations and whether they differ across varying dietary patterns and populations.

Objective: To investigate the association between early life exposures during the first 1000 days (conception to age 24 months) and aortic intima-media thickness (aIMT), an early indicator of cardiovascular disease (CVD) risk, in youths., Study Design: The MEDLINE, Embase, Scopus, CINAHL, and Allied and Complementary Medicine databases were searched from inception to July 2021. Eligibility criteria included observational controlled studies in youths aged <20 years with risk factors/exposures during the first 1000 days and aIMT measurements (unadjusted mean ± SD). Outcome data were pooled using a random-effects meta-analysis. Meta-regression was used to investigate confounders., Results: A total of 8657 articles were identified, of which 34 were included in our meta-analysis. The age of participants ranged from 22.9 weeks gestation in utero to 10.9 years. In the meta-analysis (n = 1220 cases, n = 1997 controls), the following factors were associated with greater aIMT: small for gestational age (SGA) status (14 studies, mean difference, 0.082 mm; 95% CI, 0.051-0.112; P < .001; I 2  = 97%), intrauterine growth restriction (6 studies; mean difference, 0.198 mm, 95% CI, 0.088-0.309; P < .001; I 2  = 97%), preeclampsia (2 studies; mean difference, 0.038 mm; 95% CI, 0.024-0.051; P < .001; I 2  = 38%), and large for gestational age (LGA) status (3 studies; mean difference, 0.089 mm; 95% CI, 0.043-0.0136; P < .001; I 2  = 93%). In meta-regression, older age (P < .001), higher prevalence of maternal smoking (P = .04), and SGA (P < .001) were associated with greater difference in aIMT in preterm participants compared with controls. Limitations included the high heterogeneity present in most meta-analyses and the scope of our meta-regression., Conclusions: Adverse early life exposures are associated with greater aIMT in youths, consistent with an increased risk for CVD later in life. Further research is needed to determine whether intervention and preventive strategies deliver clinical benefits to improve future cardiovascular health., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Dietary and nutritional biomarkers are objective dietary assessment tools that will enable a more accurate and precise determination of diet-disease relations. However, the lack of established biomarker panels for dietary patterns is concerning, as dietary patterns continue to be the focus of dietary guidelines., Objectives: We aimed to develop and validate a panel of objective biomarkers that reflects the Healthy Eating Index (HEI) by applying machine learning approaches to the National Health and Nutrition Examination Survey data., Methods: Cross-sectional population-based data (eligible criteria: age ≥20 y, not pregnant, no reported supplement use of dedicated vitamin A, D, E, or fish oils; n = 3481) from the 2003 to 2004 cycle of the NHANES were used to develop 2 multibiomarker panels of the HEI, 1 with (primary panel) and 1 without (secondary panel) plasma FAs. Up to 46 blood-based dietary and nutritional biomarkers (24 FAs, 11 carotenoids, and 11 vitamins) were included for variable selection using the least absolute shrinkage and selection operator controlling for age, sex, ethnicity, and education. The explanatory impact of selected biomarker panels was assessed by comparing the regression models with and without the selected biomarkers. In addition, 5 comparative machine learning models were constructed to validate the biomarker selection., Results: The primary multibiomarker panel (8 FAs, 5 carotenoids, and 5 vitamins) significantly improved the explained variability of the HEI (adjusted R 2 increased from 0.056 to 0.245). The secondary multibiomarker panel (8 vitamins and 10 carotenoids) had lesser predictive capabilities (adjusted R 2 increased from 0.048 to 0.189)., Conclusions: Two multibiomarker panels were developed and validated to reflect a healthy dietary pattern consistent with the HEI. Future research should seek to test these multibiomarker panels in randomly assigned trials and identify whether they have broad application in healthy dietary pattern assessment., (Copyright © 2022 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Preeclampsia is a serious multisystem blood pressure disorder during pregnancy that is associated with increased long-term risk of cardiovascular disease to the mother and offspring. We investigated the vascular health of children exposed to intrauterine preeclampsia., Materials and Methods: This was a cross-sectional study of offspring in a prospective cohort of women with complications during pregnancy. Children aged between 2 and 5 years [median age 4.7 (2.8, 5.1) years] exposed to intrauterine preeclampsia ( n = 26) or normotensive controls ( n = 34), were recruited between July 2020 and April 2021. Vascular health was assessed by measuring aortic intima-media thickness and pulse wave velocity. Univariate generalized linear regression models were used to explore associations between vascular measurements and explanatory variables., Results: Children exposed to preeclampsia had a lower body mass index at assessment (15.5 vs. 16.2 kg/m 2 , p = 0.04), birth weight (2.90 vs. 3.34 kg, p = 0.004), gestational age at birth (37.5 vs. 39.4 weeks, p < 0.001) and higher frequency of preterm birth (27% vs. 6%, p = 0.02). There were no differences in vascular health between children exposed to preeclampsia vs. controls (mean aortic intima-media thickness 0.575 mm vs. 0.563 mm, p = 0.51, pulse wave velocity 4.09 vs. 4.18 m/s, p = 0.54) and there were no significant associations in univariate analyses., Conclusions: There were no major adverse differences in vascular health which contrasts with existing studies. This suggests exposure to intrauterine preeclampsia may result in a less severe cardiovascular phenotype in young children. While reassuring, longitudinal studies are required to determine if and when exposure to intrauterine preeclampsia affects vascular health in children., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Varley, Henry, Roberts, Davis, Skilton, Craig and Gow.)

Context: Most methods for assessing dietary intake have considerable measurement error. Dietary biomarkers are objective tools for dietary assessment. Dietary biomarkers of dietary patterns have not been well described, despite modern dietary guidelines endorsing dietary patterns., Objective: This systematic review sought to describe the dietary biomarkers commonly used to assess dietary patterns, and the novel biomarkers of dietary patterns identified by exploratory studies., Data Sources: MEDLINE, Embase, Cochrane Central, PreMEDLINE, and CINAHL databases were searched., Data Extraction: Data extraction and bias assessment were undertaken in duplicate., Data Analysis: A qualitative approach was applied, without statistical analysis., Conclusion: In controlled settings, dietary biomarkers of single nutrients or of individual foods or food groups are commonly used to assess compliance with dietary patterns. However, currently, there are no dietary biomarkers or biomarker profiles that are able to identify the specific dietary pattern that has been consumed by an individual. Future work should seek to validate novel dietary biomarkers and biomarker profiles that are indicative of specific dietary patterns and their characteristics. A dietary biomarker panel consisting of multiple biomarkers is almost certainly necessary to capture the complexity of dietary patterns., Systematic Review Registration: PROSPERO registration no. CRD42019129839., (© The Author(s) 2022. Published by Oxford University Press on behalf of the International Life Sciences Institute.)

Aims: Greater aortic intima media thickness (aIMT), a marker of subclinical atherosclerosis, can identify individuals at risk of CVD. This systematic review with meta-analysis compared aIMT in youth with type 1 diabetes and healthy controls., Methods: A systematic search of published literature (to July 2021) was undertaken using electronic databases MEDLINE, EMBASE, Scopus, CINAHL and AMED. Eligible studies reported aIMT in participants aged <20 years with type 1 diabetes and healthy controls. Meta-analysis was used to combine outcome data, presented as forest plots. Moderator analysis and metaregression were conducted to identify study and participant characteristics associated with aIMT. Publication bias was assessed by funnel plot inspection., Results: Meta-analysis of nine studies (n = 1030 with type 1 diabetes and n = 498 healthy control participants) indicated, with high heterogeneity (I 2 98%), that youth with type 1 diabetes have higher aIMT compared with healthy controls (mean difference [95% CIs]: 0.11 [0.04, 0.18] mm, P = 0.003). Factors associated with greater aIMT in type 1 diabetes compared to controls included: use of a phased array probe versus linear array probe; longer diabetes duration; higher insulin dose; higher BMI z score and waist circumference; higher LDL cholesterol; higher triglycerides; and higher diastolic blood pressure., Conclusions: Type 1 diabetes in youth is associated with higher aIMT compared with healthy control individuals. Longer duration of diabetes and major CVD risk factors were also associated with higher aIMT. Together, these findings provide a strong rationale for targeting modifiable risk factors in CVD prevention. Registered in PROSPERO on 8 August 2019 (CRD42019137559)., (© 2022 The Authors. Pediatric Diabetes published by John Wiley & Sons Ltd.)

Purpose of Review: Early life presents a pivotal period during which nutritional exposures are more likely to cause epigenetic modifications, which may impact an individual's health during adulthood. This article reviews the current evidence regarding maternal and early childhood nutritional exposures and their role in epigenetic aging., Recent Findings: Maternal and early life consumption of diets higher in fiber, antioxidants, polyphenols, B vitamins, vitamin D, and ω-3 fatty acids is associated with slower epigenetic aging. Conversely, diets higher in glycemic load, fat, saturated fat, and ω-6 fatty acids demonstrate a positive association with epigenetic aging. Maternal and early life nutrition directly and indirectly influences epigenetic aging via changes in one-carbon metabolism, cardiometabolic health, and the microbiome. Clinical trials are warranted to determine the specific foods, dietary patterns, and dietary supplements that will normalize or lower epigenetic aging across the life course., (© 2022. The Author(s).)

Background: Genomic technologies can be subject to significant batch-effects which are known to reduce experimental power and to potentially create false positive results. The Illumina Infinium Methylation BeadChip is a popular technology choice for epigenome-wide association studies (EWAS), but presently, little is known about the nature of batch-effects on these designs. Given the subtlety of biological phenotypes in many EWAS, control for batch-effects should be a consideration., Results: Using the batch-effect removal approaches in the ComBat and Harman software, we examined two in-house datasets and compared results with three large publicly available datasets, (1214 HumanMethylation450 and 1094 MethylationEPIC BeadChips in total), and find that despite various forms of preprocessing, some batch-effects persist. This residual batch-effect is associated with the day of processing, the individual glass slide and the position of the array on the slide. Consistently across all datasets, 4649 probes required high amounts of correction. To understand the impact of this set to EWAS studies, we explored the literature and found three instances where persistently batch-effect prone probes have been reported in abstracts as key sites of differential methylation. As well as batch-effect susceptible probes, we also discover a set of probes which are erroneously corrected. We provide batch-effect workflows for Infinium Methylation data and provide reference matrices of batch-effect prone and erroneously corrected features across the five datasets spanning regionally diverse populations and three commonly collected biosamples (blood, buccal and saliva)., Conclusions: Batch-effects are ever present, even in high-quality data, and a strategy to deal with them should be part of experimental design, particularly for EWAS. Batch-effect removal tools are useful to reduce technical variance in Infinium Methylation data, but they need to be applied with care and make use of post hoc diagnostic measures., (© 2022. The Author(s).)

Adults who were born preterm are at increased risk of hypertension and cardiovascular disease in later life. Infants born late preterm are the majority of preterm births; however, the effect of late preterm on risk of cardiovascular disease is unclear. The objective of this study was to assess whether vascular health and cardiac autonomic control differ in a group of late preterm newborn infants compared to a group of term-born infants.A total of 35 healthy late preterm newborn infants, with normal growth (34-36 completed weeks' gestation) and 139 term-born infants (37-42 weeks' gestation) were compared in this study. Aortic wall thickening, assessed as aortic intima-media thickness (IMT) by high-resolution ultrasound, and cardiac autonomic control, assessed by heart rate variability, were measured during the first week of life. Postnatal age of full-term and late preterm infants at the time of the study was 5 days (standard deviation [SD] 5) and 4 days (SD 3), respectively.Infants born late preterm show reduced aortic IMT (574 μm [SD 51] vs. 612 μm [SD 73]) and reduced heart rate variability [log total power 622.3 (606.5) ms2 vs. 1180. 6 (1114.3) ms2], compared to term infants. These associations remained even after adjustment for sex and birth weight.Infants born late preterm show selective differences in markers of cardiovascular risk, with potentially beneficial differences in aortic wall thickness in contrast to potentially detrimental differences in autonomic control, when compared with term-born control infants. These findings provide pathophysiologic evidence to support an increased risk of hypertension and sudden cardiac death in individuals born late preterm.

Background: Maternal nutrition is associated with epigenetic and cardiometabolic risk factors in offspring. Research in humans has primarily focused on assessing the impact of individual nutrients., Objectives: We sought to assess the collective impact of maternal dietary MUFAs, PUFAs, and SFAs on epigenetic aging and cardiometabolic risk markers in healthy newborn infants using a geometric framework approach., Methods: Body fatness (n = 162), aortic intima-media thickness (aIMT; n = 131), heart rate variability (n = 118), and epigenetic age acceleration (n = 124) were assessed in newborn infants. Maternal dietary intake was cross-sectionally assessed in the immediate postpartum period via a validated 80-item self-administered FFQ. Generalized additive models were used to explore interactive associations of nutrient intake, with results visualized as response surfaces., Results: After adjustment for total energy intake, maternal age, gestational age, and sex there was a 3-way interactive association of MUFAs, PUFAs, and SFAs (P = 0.001) with newborn epigenetic aging. This suggests that the nature of each fat class association depends upon one another. Response surfaces revealed MUFAs were positively associated with newborn epigenetic age acceleration only at proportionately lower intakes of SFAs or PUFAs. We also demonstrate a potential beneficial association of omega-3 (n-3) PUFAs with newborn epigenetic age acceleration (P = 0.008). There was no significant association of fat class with newborn aIMT, heart rate variability, or body fatness., Conclusions: In this study, we demonstrated an association between maternal dietary fat class composition and epigenetic aging in newborns. Future research should consider other characteristics such as the source of maternal dietary fatty acids., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Dietary saturated fat raises total cholesterol and LDL cholesterol levels. It is unclear whether these effects differ by the fatty acid chain lengths of saturated fats; particularly, it is unclear whether medium-chain fatty acids increase lipid levels., Objectives: We conducted a systematic review to determine the effects of medium-chain triglyceride (MCT) oil, consisting almost exclusively of medium-chain fatty acids (6:0-10:0), on blood lipids., Methods: We searched Medline and Embase through March 2020 for randomized trials with a minimum 2-week intervention period that compared MCT oil with another fat or oil. Outcomes were total cholesterol, LDL cholesterol, HDL cholesterol, and triglyceride levels. Included studies were restricted to adults above 18 years of age. Studies conducted in populations receiving enteral or parenteral nutrition were excluded. Data were pooled using a random-effects meta-analysis., Results: Seven articles were included in the meta-analysis; LDL cholesterol and HDL cholesterol were reported in 6 studies. MCT oil intake did not affect total cholesterol (0.04 mmol/L; 95% CI, -0.11 to 0.20; I2 = 33.6%), LDL cholesterol (0.02 mmol/L; 95% CI, -0.13 to 0.17; I2 = 28.7%), or HDL cholesterol (-0.01 mmol/L; 95% CI, -0.10 to 0.09; I2 = 74.1%) levels, but did increase triglycerides (0.14 mmol/L; 95% CI, 0.01-0.27; I2 = 42.8%). Subgroup analyses showed that the effects of MCT oil on total cholesterol and LDL cholesterol differed based on the fatty acid profile of the control oil (Pinteraction = 0.003 and 0.008, respectively), with MCT oil increasing total cholesterol and LDL cholesterol when compared to a comparator consisting predominantly of unsaturated fatty acids, and with some evidence for reductions when compared to longer-chain SFAs., Conclusions: MCT oil does not affect total cholesterol, LDL cholesterol, or HDL cholesterol levels, but does cause a small increase in triglycerides., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Food production greatly contributes to greenhouse gas emissions (GHG), but there remain concerns that consuming environmentally sustainable foods can increase the likelihood of nutritional deficiencies during pregnancy. We identified commonly consumed foods of pregnant women and determined the effect of their replacement with environmentally sustainable alternatives on nutrient intake and measures of environmental sustainability. Dietary intake data from 171 pregnant women was assessed and foods that contributed the most to energy and protein intake were identified. Of these, foods producing the highest GHG emissions were matched with proposed environmentally sustainable alternatives, and their impact on nutrient provision determined. Meats, grains, and dairy products were identified as important sources of energy and protein. With the highest GHG emissions, beef was selected as the reference food. Proposed alternatives included chicken, eggs, fish, tofu, legumes, and nuts. The most pronounced reductions in CO 2 emissions were from replacing beef with tofu, legumes, and nuts. Replacing one serve per week of beef with an isocaloric serve of firm tofu during pregnancy could reduce GHG emissions by 372 kg CO 2 eq and increase folate (+28.1 µg/serve) and fiber (+3.3 g/serve) intake without compromising iron (+1.1 mg/serve) intake. Small dietary substitutions with environmentally sustainable alternatives can substantially reduce environmental impact without compromising nutrient adequacy.

Evidence from animal models indicates that maternal diet during pregnancy affects offspring cardiometabolic health. Improving carbohydrate quality during high-risk pregnancies reduces aortic intima-medial thickness; a marker for early atherosclerosis; in the infant offspring. We sought to determine whether maternal carbohydrate quantity and quality are associated with newborn aortic intima-medial thickness in healthy pregnancies. Maternal diet throughout pregnancy was evaluated in 139 mother-child dyads using a validated food frequency questionnaire. Carbohydrate intake was expressed as quantity (% total energy), quality (fibre, glycaemic index), and glycaemic burden (glycaemic load). Aortic intima-medial thickness was measured by high-frequency ultrasound of the neonatal abdominal aorta. Neither quantity nor quality of maternal carbohydrate intake during pregnancy was associated with meaningful differences in offspring maximum aortic intima-medial thickness with the exception of fibre intake in women with overweight or obesity which was inversely associated (-8 μm [95% CI -14, -1] per g fibre, p = 0.04). In healthy pregnancy, the quantity and quality of maternal carbohydrate intake is likely not a meaningful modifiable lifestyle factor for influencing offspring vascular health. The effect of carbohydrate quality may only be evident in high-risk pregnancies, consistent with previous findings. These findings may be confirmed in prospective dietary trials in pregnancy.

Background: In adults, central systolic blood pressure (cSBP) and augmentation index (cAIx) are independently associated with cardiovascular events and mortality. There is increasing interest in central hemodynamic indices in children. We aimed to assess the accuracy of current techniques against invasive intra-aortic measurements in children., Methods: Intra-aortic pressure waveforms were recorded with simultaneous brachial, radial, and carotid waveforms in 29 children (6.7 ± 3.9 years old) undergoing cardiac catheterization. Adult and age-appropriate transfer functions (TFs) (brachial adult: b-aTF; radial adult: r-aTF; radial for 8-year-old children: TF8; and radial for 14-year-old children: TF14) were used to synthesize central aortic waveforms from peripheral waveforms calibrated either to invasively or noninvasively recorded BP. Central hemodynamic indices were measured by pulse wave analysis., Results: cSBP measured from invasively calibrated r-aTF (β = 0.84; intraclass correlation coefficient = 0.91; mean error ± SDD = -1.0 ± 5.0 mm Hg), TF8 (β = 0.78; intraclass correlation coefficient = 0.84; mean error ± SDD = 4.4 ± 5.6 mm Hg), and TF14 (β = 0.82; intraclass correlation coefficient = 0.90; mean error ± SDD = 2.0 ± 4.7 mm Hg)-synthesized central waveforms correlated with and accurately estimated intra-aortic cSBP measurements, while noninvasively calibrated waveforms did not. cAIx derived from TF-synthesized central waveforms did not correlate with intra-aortic cAIx values, and degree of error was TF-dependent., Conclusions: The currently available r-aTF accurately estimates cSBP with invasive pulse pressure calibration, while. Age-appropriate TFs do not appear to provide additional benefit. Accuracy of cAIx estimation appears to be TF dependent., (© American Journal of Hypertension, Ltd 2020. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Associations between kidney disease and periodontal disease are not well documented among Aboriginal people of Australia. The purpose of this investigation was to report and compare demographic, oral health, anthropometric and systemic health status of Aboriginal Australians with kidney disease and to compare against relevant Aboriginal Australians and Australian population estimates. This provides much needed evidence to inform dental health service provision policies for Aboriginal Australians with kidney disease., Methods: Sample frequencies and means were assessed in adults represented in six datasets including: (1) 102 Aboriginal Australians with kidney disease residing in Central Australia who participated in a detailed oral health assessment; (2) 312 Aboriginal participants of the Northern Territory's PerioCardio study; (3) weighted estimates from 4775 participants from Australia's National Survey of Adult Oral Health (NSAOH); (4) Australian 2016 Census (all Australians); (5) National Health Survey 2017-2018 (all Australians) and; (6) Australian Health Survey: Biomedical Results for Chronic Diseases, 2011-2012 (all Australians). Oral health status was described by periodontal disease and experience of dental caries (tooth decay). Statistically significant differences were determined via non-overlapping 95% confidence intervals., Results: Aboriginal Australians with kidney disease were significantly older, less likely to have a tertiary qualification or be employed compared with both PerioCardio study counterparts and NSAOH participants. Severe periodontitis was found in 54.3% of Aboriginal Australians with kidney disease, almost 20 times the 2.8% reported in NSAOH. A higher proportion of Aboriginal Australians with kidney disease had teeth with untreated caries and fewer dental restorations when compared to NSAOH participants. The extent of periodontal attachment loss and periodontal pocketing among Aboriginal Australians with kidney disease (51.0%, 21.4% respectively) was several magnitudes greater than PerioCardio study (22.0%, 12.3% respectively) and NSAOH (5.4%, 1.3% respectively) estimates., Conclusions: Aboriginal Australians with kidney disease exhibited more indicators of poorer oral health than both the general Australian population and a general Aboriginal population from Australia's Northern Territory. It is imperative that management of oral health among Aboriginal Australians with kidney disease be included as part of their ongoing medical care.

Objective: Periodontal disease is associated with chronic kidney disease (CKD), with both conditions being highly prevalent among Australia's Aboriginal population. This paper reflects on the lessons learned following implementation of a periodontal intervention in the Central Australian region of the Northern Territory among Aboriginal adults with CKD., Results: Between Oct 2016 and May 2019, research staff recruited 102 eligible participants. This was far below the anticipated recruitment rate. The challenges faced, and lessons learned, were conceptualised into five specific domains. These included: (1) insufficient engagement with the Aboriginal community and Aboriginal community-controlled organisations; (2) an under-appreciation of the existing and competing patient commitments with respect to general health and wellbeing, and medical treatment to enable all study commitments; (3) most study staff employed from outside the region; (4) potential participants not having the required number of teeth; (5) invasive intervention that involved travel to, and time at, a dental clinic. A more feasible research model, which addresses the divergent needs of participants, communities and service partners is required. This type of approach, with sufficient time and resourcing to ensure ongoing engagement, partnership and collaboration in co-design throughout the conduct of research, challenges current models of competitive, national research funding.

Carotid-femoral pulse wave velocity is associated with arterial stiffness in major elastic arteries, and predicts future cardiovascular events. However, little is known about carotid-femoral pulse wave velocity as a marker of vascular health in children. Semi-automated cuff-based devices for assessing pulse wave velocity are increasingly popular, although these utilize an algorithm developed and validated in adults. Physiological differences between adults and children may, however, reduce the accuracy of cuff-based methods. We sought to determine the accuracy of a cuff-based pulse wave velocity device in healthy children, and determine whether a novel age-appropriate algorithm increases accuracy. We recruited 29 healthy children between the ages of 2 and 20 years. Pulse wave velocity was measured both by using a tonometer on the carotid artery and an inflated cuff on the thigh, and using a tonometer on both the carotid artery and femoral artery as a reference standard. Accuracy of the cuff-based device with its standard algorithm developed in adults, and a novel age-appropriate algorithm corrected for physiological differences in leg pulse wave velocity was assessed with Regression analysis and Bland-Altman plots. Cuff-based device estimates of pulse wave velocity had excellent agreement to the reference standard (Δ = -0.26 ms -1 [SD 0.44]). The novel age-appropriate algorithm improved the accuracy of the cuff-based method (Δ = 0.02 ms -1 [SD 0.44]). The cuff-based semi-automatic approach estimates carotid-femoral pulse wave velocity with excellent agreement to the reference standard. However, adjusting the algorithm for known differences in leg pulse wave velocity further improves the accuracy of cuff-based measurement in children and adolescents.

Background: Epigenetic aging is associated with higher risk of cardiovascular disease, cancer, and all-cause mortality and may be a mechanistic link between early-life exposures, such as maternal dietary characteristics during pregnancy, and risk of adult disease., Objectives: We sought to determine the early-life risk factors for newborn epigenetic aging, specifically maternal dietary macronutrient intake, and whether epigenetic aging is associated with cardiovascular health markers in the newborn., Methods: Epigenetic age acceleration of 169 newborns was measured from saliva using the Horvath age calculator. Maternal diet during pregnancy was assessed using food-frequency questionnaires., Results: Newborns with positive age acceleration were more likely to be female and have greater body fatness. Maternal intakes of saturated fat [6.2 wk epigenetic age acceleration (95% CI: 1.0, 11.3) per 5% of energy; P = 0.02] and monounsaturated fat [12.4 wk (95% CI: 4.2, 20.5) per 5% of energy; P = 0.003] were associated with higher epigenetic age acceleration in the newborn. The strongest association of individual fatty acids were for palmitoleic acid (25.3 wk; 95% CI: 11.4, 39.2; P = 0.0004), oleic acid (2.2 wk; 95% CI: 0.8, 3.6; P = 0.002), and palmitic acid (2.9 wk; 95% CI: 1.0, 4.9; P = 0.004) per 1% of energy intake. Vitamin D supplementation was associated with lower epigenetic age acceleration (-8.1 wk; 95% CI: -14.5, -1.7; P = 0.01). Epigenetic age acceleration was associated with aortic intima-media thickness in preterm infants [1.0 µm (95% CI: 0.2, 1.8) per week of epigenetic age acceleration; P = 0.01], but not among those born at term (P = 0.78). Epigenetic age acceleration was not associated with heart rate variability in either preterm or term born infants (both P > 0.2)., Conclusions: This study provides evidence of maternal dietary characteristics that are associated with epigenetic aging in the offspring. Prospective intervention studies are required to determine whether such associations are causal., (Copyright © The Author(s) 2020.)

Aims: Averaged measurements, but not the progression based on multiple assessments of carotid intima-media thickness, (cIMT) are predictive of cardiovascular disease (CVD) events in individuals. Whether this is true for conventional risk factors is unclear., Methods and Results: An individual participant meta-analysis was used to associate the annualised progression of systolic blood pressure, total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol with future cardiovascular disease risk in 13 prospective cohort studies of the PROG-IMT collaboration ( n  = 34,072). Follow-up data included information on a combined cardiovascular disease endpoint of myocardial infarction, stroke, or vascular death. In secondary analyses, annualised progression was replaced with average. Log hazard ratios per standard deviation difference were pooled across studies by a random effects meta-analysis. In primary analysis, the annualised progression of total cholesterol was marginally related to a higher cardiovascular disease risk (hazard ratio (HR) 1.04, 95% confidence interval (CI) 1.00 to 1.07). The annualised progression of systolic blood pressure, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol was not associated with future cardiovascular disease risk. In secondary analysis, average systolic blood pressure (HR 1.20 95% CI 1.11 to 1.29) and low-density lipoprotein cholesterol (HR 1.09, 95% CI 1.02 to 1.16) were related to a greater, while high-density lipoprotein cholesterol (HR 0.92, 95% CI 0.88 to 0.97) was related to a lower risk of future cardiovascular disease events., Conclusion: Averaged measurements of systolic blood pressure, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol displayed significant linear relationships with the risk of future cardiovascular disease events. However, there was no clear association between the annualised progression of these conventional risk factors in individuals with the risk of future clinical endpoints.

Aim: The objective of this study was to assess whether maternal characteristics, placental size or histological chorioamnionitis was associated with newborn body composition. Furthermore, we sought to determine whether placental weight may mediate the association between maternal pre-pregnancy weight and age with newborn body composition., Methods: A cross-sectional study was conducted at Royal Prince Alfred Hospital, Sydney, Australia. This study included 136 healthy, singleton, term-born newborns. Recruitment was stratified by newborn body fat percentiles (gender and gestational adjusted). Body fat was assessed by air displacement plethysmography. Placental examination was conducted by an anatomical pathologist. Maternal (chorioamnionitis) and fetal (chorionic and umbilical vasculitis, funisitis) inflammatory responses were classified according to Redline criteria., Results: Maternal pre-pregnancy weight, parity, labour, placental weight and surface area were associated with newborn fat mass and fat-free mass. Gestational diabetes and maternal age were associated with newborn fat mass but not fat-free mass. There was no association between histological chorioamnionitis and newborn body composition; however, spontaneous onset of labour was strongly associated with the presence of histological chorioamnionitis. Only 25-31% of the association of maternal weight and age with newborn fat mass was mediated via the placenta., Conclusions: Maternal factors associated with newborn fat mass and fat-free mass differed, indicating that different mechanisms control fat mass and fat-free mass. Our mediation analysis suggests that placental weight partly mediates the association of maternal factors with newborn body composition. Histological chorioamnionitis was not associated with newborn body composition., (© 2019 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Atherosclerosis underlies most myocardial infarctions and ischemic strokes. The timing of onset and the rate of progression of atherosclerosis differ between individuals and among arterial sites. Physical manifestations of atherosclerosis may begin in early life, particularly in the abdominal aorta. Measurement of the abdominal aortic intima-media thickness by external ultrasound is a non-invasive methodology for quantifying the extent and severity of early atherosclerosis in children, adolescents, and young adults. This review provides an evidence-based rationale for the assessment of abdominal aortic intima-media thickness-particularly as an age-appropriate methodology for studying the natural history of atherosclerosis in the young in comparison to other methodologies-establishes best practice methods for assessing abdominal aortic intima-media thickness, and identifies key gaps in the literature, including those that will identify the clinical relevance of this measure.

Background: Negative affect is shown consistently to promote unhealthy food choices and dietary intake in laboratory studies. However, this relationship in naturalistic settings is less clear and previous research is limited by dietary assessment methodology and neglects to account for several important moderating variables. This observational study aimed to examine the association of negative affect and other psychological factors associated with eating behaviour simultaneously with discretionary energy intake and total energy intake, and whether these were moderated by emotional eating predisposition or age, sex and weight status., Methods: One hundred adults completed a four-day food diary, a concurrent end-of-day questionnaire that assessed daily affect and experience of appetite, and the Three Factor Eating Questionnaire to assess trait eating behaviour. Food diaries provided data on participants' daily intake of total energy and of "discretionary items" (specific energy-dense and nutrient poor foods and beverages as defined by the Australian Guide to Healthy Eating). Stepwise random effects models were used to estimate the association of end-of-day ratings, trait eating behaviour and personal factors, and their interactions, with discretionary and total energy intake., Results: Daily rated negative affect and appetite were significantly and positively associated with discretionary intake, such that a one unit increase in each scale was associated with eating 139 kJ/d [SE 61] and 194 kJ/d [SE 68] more discretionary energy, respectively. Negative affect and its interaction with emotional eating were consistently, positively associated with discretionary energy intake. This relationship was strongest in younger participants (β = -4.9 [SE 2.2], p < .05). There was no interaction with sex or weight status. Total energy intake was not associated with negative affect nor its interaction with emotional eating but was consistently associated with appetite., Conclusion: When personal factors (age, sex, BMI), trait eating behaviours and daily rated negative affect and appetite are considered simultaneously, daily discretionary intake is associated most strongly with negative affect. Individuals, particularly young adults, may be more likely to overeat discretionary energy on days that negative affect is rated more highly. However, this may not necessarily translate into greater total energy intake which was most consistently associated with daily rated appetite., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Hypertension is an important modifiable risk factor for cardiovascular diseases. Its high prevalence, combined with the significant morbidity and mortality associated with secondary complications, make it a major public health concern. Despite decades of research, over 95% of all cases of hypertension remain of unknown etiology, necessitating that treatments target the established symptoms and not the cause. One of the important recent advances in hypertension research is an understanding that hypertension often may have a developmental origin. A substantial body of evidence indicates that exposure to an adverse intrauterine environment during critical periods of development may predispose an individual to develop hypertension later in life. A causative mechanism has yet to be identified, but may include epigenetic modifications, and/or alterations in renal, vascular or autonomic cardiovascular functions. This review will present evidence regarding changes in autonomic activity as a possible causative pathophysiological mechanism underlying the development of programmed hypertension. In man, low birth weight is the best-known risk factor for hypertension of developmental origins, although this is a broad surrogate measure for intrauterine adversity. This review will include clinical studies across the lifespan that have investigated autonomic function in individuals with fetal growth restriction and those born preterm. A determination of whether altered autonomic function is seen in these individuals in early life is imperative, as hypertensive disorders that have their origins in utero, and that can be identified early, will open the door to risk stratification, and the development of new strategies that prevent or specifically target these mechanisms.

Background: Many dietary recommendations for weight control rely on the assumption that greater core food intake will displace intake of energy-dense discretionary foods and beverages. However, there is little evidence to support these assumptions. This study examined the naturalistic relationship between daily core and discretionary energy intake, and with discretionary food and discretionary beverage intake, separately. The impact of weight status on these associations was also examined., Method: One hundred participants completed a four-day (non-consecutive) estimated food diary. Discretionary foods and beverages were identified by reference to the Australian Dietary Guidelines. Non-discretionary items were considered core items. Simultaneous-equation random effects models using disaggregated dietary data controlling for sociodemographic variables were used to determine the association between various dietary components., Result: Core energy intake correlated negatively with discretionary energy intake (cross-equation correlation, ρ = -0.49 (95% CI: -0.57, -0.39)). Its correlation with discretionary foods (-0.47 (-0.56, -0.37)) was stronger than that with discretionary beverages (-0.19 (-0.30, -0.07)) The correlation between core energy intake and discretionary energy intake was significantly stronger in participants who did not have obesity (-0.67 (-0.71, -0.50)) than those with obesity (-0.32 (-0.46, -0.17)) ( p = 0.0002)., Conclusions: Core and discretionary energy intake share an inverse and potentially bidirectional, relationship that appears to be stronger with discretionary foods than discretionary beverages. These relationships were significantly weaker in participants with obesity which may indicate less precise dietary compensation in these individuals. While strategies that promote greater intake of core foods may assist with weight maintenance in individuals of healthy weight, its impact in individuals with obesity may be limited. These strategies should be accompanied by direct messages to reduce commensurately the intake of discretionary items, with special attention paid to discretionary beverage consumption.

Introduction: Carotid Intima Media Thickness (CIMT) is a marker of subclinical atherosclerosis, associated with cardiovascular risk in adults. Telomere length (TL) is a marker of cellular ageing. We sought to determine whether telomere length in early childhood and/or at 14-years is associated with CIMT in adolescence, in a community-based cohort study., Methods: 118 children had TL measured at mean age 3.6-years and 165 children had TL and CIMT, measured at 14-years, from the community-based Childhood Asthma Prevention Study., Results: TL in early childhood was significantly inversely associated with CIMT at 14 years, p = 0.04. TL in teenage life was also significantly inversely associated with CIMT at 14 years, p = 0.03. This latter association was no longer significant, however, after adjusting for early life TL., Conclusion: TL measured in early childhood and adolescence is significantly associated with CIMT at 14-years, suggesting that telomere length is a biological marker or even early determinant of late cardiovascular risk., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: The amount and type of fat in the maternal diet during pregnancy are important contributors to fetal growth. The importance of plant-based omega-3 fatty acid (α-linolenic acid, ALA) intake in fetal growth has not been previously examined., Objective: We sought to determine the association of maternal ALA intake during pregnancy with birth weight and body composition of the offspring., Methods: Mothers and their newborn infants ( n  = 224) were recruited from the Royal Prince Alfred Hospital, Australia. Maternal diet during pregnancy was assessed using a validated food frequency questionnaire. Plasma fatty acid composition was analyzed in a subset of mothers ( n  = 41). Newborn body composition was assessed using air-displacement plethysmography. All analyses were adjusted for gestational age, sex, physical activity, and total energy intake., Results: Dietary fatty acid intakes were positively associated with plasma phospholipid fatty acids for total omega-3 fatty acids ( β  = 0.452, P  = 0.003), ALA ( β  = 0.339, P  = 0.03), linoleic acid ( β  = 0.353, P  = 0.03), eicosapentaenoic acid ( β  = 0.407, P  = 0.009), and docosahexaenoic acid ( β  = 0.388, P  = 0.01). Higher maternal intake of ALA (% total fat) was associated with higher offspring birth weight [189.7-g increase per 1% higher ALA (95% CI: 14, 365 g); P  = .04], although individually neither newborn fat mass nor fat-free mass was significant. Birth weight increased across tertiles of maternal ALA intake ( P ANOVA  = 0.05), with birth weight being 221 g (95% CI: 12, 429 g) higher in those with the highest maternal ALA intake compared with those with the lowest intake ( P  = 0.04). Mothers of infants born small for gestational age ( n  = 32) had a lower ALA intake than those born appropriate for gestational age ( n  = 162) or large for gestational age [( n  = 21); P  = 0.05]., Conclusions: In otherwise healthy women giving birth at a major tertiary hospital in Australia, intake of ALA during pregnancy is associated with higher offspring birth weight. This may have implications for dietary strategies aimed at optimizing fetal growth via modification of maternal diet.