Diet quality in young adulthood and sleep at midlife: a prospective analysis in the Bogalusa Heart Study.

BACKGROUND: Diet and sleep are both established risk factors for cardiometabolic diseases. Prior evidence suggests a potential link between these behaviors, though longitudinal evidence for how diet associates with sleep is scarce. This study aimed to determine the prospective association between diet quality in young adulthood and multiple sleep outcomes at midlife in the Bogalusa Heart Study (BHS). METHODS: This prospective study included 593 BHS subjects with dietary assessment at the 2001-2002 visit and sleep questionnaire responses from the 2013-2016 visit, after an average of 12.7 years (baseline mean age: 36 years, 36% male, 70%/30% White and Black persons). A culturally tailored, validated food frequency questionnaire assessed usual diet. Diet quality was measured with the Alternate Healthy Eating Index (AHEI) 2010, the Healthy Eating Index (HEI) 2015, and the alternate Mediterranean (aMed) dietary score. Robust Poisson regression with log-link function estimated risk ratios (RR) for insomnia symptoms, high sleep apnea score, and having a healthy sleep pattern by quintile and per standard deviation (SD) increase in dietary patterns. Models adjusted for potential confounders including multi-level socioeconomic factors, depression, and body mass index. Trends across quintiles and effect modification by sex, race, and education were tested. RESULTS: Higher diet quality in young adulthood, measured by both AHEI and HEI, was associated with lower probability of having insomnia symptoms at midlife. In the adjusted model, each SD-increase in AHEI (7.8 points; 7% of score range) conferred 15% lower probability of insomnia symptoms at follow-up (RR [95% confidence interval CI]: 0.85 [0.77, 0.93]), those in Q5 of AHEI had 0.54 times the probability as those in Q1 (95% CI: 0.39, 0.75), and there was a significant trend across quintiles (trend p = 0.001). There were no significant associations between young adult diet quality and having a high sleep apnea risk or a healthy sleep pattern at follow-up. CONCLUSIONS: A healthy diet was associated with a lower probability of future insomnia symptoms. If replicated, these findings could have implications for chronic disease prevention strategies incorporating the lifestyle behaviors of sleep and diet.

Predictors in Youth of Adult Cardiovascular Events.

BACKGROUND AND OBJECTIVES: Childhood risk factors are associated with cardiovascular events in adulthood. We compared the utility of a risk model based solely on nonlaboratory risk factors in adolescence versus a model that additionally included lipids to predict cardiovascular events in adulthood. METHODS: The study comprised 11 550 participants from 7 longitudinal cohort studies in the United States, Australia, and Finland with risk factor measurements in adolescence and followed into adulthood. The adolescent risk factors were defined by using clinical standards including overweight or obesity, elevated blood pressure, smoking, and borderline high or high levels of total cholesterol and triglycerides. The main outcomes were medically adjudicated fatal or nonfatal cardiovascular disease events occurring after age 25. RESULTS: Of 11 550 participants (55.1% female, mean age 50.0 ± 7.7 years), 513 (4.4%) had confirmed cardiovascular events. In a multivariable model (hazard ratio [95% confidence interval]), elevated blood pressure (1.25 [1.03-1.52]), overweight (1.76 [1.42-2.18]), obesity (2.19 [1.62-2.98]), smoking (1.63 [1.37-1.95]), and high total cholesterol (1.79 [1.39-2.31]) were predictors of cardiovascular events (P < .05). The addition of lipids (total cholesterol and triglycerides) into the nonlaboratory model (age, sex, blood pressure, BMI, and smoking) did not improve discrimination in predicting cardiovascular events (C-statistics for the lipid model 0.75 [SD 0.07] and nonlaboratory model 0.75 [0.07], P = .82). CONCLUSIONS: Nonlaboratory-based risk factors and lipids measured in adolescence independently predicted adult cardiovascular events. The addition of lipid measurements to nonlaboratory risk factors did not improve the prediction of cardiovascular events.

A Large-Scale Genome-Wide Gene-Sleep Interaction Study in 732,564 Participants Identifies Lipid Loci Explaining Sleep-Associated Lipid Disturbances.

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.

Sleep apnoea symptoms and sleepiness associate with future diet quality: a prospective analysis in the Bogalusa Heart Study.

Sleep apnoea is a known risk factor for cardiometabolic diseases (CMD), but it is unknown whether sleep apnoea or its symptoms contribute to increased CMD through an association with diet quality. This study assessed the association between sleep apnoea symptoms on future diet quality in the Bogalusa Heart Study (BHS). This prospective study included 445 participants who completed a sleep apnoea questionnaire in 2007-2010 and a FFQ in 2013-2016 (mean follow-up: 5·8 years; age 43·5 years; 34 % male; 71 % White/29 % Black persons). Diet quality was measured with the Alternate Healthy Eating Index (AHEI) 2010, the Healthy Eating Index (HEI) 2015 and the alternate Mediterranean diet score. Adjusted mean differences in dietary patterns by sleep apnoea risk, excessive snoring and daytime sleepiness were estimated with multivariable linear regression. Models included multi-level socio-economic factors, lifestyle and health characteristics including BMI, physical activity and depressive symptoms. Those with high sleep apnoea risk, compared with low, had lower diet quality 5·8 years later (percentage difference in AHEI (95 % CI -2·1 % (-3·5 %, -0·7 %)). Daytime sleepiness was associated with lower diet quality. After adjusting for dietary pattern scores from 2001 to 2002, having high sleep apnoea risk and excessive sleepiness were associated with 1·5 % (P < 0·05) and 3·1 % (P < 0·001) lower future AHEI scores, respectively. These findings suggest that individuals with sleep apnea or excessive sleepiness should be monitored for diet quality and targeted for dietary interventions to improve CMD risk.

Life-period associations of body mass index with adult carotid intima-media thickness: The Bogalusa Heart Study and the Cardiovascular Risk in Young Finns Study.

OBJECTIVE: Child and adult body mass index (BMI) associates with adult carotid artery intima-media thickness (cIMT). However, the relative contribution of BMI at different life-periods on adult cIMT has not been quantified. This study aimed to determine the life-course model that best explains the relative contribution of BMI at different life-periods (childhood, adolescence, and young-adulthood) on cIMT in adulthood. METHODS: BMI was calculated from direct measurements of height and weight at up to seven time-points from childhood to adulthood (1973-2007) among 2485 participants of the Cardiovascular Risk in Young Finns Study (YFS) and 1271 participants in the Bogalusa Heart Study (BHS). BMI measures at three ages representative of childhood (9-years), adolescence (18 years) and young-adulthood (30 years) life-periods were used. B-mode ultrasound was used to measure common cIMT in adulthood (>30 years). Associations were evaluated using the Bayesian relative life-course exposure model. RESULTS: In both cohorts, cumulative exposure to higher levels of BMI across the life-course was associated with greater cIMT. Of the examined life-periods, BMI in young-adulthood provided the greatest relative contribution towards the development of adult cIMT for YFS (49.9 %, 95 % CrI = 34-68 %) and white BHS participants (48.6 %, 95 % CrI = 9-86 %), whereas BMI in childhood had the greatest relative contribution for black BHS participants (54.0 %, 95 % CrI = 8-89 %). CONCLUSION: Although our data suggest sensitive periods in the life-course where prevention and intervention aimed at reducing BMI might provide most benefit in limiting the effects of BMI on cIMT, maintaining lower BMI across the life-course appears to be optimal.

A Clinical Tool to Relate Youth Risk Factors to Adult Cardiovascular Events and Type 2 Diabetes: The International Childhood Cardiovascular Cohort Consortium.

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.

Novel Metabolites Associated With Blood Pressure After Dietary Interventions.

BACKGROUND: The blood pressure (BP) etiologic study is complex due to multifactorial influences, including genetic, environmental, lifestyle, and their intricate interplays. We used a metabolomics approach to capture internal pathways and external exposures and to study BP regulation mechanisms after well-controlled dietary interventions. METHODS: In the ProBP trail (Protein and Blood Pressure), a double-blinded crossover randomized controlled trial, participants underwent dietary interventions of carbohydrate, soy protein, and milk protein, receiving 40 g daily for 8 weeks, with 3-week washout periods. We measured plasma samples collected at baseline and at the end of each dietary intervention. Multivariate linear models were used to evaluate the association between metabolites and systolic/diastolic BP. Nominally significant metabolites were examined for enriching biological pathways. Significant ProBP findings were evaluated for replication among 1311 participants of the BHS (Bogalusa Heart Study), a population-based study conducted in the same area as ProBP. RESULTS: After Bonferroni correction for 77 independent metabolite clusters (α=6.49×10-4), 18 metabolites were significantly associated with BP at baseline or the end of a dietary intervention, of which 11 were replicated in BHS. Seven emerged as novel discoveries, which are as follows: 1-linoleoyl-GPE (18:2), 1-oleoyl-GPE (18:1), 1-stearoyl-2-linoleoyl-GPC (18:0/18:2), 1-palmitoyl-2-oleoyl-GPE (16:0/18:1), maltose, N-stearoyl-sphinganine (d18:0/18:0), and N6-carbamoylthreonyladenosine. Pathway enrichment analyses suggested dietary protein intervention might reduce BP through pathways related to G protein-coupled receptors, incretin function, selenium micronutrient network, and mitochondrial biogenesis. CONCLUSIONS: Seven novel metabolites were identified to be associated with BP at the end of different dietary interventions. The beneficial effects of protein interventions might be mediated through specific metabolic pathways.

Associations of Epigenetic Age Acceleration With CVD Risks Across the Lifespan: The Bogalusa Heart Study.

Although epigenetic age acceleration (EAA) might serve as a molecular signature of childhood cardiovascular disease (CVD) risk factors and further promote midlife subclinical CVD, few studies have comprehensively examined these life course associations. This study sought to test whether childhood CVD risk factors predict EAA in adulthood and whether EAA mediates the association between childhood CVD risks and midlife subclinical disease. Among 1,580 Bogalusa Heart Study participants, we estimated extrinsic EAA, intrinsic EAA, PhenoAge acceleration (PhenoAgeAccel), and GrimAge acceleration (GrimAgeAccel) during adulthood. We tested prospective associations of longitudinal childhood body mass index (BMI), blood pressure, lipids, and glucose with EAAs using linear mixed effects models. After confirming EAAs with midlife carotid intima-media thickness and carotid plaque, structural equation models examined mediating effects of EAAs on associations of childhood CVD risk factors with subclinical CVD measures. After stringent multiple testing corrections, each SD increase in childhood BMI was significantly associated with 0.6-, 0.9-, and 0.5-year increases in extrinsic EAA, PhenoAgeAccel, and GrimAgeAccel, respectively (P < 0.001 for all 3 associations). Likewise, each SD increase in childhood log-triglycerides was associated with 0.5- and 0.4-year increases in PhenoAgeAccel and GrimAgeAccel (P < 0.001 for both), respectively, whereas each SD increase in childhood high-density lipoprotein cholesterol was associated with a 0.3-year decrease in GrimAgeAccel (P = 0.002). Our findings indicate that PhenoAgeAccel mediates an estimated 27.4% of the association between childhood log-triglycerides and midlife carotid intima-media thickness (P = 0.022). Our data demonstrate that early life CVD risk factors may accelerate biological aging and promote subclinical atherosclerosis.

Association of Age at Menarche with Inflammation and Glucose Metabolism Biomarkers in U.S. Adult Women: NHANES 1999-2018.

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.

Cardiovascular Risk Factors in Childhood and Adulthood and Cardiovascular Disease in Middle Age.

Importance: Recent evidence suggests that childhood levels of serum lipids, blood pressure, body mass index (BMI), and smoking contribute to adult risk of cardiovascular disease (CVD). Evidence is lacking on whether this is independent of adult risk levels. Objective: To quantify direct and indirect effects of childhood risk factors on adult CVD via adulthood risk factors using mediation analysis, and to quantify their relative importance during different life-course stages using a life-course approach. Design, Setting, and Participants: This prospective cohort study followed participants from the US, Finland, and Australia from childhood (1970s-1990s) until 2019, with data on CVD risk factors in childhood and adulthood. Longitudinal childhood and adulthood risk factors were summarized to describe BMI, lipids, and blood pressure cumulatively. Childhood and adulthood smoking were assessed with questionnaires. Data analysis was performed May 2022 to August 2023. Main Outcomes and Measures: The primary outcomes were fatal and nonfatal cardiovascular events in adulthood. Mediation analysis was used to estimate the direct and indirect effects of the childhood risk factors with CVD events, reported as incidence rate ratios (RRs) and 95% CIs. Results: A total of 10 634 participants (4506 male participants [42.4%]; mean [SD] age at childhood visit, 13.3 [3.0] years; mean [SD] age at adulthood visit, 32.3 [6.0] years) were included in the cohort. The mean (SD) age at CVD event or censoring was 49.2 (7.0) years. The median (IQR) follow-up time was 23.6 (18.7-30.2) years. Childhood risk factors, (low-density lipoprotein cholesterol [LDL-C], total cholesterol [TC], triglycerides, systolic blood pressure [SBP], smoking, BMI, and a combined score of these) were associated with CVD. BMI (direct effect for incidence RR per 1 SD unit, 1.18; 95% CI, 1.05-1.34) and LDL-C (direct effect incidence RR, 1.16; 95% CI, 1.01-1.34) in particular were found to play an important role via direct pathways, whereas the indirect effects were larger for TC, triglycerides, SBP, and the combined score. Childhood smoking only affected CVD via adulthood smoking. Life-course models confirmed that for the risk of CVD, childhood BMI plays nearly as important role as adulthood BMI, whereas for the other risk factors and the combined score, adulthood was the more important period. Conclusions and Relevance: In this cohort study of 10 634 participants, childhood risk factors were found to be associated both directly and indirectly to adult CVD, with the largest direct effect seen for BMI and LDL-C. These findings suggest that intervention for childhood risk factors, in particular BMI, is warranted to reduce incidence of adult CVD as it cannot be fully mitigated by risk factor management in adulthood.

Non-High-Density Lipoprotein Cholesterol Levels From Childhood to Adulthood and Cardiovascular Disease Events.

Importance: Elevated non-high-density lipoprotein cholesterol (non-HDL-C; a recommended measure of lipid-related cardiovascular risk) is common in children and increases risk of adult cardiovascular disease (CVD). Whether resolution of elevated childhood non-HDL-C levels by adulthood is associated with reduced risk of clinical CVD events is unknown. Objective: To examine the associations of non-HDL-C status between childhood and adulthood with incident CVD events. Design, Setting, and Participants: Individual participant data from 6 prospective cohorts of children (mean age at baseline, 10.7 years) in the US and Finland. Recruitment took place between 1970 and 1996, with a final follow-up in 2019. Exposures: Child (age 3-19 years) and adult (age 20-40 years) non-HDL-C age- and sex-specific z scores and categories according to clinical guideline-recommended cutoffs for dyslipidemia. Main Outcomes and Measures: Incident fatal and nonfatal CVD events adjudicated by medical records. Results: Over a mean length of follow-up of 8.9 years after age 40 years, 147 CVD events occurred among 5121 participants (60% women; 15% Black). Both childhood and adult non-HDL-C levels were associated with increased risk of CVD events (hazard ratio [HR], 1.42 [95% CI, 1.18-1.70] and HR, 1.50 [95% CI, 1.26-1.78] for a 1-unit increase in z score, respectively), but the association for childhood non-HDL-C was reduced when adjusted for adult levels (HR, 1.12 [95% CI, 0.89-1.41]). A complementary analysis showed that both childhood non-HDL-C levels and the change between childhood and adulthood were independently associated with the outcome, suggesting that from a preventive perspective, both childhood non-HDL-C levels and the change into adulthood are informative. Compared with those whose non-HDL-C levels remained within the guideline-recommended range in childhood and adulthood, participants who had incident non-HDL-C dyslipidemia from childhood to adulthood and those with persistent dyslipidemia had increased risks of CVD events (HR, 2.17 [95% CI, 1.00-4.69] and HR, 5.17 [95% CI, 2.80-9.56], respectively). Individuals who had dyslipidemic non-HDL-C in childhood but whose non-HDL-C levels were within the guideline-recommended range in adulthood did not have a significantly increased risk (HR, 1.13 [95% CI, 0.50-2.56]). Conclusions and Relevance: Individuals with persistent non-HDL-C dyslipidemia from childhood to adulthood had an increased risk of CVD events, but those in whom dyslipidemic non-HDL-C levels resolve by adulthood have similar risk to individuals who were never dyslipidemic. These findings suggest that interventions to prevent and reduce elevated childhood non-HDL-C levels may help prevent premature CVD.

Comparing Cognitive Tests and Smartphone-Based Assessment in 2 US Community-Based Cohorts.

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.

Childhood Non-HDL Cholesterol and LDL Cholesterol and Adult Atherosclerotic Cardiovascular Events.

BACKGROUND: Although low-density lipoprotein cholesterol (LDL-C) remains the primary cholesterol target in clinical practice in children and adults, non-high-density lipoprotein cholesterol (non-HDL-C) has been suggested as a more accurate measure of atherosclerotic cardiovascular disease (ASCVD) risk. We examined the associations of childhood non-HDL-C and LDL-C levels with adult ASCVD events and determined whether non-HDL-C has better utility than LDL-C in predicting adult ASCVD events. METHODS: This prospective cohort study included 21 126 participants from the i3C Consortium (International Childhood Cardiovascular Cohorts). Proportional hazards regressions were used to estimate the risk for incident fatal and fatal/nonfatal ASCVD events associated with childhood non-HDL-C and LDL-C levels (age- and sex-specific z scores; concordant/discordant categories defined by guideline-recommended cutoffs), adjusted for sex, Black race, cohort, age at and calendar year of child measurement, body mass index, and systolic blood pressure. Predictive utility was determined by the C index. RESULTS: After an average follow-up of 35 years, 153 fatal ASCVD events occurred in 21 126 participants (mean age at childhood visits, 11.9 years), and 352 fatal/nonfatal ASCVD events occurred in a subset of 11 296 participants who could be evaluated for this outcome. Childhood non-HDL-C and LDL-C levels were each associated with higher risk of fatal and fatal/nonfatal ASCVD events (hazard ratio ranged from 1.27 [95% CI, 1.14-1.41] to 1.35 [95% CI, 1.13-1.60] per unit increase in the risk factor z score). Non-HDL-C had better discriminative utility than LDL-C (difference in C index, 0.0054 [95% CI, 0.0006-0.0102] and 0.0038 [95% CI, 0.0008-0.0068] for fatal and fatal/nonfatal events, respectively). The discordant group with elevated non-HDL-C and normal LDL-C had a higher risk of ASCVD events compared with the concordant group with normal non-HDL-C and LDL-C (fatal events: hazard ratio, 1.90 [95% CI, 0.98-3.70]; fatal/nonfatal events: hazard ratio, 1.94 [95% CI, 1.23-3.06]). CONCLUSIONS: Childhood non-HDL-C and LDL-C levels are associated with ASCVD events in midlife. Non-HDL-C is better than LDL-C in predicting adult ASCVD events, particularly among individuals who had normal LDL-C but elevated non-HDL-C. These findings suggest that both non-HDL-C and LDL-C are useful in identifying children at higher risk of ASCVD events, but non-HDL-C may provide added prognostic information when it is discordantly higher than the corresponding LDL-C and has the practical advantage of being determined without a fasting sample.

A Proposed Pediatric Clinical Cardiovascular Health Reference Standard.

INTRODUCTION: Clinical cardiovascular health is a construct that includes 4 health factors-systolic and diastolic blood pressure, fasting glucose, total cholesterol, and body mass index-which together provide an evidence-based, more holistic view of cardiovascular health risk in adults than each component separately. Currently, no pediatric version of this construct exists. This study sought to develop sex-specific charts of clinical cardiovascular health for age to describe current patterns of clinical cardiovascular health throughout childhood. METHODS: Data were used from children and adolescents aged 8-19 years in six pooled childhood cohorts (19,261 participants, collected between 1972 and 2010) to create reference standards for fasting glucose and total cholesterol. Using the models for glucose and cholesterol as well as previously published reference standards for body mass index and blood pressure, clinical cardiovascular health charts were developed. All models were estimated using sex-specific random-effects linear regression, and modeling was performed during 2020-2022. RESULTS: Models were created to generate charts with smoothed means, percentiles, and standard deviations of clinical cardiovascular health for each year of childhood. For example, a 10-year-old girl with a body mass index of 16 kg/m2 (30th percentile), blood pressure of 100/60 mm Hg (46th/50th), glucose of 80 mg/dL (31st), and total cholesterol of 160 mg/dL (46th) (lower implies better) would have a clinical cardiovascular health percentile of 62 (higher implies better). CONCLUSIONS: Clinical cardiovascular health charts based on pediatric data offer a standardized approach to express clinical cardiovascular health as an age- and sex-standardized percentile for clinicians to assess cardiovascular health in childhood to consider preventive approaches at early ages and proactively optimize lifetime trajectories of cardiovascular health.

The association between preconception cannabis use and gestational diabetes mellitus: The Preconception Period Analysis of Risks and Exposures Influencing health and Development (PrePARED) consortium.

BACKGROUND: The metabolic changes that ultimately lead to gestational diabetes mellitus (GDM) likely begin before pregnancy. Cannabis use might increase the risk of GDM by increasing appetite or promoting fat deposition and adipogenesis. OBJECTIVES: We aimed to assess the association between preconception cannabis use and GDM incidence. METHODS: We analysed individual-level data from eight prospective cohort studies. We identified the first, or index, pregnancy (lasting ≥20 weeks of gestation with GDM status) after cannabis use. In analyses of pooled individual-level data, we used logistic regression to estimate study-type-specific odds ratios (OR) and 95% confidence intervals (CI), adjusting for potential confounders using random effect meta-analysis to combine study-type-specific ORs and 95% CIs. Stratified analyses assessed potential effect modification by preconception tobacco use and pre-pregnancy body mass index (BMI). RESULTS: Of 17,880 participants with an index pregnancy, 1198 (6.7%) were diagnosed with GDM. Before the index pregnancy, 12.5% of participants used cannabis in the past year. Overall, there was no association between preconception cannabis use in the past year and GDM (OR 0.97, 95% CI 0.79, 1.18). Among participants who never used tobacco, however, those who used cannabis more than weekly had a higher risk of developing GDM than those who did not use cannabis in the past year (OR 2.65, 95% CI 1.15, 6.09). This association was not present among former or current tobacco users. Results were similar across all preconception BMI groups. CONCLUSIONS: In this pooled analysis of preconception cohort studies, preconception cannabis use was associated with a higher risk of developing GDM among individuals who never used tobacco but not among individuals who formerly or currently used tobacco. Future studies with more detailed measurements are needed to investigate the influence of preconception cannabis use on pregnancy complications.

Race and sex differences in the association between lifespan glycemic status and midlife cognitive function: the Bogalusa heart study.

Introduction: Glycemic markers throughout life are associated with increased risk of midlife cognitive decline, yet it is unclear whether these associations differ by race and sex. Methods: This study used cross-sectional analysis of prospectively maintained cohort. 1,295 participants in the Bogalusa Heart Study, a biracial epidemiological cohort located in a micropolitan area core setting, provided fasting plasma insulin (FPI) and glucose (FPG) biannually from 1973 to 2016. Memory, executive function (EF), attention, working memory (WM), and global cognition (GC), collected 2013-2016. Glycemic markers (i.e., FPG, FPI, and HOMA-IR) averaged within lifespan epochs (≤ 20 years, childhood/adolescence (C/A); 21-40 years, early adulthood (EA); and 40-58 years, midlife). Linear regression models were analyzed for each epoch and separate models were analyzed with sex and race, education as a covariate. Results: Sample was 59% women, 34% African American (AA). Among women, higher C/A FPG was associated with poorer memory and poorer GC. Higher EA FPG was associated with poorer WM. Among men, higher EA HOMA-IR was associated with worse attention. Higher C/A HOMA-IR and FPI were associated with better memory, as was higher EA FPI. Among AA, higher C/A FPG was associated with worse attention, EF, and GC. Higher EA HOMA-IR was associated with worse attention. Higher midlife FPI and C/A HOMA-IR were associated with worse WM and EF among White Americans (WAs). Discussion: Markers indicative of hyperglycemia at different epochs were associated with worse midlife cognition in women, AAs, and WAs; but not in men. Differences in the relationship between lifespan glycemic exposures and midlife cognition could reflect broader health disparities.

DNA Methylation at ABCG1 and Long-term Changes in Adiposity and Fat Distribution in Response to Dietary Interventions: The POUNDS Lost Trial.

OBJECTIVE: To examine whether participants with different levels of diabetes-related DNA methylation at ABCG1 might respond differently to dietary weight loss interventions with long-term changes in adiposity and body fat distribution. RESEARCH DESIGN AND METHODS: The current study included overweight/obese participants from the POUNDS Lost trial. Blood levels of regional DNA methylation at ABCG1 were profiled by high-resolution methylC-capture sequencing at baseline among 673 participants, of whom 598 were followed up at 6 months and 543 at 2 years. Two-year changes in adiposity and computed tomography-measured body fat distribution were calculated. RESULTS: Regional DNA methylation at ABCG1 showed significantly different associations with long-term changes in body weight and waist circumference at 6 months and 2 years in dietary interventions varying in protein intake (interaction P < 0.05 for all). Among participants assigned to an average-protein (15%) diet, lower baseline regional DNA methylation at ABCG1 was associated with greater reductions in body weight and waist circumference at 6 months and 2 years, whereas opposite associations were found among those assigned to a high-protein (25%) diet. Similar interaction patterns were also observed for body fat distribution, including visceral adipose tissue, subcutaneous adipose tissue, deep subcutaneous adipose tissue, and total adipose tissue at 6 months and 2 years (interaction P < 0.05 for all). CONCLUSIONS: Baseline DNA methylation at ABCG1 interacted with dietary protein intake on long-term decreases in adiposity and body fat distribution. Participants with lower methylation at ABCG1 benefitted more in long-term reductions in body weight, waist circumference, and body fat distribution when consuming an average-protein diet.

Serum Metabolomic Markers of Dairy Consumption: Results from the Atherosclerosis Risk in Communities Study and the Bogalusa Heart Study.

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.

BMI change during childhood, DNA methylation change at TXNIP, and glucose change during midlife.

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.