Association Between High Perceived Stress Over Time and Incident Hypertension in Black Adults: Findings From the Jackson Heart Study.

Background Chronic psychological stress has been associated with hypertension, but few studies have examined this relationship in blacks. We examined the association between perceived stress levels assessed annually for up to 13 years and incident hypertension in the Jackson Heart Study, a community-based cohort of blacks. Methods and Results Analyses included 1829 participants without hypertension at baseline (Exam 1, 2000-2004). Incident hypertension was defined as blood pressure≥140/90 mm Hg or antihypertensive medication use at Exam 2 (2005-2008) or Exam 3 (2009-2012). Each follow-up interval at risk of hypertension was categorized as low, moderate, or high perceived stress based on the number of annual assessments between exams in which participants reported "a lot" or "extreme" stress over the previous year (low, 0 high stress ratings; moderate, 1 high stress rating; high, ≥2 high stress ratings). During follow-up (median, 7.0 years), hypertension incidence was 48.5%. Hypertension developed in 30.6% of intervals with low perceived stress, 34.6% of intervals with moderate perceived stress, and 38.2% of intervals with high perceived stress. Age-, sex-, and time-adjusted risk ratios (95% CI) associated with moderate and high perceived stress versus low perceived stress were 1.19 (1.04-1.37) and 1.37 (1.20-1.57), respectively (P trend<0.001). The association was present after adjustment for demographic, clinical, and behavioral factors and baseline stress (P trend=0.001). Conclusions In a community-based cohort of blacks, higher perceived stress over time was associated with an increased risk of developing hypertension. Evaluating stress levels over time and intervening when high perceived stress is persistent may reduce hypertension risk

Pterostilbene on Metabolic Parameters: A Randomized, Double-Blind, and Placebo-Controlled Trial

Introduction. The purpose of this trial was to evaluate the effect of pterostilbene on metabolic parameters. Methods. A prospective, randomized, double-blind, and placebo-controlled study that enrolled 80 patients with a total cholesterol ≥200 mg/dL and/or LDL≥100 mg/dL. Subjects were divided into four groups: (1) pterostilbene 125 mg twice daily; (2) pterostilbene 50 mg twice daily; (3) pterostilbene 50 mg + grape extract (GE) 100 mg twice daily; (4) matching placebo twice daily for 6–8 weeks. Endpoints included lipids, blood pressure, and weight. Linear mixed models were used to examine and compare changes in parameters over time. Models were adjusted for age, gender, and race. Results. LDL increased with pterostilbene monotherapy (17.1 mg/dL; P=0.001) which was not seen with GE combination (P=0.47). Presence of a baseline cholesterol medication appeared to attenuate LDL effects. Both systolic (−7.8 mmHg; P<0.01) and diastolic blood pressure (−7.3 mmHg; P<0.001) were reduced with high dose pterostilbene. Patients not on cholesterol medication (n=51) exhibited minor weight loss with pterostilbene (−0.62 kg/m2; P=0.012). Conclusion. Pterostilbene increases LDL and reduces blood pressure in adults. This trial is registered with Clinicaltrials.gov NCT01267227

Dysregulation of multiple metabolic networks related to brain transmethylation and polyamine pathways in Alzheimer disease: A targeted metabolomic and transcriptomic study.

BACKGROUND: There is growing evidence that Alzheimer disease (AD) is a pervasive metabolic disorder with dysregulation in multiple biochemical pathways underlying its pathogenesis. Understanding how perturbations in metabolism are related to AD is critical to identifying novel targets for disease-modifying therapies. In this study, we test whether AD pathogenesis is associated with dysregulation in brain transmethylation and polyamine pathways. METHODS AND FINDINGS: We first performed targeted and quantitative metabolomics assays using capillary electrophoresis-mass spectrometry (CE-MS) on brain samples from three groups in the Baltimore Longitudinal Study of Aging (BLSA) (AD: n = 17; Asymptomatic AD [ASY]: n = 13; Control [CN]: n = 13) (overall 37.2% female; mean age at death 86.118 ± 9.842 years) in regions both vulnerable and resistant to AD pathology. Using linear mixed-effects models within two primary brain regions (inferior temporal gyrus [ITG] and middle frontal gyrus [MFG]), we tested associations between brain tissue concentrations of 26 metabolites and the following primary outcomes: group differences, Consortium to Establish a Registry for Alzheimer's Disease (CERAD) (neuritic plaque burden), and Braak (neurofibrillary pathology) scores. We found significant alterations in concentrations of metabolites in AD relative to CN samples, as well as associations with severity of both CERAD and Braak, mainly in the ITG. These metabolites represented biochemical reactions in the (1) methionine cycle (choline: lower in AD, p = 0.003; S-adenosyl methionine: higher in AD, p = 0.005); (2) transsulfuration and glutathione synthesis (cysteine: higher in AD, p < 0.001; reduced glutathione [GSH]: higher in AD, p < 0.001); (3) polyamine synthesis/catabolism (spermidine: higher in AD, p = 0.004); (4) urea cycle (N-acetyl glutamate: lower in AD, p < 0.001); (5) glutamate-aspartate metabolism (N-acetyl aspartate: lower in AD, p = 0.002); and (6) neurotransmitter metabolism (gamma-amino-butyric acid: lower in AD, p < 0.001). Utilizing three Gene Expression Omnibus (GEO) datasets, we then examined mRNA expression levels of 71 genes encoding enzymes regulating key reactions within these pathways in the entorhinal cortex (ERC; AD: n = 25; CN: n = 52) and hippocampus (AD: n = 29; CN: n = 56). Complementing our metabolomics results, our transcriptomics analyses also revealed significant alterations in gene expression levels of key enzymatic regulators of biochemical reactions linked to transmethylation and polyamine metabolism. Our study has limitations: our metabolomics assays measured only a small proportion of all metabolites participating in the pathways we examined. Our study is also cross-sectional, limiting our ability to directly test how AD progression may impact changes in metabolite concentrations or differential-gene expression. Additionally, the relatively small number of brain tissue samples may have limited our power to detect alterations in all pathway-specific metabolites and their genetic regulators. CONCLUSIONS: In this study, we observed broad dysregulation of transmethylation and polyamine synthesis/catabolism, including abnormalities in neurotransmitter signaling, urea cycle, aspartate-glutamate metabolism, and glutathione synthesis. Our results implicate alterations in cellular methylation potential and increased flux in the transmethylation pathways, increased demand on antioxidant defense mechanisms, perturbations in intermediate metabolism in the urea cycle and aspartate-glutamate pathways disrupting mitochondrial bioenergetics, increased polyamine biosynthesis and breakdown, as well as abnormalities in neurotransmitter metabolism that are related to AD

Capturing a Stata dataset and releasing it into REDCap

With technology advances, researchers can now capture data using web-based applications. One such application, Research Electronic Data Capture (REDCap), allows for data entry from any computer with an Internet connection. As the use of REDCap has increased in popularity, we have observed the need to easily create data dictionaries and data collection instruments for REDCap. The command presented in this article, redcapture, demonstrates one method to create a REDCap-ready data dictionary using a loaded Stata dataset, illustrated by examples of starting from an existing dataset or completely starting from scratch

Capturing a Stata dataset and releasing it into REDCap

With technology advances, researchers can now capture data using web-based applications. One such application, Research Electronic Data Capture (REDCap), allows for data entry from any computer with an Internet connection. As the use of REDCap has increased in popularity, we have observed the need to easily create data dictionaries and data collection instruments for REDCap. The command presented in this article, redcapture, demonstrates one method to create a REDCap-ready data dictionary using a loaded Stata dataset, illustrated by examples of starting from an existing dataset or completely starting from scratch

Association Between High Perceived Stress Over Time and Incident Hypertension in Black Adults: Findings From the Jackson Heart Study.

Background Chronic psychological stress has been associated with hypertension, but few studies have examined this relationship in blacks. We examined the association between perceived stress levels assessed annually for up to 13&nbsp;years and incident hypertension in the Jackson Heart Study, a community-based cohort of blacks. Methods and Results Analyses included 1829 participants without hypertension at baseline (Exam 1, 2000-2004). Incident hypertension was defined as blood pressure≥140/90&nbsp;mm&nbsp;Hg or antihypertensive medication use at Exam 2 (2005-2008) or Exam 3 (2009-2012). Each follow-up interval at risk of hypertension was categorized as low, moderate, or high perceived stress based on the number of annual assessments between exams in which participants reported "a lot" or "extreme" stress over the previous year (low, 0 high stress ratings; moderate, 1 high stress rating; high, ≥2 high stress ratings). During follow-up (median, 7.0&nbsp;years), hypertension incidence was 48.5%. Hypertension developed in 30.6% of intervals with low perceived stress, 34.6% of intervals with moderate perceived stress, and 38.2% of intervals with high perceived stress. Age-, sex-, and time-adjusted risk ratios (95% CI) associated with moderate and high perceived stress versus low perceived stress were 1.19 (1.04-1.37) and 1.37 (1.20-1.57), respectively (P trend&lt;0.001). The association was present after adjustment for demographic, clinical, and behavioral factors and baseline stress (P trend=0.001). Conclusions In a community-based cohort of blacks, higher perceived stress over time was associated with an increased risk of developing hypertension. Evaluating stress levels over time and intervening when high perceived stress is persistent may reduce hypertension risk

Correction: Dysregulation of multiple metabolic networks related to brain transmethylation and polyamine pathways in Alzheimer disease: A targeted metabolomic and transcriptomic study.

[This corrects the article DOI: 10.1371/journal.pmed.1003012.]

Dysregulation of multiple metabolic networks related to brain transmethylation and polyamine pathways in Alzheimer disease: A targeted metabolomic and transcriptomic study.

BackgroundThere is growing evidence that Alzheimer disease (AD) is a pervasive metabolic disorder with dysregulation in multiple biochemical pathways underlying its pathogenesis. Understanding how perturbations in metabolism are related to AD is critical to identifying novel targets for disease-modifying therapies. In this study, we test whether AD pathogenesis is associated with dysregulation in brain transmethylation and polyamine pathways.Methods and findingsWe first performed targeted and quantitative metabolomics assays using capillary electrophoresis-mass spectrometry (CE-MS) on brain samples from three groups in the Baltimore Longitudinal Study of Aging (BLSA) (AD: n = 17; Asymptomatic AD [ASY]: n = 13; Control [CN]: n = 13) (overall 37.2% female; mean age at death 86.118 ± 9.842 years) in regions both vulnerable and resistant to AD pathology. Using linear mixed-effects models within two primary brain regions (inferior temporal gyrus [ITG] and middle frontal gyrus [MFG]), we tested associations between brain tissue concentrations of 26 metabolites and the following primary outcomes: group differences, Consortium to Establish a Registry for Alzheimer's Disease (CERAD) (neuritic plaque burden), and Braak (neurofibrillary pathology) scores. We found significant alterations in concentrations of metabolites in AD relative to CN samples, as well as associations with severity of both CERAD and Braak, mainly in the ITG. These metabolites represented biochemical reactions in the (1) methionine cycle (choline: lower in AD, p = 0.003; S-adenosyl methionine: higher in AD, p = 0.005); (2) transsulfuration and glutathione synthesis (cysteine: higher in AD, p ConclusionsIn this study, we observed broad dysregulation of transmethylation and polyamine synthesis/catabolism, including abnormalities in neurotransmitter signaling, urea cycle, aspartate-glutamate metabolism, and glutathione synthesis. Our results implicate alterations in cellular methylation potential and increased flux in the transmethylation pathways, increased demand on antioxidant defense mechanisms, perturbations in intermediate metabolism in the urea cycle and aspartate-glutamate pathways disrupting mitochondrial bioenergetics, increased polyamine biosynthesis and breakdown, as well as abnormalities in neurotransmitter metabolism that are related to AD

Abnormal brain cholesterol homeostasis in Alzheimer’s disease—a targeted metabolomic and transcriptomic study

The role of brain cholesterol metabolism in Alzheimer’s disease (AD) remains unclear. Peripheral and brain cholesterol levels are largely independent due to the impermeability of the blood brain barrier (BBB), highlighting the importance of studying the role of brain cholesterol homeostasis in AD. We first tested whether metabolite markers of brain cholesterol biosynthesis and catabolism were altered in AD and associated with AD pathology using linear mixed-effects models in two brain autopsy samples from the Baltimore Longitudinal Study of Aging (BLSA) and the Religious Orders Study (ROS). We next tested whether genetic regulators of brain cholesterol biosynthesis and catabolism were altered in AD using the ANOVA test in publicly available brain tissue transcriptomic datasets. Finally, using regional brain transcriptomic data, we performed genome-scale metabolic network modeling to assess alterations in cholesterol biosynthesis and catabolism reactions in AD. We show that AD is associated with pervasive abnormalities in cholesterol biosynthesis and catabolism. Using transcriptomic data from Parkinson’s disease (PD) brain tissue samples, we found that gene expression alterations identified in AD were not observed in PD, suggesting that these changes may be specific to AD. Our results suggest that reduced de novo cholesterol biosynthesis may occur in response to impaired enzymatic cholesterol catabolism and efflux to maintain brain cholesterol levels in AD. This is accompanied by the accumulation of nonenzymatically generated cytotoxic oxysterols. Our results set the stage for experimental studies to address whether abnormalities in cholesterol metabolism are plausible therapeutic targets in AD