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1.
Eur J Heart Fail ; 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32212368

RESUMO

AIMS: Chronic hyperglycaemia, assessed by elevated glycated haemoglobin (A1C), is a known risk factor for heart failure (HF) and cardiovascular (CV) death among subjects with diabetes. Whether this risk varies with left ventricular ejection fraction (LVEF) is unknown. This study evaluated whether A1C influences a composite outcome of either HF hospitalization or CV death differently along the spectrum of LVEF. METHODS AND RESULTS: We assessed the relationships of baseline A1C and LVEF with a composite outcome of either CV death or HF hospitalization in the 4091 patients with type 2 diabetes and a recent acute coronary syndrome enrolled in the ELIXA trial who had available LVEF. We assessed for interaction between A1C and LVEF as continuous variables with respect to this outcome. During a median follow-up of 25.7 months, 343 patients (8.4%) had HF hospitalization or died of CV causes. In a multivariable model, A1C and LVEF were each associated with an increased risk of HF hospitalization or CV death [adjusted hazard ratio (HR) 1.11, 95% confidence interval (CI) 1.01-1.21 per 1% higher A1C, and adjusted HR 1.39, 95% CI 1.27-1.51 per 10% lower in LVEF]. Both A1C and LVEF were independently and incrementally associated with risk without evidence of interaction (P for interaction = 0.31). Patients with A1C ≥ 8% and LVEF <40% were at threefold higher risk than those with A1C < 7% and LVEF ≥50% (adjusted HR 3.18, 95% CI 2.03-4.98, P < 0.001). CONCLUSION: In a contemporary cohort of patients with type 2 diabetes and acute coronary syndrome, baseline chronic hyperglycaemia was associated with an increased risk of HF hospitalization or CV death independently of LVEF.

2.
JAMA Netw Open ; 3(2): e200100, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32101310

RESUMO

Importance: Patients with rheumatoid arthritis (RA) are at high risk for cardiovascular (CV) mortality, attributed to chronic inflammation coupled with elevated circulatory homocysteine levels. Increasing the serum folate level reduces homocysteine, but the association of serum folate concentration with CV mortality in patients with RA has not been previously examined. Objective: To examine the association of serum folate concentration and CV mortality risk among patients with RA. Design, Setting, and Participants: A cohort study of the third National Health and Nutrition Examination Survey (1988-1994) and 2011 Linked Mortality File was performed. Adults aged 18 years or older with self-reported physician-diagnosed RA were included. Data analysis was performed between April 2019 and June 2019. Exposure: Serum folate level. Main Outcomes and Measures: All-cause and CV mortality risk estimated using Cox proportional hazards models, adjusted for the complex survey design and patient characteristics, including demographic characteristics, body mass index, C-reactive protein level, smoking, RA medication use, and comorbid conditions. Results: A total of 683 patients with RA (mean [SE] age, 55.9 [1.0] years; 225 [30.2%] men; 478 [87.0%] white) were classified into tertiles based on serum folate levels, as follows: tertile 1, folate levels less than 4.3 ng/mL (n = 239); tertile 2, folate levels 4.3 ng/mL to 8.2 ng/mL (n = 234); and tertile 3, folate levels greater than 8.2 ng/mL (n = 210). During a median (interquartile range) follow-up of 17.4 (10.0-19.4) years, a total of 392 all-cause deaths and 258 CV deaths occurred. Compared with tertile 1, patients in tertile 2 had lower all-cause mortality risk (hazard ratio [HR], 0.63; 95% CI, 0.47-0.85). The risk of CV mortality was lower among patients in tertile 2 (HR, 0.52; 95% CI, 0.30-0.92) and tertile 3 (HR, 0.44; 95% CI, 0.26-0.75) compared with those in tertile 1 (P for trend = .01). Findings for CV mortality were consistent in a sensitivity analysis that estimated 10-year risk; patients in tertile 2 (HR, 0.31; 95% CI, 0.17-0.57) and tertile 3 (HR, 0.39; 95% CI, 0.22-0.69) had lower CV mortality risk compared with those in tertile 1 (P for trend = .04). Conclusions and Relevance: Among patients with RA, a serum folate level of at least 4.3 ng/mL was associated with lower CV mortality risk. Further research is needed to examine whether a causal relationship exists between serum folate and CV risk among patients with RA.

3.
Diabetologia ; 63(2): 287-295, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31802145

RESUMO

AIMS/HYPOTHESIS: To understand the complex metabolic changes that occur long before the diagnosis of type 2 diabetes, we investigated differences in metabolomic profiles in plasma between prediabetic and normoglycaemic individuals for subtypes of prediabetes defined by fasting glucose, 2 h glucose and HbA1c measures. METHODS: Untargeted metabolomics data were obtained from 155 plasma samples from 127 Mexican American individuals from Starr County, TX, USA. None had type 2 diabetes at the time of sample collection and 69 had prediabetes by at least one criterion. We tested statistical associations of amino acids and other metabolites with each subtype of prediabetes. RESULTS: We identified distinctive differences in amino acid profiles between prediabetic and normoglycaemic individuals, with further differences in amino acid levels among subtypes of prediabetes. When testing all named metabolites, several fatty acids were also significantly associated with 2 h glucose levels. Multivariate discriminative analyses show that untargeted metabolomic data have considerable potential for identifying metabolic differences among subtypes of prediabetes. CONCLUSIONS/INTERPRETATION: People with each subtype of prediabetes have a distinctive metabolomic signature, beyond the well-known differences in branched-chain amino acids. DATA AVAILABILITY: Metabolomics data are available through the NCBI database of Genotypes and Phenotypes (dbGaP, accession number phs001166; www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001166.v1.p1).

4.
Am J Med ; 133(3): 290-296, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31520618

RESUMO

We propose a unifying perspective of heart failure in patients with type 2 diabetes mellitus. The reasoning is as follows: cellular responses to fuel overload include dysregulated insulin signaling, impaired mitochondrial respiration, reactive oxygen species formation, and the accumulation of certain metabolites, collectively termed glucolipotoxicity. As a consequence, cardiac function is impaired, with intracellular calcium cycling and diastolic dysfunction as an early manifestation. In this setting, increasing glucose uptake by insulin or insulin sensitizing agents only worsens the disrupted fuel homeostasis of the heart. Conversely, restricting fuel supply by means of caloric restriction, surgical intervention, or certain pharmacologic agents will improve cardiac function by restoring metabolic homeostasis. The concept is borne out by clinical interventions, all of which unload the heart from metabolic stress.

5.
J Neurophysiol ; 123(1): 22-33, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31747354

RESUMO

The type 5 metabotropic glutamate receptor (mGluR5) represents a novel therapeutic target for schizophrenia and other disorders. Schizophrenia is associated with progressive abnormalities in cortical oscillatory processes including reduced spindles (8-15 Hz) during sleep and increased delta (0.5-4 Hz)- and gamma-band activity (30-80 Hz) during wakefulness. mGluR5 knockout (KO) mice demonstrate many schizophrenia-like behaviors, including abnormal sleep. To examine the effects of mGluR5 on the maintenance of the neocortical circuitry responsible for such neural oscillations, we analyzed sleep/wake electroencephalographic (EEG) activity of mGluR5 KO mice at baseline, after 6 h of sleep deprivation, and during a visual method of cortical entrainment (visual steady state response). We hypothesized mGluR5-KO mice would exhibit translationally relevant abnormalities in sleep and neural oscillations that mimic schizophrenia. Power spectral and spindle density analyses were performed across 24-h EEG recordings in mGluR5-KO mice and wild-type (WT) controls. Novel findings in mGluR5 KO mice include deficits in sleep spindle density, wake alpha power, and 40-Hz visual task-evoked gamma power and phase locking. Sigma power (10-15 Hz), an approximation of spindle activity, was also reduced during non-rapid eye movement sleep transitions. Our observations on abnormal sleep/wake are generally in agreement with previous reports, although we did not replicate changes in rapid eye movement sleep. The timing of these phenotypes may suggest an impaired circadian process in mGluR5 KO mice. In conclusion, EEG phenotypes in mGluR5 KO mice resemble deficits observed in patients with schizophrenia. These findings implicate mGluR5-mediated pathways in several translationally relevant phenotypes associated with schizophrenia, and suggest that agents targeting this receptor may have harmful consequences on sleep health and daily patterns of EEG power.NEW & NOTEWORTHY Metabotropic glutamate receptor type 5 (mGluR5) knockout (KO) mice show several translationally relevant abnormalities in neural oscillatory activity associated with schizophrenia. These include deficits in sleep spindle density, sigma and alpha power, and 40-Hz task-evoked gamma power. The timing of these phenotypes suggests an impaired circadian process in these mice. Previously reported rapid eye movement sleep deficits in this model were not observed. These findings suggest mGluR5-enhancing drugs may improve sleep stability and sleep spindle density, which could impact memory and cognition.

6.
Nutrients ; 11(12)2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31783663

RESUMO

MyPlate is a guidance system for healthier eating choices. In this cross-sectional study, we investigated the influence of MyPlate food group consumption and exercise on metabolic syndrome (MetS) parameters in college students. Participant (n = 462) blood was analyzed using Cholestech for triglycerides (TG), glucose, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). In addition, weight, waist circumference (WC), and blood pressure (BP) were measured. Diet and Wellness Plus was used to compute participant diet records. Regression analysis and a recursive decision tree were made to predict MetS using RStudio (V.1.1.463). BP decision tree predicted high risk of elevated blood pressure with a recall rate of 93.7%. For males; exercise, empty calories, dairy, and protein were main predictors. For females, vegetable and empty calorie consumption were primary determinants. HDL-C decision tree had a recall rate of 91.8% and showed that the main low HDL-C risk determinants for males were; exercise and grain consumption. Conversely, for females; empty calories, grain, and vegetable consumption were the key factors determining low HDL-C risk. This study shows that MyPlate recommendations are valuable to achieve adequate HDL-C and blood pressure and provides insight into the importance of tailoring food intake guidance based on gender.

7.
Stress ; : 1-11, 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31747807

RESUMO

Objectives: The purpose of this study was to characterize the stress experienced by pregnant women in Kenya and assess the relationship between perceived stress and stress-related biomarkers of cortisol and cortisone.Background: Kenyan women are exposed to multiple stressors that may result in chronic stress. However, antenatal stress has not been examined and characterized in Kenya; nor has the relationship between pregnant women's self-reported stress and stress biomarkers been established.Methods: One hundred and fifty women were recruited between 22 and 28 weeks gestation. Participants completed the Perceived Stress Scale (PSS) and a sociodemographic questionnaire. Hair samples were obtained for analysis of cortisol and cortisone. Factor analysis was used to extract unique clusters of stress symptoms from items in the PSS. Regression models were computed to examine relationships of stress to cortisone and cortisol, controlling for obstetric risk.Results: Mean age of the women was 25 years (SD = 5, ±16-41). Their degree of perceived stress and cortisol/cortisone concentrations both indicated moderate levels of stress. There was no association between general perceived stress and either hair cortisol or cortisone. However, factor analysis of the PSS identified three clusters of stress symptoms and one cluster - a woman's negative frame of mind regarding life and inefficacy in handling its problems - was associated with higher levels of cortisone (ß= -.231, p = 0.011).Conclusions: Specific stress symptoms may have unique relationships to specific biomarkers and be more useful in assessment than general perceived stress. Assays of both hair cortisol and cortisone might enable a more comprehensive assessment of glucocorticoid activity and better prediction of health risks from stress.Lay summaryUnderstanding stress among rural pregnant Kenyan women may help in addressing risks during pregnancy that lead to adverse birth outcomes. Findings suggest that a woman's tendency to think negatively about life and to doubt her ability to handle life's problems are symptoms of stress that may contribute to higher levels of stress hormones. Assessing women's specific symptoms of stress and different stress hormones during pregnancy may more effectively identify women who need intervention to reduce their health risk.

11.
Front Psychol ; 10: 1474, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31312154

RESUMO

Enhancing creativity and developing technology skills in the classroom are the future of education and can turn out to be powerful tools to smooth out inequalities in class. This paper presents a systematic scoping review study of the literature focusing on cases of social creativity and digital technology embedded in science education. To this end, 23 empirical studies were selected from several databases-all in English and subjected to a blind peer-review process-to address the interconnectedness of key themes encapsulated in the following three research questions: (i) which digital technology roles support collaborative and creative processes in science education? (ii) which forms of technology and technological features support and organize the aforementioned creative processes? and (iii) what pedagogical principles guide the promotion of social creativity using technology in science education and involve all the students? Results show that technology can play different roles in promoting social creativity: (1) as a tutoring device that nurtures some key science creative processes; (2) as a tool that shapes students' creative thinking; and (3) as a medium that builds the supportive environment to perform collective creativity processes. In our project, these three roles were performed using a wide range of web 2.0 technologies (e.g., web-based environments, digital platforms, mobile technology) that both engaged all students in active and rich user experience for collective knowledge creation and equipped all learners with the necessary skills that would turn them into active, i.e., dynamic and resourceful, citizens in a swiftly changing world.

12.
Circulation ; 140(7): e294-e324, 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31167558

RESUMO

Type 2 diabetes mellitus is a risk factor for incident heart failure and increases the risk of morbidity and mortality in patients with established disease. Secular trends in the prevalence of diabetes mellitus and heart failure forecast a growing burden of disease and underscore the need for effective therapeutic strategies. Recent clinical trials have demonstrated the shared pathophysiology between diabetes mellitus and heart failure, the synergistic effect of managing both conditions, and the potential for diabetes mellitus therapies to modulate the risk of heart failure outcomes. This scientific statement on diabetes mellitus and heart failure summarizes the epidemiology, pathophysiology, and impact of diabetes mellitus and its control on outcomes in heart failure; reviews the approach to pharmacological therapy and lifestyle modification in patients with diabetes mellitus and heart failure; highlights the value of multidisciplinary interventions to improve clinical outcomes in this population; and outlines priorities for future research.

13.
J Card Fail ; 25(8): 584-619, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31174952

RESUMO

Type 2 diabetes mellitus is a risk factor for incident heart failure and increases the risk of morbidity and mortality in patients with established disease. Secular trends in the prevalence of diabetes mellitus and heart failure forecast a growing burden of disease and underscore the need for effective therapeutic strategies. Recent clinical trials have demonstrated the shared pathophysiology between diabetes mellitus and heart failure, the synergistic effect of managing both conditions, and the potential for diabetes mellitus therapies to modulate the risk of heart failure outcomes. This scientific statement on diabetes mellitus and heart failure summarizes the epidemiology, pathophysiology, and impact of diabetes mellitus and its control on outcomes in heart failure; reviews the approach to pharmacological therapy and lifestyle modification in patients with diabetes mellitus and heart failure; highlights the value of multidisciplinary interventions to improve clinical outcomes in this population; and outlines priorities for future research.

14.
Am J Cardiol ; 124(2): 296-302, 2019 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-31104774

RESUMO

Echocardiograms are the second most frequently utilized cardiac test after electrocardiograms and are most commonly ordered by noncardiology providers. Echocardiogram reports are designed to communicate a comprehensive interpretation of cardiac function; however, it is not known how well these reports are understood by ordering providers. In order to identify gaps in understanding and target potential areas for improvement, we developed a questionnaire testing various topics reported on a standard transthoracic echocardiogram report. This questionnaire was administered to general medicine and cardiology trainees and attending physicians at 2 large academic institutions. Questionnaire response rate was 81%. There were several topics that were not well understood by general providers; these included viability of an akinetic region, pulmonary artery systolic pressure, left ventricular filling pressure, recognition of abnormal structures, and method of identifying of intracardiac thrombus. In conclusion, strategies such as improved communication techniques and adjustment of reporting format should be implemented to increase the clinical value of the echocardiogram.


Assuntos
Competência Clínica , Ecocardiografia/normas , Clínicos Gerais/normas , Cardiopatias/diagnóstico , Feminino , Humanos , Masculino , Estudos Retrospectivos , Inquéritos e Questionários
15.
Biol Open ; 8(6)2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31142467

RESUMO

The ventricular-subventricular zone (V-SVZ) of the forebrain is the source of neurogenic stem/precursor cells for adaptive and homeostatic needs throughout the life of most mammals. Here, we report that Suppressor of Fused (Sufu) plays a critical role in the establishment of the V-SVZ at early neonatal stages by controlling the proliferation of distinct subpopulations of stem/precursor cells. Conditional deletion of Sufu in radial glial progenitor cells (RGCs) at E13.5 resulted in a dramatic increase in the proliferation of Sox2+ Type B1 cells. In contrast, we found a significant decrease in Gsx2+ and a more dramatic decrease in Tbr2+ transit amplifying cells (TACs) indicating that innate differences between dorsal and ventral forebrain derived Type B1 cells influence Sufu function. However, many precursors accumulated in the dorsal V-SVZ or failed to survive, demonstrating that despite the over-proliferation of Type B1 cells, they are unable to transition into functional differentiated progenies. These defects were accompanied by reduced Gli3 expression and surprisingly, a significant downregulation of Sonic hedgehog (Shh) signaling. Therefore, these findings indicate a potential role of the Sufu-Gli3 regulatory axis in the neonatal dorsal V-SVZ independent of Shh signaling in the establishment and survival of functional stem/precursor cells in the postnatal dorsal V-SVZ.

16.
J Clin Hypertens (Greenwich) ; 21(6): 766-773, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31099465

RESUMO

Understanding the patterns of antihypertensive drug use and blood pressure (BP) control among stroke survivors in the "real-world" setting is important to identify gaps in treatment and control, if any. The objective of our study was to assess trends and patterns in antihypertensive drug use and BP control among stroke survivors in the United States. We performed a retrospective cross-sectional analysis of the 2003-2014 National Health and Nutrition Examination Survey (NHANES). Stroke and hypertension diagnoses were self-reported. Information regarding the use of antihypertensive drugs was collected during an in-person interview. Measurement of BP was performed by trained medical professionals in mobile examination centers. A total 1244 adult stroke survivors (equating to 6 232 215 stroke survivors nationwide) were identified, of which 956 had hypertension. Antihypertensive drug use increased from 2003 (79.5%) to 2014 (92.2%; P for trend < 0.001). The prevalence of drug use was lower (52%) among survivors aged 20-39 years compared with older age groups. Use of ≥2 antihypertensive drugs was prevalent (63.8%), but diuretics alone or in combination with angiotensin-converting enzyme inhibitors were underutilized (22.4%). More than one-third of the survivors were not at BP goal (ie, BP < 140/90 mm Hg). Males were more likely to attain BP goal than female stroke survivors (odds ratio [OR] = 2.02; 95% CI: 1.34-3.05). Our findings suggest that despite improvements in antihypertensive drug use in the recent years, BP is not adequately controlled in a significant proportion of stroke survivors. Further research focusing on understanding the reasons for unmet BP goal in stroke survivors is needed.

17.
Sci Rep ; 9(1): 5845, 2019 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-30971721

RESUMO

Heart failure is a major cause for premature death. Given the heterogeneity of the heart failure syndrome, identifying genetic determinants of cardiac function and structure may provide greater insights into heart failure. Despite progress in understanding the genetic basis of heart failure through genome wide association studies, the heritability of heart failure is not well understood. Gaining further insights into mechanisms that contribute to heart failure requires systematic approaches that go beyond single trait analysis. We integrated a Bayesian multi-trait approach and a Bayesian networks for the analysis of 10 correlated traits of cardiac structure and function measured across 3387 individuals with whole exome sequence data. While using single-trait based approaches did not find any significant genetic variant, applying the integrative Bayesian multi-trait approach, we identified 3 novel variants located in genes, RGS3, CHD3, and MRPL38 with significant impact on the cardiac traits such as left ventricular volume index, parasternal long axis interventricular septum thickness, and mean left ventricular wall thickness. Among these, the rare variant NC_000009.11:g.116346115C > A (rs144636307) in RGS3 showed pleiotropic effect on left ventricular mass index, left ventricular volume index and maximal left atrial anterior-posterior diameter while RGS3 can inhibit TGF-beta signaling associated with left ventricle dilation and systolic dysfunction.

18.
Sleep Breath ; 23(4): 1107-1114, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30721387

RESUMO

PURPOSE: Sleep apnea is associated with increased risk of cardiovascular disease. Elevated plasma galectin-3 levels, a biomarker associated with myocardial fibrosis, are also associated with adverse cardiovascular events, including heart failure. Our objective was to determine the relationship between severity of sleep apnea and plasma levels of galectin-3 and to determine whether this relationship was modified by sex. METHODS: We performed a cross-sectional study of 471 Mexican Americans from Starr County, TX who underwent an overnight, in-home sleep evaluation, and plasma measurement of galectin-3. Severity of sleep apnea was based on apnea hypopnea index (AHI). Multivariable linear regression modeling was used to determine the association between categories of sleep apnea and galectin-3. We also tested for interactions by sex. RESULTS: The mean age was 53 years, and 74% of the cohort was female. The prevalence of moderate to severe sleep apnea (AHI > 15 apnea-hypopnea events per hour) was 36.7%. Moderate to severe sleep apnea was associated with increased levels of galectin-3 in the entire population, but we identified a statistically significant interaction between galectin-3 levels and category of sleep apnea by sex (p for interaction = 0.02). Plasma galectin levels were significantly higher in women with moderate or severe sleep apnea than women with no/mild sleep apnea (multivariable adjusted p < 0.001), but not in men (p = 0.5). CONCLUSIONS: Sleep apnea is associated elevated galectin-3 levels in women but not men. Our findings highlight a possible sex-specific relationship between sleep apnea and galectin-3, a biomarker of potential myocardial fibrosis that has been associated with increased cardiovascular risk.

19.
J Am Heart Assoc ; 8(4): e011971, 2019 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-30776984

RESUMO

See Article by Raghavan et al.


Assuntos
Doenças Cardiovasculares , Sistema Cardiovascular , Diabetes Mellitus Tipo 2 , Adulto , Humanos
20.
Hum Mol Genet ; 28(7): 1212-1224, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30624610

RESUMO

Interpretation of genetic association results is difficult because signals often lack biological context. To generate hypotheses of the functional genetic etiology of complex cardiometabolic traits, we estimated the genetically determined component of gene expression from common variants using PrediXcan (1) and determined genes with differential predicted expression by trait. PrediXcan imputes tissue-specific expression levels from genetic variation using variant-level effect on gene expression in transcriptome data. To explore the value of imputed genetically regulated gene expression (GReX) models across different ancestral populations, we evaluated imputed expression levels for predictive accuracy genome-wide in RNA sequence data in samples drawn from European-ancestry and African-ancestry populations and identified substantial predictive power using European-derived models in a non-European target population. We then tested the association of GReX on 15 cardiometabolic traits including blood lipid levels, body mass index, height, blood pressure, fasting glucose and insulin, RR interval, fibrinogen level, factor VII level and white blood cell and platelet counts in 15 755 individuals across three ancestry groups, resulting in 20 novel gene-phenotype associations reaching experiment-wide significance across ancestries. In addition, we identified 18 significant novel gene-phenotype associations in our ancestry-specific analyses. Top associations were assessed for additional support via query of S-PrediXcan (2) results derived from publicly available genome-wide association studies summary data. Collectively, these findings illustrate the utility of transcriptome-based imputation models for discovery of cardiometabolic effect genes in a diverse dataset.


Assuntos
Previsões/métodos , Metaboloma/genética , Metaboloma/fisiologia , Adulto , Idoso , Pressão Sanguínea , Índice de Massa Corporal , Mapeamento Cromossômico/métodos , Grupos Étnicos/genética , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Estudos de Associação Genética/métodos , Estudo de Associação Genômica Ampla/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Herança Multifatorial/genética , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Transcriptoma/genética
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