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Author(s): Shi, Mengyao; Bazzano, Lydia A; He, Jiang; Gu, Xiaoying; Li, Changwei; Li, Shengxu; Yaffe, Kristine; Kinchen, Jason M; Stuchlik, Patrick; Mi, Xuenan; Nierenberg, Jovia L; Razavi, Alexander C; Kelly, Tanika N | Abstract: BackgroundMetabolomics study provides an opportunity to identify novel molecular determinants of altered cognitive function.MethodsDuring 2013 to 2016 Bogalusa Heart Study (BHS) visit, 1,177 participants underwent untargeted, ultrahigh performance liquid chromatography-tandem mass spectroscopy metabolomics profiling. Global cognition and five cognition domains were also assessed. The cross-sectional associations of single metabolites with cognition were tested using multiple linear regression models. Weighted correlation network analysis was used to examine the covariable-adjusted correlations of modules of co-abundant metabolites with cognition. Analyses were conducted in the overall sample and according to both ethnicity and sex.ResultsFive known metabolites and two metabolite modules robustly associated with cognition across overall and stratified analyses. Two metabolites were from lipid sub-pathways including fatty acid metabolism [9-hydroxystearate; minimum P-value (min-P)=1.11×10-5], and primary bile acid metabolism (glyco-alpha-muricholate; min-P=4.10×10-5). One metabolite from the glycogen metabolism sub-pathway (maltose; min-P=9.77×10-6), one from the polyamine metabolism sub-pathway (N-acetyl-isoputreanine; min-P=1.03×10-5), and one from the purine metabolism sub-pathway (7-methylguanine; min-P=1.19×10-5) were also identified. Two metabolite modules reflecting bile acid metabolism and androgenic steroids correlated with cognition (min-P=5.00×10-4 and 3.00×10-3, respectively).ConclusionThe novel associations of 5 known metabolites and 2 metabolite modules with cognition provide insights into the physiological mechanisms regulating cognitive function.

BACKGROUND AND AIMS: In this analysis, we estimated population-level trajectory groups of life course cardiovascular risk to explore their impact on mid-life atherosclerotic and metabolic outcomes. METHODS: This prospective study followed n=1,269 Bogalusa Heart participants, each with at least 4 study visits from childhood in 1973 through adulthood in 2016. We used discrete mixture modeling to determine trajectories of cardiovascular risk percentiles from childhood to adulthood. Outcomes included mid-life subclinical atherosclerotic measures [(carotid intima-media thickness (cIMT), pulse wave velocity (PWV)], metabolic indicators [(diabetes and body mass index (BMI)], and short physical performance battery (SPPB). RESULTS: Between the mean ages of 9.6–48.3 years, we estimated five distinct trajectory groups of life course cardiovascular risk (High-Low, High-High, Mid-Low, Low-Low, and Low-High). Adult metabolic and vascular outcomes were significantly determined by life course cardiovascular risk trajectory groups (all p

Context It is unclear how adolescent glycemic status relates to brain health in adulthood. Objective To assess the association between adolescent fasting plasma glucose (FPG) and MRI-based brain measures in midlife. Design Between 1973 and 1992, the Bogalusa Heart Study (BHS) collected FPG from children, 3 to 18 years old, and followed up between 1992 and 2018. Cognitive tests and brain MRI were collected in 2013 to 2016 and 2018. Setting Observational longitudinal cohort study. Participants Of 1298 contacted BHS participants, 74 completed screening, and 50 completed MRI. Main Outcome Measures Mean FPG per participant at ages Results At MRI, participants were middle aged (51.3 ± 4.4 years) and predominantly female (74%) and white (74%). Mean FPG was impaired for zero, two, and nine participants in pre-20, 20 to 40, and over-40 periods. The pre-20 mean FPG above the pre-20 median value (i.e., above 83.5 mg/dL) was associated with greater WMH volume [mean difference: 0.029% of total cranial volume, CI: (0.0059, 0.052), P = 0.015] and less fMRI activation [−1.41 units (−2.78, −0.05), P = 0.043] on midlife MRI compared with below-median mean FPG. In controlling for over-40 mean FPG status did not substantially modify the associations. Cognitive scores did not differ by pre-20 mean FPG. Conclusions High-normal adolescent FPG may be associated with preclinical brain changes in midlife.

Although the adverse effects of elevated blood pressure on cognitive function have been well-documented, most cognitive evidence comes from older adults. In this study, we leverage repeated measurements across five decades of the Bogalusa Heart Study and latent class methodology to examine the association of the trajectories of blood pressure from childhood through early adulthood on cognitive function in middle age. From our cohort of n=1,298 adults, after adjustment for age, sex, race, BMI, antihypertensive medication use, smoking, physical activity, and depressive symptoms, we identified three trajectory classes of systolic blood pressure (SBP) over the life course: (1) “normal, stable;” (2) “slightly lower, stable;” and (3) “increasing;” and three for diastolic (DBP): (1) “modestly increasing;” (2) “modestly increasing, lower baseline;” and (3) “sharply increasing.” The distributions of trajectory class membership were modeled with a relative cognitive z-score, computed from a battery of tests covering major neuropsychological domains. Mean z-scores, where higher indicates better relative cognitive function, for SBP classes 1–3 were 1.34, 1.73, and -5.66, respectively, and 1.54, 1.41, and -5.95 for DBP, respectively. Parameter estimates were positive for classes 1–2, and negative for class 3 (p

Although the adverse effects of elevated glucose on cognitive function have been well-documented, most cognitive evidence comes from older adults. In this study, we make use of repeated measurements across five decades of the Bogalusa Heart Study and latent class methodology to examine the association of glucose from childhood through early adulthood on cognitive function in middle age. From our cohort of n=1,298 adults, after adjustment for age, sex, race, BMI, diabetic status, smoking, physical activity, and depressive symptoms, we identified four trajectory classes of glucose over the life course: (1) “healthy and stable;” (2) “healthy but slightly increasing;” (3) “decreasing;” and (4) “sharply increasing” (Figure). The distributions of trajectory class membership were modeled with a relative cognitive z-score, computed from a battery of tests covering major neuropsychological domains. Mean z-scores, where higher indicates better relative cognitive function, for classes 1-4 were 1.04, 0.85, 0.19, and -6.69, respectively. Parameter estimates were positive for classes 1-3, and negative for class 4 (p Disclosure P. Stuchlik: None. O. Carmichael: None. E. Harville: None. H. He: None. M. Romero: None. J. Gustat: None. V. Fonseca: Consultant; Self; Abbott. Board Member; Self; American Association of Clinical Endocrinologists. Consultant; Self; Eli Lilly and Company. Stock/Shareholder; Self; Amgen Inc.. Consultant; Self; Asahi Kasei Corporation, AstraZeneca, Novo Nordisk Inc., ADOCIA, Intarcia Therapeutics, Inc., Sanofi-Aventis. L.A. Bazzano: None.

Importance Clinical trials have documented that lowering blood pressure reduces cardiovascular disease and premature deaths. However, the optimal target for reduction of systolic blood pressure (SBP) is uncertain. Objective To assess the association of mean achieved SBP levels with the risk of cardiovascular disease and all-cause mortality in adults with hypertension treated with antihypertensive therapy. Data Sources MEDLINE and EMBASE were searched from inception to December 15, 2015, supplemented by manual searches of the bibliographies of retrieved articles. Study Selection Studies included were clinical trials with random allocation to an antihypertensive medication, control, or treatment target. Studies had to have reported a difference in mean achieved SBP of 5 mm Hg or more between comparison groups. Data Extraction and Synthesis Data were extracted from each study independently and in duplicate by at least 2 investigators according to a standardized protocol. Network meta-analysis was used to obtain pooled randomized results comparing the association of each 5–mm Hg SBP category with clinical outcomes after adjusting for baseline risk. Main Outcomes and Measures Cardiovascular disease and all-cause mortality. Results Forty-two trials, including 144 220 patients, met the eligibility criteria. In general, there were linear associations between mean achieved SBP and risk of cardiovascular disease and mortality, with the lowest risk at 120 to 124 mm Hg. Randomized groups with a mean achieved SBP of 120 to 124 mm Hg had a hazard ratio (HR) for major cardiovascular disease of 0.71 (95% CI, 0.60-0.83) compared with randomized groups with a mean achieved SBP of 130 to 134 mm Hg, an HR of 0.58 (95% CI, 0.48-0.72) compared with those with a mean achieved SBP of 140 to 144 mm Hg, an HR of 0.46 (95% CI, 0.34-0.63) compared with those with a mean achieved SBP of 150 to 154 mm Hg, and an HR of 0.36 (95% CI, 0.26-0.51) compared with those with a mean achieved SBP of 160 mm Hg or more. Likewise, randomized groups with a mean achieved SBP of 120 to 124 mm Hg had an HR for all-cause mortality of 0.73 (95% CI, 0.58-0.93) compared with randomized groups with a mean achieved SBP of 130 to 134 mm Hg, an HR of 0.59 (95% CI, 0.45-0.77) compared with those with a mean achieved SBP of 140 to 144 mm Hg, an HR of 0.51 (95% CI, 0.36-0.71) compared with those with a mean achieved SBP of 150 to 154 mm Hg, and an HR of 0.47 (95% CI, 0.32-0.67) compared with those with a mean achieved SBP of 160 mm Hg or more. Conclusions and Relevance This study suggests that reducing SBP to levels below currently recommended targets significantly reduces the risk of cardiovascular disease and all-cause mortality. These findings support more intensive control of SBP among adults with hypertension.

Evidence has suggested the existence of a bi-directional relationship between cardiovascular disease and physical performance in elderly adults, with several potential common mechanisms including chronic inflammation and sarcopenia. Yet, there remains little data on the relationship between CVD risk and physical performance in mid-life. The objective of this study was to determine if global cardiovascular risk measures were associated with score on the short physical performance battery (SPPB) in a mid-life cohort of African-American and white adults followed since childhood. Our study included 845 participants of the Bogalusa Heart Study cohort. We separately examined the relationships between both 10-year AtheroSclerotic CardioVascular Disease (ASCVD) and Framingham CHD risks and poor physical performance, defined as SPPB

Background: Studies conducted in elderly and frail adult populations, especially those with heart failure, have shown a consistent relationship between poor sleep and poor physical performance. Likewise, a similar association between poor sleep and lower performance has been found in extremely fit, elite athletes. However, this relationship has not been examined in healthy, middle-aged adult populations. Here, we test the cross-sectional association of daytime sleepiness with poor physical performance in our large, bi-racial cardiovascular cohort. Methods: From 2013-2016, 1,223 adults from the Bogalusa Heart Study attended follow-up visits to assess physical and cognitive performance and answer questionnaires pertaining to sleep habits. The Epworth Sleepiness Scale (ESS) was used to measure daytime sleepiness on an ordinal scale from 0-24. Short Physical Performance Battery (SPPB), which consists of chair stands, balance testing, and walk speed, was the outcome measure, with a score of 10) vs. normal (ESS≤10)] and poor physical performance. Results: Our study population had a mean(SD) age of 48.1(5.2) and was 58.6% female and 34.7% black. Mean(SD) ESS was 6.3(4.7). 252 (20.6%) adults exhibited poor physical performance. After covariate adjustment, ESS was significantly associated with an increased risk of poor physical performance (Odds Ratio per 1 SD increase=1.17; 95% Confidence Interval=1.01-1.35; p =0.03). As a dichotomous exposure, an abnormal ESS resulted in a 53% increased risk of poor physical performance (OR=1.53; 95% CI=1.05-2.23; p =0.03). Conclusions: Even among relatively healthy middle-aged adults, daytime sleepiness appears to be associated with poor physical performance.

Introduction: That adverse health outcomes, including atherosclerosis, are associated with sleep disturbance is well-documented; however, evidence from diverse populations on the magnitude of this association, or investigating sleepiness as an outcome, is scarce. Methods: We examined data from theBogalusa Heart Study, a long-term community-based observational study of a biracial cohort, with first measurements in childhood in 1973. Men and women (n=546) who underwent a measure of carotid intima-media thickness (IMT), calculated as the composite IMT (cIMT), mean of six segments (common and internal carotid, and carotid bifurcation, each left and right), and completed the Epworth Sleepiness Scale (ESS), were included. Multivariable logistic regression was employed to model the association between ordinal self-rated sleepiness and cIMT per standard deviation, adjusted for age, sex, smoking status (at time of IMT measurement), hours of sleep, symptoms of sleep disturbance, and previous heart attack. Based on previous race-specific findings, data were analyzed separately by race. Results: Of whites (n=356), 59.6% were female and 22.5% were current smokers. Mean (SD) age was 43.1 (4.4) years, and cIMT was 0.6 (0.1) mm. Of African-Americans (n=190), 66.8% were female, 34.7% were current smokers. Mean (SD) age was 42.8 (4.6) years, and cIMT was 0.7 (0.2) mm. Multivariate modeling found a significant race-cIMT interaction term (p=0.04). In stratified analyses, the adjusted odds of abnormal sleepiness (vs. normal sleepiness) were 1.40 times greater (95% CI: 1.04-1.90) per 1-SD increase in cIMT in whites, while among black participants, the odds ratio (95% CI) was 1.01 (0.68-1.50). Conclusions: There was a significant association between unfavorable subclinical measures of atherosclerosis and excessive daytime sleepiness among white participants.

Introduction: Few studies have examined the long term patterns of blood pressure change in relation to depression in middle age. Methods: We examined data from the Bogalusa Heart Study, a long-term community-based observational study of a biracial cohort, with first measurements in childhood in 1973. Men and women (n=909) who completed the Center for Epidemiologic Studies Depression Scale (CES-D) in 2010 with at least two childhood and two adult SBP measurements were included. CES-D scores were categorized using established cut points (15). Discrete mixture modeling was employed to identify trajectory groupings of (SBP), adjusted for race (time-independent) and body mass index (time-varying). The association between SBP trajectory and CES-D scores were determined using multivariable logistic regression adjusted for antihypertensive use, education, and physical activity in 2010. Results: Mean (±SD) age was 43.1±4.5 years, 57.9% were female, and 31.7% were Black. 27.7% of participants were current smokers in 2010. Mean (SD) BMI was 31.0 (7.7). We identified four SBP patterns: always low but slightly increasing (46.8%), low and modestly increasing (22.6%), healthy and stable (21.8%), and profoundly increasing (8.9%). Relative to the largest group, the multivariable adjusted odds ratio (OR) of higher CES-D categorization, i.e. more depressed, for the modestly increasing was 1.47 (95% CI, 1.01-2.15), for the stable, 0.96 (95% CI, 0.66-1.39), and for the profoundly increasing, 1.93 (95% CI, 0.66-1.39). Each additional year of education was associated with 33% decreased odds of higher CES-D categorization (OR=0.67, 95% CI 0.59-0.77). Conclusions: Trajectories of SBP from childhood through adulthood are associated with depression in middle age. Individuals with increasing SBP may benefit from depression screening in early adulthood.

Introduction: It is well known that depression and heart disease are closely linked. However, it remains unclear whether changes in cardiovascular (CV) risk factors over time may be related to depression. Few studies have examined the long term patterns of CV risk factors in relation to depression in middle age. Hypothesis: The trajectories of cardiovascular risk factors are associated with depression and depressive symptoms. Methods: We examined data from the Bogalusa Heart Study, a long-term community-based observational study of a biracial cohort, with first measurements in childhood in 1976. Men and women who completed the CES-D in 2010 with at least two childhood and two adult CV measurements (n=913) were included. Age, systolic blood pressure, antihypertensive treatment status, smoking status, total and HDL cholesterol, were used to calculate standardized 10-year Framingham CV risk scores at each follow-up. CES-D scores were categorized using established cut points (15). Discrete mixture modeling was employed to identify trajectory groupings of CV risk. The association between CV risk score trajectory and CES-D were determined using multivariable logistic regression adjusted for smoking, education, physical activity, and BMI in 2010. Results: Mean (±SD) age was 43.06±4.48 years, 57.9% were female, and 31.7% were black race. 27.7% of participants were current smokers in 2010. Mean (±SD) BMI was 30.97±7.73. We identified three CV risk patterns: stable (63.8%), slightly elevated (28.8%), and increasingly elevated (7.5%). Relative to stable CV risk, the multivariable adjusted odds ratio of higher CES-D categorization, i.e. more depressed, for slightly elevated was 1.49 (95% CI, 1.08-2.06), and for increasingly elevated, 1.53 (95% CI, 0.90-2.59). Smokers had increased odds of higher CES-D categorization over nonsmokers (OR=2.16, 95% CI 1.58-2.95). One-unit increases of BMI were associated with 1.02 times greater odds of higher CES-D categorization (95% CI, 1.01-1.04). Conclusions: Trajectories of cardiovascular risk from childhood through adulthood are associated with depression in middle age. Individuals with elevated or increasing cardiovascular risk profiles may benefit from depression screening in early middle age.

Introduction: Systemic inflammation -as measured by high-sensitivity C-reactive protein (hs-CRP)- is adversely associated with arterial compliance. However, information is scant on whether this association in consistent throughout the different non-invasive measurements of arterial compliance. Hypothesis: We assessed the hypothesis that divergences exist in the association between hs-CRP and measurements of arterial compliance, and that this association differs among race (white/black) groups in relatively young adults. Methods: Measurements of hsCRP and non-invasive arterial compliance --large-artery elasticity index (C1), small-artery elasticity index (C2), brachial-ankle pulse-wave velocity (ba-PWV) and augmentation index (AI@75)-- were assessed in 702 non-institutionalized participants with a mean age of 43.5 years (29.4-51.1 years); 70.8% whites and 43.7% males, as a part of the Bogalusa Heart Study. Race-specific independent associations were tested through multivariable-adjusted linear regression analyses. Results: Black vs white participants had higher hs-CRP, baPWV and AI@75 (p Conclusion: In conclusion, these findings help enhance the concept that the association of inflammation and arterial compliance is seemingly relative, as it is dependent on the measurement used to assess the latter; with its impact varying by race (black-white). Further, these observations may aid in revising existing methodologies used in the diagnosis of inflammation-mediated structural and functional damage, in addition to enhance race-specific approaches for screening and prevention of cardio-metabolic risk factors.

Decreased cerebral perfusion due to reduced arterial compliance is linked to cognitive and physical impairment in aging adults with overt vascular disease. However, this association, as well as its racial (black-white) disparities, have not been thoroughly elucidated in non-institutionalized middle-aged adults. Our analyses considered 471 participants of the Bogalusa Heart Study (mean age 48.2 years, 33.8% blacks, 58.6% females) with available information on arterial compliance —assessed non-invasively via aorto-femoral pulse wave velocity (afPWV)— in two time points (mean follow-up 12.7 years), as well as cognitive and physical function assessed later in life. Black participants with impaired physical and cognitive function showed significantly greater yearly progression of afPWV compared to white participants. In multivariable-adjusted logistic regression analyses, yearly progression of afPWV was significantly associated with decreased cognitive and physical function, in black participants only. These findings suggest a race-specific differential impact of decreasing vascular compliance over time on impaired cognitive/physical function in middle-aged adults. More multidisciplinary research initiatives should be undertaken to explore race-specific physiopatological mechanisms involved in the effect of vascular aging on cognitive and physical function deterioration.

It is unclear whether BMI from childhood and young adulthood predicts cognition and physical performance in mid-life. Using data from Bogalusa Heart Study (n=880; mean (SD) age at baseline=10.6 years (2.8), BMI=18.1 (3.6), 64.1% female, 33.0% black), we examined the longitudinal association of BMI, measured at recurrent clinic visits, with cognition (the sum of standardized scores on 11 validated neuropsychological tests) and physical performance (the Short Physical Performance Battery [SPPB]). A one-unit increase in BMI was associated with a decrease of 0.14 points (p