Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 270
Filtrar
1.
Sci Rep ; 11(1): 332, 2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33432005

RESUMO

Among multiple subtypes of tissue or cell, subtype-specific differentially-expressed genes (SDEGs) are defined as being most-upregulated in only one subtype but not in any other. Detecting SDEGs plays a critical role in the molecular characterization and deconvolution of multicellular complex tissues. Classic differential analysis assumes a null hypothesis whose test statistic is not subtype-specific, thus can produce a high false positive rate and/or lower detection power. Here we first introduce a One-Versus-Everyone Fold Change (OVE-FC) test for detecting SDEGs. We then propose a scaled test statistic (OVE-sFC) for assessing the statistical significance of SDEGs that applies a mixture null distribution model and a tailored permutation test. The OVE-FC/sFC test was validated on both type 1 error rate and detection power using extensive simulation data sets generated from real gene expression profiles of purified subtype samples. The OVE-FC/sFC test was then applied to two benchmark gene expression data sets of purified subtype samples and detected many known or previously unknown SDEGs. Subsequent supervised deconvolution results on synthesized bulk expression data, obtained using the SDEGs detected from the independent purified expression data by the OVE-FC/sFC test, showed superior performance in deconvolution accuracy when compared with popular peer methods.

2.
Am Heart J ; 232: 125-136, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33160945

RESUMO

BACKGROUND: The HEART Pathway is an accelerated diagnostic protocol for Emergency Department patients with possible acute coronary syndrome. The objective was to compare the safety and effectiveness of the HEART Pathway among women vs men and whites vs non-whites. METHODS: A subgroup analysis of the HEART Pathway Implementation Study was conducted. Adults with chest pain were accrued from November 2013 to January 2016 from 3 Emergency Departments in North Carolina. The primary outcomes were death and myocardial infarction (MI) and hospitalization rates at 30 days. Logistic regression evaluated for interactions of accelerated diagnostic protocol implementation with sex or race and changes in outcomes within subgroups. RESULTS: A total of 8,474 patients were accrued, of which 53.6% were female and 34.0% were non-white. The HEART Pathway identified 32.6% of females as low-risk vs 28.5% of males (P = 002) and 35.6% of non-whites as low-risk vs 28.0% of whites (P < .0001). Among low-risk patients, death or MI at 30 days occurred in 0.4% of females vs 0.5% of males (P = .70) and 0.5% of non-whites vs 0.3% of whites (P = .69). Hospitalization at 30 days was reduced by 6.6% in females (aOR: 0.74, 95% CI: 0.64-0.85), 5.1% in males (aOR: 0.87, 95% CI: 0.75-1.02), 8.6% in non-whites (aOR: 0.72, 95% CI: 0.60-0.86), and 4.5% in whites (aOR: 0.83, 95% CI: 0.73-0.94). Interactions were not significant. CONCLUSION: Women and non-whites are more likely to be classified as low-risk by the HEART Pathway. HEART Pathway implementation is associated with decreased hospitalizations and a very low death and MI rate among low-risk patients regardless of sex or race.

3.
J Am Coll Cardiol ; 76(12): 1455-1465, 2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-32943164

RESUMO

BACKGROUND: Whether cardiovascular (CV) disease risk factors and biomarkers associate differentially with heart failure (HF) risk in men and women is unclear. OBJECTIVES: The purpose of this study was to evaluate sex-specific associations of CV risk factors and biomarkers with incident HF. METHODS: The analysis was performed using data from 4 community-based cohorts with 12.5 years of follow-up. Participants (recruited between 1989 and 2002) were free of HF at baseline. Biomarker measurements included natriuretic peptides, cardiac troponins, plasminogen activator inhibitor-1, D-dimer, fibrinogen, C-reactive protein, sST2, galectin-3, cystatin-C, and urinary albumin-to-creatinine ratio. RESULTS: Among 22,756 participants (mean age 60 ± 13 years, 53% women), HF occurred in 2,095 participants (47% women). Age, smoking, type 2 diabetes mellitus, hypertension, body mass index, atrial fibrillation, myocardial infarction, left ventricular hypertrophy, and left bundle branch block were strongly associated with HF in both sexes (p < 0.001), and the combined clinical model had good discrimination in men (C-statistic = 0.80) and in women (C-statistic = 0.83). The majority of biomarkers were strongly and similarly associated with HF in both sexes. The clinical model improved modestly after adding natriuretic peptides in men (ΔC-statistic = 0.006; likelihood ratio chi-square = 146; p < 0.001), and after adding cardiac troponins in women (ΔC-statistic = 0.003; likelihood ratio chi-square = 73; p < 0.001). CONCLUSIONS: CV risk factors are strongly and similarly associated with incident HF in both sexes, highlighting the similar importance of risk factor control in reducing HF risk in the community. There are subtle sex-related differences in the predictive value of individual biomarkers, but the overall improvement in HF risk estimation when included in a clinical HF risk prediction model is limited in both sexes.

4.
Am J Cardiol ; 136: 100-106, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-32910930

RESUMO

There is no clear consensus on a lower cutoff value for normal left ventricular ejection fraction (EF) and the prognostic implications of low normal EF (LNEF) are poorly understood, particularly in Blacks. Therefore, we investigated the association of LNEF and incident heart failure (HF) in a community-based cohort of Blacks. We studied 3,669 participants (mean age 54 years, 63% women) of the Jackson Heart Study without prevalent HF or coronary heart disease (CHD). Participants were divided into three groups: (1) Reduced EF (<50%), (2) LNEF (≥50%, <55%), and (3) Normal EF (≥55%). There were 197 cases of incident HF hospitalizations over a median follow-up of 10 years (interquartile range 9.4 to 10). After adjustment for conventional risk factors and incident CHD, the LNEF group had a higher rate of incident HF hospitalization than the Normal EF group (HR 1.58, 95% CI 1.04 to 2.38, p<0.05). Furthermore, this relation remained statistically significant after additionally adjusting for LV mass index but was not significant after adjusting for LV diastolic dysfunction grade. In participants with LNEF with incident HF, 63% developed HF with reduced EF and 37% developed HF with preserved EF. In conclusion, LNEF is associated with higher risk of incident HF hospitalization in comparison with normal EF in a community-based cohort of Blacks. In those with LNEF who went on to develop HF, most cases were HF with reduced EF. These findings suggest that strategies are needed for risk stratification and management to improve outcomes in patients with LNEF.


Assuntos
Afro-Americanos/estatística & dados numéricos , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/fisiopatologia , Hospitalização/estatística & dados numéricos , Volume Sistólico , Adulto , Idoso , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Mississippi/epidemiologia , Estudos Prospectivos , Medição de Risco
5.
Alcohol Clin Exp Res ; 44(9): 1825-1833, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32735738

RESUMO

BACKGROUND: Observational studies have shown that alcohol consumption above the recommended limit is associated with increased cardiovascular disease (CVD), although its association in South Asians is unclear. Less is known regarding the association between alcohol consumption and cardiovascular health (CVH), assessed by the American Heart Association's Life's Simple 7 (LS7) health metrics among those with South Asian ancestry. METHODS: This analysis included 701 participants without CVD from the Mediators of Atherosclerosis in South Asians Living in America (MASALA) cohort (2015 to 2018). Based on a personal history questionnaire, participants were divided into never, former, and current drinkers. The current drinking category was further classified into 1 to 3 drinks/wk, 4 to 7 drinks/wk, and >7 drinks/wk. The consumption of 5 or more drinks on 1 occasion in the past month was defined as binge drinking. Each LS7 component was given a point score of 0, 1, or 2. The total score was categorized into 0 to 6, 7 to 10, and 11 to 14 to represent poor, intermediate, and ideal CVH, respectively. We use multinomial logistic regression to examine the association between alcohol consumption and CVH. RESULTS: In the MASALA cohort (mean age = 59 years, 43% female), participants consuming >7 drinks/wk had the lowest mean CVH score. Compared with never drinkers, male participants consuming >7 drinks/wk were less likely to have intermediate CVH (0.44 [0.08, 0.91]) and ideal CVH (0.23 [0.03, 0.96]). Binge drinking was associated with significantly lower odds of ideal CVH compared with never drinkers. CONCLUSION: We found evidence of an inverse association of moderate to heavy alcohol consumption and ideal CVH in South Asian men. These findings further underscore the important relationship between alcohol consumption and CVH in this unique population of South Asians.

6.
Ann Emerg Med ; 76(5): 555-565, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32736933

RESUMO

STUDY OBJECTIVE: We determine whether implementation of the HEART (History, ECG, Age, Risk Factors, Troponin) Pathway is safe and effective in emergency department (ED) patients with possible acute coronary syndrome through 1 year of follow-up. METHODS: A preplanned analysis of 1-year follow-up data from a prospective pre-post study of 8,474 adult ED patients with possible acute coronary syndrome from 3 US sites was conducted. Patients included were aged 21 years or older, evaluated for possible acute coronary syndrome, and without ST-segment elevation myocardial infarction. Accrual occurred for 12 months before and after HEART Pathway implementation, from November 2013 to January 2016. The HEART Pathway was integrated into the electronic health record at each site as an interactive clinical decision support tool. After integration, ED providers prospectively used the HEART Pathway to identify patients with possible acute coronary syndrome as low risk (appropriate for early discharge without stress testing or angiography) or nonlow risk (appropriate for further inhospital evaluation). Safety (all-cause death and myocardial infarction) and effectiveness (hospitalization) at 1 year were determined from health records, insurance claims, and death index data. RESULTS: Preimplementation and postimplementation cohorts included 3,713 and 4,761 patients, respectively. The HEART Pathway identified 30.7% of patients as low risk; 97.5% of them were free of death and myocardial infarction within 1 year. Hospitalization at 1 year was reduced by 7.0% in the postimplementation versus preimplementation cohort (62.1% versus 69.1%; adjusted odds ratio 0.70; 95% confidence interval 0.63 to 0.78). Rates of death or myocardial infarction at 1 year were similar (11.6% versus 12.4%; adjusted odds ratio 1.00; 95% confidence interval 0.87 to 1.16). CONCLUSION: HEART Pathway implementation was associated with decreased hospitalizations and low adverse event rates among low-risk patients at 1-year follow-up.


Assuntos
Síndrome Coronariana Aguda/diagnóstico , Dor no Peito , Hospitalização/estatística & dados numéricos , Síndrome Coronariana Aguda/complicações , Adulto , Idoso , Dor no Peito/sangue , Dor no Peito/etiologia , Dor no Peito/mortalidade , Eletrocardiografia , Serviço Hospitalar de Emergência , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Valor Preditivo dos Testes , Estudos Prospectivos , Medição de Risco , Troponina/sangue
7.
Emerg Med J ; 37(11): 690-695, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32753395

RESUMO

BACKGROUND: The HEART Pathway combines a History ECG Age Risk factor (HEAR) score and serial troponins to risk stratify patients with acute chest pain. However, it is unclear whether patients with HEAR scores of <1 require troponin testing. The objective of this study is to measure the major adverse cardiac event (MACE) rate among patients with <1 HEAR scores and determine whether serial troponin testing is needed to achieve a miss rate <1%. METHODS: A secondary analysis of the HEART Pathway Implementation Study was conducted. HEART Pathway risk assessments (HEAR scores and serial troponin testing at 0 and 3 hours) were completed by the providers on adult patients with chest pain from three US sites between November 2014 and January 2016. MACE (composite of death, myocardial infarction (MI) and coronary revascularisation) at 30 days was determined. The proportion of patients with HEAR scores of <1 diagnosed with MACE within 30 days was calculated. The impact of troponin testing on patients with HEAR scores of <1 was determined using Net Reclassification Improvement Index (NRI). RESULTS: Providers completed HEAR assessments on 4979 patients and HEAR scores<1 occurred in 9.0% (447/4979) of patients. Among these patients, MACE at 30 days occurred in 0.9% (4/447; 95% CI 0.2% to 2.3%) with two deaths, two MIs and 0 revascularisations. The sensitivity and negative predictive value for MACE in the HEAR <1 was 97.8% (95%CI 94.5% to 99.4%) and 99.1% (95% CI 97.7% to 99.8%), respectively, and were not improved by troponin testing. Troponin testing in patients with HEAR <1 correctly reclassified two patients diagnosed with MACE, and was elevated among seven patients without MACE yielding an NRI of 0.9% (95%CI -0.7 to 2.4%). CONCLUSION: These data suggest that patients with HEAR scores of 0 and 1 represent a very low-risk group that may not require troponin testing to achieve a missed MACE rate <1%. Trial registration number NCT02056964.

8.
Heart ; 106(13): 977-984, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32269131

RESUMO

BACKGROUND: The History Electrocardiogram Age Risk factor Troponin (HEART) Pathway and Emergency Department Assessment of Chest pain Score (EDACS) are validated accelerated diagnostic pathways designed to risk stratify patients presenting to the emergency department with chest pain. Data from large multisite prospective studies comparing these accelerated diagnostic pathways are limited. METHODS: The HEART Pathway Implementation is a prospective three-site cohort study, which accrued adults with symptoms concerning for acute coronary syndrome. Physicians completed electronic health record HEART Pathway and EDACS risk assessments on participants. Major adverse cardiac events (death, myocardial infarction and coronary revascularisation) at 30 days were determined using electronic health record, insurance claims and death index data. Test characteristics for detection of major adverse cardiac events were calculated for both accelerated diagnostic pathways and McNemar's tests were used for comparisons. RESULTS: 5799 patients presenting to the emergency department were accrued, of which HEART Pathway and EDACS assessments were completed on 4399. Major adverse cardiac events at 30 days occurred in 449/4399 (10.2%). The HEART Pathway identified 38.4% (95% CI 37.0% to 39.9%) of patients as low-risk compared with 58.1% (95% CI 56.6% to 59.6%) identified as low-risk by EDACS (p<0.001). Major adverse cardiac events occurred in 0.4% (95% CI 0.2% to 0.9%) of patients classified as low-risk by the HEART Pathway compared with 1.0% (95% CI 0.7% to 1.5%) of patients identified as low-risk by EDACS (p<0.001). Thus, the HEART Pathway had a negative predictive value of 99.6% (95% CI 99.1% to 99.8%) for major adverse cardiac events compared with a negative predictive value of 99.0% (95% CI 98.5% to 99.3%) for EDACS. CONCLUSIONS: EDACS identifies a larger proportion of patients as low-risk than the HEART Pathway, but has a higher missed major adverse cardiac events rate at 30 days. Physicians will need to consider their risk tolerance when deciding whether to adopt the HEART Pathway or EDACS accelerated diagnostic pathway. TRIAL REGISTRATION NUMBER: NCT02056964.

9.
Am J Cardiol ; 125(9): 1324-1331, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32139160

RESUMO

Patients with hypertension who develop atrial premature complexes (APCs) are at a particularly high risk for atrial fibrillation (AF). We sought to identify medications and modifiable risk factors that could reduce the risk of AF imposed by presence of APCs in such a high risk group. This analysis included 4,331 participants with treated hypertension from the Reasons for Geographic and Racial Differences in Stroke study who were free of AF and cardiovascular disease at the time of enrollment (2003-2007). APCs were detected in 8.2% (n = 356) of the participants at baseline. During a median follow-up of 9.4 years, 9.9% (n = 429) of the participants developed AF. Participants with APCs, compared with those without, were more than twice as likely to develop AF (Odds ratio [95% confidence interval]: 2.36[1.75, 3.19]). This association was significantly weaker in statin users than nonusers (Odds ratio [95% confidence interval]:1.42[0.81,2.48] vs 3.01[2.11,4.32], respectively; interaction p-value = 0.02), and in angiotensin-II receptor blocker users than nonusers (Odds ratio [95% confidence interval]:1.31[0.66,2.61] vs 2.78[1.99,3.89], respectively; interaction p-value = 0.05). Borderline weaker associations between APCs and AF were also observed in alpha-blocker users than nonusers, nondiabetics than diabetics, and in those with systolic blood pressure level 130 to 139 mm Hg compared with those with other systolic blood pressure levels. No significant effect modifications were observed by use of other medications or by presence of other cardiovascular risk factors. In conclusion, the significant AF risk associated with APCs in patients with hypertension could potentially be reduced by treatment with angiotensin-II receptor blockers and statins along with lowering blood pressure and management of diabetes.


Assuntos
Fibrilação Atrial/epidemiologia , Fibrilação Atrial/etiologia , Complexos Atriais Prematuros/complicações , Hipertensão/complicações , Idoso , Antagonistas de Receptores de Angiotensina/uso terapêutico , Complexos Atriais Prematuros/etiologia , Estudos de Coortes , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipertensão/tratamento farmacológico , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco
10.
J Am Heart Assoc ; 9(7): e013827, 2020 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-32200711

RESUMO

Background Heart rate variability (HRV) is associated with vascular risk factors for dementia, but whether HRV is associated with specific domains of cognitive performance is unclear. Methods and Results In the Multi-Ethnic Study of Atherosclerosis (N=3018; mean age 59.3±9.2 years), we assessed the relationship of 10-second HRV to scores on tests of global cognitive performance (Cognitive Abilities Screening Instrument), processing speed (Digit Symbol Coding), and working memory (Digit Span). HRV was computed as the SD of normal-normal intervals (SDNN) and root mean square of successive differences (RMSSD) at Exam 1 (2000-2002) and Exam 5 (2010-2012). Cognitive tests were administered at Exam 5. We report regression coefficients (ß [95% CI]) representing cognitive test score change per 2-fold increase in HRV. After adjustment for age, race/ethnicity, sex, education, apolipoprotein E genotype, and cardiovascular risk factors and incident disease, higher Exam 1 (ß=0.37 [0.06, 0.67]) and Exam 5 (ß=0.31 [0.04, 0.59]) SDNN were associated with better Cognitive Abilities Screening Instrument performance. Higher Exam 1 (ß=0.80 [0.17, 1.43]) and Exam 5 (ß=0.63 [0.06, 1.20]) SDNN, and Exam 5 RMSSD (ß=0.54 [0.01, 1.08]) were associated with better Digit Symbol Coding performance. Finally, higher Exam 5 SDNN was associated with better Digit Span performance (ß=0.17 [0.01, 0.33]). Associations were attenuated after adjustment for resting heart rate. Conclusions Higher HRV is generally associated with better cognitive performance in this multi-ethnic cohort of aging adults, and further study of the relationship of autonomic function to cognition is warranted.

11.
J Nutr ; 150(6): 1509-1515, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32133497

RESUMO

BACKGROUND: Diet quality is an important risk factor for type 2 diabetes (T2D) and cardiovascular disease (CVD). Little is known about the diet quality of South Asians in the United States, a group with higher rates of T2D and CVD compared with other racial/ethnic groups. OBJECTIVE: This study determined whether diet quality differs between South Asian adults in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) Study and whites, Chinese Americans, African Americans, and Hispanics in the Multi-Ethnic Study of Atherosclerosis (MESA). METHODS: Cross-sectional data from 3926 participants free of CVD from MESA visit 5 (2010-2011) and 889 South Asian participants from MASALA visit 1 (2010-2013) were pooled. Diet quality was assessed using the Alternative Healthy Eating Index (AHEI-2010) derived using FFQs. Multivariable linear regression models adjusted for age, sex, and total energy intake were used to compare mean differences in diet quality between the racial/ethnic groups. RESULTS: MESA participants were, on average, 14 y older than MASALA participants. The adjusted mean (95% CI) scores for the AHEI-2010 were 70.2 (69.5, 70.9) among South Asians, 66.2 (66.3, 68.2) among Chinese Americans, 61.1 (60.7, 61.6) among whites, 59.0 (58.4, 59.7) among Hispanics, and 57.5 (56.9, 58.1) among African Americans. The mean AHEI scores among South Asians were 3.1 (1.8, 4.3), 9.2 (8.3, 10.1), 11.2 (10.2, 12.3), and 12.8 (11.8, 13.7) points higher compared with Chinese Americans, whites, Hispanics, and African Americans, respectively. CONCLUSIONS: South Asian adults in the United States have a higher diet quality compared with other racial/ethnic groups. This paradoxical finding is not consistent with the observed higher rates of T2D and CVD compared with other groups. This is further evidence of the importance of studying the South Asian population to better understand the causes of chronic disease not explained by diet quality.


Assuntos
Aterosclerose/etnologia , Dieta , Idoso , Ásia/etnologia , Estudos Transversais , Registros de Dieta , Emigração e Imigração , Grupos Étnicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Estados Unidos
12.
J Proteome Res ; 19(7): 2794-2806, 2020 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-32202800

RESUMO

Coronary artery disease remains a leading cause of death in industrialized nations, and early detection of disease is a critical intervention target to effectively treat patients and manage risk. Proteomic analysis of mixed tissue homogenates may obscure subtle protein changes that occur uniquely in underlying tissue subtypes. The unsupervised 'convex analysis of mixtures' (CAM) tool has previously been shown to effectively segregate cellular subtypes from mixed expression data. In this study, we hypothesized that CAM would identify proteomic information specifically informative to early atherosclerosis lesion involvement that could lead to potential markers of early disease detection. We quantified the proteome of 99 paired abdominal aorta (AA) and left anterior descending coronary artery (LAD) specimens (N = 198 specimens total) acquired during autopsy of young adults free of diagnosed cardiac disease. The CAM tool was then used to segregate protein subsets uniquely associated with different underlying tissue types, yielding markers of normal and fibrous plaque (FP) tissues in LAD and AA (N = 62 lesions markers). CAM-derived FP marker expression was validated against pathologist estimated luminal surface involvement of FP, as well as in an orthogonal cohort of "pure" fibrous plaque, fatty streak, and normal vascular specimens. A targeted mass spectrometry (MS) assay quantified 39 of 62 CAM-FP markers in plasma from women with angiographically verified coronary artery disease (CAD, N = 46) or free from apparent CAD (control, N = 40). Elastic net variable selection with logistic regression reduced this list to 10 proteins capable of classifying CAD status in this cohort with <6% misclassification error, and a mean area under the receiver operating characteristic curve of 0.992 (confidence interval 0.968-0.998) after cross validation. The proteomics-CAM workflow identified lesion-specific molecular biomarker candidates by distilling the most representative molecules from heterogeneous tissue types.

13.
Bioinformatics ; 36(12): 3927-3929, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32219387

RESUMO

SUMMARY: We develop a fully unsupervised deconvolution method to dissect complex tissues into molecularly distinctive tissue or cell subtypes based on bulk expression profiles. We implement an R package, deconvolution by Convex Analysis of Mixtures (debCAM) that can automatically detect tissue/cell-specific markers, determine the number of constituent subtypes, calculate subtype proportions in individual samples and estimate tissue/cell-specific expression profiles. We demonstrate the performance and biomedical utility of debCAM on gene expression, methylation, proteomics and imaging data. With enhanced data preprocessing and prior knowledge incorporation, debCAM software tool will allow biologists to perform a more comprehensive and unbiased characterization of tissue remodeling in many biomedical contexts. AVAILABILITY AND IMPLEMENTATION: http://bioconductor.org/packages/debCAM. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Proteômica , Software , Expressão Gênica
14.
J Electrocardiol ; 58: 150-154, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31895990

RESUMO

BACKGROUND: QRS-duration predicts mortality in patients with heart failure and, to a lesser extent, the general population. However, in patients with diabetes, its prognostic significance is unknown. To better understand how QRS-duration relates to mortality among those with diabetes, we explored survival as a function of QRS-duration in the Diabetes Heart Study. METHODS: The study population included 1335 participants. Cox proportional hazards modeling was used to evaluate the relationship between QRS-duration and all-cause mortality, comparing those with QRS-duration ≤120 vs. >120 (ms). Multivariable models adjusted for age, sex, race, hypertension, smoking, years with diabetes, BMI, systolic blood pressure, cholesterol, triglycerides, glomerular filtration rate, and hemoglobin A1c. RESULTS AND CONCLUSIONS: Participants were: mean age 61 ± 9, 55% women, 83% white; 99 participants (7.5%) had a QRS-duration >120. After 11,000 person-years of follow-up (median 8.5 years; maximum 13.9 years), 266 participants had died (20%). Participants with baseline QRS-duration >120 had an adjusted hazard ratio for all-cause mortality of 1.56 (95% CI 1.05-2.24; p = 0.027). Modeling QRS-duration as a continuous variable, we found an 11% increase in all-cause mortality for each 10 ms increase in QRS-duration. In conclusion, QRS-duration is associated with subsequent all-cause mortality among those with type 2 diabetes-participants with QRS-duration >120 ms had a 56% increase in all-cause mortality, even after adjustment for conventional risk factors. Given the ubiquitous presence of ECG data in the medical record, QRS-duration may prove to be a useful prognostic measure, especially among those with diabetes.

15.
Bioinformatics ; 36(9): 2862-2871, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31950989

RESUMO

MOTIVATION: Liquid chromatography-mass spectrometry (LC-MS) is a standard method for proteomics and metabolomics analysis of biological samples. Unfortunately, it suffers from various changes in the retention times (RT) of the same compound in different samples, and these must be subsequently corrected (aligned) during data processing. Classic alignment methods such as in the popular XCMS package often assume a single time-warping function for each sample. Thus, the potentially varying RT drift for compounds with different masses in a sample is neglected in these methods. Moreover, the systematic change in RT drift across run order is often not considered by alignment algorithms. Therefore, these methods cannot effectively correct all misalignments. For a large-scale experiment involving many samples, the existence of misalignment becomes inevitable and concerning. RESULTS: Here, we describe an integrated reference-free profile alignment method, neighbor-wise compound-specific Graphical Time Warping (ncGTW), that can detect misaligned features and align profiles by leveraging expected RT drift structures and compound-specific warping functions. Specifically, ncGTW uses individualized warping functions for different compounds and assigns constraint edges on warping functions of neighboring samples. Validated with both realistic synthetic data and internal quality control samples, ncGTW applied to two large-scale metabolomics LC-MS datasets identifies many misaligned features and successfully realigns them. These features would otherwise be discarded or uncorrected using existing methods. The ncGTW software tool is developed currently as a plug-in to detect and realign misaligned features present in standard XCMS output. AVAILABILITY AND IMPLEMENTATION: An R package of ncGTW is freely available at Bioconductor and https://github.com/ChiungTingWu/ncGTW. A detailed user's manual and a vignette are provided within the package. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Metabolômica , Espectrometria de Massas em Tandem , Algoritmos , Cromatografia Líquida , Proteômica , Software
16.
Nutr Metab Cardiovasc Dis ; 30(1): 123-131, 2020 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-31753783

RESUMO

BACKGROUND: South Asians are the second fastest growing ethnic group in the United States, and they have a high risk for cardiovascular disease (CVD). Moderate alcohol consumption has been associated with lower CVD risk in some race/ethnic groups, but the association of alcohol consumption and atherosclerosis in South Asians has not been investigated. METHODS AND RESULTS: We used data from 906 South Asian participants who participated in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) cohort (2010-2012). Alcohol consumption was ascertained via questionnaire, coronary artery calcium (CAC) was measured with computed tomography, and common carotid artery intima-media thickness (cIMT) was measured using B-mode ultrasonography. We used multivariable regression models to examine cross-sectional associations of alcohol consumption with the presence and amount of CAC and cIMT. Compared with never drinkers, participants consuming 4-7 drinks/week had a 63% decreased odds of any CAC after adjusting for potential confounders and mediators. Participants consuming 4-7 drinks/week had significantly lower odds of CAC score between 1 and 300 [OR (95% CI): 0.34 (0.16-0.72)]. A similar inverse association was seen for the odds of CAC>300 [OR (95% CI): 0.28 (0.07-0.97)]. Alcohol consumption of >7 drinks/week was associated with a 0.096 mm increase in common-cIMT. CONCLUSION: There was an inverse association between the amount of alcohol intake and CAC among South Asians while a positive association was found between alcohol consumption and common-cIMT. Long-term follow-up of the MASALA cohort will examine prospective associations of alcohol intake with the progression of subclinical atherosclerosis, incident CVD events, and mortality.

17.
JACC Heart Fail ; 7(8): 651-661, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31302044

RESUMO

OBJECTIVES: The aim of this study was to determine if plasma eicosapentaenoic acid (EPA) abundance (%EPA) is associated with reduced hazard for primary heart failure (HF) events in the MESA (Multi-Ethnic Study of Atherosclerosis) trial. BACKGROUND: Clinical trials suggest that omega-3 polyunsaturated fatty acids (ω3 PUFAs) prevent sudden death in coronary heart disease and HF, but this is controversial. In mice, the authors demonstrated that the ω3 PUFA EPA prevents contractile dysfunction and fibrosis in an HF model, but whether this extends to humans is unclear. METHODS: In the MESA cohort, the authors tested if plasma phospholipid EPA predicts primary HF incidence, including HF with reduced ejection fraction (EF) (EF <45%) and HF with preserved EF (EF ≥45%) using Cox proportional hazards modeling. RESULTS: A total of 6,562 participants 45 to 84 years of age had EPA measured at baseline (1,794 black, 794 Chinese, 1,442 Hispanic, and 2,532 white; 52% women). Over a median follow-up period of 13.0 years, 292 HF events occurred: 128 HF with reduced EF, 110 HF with preserved EF, and 54 with unknown EF status. %EPA in HF-free participants was 0.76% (0.75% to 0.77%) but was lower in participants with HF at 0.69% (0.64% to 0.74%) (p = 0.005). Log %EPA was associated with lower HF incidence (hazard ratio: 0.73 [95% confidence interval: 0.60 to 0.91] per log-unit difference in %EPA; p = 0.001). Adjusting for age, sex, race, body mass index, smoking, diabetes mellitus, blood pressure, lipids and lipid-lowering drugs, albuminuria, and the lead fatty acid for each cluster did not change this relationship. Sensitivity analyses showed no dependence on HF type. CONCLUSIONS: Higher plasma EPA was significantly associated with reduced risk for HF, with both reduced and preserved EF. (Multi-Ethnic Study of Atherosclerosis [MESA]; NCT00005487).

18.
Metabolites ; 9(6)2019 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-31216675

RESUMO

It is not controversial that study design considerations and challenges must be addressed when investigating the linkage between single omic measurements and human phenotypes. It follows that such considerations are just as critical, if not more so, in the context of multi-omic studies. In this review, we discuss (1) epidemiologic principles of study design, including selection of biospecimen source(s) and the implications of the timing of sample collection, in the context of a multi-omic investigation, and (2) the strengths and limitations of various techniques of data integration across multi-omic data types that may arise in population-based studies utilizing metabolomic data.

19.
J Womens Health (Larchmt) ; 28(7): 900-909, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31170017

RESUMO

Background: The relationship of endogenous sex hormones (SH) with vascular endothelial function and with cardiovascular disease (CVD) is incompletely understood. We examined the associations between SH and endothelial function measured by brachial artery flow-mediated dilation (FMD). Materials and Methods: We included 1368 postmenopausal women and 1707 men, free of clinical CVD, participating in MESA Visit 1 (2000-2002). Serum SH [total testosterone, SH binding globulin (SHBG), dehydroepiandrosterone (DHEA), estradiol] were measured; free testosterone was calculated. The percent FMD difference (%FMD) was measured by high-resolution ultrasound. Using multivariable-adjusted linear regression, we tested the cross-sectional associations of SH (log transformed, compared per one SD increment) with %FMD. Results: The mean age of women and men were 64.2 and 61.4 years, respectively. Among women, after adjusting for demographics, CVD risk factors, and hormone therapy, higher SHBG was associated with greater %FMD [ß = 0.215% (95% CI 0.026-0.405)], whereas higher free testosterone was associated with a smaller %FMD [-0.209% (-0.402, -0.017)]. Estradiol and DHEA were not associated with %FMD in women after multivariable adjustment. There was an age interaction, with higher free testosterone and lower SHBG associated with worse FMD in women <65 years of age, but not in those ≥65 years (p = 0.04). We did not see similar associations in men. Conclusions: A more androgenic SH profile of higher free testosterone and lower SHBG was associated with worse %FMD in postmenopausal women. Changes in SH with aging and menopause may result in vascular changes in women. Further studies are needed to assess longitudinal changes in SH levels and their association with vascular function.

20.
Am J Epidemiol ; 188(6): 991-1012, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-31155658

RESUMO

The Consortium of Metabolomics Studies (COMETS) was established in 2014 to facilitate large-scale collaborative research on the human metabolome and its relationship with disease etiology, diagnosis, and prognosis. COMETS comprises 47 cohorts from Asia, Europe, North America, and South America that together include more than 136,000 participants with blood metabolomics data on samples collected from 1985 to 2017. Metabolomics data were provided by 17 different platforms, with the most frequently used labs being Metabolon, Inc. (14 cohorts), the Broad Institute (15 cohorts), and Nightingale Health (11 cohorts). Participants have been followed for a median of 23 years for health outcomes including death, cancer, cardiovascular disease, diabetes, and others; many of the studies are ongoing. Available exposure-related data include common clinical measurements and behavioral factors, as well as genome-wide genotype data. Two feasibility studies were conducted to evaluate the comparability of metabolomics platforms used by COMETS cohorts. The first study showed that the overlap between any 2 different laboratories ranged from 6 to 121 metabolites at 5 leading laboratories. The second study showed that the median Spearman correlation comparing 111 overlapping metabolites captured by Metabolon and the Broad Institute was 0.79 (interquartile range, 0.56-0.89).


Assuntos
Epidemiologia/organização & administração , Saúde Global , Metabolômica/organização & administração , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Índice de Massa Corporal , Criança , Métodos Epidemiológicos , Feminino , Comportamentos Relacionados com a Saúde , Testes Hematológicos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores Socioeconômicos , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA