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Objective: The Developmental Origins of Disease hypothesis has spurred increased interest in how prenatal exposures affect lifelong health, while mechanisms such as epigenetics may explain the multigenerational influences on health. Such factors are not well captured within conventional epidemiologic study designs. We explored the feasibility of collecting information on the offspring and grand-offspring of participants in a long-running study. Design: The Bogalusa Heart Study is a study, begun in 1973, of life-course cardiovascular health in a semirural population (65% white and 35% black). Main measures: Female participants who had previously provided information on their pregnancies were contacted to obtain contact information for their daughters aged 12 and older. Daughters were then contacted to obtain reproductive histories, and invited for a clinic or lab visit to measure cardiovascular risk factors. Results: Two hundred seventy-four daughters of 208 mothers were recruited; 81% (223) had a full clinic visit and 19% (51) a phone interview only. Forty-five percent of the daughters were black, and 55% white. Mean and median age at interview was 27, with 15% under the age of 18. The strongest predictors of participation were black race, recent maternal participation in the parent study, and living in or near Bogalusa. Simple correlations for cardiovascular risk factors across generations were between r = 0.19 (systolic blood pressure) and r = 0.39 (BMI, LDL). Conclusion: It is feasible to contact the children of study participants even when participants are adults, and initial information on the grandchildren can also be determined in this manner. [ABSTRACT FROM AUTHOR]

The authors examined the association between cigarette smoking and risk of erectile dysfunction among 7,684 Chinese men aged 35-74 years without clinical vascular disease. Cigarette smoking and erectile dysfunction were assessed by questionnaire. Vascular risk factors were measured according to standard methods. After adjustment for age, education, alcohol consumption, physical inactivity, diabetes, hypertension, overweight, and hypercholesterolemia, the odds ratio of erectile dysfunction was 1.41 (95% confidence interval (CI): 1.09, 1.81) for cigarette smokers compared with never smokers. There was a statistically significant dose-response relation between cigarette smoking and risk of erectile dysfunction (p(trend) = 0.005). Multivariate-adjusted odds ratios of erectile dysfunction were 1.27 (95% CI: 0.91, 1.77), 1.45 (95% CI: 1.08, 1.95), and 1.65 (95% CI: 1.08, 2.50) for those who smoked 1-10, 11-20, and more than 20 cigarettes per day, respectively, compared with never smokers. The association was stronger in participants with diabetes (odds ratio = 3.29, 95% CI: 1.49, 7.27) than in participants without diabetes (odds ratio = 1.33, 95% CI: 1.03, 1.73). If the association is causal, an estimated 22.7% of erectile dysfunction cases (11.8 million cases) among Chinese men are attributable to cigarette smoking. This 2000-2001 study of Chinese men documented an independent and dose-response relation between cigarette smoking and risk of erectile dysfunction. [ABSTRACT FROM AUTHOR]

Context: Epidemiologic studies have suggested that folate intake decreases risk of cardiovascular diseases. However, the results of randomized controlled trials on dietary supplementation with folic acid to date have been inconsistent.Objective: To evaluate the effects of folic acid supplementation on risk of cardiovascular diseases and all-cause mortality in randomized controlled trials among persons with preexisting cardiovascular or renal disease.Data Sources: Studies were retrieved by searching MEDLINE (January 1966-July 2006) using the Medical Subject Headings cardiovascular disease, coronary disease, coronary thrombosis, myocardial ischemia, coronary stenosis, coronary restenosis, cerebrovascular accident, randomized controlled trial, clinical trials, homofolic acid, and folic acid, and the text words folic acid and folate. Bibliographies of all retrieved articles were also searched, and experts in the field were contacted.Study Selection: From 165 relevant retrieved reports, 12 randomized controlled trials compared folic acid supplementation with either placebo or usual care for a minimum duration of 6 months and with clinical cardiovascular disease events reported as an end point.Data Extraction: Data on study design, characteristics of participants, changes in homocysteine levels, and cardiovascular disease outcomes were independently abstracted by 2 investigators using a standardized protocol.Data Synthesis: Studies including data from 16 958 participants with preexisting vascular disease were analyzed using a random-effects model. The overall relative risks (95% confidence intervals) of outcomes for patients treated with folic acid supplementation compared with controls were 0.95 (0.88-1.03) for cardiovascular diseases, 1.04 (0.92-1.17) for coronary heart disease, 0.86 (0.71-1.04) for stroke, and 0.96 (0.88-1.04) for all-cause mortality. The relative risk was consistent among participants with preexisting cardiovascular or renal disease.Conclusions: Folic acid supplementation has not been shown to reduce risk of cardiovascular diseases or all-cause mortality among participants with prior history of vascular disease. Several ongoing trials with large sample sizes might provide a definitive answer to this important clinical and public health question. [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]

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.

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., 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 © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: None.

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.

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.

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., Competing Interests: The Bogalusa Heart Study was supported by the National Institute on Aging of the National Institutes of Health (awards R01AG041200, R01AG062309, R01AG077000, and R33AG057983) and the National Institute of General Medical Sciences of the National Institutes of Health (award P20GM109036). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

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/m 2 (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., (Copyright © 2023 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: Disclosures None.

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., (© 2023 The Authors. Paediatric and Perinatal Epidemiology published by John Wiley & Sons Ltd. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Background: Diabetes and diabetes complications are on the rise in US adults aged <65 years, while onset of menarche at a younger age is also increasing. We examined the associations of age at menarche with type 2 diabetes among women aged <65 years and with cardiovascular disease (CVD) complications among women with diabetes., Methods: Using the nationally representative cross-sectional National Health and Nutrition Examination Survey 1999-2018, women aged 20-65 years free of cancer were included in the current analysis. Diabetes was defined as a self-reported diabetes diagnosis. CVD was defined as coronary heart disease or stroke. Age at menarche was self-reported age of first menstruation and categorised into ≤10, 11, 12, 13, 14 and ≥15 years., Results: Of 17 377 women included in the analysis, 1773 (10.2%) reported having type 2 diabetes. Earlier age at menarche was associated with type 2 diabetes compared with median age at menarche of 13 years, after adjustment for age, race/ethnicity, education, parity, menopause status and family history of diabetes, smoking status, physical activity, alcohol consumption and body mass index (p for trend=0.02). Among women with diabetes, earlier age at menarche was associated with stroke with similar adjustment (p for trend=0.03), but not with total CVD. Extremely early age at menarche (≤10 years) was significantly associated with stroke (adjusted OR 2.66 (95% CI 1.07 to 6.64)) among women aged <65 years with diabetes with similar adjustment., Conclusions: Earlier age at menarche was associated with type 2 diabetes among young and middle-aged women in the USA and with stroke complications among these women living with diabetes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (© 2023 by the American Diabetes Association.)

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., 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 Gwizdala, Bazzano, Newton and Carmichael.)

The Preconception Period Analysis of Risks and Exposures Influencing Health and Development (PrePARED) Consortium creates a novel resource for addressing preconception health by merging data from numerous cohort studies. In this paper, we describe our data harmonization methods and results. Individual-level data from 12 prospective studies were pooled. The crosswalk-cataloging-harmonization procedure was used. The index pregnancy was defined as the first postbaseline pregnancy lasting more than 20 weeks. We assessed heterogeneity across studies by comparing preconception characteristics in different types of studies. The pooled data set included 114,762 women, and 25,531 (22%) reported at least 1 pregnancy of more than 20 weeks' gestation during the study period. Babies from the index pregnancies were delivered between 1976 and 2021 (median, 2008), at a mean maternal age of 29.7 (standard deviation, 4.6) years. Before the index pregnancy, 60% of women were nulligravid, 58% had a college degree or more, and 37% were overweight or obese. Other harmonized variables included race/ethnicity, household income, substance use, chronic conditions, and perinatal outcomes. Participants from pregnancy-planning studies had more education and were healthier. The prevalence of preexisting medical conditions did not vary substantially based on whether studies relied on self-reported data. Use of harmonized data presents opportunities to study uncommon preconception risk factors and pregnancy-related events. This harmonization effort laid the groundwork for future analyses and additional data harmonization., (Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2023.)

Context: Carnitine palmitoyltransferase-1A, encoded by the CPT1A gene, plays a key role in the oxidation of long-chain fatty acids in the mitochondria and may be important in triglyceride metabolism. Previous work has shown that high fat intake was negatively associated with CPT1A methylation and positively associated with CPT1A expression., Objective: We aim to investigate the association of DNA methylation (DNAm) at the CPT1A gene with reductions in triglycerides and triglyceride-rich lipoproteins (TRLs) in response to weight-loss diet interventions., Methods: The current study included 538 White participants, who were randomly assigned to 1 of 4 diets varying in macronutrient components. We defined the regional DNAm at CPT1A as the average methylation level over CpGs within 500 bp of the 3 triglyceride-related DNAm sites., Results: Dietary fat intake significantly modified the association between baseline DNAm at CPT1A and 2-year changes in total plasma triglycerides, independent of concurrent weight loss. Among participants assigned to a low-fat diet, a higher regional DNAm level at CPT1A was associated with a greater reduction in total plasma triglycerides at 2 years (P = .01), compared with those assigned to a high-fat diet (P = .64) (P interaction = .018). Further investigation on lipids and apolipoproteins in very low-density lipoprotein (VLDL) revealed similar interaction patterns for 2-year changes in VLDL-triglycerides, VLDL-cholesterol, and VLDL-apolipoprotein B (P interaction = .009, .002, and .016, respectively), but not for VLDL-apoC-III (P interaction = .36)., Conclusion: Participants with a higher regional DNAm level at CPT1A benefit more in long-term improvement in triglycerides, particularly in the TRLs and related apolipoproteins when consuming a low-fat weight-loss diet., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose of Review: The aim of this study was to provide an overview of the burden, pathogenesis, and recent recommendations for treating hypertension among people living with HIV (PLWH). This review is relevant because of the increase in the prevalence of HIV as a chronic disease and the intersection of the increasing prevalence of hypertension., Recent Findings: The contribution of HIV to the pathogenesis of hypertension is complex and still incompletely understood. Evidence suggests that chronic inflammation from HIV, antiretroviral treatment (ART), and comorbidities such as renal disease and insulin resistance contribute to developing hypertension in PLWH. Treatment is not distinct from guidelines for HIV-noninfected people. Nonpharmacological guidelines such as decreasing blood pressure by promoting a healthy lifestyle emphasizing exercise, weight loss, and smoking cessation are still recommended in the literature. The pharmacological management of hypertension in PLWH is similar, but special attention must be given to specific drugs with potential interaction with ART regimens. Further research is needed to investigate the pathways and effects of hypertension on HIV., Summary: There are different pathways to the pathogenesis of hypertension in PLWH. Clinicians should take it into consideration to provide more precise management of hypertension in PLWH. Further research into the subject is still required., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Sleep and diet contribute to cardiometabolic disease, but evidence is sparse for the association between these behaviors. This study analyzed the cross-sectional relationship between diet quality and multiple sleep outcomes in the Bogalusa Heart Study (BHS)., Methods: Diet and sleep characteristics, including insomnia and sleep apnea symptoms, were measured with validated questionnaires. Poisson regression using generalized estimating equations with a log link estimated prevalence rate ratios (PRR) of sleep outcomes by dietary pattern scores (quintile (Q) and per SD). Models were adjusted for body mass index (BMI), multi-level socioeconomic factors, physical activity, depressive symptoms, and other potential confounders., Results: In 824 participants, higher diet quality, measured by the Alternate Healthy Eating Index-2010, was associated with lower sleep apnea risk score after adjustment (PRR [95% confidence interval (CI)] Q5 vs. Q1: 0.59 [0.44, 0.79], per SD increase: 0.88 [0.81, 0.95], p -trend < 0.0001). There were no statistically significant associations with the Healthy Eating Index 2015 or the Alternate Mediterranean dietary patterns, or for insomnia symptoms or a healthy sleep score., Conclusions: Higher diet quality, after adjustment for BMI, was associated with a lower sleep apnea risk score in a cohort with substantial minority representation from a semi-rural, lower-income community., Competing Interests: The authors declare no conflict of interest.

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.

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 < 0.001] compared to Optimal. After adjusting for education and cardiovascular (CV) risks, results remained. The association with GCS tertiles was more attenuated [lowest (34%, n = 407) versus highest (33%, n = 403) tertile: adjusted OR = 1.66, 95% CI (1.07, 2.60), p = 0.024]., Conclusion: As early as midlife, individuals with higher subclinical atherosclerosis were more likely to be in the Mixed-low profile, underscoring the potential malignancy of CV risk as related to NP test performance, suggesting that classification approaches may aid in identifying those at risk for AD/vascular dementia spectrum illness.

Importance: Low-carbohydrate diets decrease hemoglobin A1c (HbA1c) among patients with type 2 diabetes at least as much as low-fat diets. However, evidence on the effects of low-carbohydrate diets on HbA1c among individuals with HbA1c in the range of prediabetes to diabetes not treated by diabetes medications is limited., Objective: To study the effect of a behavioral intervention promoting a low-carbohydrate diet compared with usual diet on 6-month changes in HbA1c among individuals with elevated untreated HbA1c., Design, Setting, and Participants: This 6-month randomized clinical trial with 2 parallel groups was conducted from September 2018 to June 2021 at an academic medical center in New Orleans, Louisiana. Laboratory analysts were blinded to assignment. Participants were aged 40 to 70 years with untreated HbA1c of 6.0% to 6.9% (42-52 mmol/mol). Data analysis was performed from November 2021 to September 2022., Interventions: Participants were randomized to a low-carbohydrate diet intervention (target <40 net grams of carbohydrates during the first 3 months; <60 net grams for months 3 to 6) or usual diet. The low-carbohydrate diet group received dietary counseling., Main Outcomes and Measures: Six-month change in HbA1c was the primary outcome. Outcomes were measured at 0, 3, and 6 months., Results: Of 2722 prescreened participants, 962 underwent screening, and 150 were enrolled (mean [SD] age, 58.9 [7.9] years; 108 women [72%]; 88 Black participants [59%]) and randomized to either the low-carbohydrate diet intervention (75 participants) or usual diet (75 participants) group. Six-month data were collected on 142 participants (95%). Mean (SD) HbA1c was 6.16% (0.30%) at baseline. Compared with the usual diet group, the low-carbohydrate diet intervention group had significantly greater 6-month reductions in HbA1c (net difference, -0.23%; 95% CI, -0.32% to -0.14%; P < .001), fasting plasma glucose (-10.3 mg/dL; 95% CI, -15.6 to -4.9 mg/dL; P < .001), and body weight (-5.9 kg; 95% CI, -7.4 to -4.4 kg; P < .001)., Conclusions and Relevance: In this randomized clinical trial, a low-carbohydrate dietary intervention led to improvements in glycemia in individuals with elevated HbA1c not taking glucose-lowering medication, but the study was unable to evaluate its effects independently of weight loss. This diet, if sustained, might be a useful dietary approach for preventing and treating type 2 diabetes, but more research is needed., Trial Registration: ClinicalTrials.gov Identifier: NCT03675360.

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 <0.0001). No associations were observed in Black participants., 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.

Purpose of Review: Dementia is a life-course condition with modifiable risk factors many from cardiovascular (CV) origin, and disproportionally affects some race/ethnic groups and underserved communities in the USA. Hypertension (HTN) 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 HTN management in midlife as an avenue to lower the risk for late-life cognitive decline. However, the association between HTN and cognition differs over the life course. SDoH including higher education modify the association between HTN and cognition which may differ by race and ethnicity. The role of blood pressure (BP) 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 HTN and prevent dementia syndromes. Where clinical trials to assess BP management from childhood to late-life are not feasible, observational studies remain the best available evidence., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

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 1249 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., Competing Interests: Declaration of competing interest The authors have no competing interests to declare that are relevant to the content of this article., (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.)

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 for all). Significant interactions were observed between dietary protein intake and DNAm on changes in insulin (P-interaction = 0.007) and HOMA-IR (P-interaction = 0.009) at 6 months. In participants with the highest tertile of regional DNAm at TXNIP, average protein (15%) intake was associated with a greater reduction in insulin (β: -0.14; 95% CI: -0.24, -0.03; P = 0.011) and HOMA-IR (β: -0.15; 95% CI: -0.26, -0.03; P = 0.014) than high protein (25%) intake, whereas no significant associations were found in those with the lower tertiles (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., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Background and Objectives: Carotid intima-media thickness (c-IMT) is a measurement of atherosclerosis, a progressive disease that develops as early as childhood and has been linked with cognitive impairment and dementia in the elderly. However, the relationship between c-IMT and midlife cognitive function and the race and social disparities in this relationship remain unclear. We examined the association between c-IMT and cognitive function in midlife among Black and White participants from a semirural community-based cohort in Bogalusa, Louisiana., Methods: In this cross-sectional analysis of participants from the Bogalusa Heart Study, linear regression models were used to determine the association between c-IMT dichotomized above the 50th percentile (>0.87 mm), an a demographically standardized global cognitive score (GCS), and individual cognitive domain-based z scores. Stratified analyses were performed to evaluate the impact of race and the individual's education status., Results: A total of 1,217 participants (age 48 ± 5.28 years) were included; 66% (804) self-identified as White, and 34% (413) self-identified as Black. Of those, 58% (708) were women, and 42% (509) were men. Having a c-IMT ≥50th percentile was inversely associated with GCS ( B ± SE -0.39 ± 0.18, p = 0.03), independently of cardiovascular risk factors (CVRFs) and achieved education. The effect remained significant in Black and White participants after adjustment for CVRFs (Black participants: B ± SE -1.25 ± 0.45, p = 0.005; White participants: B ± SE -0.92 ± 0.35, p = 0.008) but not for education. The interaction between c-IMT ≥50th percentile and education was significant ( p = 0.03), and stratified analysis showed an association with GCS among those with lower achieved education ( B ± SE -0.81 ± 0.33, p = 0.013) independently of major CVRFs., Discussion: Subclinical atherosclerosis, measured as c-IMT, was associated with worse midlife cognitive function, independently of major CVRFs. The association was buffered by education and may be stronger among Black than White participants, likely due to corresponding structural and social determinants. These findings underscore the importance of establishing preventive measures in midlife and suggest subclinical atherosclerosis as a potential target to prevent cognitive decline., (© 2022 American Academy of Neurology.)

Aim: To examine the effects of changes in body size phenotypes between childhood and adulthood on risks of diabetes and left ventricular hypertrophy (LVH) in adulthood., Methods: We included 3,351 individuals who participated as both children and adults in the Bogalusa Heart Study., Results: Compared with participants with persistently metabolically healthy normal weight (MHNW) from childhood to adulthood, MHNW children who became metabolically unhealthy in adulthood had increased diabetes burden and LVH risk in adulthood; Metabolically unhealthy normal weight (MUNW) children who became MHNW or metabolically healthy obese (MHO) as adults and individuals with persistent MHO from childhood to adulthood were not at increased risks of diabetes or LVH. The risks were increased if MHO during childhood transitioned to metabolically unhealthy obesity (MUO) by adulthood or MUO stayed from childhood to adulthood. MUO children who became MHO or MHNW as adults had decreased diabetes burden and LVH risk in adulthood., Conclusions: Individuals maintained MHO from childhood to adulthood and MUNW children who became MHO as adults had a diabetes burden and LVH risk similar to individuals with persistent MHNW. Progression to metabolically unhealthy status and maintenance of metabolically unhealthy status, regardless of childhood BMI status, were associated with increased cardiometabolic outcomes., (Copyright © 2022 Elsevier B.V. All rights reserved.)