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Background: Individuals with Alzheimer’s disease (AD) often present with coexisting vascular pathology that is expressed to different degrees and can lead to clinical heterogeneity. Objective: To examine the utility of unsupervised statistical clustering approaches in identifying neuropsychological (NP) test performance subtypes that closely correlate with carotid intima-media thickness (cIMT) in midlife. Methods: A hierarchical agglomerative and k-means clustering analysis based on NP scores (standardized for age, sex, and race) was conducted among 1,203 participants (age 48±5.3 years) from the Bogalusa Heart Study. Regression models assessed the association between cIMT ≥50th percentile and NP profiles, and global cognitive score (GCS) tertiles for sensitivity analysis. Results: Three NP profiles were identified: Mixed-low performance [16%, n = 192], scores ≥1 SD below the mean on immediate, delayed free recall, recognition verbal memory, and information processing; Average [59%, n = 704]; and Optimal [26%, n = 307] NP performance. Participants with greater cIMT were more likely to have a Mixed-low profile [OR = 3.10, 95% CI (2.13, 4.53), p

Background: Elevated lipoprotein(a) [Lp(a)] is a common risk factor for cardiovascular disease outcomes with unknown mechanisms. We examined its potential role in identifying youths who are at increased risk of developing adult atherosclerotic cardiovascular disease (ASCVD). Methods: Lp(a) levels measured in youth 9 to 24 years of age were linked to adult ASCVD and carotid intima-media thickness in the YFS (Cardiovascular Risk in Young Finns Study), in which 95 of the original 3596 participants (2.7%) recruited as children have been diagnosed with ASCVD at a median of 47 years of age. Results observed in YFS were replicated with the use of data for White participants from the BHS (Bogalusa Heart Study). In BHS, 587 White individuals had data on youth Lp(a) (measured at 8–17 years of age) and information on adult events, including 15 cases and 572 noncases. Analyses were performed with the use of Cox proportional hazard regression. Results: In YFS, those who had been exposed to high Lp(a) level in youth [defined as Lp(a) ≥30 mg/dL] had ≈2 times greater risk of developing adult ASCVD compared with nonexposed individuals (hazard ratio, 2.0 [95% CI, 1.4–2.6]). Youth risk factors, including Lp(a), low-density lipoprotein cholesterol, body mass index, and smoking, were all independently associated with higher risk. In BHS, in an age- and sex-adjusted model, White individuals who had been exposed to high Lp(a) had 2.5 times greater risk (95% CI, 0.9–6.8) of developing adult ASCVD compared with nonexposed individuals. When also adjusted for low-density lipoprotein cholesterol and body mass index, the risk associated with high Lp(a) remained unchanged (hazard ratio, 2.4 [95% CI, 0.8–7.3]). In a multivariable model for pooled data, individuals exposed to high Lp(a) had 2.0 times greater risk (95% CI, 1.0–3.7) of developing adult ASCVD compared with nonexposed individuals. No association was detected between youth Lp(a) and adult carotid artery thickness in either cohort or pooled data. Conclusions: Elevated Lp(a) level identified in youth is a risk factor for adult atherosclerotic cardiovascular outcomes but not for increased carotid intima-media thickness.

PURPOSE OF REVIEW: Dementia is a life-course condition with modifiable risk factors from cardiovascular (CV) origin, that disproportionally affects some race/ethnic groups and underserved communities in the U.S. Hypertension is the most common preventable and treatable condition that increases the risk for dementia and exacerbates dementia pathology. Epidemiological studies beginning in midlife provide strong evidence for this association. This study provides an overview of the differences in the associations across the lifespan, and the role of social determinants of health (SDoH). RECENT FINDINGS: Clinical trials support hypertension management in midlife as an avenue to lower the risk for late-life cognitive decline. However, the association between hypertension and cognition differs over the life course SDoH including higher education modify the association between hypertension and cognition which may differ by race and ethnicity. The role of blood pressure variability, interactions among CV risk factors, and cognitive assessment modalities may provide information to better understand the relationship between HTN and cognition. SUMMARY: Adopting a life-course approach that considers SDoH, may help develop tailored interventions to manage hypertension and prevent dementia syndromes. Where clinical trials to assess blood pressure management from childhood to late-life are not feasible, observational studies remain the best available evidence.

BACKGROUND AND AIMS: Identify novel metabolite associations with blood pressure (BP) salt-sensitivity and hypertension. METHODS AND RESULTS: The Genetic Epidemiology Network of Salt Sensitivity (GenSalt) Replication study includes 698 Chinese participants who underwent a 3-day baseline examination followed by a 7-day low-sodium feeding and 7-day high-sodium feeding. Latent mixture models identified three trajectories of blood pressure (BP) responses to the sodium interventions. We selected 50 most highly salt-sensitive and 50 most salt-resistant participants for untargeted metabolomics profiling. Multivariable adjusted mixed logistic regression models tested the associations of baseline metabolites with BP salt-sensitivity. Multivariable adjusted mixed linear regression models tested the associations of BP salt-sensitivity with metabolite changes during the sodium interventions. Identified metabolites were tested for associations with hypertension among 1,249 Bogalusa Heart Study (BHS) participants using multiple logistic regression. Fifteen salt-sensitivity metabolites were associated with hypertension in the BHS. Baseline values of serine, 2-methylbutyrylcarnitine and isoleucine directly associated with high salt-sensitivity. Among them, serine indirectly associated with hypertension while 2-methylbutyrylcarnitine and isoleucine directly associated with hypertension. Baseline salt-sensitivity status predicted changes in 14 metabolites when switching to low-sodium or high-sodium interventions. Among them, glutamate, 1-carboxyethylvaline, 2-methylbutyrylcarnitine, 3-methoxytyramine sulfate, glucose, alpha-ketoglutarate, hexanoylcarnitine, gamma-glutamylisoleucine, gamma-glutamylleucine, and gamma-glutamylphenylalanine directly associated with hypertension. Conversely, serine, histidine, threonate and 5-methyluridine indirectly associated with hypertension. Together, these metabolites explained an additional 7% of hypertension susceptibility when added to a model including traditional risk factors. CONCLUSIONS: Our findings contribute to the molecular characterization of BP response to sodium and provide novel biological insights into salt-sensitive hypertension.

Background Thioredoxin Interacting Protein (TXNIP) functions as a master regulator for glucose homeostasis. Hypomethylation at the 5’-cytosine-phosphate-guanine-3’ (CpG) site cg19693031 of TXNIP has been consistently related to islet dysfunction, hyperglycemia, and type 2 diabetes. DNA methylation (DNAm) may reveal the missing mechanistic link between obesity and type 2 diabetes. We hypothesize that baseline DNAm level at TXNIP in blood may be associated with glycemic traits and their changes in response to weight-loss diet interventions. Methods We included 639 adult participants with overweight or obesity, who participated in a 2-year randomized weight-loss diet intervention. Baseline blood DNAm levels were profiled by high-resolution methylC-capture sequencing. We defined the regional DNAm level of TXNIP as the average methylation level over CpGs within 500 bp of cg19693031. Generalized linear regression models were used for main analyses. Results We found that higher regional DNAm at TXNIP was significantly correlated with lower fasting glucose, HbA1c, and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at baseline (P 0.05). The interaction was attenuated to be non-significant at 2 years, presumably related to decreasing adherence to the diet intervention. Conclusions Our data indicate that higher regional DNAm level at TXNIP was significantly associated with better fasting glucose, HbA1c, and HOMA-IR; and people with higher regional DNAm levels benefited more in insulin and HOMA-IR improvement by taking the average-protein weight-loss diet.

Background: Short periods of weight loss followed by weight gain (BMI variability) has been linked to adverse cardiovascular outcomes in adults. However, less is known about the effect of long-term BMI variability from childhood on midlife class II and class III obesity. We identified this effect in a cohort of Black and White midlife adults living in a rural community. Methods: We studied 1,268 midlife participants of the Bogalusa Heart Study (age at baseline 9.5 ± 3.5 years, age at midlife 48.2 ± 5.2 years, 59.5% women, 34.4% Black) with ≥4 measurements of BMI and other traditional cardiovascular risk factors (CVRF) from childhood. Long-term BMI variability was computed as deviation from age-predicted values (DEV). Logistic regression, adjusting for age, sex, race, CVRF, depression, alcohol use, education, and employment status, was conducted to assess associations between long-term BMI variability and midlife obesity (class II and III, BMI ≥35kg/m 2 and ≥40kg/m 2 , respectively). Interactions between race, sex and long-term BMI variability were assessed. Results: Prevalence of midlife class II and class III obesity were 26.81%(n=340) and 12.7%(n=161), respectively. DEV was positively significantly associated with having midlife class II and class III obesity. For class II obesity, no significant interactions between DEV and race or sex were observed. For class III obesity, interactions of DEV with race and sex were significant; the odds of having class III midlife obesity per unit increase in DEV were greater in White participants and in men compared with Black participants and women(see Table 1). Conclusions: We identified associations between long-term BMI variability from childhood and midlife obesity. Race and sex were observed to modify the effect of BMI variability on having midlife obesity. Further studies are needed to elucidate the role of long-term BMI variability as a predictor for increased risk of midlife obesity.

Background: In adults, short periods of weight loss followed by weight gain, known as body mass index(BMI) variability, has been linked to adverse cardiovascular outcomes. However, the impact of long-term BMI variability from childhood on midlife dyslipidemia is unclear. We identified this effect in a cohort of Black and White midlife adults living in a rural community. Methods: We studied 1,268 midlife participants of the Bogalusa Heart Study (age at baseline 9.5 ± 3.5 years, age at midlife 48.2 ± 5.2 years, 59.5% women, 34.4% black) with ≥4 measurements of BMI and other traditional cardiovascular risk factors (CVRF) from childhood. Long-term BMI variability was computed as deviation from age-predicted values (DEV). The associations between long-term BMI variability and dyslipidemia and dyslipidemia subtypes were assessed by logistic regression, adjusting for age, sex, race, CVRF, depression, alcohol use, education, and employment status. Interactions between race, sex and long-term BMI variability were assessed. Results: Prevalence of midlife dyslipidemia were 88.01%(n=1116). DEV was positively significantly associated with having midlife dyslipidemia. Stratified analyses showed that men had higher odds of having midlife dyslipidemia, HDL-C Conclusions: We identified associations between long-term BMI variability from childhood and midlife dyslipidemia. Race and sex were found to modify the associations of long-term BMI variability on having midlife dyslipidemia and dyslipidemia subtypes. Further studies are needed to determine the role of long-term BMI variability as a predictor for increased risk of midlife dyslipidemia.

Introduction: Low-carbohydrate diets lead to weight loss and improvement in hemoglobin A1c and other cardiometabolic outcomes. However, there is limited research on how much of the glycemic effects of low-carbohydrate diets are mediated by weight loss. Hypothesis: The effect of a low-carbohydrate dietary intervention on hemoglobin A1c would be mediated by weight loss. Methods: We conducted a 6-month randomized clinical trial on the effects of a low-carbohydrate diet intervention (target Results: 150 participants (mean [SD] age 59 [8] years; 108 [72%] female; 88 [59%] Black) were randomized to either the low-carbohydrate diet intervention (75 participants) or usual diet (75 participants) arm. Mean (SD) HbA1c was 6.16% (0.30%) at baseline. Six-month data was collected on 142 participants (95%). Compared with the usual diet arm, the low-carbohydrate diet intervention arm had significantly greater 6-month reduction in HbA1c (net difference, -0.23% [95% CI, -0.32 to -0.14%]) and body weight (-5.9 kg [95% CI, -7.4 to -4.4 kg]). In mediation analyses, 59% of the total effect of intervention on 6-month change in hemoglobin A1c was mediated by weight measured at 3 months (Table). Conclusions: In mediation analyses, a substantial proportion (59%) of the total effect of intervention on 6-month change in hemoglobin A1c was mediated through weight measured at 3 months. Future research should further explore contributions of weight loss to reductions in glycemia in other populations.

Introduction: Current guidelines recommend ≥2 servings of fish/week for the prevention of atherosclerotic cardiovascular disease (ASCVD). However, a recent large meta-analysis suggested that the benefit may exist only for persons with a prior ASCVD event. Whether coronary artery calcium (CAC) can help to identify individuals who are likely to benefit from habitual fish consumption is unknown. Hypothesis: CAC will stratify persons who may and may not benefit from habitual fish consumption. Methods: There were 4977 participants in the Multi-Ethnic Study of Atherosclerosis who reported their frequency of fish intake and underwent CAC scanning at Visit 1. Adjusted Cox proportional hazards regression models stratified by the presence/absence of CAC assessed the association between fish intake and incident ASCVD over a median follow-up of 15.7 years. Results: The mean age was 61 years old, 53% were women, 26% were Black, and 49% of participants had prevalent CAC. A similar proportion of individuals reported consuming ≥2 servings of fish/week for those with CAC=0 and CAC >0 (35% versus 33%, p=0.12). The absolute ASCVD event rate for those with 0 (Figure 1). Each additional serving of fish/week was associated with a 9% lower risk of ASCVD for participants with CAC=0 (HR=0.91, 95% CI: 0.83-0.99) whereas there was no significant association for persons with CAC >0 (HR=1.03, 95% CI: 0.99-1.07). Conclusions: A higher amount of fish consumption was associated with a lower risk of incident ASCVD for participants with CAC=0, but not those with CAC >0, although the absolute ASCVD event rate was low for persons with CAC=0 regardless of fish consumption frequency.

Introduction: Uncontrolled high dose aspirin use impairs kidney function. Short-term low dose aspirin treatment has also been associated with kidney function in older patients. We aimed to evaluate the association of regular aspirin use with kidney function in middle-aged adults and to identify factors modifying the association. Methods: We performed cross-sectional analyses among 1,261 participants of the 2016 Bogalusa Heart Study (BHS) visit. Regular aspirin use was self-reported and confirmed by serum biomarker, salicyluric glucuronide . Aspirin users were categorized at the median of salicyluric glucuronide levels into low and high dose users. A total of 887 known metabolites were profiled from the serum. Estimated glomerular filtration rate (eGFR) was calculated using the CKD-Epi equation. We tested associations of aspirin use with eGFR and examined interactions of aspirin with serum metabolites on eGFR. Age, sex, race, education, smoking, drinking, physical activity, BMI, blood pressure, and fasting glucose were adjusted in all analyses. Results: The mean age of BHS participants was 48.2, and 133 (10.5%) were self-reported aspirin users. Serum salicyluric glucuronide level was significantly correlated with self-reported aspirin usage (P=2.00х10 -21 ). After adjusting for all covariables, mean eGFR for never, low dose, and high dose aspirin users were 92.9, 90.2, and 89.9 mL/min/1.73m 2 , respectively (P for trend=0.004). After Bonferroni correction, 28 metabolites modified the associations of aspirin use with eGFR (P-5 ), of which, 26 increased the aspirin's nephrotoxicity effect, while behenoylsphingomyelin and tricosanoylsphingomyelin significantly attenuated the eGFR lowering effect of aspirin (Table). Conclusion: Aspirin use is associated with decreased eGFR among middle-aged adults, and this association was modified by dietary, gut microbiome, and biomarkers of kidney disease, cardiovascular disease, and cancer. The findings may help develop better use strategies for regular users.

Background: Multiple chronic conditions, primarily of cardiovascular origins, are a major cause of disability, death, and health care spending. Cardiovascular multimorbidity is also associated with multiplicative risk of morality and substantially lower life expectancy, which may exacerbate health disparities. However, its impact in a rural and low socioeconomic community with a high proportion of minorities is understudied. We aimed to describe multimorbidity prevalence and patterns by race, sex, and socioeconomic status in a middle-aged, community-based cohort. Methods: We examined 1,298 Black (35%) and White (65%) individuals (mean age 48.17 ± SD 5.27 years; 59% female) from the Bogalusa Heart Study, a rural, community-based, longitudinal cohort in Bogalusa, Louisiana, between 2013 and 2016. Eight chronic conditions (CCs) selected based on CMS (Centers for Medicare & Medicaid Services) guidance were defined using data from self-reported medical history, medication use, and physiological or laboratory measures. We defined multimorbidity as the coexistence of two or more of these conditions. The prevalence of cardiovascular multimorbidity and the most commonly occurring dyads and triads were assessed by race, sex, and socioeconomic factors using chi-square tests. Results: We found that 70% of the 1,298 participants had ≥2 CCs, while 31% had ≥3 CCs. The most prevalent conditions were dyslipidemia (87.9%, n=1,141), hypertension (66.6%, n=864), and diabetes (19.7%, n=255). The prevalence of multimorbidity was higher in Black than in White (76.8%, n=344 vs. 66.5%, n=565; p Conclusion: Cardiovascular multimorbidity is highly prevalent in midlife among participants of the Bogalusa cohort compared to national and even state-wide levels. These findings have critical public health ramifications and support the need to better study multiple CCs in rural, underserved populations to create tailored interventions that are effective among adults in their most productive years of life despite geographic and income barriers.

Introduction: Mechanisms for metabolically healthy obesity (MHO) are not well studied. Methods: We performed cross-sectional analyses among 1,261 participants of the Bogalusa Heart Study 2013-2016 survey. A total of 887 known serum metabolites were profiled using an untargeted approach. Participants who met all the following five criteria were considered metabolically healthy, otherwise, unhealthy: 1) SBP Results: Among 648 obese participants (BMI≥30 kg/m 2 ), 66 (10.2%) had MHO. After Bonferroni correction, 26 metabolites differed between MHO and metabolically unhealthy obesity (MUO) groups. Amino acids serine , glycine, and histidine , fatty acid N-linoleoylserine , 4 sphingolipids, and 3 plasmalogens were significantly higher among MHO individuals. These metabolites are functionally relevant to metabolic health ( Table ). Carbohydrates mannose , lactate, and pyruvate , urate , amino acids glutamate , 1-carboxyethylvaline , 1-carboxyethylleucine , 3-methyl-2-oxovalerate , and 3-methyl-2-oxobutyrate , PE(18:0/18:2(9Z,12Z)) , and 5 diacylglycerols were significantly higher in the MUO group. These metabolites are mostly food additives or reduce gut microbiota diversity ( Table ). Furthermore, histidine was associated with metabolic health only among overweight and obese participants. Odds ratios of being metabolically healthy per SD increase of histidine among normal weight, overweight, and obese participants were 1.05 (95% CI: 0.83-1.32), 1.54 (95% CI: 1.10-2.14), and 2.12 (95% CI: 1.56-2.89), respectively (P for group difference=1.41E-4). Conclusion: We identified potential intervention targets to improve metabolic health in obesity.

Background: Despite known associations of epigenetic age acceleration (EAA), or increased DNA methylation (DNAm)-based age relative to chronological age, with Alzheimer’s disease, few studies have investigated the relation of EAA with midlife cognitive function. We examined cross-sectional associations of EAA with cognition among the 1,252 middle-aged participants of the Bogalusa Heart Study 2013-2016 study visit. Methods: Whole-blood DNA methylation data was generated using the Illumina HumanMethylation450 BeadChip. Four EAA measures, including extrinsic EAA (EEAA), intrinsic EAA (IEAA), PhenoAA and GrimAA, were derived from the methylation data. Cognitive function was assessed by a standard battery of eight neurocognitive tests covering five cognition domains, and a global cognition score was calculated. Associations of EAA measures with cognitive function were assessed by 3 multivariable models sequentially adding (i) demographics (age, sex, race, education) and vocabulary; (ii) lifestyle behaviors (smoking, alcohol drinking, and depression), and (iii) clinical measures (blood pressure, lipids, body mass index, glycated hemoglobin, medication, and white blood cell count. Results: After Bonferroni correction (α=1.39E-3), PhenoAA and GrimAA were significantly associated with decreased processing speed (lower Digit coding test score) and decreased working memory (higher trail making test A score). GrimAA was also associated with lower global cognition score ( Table ). EEAA was associated with decreased processing speed (lower Digit coding test). After adjusting for lifestyle and clinical measures, such associations were slightly attenuated but remained at least nominally significant. IEAA was not associated with any cognitive test results. Conclusions: EAA measured by PhenoAA, GrimAA, and EEAA were significantly associated with decreased processing speed, working memory, and/or global cognition. The associations were independent of known cognitive decline risk factors.

Background: Thioredoxin-interacting protein (TXNIP) is a central master regulator of whole-body glucose homeostasis in humans; and DNA methylation (DNAm) at TXNIP has been identified to be related to diabetes. It remains unknown whether dynamic changes in DNAm at TXNIP are associated with glycemic changes; and whether early-life adiposity changes modify such association. Hypothesis: We hypothesized that dynamic changes in DNAm at TXNIP are associated with glycemic changes in midlife, and early-life adiposity changes may modify such association. Methods: A total of 594 Bogalusa Heart Study participants who had DNAm measurements at two time points in midlife were included in this study. Of them, 353 participants had at least 4 examinations of BMI during childhood and adolescence (aged 4–19 years). The area under the curve (AUC) was calculated as a measure of long-term burden (total AUC) and trends (incremental AUC) of BMI during childhood and adolescence. Results: We found 25.3% of participants showed greater than 5% DNAm change at TXNIP during a mean of 6.2 years follow-up. Increase in DNAm at TXNIP was significantly associated with decrease in FPG independent of cell-type composition and other covariates ( P P -interaction=0.003). Conclusions: Our results indicate that changes in DNAm at TXNIP are significantly associated with dynamics in FPG in midlife, and such association is modified by BMI changes during childhood and adolescence.

Objective: Adiponectin (ApN), has anti-inflammatory and anti-atherogenic properties. Low levels of ApN are found even after normalization of glucose in patients with diabetes, and are implicated in atherosclerosis, and dementia onset but results vary across the lifespan. We assessed the relation of ApN levels in young adulthood, with midlife atherosclerosis, measured by carotid intima media thickness (cIMT), and with cognitive function among Black and White individuals from the Bogalusa Heart Study (BHS). Methods: A total of 604 participants from the BHS, a community cohort in rural Louisiana, were examined for ApN levels with lowest quartile of ApN levels (th percentile (>0.88mm), and a global cognitive score(GCS) standardized for age, race and sex. Adjusted models included education attendance. Results: Individuals with low-ApN were more likely men [ 56.2% (77), pth (P=0.001), and cIMT ≥ 50 th and GCS (P=0.002). ( Figure1) In mediation analysis, the ratio of Indirect effect/Total effect was 0.108, indicating that ~11% of the effect of low-ApN on GCS was mediated by cIMT. Education was not associated with low-ApN. Conclusion: Low-ApN levels in early adulthood was associated with poor cognition after ~10 years of follow-up, and the association was partially mediated by subclinical atherosclerosis. This suggests that ApN may play a role in neurodegeneration mechanisms and contribute to the development of dementia, underscoring the importance of addressing cardiometabolic influences earlier in the lifespan to prevent/delay cognitive decline.

Introduction: There is a lack of objective biomarkers of dietary intake. Untargeted studies can unbiasedly identify dairy biomarkers and inform the creation of robust dietary assessment tools that integrate questionnaire and biospecimen data. Methods: Dairy products from interviewer-administered questionnaires were categorized as either low-fat or high-fat dairy. Total dairy was a composite of low-fat and high-fat dairy items. Linear regression models were used to assess associations between dairy intake and 360 serum metabolites in the Atherosclerosis Risk in Communities (ARIC) Study (n=3907). Significant associations were then tested for replication in the Bogalusa Heart Study (BHS) (n=819). Results: In the ARIC study, 34 dairy-metabolite associations were identified (total dairy, n = 16; low-fat dairy, n = 10; high-fat dairy, n = 8). Total dairy shared 7 metabolic associations each with low-fat dairy and high-fat dairy. Low-fat dairy was associated with pantothenate, vitamin B5, and the catabolic product of vitamin B6, pyridoxate. High-fat dairy was associated with one amino acid, 3-hydroxy-2-ethylpropionate, and eight lipid metabolites, including myristate (14:0), 10-nonadecenoate (19:1n9), and myristoleate (14:1n5). Of the metabolites available for replication in BHS (total dairy, n = 15; low-fat dairy, n = 9; high-fat dairy, n = 8), 2 total dairy metabolites were replicated and 2 low-fat dairy metabolites were replicated ( Table ). Conclusions: We identified metabolomic markers of total, low-fat, and high-fat dairy. Pantothenate, myristate (14:0), and tiglyl carnitine replicated across two large, diverse study populations, suggesting that they are markers of dairy consumption.

Longitudinal studies provide rich sources of data to explore early risk factors for future CV diseases. However, cohort participants often move away from their initial recruitment site. Therefore, we are assessing feasibility of mailing of devices to the home for collection of biometric data followed by an in-person assessment to validate the home devices. Participants (N=215) from the Bogalusa Heart Study, National Growth & Health Study and the Princeton Lipid Research Study who were initially enrolled as children in the 1970s and 1980s were recruited. Devices sent to the home ( Table ) measure anthropometrics, BP, HR, heart rhythm, resting metabolic rate, O2 saturation, glucose, total cholesterol, physical activity, diet, sleep duration/quality, and arterial stiffness. Stool and saliva are also collected for microbiome, DNA and cotinine. General issues encountered include institutional firewall requiring permission to load apps on an iPAD, apps requiring wi-fi or an email, complicated instructions for participants, different processes for account setup, data retrieval, cleaning/disinfection, need to delete old data/resetting for each device, and differing exported data file formats requiring extensive programming to import into statistical software. This feasibility study will provide new opportunities to continue to follow our participants who have provided invaluable contributions to science for the last 40 years.

Introduction: Childhood cardiovascular risk factors have been associated with increased risk of adult cardiovascular disease, but how they are associated with adult physical, emotional and social functioning is not well understood. Hypothesis: We addressed the hypothesis that the International Childhood Cardiovascular Cohort (i3C) Consortium childhood risk score would be associated with worse physical, social and emotional functioning in adulthood. Methods: The i3C childhood combined risk score is the average of five childhood risk factors (body mass index, systolic blood pressure, youth smoking, total cholesterol and triglycerides) on the z-score scale. Self-reported measures of physical (e.g., pain, functioning, fatigue), social (e.g., social isolation, satisfaction with social role) and emotional functioning (e.g., anxiety, depression) were assessed in adulthood in a subset of two i3C cohorts, the NHLBI Growth and Health Study (NGHS) and the Princeton Lipid Research Study (PLRS). Potential covariates included cohort (as a proxy for age, given no overlap in ages between cohorts), sex, race (Black vs. White), own education, parental education, marital status, and self-reported hypertension, diabetes and cancer. Interactions between the i3C risk score and cohort (age) were evaluated. Results: Ninety-two NGHS (100% female, 46% Black, mean±SD age 44.5±0.6 years) and 75 PLRS (77% female, 31% Black, 60.6±3.4 years) participants were included in analyses. In adjusted models, a higher i3C risk score was associated with worse physical functioning, global pain score, pain interference with everyday activities, and fatigue in the older PLRS participants, but only with global pain score in the younger NGHS participants (all p[int] Conclusions: In conclusion, higher childhood cardiovascular risk factors are associated with worse physical, social and emotional health in adulthood, even in this limited sample of predominantly Black and White women followed from childhood. These effects are more prominent in older than younger adults, when issues such as pain and sleep problems become more prevalent.

Current guidelines call for peer-reviewed evidence of efficacy and safety for commercial weight loss programs to be recommended as options for those seeking to lose weight.This study investigated the Ideal Protein (IP) system, a commercial weight loss program, compared to a guideline-based, low-calorie/low-fat (LCLF) dietary behavioral intervention on body weight and CVD risk factors in adults with obesity.In this randomized, assessor-blinded, parallel-group trial, 192 participants with body mass index (BMI) ≥30 and ≤49 kg/mThe mean ± SD of change in weight at 3 months was -9.6 ± 12.7 kg in the IP group as compared to -1.6 ± 27.2 kg in the LFLC group. The mean between-group difference in change at 3 months was -8.1 kg (95% confidence interval [CI] -16.6 to 0.6;The present findings demonstrate the efficacy and safety of the IP weight loss program as compared to a guideline-based LCLF dietary behavioral intervention among black and white adults with obesity and CVD risk factors, providing support for the effectiveness of the program.

Cross-sectional studies have reported that high sodium sensitivity is more common among individuals with hypertension. Experimental studies have also reported various animal models with sodium-resistant hypertension. It is unknown, however, whether sodium sensitivity and resistance precede the development of hypertension. We conducted a feeding study, including a 7-day low-sodium diet (1180 mg/day) followed by a 7-day high-sodium diet (7081 mg/day), among 1718 Chinese adults with blood pressure (BP) P P =0.006 for nonlinear trend). Furthermore, a J-shaped association between systolic BP responses to sodium intake and incident hypertension was identified ( P

Genetic information may help to identify individuals at increased risk for hypertension in early life, prior to the manifestation of elevated blood pressure (BP) values. We examined 369 Black and 832 White Bogalusa Heart Study (BHS) participants recruited in childhood and followed for approximately 37 years. The multi-ancestry genome-wide polygenic risk scores (PRSs) for systolic BP (SBP), diastolic BP (DBP), and hypertension were tested for an association with incident hypertension and stage 2 hypertension using Cox proportional hazards models. Race-stratified analyses were adjusted for baseline age, age2, sex, body mass index, genetic principal components, and BP. In Black participants, each standard deviation increase in SBP and DBP PRS conferred a 38% (p = 0.009) and 22% (p = 0.02) increased risk of hypertension and a 74% (p < 0.001) and 50% (p < 0.001) increased risk of stage 2 hypertension, respectively, while no association was observed with the hypertension PRSs. In Whites, each standard deviation increase in SBP, DBP, and hypertension PRS conferred a 24% (p < 0.05), 29% (p = 0.01), and 25% (p < 0.001) increased risk of hypertension, and a 27% (p = 0.08), 29% (0.01), and 42% (p < 0.001) increased risk of stage 2 hypertension, respectively. The addition of BP PRSs to the covariable-only models generally improved the C-statistics (p < 0.05). Multi-ancestry BP PRSs demonstrate the utility of genomic information in the early life prediction of hypertension.

Background: Genetic information may help to identify individuals in childhood who are at increased risk for cardiometabolic disease. Methods: We included 1201 BHS (Bogalusa Heart Study) participants (832 White participants and 369 Black participants) who were followed up to 42.3 years, starting at a mean age of 9.8 years. A validated genome-wide polygenic risk score (PRS) was tested for association with midlife body mass index (BMI), fasting plasma glucose, and systolic blood pressure using multiple linear regression models. Cox proportional hazards models tested associations of the PRS with incident obesity, diabetes, and hypertension. All analyses were conducted according to race and adjusted for baseline age, sex, ancestry, and BMI. Results: The constructed PRS was significantly and modestly correlated with midlife BMI in both White and Black participants, with correlation coefficients of 0.27 ( P =1.94×10 −8 ) and 0.16 ( P =5.50×10 −3 ), respectively. In White participants, per SD increase of PRS was associated with an average 1.29 kg/m 2 higher BMI ( P =4.44×10 −9 ), 2.82 mg/dL higher fasting plasma glucose ( P =1.17×10 −3 ), and 1.09 mm Hg higher systolic blood pressure ( P =3.57×10 −2 ) at midlife. The PRS also conferred a 26% higher increased risk of obesity ( P =3.50×10 −6 ) in White participants. In addition, the variance in midlife BMI explained increased from 0.1973 to 0.2293 when PRS was added to the model including age, sex, principal components, and baseline BMI ( P Conclusions: Adiposity-related genetic information independently predicted cardiometabolic health in White BHS participants. Null associations observed in Black BHS participants highlight the urgent need for PRS development in multi-ancestry populations.

Background: Low-carbohydrate diets decrease hemoglobin A1c among patients with type 2 diabetes mellitus. However, evidence on effects of low-carbohydrate diets on hemoglobin A1c among individuals with prediabetes is limited. Methods: We conducted a randomized parallel-group trial of 150 adults aged 40-70 years with untreated hemoglobin A1c from 6.0-6.9%. Participants were assigned to a healthy low-carbohydrate diet (target Results: Mean age was 59 years; 72% were female and 59% were Black. 95% completed the study. Participants in the low-carbohydrate arm had significantly greater 6-month decrease in hemoglobin A1c (net difference, -0.23% [95% CI, -0.32 to -0.14%]) , fasting plasma glucose (net difference, -10.3 mg/dL [95% CI, -15.7 to -4.9 mg/dL]) , and body weight (net difference, -5.9 kg [95% CI, -7.2 to -4.7 kg]) compared with usual diet arm. At 6 months, 53% in the low-carbohydrate arm and 32% in the usual diet arm had hemoglobin A1c Conclusion: A healthy low-carbohydrate diet led to improvements in glycemic and other cardiometabolic outcomes in adults with elevated hemoglobin A1c and could be recommended for prevention of type 2 diabetes mellitus. Disclosure K.S.Dorans: None. M.J.O'brien: None. G.I.Uwaifo: None. J.He: None. L.A.Bazzano: None. L.Qi: None. H.He: None. J.Chen: None. L.J.Appel: n/a. F.Hu: None. J.Samet: None. K.T.Mills: None. Funding National Institute of General Medical Sciences (1P20GM109036-01A1) . The California Walnut Commission (Folsom, CA) supported the study by providing walnuts. Shakes and bars were donated by The Simply Good Foods Company (Denver, CO) . Sugar replacement samples were provided by Swerve LLC (New Orleans, LA) .

Objective This study aimed to examine the temporal relationship between body mass index (BMI) and uric acid (UA), and their joint effect on blood pressure (BP) in children and adults. Methods The longitudinal cohorts for temporal relationship analyses consisted of 564 and 911 subjects examined twice 5–14 years apart from childhood to adulthood. The cross-sectional cohorts for mediation analyses consisted of 3102 children and 3402 nondiabetic adults. Cross-lagged panel analysis models were used to examine the temporal relationship between BMI and UA, and mediation analysis models the mediation effect of UA on the BMI–BP association. Results After adjusting for age, race, sex and follow-up years in children, and additionally smoking and alcohol drinking in adults, the path coefficients (standardized regression coefficients) from baseline BMI to follow-up UA (0.145 in children and 0.068 in adults) were significant, but the path coefficients from baseline UA to follow-up BMI (0.011 in children and 0.016 in adults) were not. In mediation analyses, indirect effects through UA on the BMI-systolic BP association were estimated at 0.028 (mediation effect = 8.8%) in children and 0.033 (mediation effect = 13.5%) in adults (P Conclusions Changes in BMI precede alterations in UA, and the BMI–BP association is in part mediated through BMI-related increase in UA both in children and in adults. These findings have implications for addressing mechanisms of obesity hypertension beginning in early life.

Importance The impact of long‐term burden of excessive body weight, beginning in childhood, on inflammatory status in adulthood has been poorly described. Objective To characterize the longitudinal body mass index (BMI) trajectory from childhood and examine its relationship with inflammatory status in adulthood. Methods We included 1285 adults who had 4–15 repeat measurements of BMI from childhood to adulthood. The area under the curve (AUC) of growth curves was calculated to characterize long‐term burden (total AUC) and trends (incremental AUC) of BMI. Results After adjusting for covariates, higher values of BMI in terms of childhood and adulthood, as well as total and incremental AUC, were strongly associated with elevated levels of adult C‐reactive protein (CRP) in the four race‐sex groups. There were significant differences in linear and nonlinear curve parameters between the normal and high CRP groups for all race‐sex groups (P < 0.01). Compared with participants who had consistently low BMI in both childhood and adulthood, participants with high BMI in adulthood had higher CRP levels (P < 0.001), irrespective of their childhood BMI status; participants with high BMI in childhood but low BMI in adulthood had similar adult CRP levels. Interpretation The impact of excessive body weight on inflammation is cumulative and exacerbated over time. The influence of childhood overweight/obesity on inflammatory status in adulthood can be alleviated by reducing adiposity in adulthood., Low‐grade inflammation is a mechanistic link between obesity and cardiometabolic disorders. We utilized longitudinal data from the Bogalusa Heart Study to examine the associations of cumulative burden and trajectory measures of body weight from childhood with chronic inflammation in adulthood.

OBJECTIVES Heart disease is the most common cause of death in patients with nonalcoholic fatty liver disease (NAFLD). Emerging data have shown that NAFLD may affect subclinical myocardial remodeling, mainly left ventricular hypertrophy; however, evidence from the prospective studies is still lacking. METHODS Prospective analyses were performed to investigate the association of fatty liver index (FLI) with left ventricular mass (LVM) among 1962 participants from the Bogalusa Heart Study (BHS, 1995-2010) and 1547 participants from the Cardiovascular Risk in Young Finns Study (YFS, 2001-2011) free of cardiovascular diseases (CVD) at baseline. LVM was assessed by two-dimensional guided M-mode echocardiography and indexed (LVMI) to body height (m2.7). Multivariable regression models were applied after adjustment for traditional CVD risk factors. RESULTS In both cohorts, we observed significant and positive associations between FLI and LVM (BHS: β=0.59, P