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This study assessed the temporal relationship between elevated blood pressure (BP) and arterial stiffness in a biracial (black-white) cohort of middle-aged adults aged 32-51 years from the semirural community of Bogalusa, Louisiana. Measurements of aortic-femoral pulse wave velocity (afPWV; n = 446) and large-and small-arterial compliance (n = 381) were obtained at 2 time points between 2000 and 2010, with an average follow-up period of 7 years. A cross-lagged path analysis model was used to examine the temporal relationship of elevated BP to arterial stiffness and elasticity. The cross-lagged path coefficients did not differ significantly between blacks and whites. The path coefficient (ρ2) from baseline BP to follow-up afPWV was significantly greater than the path coefficient (ρ2 from baseline afPWV to follow-up BP(ρ2 = 0.20 vs. ρ1 = 0.07 (P= 0.048) for systolic BP; ρ2 = 0.19vs. ρ1 =0.05 (P= 0.034) for diastolic BP). The results for this 1 -directional path from baseline BP to follow-up afPWV were confirmed, although marginally significant, by using large- and small-artery elasticity measurements. These findings provide strong evidence that elevated BP precedes large-artery stiffening in middle-aged adults. Unlike the case in older adults, the large-arterial wall is not stiff enough in youth to alter BP levels during young adulthood. [ABSTRACT FROM AUTHOR]

Background: Coenzyme Q10 (Co Q10 also called ubiquinone) is an antioxidant that has been postulated to improve functional status in congestive heart failure (CHF). Several randomized controlled trials have examined the effects of Co Q10 on CHF with inconclusive results. Objective: The objective of this meta-analysis was to evaluate the impact of Co Q10 supplementation on the ejection fraction (EF) and New York Heart Association (NYHA) functional classification in patients with CHE Design: A systematic review of the literature was conducted by using databases including MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and manual examination of references from selected studies. Studies included were randomized controlled trials of CoQ10 supplementation that reported the EF or NYHA functional class as a primary outcome. Information on participant characteristics, trial design and duration, treatment, dose, control, EF, and NYHA classification were extracted by using a standardized protocol. Results: Supplementation with CoQ10 resulted in a pooled mean net change of 3.67% (95% CI: 1.60%, 5.74%) in the EF and -0.30 (95% CI: -0.66, 0.06) in the NYHA functional class. Subgroup analyses showed significant improvement in EF for crossover trials, trials with treatment duration ≤ 12 wk in length, studies published before 1994, and studies with a dose ≤100 mg CoQ10/d and in patients with less severe CHE These subgroup analyses should be interpreted cautiously because of the small number of studies and patients included in each subgroup. Conclusions: Pooled. analyses of available randomized controlled trials suggest that CoQ10 may improve the EF in patients with CHF. Additional well-designed studies that include more diverse populations are needed. [ABSTRACT FROM AUTHOR]

Objectives: This prospective cohort study examines the clinical effectiveness of electronic medical record clinical decision support (EMR CDS) for opioid prescribing.Methods: Data analysis included primary care patients with chronic opioid therapy for noncancer pain seen within an integrated health delivery system in Louisiana between January 2017 and October 2018. EMR CDS incorporated an opioid health maintenance tool to display the status of risk mitigation, and the medication order embedded the morphine equivalent daily dose (MEDD) calculator and a hyperlink to the Louisiana pharmacy drug monitoring program. Outcome measures included change in the average MEDD and rates of opioid risk mitigation, hospitalization, and emergency department use.Results: Among 14 221 patients, 9% had prescriptions with an average MEDD ≥90 mg. There were no significant changes in MEDD after EMR CDS implementation. Increasing age, Charlson Comorbidity Index score, female sex, black non-Hispanic race, non-opioid pain medication co-prescriptions, and specialty referrals were associated with a lower odds of MEDD ≥90 (high-dose threshold). Medicare or self-pay, substance abuse history, and pain agreements were associated with increased odds of prescribing above this high-dose threshold. After incorporation of EMR CDS, patients had higher rates of urine drug screens (17% vs 7%) and naloxone prescriptions (3% vs 1%, all P < .001). In addition, specialty referrals to physical or occupational therapy, orthopedics, neurology, and psychiatry or psychology increased in the postintervention period. Although emergency department use decreased (rate ratio 0.92; 95% confidence interval 0.89-0.95), hospitalization rates did not change.Conclusions: EMR CDS improved adherence to opioid risk mitigation strategies. Further research examining which practice redesign interventions effectively reduce high-dose opioid prescribing is needed. [ABSTRACT FROM AUTHOR]

Aims: To evaluate several adult diabetes risk calculation tools for predicting the development of incident diabetes and pre-diabetes in a bi-racial, young adult population.Methods: Surveys beginning in young adulthood (baseline age ≥18) and continuing across multiple decades for 2122 participants of the Bogalusa Heart Study were used to test the associations of five well-known adult diabetes risk scores with incident diabetes and pre-diabetes using separate Cox models for each risk score. Racial differences were tested within each model. Predictive utility and discrimination were determined for each risk score using the Net Reclassification Index (NRI) and Harrell's c-statistic.Results: All risk scores were strongly associated (p<.0001) with incident diabetes and pre-diabetes. The Wilson model indicated greater risk of diabetes for blacks versus whites with equivalent risk scores (HR=1.59; 95% CI 1.11-2.28; p=.01). C-statistics for the diabetes risk models ranged from 0.79 to 0.83. Non-event NRIs indicated high specificity (non-event NRIs: 76%-88%), but poor sensitivity (event NRIs: -23% to -3%).Conclusions: Five diabetes risk scores established in middle-aged, racially homogenous adult populations are generally applicable to younger adults with good specificity but poor sensitivity. The addition of race to these models did not result in greater predictive capabilities. A more sensitive risk score to predict diabetes in younger adults is needed. [ABSTRACT FROM AUTHOR]

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.

Background Early identification of healthy arterial aging versus premature atherosclerosis is important for optimal atherosclerotic cardiovascular disease risk stratification and prevention. We sought to identify predictors for the long-term absence of carotid plaque among young adults. Methods and Results We included 508 participants from the Bogalusa Heart Study without clinical atherosclerotic cardiovascular disease who were free of carotid plaque at baseline (2001-2002) and underwent ultrasound imaging at follow-up (2013-2016). Modified Poisson regression estimated the persistent absence of plaque over 12.8 years. Participants were on average age 36.2 years at baseline, 64% were women, and 29% were Black. Although nearly all participants (97%) had a 10-year atherosclerotic cardiovascular disease risk <7.5%, there were 162 people (32%) who developed premature atherosclerosis. Aside from younger age (risk ratio [RR], 1.21; 95% CI, 1.07-1.36, per 10 years) and a total cholesterol/high-density lipoprotein cholesterol ratio <3.5 (RR, 1.15; 95% CI, 1.01-1.30), normal values of traditional risk factors did not predict long-term absence of plaque. Independent from traditional markers including glomerular filtration rate, serum calcium-phosphate product (RR, 1.07; 95% CI, 1.01-1.14, per 1-SD lower), phosphate (RR, 1.15; 95% CI, 1.03-1.29, per 1 mg/dL lower), and dietary sodium <2300 mg/day (RR, 1.20; 95% CI, 1.02-1.41) were significantly associated with the non-development of plaque. Conclusions Nearly one third of young adults with a low burden of traditional risk factors developed premature atherosclerosis. Beyond younger age and an ideal lipoprotein profile, lower calcium-phosphate homeostasis and low sodium intake were associated with long-term absence of carotid plaque. These results suggest that dietary and intrinsic minerals are early contributors to the development of arterial aging phenotypes.

Background: Insufficient physical activity (PA) is a common health risk and more prevalent in rural populations. Few studies have assessed relationships between the built environment and PA in rural settings, and community policy guidance to promote PA through built environment interventions is primarily based on evidence from urban studies., Methods: Participants in the Bogalusa Heart Study, a longitudinal study in rural Louisiana, with International Physical Activity Questionnaire data from 2012 to 2013 and a valid residential address (N = 1245) were included. PA was summarized as the number of weekly metabolic equivalent (MET)-minutes of total, transportation, and leisure time PA. The Rural Active Living Assessment street segment audit tool and Google Street View were used to assess features of the built environment overall and in six categories (path features, pedestrian safety features, aesthetics, physical security, destinations and land use) that influence PA. Scores for street segment built environment (overall and in categories) were calculated, for segments and buffers of 0.25, 0.50, 1.00 and 1.50 miles. Associations between built environment scores and PA were assessed with generalized estimating equations., Results: Participants reported little weekly total, leisure time, and transportation PA (mean 470, 230 and 43 MET-minutes per week, respectively). A 1-point increase in the overall built environment score was associated with 10.30 additional weekly leisure time MET-minutes within a 1.50 mile buffer (p-value 0.05), with a similar magnitude observed for a 1.00-mile buffer. A 1-point increase in the aesthetic score was associated with significantly higher leisure time PA for all geographic units (from 22.21 to 38.75 MET-minutes weekly) when adjusted for individual covariates, but was attenuated and only significant for the segment of the residence after accounting for other neighborhood characteristics., Conclusions: Significant associations between features of the environment (overall and aesthetic scores) with leisure time PA were observed among adults in this rural population. Built environment interventions in rural settings face additional barriers of lower population density and greater distances for infrastructure projects, and it is important to identify approaches that are both feasible for rural communities and can promote PA.

Background: Elevated cardiovascular disease risk factor burden is a recognized contributor to poorer cognitive function; however, the physiological mechanisms underlying this association are not well understood. We sought to assess the potential mediation effect of left ventricular (LV) remodeling on the association between lifetime systolic blood pressure and cognitive function in a community-based cohort of middle-aged adults., Methods: Nine hundred sixty participants of the Bogalusa Heart Study (59.2% women, 33.8% black, aged 48.4±5.1 years) received 2-dimensional echocardiography to quantify relative wall thickness, LV mass, and diastolic and systolic LV function; and a standardized neurocognitive battery to assess memory, executive functioning, and language processing. Multivariable linear regression assessed the association of cardiac structure and function with a global composite cognitive function score, adjusting for traditional cardiovascular disease risk factors. Mediation analysis assessed the effect of LV mass index on the association between lifetime systolic blood pressure burden and cognitive function., Results: There were 233 (24.3%) and 136 (14.2%) individuals with concentric LV remodeling and concentric LV hypertrophy, respectively. Each g/m 2.7 increment in LV mass index was associated with a 0.03 standardized unit decrement in global cognitive function ( P =0.03). Individuals with concentric LV remodeling and isolated diastolic dysfunction had the poorest cognitive function, and a greater ratio between early mitral inflow velocity and early diastolic mitral annular velocity (E/e') was associated with poorer cognitive function, even after adjustment for LV mass index (B=-0.12; P =0.03). A total of 18.8% of the association between lifetime systolic blood pressure burden and midlife cognitive function was accounted for by LV mass index., Conclusions: Cardiac remodeling partially mediates the association between lifespan systolic blood pressure burden and adult cognition in individuals without dementia or clinical cardiovascular disease. Slowing or reversing the progression of cardiac remodeling in middle-age may be a novel therapeutic approach to prevent cognitive decline.

Background and Aims: Dyslipidemia has been identified as a major risk factor for cardiovascular disease. We aimed to identify metabolites and metabolite modules showing novel association with lipids among Bogalusa Heart Study (BHS) participants using untargeted metabolomics., Methods and Results: Untargeted ultrahigh performance liquid chromatography-tandem mass spectroscopy was used to quantify serum metabolites of 1 243 BHS participants (816 whites and 427 African-Americans). The association of single metabolites with lipids was assessed using multiple linear regression models to adjust for covariables. Weighted correlation network analysis was utilized to identify modules of co-abundant metabolites and examine their covariable adjusted correlations with lipids. All analyses were conducted according to race and using Bonferroni-corrected α-thresholds to determine statistical significance. Thirteen metabolites with known biochemical identities showing novel association achieved Bonferroni-significance, p < 1.04 × 10 -5 , and showed consistent effect directions in both whites and African-Americans. Twelve were from lipid sub-pathways including fatty acid metabolism (arachidonoylcholine, dihomo-linolenoyl-choline, docosahexaenoylcholine, linoleoylcholine, oleoylcholine, palmitoylcholine, and stearoylcholine), monohydroxy fatty acids (2-hydroxybehenate, 2-hydroxypalmitate, and 2-hydroxystearate), and lysoplasmalogens [1-(1-enyl-oleoyl)-GPE (P-18:1) and 1-(1-enyl-stearoyl)-GPE (P-18:0)]. The gamma-glutamylglutamine, peptide from the gamma-glutamyl amino acid sub-pathway, were also identified. In addition, four metabolite modules achieved Bonferroni-significance, p < 1.39 × 10 -3 , in both whites and African-Americans. These four modules were largely comprised of metabolites from lipid sub-pathways, with one module comprised of metabolites which were not identified in the single metabolite analyses., Conclusion: The current study identified 13 metabolites and 4 metabolite modules showing novel association with lipids, providing new insights into the physiological mechanisms regulating lipid levels., Competing Interests: Declaration of Competing Interest J.K. is employed by Metabolon, Inc., and he contributed to the logistics and optimization of the untargeted metabolomics and the untargeted metabolomics data interpretation. Metabolon, Inc. was not involved in the design of the study, statistical analysis, or interpretation of the results. The other authors declared no conflict of interest., (Copyright © 2020 The Italian Society of Diabetology, 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 Diastolic dysfunction is one important causal factor for heart failure with preserved ejection fraction, yet the metabolic signature associated with this subclinical phenotype remains unknown. Methods and Results Ultra-high-performance liquid chromatography-tandem mass spectroscopy was used to conduct untargeted metabolomic analysis of fasting serum samples in 1050 white and black participants of the BHS (Bogalusa Heart Study). After quality control, 1202 metabolites were individually tested for association with 5 echocardiographic measures of left ventricular diastolic function using multivariable-adjusted linear regression. Measures of left ventricular diastolic function included the ratio of peak early filling velocity to peak late filling velocity, ratio of peak early filling velocity to mitral annular velocity, deceleration time, isovolumic relaxation time, and left atrial maximum volume index (LAVI). Analyses adjusted for multiple cardiovascular disease risk factors and used Bonferroni-corrected alpha thresholds. Eight metabolites robustly associated with left ventricular diastolic function in the overall population and demonstrated consistent associations in white and black study participants. N-formylmethionine (B=0.05; P =1.50×10 -7 ); 1-methylhistidine (B=0.05; P =1.60×10 -7 ); formiminoglutamate (B=0.07; P =5.60×10 -7 ); N2, N5-diacetylornithine (B=0.05; P =1.30×10 -7 ); N-trimethyl 5-aminovalerate (B=0.04; P =5.10×10 -6 ); 5-methylthioadenosine (B=0.04; P =1.40×10 -5 ); and methionine sulfoxide (B=0.04; P =3.80×10 -6 ) were significantly associated with the natural log of the ratio of peak early filling velocity to mitral annular velocity. Butyrylcarnitine (B=3.18; P =2.10×10 -6 ) was significantly associated with isovolumic relaxation time. Conclusions The current study identified novel findings of metabolite associations with left ventricular diastolic function, suggesting that the serum metabolome, and its underlying biological pathways, may be implicated in heart failure with preserved ejection fraction pathogenesis.

Background: Dementia and late-life cognitive decline are leading causes of death and disability in the United States. Prevention of these diseases, by maintaining brain health throughout the life course, is essential. Diet and lifestyle changes are the chief strategies aimed at primary prevention for many of the risk factors of cognitive decline., Objective: The aim of this study was to examine the potential impact of dietary factors on cognitive function., Methods: This prospective cohort study followed 516 young adults through midlife. The Youth/Adolescent Questionnaire was used to collect habitual nutrition data (mean age: 32.03 ± 5.96 y) at baseline. Scores from a neurocognitive battery were used to assess cognitive function (mean age: 49.03 ± 4.86 y) at follow-up and were transformed to z scores. Separate multivariable-adjusted linear regression models were fitted. The trend across quintiles for each dietary variable was assessed., Results: Vitamin B-6, whole grains, processed meats, and foods fried at home all displayed significant linear trends in their relation with cognitive function. Dietary intake of vitamin B-6 and whole grains was directly associated with better cognitive function after adjustment for age, race, sex, and total calorie intake (β coefficient from linear regression and SE: 1.755 ± 0.621, P = 0.005, and 0.001 ± 0.000, P = 0.018, respectively). Processed meat and foods fried at home consistently displayed inverse associations with cognitive function across crude and adjusted models (linear trend P values were 0.05 and <0.0001, respectively)., Conclusions: Our findings suggest that dietary consumption in young adulthood may affect cognitive function in midlife. Strong associations between dietary intake and cognition were observed in our analysis, but as with all observational studies, the possibility of residual confounding cannot be excluded., (Copyright © American Society for Nutrition 2019.)

Background: Short sleep duration has been consistently associated with obesity. However, few studies in adults have assessed whether this association varies by sex and race., Methods: In the 2013-2016 examination of 1116 participants from the biracial Bogalusa Heart Study, habitual sleep duration was measured in categories (<6 hours, 6-7 hours, 7-8 hours, > 8 hours) using self-report. Anthropometry was performed and adiposity was assessed using body mass index (BMI) and waist circumference. Linear regression models estimated the relationship between sleep duration and adiposity adjusting for age, education, employment, bed partner status, depressive symptoms, smoking status, physical activity, and the use of alcohol and sleeping pills. Effect modification by sex and race was examined using cross-product terms in the models and marginal means were reported., Results: Of 1116 participants (mean age 48.2 years), 58.3% were female, and 31.7% were Black. In adjusted analyses, women sleeping <6 hours had a 3.2 (95% CI 1.4, 5.0) kg/m 2 greater BMI and 6.1 (1.8, 10.4) cm greater waist circumference compared to women sleeping 7-8 hours. In contrast, men had similar BMIs and waist circumferences regardless of sleep duration (p's for interaction = 0.04 & 0.11). There was no effect modification by race., Conclusions: In this sample, lower habitual sleep duration was associated with greater adiposity among women compared to men. Further research is needed to understand the potential mechanisms of the adverse metabolic effects of short sleep in women., (Copyright © 2018 National Sleep Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Economic literature shows that a child's future earnings are predictably influenced by parental income, providing an index of "socioeconomic mobility," or the ability of a person to move towards a higher socioeconomic status from childhood to adulthood. We adapted this economic paradigm to examine cardiovascular risk mobility (CRM), or whether there is life course mobility in relative cardiovascular risk., Methods and Results: Participants from the BHS (Bogalusa Heart Study) with 1 childhood and 1 adult visit from 1973 to 2016 (n=7624) were considered. We defined population-level CRM as the rank-rank slope (β) from the regression of adult cardiovascular disease (CVD) risk percentile ranking onto childhood CVD risk percentile ranking (β=0 represents complete mobility; β=1 represents no mobility). After defining and measuring relative CRM, we assessed its correlation with absolute cardiovascular health using the American Heart Association's Ideal Cardiovascular Health metrics. Overall, there was substantial mobility, with black participants having marginally better CRM than whites (β black =0.10 [95% confidence interval, 0.05-0.15]; β white =0.18 [95% confidence interval, 0.14-0.22]; P =0.01). Having high relative CVD risk at an earlier age significantly reduced CRM (β age×slope =-0.02; 95% confidence interval, -0.03 to -0.01; P <0.001). Relative CRM was strongly correlated with life course changes in Ideal Cardiovascular Health sum ( r =0.62; 95% confidence interval, 0.60-0.65)., Conclusions: Results from this novel application of an economic mobility index to cardiovascular epidemiology indicated substantial CRM, supporting the paradigm that life course CVD risk is highly modifiable. High CRM implies that the children with the best relative CVD profiles may only maintain a slim advantage over their peers into adulthood., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background: Hand tremor and blood pressure (BP) are both increased by adrenergic stimulation and reduced by β-blockade, indicating that they may share a common underlying pathophysiology., Methods: We prospectively examined the relationship between postural hand tremor and incident hypertension in a community-based cohort of 715 (184 blacks and 531 whites) adults without hypertension and not using medications to control tremor (e.g. β-blockers). At baseline, tremor was measured with participants holding a laser pointer aimed at a sheet of Polaroid film 8 feet away with arm outstretched for 8 s in a darkened room, and characterized by the width of the circle diameter encompassing all exposures and enumeration of exposure dots in the same area. Incident hypertension was defined as new elevation of BP (SBP ≥ 140 or DBP ≥ 90 mmHg, based on an average of six readings over two visits) or antihypertensive medication use., Results: During a median follow-up of 6.4 years, 198 (69 blacks and 129 whites) participants developed hypertension. Tremor measurements (by quartile) were positively associated with incident hypertension after adjustment for baseline demographics, lifestyle characteristics, and BP. There was significant interaction by race (P = 0.01). Among whites, tremor was positively associated with incident hypertension [hazard ratio highest vs. lowest quartile: 2.50 (95% confidence interval: 1.40-4.48) dot method and 3.24 (1.78-5.90) circular method; both P trend <0.01]. Among blacks, tremor was not associated with hypertension., Conclusion: In this community-based cohort, postural hand tremor was strongly associated with the risk of incident hypertension among whites and merits further study as a potential indicator of risk for hypertension.

Childhood adiposity and insulin resistance are well-known risk factors for adult metabolic syndrome (MetS). This study aims to examine whether the association between childhood adiposity and adult MetS is modified by insulin resistance. The cohort consisted of 1,593 black and white subjects, aged 19-50 years at follow-up, who were examined 19 years apart on average as children and adults for MetS variables. The prevalence of adult MetS was compared between the insulin-sensitive obesity and insulin-resistant obesity groups in childhood. Adult MetS prevalence was higher in the insulin-resistant obesity group than in the insulin-sensitive obesity group (34.9% vs. 24.3%, p = 0.008). In multivariable logistic regression analyses adjusted for age, race, gender, and follow-up years, individuals with insulin-resistant obesity in childhood were 1.7 times (p = 0.011) more likely to have MetS 19 years later on average than those with insulin-sensitive obesity in childhood. Odds ratio did not differ significantly between blacks and whites (p = 0.724). ORs for the association of childhood BMI with adult MetS significantly increased with increasing tertiles of childhood HOMA (p < 0.001 for trend). These findings suggest that insulin resistance amplifies the association between childhood adiposity and adult MetS and underscore the importance of preventing both adiposity and insulin resistance in early life.