Search

Study Question: Is high adiposity in childhood associated with menstrual irregularity and polycystic ovary syndrome (PCOS) in later life?Summary Answer: Overall, greater childhood BMI was associated with menstrual irregularity, and greater childhood BMI and waist/height ratio (WHtR) in white but not black participants were associated with PCOS in adulthood.What Is Known Already: Increased childhood BMI has been associated with irregular menstrual cycles and PCOS symptoms in adulthood in two longitudinal population-based studies, but no study has reported on associations with childhood abdominal obesity. Few studies have investigated whether there are racial differences in the associations of adiposity with PCOS though there has been some suggestion that associations with high BMI may be stronger in white girls than in black girls.Study Design, Size, Duration: The study included 1516 participants (aged 26-41 years) from the Australian Childhood Determinants of Adult Health study (CDAH) and 1247 participants (aged 26-57 years) from the biracial USA Babies substudy of the Bogalusa Heart Study (BBS) who were aged 7-15 years at baseline. At follow-up, questions were asked about menstruation (current for CDAH or before age 40 years for BBS), ever having had a diagnosis of PCOS and symptoms of PCOS.Participants/materials, Setting, Methods: In CDAH, a single childhood visit was conducted in 1985. In BBS, multiple childhood visits occurred from 1973 to 2000 and race was reported (59% white; 41% black). In childhood, overweight and obesity were defined by international age-sex-specific standards for BMI and WHtR was considered as an indicator of abdominal obesity. Multilevel mixed-effects Poisson regression estimated relative risks (RRs) adjusting for childhood age, highest parental and own education and age at menarche.Main Results and the Role Of Chance: The prevalence of childhood obesity was 1.1% in CDAH and 7.5% in BBS. At follow-up, menstrual irregularity was reported by 16.7% of CDAH and 24.5% of BBS participants. The prevalence of PCOS was 7.4% in CDAH and 8.0% in BBS participants. In CDAH, childhood obesity was associated with menstrual irregularity (RR = 2.84, 95% CI: 1.63-4.96) and PCOS (RR = 4.05, 95% CI: 1.10-14.83) in adulthood. With each 0.01 unit increase in childhood WHtR there was a 6% (95% CI: 1-11%) greater likelihood of PCOS. Overall, in BBS, childhood obesity was associated with increased risk of menstrual irregularity (RR = 1.44, 95% CI: 1.08-1.92) in adulthood. Significant interaction effects between race and childhood adiposity were detected in associations with PCOS. In BBS white participants, childhood obesity was associated with PCOS (RR = 2.93, 95% CI: 1.65-5.22) and a 0.01 unit increase in childhood WHtR was associated with an 11% (95% CI: 5-17%) greater likelihood of PCOS in adulthood. In BBS black participants, no statistically significant associations of childhood adiposity measures with PCOS were observed.Limitations, Reasons For Caution: The classification of menstrual irregularity and PCOS was based on self-report by questionnaire, which may have led to misclassification of these outcomes. However, despite the limitations of the study, the prevalence of menstrual irregularity and PCOS in the two cohorts was consistent with the literature. While the study samples at baseline were population-based, loss to follow-up means the generalizability of the findings is uncertain.Wider Implications Of the Findings: Greater childhood adiposity indicates a higher risk of menstrual irregularity and PCOS in adulthood. Whether this is causal or an early indicator of underlying hormonal or metabolic disorders needs clarification. The stronger associations of adiposity with PCOS in white than black participants suggest that there are racial differences in childhood adiposity predisposing to the development of PCOS and other environmental or genetic factors are also important.Study Funding/competing Interest(s): The CDAH study was supported by grants from the Australian National Health and Medical Research Council (grants 211316, 544923 and 1128373). The Bogalusa Heart Study is supported by US National Institutes of Health grants R01HD069587, AG16592, HL121230, HD032194 and P50HL015103. No competing interests existed. [ABSTRACT FROM AUTHOR]

Despite the interest in the relationship of fetal exposures to adult cardiovascular disease, few studies have examined indicators of adult fatty liver disease as an outcome. Previous results are inconsistent, and indicate possible variation by sex. Adult liver enzymes [γ-glutamyl transferase (GGT), alanine transaminase (ALT) and aspartase transaminase (AST)] were measured in two cohort studies: the Bogalusa Heart Study (BHS; n=1803) and the Cardiovascular Risk in Young Finns (YF; n=3571) study, which also had ultrasound measures of liver fat (n=2546). Predictors of dichotomized (clinical cut-offs) and continuous (within the reference range) liver enzymes included low birthweight (<2500 g), macrosomia (>4000 g), small-for-gestational-age (birthweight <10th percentile for gestational age for population), large-for-gestational-age (>90th percentile), and preterm birth. Multiple logistic and linear regression were conducted, adjusted for medical, behavioral and socioeconomic indicators. Interactions with sex were also examined. In BHS, birth measures were not strongly associated with clinically high levels of liver enzymes, and within the reference range measures of reduced growth were associated with increased AST in women. In the YF study, at least one marker of reduced growth was associated with higher GGT, higher ALT and higher AST (in women). Probable fatty liver on ultrasound was associated with low birthweight (2.41, 1.42–4.09) and preterm birth (2.84, 1.70–4.76). These results suggest a link between birth parameters and adult fatty liver, but encourage consideration of population variation in these relationships. [ABSTRACT FROM PUBLISHER]

Background and Aims: The relationship between dietary macronutrient composition and appetite is controversial. We examined the effects of a year-long low-carbohydrate diet compared to a low-fat diet on appetite-related hormones and self-reported change in appetite.Methods and Results: A total of 148 adults with a body mass index 30-45 kg/m(2), who were free of diabetes, cardiovascular disease and chronic kidney disease at baseline were randomly assigned to either a low-carbohydrate diet (carbohydrate [excluding dietary fiber]<40 g/day; N = 75) or a low-fat diet (<30% energy from fat, <7% from saturated fat; N = 73). Participants in both groups attended individual and group dietary counseling sessions where they were provided the same behavioral curriculum and advised to maintain baseline levels of physical activity. Appetite and appetite-related hormones were measured at 0, 3, 6 and 12 months of intervention. At 12 months, mean changes (95% CI) in peptide YY were -34.8 pg/mL (-41.0 to -28.6) and in the low-carbohydrate group and -44.2 pg/mL (-50.4 to -38.0) in the low-fat group (net change: 9.54 pg/mL [0.6 to 18.2]; p = 0.036). Approximately 99% of dietary effects on peptide YY are explained by differences in dietary macronutrient content. There was no difference in change in ghrelin or self-reported change in appetite between the groups.Conclusions: A low-fat diet reduced peptide YY more than a low-carbohydrate diet. These findings suggest that satiety may be better preserved on a low-carbohydrate diet, as compared to a low fat diet.Trial Registration: clinicaltrials.gov Identifier: NCT00609271. [ABSTRACT FROM AUTHOR]

Background and aims Left ventricular (LV) hypertrophy increases the risk of future cardiovascular events. The relationship between obesity in young adulthood and later LV geometry is unknown. We examined the association between long-term changes in measures of adiposity and subsequent LV geometry among 1073 young adults from the Bogalusa Heart Study. Methods and results Echocardiography-measured LV geometry was classified into normal ( N = 796), concentric remodeling ( N = 124), eccentric hypertrophy ( N = 99), and concentric hypertrophy ( N = 54) by integrating relative wall thickness and LV mass index. The mean age of our population was 38 years when the LV geometry was measured. Body mass index (BMI) increased by a mean of 4.9 kg/m 2 over a median of 20 years, waist circumference (WC) by 10.9 cm over 17 years, waist/hip ratio by 0.02 over 10 years, waist/height ratio by 0.06 over 17 years, abdominal height by 0.9 cm over 10 years, body fat (BF) percentage by 12.7% over 20 years, and Visceral Adiposity Index by 0.30 over 17 years. In polytomous logistic regression models corrected for multiple comparisons, participants with one-standard-deviation increases in BMI, WC, waist/height ratio, and BF had 2.00 (95% confidence interval (CI): 1.53–2.61), 1.33 (1.06–1.68), 1.35 (1.07–1.70), and 1.60 (1.26–2.03) times the risk of eccentric hypertrophy, respectively, after adjustment for demographic, lifestyle, metabolic risk factors, and follow-up time. Likewise, the rates of change in BMI, WC, waist/height ratio, and BF were associated with eccentric hypertrophy. There was no association with concentric remodeling or concentric hypertrophy. Conclusions Our findings suggest that increases in BMI, WC, waist/height ratio, and BF were strong predictors of eccentric hypertrophy in middle age. [ABSTRACT FROM AUTHOR]

Context: Dietary sodium is positively associated with blood pressure, and ecological and animal studies both have suggested that high dietary sodium intake increases stroke mortality.Objective: To examine the risk of cardiovascular disease associated with dietary sodium intake in overweight and nonoverweight persons.Design: Prospective cohort study.Setting: The first National Health and Nutrition Examination Survey Epidemiologic Follow-up Study, conducted in 1982-1984, 1986, 1987, and 1992.Participants: Of those aged 25 to 74 years when the survey was conducted in 1971 -1975 (14407 participants), a total of 2688 overweight and 6797 nonoverweight persons were included in the analysis.Main Outcome Measures: Dietary sodium and energy intake were estimated at baseline using a single 24-hour dietary recall method. Incidence and mortality data for cardiovascular disease were obtained from medical records and death certificates.Results: For overweight and nonoverweight persons, over an average of 19 years of follow-up, the total number of documented cases were as follows: 680 stroke events (210 fatal), 1727 coronary heart disease events (614 fatal), 895 cardiovascular disease deaths, and 2486 deaths from all causes. Among overweight persons with an average energy intake of 7452 kJ, a 100 mmol higher sodium intake was associated with a 32% increase (relative risk [RR], 1.32; 95% confidence interval [CI], 1.07-1.64; P = .01) in stroke incidence, 89% increase (RR, 1.89; 95% CI, 1.31-2.74; P<.001) in stroke mortality, 44% increase (RR, 1.44; 95% CI, 1.14-1.81; P = .002) in coronary heart disease mortality, 61% increase (RR, 1.61; 95% CI, 1.32-1.96; P<.001) in cardiovascular disease mortality, and 39% increase (RR, 1.39; 95% CI, 1.23-1.58; P<.001) in mortality from all causes. Dietary sodium intake was not significantly associated with cardiovascular disease risk in nonoverweight persons.Conclusions: Our analysis indicates that high sodium intake is strongly and independently associated with an increased risk of cardiovascular disease and all-cause mortality in overweight persons. [ABSTRACT FROM AUTHOR]

Abstract Background We examined the association of biomarkers of inflammation and endothelial dysfunction with diabetes and metabolic syndrome (MetS) in persons from Inner Mongolia. Methods A cross-sectional study was conducted among 2,536 people aged 20 years and older from Inner Mongolia, China. Overnight fasting blood samples were obtained to measure plasma concentrations of high sensitivity C-reactive protein (hsCRP), soluble inter-cellular adhesion molecule-1 (sICAM-1), sE-selectin, angiotensin II, high density lipoprotein cholesterol, triglycerides, and blood glucose. Waist circumference and blood pressure were measured by trained staff. MetS was defined according to the modified ATP III definition for Asians. Elevated level of the biomarker was defined as values in the upper tertile of the distribution. Participants were categorized into one of four groups based on the presence or absence of metabolic and glycemic abnormalities: 1) free of prediabetes, diabetes and MetS (reference group), 2) prediabetes or diabetes only, 3) MetS without prediabetes or diabetes, and 4) MetS plus prediabetes or diabetes. The multivariable models are adjusted for age, gender, smoking, drinking, family history of hypertension, and body mass index. Results Among study participants, 18.5% had prediabetes, 3.6% had diabetes, and 27.4% of the entire study population had 3 or more components of the MetS. Elevated hsCRP was associated with an increased odds of prediabetes or diabetes only, MetS without prediabetes or diabetes, and MetS plus prediabetes or diabetes with multivariable adjusted odds ratios (95% confidence intervals) of 2.3 (1.7-3.1), 3.0 (2.4-3.8), and 5.8 (4.5-7.5), respectively. Elevated sICAM-1 was associated with increased odds (95% CI) of prediabetes or diabetes only (2.1, 1.6-2.9) and MetS plus prediabetes or diabetes (4.2, 3.2-5.3) but was not associated with MetS alone. Elevated sE-selectin was associated with a modestly increased risk of MetS (OR 1.7, 95% CI 1.4-2.2). Elevated levels of Angiotensin II were not associated with the MetS plus prediabetes or diabetes in this study. Conclusions Diabetes and the MetS are common in the Inner Mongolia population. The biomarkers of inflammation and endothelial dysfunction are associated with increased risk for diabetes and MetS in this population. These results are consistent with results from other populations.

Abstract Background The World Health Organization has estimated that by 2030, chronic obstructive pulmonary disease will be the third leading cause of death worldwide. Most knowledge of chronic obstructive pulmonary disease is based on studies performed in Europe or North America and little is known about the prevalence, patient characteristics and change in lung function over time in patients in developing countries, such as those of Latin America. This lack of knowledge is in sharp contrast to the high levels of tobacco consumption and exposure to biomass fuels exhibited in Latin America, both major risk factors for the development of chronic obstructive pulmonary disease. Studies have also demonstrated that most Latin American physicians frequently do not follow international chronic obstructive pulmonary disease diagnostic and treatment guidelines. The PRISA Study will expand the current knowledge regarding chronic obstructive pulmonary disease and risk factors in Argentina, Chile and Uruguay to inform policy makers and health professionals on the best policies and practices to address this condition. Methods/Design PRISA is an observational, prospective cohort study with at least four years of follow-up. In the first year, PRISA has employed a randomized three-staged stratified cluster sampling strategy to identify 6,000 subjects from Marcos Paz and Bariloche, Argentina, Temuco, Chile, and Canelones, Uruguay. Information, such as comorbidities, socioeconomic status and tobacco and biomass exposure, will be collected and spirometry, anthropometric measurements, blood sampling and electrocardiogram will be performed. In year four, subjects will have repeat measurements taken. Discussion There is no longitudinal data on chronic obstructive pulmonary disease incidence and risk factors in the southern cone of Latin America, therefore this population-based prospective cohort study will fill knowledge gaps in the prevalence and incidence of chronic obstructive pulmonary disease, patient characteristics and changes in lung function over time as well as quality of life and health care resource utilization. Information gathered during the PRISA Study will inform public health interventions and prevention practices to reduce risk of COPD in the region.

Abstract Background Premature death from suicide is a leading cause of death worldwide. However, the pattern and risk factors for suicide and other external cause injuries are not well understood. This study investigates mortality from suicide and other injuries and associated risk factors in China. Methods A prospective cohort study of 169,871 Chinese adults aged 40 years and older was conducted. Mortality due to suicide or other external cause injuries was recorded. Results Mortality from all external causes was 58.7/100,000 (72.3 in men and 44.4 in women): 14.1/100,000 (14.2 in men and 14.2 in women) for suicide and 44.6/100,000 (58.1 in men and 30.2 in women) for other external cause injuries. Transport accidents (17.2/100,000 overall, 23.4 in men and 10.8 in women), accidental poisoning (7.5/100,000 overall, 10.2 in men and 4.8 in women), and accidental falls (5.7/100,000 overall, 6.5 in men and 5.0 in women) were the three leading causes of death from other external cause injuries in China. In the multivariable analysis, male sex (relative risk [RR] 1.56, 95% confidence interval [CI] 1.03-2.38), age 70 years and older (2.27, 1.29-3.98), living in north China (1.68, 1.20-2.36) and rural residence (2.82, 1.76-4.51) were associated with increased mortality from suicide. Male sex (RR 2.50, 95% CI 1.95-3.20), age 60-69 years (1.93, 1.45-2.58) and 70 years and older (3.58, 2.58-4.97), rural residence (2.29, 1.77-2.96), and having no education (1.56, 1.00-2.43) were associated with increased mortality from other external cause injuries, while overweight (0.60, 0.43-0.83) was associated with decreased risk of mortality from other external cause injuries. Conclusions External cause mortality has become a major public health problem in China. Developing an integrated national program for the prevention of mortality due to external cause injuries in China is warranted.

Background: Childhood cardiovascular risk factors predict subclinical adult cardiovascular disease, but links to clinical events are unclear.Methods: In a prospective cohort study involving participants in the International Childhood Cardiovascular Cohort (i3C) Consortium, we evaluated whether childhood risk factors (at the ages of 3 to 19 years) were associated with cardiovascular events in adulthood after a mean follow-up of 35 years. Body-mass index, systolic blood pressure, total cholesterol level, triglyceride level, and youth smoking were analyzed with the use of i3C-derived age- and sex-specific z scores and with a combined-risk z score that was calculated as the unweighted mean of the five risk z scores. An algebraically comparable adult combined-risk z score (before any cardiovascular event) was analyzed jointly with the childhood risk factors. Study outcomes were fatal cardiovascular events and fatal or nonfatal cardiovascular events, and analyses were performed after multiple imputation with the use of proportional-hazards regression.Results: In the analysis of 319 fatal cardiovascular events that occurred among 38,589 participants (49.7% male and 15.0% Black; mean [±SD] age at childhood visits, 11.8±3.1 years), the hazard ratios for a fatal cardiovascular event in adulthood ranged from 1.30 (95% confidence interval [CI], 1.14 to 1.47) per unit increase in the z score for total cholesterol level to 1.61 (95% CI, 1.21 to 2.13) for youth smoking (yes vs. no). The hazard ratio for a fatal cardiovascular event with respect to the combined-risk z score was 2.71 (95% CI, 2.23 to 3.29) per unit increase. The hazard ratios and their 95% confidence intervals in the analyses of fatal cardiovascular events were similar to those in the analyses of 779 fatal or nonfatal cardiovascular events that occurred among 20,656 participants who could be evaluated for this outcome. In the analysis of 115 fatal cardiovascular events that occurred in a subgroup of 13,401 participants (31.0±5.6 years of age at the adult measurement) who had data on adult risk factors, the adjusted hazard ratio with respect to the childhood combined-risk z score was 3.54 (95% CI, 2.57 to 4.87) per unit increase, and the mutually adjusted hazard ratio with respect to the change in the combined-risk z score from childhood to adulthood was 2.88 (95% CI, 2.06 to 4.05) per unit increase. The results were similar in the analysis of 524 fatal or nonfatal cardiovascular events.Conclusions: In this prospective cohort study, childhood risk factors and the change in the combined-risk z score between childhood and adulthood were associated with cardiovascular events in midlife. (Funded by the National Institutes of Health.). [ABSTRACT FROM AUTHOR]

We performed large-scale genome-wide gene-sleep interaction analyses of lipid levels to identify novel genetic variants underpinning the biomolecular pathways of sleep-associated lipid disturbances and to suggest possible druggable targets. We collected data from 55 cohorts with a combined sample size of 732,564 participants (87% European ancestry) with data on lipid traits (high-density lipoprotein [HDL-c] and low-density lipoprotein [LDL-c] cholesterol and triglycerides [TG]). Short (STST) and long (LTST) total sleep time were defined by the extreme 20% of the age- and sex-standardized values within each cohort. Based on cohort-level summary statistics data, we performed meta-analyses for the one-degree of freedom tests of interaction and two-degree of freedom joint tests of the main and interaction effect. In the cross-population meta-analyses, the one-degree of freedom variant-sleep interaction test identified 10 loci (P int <5.0e-9) not previously observed for lipids. Of interest, the ASPH locus (TG, LTST) is a target for aspartic and succinic acid metabolism previously shown to improve sleep and cardiovascular risk. The two-degree of freedom analyses identified an additional 7 loci that showed evidence for variant-sleep interaction (P joint <5.0e-9 in combination with P int <6.6e-6). Of these, the SLC8A1 locus (TG, STST) has been considered a potential treatment target for reduction of ischemic damage after acute myocardial infarction. Collectively, the 17 (9 with STST; 8 with LTST) loci identified in this large-scale initiative provides evidence into the biomolecular mechanisms underpinning sleep-duration-associated changes in lipid levels. The identified druggable targets may contribute to the development of novel therapies for dyslipidemia in people with sleep disturbances.

Objective: To translate data relating childhood cardiovascular (CV) risk factors and adult CV disease and type 2 diabetes mellitus (T2DM) to clinically actionable values., Study Design: This was a prospective observational study (n = 38 589) in the International Childhood Cardiovascular Cohort Consortium. Children at age 3 through 19 years were enrolled in the 1970s and 1980s and followed for more than 30 years. Five childhood CV risk factors (smoking, body mass index [BMI], systolic blood pressure, triglycerides, and total cholesterol) were related to adult CV events. Secondary analyses in a subset included low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, glucose, and insulin level. Age- and sex-specific z scores were calculated for each risk factor, and a combined-risk z score was calculated by averaging z scores for the 5 key CV risk factors. Risk factor z scores were back-transformed to natural units for clinical interpretation, with hazard ratios for adult CV events presented in color-coded tables (green: no increased risk; orange: 1.4 to <2.0-fold increased risk; red: at least doubling of risk). Risk levels for development of adult T2DM on the basis of BMI, glucose, and insulin were similarly calculated and presented., Results: Increased risk for CV events was observed at levels lower than currently defined abnormal clinical thresholds except for TC. Doubling of risk was observed at high normal levels just below the clinical cut point for abnormality. Risk for adult T2DM began at levels of BMI and glucose currently considered normal., Conclusions: On the basis of data showing significant relationships between childhood CV risk factors and adult CV events and T2DM, this study shows that risk in childhood begins below levels currently considered normal., Competing Interests: Declaration of Competing Interest Supported by a grant from the National Institutes of Health (NIH) (HL121230). Historical funding sources for cohorts in the International Childhood Cardiovascular Cohort (i3C) Consortium are listed in our previous publication.(5) J.W., D.J., L.B., T.D., M.J., O.R., A.S., J.S., A.V., and E.U. received grant funding for this project from the NIH. E.U. also received grant funding from DSMB Astellas Pharma, and Honorarium Targus Medical Inc. The other authors have no disclosures or relationships with industry to report., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Although both short and long sleep duration are associated with elevated hypertension risk, our understanding of their interplay with biological pathways governing blood pressure remains limited. To address this, we carried out genome-wide cross-population gene-by-short-sleep and long-sleep duration interaction analyses for three blood pressure traits (systolic, diastolic, and pulse pressure) in 811,405 individuals from diverse population groups. We discover 22 novel gene-sleep duration interaction loci for blood pressure, mapped to 23 genes. Investigating these genes' functional implications shed light on neurological, thyroidal, bone metabolism, and hematopoietic pathways that necessitate future investigation for blood pressure management that caters to sleep health lifestyle. Non-overlap between short sleep (12) and long sleep (10) interactions underscores the plausible nature of distinct influences of both sleep duration extremes in cardiovascular health. Several of our loci are specific towards a particular population background or sex, emphasizing the importance of addressing heterogeneity entangled in gene-environment interactions, when considering precision medicine design approaches for blood pressure management., Competing Interests: Declarations CONFLICT OF INTEREST C.L.M. has received funding from AstraZeneca not related to the current study. B.M.P. serves on the steering committee of the Yale Open Data Access Project funded by Johnson & Johnson. D.C. receives consultancy fees from Roche Diagnostics and Trimedics and speaker fees from Servier. D.A.L. has received support from Medtronic LTD and Roche Diagnostics for biomarker research not related to the current study. The remaining authors declare no competing interests.

Context: Early age at menarche (AAM) is a risk factor for type 2 diabetes later in life, but the pathogenic pathways that confer increased risk remain unknown., Objective: We examined the associations between AAM and inflammatory and glucose metabolism biomarkers among U.S. adult women who were free of diabetes., Methods: Using the National Health and Nutrition Examination Survey (NHANES) 1999-2018, 19,228 women over 20 years old who were free of self-reported cancer and diabetes were included in this cross-sectional analysis. AAM was the self-reported age at first menstruation. CRP, fasting glucose, fasting insulin, and ferritin levels were measured as biomarkers of inflammation and glucose metabolism in adult blood samples using latex-enhanced nephelometry, enzymatic, and immunoassay methods. Multiple linear regression was used to relate AAM to the biomarkers., Results: The median age at the time of blood sample collection was 44 years (IQR, 33-62). After age adjustment, there was an association between a lower AAM and higher CRP (P-trend=0.006); fasting glucose (P-trend<0.0001); fasting insulin (P-trend <0.0001); and ferritin (p-trend<0.0001). These remained significant after additional adjustment for demographic, reproductive, lifestyle, and adiposity variables, except for ferritin. Smoking modified the effect of AAM on CRP (p-interaction = 0.014), fasting insulin (p-interaction <0.001), and fasting glucose (p-interaction<0.001). In stratified analysis, the observed associations became more pronounced in non-smokers, while they were attenuated to non-significance in active smokers., Conclusion: Earlier age at menarche is associated with an unfavorable inflammatory and glucose metabolic biomarker profile in a nationally representative sample of adult women free of diabetes, especially among non-smokers., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Background: Smartphone-based cognitive assessments have emerged as promising tools, bridging gaps in accessibility and reducing bias in Alzheimer disease and related dementia research. However, their congruence with traditional neuropsychological tests and usefulness in diverse cohorts remain underexplored., Methods and Results: A total of 406 FHS (Framingham Heart Study) and 59 BHS (Bogalusa Heart Study) participants with traditional neuropsychological tests and digital assessments using the Defense Automated Neurocognitive Assessment (DANA) smartphone protocol were included. Regression models investigated associations between DANA task digital measures and a neuropsychological global cognitive Z score (Global Cognitive Score [GCS]), and neuropsychological domain-specific Z scores. FHS participants' mean age was 57 (SD, 9.75) years, and 44% (179) were men. BHS participants' mean age was 49 (4.4) years, and 28% (16) were men. Participants in both cohorts with the lowest neuropsychological performance (lowest quartile, GCS1) demonstrated lower DANA digital scores. In the FHS, GCS1 participants had slower average response times and decreased cognitive efficiency scores in all DANA tasks ( P <0.05). In BHS, participants in GCS1 had slower average response times and decreased cognitive efficiency scores for DANA Code Substitution and Go/No-Go tasks, although this was not statistically significant. In both cohorts, GCS was significantly associated with DANA tasks, such that higher GCS correlated with faster average response times ( P <0.05) and increased cognitive efficiency (all P <0.05) in the DANA Code Substitution task., Conclusions: Our findings demonstrate that smartphone-based cognitive assessments exhibit concurrent validity with a composite measure of traditional neuropsychological tests. This supports the potential of using smartphone-based assessments in cognitive screening across diverse populations and the scalability of digital assessments to community-dwelling individuals.

Background: Dairy consumption is related to chronic disease risk; however, the measurement of dairy consumption has largely relied upon self-report. Untargeted metabolomics allows for the identification of objective markers of dietary intake., Objectives: We aimed to identify associations between dietary dairy intake (total dairy, low-fat dairy, and high-fat dairy) and serum metabolites in 2 independent study populations of United States adults., Methods: Dietary intake was assessed with food frequency questionnaires. Multivariable linear regression models were used to estimate cross-sectional associations between dietary intake of dairy and 360 serum metabolites analyzed in 2 subgroups of the Atherosclerosis Risk in Communities study (ARIC; n = 3776). Results from the 2 subgroups were meta-analyzed using fixed effects meta-analysis. Significant meta-analyzed associations in the ARIC study were then tested in the Bogalusa Heart Study (BHS; n = 785)., Results: In the ARIC study and BHS, the mean age was 54 and 48 years, 61% and 29% were Black, and the mean dairy intake was 1.7 and 1.3 servings/day, respectively. Twenty-nine significant associations between dietary intake of dairy and serum metabolites were identified in the ARIC study (total dairy, n = 14; low-fat dairy, n = 10; high-fat dairy, n = 5). Three associations were also significant in BHS: myristate (14:0) was associated with high-fat dairy, and pantothenate was associated with total dairy and low-fat dairy, but 23 of the 27 associations significant in the ARIC study and tested in BHS were not associated with dairy in BHS., Conclusions: We identified metabolomic associations with dietary intake of dairy, including 3 associations found in 2 independent cohort studies. These results suggest that myristate (14:0) and pantothenate (vitamin B5) are candidate biomarkers of dairy consumption., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Objective: This study investigated whether changes in DNA methylation (DNAm) at TXNIP are associated with glycemic changes and whether such an association differs with early-life adiposity changes., Methods: A total of 594 Bogalusa Heart Study participants who had blood DNAm measurements at two time points in midlife were included. Of them, 353 participants had at least four BMI measurements during childhood and adolescence. The incremental area under the curve was calculated as a measure of long-term trends of BMI during childhood and adolescence., Results: Increase in DNAm at TXNIP was significantly associated with decrease in fasting plasma glucose (FPG) independent of covariates (p < 0.001). The study found that the strength of this relationship was significantly modified by a trend of increasing BMI during childhood and adolescence (p-interaction = 0.003). Each 1% increase in DNAm at TXNIP was associated with a 2.90- (0.77) mg/dL decrease in FPG among participants with the highest tertile of BMI incremental area under the curve and a 0.96- (0.38) mg/dL decrease among those with the middle tertile, whereas no association was observed among participants with the lowest tertile., Conclusions: These results indicate that changes in blood DNAm at TXNIP are significantly associated with changes in FPG in midlife, and this association was modified by BMI trends during childhood and adolescence., (© 2023 The Authors. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society.)

Background The temporal relationship between type 2 diabetes (T2DM) and left ventricular hypertrophy (LVH) is not well established. This study aims to examine the temporal sequence between T2DM and LVH/cardiac geometry patterns in middle-aged adults. Methods and Results The longitudinal cohort consisted of 1000 adults (682 White individuals and 318 Black individuals; 41.1% men; mean age, 36.2 years at baseline) who had data on fasting glucose/T2DM, left ventricular mass index (LVMI), and relative wall thickness collected twice at baseline and follow-up over 9.4 years on average. The cross-lagged path analysis model in 905 adults who did not take antidiabetic medications and the longitudinal prediction model in 1000 adults were used to examine the temporal relationships of glucose/T2DM with LVMI, LVH, relative wall thickness, and remodeling patterns. After adjustment for age, race, sex, smoking, alcohol drinking, body mass index, heart rate, hypertension, and follow-up years, the path coefficient from baseline LVMI to follow-up glucose was 0.088 ( P =0.005); the path from baseline glucose to follow-up LVMI was -0.009 ( P =0.758). The 2 paths between glucose and relative wall thickness were not significant. The path analysis parameters did not differ significantly between race, sex, and follow-up duration subgroups. Incidence of T2DM was higher in the baseline LVH group than in the normal LVMI group (24.8% versus 8.8%; P =0.017 for difference). Incidence of LVH and concentric LVH was higher in the baseline T2DM group than in the group without T2DM (50.0% versus 18.2% for LVH [ P =0.005 for difference]; 41.7% versus 12.6% for concentric LVH [ P =0.004 for difference]), with adjustment for covariates. Conclusions This study suggests that the temporal relationship between T2DM and LVH is likely bidirectional. The path from LVMI/LVH to glucose/T2DM is stronger than the path from glucose/T2DM to LVMI/LVH.

Introduction: Effective connectivity (EC), the causal influence that functional activity in a source brain location exerts over functional activity in a target brain location, has the potential to provide different information about brain network dynamics than functional connectivity (FC), which quantifies activity synchrony between locations. However, head-to-head comparisons between EC and FC from either task-based or resting-state functional MRI (fMRI) data are rare, especially in terms of how they associate with salient aspects of brain health., Methods: In this study, 100 cognitively-healthy participants in the Bogalusa Heart Study aged 54.2 ± 4.3years completed Stroop task-based fMRI, resting-state fMRI. EC and FC among 24 regions of interest (ROIs) previously identified as involved in Stroop task execution (EC-task and FC-task) and among 33 default mode network ROIs (EC-rest and FC-rest) were calculated from task-based and resting-state fMRI using deep stacking networks and Pearson correlation. The EC and FC measures were thresholded to generate directed and undirected graphs, from which standard graph metrics were calculated. Linear regression models related graph metrics to demographic, cardiometabolic risk factors, and cognitive function measures., Results: Women and whites (compared to men and African Americans) had better EC-task metrics, and better EC-task metrics associated with lower blood pressure, white matter hyperintensity volume, and higher vocabulary score (maximum value of p = 0.043). Women had better FC-task metrics, and better FC-task metrics associated with APOE-ε4 3-3 genotype and better hemoglobin-A1c, white matter hyperintensity volume and digit span backwards score (maximum value of p = 0.047). Better EC rest metrics associated with lower age, non-drinker status, and better BMI, white matter hyperintensity volume, logical memory II total score, and word reading score (maximum value of p = 0.044). Women and non-drinkers had better FC-rest metrics (value of p = 0.004)., Discussion: In a diverse, cognitively healthy, middle-aged community sample, EC and FC based graph metrics from task-based fMRI data, and EC based graph metrics from resting-state fMRI data, were associated with recognized indicators of brain health in differing ways. Future studies of brain health should consider taking both task-based and resting-state fMRI scans and measuring both EC and FC analyses to get a more complete picture of functional networks relevant to brain health., 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 © 2023 Chuang, Ramakrishnapillai, Madden, St Amant, McKlveen, Gwizdala, Dhullipudi, Bazzano and Carmichael.)

Background and Aims: This study aims to examine the temporal relationship between uric acid (UA) and insulin and their joint impact on T2DM in middle-aged adults., Methods and Results: The cohort consisted of 1351 non-diabetic adults who had serum UA and insulin measured twice at baseline and follow-up over 7.7 years on average, and incidence of T2DM in the outcome survey12.2 years later. After adjusting for covariates, the path coefficient from baseline UA to follow-up insulin was 0.082 (p < 0.001); the path from baseline insulin to follow-up UA was 0.060 (p = 0.030). In the mediation model with baseline UA as the predictor, total effect of baseline UA on incident T2DM was 0.089 (p = 0.016). The mediation effect through follow-up insulin on the UA-T2DM association was 28.1%. The direct effect of baseline UA on T2DM (0.064) became nonsignificant (p = 0.078). In the mediation model with baseline insulin as the predictor, total effect of baseline insulin on T2DM was 0.218 (p < 0.001). The mediation effect through follow-up UA on the insulin-T2DM association was 5.5%. The direct effect of baseline insulin on T2DM (0.206) remained significant (p < 0.001). The baseline hyperinsulinemia-follow-up hyperuricemia group showed the highest incidence rate of T2DM (27.9%)., Conclusions: The bidirectional temporal relationship suggests that UA and insulin influence each other in non-diabetic individuals, and the directionality plays pathogenic roles in the development of T2DM., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Objective: This study aims to determine quantitatively the mediation effects of multiple cardiovascular risk factors on the associations of childhood body mass index (BMI) and its cumulative burden with adult carotid intima-media thickness (cIMT)., Methods: The longitudinal cohort consisted of 1391 adults who had been examined for BMI 4-15 times over 35.0 years on average since childhood and had data on adult cIMT, systolic blood pressure, low-density lipoprotein cholesterol, atherogenic index of plasma, and serum glucose. The area under the curve was used as a measure of cumulative burden of BMI., Results: After adjusting for covariates, the total effects (standardized regression coefficient) of childhood BMI (0.138), adult BMI (0.111), and area under the curve of BMI (0.150) on cIMT were all significant ( P <0.001) without mediators included in the model. The mediation effects of adult systolic blood pressure, glucose, atherogenic index of plasma and low-density lipoprotein cholesterol were 8.0%, 4.3%, 3.6%, and 0.0%, respectively, in the model with childhood BMI as the predictor, 23.4%, 15.3%, 12.6%, and 7.2%, respectively, with adult BMI as the predictor, and 14.7%, 8.7%, 6.0%, and 2.0%, respectively, with area under the curve of BMI as the predictor. The direct effects on cIMT were 0.117 ( P <0.001) for childhood BMI, 0.046 ( P =0.224) for adult BMI, and 0.103 ( P <0.001) for area under the curve of BMI after removing the mediation effects., Conclusions: The long-term deleterious impact of adiposity on subclinical changes in vascular structure begins early in life and is accumulated over lifetime. Excess adiposity and higher cIMT are linked partly through other cardiovascular risk factors in later life, especially elevated blood pressure and glucose.

Complementary foods and beverages (CFBs) are key components of an infant's diet in the second 6 months of life. This article summarizes nutrition and feeding practices examined by the 2020 Dietary Guidelines Advisory Committees during the CFB life stage. Breastfeeding initiation is high (84%), but exclusive breastfeeding at 6 months (26%) is below the Healthy People 2030 goal (42%). Most infants (51%) are introduced to CFBs sometime before 6 months. The primary mode of feeding (ie, human milk fed [HMF]; infant formula or mixed formula and human milk fed [FMF]) at the initiation of CFBs is associated with the timing of introduction and types of CFBs reported. FMF infants (42%) are more likely to be introduced to CFBs before 4 months compared with HMF infants (19%). Different dietary patterns, such as higher prevalence of consumption and mean amounts, were observed, including fruit, grains, dairy, proteins, and solid fats. Compared with HMF infants of the same age, FMF infants consume more total energy (845 vs 631 kcal) and protein (22 vs 12 g) from all sources, and more energy (345 vs 204 kcal) and protein (11 vs 6 g) from CFBs alone. HMF infants have a higher prevalence of risk of inadequate intakes of iron (77% vs 7%), zinc (54% vs <3%), and protein (27% vs <3%). FMF infants are more likely to have an early introduction (<12 months) to fruit juice (45% vs 20%) and cow's milk (36% vs 24%). Registered dietitian nutritionists and nutritional professionals should consider tailoring their advice to caregivers on dietary and complementary feeding practices, taking into account the primary mode of milk feeding during this life stage to support infants' nutrient adequacy. National studies that address the limitations of this analysis, including small sample sizes and imputed breast milk volume, could refine findings from this analysis., (Copyright © 2022 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

Importance: Patients with lower extremity peripheral artery disease (PAD) have reduced lower extremity perfusion, impaired lower extremity skeletal muscle function, and poor walking performance. Telmisartan (an angiotensin receptor blocker) has properties that reverse these abnormalities., Objective: To determine whether telmisartan improves 6-minute walk distance, compared with placebo, in patients with lower extremity PAD at 6-month follow-up., Design, Setting, and Participants: Double-blind, randomized clinical trial conducted at 2 US sites and involving 114 participants. Enrollment occurred between December 28, 2015, and November 9, 2021. Final follow-up occurred on May 6, 2022., Interventions: The trial randomized patients using a 2 × 2 factorial design to compare the effects of telmisartan plus supervised exercise vs telmisartan alone and supervised exercise alone and to compare telmisartan alone vs placebo. Participants with PAD were randomized to 1 of 4 groups: telmisartan plus exercise (n = 30), telmisartan plus attention control (n = 29), placebo plus exercise (n = 28), or placebo plus attention control (n = 27) for 6 months. The originally planned sample size was 240 participants. Due to slower than anticipated enrollment, the primary comparison was changed to the 2 combined telmisartan groups vs the 2 combined placebo groups and the target sample size was changed to 112 participants., Main Outcomes and Measures: The primary outcome was the 6-month change in 6-minute walk distance (minimum clinically important difference, 8-20 m). The secondary outcomes were maximal treadmill walking distance; Walking Impairment Questionnaire scores for distance, speed, and stair climbing; and the 36-Item Short-Form Health Survey physical functioning score. The results were adjusted for study site, baseline 6-minute walk distance, randomization to exercise vs attention control, sex, and history of heart failure at baseline., Results: Of the 114 randomized patients (mean age, 67.3 [SD, 9.9] years; 46 were women [40.4%]; and 81 were Black individuals [71.1%]), 105 (92%) completed 6-month follow-up. At 6-month follow-up, telmisartan did not significantly improve 6-minute walk distance (from a mean of 341.6 m to 343.0 m; within-group change: 1.32 m) compared with placebo (from a mean of 352.3 m to 364.8 m; within-group change: 12.5 m) and the adjusted between-group difference was -16.8 m (95% CI, -35.9 m to 2.2 m; P = .08). Compared with placebo, telmisartan did not significantly improve any of the 5 secondary outcomes. The most common serious adverse event was hospitalization for PAD (ie, lower extremity revascularization, amputation, or gangrene). Three participants (5.1%) in the telmisartan group and 2 participants (3.6%) in the placebo group were hospitalized for PAD., Conclusions and Relevance: Among patients with PAD, telmisartan did not improve 6-minute walk distance at 6-month follow-up compared with placebo. These results do not support telmisartan for improving walking performance in patients with PAD., Trial Registration: ClinicalTrials.gov Identifier: NCT02593110.

Importance: Childhood lipid levels have been associated with adult subclinical atherosclerosis; however, life-course lipid trajectories and their associations with cardiovascular disease risk are poorly characterized., Objectives: To examine the associations of lipid levels at different ages and discrete lipid trajectory patterns from childhood to adulthood with subclinical atherosclerosis in midlife., Design, Setting, and Participants: This cohort study used data from the Bogalusa Heart Study, a prospective, population-based cohort study conducted in a semirural, biracial community in Bogalusa, Louisiana, with follow-up from 1973 to 2016 (median follow-up, 36.8 years). Participants had 4 to 16 repeated measurements of lipids, including total cholesterol (TC), non-high-density lipoprotein cholesterol (non-HDL-C), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG), from childhood to midlife and adult measurement of carotid intima-media thickness (IMT). Statistical analyses were conducted from July 1 to December 31, 2021., Exposures: Age-specific lipid levels were estimated, and lipid trajectory patterns were identified using latent mixture modeling., Main Outcomes and Measures: Subclinical atherosclerosis measured by carotid IMT., Results: The study evaluated 1201 adults (mean [SD] age, 45.7 [6.8] years; 691 [57.5%] women and 510 [42.5%] men; 392 Black [32.6%] and 809 White [67.4%] individuals). Levels of all lipids at each age from 5 to 45 years were significantly associated with adult IMT. The magnitude of associations generally increased with age, and non-HDL-C (age 5 y: β, 0.040; 95% CI, 0.025-0.055; age 45 y, β, 0.049; 95% CI, 0.026-0.072) and LDL-C (age 5 y: β, 0.039; 95% CI, 0.024-0.054; age 45 y, β, 0.043; 95% CI, 0.023-0.063) showed the strongest associations. After adjusting for race, sex, and other cardiovascular risk factors, mean IMT values were significantly higher in the low-slow increase, low-rapid increase, and high-stable trajectory groups for TC (eg, high-stable group: mean difference, 0.152 mm; 95% CI, 0.059-0.244 mm), the low-slow increase, low-rapid increase, moderate-stable, and high-stable trajectory groups for non-HDL-C (eg, low-slow increase group: mean difference, 0.048 mm; 95% CI, 0.012-0.085 mm) and LDL-C (eg, low-rapid increase group: mean difference, 0.104 mm; 95% CI, 0.056-0.151 mm) and the low-rapid increase and moderate-stable trajectory groups for TG (eg, moderate-stable group: mean difference, 0.071 mm; 95% CI, 0.019-0.122 mm) vs the corresponding low-stable trajectory groups. These associations were slightly attenuated after further adjustment for lipid levels at baseline or follow-up. There were no significant differences in mean IMT among HDL-C trajectory groups., Conclusions and Relevance: In this cohort study, discrete life-course lipid trajectories were associated with the development of atherosclerosis in midlife. The findings emphasize the importance of maintaining optimal lipid levels across the lifespan.

Background In people with peripheral artery disease, post hoc analyses of the LITE (Low Intensity Exercise Intervention in Peripheral Artery Disease) randomized trial were conducted to evaluate the effects of walking exercise at a pace inducing ischemic leg symptoms on walking velocity and the Short Physical Performance Battery, compared with walking exercise without ischemic leg symptoms and compared with a nonexercising control group. Methods and Results Participants with peripheral artery disease were randomized to: home-based walking exercise that induced ischemic leg symptoms; home-based walking exercise conducted without ischemic leg symptoms; or a nonexercising control group for 12 months. Outcomes were change of walking velocity over 4 m and change of the Short Physical Performance Battery (0-12, with 12=best) at 6- and 12-month follow-up. A total of 264 participants (48% women, 61% Black race) were included. Compared with walking exercise without ischemic symptoms, walking exercise that induced ischemic symptoms improved change in usual-paced walking velocity over 4 m at 6-month (0.056 m/s [95% CI, 0.019-0.094 m/s]; P <0.01) and 12-month follow-up (0.084 m/s [95% CI, 0.049-0.120 m/s]; P <0.01), change in fast-paced of walking velocity over 4 m at 6-month follow-up ( P =0.03), and change in the Short Physical Performance Battery at 12-month follow-up (0.821 [95% CI, 0.309-1.334]; P <0.01). Compared with control, walking exercise at a pace inducing ischemic symptoms improved change in usual-paced walking velocity over 4 m at 6-month follow-up (0.066 m/s [95% CI, 0.021-0.111 m/s]; P <0.01). Conclusions In people with peripheral artery disease, those who walked for exercise at a comfortable pace without ischemic leg symptoms slowed their walking speed during daily life and worsened the Short Physical Performance Battery score, a potentially harmful effect, compared with people who walked for exercise at a pace inducing ischemic leg symptoms. Compared with a control group who did not exercise, home-based walking exercise at a pace inducing ischemic leg symptoms significantly improved change of walking velocity over 4 m at 6-month follow-up, but this benefit did not persist at 12-month follow-up. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02538900.

Background: Data are limited regarding differential and common effects of cardiovascular risk factors on subclinical changes in vascular structure and function. We aimed to examine the relationships of life-course cumulative burdens of cardiovascular risk factors with adult arterial pulse wave velocity (PWV) and carotid intima-media thickness (CIMT) in a longitudinal cohort of the Bogalusa Heart Study., Methods: The cohort consisted of 900 subjects who had aortic-femoral PWV and CIMT measurements. These participants were examined 5-16 times for body mass index (BMI), blood pressure, atherogenic index of plasma (AIP), and low-density lipoprotein cholesterol (LDLC) from childhood to adulthood. The area under the curve (AUC) was calculated as a measure of long-term burden of the risk factors., Results: Adjusting for covariates, adult PWV was associated with AUCs of BMI, systolic blood pressure (SBP) and AIP (standardized regression coefficient [β] = 0.191, 0.321, 0.153, respectively; P < 0.001 for all). Adult CIMT was associated with AUCs of BMI, SBP, AIP and LDLC (β = 0.115, 0.202, 0.141, 0.152, respectively; P < 0.001 for all). Moreover, childhood BMI was associated with adult PWV and CIMT (β = 0.088 and 0.075, respectively; false discovery rate q values < 0.05 for both), and childhood LDLC with adult CIMT (β = 0.079; false discovery rate q value < 0.05). These associations did not differ significantly among race and sex groups., Conclusions: The life-course cumulative burden of BMI, SBP, and AIP has common effects on arterial wall stiffening and thickening, whereas LDLC is specifically associated with arterial wall thickness, and this effect starts in early life., (Copyright © 2022 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Understanding lifecourse trajectories of body-mass index (BMI) is important for identifying groups at high risk of poor health and potential target points for intervention. This study aimed to describe BMI trajectories from childhood to mid-adulthood in four population-based cohorts established in the 1970s and 1980s and to identify childhood sociodemographic factors related to trajectory membership., Methods: Between Dec 17, 1970 and Dec 15, 1994, data were collected at the first visit from 9830 participants from the International Childhood Cardiovascular Cohort (i3C) Consortium, which includes participants from Australia (1985), Finland (1980) and the USA (1970-1994). Participants had at least three measures of height and weight, including one in childhood (6-18 years) and one in adulthood (>18 years), and were aged 30-49 years at last measurement. Latent Class Growth Mixture Modelling was used to identify lifecourse BMI trajectory groups and log multinomial regression models were fit to identify their childhood sociodemographic predictors., Findings: Five consistent BMI trajectory groups were identified amongst the four cohorts: persistently low (35.9-58.6%), improving from high (0.7-4.8%), progressing to moderate (9.3-43.7%), progressing to high (1.1-6.0%), and progressing to very high (0.7-1.3%). An additional three BMI trajectory groups were identified in some, but not all, cohorts: adult onset high (three cohorts; 1.8-20.7%), progressing to moderate-high (two cohorts; 5.2-13.8%), and relapsing yo-yoers (alternating upward and downward; one cohort; 1.3%). In pooled analyses, each predictor variable in childhood, including age, gender, parental education and race, was associated with increased likelihood of belonging to the most (e.g., improving from high) and least (e.g., progressing to very high) favourable BMI trajectory groups, suggesting a U-shaped (or inverse U-shaped) pattern of association., Interpretation: Five consistent BMI trajectory groups were identified across four cohorts from Australia, Finland, and the USA, mainly across two eras of birth. While most participants remained on a persistently low trajectory (50%), many demonstrated worsening BMI trajectories (47%), with only few demonstrating improving trajectories (<5%). Age, gender, parental education, and race appear to be important predictors of BMI trajectory group membership and need consideration in preventive and management strategies., Funding: This study was supported by funding from the National Institutes of Health, National Heart, Lung and Blood Institute (grant number R01 HL121230)., Competing Interests: We declare no competing interests., (© 2022 The Author(s).)

Objective: The authors hypothesize that an untargeted metabolomics study will identify novel mechanisms underlying smoking-associated weight loss., Methods: This study performed cross-sectional analyses among 1,252 participants in the Bogalusa Heart Study and assessed 1,202 plasma metabolites for mediation effects on smoking-BMI associations. Significant metabolites were tested for associations with smoking genetic risk scores among a subset of participants (n = 654) with available genomic data, followed by direction dependence analysis to investigate causal relationships between the metabolites and smoking and BMI. All analyses controlled for age, sex, race, education, alcohol drinking, and physical activity., Results: Compared with never smokers, current and former smokers had a 3.31-kg/m 2 and 1.77-kg/m 2 lower BMI after adjusting for all covariables, respectively. A total of 22 xenobiotics and 94 endogenous metabolites were significantly associated with current smoking. Eight xenobiotics were also associated with former smoking. Forty metabolites mediated the smoking-BMI associations, and five showed causal relationships with both smoking and BMI. These metabolites, including 1-oleoyl-GPE (18:1), 1-linoleoyl-GPE (18:2), 1-stearoyl-2-arachidonoyl-GPE (18:0/20:4), α-ketobutyrate, and 1-palmitoyl-GPE (16:0), mediated 26.0% of the association between current smoking and BMI., Conclusions: This study cataloged plasma metabolites altered by cigarette smoking and identified five metabolites that partially mediated the association between current smoking and BMI., (© 2022 The Obesity Society.)

Background: In search of innovative approaches to the challenge of uncontrolled hypertension, we assessed the association between preference for immediate gratification (i.e., high discounting rate), low medication adherence, and uncontrolled blood pressure (BP) in adults with hypertension., Methods: Using a probability discounting model and the Collier-Williams hypothetical discount rate framework, participants in this cross-sectional study reported their preference for a smaller amount of money available immediately (high discount rate; immediate gratification preference) vs. a larger amount available 1 year later (low discount rate; delayed gratification preference). Multivariable Poisson regression was used to test the association of high discounting rates with low antihypertensive medication adherence using the validated 4-item Krousel-Wood Medication Adherence Scale (K-Wood-MAS-4 score ≥1). Mediation of the association between high discounting rate and uncontrolled BP (systolic/diastolic BP ≥ 130/80 mm Hg) by low adherence was tested using the counterfactual approach., Results: Among 235 participants (mean age 63.7 ± 6.7 years; 51.1% women; 41.9% Black), 50.6% had a high 1-year discount rate, 51.9% had low K-Wood-MAS-4 adherence, and 59.6% had uncontrolled BP. High discounting rates were associated with low adherence (adjusted prevalence ratio 1.58, 95% confidence interval (CI) 1.18, 2.12). Forty-three percent (95% CI 40.9%, 45.8%) of the total effect of high discount rate on uncontrolled BP was mediated by low adherence., Conclusions: Adults with preference for immediate gratification had worse adherence; low adherence partially mediated the association of high discount rate with uncontrolled BP. These results support preference for immediate gratification as an innovative factor underlying low medication adherence and uncontrolled BP., (© American Journal of Hypertension, Ltd 2021. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)