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1.
Stat Med ; 39(2): 156-170, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31758598

RESUMO

We propose time-varying coefficient model selection and estimation based on the spline approach, which is capable of capturing time-dependent covariate effects. The new penalty function utilizes local-region information for varying-coefficient estimation, in contrast to the traditional model selection approach focusing on the entire region. The proposed method is extremely useful when the signals associated with relevant predictors are time-dependent, and detecting relevant covariate effects in the local region is more scientifically relevant than those of the entire region. Our simulation studies indicate that the proposed model selection incorporating local features outperforms the global feature model selection approaches. The proposed method is also illustrated through a longitudinal growth and health study from National Heart, Lung, and Blood Institute.

2.
Hypertension ; 75(2): 316-323, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31865797

RESUMO

Cross-sectionally measured NT-proBNP (N-terminal pro-B-type natriuretic peptide) is related to incident dementia. However, data linking changes in NT-proBNP to risk of future dementia are lacking. We aimed to examine the association of change in NT-proBNP over 3.2 years with incident dementia. We included 4563 participants in MESA (Multi-Ethnic Study of Atherosclerosis) prospective cohort who were free of cardiovascular disease at enrollment, had NT-proBNP level measured at MESA exams 1 (baseline, 2000-2002) and 3 (2004-2005), and had no diagnosis of dementia before exam 3. The association of change in NT-proBNP level between MESA exams 1 through 3 and all-cause hospitalized dementia (by International Classification of Diseases, Ninth Revision, codes) after MESA exam 3 (2004-2005) through 2015 was assessed using competing-risks Cox proportional hazard regression analysis. During 45 522 person-years of follow-up, 223 dementia cases were documented. Increase in log-NT-proBNP from MESA exams 1 through 3 was positively associated with incidence of dementia (multivariable hazard ratio, 1.28 [95% CI, 1.001-1.64]; P=0.049). An increase of at least 25% in NT-proBNP level from MESA exam 1 through 3 was associated with a 55% (P=0.02) increase in the risk of dementia in multivariable analysis. Addition of temporal NT-proBNP change to a model including risk factors and baseline NT-proBNP improved the prediction of dementia (Harrell C statistic from 0.85 to 0.87, P=0.049). Increase in NT-proBNP is independently associated with future all-cause hospitalized dementia and offers a moderately better predictive performance for risk of dementia compared with risk factors and baseline NT-proBNP. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT00005487.

3.
Stat Med ; 38(23): 4574-4582, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31304613

RESUMO

Feature selection is an important initial step of exploratory analysis in biomedical studies. Its main objective is to eliminate the covariates that are uncorrelated with the outcome. For highly correlated covariates, traditional feature selection methods, such as the Lasso, tend to select one of them and eliminate the others, although some of the eliminated ones are still scientifically valuable. To alleviate this drawback, we propose a feature selection method based on covariate space decomposition, referred herein as the "Decomposition Feature Selection" (DFS), and show that this method can lead to scientifically meaningful results in studies with correlated high dimensional data. The DFS consists of two steps: (i) decomposing the covariate space into disjoint subsets such that each of the subsets contains only uncorrelated covariates and (ii) identifying significant predictors by traditional feature selection within each covariate subset. We demonstrate through simulation studies that the DFS has superior practical performance over the Lasso type methods when multiple highly correlated covariates need to be retained. Application of the DFS is demonstrated through a study of bipolar disorders with correlated biomarkers.

4.
Stat Methods Med Res ; : 962280219839427, 2019 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-30945590

RESUMO

Tracking a subject's risk factors or health status over time is an important objective in long-term epidemiological studies with repeated measurements. An important issue of time-trend tracking is to define appropriate statistical indices to quantitatively measure the tracking abilities of the targeted risk factors or health status over time. We present a number of local and global statistical tracking indices based on the rank-tracking probabilities, which are derived from the conditional distribution functions, and propose a class of kernel-based nonparametric estimation methods. Confidence intervals for the estimators of the tracking indices are constructed through a resampling subject bootstrap procedure. We demonstrate the application of the tracking indices using the body mass index and systolic blood pressure data from the Coronary Artery Risk Development in Young Adults (CARDIA) study. Statistical properties of the estimation methods and bootstrap inference are investigated through a simulation study and an asymptotic development.

5.
Eur Heart J Cardiovasc Imaging ; 20(2): 168-176, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30325426

RESUMO

Aims: We used contrast-enhanced cardiac magnetic resonance (CMR) to evaluate differences in myocardial fibrosis measured at the year-10 examination between participants with and without cardiovascular (CV) events accrued in a large population based study over the preceding 10-year follow-up period in this retrospective study. Methods and results: The MESA study enrolled 6814 participants free of CV disease at baseline (2000-2002). We included MESA participants who underwent contrast-enhanced CMR at the MESA year-10 exam (N = 1840). We defined a composite CV endpoint of coronary heart disease, heart failure, atrial fibrillation, stroke, and peripheral artery disease. Using CMR, we characterized myocardial fibrosis with late-gadolinium enhancement for scar and T1 mapping indices of diffuse fibrosis. Demographic and CV-risk adjusted logistic (presence of scar) and linear regression (pre-contrast T1, T1 at 12 and 25 min post-contrast, and extracellular volume fraction or ECV) models were used to assess the relationship between fibrosis and events. The mean values of T1 indices were-pre-contrast T1: 977 ± 45 ms; T1 at 12': 456 ± 40 ms; T1 at 25': 519 ± 41 ms; ECV: 27.1 ± 3.2%. One-hundred and forty-six (7.9%) participants had myocardial scar. The presence of scar was strongly associated with prior CV events (adjusted coeff: 1.36, P < 0.001). Lower post-contrast T1 times and higher ECV, indicative of greater diffuse fibrosis were strongly associated with CV events (T1 at 12': coeff = -10.0 ms, P = 0.004; T1 at 25': coeff =-9.2 ms, P = 0.008; ECV: coeff = 1.31%, P < 0.001). Conclusion: Individuals who suffered prior CV events have greater likelihood of diffuse myocardial fibrosis when compared with event-free individuals living in the same community.


Assuntos
Aterosclerose/diagnóstico por imagem , Aterosclerose/patologia , Doenças Cardiovasculares/diagnóstico por imagem , Doenças Cardiovasculares/patologia , Imagem por Ressonância Magnética/métodos , Miocárdio/patologia , Idoso , Idoso de 80 Anos ou mais , Meios de Contraste , Feminino , Fibrose/patologia , Gadolínio DTPA , Humanos , Interpretação de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
6.
J Cardiovasc Magn Reson ; 20(1): 53, 2018 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-30064457

RESUMO

BACKGROUND: Although diabetes mellitus (DM) and insulin resistance associate with adverse cardiac events, the associations of left ventricular (LV) remodeling and function with compromised glucose metabolism have not been fully evaluated in a general population. We used cardiovascular magnetic resonance (CMR) to evaluate how CMR indices are associated with DM or insulin resistance among participants before developing cardiac events. METHODS: We studied 1476 participants who were free of clinical cardiovascular disease and who underwent tagged CMR in the Multi-Ethnic Study of Atherosclerosis (MESA). LV shape and longitudinal myocardial shortening and torsion were assessed by CMR. A higher sphericity index represents a more spherical LV shape. Multivariable linear regression was used to evaluate the associations of DM or homeostasis model assessment-estimated insulin resistance (HOMA-IR) with CMR indices. RESULTS: In multiple linear regression, longitudinal shortening was lower in impaired fasting glucose than normal fasting glucose (NFG) (0.36% lower vs. NFG, p < 0.05); torsion was greater in treated DM (0.24 °/cm greater vs. NFG, p < 0.05) after full adjustments. Among participants without DM, greater log-HOMA-IR was correlated with greater LV mass (3.92 g/index, p < 0.05) and LV mass-to-volume ratio (0.05 /index, p < 0.01), and lower sphericity index (- 1.26/index, p < 0.01). Greater log-HOMA IR was associated with lower longitudinal shortening (- 0.26%/index, p < 0.05) and circumferential shortening (- 0.30%/index, p < 0.05). Torsion was positively correlated with log-HOMA-IR until 1.5 of log-HOMA-IR (0.16 °/cm/index, p = 0.030).), and tended to fall once above 1.5 of log-HOMA-IR (- 0.50 °/cm/index, p = 0.203). The sphericity index was associated negatively with LV mass-to-volume ratio (- 0.02/%, p < 0.001) and torsion (- 0.03°/cm/%, p < 0.001). CONCLUSIONS: Glucose metabolism disorders are associated with LV concentric remodeling, less spherical shape, and reduced systolic myocardial shortening in the general population. Although torsion is higher in participants who are treated for DM and impaired insulin resistance, myocardial shortening was progressively decreased with higher HOMA-IR and torsion was increased only with less severe insulin resistance. CLINICAL TRIAL REGISTRATION: Multi-Ethnic Study of Atherosclerosis (MESA): A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org/ . Study Start Date: January 1999 ( NCT00005487 ).


Assuntos
Glicemia/metabolismo , Diabetes Mellitus/sangue , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Resistência à Insulina , Imagem por Ressonância Magnética , Contração Miocárdica , Disfunção Ventricular Esquerda/diagnóstico por imagem , Função Ventricular Esquerda , Remodelação Ventricular , Idoso , Idoso de 80 Anos ou mais , Doenças Assintomáticas , Biomarcadores/sangue , Fenômenos Biomecânicos , Estudos Transversais , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/etnologia , Feminino , Humanos , Hipertrofia Ventricular Esquerda/etnologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Torção Mecânica , Estados Unidos/epidemiologia , Disfunção Ventricular Esquerda/etnologia , Disfunção Ventricular Esquerda/fisiopatologia
7.
Circ Cardiovasc Imaging ; 11(3): e007241, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29523555

RESUMO

BACKGROUND: The association of cardiovascular diseases (CVD) with liver fibrosis is poorly understood. We aim to assess the association of liver fibrosis by T1-mapping magnetic resonance imaging and CVD in MESA (Multi-Ethnic Study of Atherosclerosis). METHODS AND RESULTS: MESA enrolled 6814 participants free of clinical CVD at baseline (2000-2002). A subsample of participants underwent T1-mapping magnetic resonance imaging 10 years after the baseline (Y10 MESA exam, 2010-2012). Liver T1 maps were generated avoiding vessels and biliary ducts from which native T1 (n=2087) and extracellular volume fraction (ECV, n=1234) were determined. Higher ECV and native T1 were indicators of liver fibrosis. Linear regression analysis evaluated the cross-sectional relationship between liver native T1 and ECV at Y10 MESA exam with a history of CVD events (atrial fibrillation, heart failure, and coronary heart disease [CHD]). Of the 2087 participants (68.7±9.1 years; 46% females), 153 had prior CVD events (78 atrial fibrillation, 25 heart failure, and 78 CHD). History of CVD events was associated with 18.5 ms higher liver native T1 (P<0.001) and 1.4% greater ECV (P=0.06). Prior atrial fibrillation was related to higher liver native T1 (ß=21.1; P=0.001) and greater ECV (ß=2.2; P=0.02), whereas previous heart failure was associated with greater liver ECV (ß=4.1; P=0.02). There was also a relationship of prior CHD with liver native T1 (ß=13; P=0.05) and ECV (ß=1.9; P=0.05), which was attenuated by adjustment for coronary artery calcium score (ß=7.1 and 1.6; P=0.37 and 0.13, respectively). CONCLUSIONS: Liver fibrosis by T1-mapping magnetic resonance imaging is associated with history of heart failure, atrial fibrillation, and CHD in a multiethnic cohort. The association of liver fibrosis and CHD is at least in part mediated by atherosclerosis.


Assuntos
Aterosclerose/etnologia , Grupos Étnicos , Cirrose Hepática/etnologia , Fígado/patologia , Vigilância da População , Idoso , Idoso de 80 Anos ou mais , Aterosclerose/diagnóstico , Aterosclerose/etiologia , Estudos Transversais , Feminino , Seguimentos , Humanos , Incidência , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Estados Unidos/epidemiologia
8.
Hypertension ; 71(3): 368-374, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29386350

RESUMO

In the past 30 years, several organizations, such as the US Association for the Advancement of Medical Instrumentation (AAMI), the British Hypertension Society, the European Society of Hypertension (ESH) Working Group on Blood Pressure (BP) Monitoring, and the International Organization for Standardization (ISO), have developed protocols for clinical validation of BP measuring devices. However, it is recognized that science, as well as patients, consumers, and manufacturers, would be best served if all BP measuring devices were assessed for accuracy according to an agreed single validation protocol that had global acceptance. Therefore, an international initiative was taken by the AAMI, ESH, and ISO experts who agreed to develop a universal standard for device validation. This statement presents the key aspects of a validation procedure, which were agreed by the AAMI, ESH, and ISO representatives as the basis for a single universal validation protocol. As soon as the AAMI/ESH/ISO standard is fully developed, this will be regarded as the single universal standard and will replace all other previous standards/protocols.


Assuntos
Determinação da Pressão Arterial/normas , Monitores de Pressão Arterial/normas , Consenso , Guias de Prática Clínica como Assunto/normas , Europa (Continente) , Humanos , Cooperação Internacional , Padrões de Referência , Reprodutibilidade dos Testes , Sociedades Médicas/normas
9.
J Hypertens ; 36(3): 472-478, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29384983

RESUMO

: In the last 30 years, several organizations, such as the US Association for the Advancement of Medical Instrumentation (AAMI), the British Hypertension Society, the European Society of Hypertension (ESH) Working Group on Blood Pressure (BP) Monitoring and the International Organization for Standardization (ISO) have developed protocols for clinical validation of BP measuring devices. However, it is recognized that science, as well as patients, consumers and manufacturers would be best served if all BP measuring devices were assessed for accuracy according to an agreed single validation protocol that had global acceptance. Therefore, an international initiative was taken by AAMI, ESH and ISO experts who agreed to develop a universal standard for device validation. This statement presents the key aspects of a validation procedure, which were agreed by the AAMI, ESH and ISO representatives as the basis for a single universal validation protocol. As soon as the AAMI/ESH/ISO standard is fully developed, this will be regarded as the single universal standard and will replace all other previous standards/protocols.


Assuntos
Determinação da Pressão Arterial/instrumentação , Hipertensão/diagnóstico , Esfigmomanômetros/normas , Estudos de Validação como Assunto , Pressão Sanguínea , Consenso , Humanos , Cooperação Internacional , Reprodutibilidade dos Testes , Projetos de Pesquisa
10.
Stat Methods Med Res ; 27(5): 1464-1475, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-27507288

RESUMO

Genetic association studies often collect information on secondary phenotypes related to the primary disease status. In many situations, the secondary phenotypes are only measured in subjects with the disease condition. It would be advantageous to model the primary trait and the secondary phenotype together if they share certain level of genetic heritability. We propose a family of multi-locus testing procedures to detect the composite association between a set of genetic markers and two traits (the primary trait and a secondary phenotype), in order to identify genes influencing both traits. The proposed test is derived from a random effect model with two variance components, with each presenting the genetic effect on one trait, and incorporates a model selection procedure for seeking the optimal model to represent the two sources of genetic effects. We conduct simulation studies to evaluate performance of the proposed procedure and apply the method to a genome-wide association study of prostate cancer with the Gleason score as the secondary phenotype.


Assuntos
Estudos de Associação Genética/métodos , Característica Quantitativa Herdável , Loci Gênicos/genética , Marcadores Genéticos , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla , Humanos , Masculino , Modelos Estatísticos , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Neoplasias da Próstata/genética
11.
J Am Heart Assoc ; 6(9)2017 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-28931529

RESUMO

BACKGROUND: Both ECG strain pattern and QRS measured left ventricular (LV) hypertrophy criteria are associated with LV hypertrophy and have been used for risk stratification. However, the independent predictive value of ECG strain in apparently healthy individuals in predicting mortality and adverse cardiovascular events is unclear. METHODS AND RESULTS: MESA (Multi-Ethnic Study of Atherosclerosis) is a multicenter, prospective cohort of 6441 participants (mean age, 62 years; 54% women). In 2847 of these participants, cardiac magnetic resonance imaging was repeated ≈10 years later (Year-10). At Year-10, 1759 participants underwent cardiac magnetic resonance imaging with gadolinium to detect myocardial scar. During a median follow-up of 11.7 years, ECG strain (n=168, 2.6%) was significantly associated with all-cause death (adjusted hazard ratio, 1.33; 95% confidence interval, 1.01-1.77; P=0.045), heart failure (2.62; 1.73-3.97; P<0.001), myocardial infarction (1.86; 1.09-3.18; P=0.024), and incident cardiovascular disease (1.45; 1.06-2.00; P=0.022). ECG strain was also associated with an increase in LV mass (ß=9.29 g; P<0.001) and LV mass-to-volume ratio (ß=0.07 g/mL; P=0.007) and a decline in LV ejection fraction (ß=-3.30%; P<0.001). Moreover, ECG strain either at baseline and Year-10 was associated with LV scar (odds ratio, 4.93 and 5.22; P=0.002 and <0.001, respectively), whereas these associations were not observed in ECG LV hypertrophy. CONCLUSIONS: ECG strain is independently associated with all-cause mortality, adverse cardiovascular events, development of LV concentric remodeling and systolic dysfunction, and myocardial scar over 10 years in multiethnic participants without past cardiovascular disease. ECG strain may be an early marker of LV structural remodeling that contributes to development of adverse cardiovascular events. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00005487.


Assuntos
Aterosclerose/fisiopatologia , Eletrocardiografia , Grupos Étnicos , Previsões , Miocárdio/patologia , Função Ventricular Esquerda/fisiologia , Remodelação Ventricular/fisiologia , Idoso , Aterosclerose/diagnóstico , Aterosclerose/etnologia , Causas de Morte/tendências , Seguimentos , Ventrículos do Coração/fisiopatologia , Humanos , Imagem Cinética por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Morbidade/tendências , Estudos Prospectivos , Taxa de Sobrevida/tendências , Estados Unidos/epidemiologia
12.
Circ Res ; 121(9): 1092-1101, 2017 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-28794054

RESUMO

RATIONALE: Machine learning may be useful to characterize cardiovascular risk, predict outcomes, and identify biomarkers in population studies. OBJECTIVE: To test the ability of random survival forests, a machine learning technique, to predict 6 cardiovascular outcomes in comparison to standard cardiovascular risk scores. METHODS AND RESULTS: We included participants from the MESA (Multi-Ethnic Study of Atherosclerosis). Baseline measurements were used to predict cardiovascular outcomes over 12 years of follow-up. MESA was designed to study progression of subclinical disease to cardiovascular events where participants were initially free of cardiovascular disease. All 6814 participants from MESA, aged 45 to 84 years, from 4 ethnicities, and 6 centers across the United States were included. Seven-hundred thirty-five variables from imaging and noninvasive tests, questionnaires, and biomarker panels were obtained. We used the random survival forests technique to identify the top-20 predictors of each outcome. Imaging, electrocardiography, and serum biomarkers featured heavily on the top-20 lists as opposed to traditional cardiovascular risk factors. Age was the most important predictor for all-cause mortality. Fasting glucose levels and carotid ultrasonography measures were important predictors of stroke. Coronary Artery Calcium score was the most important predictor of coronary heart disease and all atherosclerotic cardiovascular disease combined outcomes. Left ventricular structure and function and cardiac troponin-T were among the top predictors for incident heart failure. Creatinine, age, and ankle-brachial index were among the top predictors of atrial fibrillation. TNF-α (tissue necrosis factor-α) and IL (interleukin)-2 soluble receptors and NT-proBNP (N-Terminal Pro-B-Type Natriuretic Peptide) levels were important across all outcomes. The random survival forests technique performed better than established risk scores with increased prediction accuracy (decreased Brier score by 10%-25%). CONCLUSIONS: Machine learning in conjunction with deep phenotyping improves prediction accuracy in cardiovascular event prediction in an initially asymptomatic population. These methods may lead to greater insights on subclinical disease markers without apriori assumptions of causality. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00005487.


Assuntos
Aterosclerose/diagnóstico por imagem , Aterosclerose/etnologia , Doenças Cardiovasculares/diagnóstico por imagem , Doenças Cardiovasculares/etnologia , Grupos Étnicos , Aprendizado de Máquina/tendências , Idoso , Idoso de 80 Anos ou mais , Aterosclerose/mortalidade , Doenças Cardiovasculares/mortalidade , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Taxa de Sobrevida/tendências
13.
Hypertension ; 70(3): 524-530, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28674039

RESUMO

The predictive value of aortic arch pulse wave velocity (PWV) assessed by magnetic resonance imaging for cardiovascular disease (CVD) events has not been fully established. The aim of the present study was to evaluate the association of arch PWV with incident CVD events in MESA (Multi-Ethnic Study of Atherosclerosis). Aortic arch PWV was measured using magnetic resonance imaging at baseline in 3527 MESA participants (mean age, 62±10 years at baseline; 47% men) free of overt CVD. Cox regression was used to evaluate the risk of incident CVD (coronary heart disease, stroke, transient ischemic attack, or heart failure) in relation to arch PWV adjusted for age, sex, race, and CVD risk factors. The median value of arch PWV was 7.4 m/s (interquartile range, 5.6-10.2). There was significant interaction between arch PWV and age for outcomes, so analysis was stratified by age categories (45-54 and >54 years). There were 456 CVD events during the 10-year follow-up. Forty-five to 54-year-old participants had significant association of arch PWV with incident CVD independent of CVD risk factors (hazard ratio, 1.44; 95% confidence interval, 1.07-1.95; P=0.018; per 1-SD increase for logarithmically transformed PWV), whereas >54-year group did not (P=0.93). Aortic arch PWV assessed by magnetic resonance imaging is a significant predictor of CVD events among middle-aged (45-54 years old) individuals, whereas arch PWV is not associated with CVD among an elderly in a large multiethnic population.


Assuntos
Aorta Torácica , Aterosclerose , Doenças Cardiovasculares , Análise de Onda de Pulso/métodos , Fatores Etários , Idoso , Aorta Torácica/diagnóstico por imagem , Aorta Torácica/fisiopatologia , Aterosclerose/diagnóstico , Aterosclerose/etnologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/fisiopatologia , Doenças Cardiovasculares/prevenção & controle , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Estados Unidos/epidemiologia , Rigidez Vascular/fisiologia
14.
J Am Heart Assoc ; 6(4)2017 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-28428195

RESUMO

BACKGROUND: Although the association between coronary artery calcium (CAC) and future heart failure (HF) has been shown previously, the value of CAC progression in the prediction of HF has not been investigated. In this study, we investigated the association of CAC progression with subclinical left ventricular (LV) dysfunction and incident HF in the Multi-Ethnic Study of Atherosclerosis. METHODS AND RESULTS: The Multi-Ethnic Study of Atherosclerosis is a population-based study consisting of 6814 men and women aged 45 to 84, free of overt cardiovascular disease at enrollment, who were recruited from 4 ethnicities. We included 5644 Multi-Ethnic Study of Atherosclerosis participants who had baseline and follow-up cardiac computed tomography and were free of HF and coronary heart disease before the second cardiac computed tomography. Mean (±SD) age was 61.7±10.2 years and 47.2% were male. The Cox proportional hazard models and multivariable linear regression models were deployed to determine the association of CAC progression with incident HF and subclinical LV dysfunction, respectively. Over a median follow-up of 9.6 (interquartile range: 8.8-10.6) years, 182 participants developed incident HF. CAC progression of 10 units per year was associated with 3% of increased risk of HF independent of overt coronary heart disease (P=0.008). In 2818 participants with available cardiac magnetic resonance images, CAC progression was associated with increased LV end diastolic volume (ß=0.16; P=0.03) and LV end systolic volume (ß=0.12; P=0.006) after excluding participants with any coronary heart disease. CONCLUSIONS: CAC progression was associated with incident HF and modestly increased LV end diastolic volume and LV end systolic volume at follow-up exam independent of overt coronary heart disease.


Assuntos
Doença da Artéria Coronariana/epidemiologia , Insuficiência Cardíaca/epidemiologia , Calcificação Vascular/epidemiologia , Disfunção Ventricular Esquerda/epidemiologia , Idoso , Doença da Artéria Coronariana/diagnóstico por imagem , Progressão da Doença , Feminino , Seguimentos , Humanos , Incidência , Modelos Lineares , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Volume Sistólico , Calcificação Vascular/diagnóstico por imagem
15.
Heart ; 103(7): 499-507, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27694110

RESUMO

OBJECTIVE: To investigate whether sphericity volume index (SVI), an indicator of left ventricular (LV) remodelling, predicts incident cardiovascular events (coronary heart disease, CHD; all cardiovascular disease, CVD; heart failure, HF; atrial fibrillation, AF) over 10 years of follow-up in a multiethnic population (Multi-Ethnic Study of Atherosclerosis). METHODS: 5004 participants free of known CVD had magnetic resonance imaging (MRI) in 2000-2002. Cine images were analysed to compute, [Formula: see text] equivalent to LV volume/volume of sphere with length of LV as the diameter. The highest (greatest sphericity) and lowest (lowest sphericity) quintiles of SVI were compared against the reference group (2-4 quintiles combined). Risk-factor adjusted hazard's ratio (HR) from Cox regression assessed the predictive performance of SVI at end-diastole (ED) and end-systole (ES) to predict incident outcomes over 10 years in retrospective interpretation of prospective data. RESULTS: At baseline, participants were aged 61±10 years; 52% men and 39%/13%/26%/22% Cauc/Chinese/Afr-Amer/Hispanic. Low sphericity was associated with higher Framingham CVD risk, greater coronary calcium score and higher N-terminal pro-brain natriuretic peptide (NT-proBNP); while increased sphericity was associated with higher NT-proBNP and lower ejection fraction. Low sphericity predicted incident CHD (HR: 1.48, 1.55-2.59 at ED) and CVD (HR: 1.82, 1.47-2.27 at ED). However, both low (HR: 1.81, 1.20-2.73 at ES) and high (HR: 2.21, 1.41-3.46 at ES) sphericity predicted incident HF. High sphericity also predicted AF. CONCLUSIONS: In a multiethnic population free of CVD at baseline, lowest sphericity was a predictor of incident CHD, CVD and HF over a 10-year follow-up period. Extreme sphericity was a strong predictor of incident HF and AF. SVI improved risk prediction models beyond established risk factors only for HF, but not for all CVD or CHD.


Assuntos
Doenças Cardiovasculares/etnologia , Ventrículos do Coração/diagnóstico por imagem , Imagem Cinética por Ressonância Magnética , Função Ventricular Esquerda , Remodelação Ventricular , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/etnologia , Fibrilação Atrial/fisiopatologia , Biomarcadores/sangue , Doenças Cardiovasculares/fisiopatologia , Doença das Coronárias/etnologia , Doença das Coronárias/fisiopatologia , Feminino , Insuficiência Cardíaca/etnologia , Insuficiência Cardíaca/fisiopatologia , Ventrículos do Coração/fisiopatologia , Humanos , Interpretação de Imagem Assistida por Computador , Incidência , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Estados Unidos/epidemiologia
16.
Radiology ; 282(3): 690-698, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27740904

RESUMO

Purpose To examine the associations of myocardial diffuse fibrosis and scar with surface electrocardiographic (ECG) parameters in individuals free of prior coronary heart disease in four different ethnicities. Materials and Methods This prospective cross-sectional study was approved by the institutional review boards, and all participants gave informed consent. A total of 1669 participants in the Multi-Ethnic Study of Atherosclerosis, or MESA, who were free of prior myocardial infarction underwent both ECG and cardiac magnetic resonance imaging. In individuals without a late gadolinium enhancement-defined myocardial scar (n = 1131), T1 mapping was used to assess left ventricular (LV) interstitial diffuse fibrosis. The associations of LV diffuse fibrosis or myocardial scar with ECG parameters (QRS voltage, QRS duration, and corrected QT interval [QTc]) were evaluated by using multivariable regression analyses adjusted for demographic data, risk factors for scar, LV end-diastolic volume, and LV mass. Results The mean age of the 1669 participants was 67.4 years ± 8.7 (standard deviation); 49.8% were women. Lower postcontrast T1 time at 12 minutes was significantly associated with lower QRS Sokolow-Lyon voltage (ß = 15.1 µV/10 msec, P = .004), lower QRS Cornell voltage (ß = 9.2 µV/10 msec, P = .031), and shorter QRS duration (ß = 0.16 msec/10 msec, P = .049). Greater extracellular volume (ECV) fraction was also significantly associated with lower QRS Sokolow-Lyon voltage (ß = -35.2 µV/1% ECV increase, P < .001) and Cornell voltage (ß = -23.7 µV/1% ECV increase, P < .001), independent of LV structural indexes. In contrast, the presence of LV scar (n = 106) was associated with longer QTc (ß = 4.3 msec, P = .031). Conclusion In older adults without prior coronary heart disease, underlying greater LV diffuse fibrosis is associated with lower QRS voltage and shorter QRS duration at surface ECG, whereas clinically unrecognized myocardial scar is associated with a longer QT interval. © RSNA, 2016 Online supplemental material is available for this article.


Assuntos
Eletrocardiografia , Grupos Étnicos , Cardiopatias/patologia , Cardiopatias/fisiopatologia , Miocárdio/patologia , Idoso , Idoso de 80 Anos ou mais , Cicatriz , Estudos Transversais , Feminino , Fibrose , Cardiopatias/diagnóstico por imagem , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/patologia , Ventrículos do Coração/fisiopatologia , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade
17.
Radiology ; 281(3): 737-748, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27636027

RESUMO

Purpose To determine reader and computed tomography (CT) scan variability for measurement of coronary plaque volume. Materials and Methods This HIPAA-compliant study followed Standards for Reporting of Diagnostic Accuracy guidelines. Baseline coronary CT angiography was performed in 40 prospectively enrolled subjects (mean age, 67 years ± 6 [standard deviation]) with asymptomatic hyperlipidemia by using a 320-detector row scanner (Aquilion One Vision; Toshiba, Otawara, Japan). Twenty of these subjects underwent coronary CT angiography repeated on a separate day with the same CT scanner (Toshiba, group 1); 20 subjects underwent repeat CT performed with a different CT scanner (Somatom Force; Siemens, Forchheim, Germany [group 2]). Intraclass correlation coefficients (ICCs) and Bland-Altman analysis were used to assess interreader, intrareader, and interstudy reproducibility. Results Baseline and repeat coronary CT angiography scans were acquired within 19 days ± 6. Interreader and intrareader agreement rates were high for total, calcified, and noncalcified plaques for both CT scanners (all ICCs ≥ 0.96) without bias. Scanner variability was ±18.4% (coefficient of variation) with same-vendor follow-up. However, scanner variability increased to ±29.9% with different-vendor follow-up. The sample size to detect a 5% change in noncalcified plaque volume with 90% power and an α error of .05 was 286 subjects for same-CT scanner follow-up and 753 subjects with different-vendor follow-up. Conclusion State-of-the-art coronary CT angiography with same-vendor follow-up has good scan-rescan reproducibility, suggesting a role of coronary CT angiography in monitoring coronary artery plaque response to therapy. Differences between coronary CT angiography vendors resulted in lower scan-rescan reproducibility. © RSNA, 2016 Online supplemental material is available for this article.


Assuntos
Doença da Artéria Coronariana/diagnóstico por imagem , Placa Aterosclerótica/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Angiografia por Tomografia Computadorizada/normas , Doença da Artéria Coronariana/patologia , Humanos , Pessoa de Meia-Idade , Variações Dependentes do Observador , Placa Aterosclerótica/patologia , Tomógrafos Computadorizados/normas
18.
JACC Cardiovasc Imaging ; 9(10): 1164-1173, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27639760

RESUMO

OBJECTIVES: The aim of this longitudinal study was to define the determinants of aging-related left ventricular (LV) remodeling and function in a large multiethnic population. BACKGROUND: The influence of risk factor exposure on myocardial remodeling and function in humans across adult life remains incompletely understood. MESA (Multi-Ethnic Study of Atherosclerosis) is a longitudinal population-based cohort of asymptomatic adults at baseline. METHODS: We examined 757 participants who were free of clinical cardiovascular disease and underwent tagged cardiac magnetic resonance both at baseline and at the 10-year follow-up as part of the MESA study. LV remodeling, circumferential shortening (CS), and torsion were assessed by tagged cardiac magnetic resonance. Multivariable linear regression was used to determine the association of changes in risk factors with changes in cardiac geometry and function. RESULTS: The mean age of participants was 63 ± 9 years at baseline; 50% were women. Overall, the LV mass-to-volume ratio increased by 10% over 10 years (p < 0.01). CS was unchanged (17.8% to 17.9%, p = 0.246), whereas torsion increased by 13% (3.8°/cm to 4.3°/cm, p < 0.001). Increased systolic blood pressure was associated with reduced CS (-0.02%/mm Hg, p < 0.01). Participants who remained on antihypertensive therapy during the whole study had a greater decrease in LV mass-to-volume ratio (-0.045 vs. no medication, p < 0.05) with a greater increase in CS (0.78% vs. no medication, p < 0.01). Moreover, greater LV mass at baseline was significantly associated with reduced CS (-0.02%/g, p < 0.01) and torsion (-0.02°/cm/g, p < 0.01) independently of risk factors. CONCLUSIONS: Longitudinal observation demonstrates that LV mass and worsening risk factors are fundamental determinants of reduced regional myocardial shortening over 10 years. Increased torsion of the myocardial wall is seen with progressive concentric remodeling and may explain why systolic function is maintained with aging.


Assuntos
Envelhecimento , Cardiopatias/fisiopatologia , Contração Miocárdica , Função Ventricular Esquerda , Remodelação Ventricular , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Fenômenos Biomecânicos , Feminino , Cardiopatias/diagnóstico por imagem , Cardiopatias/etnologia , Humanos , Modelos Lineares , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Estudos Prospectivos , Fatores de Risco , Fatores de Tempo , Estados Unidos/epidemiologia
19.
Artigo em Inglês | MEDLINE | ID: mdl-27353852

RESUMO

BACKGROUND: This study sought to assess cross-sectional associations of aortic stiffness assessed by magnetic resonance imaging with left ventricular (LV) remodeling and myocardial deformation in the Multi-Ethnic Study of Atherosclerosis (MESA). METHODS AND RESULTS: Aortic arch pulse wave velocity (PWV) was measured with phase contrast cine magnetic resonance imaging. LV circumferential strain (Ecc), torsion, and early diastolic strain rate were determined by tagged magnetic resonance imaging. Multivariable linear regression models were used to adjust for demographics and cardiovascular risk factors. Of 2093 participants, multivariable linear regression models demonstrated that higher arch PWV was associated with higher LV mass index (B=0.53 per 1 SD increase for log-transformed PWV, P<0.05) and LV mass to volume ratio (B=0.015, P<0.01), impaired LV ejection fraction (LVEF; B=-0.84; P<0.001), Ecc (B=0.55; P<0.001), torsion (B=-0.11; P<0.001), and early diastolic strain rate (B=-0.003; P<0.05). In sex stratified analysis, higher arch PWV was associated with higher MVR (B=0.02; P<0.05), impaired Ecc (B=0.60; P<0.001), and LVEF (B=-0.45; P<0.05), but with maintained torsion in women. Higher PWV was associated with impaired Ecc (B=0.49; P<0.001) and LVEF (B=-1.21; P<0.001), with lower torsion (B=-0.17; P<0.001) in men. CONCLUSIONS: Higher arch PWV is associated with LV remodeling, and reduced LV systolic and diastolic function in a large multiethnic population. Greater aortic arch stiffness is associated with concentric LV remodeling and relatively preserved LVEF with maintained torsion in women, whereas greater aortic arch stiffness is associated with greater LV dysfunction demonstrated as impaired Ecc, torsion, and LVEF, with less concentric LV remodeling in men.


Assuntos
Aorta Torácica/diagnóstico por imagem , Aterosclerose/diagnóstico por imagem , Imagem Cinética por Ressonância Magnética , Contração Miocárdica , Rigidez Vascular , Disfunção Ventricular Esquerda/diagnóstico por imagem , Função Ventricular Esquerda , Remodelação Ventricular , Idoso , Idoso de 80 Anos ou mais , Aorta Torácica/fisiopatologia , Aterosclerose/etnologia , Aterosclerose/fisiopatologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Análise de Onda de Pulso , Fatores Sexuais , Volume Sistólico , Torção Mecânica , Estados Unidos/epidemiologia , Disfunção Ventricular Esquerda/etnologia , Disfunção Ventricular Esquerda/fisiopatologia
20.
N Engl J Med ; 374(20): 1922-31, 2016 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-27192671

RESUMO

BACKGROUND: Genetic defects in telomere maintenance and repair cause bone marrow failure, liver cirrhosis, and pulmonary fibrosis, and they increase susceptibility to cancer. Historically, androgens have been useful as treatment for marrow failure syndromes. In tissue culture and animal models, sex hormones regulate expression of the telomerase gene. METHODS: In a phase 1-2 prospective study involving patients with telomere diseases, we administered the synthetic sex hormone danazol orally at a dose of 800 mg per day for a total of 24 months. The goal of treatment was the attenuation of accelerated telomere attrition, and the primary efficacy end point was a 20% reduction in the annual rate of telomere attrition measured at 24 months. The occurrence of toxic effects of treatment was the primary safety end point. Hematologic response to treatment at various time points was the secondary efficacy end point. RESULTS: After 27 patients were enrolled, the study was halted early, because telomere attrition was reduced in all 12 patients who could be evaluated for the primary end point; in the intention-to-treat analysis, 12 of 27 patients (44%; 95% confidence interval [CI], 26 to 64) met the primary efficacy end point. Unexpectedly, almost all the patients (11 of 12, 92%) had a gain in telomere length at 24 months as compared with baseline (mean increase, 386 bp [95% CI, 178 to 593]); in exploratory analyses, similar increases were observed at 6 months (16 of 21 patients; mean increase, 175 bp [95% CI, 79 to 271]) and 12 months (16 of 18 patients; mean increase, 360 bp [95% CI, 209 to 512]). Hematologic responses occurred in 19 of 24 patients (79%) who could be evaluated at 3 months and in 10 of 12 patients (83%) who could be evaluated at 24 months. Known adverse effects of danazol--elevated liver-enzyme levels and muscle cramps--of grade 2 or less occurred in 41% and 33% of the patients, respectively. CONCLUSIONS: In our study, treatment with danazol led to telomere elongation in patients with telomere diseases. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01441037.).


Assuntos
Doenças da Medula Óssea/tratamento farmacológico , Danazol/uso terapêutico , Antagonistas de Estrogênios/uso terapêutico , Cirrose Hepática/tratamento farmacológico , Fibrose Pulmonar/tratamento farmacológico , Telômero/efeitos dos fármacos , Administração Oral , Adolescente , Adulto , Idoso , Feminino , Cor de Cabelo/genética , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Estudos Prospectivos , Telomerase/genética , Telomerase/metabolismo , Telômero/ultraestrutura , Regulação para Cima , Adulto Jovem
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