Macronutrient composition of plant-based diets and breast cancer risk: the E3N prospective cohort study.

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.

Early Life Determinants of Vascular Structure in Fetuses, Infants, Children, and Adolescents: A Systematic Review and Meta-Analysis.

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; I2 = 97%), intrauterine growth restriction (6 studies; mean difference, 0.198 mm, 95% CI, 0.088-0.309; P < .001; I2 = 97%), preeclampsia (2 studies; mean difference, 0.038 mm; 95% CI, 0.024-0.051; P < .001; I2 = 38%), and large for gestational age (LGA) status (3 studies; mean difference, 0.089 mm; 95% CI, 0.043-0.0136; P < .001; I2 = 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.

Development of a Multibiomarker Panel of Healthy Eating Index in United States Adults: A Machine Learning Approach.

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 R2 increased from 0.056 to 0.245). The secondary multibiomarker panel (8 vitamins and 10 carotenoids) had lesser predictive capabilities (adjusted R2 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.

Aortic intima media thickness in children and adolescents with type 1 diabetes: A systematic review.

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 (I2 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).

Carotid Intima-Media Thickness Progression as Surrogate Marker for Cardiovascular Risk: Meta-Analysis of 119 Clinical Trials Involving 100 667 Patients.

BACKGROUND: To quantify the association between effects of interventions on carotid intima-media thickness (cIMT) progression and their effects on cardiovascular disease (CVD) risk. METHODS: We systematically collated data from randomized, controlled trials. cIMT was assessed as the mean value at the common-carotid-artery; if unavailable, the maximum value at the common-carotid-artery or other cIMT measures were used. The primary outcome was a combined CVD end point defined as myocardial infarction, stroke, revascularization procedures, or fatal CVD. We estimated intervention effects on cIMT progression and incident CVD for each trial, before relating the 2 using a Bayesian meta-regression approach. RESULTS: We analyzed data of 119 randomized, controlled trials involving 100 667 patients (mean age 62 years, 42% female). Over an average follow-up of 3.7 years, 12 038 patients developed the combined CVD end point. Across all interventions, each 10 µm/y reduction of cIMT progression resulted in a relative risk for CVD of 0.91 (95% Credible Interval, 0.87-0.94), with an additional relative risk for CVD of 0.92 (0.87-0.97) being achieved independent of cIMT progression. Taken together, we estimated that interventions reducing cIMT progression by 10, 20, 30, or 40 µm/y would yield relative risks of 0.84 (0.75-0.93), 0.76 (0.67-0.85), 0.69 (0.59-0.79), or 0.63 (0.52-0.74), respectively. Results were similar when grouping trials by type of intervention, time of conduct, time to ultrasound follow-up, availability of individual-participant data, primary versus secondary prevention trials, type of cIMT measurement, and proportion of female patients. CONCLUSIONS: The extent of intervention effects on cIMT progression predicted the degree of CVD risk reduction. This provides a missing link supporting the usefulness of cIMT progression as a surrogate marker for CVD risk in clinical trials.

Medium-Chain Triglyceride Oil and Blood Lipids: A Systematic Review and Meta-Analysis of Randomized Trials.

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.

Oral health of aboriginal people with kidney disease living in Central Australia.

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.

Influence of maternal and placental factors on newborn body composition.

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.

Marine Omega-3 Fatty Acids, Complications of Pregnancy and Maternal Risk Factors for Offspring Cardio-Metabolic Disease.

Marine omega-3 polyunsaturated fatty acids (n-3 PUFA) are important nutrients during periods of rapid growth and development in utero and infancy. Maternal health and risk factors play a crucial role in birth outcomes and subsequently offspring cardio-metabolic health. Evidence from observational studies and randomized trials have suggested a potential association of maternal intake of marine n-3 PUFAs during pregnancy with pregnancy and birth outcomes. However, there is inconsistency in the literature on whether marine n-3 PUFA supplementation during pregnancy can prevent maternal complications of pregnancy. This narrative literature review summarizes recent evidence on observational and clinical trials of marine n-3 PUFA intake on maternal risk factors and effects on offspring cardio-metabolic health. The current evidence generally does not support a role of maternal n-3 PUFA supplementation in altering the incidence of gestational diabetes, pregnancy-induced hypertension, or pre-eclampsia. It may be that benefits from marine n-3 PUFA supplementation are more pronounced in high-risk populations, such as women with a history of complications of pregnancy, or women with low marine n-3 PUFA intake. Discrepancies between studies may be related to differences in study design, dosage, fatty acid interplay, and length of treatment. Further prospective double-blind studies are needed to clarify the impact of long-chain marine n-3 PUFAs on risk factors for cardio-metabolic disease in the offspring.

Continuous and Dichotomous Metabolic Syndrome Definitions in Youth Predict Adult Type 2 Diabetes and Carotid Artery Intima Media Thickness: The Cardiovascular Risk in Young Finns Study.

OBJECTIVES: To examine the utility of continuous metabolic syndrome (cMetS) scores vs a dichotomous metabolic syndrome (MetS) definition in youth to predict adult type 2 diabetes mellitus (T2DM) and carotid intima-media thickness (IMT). STUDY DESIGN: Participants (n = 1453) from the population-based, prospective, observational Cardiovascular Risk in Young Finns Study who were examined in youth (when aged 9-18 years) and re-examined 15-25 years later. Four cMetS scores were constructed according to procedures most often used in the literature that comprised the youth risk factor inputs of body mass index, blood pressure, glucose, insulin, high-density lipoprotein-cholesterol, and triglycerides. Adult outcomes included T2DM and high carotid IMT (≥ 90 th percentile). RESULTS: For a 1 SD increase in cMetS scores in youth, participants had a 30%-78% increased risk of T2DM and 12%-61% increased risk of high carotid IMT. Prediction of adult T2DM and high carotid IMT using cMetS scores in youth was essentially no different to a dichotomous MetS definition with area under the receiver-operating characteristic curve ranging from 0.54-0.60 (continuous definitions) and 0.55-0.59 (dichotomous) with 95% CIs often including 0.5, and integrated discrimination improvement from -0.2% to -0.6%. CONCLUSIONS: cMetS scores in youth are predictive of cardiometabolic outcomes in adulthood. However, they do not have increased predictive utility over a dichotomous definition of MetS.

Infant adiposity at birth and early postnatal weight gain predict increased aortic intima-media thickness at 6 weeks of age: a population-derived cohort study.

Infant body composition and postnatal weight gain have been implicated in the development of adult obesity and cardiovascular disease, but there are limited prospective data regarding the association between infant adiposity, postnatal growth and early cardiovascular parameters. Increased aortic intima-media thickness (aortic IMT) is an intermediate phenotype of early atherosclerosis. The aim of the present study was to investigate the relationship between weight and adiposity at birth, postnatal growth and aortic IMT. The Barwon Infant Study (n=1074 mother-infant pairs) is a population-derived birth cohort. Infant weight and other anthropometry were measured at birth and 6 weeks of age. Aortic IMT was measured by trans-abdominal ultrasound at 6 weeks of age (n=835). After adjustment for aortic size and other factors, markers of adiposity including increased birth weight (ß=19.9 µm/kg, 95%CI 11.1, 28.6; P<0.001) and birth skinfold thickness (ß=6.9 µm/mm, 95%CI 3.3, 10.5; P<0.001) were associated with aortic IMT at 6 weeks. The association between birth skinfold thickness and aortic IMT was independent of birth weight. In addition, greater postnatal weight gain was associated with increased aortic IMT, independent of birth weight and age at time of scan (ß=11.3 µm/kg increase, 95%CI 2.2, 20.3; P=0.01). Increased infant weight and adiposity at birth, as well as increased early weight gain, were positively associated with aortic IMT. Excessive accumulation of adiposity during gestation and early infancy may have adverse effects on cardiovascular risk.

Fetal growth and the ethnic origins of type 2 diabetes.

Birthweight is known to differ by ethnicity, with South Asian, black African and Caribbean, and Hispanic ethnic groups having lower birthweight on average, when compared with people of white European ethnicity. Birthweight is the most frequently used proxy of fetal growth, and represents the net effect of a host of genetic, physiological and pathophysiological factors. These same ethnic groups that have lower average birthweight also tend to have a higher prevalence of type 2 diabetes in adulthood. It is not unreasonable to propose that the well-established inverse association between birthweight and risk of type 2 diabetes may at least partially contribute to these differences in prevalence of type 2 diabetes between ethnic groups. This hypothesis would rely on the mechanisms that drive the ethnic differences in birthweight aligning with those that modify the risk of type 2 diabetes. In this issue of Diabetologia (DOI: 10.1007/s00125-014-3474-7), Nightingale et al have furthered this field by determining whether ethnic differences in markers of cardio-metabolic risk are consistent with the differences in birthweight in an ethnically diverse cohort of children. The likely contribution of fetal growth to ethnic differences in risk of type 2 diabetes and cardiovascular disease is discussed, particularly in light of the magnitude of the birthweight differences, as are implications for the prevention of type 2 diabetes.

Impact of fetal growth and preterm birth on the retinal microvasculature in mid-adulthood.

OBJECTIVE: We hypothesized that preterm birth and being born SGA would be associated with changes in retinal microvascular architecture and that these changes would be more marked among those born preterm. We further hypothesized that these microvascular changes would correlate with early markers of CVD in mid-adulthood. METHODS: The Cardiovascular Risk in Young Finns Study included randomly selected children from 5 Finnish University cities. Retinal microvascular architecture of participants born preterm, born at term and SGA and a control group born at term and AGA were compared (aged 34-49 years). RESULTS: In participants born preterm, arteriolar tortuosity (×10(2)) was higher-means (standard error), 0.06 (0.01) versus 0.04 (0.01), p = 0.001, arteriolar length (pixels) were greater-644.9 (35.9) versus 591.7 (33.5), p = 0.007 and arteriolar diameters (pixels) were narrower-19.9 (0.4) versus 20.3 (0.3), p = 0.034 compared to participants born AGA, after adjustment. In participants born SGA, only arteriolar tortuosity was higher-0.05 (0.01) versus 0.04 (0.01), p = 0.074 compared to participants born AGA. CONCLUSION: This study demonstrated that being born SGA and in particular preterm birth are associated with changes in retinal microvascular architecture. The prenatal and immediate postnatal environment may contribute to the mechanisms.

The association of dietary alpha-linolenic acid with blood pressure and subclinical atherosclerosis in people born small for gestational age: the Special Turku Coronary Risk Factor Intervention Project study.

OBJECTIVE: To determine whether dietary alpha-linolenic (omega-3) fatty acid intake is associated with lower blood pressure and aortic intima-media thickness (IMT) in people born small for gestational age (SGA). STUDY DESIGN: Participants were recruited at age 6 months and followed up every 6-12 months until age 19 years. Blood pressure and food records were assessed at each visit. A total of 1009 participants had at least one blood pressure measure and complete birth weight and gestational age data, including 115 (11%) born SGA (birth weight≤10th percentile). Aortic IMT was assessed by ultrasound at 19 years (n=413). Analysis was by linear mixed models and multivariable linear regression. RESULTS: Children born SGA had greater systolic and pulse pressure from age 14 years onwards. In those born SGA, systolic blood pressure was 2.1 mm Hg lower ([95% CI 0.8-3.3]; P=.001) and pulse pressure 1.4 mm Hg lower ([95% CI 0.3-2.4]; P=.01), per exponential increase in alpha-linolenic acid (ALA) intake; weakened by adjustment for anthropometric measures. Long-term ALA intake was inversely associated with aortic IMT at 19 years in those born SGA (-0.30 mm [95% CI -0.52, -0.08] per exponential greater ALA intake; P=.008), independent of other dietary and anthropometric factors. CONCLUSION: Long-term dietary ALA intake during childhood is associated with improved vascular health in people born SGA.

High birth weight is associated with obesity and increased carotid wall thickness in young adults: the cardiovascular risk in young Finns study.

OBJECTIVE: There is some evidence that people born with high birth weight may be at increased risk of cardiovascular disease in adulthood. Details of the underlying mechanisms remain unknown. We sought to determine whether people born large for gestational age have poor arterial health, increased adiposity, and a poor cardiovascular risk factor profile. APPROACH AND RESULTS: Carotid intima-media thickness, brachial flow-mediated dilatation, and cardiovascular risk factors were compared between young adults (24-45 years) born at term who were large for gestational age (birth weight >90th percentile; n=171), and a control group with normal birth weight (50-75th percentile; n=525), in the Cardiovascular Risk in Young Finns Study. Those born large for gestational age had higher body mass index throughout childhood, adolescence, and as young adults (26.4 kg/m(2) [SD 4.9], versus normal birth weight 25.1 kg/m(2) [SD 4.6]; P=0.002), and 2-fold greater risk of obesity. Other cardiovascular risk factors and arterial function did not differ; however, carotid intima-media thickness was increased in people born large for gestational age (0.60 mm [SD 0.09], versus normal birth weight 0.57 mm [SD 0.09]; P=0.003), independent of cardiovascular risk factors (P=0.001 after adjustment). Both obesity and high birth weight were independently associated with carotid intima-media thickness in a graded and additive fashion. CONCLUSIONS: Young adults born large for gestational age are more likely to be obese, yet have an otherwise healthy cardiovascular risk profile. Nonetheless, they have increased carotid intima-media thickness, a marker of subclinical atherosclerosis, consistent with an increased risk of cardiovascular disease.

Periodontal disease and chronic kidney disease among Aboriginal adults; an RCT.

BACKGROUND: This study will assess measures of vascular health and inflammation in Aboriginal Australian adults with chronic kidney disease (CKD), and determine if intensive periodontal intervention improves cardiovascular health, progression of renal disease and periodontal health over a 24-month follow-up. METHODS: The study will be a randomised controlled trial. All participants will receive the periodontal intervention benefits, with the delayed intervention group receiving periodontal treatment 24 months following baseline. Inclusion criteria include being an Aboriginal Australian, having CKD (a. on dialysis; b. eGFR levels of < 60 mls/min/1.73 m(2) (CKD Stages 3 to 5); c. ACR ≥ 30 mg/mmol irrespective of eGFR (CKD Stages 1 and 2); d. diabetes plus albuminuria (ACR ≥ 3 mg/mmol) irrespective of eGFR), having moderate or severe periodontal disease, having at least 12 teeth, and living in Central Australia for the 2-year study duration. The intervention involves intensive removal of dental plaque biofilms by scaling, root-planing and removal of teeth that cannot be saved. The intervention will occur in three visits; baseline, 3-month and 6-month follow-up. The primary outcome will be changes in carotid intima-media thickness (cIMT). Secondary outcomes will include progression of CKD or death as a consequence of CKD/cardiovascular disease. Progression of CKD will be defined by time to the development of the first of: (1) new development of macroalbuminuria; (2) 30 % loss of baseline eGFR; (3) progression to end stage kidney disease defined by eGFR < 15 mLs/min/1.73 m(2); (4) progression to end stage kidney disease defined by commencement of renal replacement therapy. A sample size of 472 is necessary to detect a difference in cIMT of 0.026 mm (SD 0.09) at the significance criterion of 0.05 and a power of 0.80. Allowing for 20 % attrition, 592 participants are necessary at baseline, rounded to 600 for convenience. DISCUSSION: This will be the first RCT evaluating the effect of periodontal therapy on progression of CKD and cardiovascular disease among Aboriginal patients with CKD. Demonstration of a significant attenuation of CKD progression and cardiovascular disease has the potential to inform clinicians of an important, new and widely available strategy for reducing CKD progression and cardiovascular disease for Australia's most disadvantaged population. TRIAL REGISTRATION: This trial is registered with the Australian New Zealand Clinical Trial Registry ANZCTR12614001183673.

Right Ventricular Mass is Associated with Exercise Capacity in Adults with Repaired Tetralogy of Fallot.

The relationship between exercise capacity and right ventricular (RV) structure and function in adult repaired tetralogy of Fallot (TOF) is poorly understood. We therefore aimed to examine the relationships between cardiac MRI and cardiopulmonary exercise test variables in adult repaired TOF patients. In particular, we sought to determine the role of RV mass in determining exercise capacity. Eighty-two adult repaired TOF patients (age at evaluation 26 ± 10 years; mean age at repair 2.5 ± 2.8 years; 23.3 ± 7.9 years since repair; 53 males) (including nine patients with tetralogy-type pulmonary atresia with ventricular septal defect) were prospectively recruited to undergo cardiac MRI and cardiopulmonary exercise testing. As expected, these repaired TOF patients had RV dilatation (indexed RV end-diastolic volume: 153 ± 43.9 mL/m(2)), moderate-severe pulmonary regurgitation (pulmonary regurgitant fraction: 33 ± 14 %) and preserved left (LV ejection fraction: 59 ± 8 %) and RV systolic function (RV ejection fraction: 51 ± 7 %). Exercise capacity was near-normal (peak work: 88 ± 17 % predicted; peak oxygen consumption: 84 ± 17 % predicted). Peak work exhibited a significant positive correlation with RV mass in univariate analysis (r = 0.45, p < 0.001) and (independent of other cardiac MRI variables) in multivariate analyses. For each 10 g higher RV mass, peak work was 8 W higher. Peak work exhibits a significant positive correlation with RV mass, independent of other cardiac MRI variables. RV mass measured on cardiac MRI may provide a novel marker of clinical progress in adult patients with repaired TOF.

Reproducibility of aortic intima-media thickness in infants using edge-detection software and manual caliper measurements.

BACKGROUND: Aortic intima-media thickness measured by transabdominal ultrasound (aIMT) is an intermediate phenotype of cardiovascular risk. We aimed to (1) investigate the reproducibility of aIMT in a population-derived cohort of infants; (2) establish the distribution of aIMT in early infancy; (3) compare measurement by edge-detection software to that by manual sonographic calipers; and (4) assess the effect of individual and environmental variables on image quality. METHODS: Participants were term infants recruited to a population-derived birth cohort study. Transabdominal ultrasound was performed at six weeks of age by one of two trained operators. Thirty participants had ultrasounds performed by both operators on the same day. Data were collected on environmental (infant sleeping, presence of a sibling, use of sucrose, timing during study visit) and individual (post-conception age, weight, gender) variables. Two readers assessed image quality and measured aIMT by edge-detection software and a subset by manual sonographic calipers. Measurements were repeated by the same reader and between readers to obtain intra-observer and inter-observer reliability. RESULTS: Aortic IMT was measured successfully using edge-detection in 814 infants, and 290 of these infants also had aIMT measured using manual sonographic calipers. The intra-reader intra-class correlation (ICC) (n = 20) was 0.90 (95% CI 0.76, 0.96), mean difference 1.5 µm (95% LOA -39, 59). The between reader ICC using edge-detection (n = 20) was 0.92 (95% CI 0.82, 0.97) mean difference 2 µm (95% LOA -45.0, 49.0) and with manual caliper measurement (n = 290) the ICC was 0.84 (95% CI 0.80, 0.87) mean difference 5 µm (95% LOA -51.8, 61.8). Edge-detection measurements were greater than those from manual sonographic calipers (mean aIMT 618 µm (50) versus mean aIMT 563 µm (49) respectively; p < 0.001, mean difference 44 µm, 95% LOA -54, 142). With the exception of infant crying (p = 0.001), no associations were observed between individual and environmental variables and image quality. CONCLUSION: In a population-derived cohort of term infants, aIMT measurement has a high level of intra and inter-reader reproducibility. Measurement of aIMT using edge-detection software gives higher inter-reader ICC than manual sonographic calipers. Image quality is not substantially affected by individual and environmental factors.

Aortic intima-media thickness measured by trans-abdominal ultrasound as an early life marker of subclinical atherosclerosis.

UNLABELLED: Atherosclerosis is a chronic inflammatory process that begins in early life. Improved identification of markers of early atherosclerosis via neonatal aortic intima-media thickness (aIMT) measurement may allow the development of interventions to prevent or reduce later cardiovascular disease. CONCLUSION: Using aIMT, studies have shown that antenatal factors such as intra-uterine growth retardation, prematurity, maternal factors and inflammation are associated with early cardiovascular changes.

The Relationship between Dietary Macronutrient Composition and Telomere Length Among US Adults.

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.