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

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

Childhood Cardiovascular Risk Factors and Adult Cardiovascular Events.

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

Lipoprotein(a) in Youth and Prediction of Major Cardiovascular Outcomes in Adulthood.

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.

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

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

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

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

Large-Scale Data Harmonization Across Prospective Studies.

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.

HIV and hypertension epidemiology.

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.

Blood DNA methylation at TXNIP and glycemic changes in response to weight-loss diet interventions: the POUNDS lost trial.

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 (ß: -0.14; 95% CI: -0.24, -0.03; P = 0.011) and HOMA-IR (ß: -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.

Obesity during childhood is associated with higher cancer mortality rate during adulthood: the i3C Consortium.

BACKGROUND: In high-income countries, cancer is the leading cause of death among middle-aged adults. Prospective data on the effects of childhood risk exposures on subsequent cancer mortality are scarce. METHODS: We examined whether childhood body mass index (BMI), blood pressure, glucose and lipid levels were associated with adult cancer mortality, using data from 21,012 children enrolled aged 3-19 years in seven prospective cohort studies from the U.S., Australia, and Finland that have followed participants from childhood into adulthood. Cancer mortality (cancer as a primary or secondary cause of death) was captured using registries. RESULTS: 354 cancer deaths occurred over the follow-up. In age-, sex, and cohort-adjusted analyses, childhood BMI (Hazard ratio [HR], 1.13; 95% confidence interval [CI] 1.03-1.24 per 1-SD increase) and childhood glucose (HR 1.22; 95%CI 1.01-1.47 per 1-SD increase), were associated with subsequent cancer mortality. In a multivariable analysis adjusted for age, sex, cohort, and childhood measures of fasting glucose, total cholesterol, triglycerides, and systolic blood pressure, childhood BMI remained as an independent predictor of subsequent cancer mortality (HR, 1.24; 95%CI, 1.03-1.49). The association of childhood BMI and subsequent cancer mortality persisted after adjustment for adulthood BMI (HR for childhood BMI, 1.35; 95%CI 1.12-1.63). CONCLUSIONS: Higher childhood BMI was independently associated with increased overall cancer mortality.

Hypertension and cognitive function: a review of life-course factors and disparities.

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.

Lifestyle behaviors and cardiovascular risk profiles among parous women by gestational diabetes status, 2007-2018.

BACKGROUND AND AIMS: Women with prior gestational diabetes mellitus (GDM) are at elevated risk of type 2 diabetes mellitus and cardiovascular disease. We compared cardiometabolic risk factors among parous U.S. women ages 20-44 by history of GDM. METHODS AND RESULTS: Using data from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2018, 3537 parous women were classified by self-reported GDM history. We compared anthropometric measures, glycemia, blood pressure, lipids, lifestyle factors, cardiovascular health, and cardiometabolic disease prevalence by GDM status. NHANES survey design was taken into account. Women without history of GDM were younger and, after adjusting for age, race/ethnicity, and education, had more favorable cardiometabolic risk factor profiles for measures of anthropometry, glycemia, diabetes, many lipids, physical activity, diet, and overall cardiovascular health than women with history of GDM. Many patterns persisted after further adjustment for lifestyle factors. In analyses stratified by race/ethnicity, many patterns persisted, though there were key differences. Hypertension prevalence differed by GDM history only among Hispanic women. In women of other race/ethnicity, there was no difference in healthy eating or body mass index by GDM history. In non-Hispanic Black women, there was no difference in healthy eating by GDM history. CONCLUSION: Among parous U.S. women ages 20-44, those with history of GDM had less favorable cardiometabolic risk factor profiles than those without history of GDM. This highlights the importance of continued efforts to develop and test multilevel interventions to improve cardiometabolic risk factors among reproductive-age women with a history of GDM.

Metabolomics study of blood pressure salt-sensitivity and hypertension.

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.

Do diets with higher carbon footprints increase the risk of mortality? A population-based simulation study using self-selected diets from the USA.

OBJECTIVE: Are diets with a greater environmental impact less healthy? This is a key question for nutrition policy, but previous research does not provide a clear answer. To address this, our objective here was to test whether American diets with the highest carbon footprints predicted greater population-level mortality from diet-related chronic disease than those with the lowest. DESIGN: Baseline dietary recall data were combined with a database of greenhouse gases emitted in the production of foods to estimate a carbon footprint for each diet. Diets were ranked on their carbon footprints and those in the highest and lowest quintiles were studied here. Preventable Risk Integrated Model (PRIME), an epidemiological modelling software, was used to assess CVD and cancer mortality for a simulated dietary change from the highest to the lowest impact diets. The diet-mortality relationships used by PRIME came from published meta-analyses of randomised controlled trials and prospective cohort studies. SETTING: USA. PARTICIPANTS: Baseline diets came from adults (n 12 865) in the nationally representative 2005-2010 National Health and Nutrition Examination Survey. RESULTS: A simulated change at the population level from the highest to the lowest carbon footprint diets resulted in 23 739 (95 % CI 20 349, 27 065) fewer annual deaths from CVD and cancer. This represents a 1·83 % (95 % CI 1·57 %, 2·08 %) decrease in total deaths. About 95 % of deaths averted were from CVD. CONCLUSIONS: Diets with the highest carbon footprints were associated with a greater risk of mortality than the lowest, suggesting that dietary guidance could incorporate sustainability information to reinforce health messaging.

Sustained physical activity in peripheral artery disease: Associations with disease severity, functional performance, health-related quality of life, and subsequent serious adverse events in the LITE randomized clinical trial.

This study investigated cross-sectional associations of peripheral artery disease (PAD) severity (defined by the ankle-brachial index (ABI)) and amounts of daily sustained physical activity (PA) (defined as > 100 activity counts per minute lasting 5 consecutive minutes or more). This study also investigated associations of amounts of daily sustained PA with 6-minute walk (6MW) distance and the Short Form-36 physical functioning domain (SF-36 PF) score in cross-sectional analyses and with serious adverse events (SAEs) in longitudinal analyses of people with PAD. PA was measured continuously for 10 days using a tri-axial accelerometer at baseline in 277 participants with PAD randomized to the LITE clinical trial. In regression analyses, each 0.15 lower ABI value was associated with a 5.67% decrease in the number of daily bouts of sustained PA (95% CI: 3.85-6.54; p < 0.001). Every additional bout of sustained PA per day was associated with a 4.56-meter greater 6MW distance (95% CI: 2.67-6.46; p < 0.0001), and a 0.81-point improvement in SF-36 PF score (95% CI: 0.34-1.28; p < 0.001). Participants with values of daily bouts of sustained PA below the median had higher rates of SAEs during follow-up, compared to participants above the median (41% vs 24%; p = 0.002). In conclusion, among participants with PAD, lower ABI values were associated with fewer bouts of daily sustained PA. A greater number of bouts of daily sustained PA were associated with better 6MW performance and SF-36 PF score, and, in longitudinal analyses, lower rates of SAEs. Clinicaltrials.gov ID: NCT02538900.

Association of the Neighborhood Built Environment With Incident and Prevalent Depression in the Rural South.

INTRODUCTION: A neighborhood's built environment is associated with physical activity among its residents, and physical activity is associated with depression. Our study aimed to determine whether the built environment was associated with depression among residents of the rural South and whether observed associations were mediated by physical activity. METHODS: We selected 2,000 participants from the Bogalusa Heart Study who had a valid residential address, self-reported physical activity (minutes/week), and a complete Center for Epidemiologic Study-Depression (CES-D) scale assessment from 1 or more study visits between 1998 and 2013. We assessed the built environment with the Rural Active Living Assessment street segment audit tool and developed built environment scores. The association between built environment scores and depression (CES-D ≥16) in geographic buffers of various radii were evaluated by using modified Poisson regression, and mediation by physical activity was evaluated with mixed-effects models. RESULTS: Depression was observed in 37% of study participants at the first study visit. One-point higher physical security and aesthetic scores for the street segment of residence were associated with 1.07 times higher (95% CI, 1.02-1.11) and 0.96 times lower (95% CI, 0.92-1.00) baseline depression prevalence. One-point higher destination scores (ie, more commercial and civic facilities) in radius buffers of 0.25 miles or more were associated with 1.06 times (95% CI, 1.00-1.13) the risk of depression during follow-up. Neighborhood poverty (defined as percentage of residents with incomes below the federal poverty level and dichotomized at 28.3%) modified cross-sectional and longitudinal associations. Associations were not mediated by physical activity. CONCLUSION: The built environment was associated with prevalence and risk of depression, and associations were stronger in high-poverty neighborhoods. Built environment improvements to promote physical activity should take neighborhood context into consideration to minimize negative side effects on mental health in high-poverty communities.

Cardiovascular risk factors before and during pregnancy: Does pregnancy unmask or initiate risk?

OBJECTIVES: To understand if pregnancy unmasks previously silent cardiovascular (CV) adverse factors, or initiates lasting injury. METHODS: Pre-pregnancy and during pregnancy CV risk factors (blood pressure, fasting lipids, and glucose) from 296 women belonging to studies in the International Childhood Cardiovascular Cohort (i3C) Consortium, a group of studies assessing the relationship between child and adolescent CV risk factors and adult outcomes, were used. Correlation coefficients between the pre- and during pregnancy measures were calculated, and the mean difference between the measures was modeled with adjustment for age, body mass index, race, smoking, and study. RESULTS: Measures were strongly correlated at pre- and during-pregnancy visits (p < 0.01), with r of between 0.30 and 0.55. In most cases, the difference between pre-pregnancy and during-pregnancy did not differ significantly from 0 after adjustment for confounders. Stratification by gestational age indicated stronger correlations with measurements obtained during the first and second trimesters than the third. The correlation did not differ by the time elapsed between the pre-pregnancy and pregnancy visits. CONCLUSIONS: Pre- and during-pregnancy CV risk factors are moderately well correlated. This may indicate that susceptible women enter pregnancy with higher risk rather than pregnancy inducing new vascular or metabolic effects.

Pseudouridine and N-formylmethionine associate with left ventricular mass index: Metabolome-wide association analysis of cardiac remodeling.

BACKGROUND: Heart failure (HF) is the fastest growing form of cardiovascular disease both nationally and globally, underlining a need to phenotype subclinical HF intermediaries to improve primary prevention. OBJECTIVES: We aimed to identify novel metabolite associations with left ventricular (LV) remodeling, one upstream HF intermediary, among a community-based cohort of individuals. METHODS: We examined 1052 Bogalusa Heart Study participants (34.98% African American, 57.41% female, aged 33.6-57.5 years). Measures of LV mass and relative wall thickness (RWT) were obtained using two-dimensional-guided echocardiographic measurements via validated eqs. LV mass was indexed to height2.7 to calculate left ventricular mass index (LVMI). Untargeted metabolomic analysis of fasting serum samples was conducted. In combined and ethnicity-stratified analyses, multivariable linear and multinomial logistic regression models tested the associations of metabolites with the continuous LVMI and RWT and categorical LV geometry phenotypes, respectively, after adjusting for demographic and traditional cardiovascular disease risk factors. RESULTS: Pseudouridine (B = 1.38; p = 3.20 × 10-5) and N-formylmethionine (B = 1.65; 3.30 × 10-6) were significantly associated with LVMI in the overall sample as well significant in Caucasians, with consistent effect direction and nominal significance (p < .05) in African Americans. Upon exclusion of individuals with self-report myocardial infarction or congestive HF, we similarly observed a 1.33 g/m2.7 and 1.52 g/m2.7 higher LVMI for each standard deviation increase in pseudouridine and N-formylmethionine, respectively. No significant associations were observed for metabolites with RWT or categorical LV remodeling outcomes. CONCLUSIONS: The current analysis identified novel associations of pseudouridine and N-formylmethionine with LVMI, suggesting that mitochondrial-derived metabolites may serve as early biomarkers for LV remodeling and subclinical HF.

Sleep Extension: A Potential Target for Obesity Treatment.

PURPOSE OF REVIEW: Sleep and obesity share a bidirectional relationship, and weight loss has been shown to enhance sleep. Aiming to extend sleep on its own or as part of a lifestyle intervention may attenuate health consequences of short sleep. This review highlights several sleep extension approaches, discusses feasibility of each, and summarizes findings relevant to obesity. RECENT FINDINGS: Sleep extension in response to experimental sleep restriction demonstrates partial rescue of cardiometabolic dysfunction in some but not all studies. Adequate sleep on a nightly basis may be necessary for optimal health. While initial sleep extension interventions in habitually short sleepers have been met with obstacles, preliminary findings suggest that sleep extension or sleep hygiene interventions may improve glycemic control, decrease blood pressure, and enhance weight loss. Sleep extension has the potential to attenuate obesity risk and cardiometabolic dysfunction. There is tremendous opportunity for future research that establishes a minimum threshold for sleep extension effectiveness and addresses logistical barriers identified in seminal studies.

Reproductive History and Cognitive Aging: The Bogalusa Heart Study.

BACKGROUND: Although it has become increasingly clear that pregnancy-related health predicts later-life cardiometabolic health, the relationship between reproductive history and cognitive health is less frequently studied. Although some research has identified associations between parity or hypertensive disorders of pregnancy and cognitive changes, the evidence is mixed. OBJECTIVE: To examine the association between reproductive history and midlife cognition in a community-based population. STUDY DESIGN: Seven hundred and thirty midlife women in the Bogalusa Heart Study completed a brief cognitive battery (memory, attention, executive function, and processing speed) and were interviewed about their reproductive history. Reproductive history (parity, age at first pregnancy, and breastfeeding) and pregnancy complications (low birthweight, preterm birth, hypertensive disorders, and miscarriage) were examined as predictors of cognitive function, with adjustment for potential confounders. RESULTS: Nulliparous women had an overall lower cognitive score (adjusted beta -1.50, standard error [SE]: 0.41). Adolescent birth was associated with a somewhat better performance on the Trail Making Test (beta -0.31, SE: 0.15 for birth <16 years), while high parity was not strongly associated with any of the cognitive measures. History of pregnancy complications was not strongly associated with cognitive function, whereas history of miscarriage was associated with better cognitive function, as was a history of breastfeeding (beta overall score 0.90, SE: 0.29), particularly noticeable for semantic memory and in those with more total breastfeeding time (beta for overall score among those with >24 weeks lifetime breastfeeding, beta 1.21, SE: 0.44). CONCLUSION: Nulliparity and breastfeeding are associated with midlife cognition in women. Future studies should examine possible mechanisms by which these associations are created.

Pooled cohort equations heart failure risk score predicts cardiovascular disease and all-cause mortality in a nationally representative sample of US adults.

BACKGROUND: Heart failure (HF) represents an accumulated burden of systemic vascular damage and is the fastest growing form of cardiovascular disease (CVD). Due to increasing HF-attributable mortality rates, we sought to assess the association of the new 2019 Pooled Cohort equations to Prevent Heart Failure (PCP-HF) risk score with CVD and all-cause mortality. METHODS: We linked data for 6333 black and white men and women aged 40-79 years, whom underwent electrocardiographic examination from the Third National Health and Nutrition Exam Survey, to National Death Index record matches. Sex- and race-specific PCP-HF risk scores were calculated using data on age, smoking, body mass index, systolic blood pressure, total cholesterol, HDL-cholesterol, fasting blood glucose, QRS complex duration, and antihypertensive and/or glucose-lowering medications. Cox regression estimated hazard ratios for the association of the PCP-HF risk score with CVD and all-cause mortality. RESULTS: Individuals were on average 54.9 years old (51.7% women, 25.4% black) and the median 10-year HF risk was 1.6% (Q1 = 0.5, Q3 = 4.8). There were 3178 deaths, 1116 from CVD, over a median follow-up time of 22.3 years. Black women had a higher 10-year HF risk compared to white women (2.1% vs. 1.1%; p < 0.01), while no significant difference was observed in predicted HF risk between black men and white men (2.3% vs. 2.1%, p = 0.16). A two-fold higher PCP-HF risk score was associated with a significant 58% (HR = 1.58; 95% CI, 1.48-1.70; p < 0.0001) and 38% (HR = 1.38; 95% CI, 1.32-1.46; p < 0.0001) greater risk of CVD and all-cause mortality, respectively. CONCLUSION: The PCP-HF risk score predicts CVD and all-cause mortality, in addition to the 10-year risk of incident HF among white and black men and women. These results underline the expanded utility of the PCP-HF risk score and suggest that its implementation in the clinical and population health settings may improve primary CVD prevention in the United States.