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1.
J Hypertens ; 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33196557

RESUMO

OBJECTIVE: Angiogenic T cells (Tang cells), a recently discovered T-cell subset, have been reported involved in the repair of endothelial injury. The purpose of this study was to explore the correlation of immunologic senescence and pro-inflammatory capacity of Tang cells with endothelial dysfunction in hypertensive patients. METHODS: Immunological characteristics of Tang cells (CD3CD31CXCR4) from hypertensive patients with or without endothelial dysfunction were elucidated by surface immunophenotyping and intracellular cytokine staining. Endothelial function was measured by flow-mediated dilation (FMD). RESULTS: The frequency of CD28 subset in CD4 Tang cells was notably elevated in hypertensive patients with endothelial dysfunction, which was negatively associated with FMD. The high frequency of CD28CD4 Tang cells was an independent risk factor of endothelial dysfunction with good diagnostic performance in ROC curve analysis. Immunophenotyping revealed that this specific subset of Tang cells exhibited senescent profile and has low hTERT expression. CD28CD4 Tang cells produced high levels of inflammatory cytokines, IL-6, IFN-γ and TNF-α, and significantly correlated with the systemic inflammation in hypertensive patients with endothelial dysfunction. CONCLUSION: Collectively, our findings demonstrate for the first time that CD28 subset in CD4 Tang cells with senescent and pro-inflammatory phenotype is dependently correlated with impaired FMD and systemic inflammation, which might contribute to the immunopathologic mechanism of endothelial dysfunction. Identification of a pathogenic CD4 Tang-cell subset lacking CD28 may offer opportunities for the evaluation and management of endothelial dysfunction in hypertension.

2.
Medicine (Baltimore) ; 99(47): e21856, 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33217787

RESUMO

BACKGROUND: To systematically evaluate the efficacy and safety of combined aclidinium bromide and formoterol fumarate for chronic obstructive pulmonary disease (COPD). METHODS: Electronic databases including PubMed, MEDLINE, EMBASE, Cochrane Library Central Register of Controlled Trials, WanFang, and China National Knowledge Infrastructure (CNKI) database were searched for studies on the use of combined aclidinium bromide and formoterol fumarate in the treatment of COPD. Two independent researchers performed literature screening, data extraction, and assessment of quality of studies. The strength of the association of the efficacy and safety of combined aclidinium bromide and formoterol fumarate in the treatment of COPD was evaluated according to the odds ratio (OR), mean differences (MDs), and 95% confidence interval (CI). Statistical analysis was carried out via using RevMan 5.3 software. RESULTS: The results of the present study will be published in a peer-reviewed journal. CONCLUSION: The conclusion of the present study will provide evidence to judge whether combined aclidinium bromide and formoterol fumarate is an effective and safety intervention in the treatment of COPD. SYSTEMATIC REVIEW REGISTRATION NUMBER: INPLASY202070063.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33129732

RESUMO

OBJECTIVES: The purpose of this study was to identify predictors of healthy arterial aging (long-term coronary artery calcification [CAC] of 0) among individuals with metabolic syndrome (MetS) or type 2 diabetes (T2D), which may improve primary prevention strategies. BACKGROUND: Individuals with MetS or T2D have a heterogeneously increased risk of atherosclerotic cardiovascular disease and not all have a high-intermediate risk. METHODS: We included 574 participants from the MESA (Multi-Ethnic Study of Atherosclerosis) with MetS or T2D who had CAC=0 at baseline and a repeat CAC scan 10 years later. Multivariable logistic regression assessed the association of traditional and novel atherosclerotic cardiovascular disease risk factors and the MetS severity score (based on the 5 MetS criteria) with healthy arterial aging. RESULTS: The mean age of participants was 58.9 years, 67% were women, 422 participants had MetS, and 152 had T2D. The proportion with long-term CAC=0 was similar for MetS (42%) and T2D (44%). A younger age was the only individual low/normal traditional risk factor associated with an increased likelihood of long-term CAC=0 (odds ratio [OR]: 1.50; 95% confidence interval [CI]: 1.22 to 1.85 per 10-years younger). The strongest associations of nontraditional risk factors were observed for an absence of thoracic calcification (OR: 2.42; 95% CI: 1.24 to 4.72), absence of carotid plaque (OR: 1.81; 95% CI: 1.25 to 2.61), and among persons with a high sensitivity troponin <3 ng/ml (OR: 1.55; 95% CI: 1.01 to 2.38). In addition, persons with the lowest quartile MetS severity score had a substantially higher odds of healthy long-term CAC=0 (OR: 2.71; 95% CI: 1.27 to 5.76). CONCLUSIONS: More than 40% of adults with MetS or T2D and baseline CAC=0 had long-term absence of CAC, which was most strongly associated with an absence of extracoronary atherosclerosis and a low MetS score. An optimal overall cardiovascular profile appears to be more important than an ideal value of any individual risk factor to maintain healthy arterial aging.

4.
Adv Mater ; : e2004290, 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33174265

RESUMO

There is an increasing interest to develop a next generation of touch pads that require stretchability and biocompatibility to allow their integration with a human body, and even to mimic the self-healing behavior with fast functionality recovery upon damage. However, most touch pads are developed based on stiff and brittle electrodes with the lack of the important nature of self-healing. Polyzwitterion-clay nanocomposite hydrogels as a soft, stretchable, and transparent ionic conductor with transmittance of 98.8% and fracture strain beyond 1500% are developed, which can be used as a self-healing human-machine interactive touch pad with pressure-sensitive adhesiveness on target substrates. A surface-capacitive touch system is adopted to sense a touched position. Finger positions are perceived during both point-by-point touch and continuous moving. Hydrogel touch pads are adhered to curved or flat insulators, with the high-resolution and self-healable input functions demonstrated by drawing, writing, and playing electronic games.

5.
Proc Natl Acad Sci U S A ; 117(46): 29013-29024, 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33144501

RESUMO

Poor metabolic control and host genetic predisposition are critical for diabetic kidney disease (DKD) development. The epigenome integrates information from sequence variations and metabolic alterations. Here, we performed a genome-wide methylome association analysis in 500 subjects with DKD from the Chronic Renal Insufficiency Cohort for DKD phenotypes, including glycemic control, albuminuria, kidney function, and kidney function decline. We show distinct methylation patterns associated with each phenotype. We define methylation variations that are associated with underlying nucleotide variations (methylation quantitative trait loci) and show that underlying genetic variations are important drivers of methylation changes. We implemented Bayesian multitrait colocalization analysis (moloc) and summary data-based Mendelian randomization to systematically annotate genomic regions that show association with kidney function, methylation, and gene expression. We prioritized 40 loci, where methylation and gene-expression changes likely mediate the genotype effect on kidney disease development. Functional annotation suggested the role of inflammation, specifically, apoptotic cell clearance and complement activation in kidney disease development. Our study defines methylation changes associated with DKD phenotypes, the key role of underlying genetic variations driving methylation variations, and prioritizes methylome and gene-expression changes that likely mediate the genotype effect on kidney disease pathogenesis.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33231909

RESUMO

Using 4-phenylpyridine or 2-phenylpyridine in place of biphenyl, two electron-poor phenylpyridyl-fused boroles, [TipPBB1] 4 and TipPBB2 were prepared. [TipPBB1] 4 adopts a unique coordination mode and forms a tetramer with a cavity in both the solid state and solution. The boron center of TipPBB2 is 4-coordinate in the solid state but the system dissociates in solution, leading to 3-coordinate borole species. Compared to its borafluorene analogues, the electron accepting ability of TipPBB2 is largely enhanced by the pyridyl group. TipPBB2 exhibits dual fluorescence in solution due to an equilibrium between free TipPBB2 and a weak intermolecular coordination adduct with a second molecule. This equilibrium was further investigated by low temperature NMR and photophysical studies. Theoretical studies indicate that the highest occupied molecular orbital (HOMO) of TipPBB2 localizes at the Tip group, in contrast to its borafluorene derivatives wherein the HOMOs are localized on borafluorene cores.

7.
Nature ; 586(7831): 763-768, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33057201

RESUMO

Age is the dominant risk factor for most chronic human diseases, but the mechanisms through which ageing confers this risk are largely unknown1. The age-related acquisition of somatic mutations that lead to clonal expansion in regenerating haematopoietic stem cell populations has recently been associated with both haematological cancer2-4 and coronary heart disease5-this phenomenon is termed clonal haematopoiesis of indeterminate potential (CHIP)6. Simultaneous analyses of germline and somatic whole-genome sequences provide the opportunity to identify root causes of CHIP. Here we analyse high-coverage whole-genome sequences from 97,691 participants of diverse ancestries in the National Heart, Lung, and Blood Institute Trans-omics for Precision Medicine (TOPMed) programme, and identify 4,229 individuals with CHIP. We identify associations with blood cell, lipid and inflammatory traits that are specific to different CHIP driver genes. Association of a genome-wide set of germline genetic variants enabled the identification of three genetic loci associated with CHIP status, including one locus at TET2 that was specific to individuals of African ancestry. In silico-informed in vitro evaluation of the TET2 germline locus enabled the identification of a causal variant that disrupts a TET2 distal enhancer, resulting in increased self-renewal of haematopoietic stem cells. Overall, we observe that germline genetic variation shapes haematopoietic stem cell function, leading to CHIP through mechanisms that are specific to clonal haematopoiesis as well as shared mechanisms that lead to somatic mutations across tissues.

8.
Physiol Plant ; 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33090487

RESUMO

Rising levels of atmospheric carbon dioxide (CO2 ) could, potentially, be exploited as a means to increase seed yield and maintain food security, especially for cereal grains. Although there have been multiple cultivar trials indicating that significant yield variation occurs, the basis for these differences has not been entirely elucidated. Here, we focus on two rice cultivars that differed in field trials to their yield sensitivity to elevated CO2 : Yangdao6hao (YD6), and Wuyunjing23 (W23) to assess whether observed yield differences (YD6 > W23) were associated with concurrent changes in leaf-level characteristics. At ambient levels of CO2 , leaf net photosynthesis (A) of YD6 was compatible with that of W23. However, at elevated CO2 , A was higher for YD6 relative to W23. The stability of leaf Rubisco content, biochemical characteristics (Vc,max, and Jmax ), nitrogen enzymatic activity, and chlorophyll concentration differed significantly, with greater values observed for YD6 relative to W23 at elevated CO2 . While such results are consistent with other studies, we also demonstrate that a higher ratio of carbon sinks (seed) to carbon sources (leaf), were linked to increases in cytokinins, and slower flag leaf senescence for the YD6 relative to the W23 cultivar at elevated CO2 . While additional data for a broader genetic selection are needed, the current study suggests a link between source/sink carbon assimilation, maintenance of photosynthetic biochemistry, and slower leaf senescence for rice cultivars that show a stronger yield response to projected CO2 levels. This information, in turn, may provide suitable metrics for future CO2 selection among rice cultivars.

9.
Clin J Am Soc Nephrol ; 15(11): 1566-1575, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33023894

RESUMO

BACKGROUND AND OBJECTIVES: Endothelial dysfunction is common among patients with CKD. We tested the efficacy and safety of combination treatment with sodium nitrite and isoquercetin on biomarkers of endothelial dysfunction in patients with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This randomized, double-blind, placebo-controlled phase 2 pilot trial enrolled 70 patients with predialysis CKD. Thirty-five were randomly assigned to combination treatment with sodium nitrite (40 mg twice daily) and isoquercetin (225 mg once daily) for 12 weeks, and 35 were randomly assigned to placebo. The primary outcome was mean change in flow-mediated vasodilation over the 12-week intervention. Secondary and safety outcomes included biomarkers of endothelial dysfunction, inflammation, and oxidative stress as well as kidney function, methemoglobin, and adverse events. Intention-to-treat analysis was conducted. RESULTS: Baseline characteristics, including age, sex, race, cigarette smoking, history of hypertension and diabetes, use of renin-angiotensin system blockers, BP, fasting glucose, lipid profile, kidney function, urine albumin-creatinine ratio, and endothelial biomarkers, were comparable between groups. Over the 12-week intervention, flow-mediated vasodilation increased 1.1% (95% confidence interval, -0.1 to 2.3) in the treatment group and 0.3% (95% confidence interval, -0.9 to 1.5) in the placebo group, and net change was 0.8% (95% confidence interval, -0.9 to 2.5). In addition, changes in biomarkers of endothelial dysfunction (vascular adhesion molecule-1, intercellular adhesion molecule-1, E-selectin, vWf, endostatin, and asymmetric dimethylarginine), inflammation (TNF-α, IL-6, C-reactive protein, IL-1 receptor antagonist, and monocyte chemoattractant protein-1), and oxidative stress (oxidized LDL and nitrotyrosines) were not significantly different between the two groups. Furthermore, changes in eGFR, urine albumin-creatinine ratio, methemoglobin, and adverse events were not significantly different between groups. CONCLUSIONS: This randomized phase 2 pilot trial suggests that combination treatment with sodium nitrite and isoquercetin did not significantly improve flow-mediated vasodilation or other endothelial function biomarkers but also did not increase adverse events compared with placebo among patients with CKD. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Nitrite, Isoquercetin, and Endothelial Dysfunction (NICE), NCT02552888.

10.
J Am Soc Nephrol ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33023926

RESUMO

BACKGROUND: Slopes of eGFR have been associated with increased risks of death and cardiovascular events in a U-shaped fashion. Poor outcomes in individuals with rising eGFR are potentially attributable to sarcopenia, hemodilution, and other indicators of clinical deterioration. METHODS: To investigate the association between eGFR slopes and risks of death or cardiovascular events, accounting for multiple confounders, we studied 2738 individuals with moderate to severe CKD participating in the multicenter Chronic Renal Insufficiency Cohort (CRIC) Study. We used linear, mixed-effects models to estimate slopes with up to four annual eGFR assessments, and Cox proportional hazards models to investigate the association between slopes and the risks of death and cardiovascular events. RESULTS: Slopes of eGFR had a bell-shaped distribution (mean [SD], -1.5 [-2] ml/min per 1.73 m2 per year). Declines of eGFR that were steeper than the average decline associated with progressively increasing risks of death (hazard ratio [HR], 1.23; 95% confidence interval [95% CI], 1.09 to 1.39; for a slope 1 SD below the average) and cardiovascular events (HR, 1.19; 95% CI, 1.03 to 1.38). Rises of eGFR or declines lower than the average decline were not associated with the risk of death or cardiovascular events. CONCLUSIONS: In a cohort of individuals with moderate to severe CKD, we observed steep declines of eGFR were associated with progressively increasing risks of death and cardiovascular events; however, we found no increased risks associated with eGFR improvement. These findings support the potential value of eGFR slopes in clinical assessment of adults with CKD.

11.
Artigo em Inglês | MEDLINE | ID: mdl-33026583

RESUMO

Ethiprole has been widely used in agriculture, but there have been few studies on the adverse effects of ethiprole on nontarget organisms. This study focused on the mechanism of the sublethal effects of ethiprole on the development, antioxidation mechanisms, detoxification mechanisms and immune-related gene expression of honeybees (Apis mellifera L.). Honeybee larvae were found to be more sensitive than pupae to ethiprole. It was found that ethiprole inhibited the pupation and eclosion of bee larvae in a dose-dependent manner, with ethiprole doses of 1 × 10-3 mg/L decreasing pupation and eclosion rates to 50.00 ± 8.84% and 20.83 ± 10.62%, respectively. The activities of antioxidative enzymes (superoxide dismutase and catalase) and detoxification factors (glutathione and glutathione S-transferase) were also significantly increased in ethiprole-exposed honeybees, indicating that a sublethal dose of ethiprole also induced oxidative stress in honeybees. In the 1 × 10-3 mg/L ethiprole-exposure group, the expression of pathogen recognition-related gene PGRP-4300 was upregulated 11.10 ± 0.45-fold, and that of detoxification-related gene CYP4G11 was upregulated 8.84 ± 0.11-fold, indicating that ethiprole induced an immune reaction in honeybees. To the best our knowledge, this study represents the first demonstration that sublethal concentrations of ethiprole inhibit honeybee development and activate honeybee defense and immune systems.

12.
Am J Kidney Dis ; 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32866540

RESUMO

RATIONALE & OBJECTIVE: Identification of novel risk factors for chronic kidney disease (CKD) progression may inform mechanistic investigations and improve identification of high-risk subgroups. The current study aimed to characterize CKD progression across levels of numerous risk factors and identify independent risk factors for CKD progression among those with and without diabetes. STUDY DESIGN: The Chronic Renal Insufficiency Cohort (CRIC) Study is a prospective cohort study of adults with CKD conducted at 7 US clinical centers. SETTING & PARTICIPANTS: Participants (N=3,379) had up to 12.3 years of follow-up; 47% had diabetes. PREDICTORS: 30 risk factors for CKD progression across sociodemographic, behavioral, clinical, and biochemical domains at baseline. OUTCOMES: Study outcomes were estimated glomerular filtration rate (eGFR) slope and the composite of halving of eGFR or initiation of kidney replacement therapy. ANALYTICAL APPROACH: Stepwise selection of independent risk factors was performed stratified by diabetes status using linear mixed-effects and Cox proportional hazards models. RESULTS: Among those without and with diabetes, respectively, mean eGFR slope was-1.4±3.3 and-2.7±4.7mL/min/1.73m2 per year. Among participants with diabetes, multivariable-adjusted hazard of the composite outcome was approximately 2-fold or greater with higher levels of the inflammatory chemokine CXCL12, the cardiac marker N-terminal pro-B-type natriuretic peptide (NT-proBNP), and the kidney injury marker urinary neutrophil gelatinase-associated lipocalin (NGAL). Among those without diabetes, low serum bicarbonate and higher high-sensitivity troponin T, NT-proBNP, and urinary NGAL levels were all significantly associated with a 1.5-fold or greater rate of the composite outcome. LIMITATIONS: The observational study design precludes causal inference. CONCLUSIONS: Strong associations for cardiac markers, plasma CXCL12, and urinary NGAL are comparable to that of systolic blood pressure≥140mm Hg, a well-established risk factor for CKD progression. This warrants further investigation into the potential mechanisms that these markers indicate and opportunities to use them to improve risk stratification.

13.
Nutr Metab Cardiovasc Dis ; 30(12): 2328-2334, 2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-32917498

RESUMO

BACKGROUND AND AIMS: Netrin-1 was a laminin-related protein involved in neurovascular protection, and we previously discovered that decreased serum netrin-1 was associated with poor prognosis of ischemic stroke. However, the relationship between serum netrin-1 level and the risk of ischemic stroke remains unclear. The aim of this study was to investigate the association between netrin-1 level and risk of ischemic stroke. METHODS AND RESULTS: A case-control study including 591 ischemic stroke patients and 591 age- and sex-matched healthy individuals was conducted, and serum netrin-1 concentrations were quantitatively determined via enzyme-linked immunosorbent assay for all participants. The serum netrin-1 levels were significantly lower in the ischemic stroke patients than those in matched controls (median, 496.4 vs 652.1 pg/mL; P < 0.001). After adjustment for potential confounders, the odds ratio of ischemic stroke associated with the highest quartile of netrin-1 was 0.07 (95% CI: 0.01-0.65; Ptrend = 0.018) compared with the lowest quartile of netrin-1. Each 1-standard deviation increase of log-transformed netrin-1 was associated with a lower odds of ischemic stroke (odds ratio: 0.45, 95% CI: 0.22-0.94; P = 0.032), and a dose-response relationship between serum netrin-1 and ischemic stroke was observed (Plinearity = 0.003). Incorporating netrin-1 to conventional risk factors improved the discriminatory power for ischemic stroke (net reclassification index = 98.0%, P < 0.001; integrated discrimination improvement = 0.28%, P = 0.027). CONCLUSIONS: Serum netrin-1 was decreased in patients with ischemic stroke compared with healthy controls, suggesting that there was a potential role of netrin-1 in the pathogenesis of ischemic stroke.

14.
Neuroreport ; 31(15): 1072-1083, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-32881772

RESUMO

Acupuncture is widely used to treat various neurodegenerative diseases and can effectively improve cognitive and memory states in Alzheimer's disease. However, its mechanism is unclear. We speculated that the effect of acupuncture on cognitive function may be associated with reductions in the levels of Aß and phosphorylated tau in the brain. In this experiment, 60 male Sprague-Dawley rats were randomly divided into control, model, electroacupuncture and nonacupoint groups. We perform electroacupuncture at Shenting (GV24) and bilateral Benshen (GB13) acupoints once a day for 4 weeks in electroacupuncture group (with 1 day of rest after every 6 days of treatment). The electroacupuncture group showed a better performance in cognitive-related behavior tests and significantly lowers the levels of Aß, p-tau (s396) and p-tau (s404) in the hippocampus. These results may suggest that electroacupuncture at the GV24 and bilateral GB13 acupoints might improve cognitive functions in Alzheimer's disease by decreasing the levels of Aß, p-tau (s396) and p-tau (s404) in the brain as these proteins are the main causes of neurological damage and cognitive dysfunction during the pathogenesis underlying Alzheimer's disease.

15.
Clin Chim Acta ; 511: 33-39, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32986993

RESUMO

RATIONALE: N-terminal pro-brain natriuretic peptide (NT-proBNP) and galectin-3 are important biomarkers related to ischemic stroke. However, the predictive value of the combination of them has not been examined in previous studies. OBJECTIVE: The aim of this study was to investigate the combined effect of NT-proBNP and galectin-3 on clinical outcomes in ischemic stroke patients. METHODS: A total of 2694 patients (63.62% males; mean age = 62.4 in admission) with serum NT-proBNP and galectin-3 measured simultaneously were included in this study. The primary outcome was composite outcome of death or major disability 1 year after stroke onset. Secondary outcomes were separately death, major disability, vascular events and the composite outcome of vascular events or death. The participants were divided into 4 groups according to NT-proBNP and galectin-3. Odd ratios (ORs; for nonevent outcome without time variables: primary outcome, major disability) or hazard ratios (HRs; for event outcome with time variables: death, vascular events, and the composite outcome of vascular events or death) were calculated to assess the association of NT-proBNP and galectin-3 status with adverse outcomes. RESULTS: At the 1-year follow-up, 589 patients experienced a primary outcome after stroke onset. After adjustment for potential confounders, high NT-proBNP/high galectin-3 group were associated with increased risks of primary outcome (OR: 1.43; 95% confidence interval [CI], 1.02-2.00; P value = 0.039), death (HR: 2.74; 95% CI, 1.42-5.29; P value = 0.003), and the composite outcome of vascular events or death (HR: 1.66; 95% CI, 1.06-2.58; P value = 0.026). Statistical tests for interactions between the 4 groups and primary outcome or death were not significant (all P interaction > 0.05). CONCLUSION: Simultaneously increased NT-proBNP and galectin-3 significantly increased the risk of poor clinical outcomes 1 year after ischemic stroke. Using NT-proBNP and galectin-3 together can result in an accurate prediction of ischemic stroke prognosis.

16.
Nutr Metab Cardiovasc Dis ; 30(11): 2077-2084, 2020 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-32819784

RESUMO

BACKGROUND AND AIMS: To examine the associations between history of gestational diabetes mellitus (GDM) and breastfeeding with branched-chain amino acids (BCAA) and their metabolites in later life. METHODS AND RESULTS: 638 women (mean age 48.0 y) who had participated in the Bogalusa Heart Study and substudies of pregnancy history had untargeted, ultrahigh performance liquid chromatography-tandem mass spectroscopy conducted by Metabolon© on serum samples. Metabolites were identified that were BCAA or associated with BCAA metabolic pathways. History of GDM at any pregnancy (self-reported, confirmed with medical records when possible) as well as breastfeeding were examined as predictors of BCAA using linear models, controlling for age, race, BMI, waist circumference, and menopausal status. None of the BCAA differed statistically by history of either GDM or breastfeeding, although absolute levels of each of the BCAA were higher with GDM and lower with breastfeeding. Of the 27 metabolites on the leucine, isoleucine and valine metabolism subpathway, 1-carboxyethylleucine, 1-carboxyethyvaline, and 3-hydroxy-2-ethylpropionate were higher in women with a history of GDM, but lower in women in women with a history of breastfeeding. Similar results were found for alpha-hydroxyisocaproate, 1-carboxyethylisoleucine, and N-acetylleucine. CONCLUSIONS: GDM and breastfeeding are associated in opposite directions with several metabolites on the BCAA metabolic pathway.

17.
J Am Heart Assoc ; 9(16): e016671, 2020 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-32779506

RESUMO

Background Epidemiological studies have reported discrepant findings on the relationship between education level and outcomes after stroke. We aimed to prospectively investigate the relationship between education level and mortality, recurrent stroke, and cardiovascular events in Chinese patients with ischemic stroke. Methods and Results We included 3861 participants from the China Antihypertensive Trial in Acute Ischemic Stroke. Education level was categorized as illiteracy, primary school, middle school, and college. Study outcomes were all-cause mortality, stroke-specific mortality, recurrent stroke, and cardiovascular events within 2 years after ischemic stroke. A meta-analysis was conducted to incorporate the results of the current study and previous other studies on the association of education level with outcomes after stroke. Within 2 years after ischemic stroke, there were 327 (8.5%) all-cause deaths, 264 (6.8%) stroke-specific deaths, 303 (7.9%) recurrent strokes, and 364 (9.4%) cardiovascular events, respectively. The Kaplan-Meier curves showed that patients with the lowest education level had the highest cumulative incidence rates of all-cause mortality, stroke-specific mortality, and cardiovascular events (log-rank P≤0.01). After adjusted for covariates, hazard ratios and 95% CIs of illiteracy versus college education were 2.79 (1.32-5.87) for all-cause mortality, 3.68 (1.51-8.98) for stroke-specific mortality, 2.82 (1.20-6.60) for recurrent stroke, and 3.46 (1.50-7.95) for cardiovascular events. The meta-analysis confirmed the significant association between education status and mortality after stroke (pooled relative risk for lowest versus highest education level, 1.24 [95% CI, 1.05-1.46]). Conclusions Low education level was significantly associated with increased risk of mortality, recurrent stroke, and cardiovascular events after ischemic stroke, independently of established risk factors. Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT01840072.

18.
J Am Heart Assoc ; 9(16): e016405, 2020 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-32779511

RESUMO

Background Data are limited regarding the relationship between the life-course burden of risk factors and adult cardiac function. This study sought to examine the impact of long-term burden of body mass index (BMI) and blood pressure (BP) levels on changes in adult left ventricular (LV) structure and function in a community-based cohort. Methods and Results The longitudinal study cohort consisted of 1108 adult patients (726 White; 41.9% men; mean age, 48.2 years in the last survey) who had been examined 4 to 16 times for BMI and BP and echocardiographic LV structure and function in adulthood, with a mean follow-up period of 38.8 years. The area under the curve was used as a measure of long-term burden of BMI and BP. Adult LV mass index was significantly associated with childhood and adulthood BMI and systolic BP (SBP), and their area under the curve values (ß=0.07-0.37; P<0.05 for all). Adult LV ejection fraction was negatively associated with childhood BMI (ß=-0.08), adult BMI (ß=-0.07) and BMI area under the curve (ß=-0.07) (P<0.05 for all); the effects of SBP measures were not significant. Adult E/A ratio was negatively associated with adulthood SBP (ß=-0.13; P<0.01) and total area under the curve of SBP (ß=-0.13; P<0.01). E/e' ratio was positively associated with BMI and SBP measures. The effects of diastolic BP measures were substantially similar to those of SBP measures. Participants with LV hypertrophy, eccentric hypertrophy, and concentric hypertrophy had significantly lower LV ejection fraction and higher E/e' ratio. Conclusions These observations provide strong evidence that early-life adiposity and BP levels and their life-course cumulative burdens are associated with subclinical changes in adult LV structure and function in the general population.

19.
Circ Cardiovasc Imaging ; 13(8): e010335, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32772573

RESUMO

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/m2.7 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.

20.
Am Heart J ; 230: 13-24, 2020 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-32827458

RESUMO

BACKGROUND: The Systolic Blood Pressure Intervention Trial (SPRINT) reported that intensive blood pressure (BP) treatment reduced cardiovascular disease and mortality compared to standard BP treatment in hypertension patients. The next important question is how to implement more intensive BP treatment in real-world clinical practice. We designed an effectiveness-implementation hybrid trial to simultaneously test the effectiveness of a multifaceted intervention for intensive BP treatment and its feasibility, fidelity, and sustainability in underserved hypertension patients. METHODS: Implementation of Multifaceted Patient-Centered Treatment Strategies for Intensive Blood Pressure Control (IMPACTS) is a cluster randomized trial conducted in 36 Federally Qualified Health Center clinics in Louisiana and Mississippi. Federally Qualified Health Center clinics were randomized to either a multifaceted intervention for intensive BP treatment, including protocol-based treatment using the SPRINT intensive BP management algorithm, dissemination of SPRINT findings, BP audit and feedback, home BP monitoring, and health coaching, or enhanced usual care. Difference in mean systolic BP change from baseline to 18 months is the primary clinical effectiveness outcome, and intervention fidelity, measured by treatment intensification and medication adherence, is the primary implementation outcome. The planned sample size of 1,260 participants (36 clinics with 35 participants each) has 90% power to detect a 5.0-mm Hg difference in systolic BP at a .05 significance level and 80% follow-up rate. CONCLUSIONS: IMPACTS will generate critical data on the effectiveness and implementation of a multifaceted intervention for intensive BP treatment in real-world clinical practice and could directly impact the BP-related disease burden in minority and low-income populations in the United States.

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