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1.
Eur J Neurol ; 30(3): 612-621, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36421025

RESUMO

BACKGROUND AND PURPOSE: Juvenile-onset Huntington disease (JHD) is defined when symptoms initiate before 20 years of age. Mechanisms explaining differences between juvenile and adult onset are not fully understood. Our aim was to analyze the distribution of initial symptoms in a cohort of JHD patients and to explore its relationship with CAG expansion and relative telomere length (RTL). METHODS: A total of 84 JHD patients and 54 neurologically healthy age and sex matched individuals were recruited. CAG length was measured by southern blot or triplet repeat primed polymerase chain reaction. RTL was measured using the Cawthon method. RESULTS: Psychiatric symptoms were most frequent when considering the entire cohort. When divided into onset before or after 10 years, cognitive symptoms were more frequent in the youngest, whilst in the older group psychiatric symptoms prevailed. Motor symptoms were rare in the youngest and epilepsy was observed only in this group as well as a larger CAG expansion. RTL analysis revealed shorter telomeres in JHD patients compared to controls. This difference is not influenced by age, initial symptoms, time of disease or CAG expansion. CONCLUSIONS: To the best of our knowledge this is the largest cohort of JHD patients reported. Psychiatric manifestations deserve special attention when JHD is suspected and epilepsy is especially important in the youngest patients. Initial symptoms seem to be influenced by CAG expansion and therefore age of onset. RTL is significantly reduced in JHD patients which can influence the characteristic neurodegeneration of JHD and contribute to the clinical discrepancy between adult and juvenile forms of Huntington disease.


Assuntos
Doença de Huntington , Adulto , Humanos , Doença de Huntington/genética , Doença de Huntington/diagnóstico , Repetições de Trinucleotídeos/genética , Telômero , Idade de Início
2.
Circulation ; 135(22): 2133-2144, 2017 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-28275165

RESUMO

BACKGROUND: Although risk factors for atherosclerotic cardiovascular disease (ASCVD) in familial hypercholesterolemia (FH) have been described, models for predicting incident ASCVD have not been reported. Our aim was to use the SAFEHEART registry (Spanish Familial Hypercholesterolemia Cohort Study) to define key risk factors for predicting incident ASCVD in patients with FH. METHODS: SAFEHEART is a multicenter, nationwide, long-term prospective cohort study of a molecularly defined population with FH with or without previous ASCVD. Analyses to define risk factors and to build a risk prediction equation were developed, and the risk prediction equation was tested for its ability to discriminate patients who experience incident ASCVD from those who did not over time. RESULTS: We recruited 2404 adult patients with FH who were followed up for a mean of 5.5 years (SD, 3.2 years), during which 12 (0.5%) and 122 (5.1%) suffered fatal and nonfatal incident ASCVD, respectively. Age, male sex, history of previous ASCVD, high blood pressure, increased body mass index, active smoking, and low-density lipoprotein cholesterol and lipoprotein(a) levels were independent predictors of incident ASCVD from which a risk equation with a Harrell C index of 0.85 was derived. The bootstrap resampling (100 randomized samples) of the original set for internal validation showed a degree of overoptimism of 0.003. Individual risk was estimated for each person without an established diagnosis of ASCVD before enrollment in the registry by use of the SAFEHEART risk equation, the modified Framingham risk equation, and the American College of Cardiology/American Heart Association ASCVD Pooled Cohort Risk Equations. The Harrell C index for these models was 0.81, 0.78, and 0.8, respectively, and differences between the SAFEHEART risk equation and the other 2 were significant (P=0.023 and P=0.045). CONCLUSIONS: The risk of incident ASCVD may be estimated in patients with FH with simple clinical predictors. This finding may improve risk stratification and could be used to guide therapy in patients with FH. CLINICAL TRIAL REGISTRATION: URL: http://clinicaltrials.gov. Unique identifier: NCT02693548.


Assuntos
Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/epidemiologia , Sistema de Registros , Adulto , Estudos de Coortes , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Risco , Espanha/epidemiologia
3.
Echocardiography ; 35(11): 1812-1817, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30079468

RESUMO

INTRODUCTION: Mitral regurgitation severity assessment is usually carried out using qualitative, semiquantitative, and quantitative parameters. The mitral valve navigation (MVN) tool allows to measure the mitral effective regurgitant orifice (MERO) from 3D echo datasets. Our aim was to validate the MVN as a new tool to quantify MERO. A secondary aim was to assess the intra- and interobserver variability. METHODS: This is a retrospective study in which consecutive subjects undergoing a transoesophageal echocardiogram for more than mild mitral regurgitation evaluation were included. MERO measurement obtained by means of 3D color Doppler was used as the gold standard method for comparison. In every patient, MERO was also obtained using the MVN tool. RESULTS: Fifty-nine consecutive patients were analyzed (47.5% female; mean age 50.8 years). Mitral regurgitation was moderate in 23 (39%) and severe in 36 (61%) patients. Forty patients (67.8%) had a primary and 19 (32.2%) a secondary mitral regurgitation. The intraclass correlation coefficient (ICC) between 3D color Doppler and MVN was excellent (ICC: 0.95; 95% CI: 0.82 to 0.98; P < 0.001) in the total group and for patients with primary and secondary mitral regurgitation. Intra- and interobserver agreements were also good. CONCLUSIONS: Mitral valve navigator shows an excellent accuracy for measuring MERO when the transoesophageal 3D color Doppler is used as the reference method, either primary or secondary mitral regurgitation. Intraobserver reproducibility and interobserver reproducibility are also excellent. These findings make this software a good alternative method to measure mitral regurgitation severity.


Assuntos
Ecocardiografia Tridimensional/instrumentação , Ecocardiografia Tridimensional/métodos , Ecocardiografia Transesofagiana/instrumentação , Ecocardiografia Transesofagiana/métodos , Insuficiência da Valva Mitral/diagnóstico por imagem , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valva Mitral/diagnóstico por imagem , Valva Mitral/fisiopatologia , Insuficiência da Valva Mitral/fisiopatologia , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Índice de Gravidade de Doença
4.
Arterioscler Thromb Vasc Biol ; 36(9): 2004-10, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27444203

RESUMO

OBJECTIVE: Heterozygous familial hypercholesterolemia (FH) is the most common premature atherosclerotic cardiovascular disease (ASCVD)-related monogenic disorder, and it is associated with ischemic heart disease. There is limited information whether FH increases the risk of peripheral arterial and cerebrovascular disease. Our aim was to analyze ASCVD prevalence and characteristics in different arterial territories in a large FH population, to compare them with an unaffected control population and to determine which factors are associated to ASCVD. APPROACH AND RESULTS: SAFEHEART (Spanish Familial Hypercholesterolaemia Cohort Study) is an ongoing registry of molecularly defined patients with heterozygous FH in Spain. ASCVD in the different arterial territories was analyzed, as well as individual characteristics, genetic variables, and lipid-lowering therapies. The study recruited 4132 subjects (3745 ≥18 years); 2,752 of those enrolled were molecularly diagnosed FH cases. Median age was 44.0 years (45.9% men) and 40 years (46.6% men) in FH patients and unaffected relatives (P<0.001). ASCVD was present in 358 (13.0%) and 47 (4.7%) FH patients and unaffected relatives, respectively (P<0.001). History of premature ASCVD was more prevalent in FH patients (9.4% and 2.4% in FH patients and unaffected relatives, respectively; P<0.001). Coronary artery-related manifestations and peripheral artery disease were more prevalent in FH patients than in controls, but no significant differences were found for cerebrovascular events. Age, body mass index, type 2 diabetes mellitus, high blood pressure, previous use of tobacco, and lipoprotein(a) >50 mg/dL were independently associated with ASCVD. CONCLUSIONS: The prevalence of ASCVD is higher, and the involvement of the arterial territories is different in FH patients when compared with their unaffected relatives. Age, male sex, increased body mass index, hypertension, type 2 diabetes mellitus, smoking habit, and lipoprotein(a) >50 mg/dL were independently associated to ASCVD. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02693548.


Assuntos
Doença das Coronárias/epidemiologia , Hiperlipoproteinemia Tipo II/epidemiologia , Doença Arterial Periférica/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Adulto , Idade de Início , Idoso , Apolipoproteína B-100/genética , Estudos de Casos e Controles , Comorbidade , Doença das Coronárias/diagnóstico , Doença das Coronárias/genética , Feminino , Predisposição Genética para Doença , Hereditariedade , Heterozigoto , Humanos , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/genética , Masculino , Pessoa de Meia-Idade , Epidemiologia Molecular , Mutação , Linhagem , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/genética , Fenótipo , Prevalência , Estudos Prospectivos , Receptores de LDL/genética , Sistema de Registros , Medição de Risco , Fatores de Risco , Fatores Sexuais , Fumar/efeitos adversos , Fumar/epidemiologia , Espanha/epidemiologia , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/genética
5.
Echocardiography ; 32(4): 644-53, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25091933

RESUMO

BACKGROUND/OBJECTIVES: Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with a significantly high risk of stroke and systemic embolism. The aim of our study was to assess the association between left atrium (LA) mechanics measured by 3D wall-motion tracking (3DWMT) technology and the most common thromboembolic risk scores (CHADS2, CHA2DS2-VASc). METHODS: A total of 101 consecutive patients with permanent AF referred were included. Conventional bidimensional (2D) LA parameters, and LA mechanics by means of 3DWMT were studied. Association between LA 2D and 3DWMT parameters and both risk scores was evaluated as well as its correlation with every component of the score individually. RESULTS: Mean age was 78 ± 10 years. Mean CHADS2 was 2.7 ± 1.3 and mean CHA2DS2-VASc was 4.4 ± 1.7. Values of 2D and 3DWTM LA parameters were: 2D area 26.4 ± 9.7 cm(2) , 2D volume index 49.4 ± 10.1 mL/m(2) , 3DWMT left atrial emptying fraction (LAEF) 15.9 ± 8.4%, longitudinal strain 9.1 ± 4.5% and area strain 14.9 ± 8.8%. Linear regression analysis showed statistically significant correlation between LA longitudinal strain and LAEF with CHADS2 and CHA2DS2-VASc scores. For each 10% variation in longitudinal strain, CHADS2 and CHA2DS2-VASc scores change in 0.7 and 0.8 points, respectively. CONCLUSIONS: Left atrial longitudinal strain and emptying fraction assessed by 3D WMT technology have correlation with both CHADS2 and CHA2DS2-VASc scores. Each 10% of variation in longitudinal strain represents a 0.7 and 0.8 points change in those risk scores. LA mechanics evaluation might provide additional value to risk scores and could be considered to be a predictor of stroke in patients with AF.


Assuntos
Fibrilação Atrial/epidemiologia , Ecocardiografia Tridimensional/estatística & dados numéricos , Átrios do Coração/diagnóstico por imagem , Átrios do Coração/fisiopatologia , Tromboembolia/diagnóstico por imagem , Tromboembolia/epidemiologia , Idoso , Fibrilação Atrial/diagnóstico por imagem , Causalidade , Comorbidade , Ecocardiografia Tridimensional/métodos , Feminino , Humanos , Aumento da Imagem/métodos , Interpretação de Imagem Assistida por Computador/métodos , Incidência , Masculino , Reprodutibilidade dos Testes , Medição de Risco , Sensibilidade e Especificidade , Espanha/epidemiologia
6.
Echocardiography ; 30(6): 667-71, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23336434

RESUMO

BACKGROUND: Current guidelines do not recommend routine assessment of right atrial volume due to the lack of standardized data. Three-dimensional wall-motion tracking (3D-WMT) is a new technology that allows us to calculate volumes without any geometric assumptions. The aim of this study was to define the indexed reference values for two-dimensional echocardiography (2D-echo) and 3D-WMT in adult healthy population and to assess the intermethod, intra- and interobserver agreement. METHODS: Prospective study. Nonselected healthy subjects were enrolled. Every patient underwent a 2D-echo and a 3D-WMT examination. 2D-echo right atrial volume was obtained by using the area-length method (A-L) from four- and two-chamber view. 3D-echo volumes were assessed by 3D-WMT. Values were indexed by the patient's body surface area. RESULTS: Sixty consecutive healthy subjects were enrolled. Mean age was 57 ± 12-years old and 27 patients (45%) were male. Average indexed right atrial volume obtained by 2D-echo and 3D-echo was 16.76 ± 8.15 mL/m(2) and 19.05 ± 6.87 mL/m(2) , respectively. Univariate linear regression analysis between 2D-echo and 3D-echo right atrial volumes shows a weak correlation between right atrial volume obtained with 2D-echo compared with 3D-WMT (r = 0.29, CI 95% 0.029-0.66, P = 0.033). The agreement analysis shows a similar result (intraclass correlation coefficient [ICC] = 0.28). The intra- and interobserver agreement analysis showed a better agreement when using 3D-WMT. CONCLUSIONS: This is the first study that reports the reference indexed right atrial volume values by means of 2D-echo and 3D-echo in healthy population. 3D-WMT is a feasible and reproducible method to determine right atrial volume.


Assuntos
Função Atrial/fisiologia , Ecocardiografia Tridimensional/estatística & dados numéricos , Ecocardiografia Tridimensional/normas , Átrios do Coração/diagnóstico por imagem , Tamanho do Órgão/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Valores de Referência , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Espanha/epidemiologia
7.
Mol Neurobiol ; 60(4): 2223-2235, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36646969

RESUMO

Epigenetic processes have become increasingly relevant in understanding disease-modifying mechanisms. 5-Methylcytosine methylations of DNA (5mC) and RNA (m5C) have functional transcriptional and RNA translational consequences and are tightly regulated by writer, reader and eraser effector proteins. To investigate the involvement of 5mC/5hmC and m5C effector proteins contributing to the development of dementia neuropathology, RNA sequencing data of 31 effector proteins across four brain regions was examined in 56 aged non-affected and 51 Alzheimer's disease (AD) individuals obtained from the Aging, Dementia and Traumatic Brain Injury Study. Gene expression profiles were compared between AD and controls, between neuropathological Braak and CERAD scores and in individuals with a history of traumatic brain injury (TBI). We found an increase in the DNA methylation writers DNMT1, DNMT3A and DNMT3B messenger RNA (mRNA) and a decrease in the reader UHRF1 mRNA in AD samples across three brain regions whilst the DNA erasers GADD45B and AICDA showed changes in mRNA abundance within neuropathological load groupings. RNA methylation writers NSUN6 and NSUN7 showed significant expression differences with AD and, along with the reader ALYREF, differences in expression for neuropathologic ranking. A history of TBI was associated with a significant increase in the DNA readers ZBTB4 and MeCP2 (p < 0.05) and a decrease in NSUN6 (p < 0.001) mRNA. These findings implicate regulation of protein pathways disrupted in AD and TBI via multiple pre- and post-transcriptional mechanisms including potentially acting upon transfer RNAs, enhancer RNAs as well as nuclear-cytoplasmic shuttling and cytoplasmic translational control. The targeting of such processes provides new therapeutic avenues for neurodegenerative brain conditions.


Assuntos
Doença de Alzheimer , Lesões Encefálicas Traumáticas , Humanos , Idoso , Doença de Alzheimer/patologia , RNA/metabolismo , Lesões Encefálicas Traumáticas/patologia , Metilação de DNA , Metiltransferases/metabolismo , RNA Mensageiro/metabolismo , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , tRNA Metiltransferases/genética , tRNA Metiltransferases/metabolismo
8.
Arch Bronconeumol ; 58(1): 52-68, 2022 Jan.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-33875282

RESUMO

The main aim of this international consensus document on obstructive sleep apnea is to provide guidelines based on a critical analysis of the latest literature to help health professionals make the best decisions in the care of adult patients with this disease. The expert working group was formed primarily of 17 scientific societies and 56 specialists from a wide geographical area (including the participation of 4 international societies), an expert in methodology, and a documentalist from the Iberoamerican Cochrane Center. The document consists of a main section containing the most significant innovations and a series of online manuscripts that report the systematic literature searches performed for each section of the international consensus document. This document does not discuss pediatric patients or the management of patients receiving chronic non-invasive mechanical ventilation (these topics will be addressed in separate consensus documents).

9.
Atherosclerosis ; 317: 52-58, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33261814

RESUMO

BACKGROUND AND AIMS: Heterozygous familial hypercholesterolemia (FH) is associated with premature atherosclerotic cardiovascular disease. Semi-automated plaque characterization (SAPC) by coronary computed tomographic angiography (CTA) provides information regarding coronary plaque burden and plaque characterization. Our aim was to quantify and characterize the coronary plaque burden of patients with FH using SAPC analysis and to identify which factors are related to plaque burden and plaque characteristics. A second aim was to analyse the prognostic implications of these parameters. METHODS: Two hundred and fifty-nine asymptomatic individuals with molecularly determined FH were enrolled in this follow-up cohort study and underwent a coronary CTA analysed with SAPC. RESULTS: Mean follow-up time after coronary CTA was 3.9 ± 2 years. Mean age was 46.9 (10.7) years (130 women, 50.2%). Median plaque burden was 25.0% (19.0-29.0), non-calcified plaque burden 22.83% (17.94-26.88), calcified plaque-burden 1.12% (0.31-2.86) and CCS 8.9 (0-93). Five-year risk was independently related to plaque burden, non-calcified plaque burden, calcified plaque burden and coronary calcium score (B:3.75, 95%CI:2.92-4.58; p < 0.001, B:2.9, 95%CI:2.15-3.66; p < 0.001, B:0.75, 95%CI 0.4-1.1; p < 0.001 and B:82.2, 95%CI:49.28-115.16; p < 0.001 respectively). During follow-up, there were 15 (5.81%) nonfatal events and 1 (0.4%) fatal event. Plaque burden was significantly related to event-free survival during follow-up (HR:1.11; 95%CI:1.05-1.18; p < 0.001). CONCLUSIONS: Coronary atherosclerosis and its qualitative components may be quantified by means of SAPC in patients with FH. Plaque burden, calcified plaque burden and non-calcified plaque burden were independently related to the estimated cardiovascular risk. Plaque burden was also related to prognosis.


Assuntos
Doença da Artéria Coronariana , Hiperlipoproteinemia Tipo II , Placa Aterosclerótica , Angiografia por Tomografia Computadorizada , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Feminino , Seguimentos , Humanos , Hiperlipoproteinemia Tipo II/complicações , Hiperlipoproteinemia Tipo II/diagnóstico por imagem , Hiperlipoproteinemia Tipo II/genética , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco
10.
Mol Neurobiol ; 58(12): 6222-6231, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34476673

RESUMO

Huntington disease (HD) is the most common neurogenetic disorder caused by expansion of the CAG repeat in the HTT gene; nevertheless, the molecular bases of the disease are not fully understood. Non-coding RNAs have demonstrated to be involved in the physiopathology of HD. However, the role of circRNAs has not been investigated. The aim of this study was to identify the circRNAs with differential expression in a murine cell line model of HD and to identify the biological pathways regulated by the differentially expressed circRNAs. CircRNA expression was analyzed through a microarray, which specifically detects circular species of RNA. The expression patterns between a murine cell line expressing mutant Huntingtin and cells expressing wild-type Huntingtin were compared. We predicted the miRNAs with binding sites for the differentially expressed circRNAs and the corresponding target genes for those miRNAs. Using the target genes, we performed a function enrichment analysis. We identified 23 circRNAs differentially expressed, 19 downregulated and four upregulated. Most of the downregulated circRNAs derive from the Rere gene. The dopaminergic synapse, MAPK, and long-term depression pathways were significantly enriched. The three identified pathways have been previously associated with the physiopathology of HD. The understanding of the circRNA-miRNA-mRNA network involved in the molecular mechanisms driving HD can lead us to identify novel biomarkers and potential therapeutic targets. To the best of our knowledge, this is the first study analyzing circRNAs in a model of Huntington disease.


Assuntos
Neurônios Dopaminérgicos/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Doença de Huntington/metabolismo , Depressão Sináptica de Longo Prazo/fisiologia , RNA Circular/metabolismo , Sinapses/metabolismo , Animais , Regulação para Baixo , Perfilação da Expressão Gênica , Doença de Huntington/fisiopatologia , MicroRNAs/metabolismo , Células PC12 , RNA Mensageiro/metabolismo , Ratos
11.
Echocardiography ; 27(10): 1238-46, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20584068

RESUMO

BACKGROUND: High blood pressure increases left ventricular (LV) after-load. Furthermore, LV response to that high blood pressure varies among different subjects. Nevertheless, myocardial deformation behavior in these different adaptative responses has not been analyzed until now. METHODS: Prospective study in which 66 consecutive hypertensive patients were enrolled in between May and August 2009. Every patient underwent a standard echocardiographic study and a three-dimensional-wall motion tracking (3D-WMT) study. The patients were classified according to parameters derived from echocardiography in four different groups: normal geometry, concentric remodelling, concentric hypertrophy, and eccentric hypertrophy. RESULTS: Mean age was 68 years (57-74.25; 51.5% male). Comparing the four groups, significant differences were found for the five 3D-WMT-derived parameters. When patients were compared with hypertensive patients with normal geometry, our finding show that: (a) LV average torsion is the only impaired parameter that is found in the LV concentric remodelling group (P < 0.05 vs. group 1); (b) there is a trend for an increase (P = 0.055) in LV average radial strain in the group with concentric hypertrophy and this increase is accompanied by a significant decrease in the remaining studied parameters (P < 0.05); and (c) in the LV eccentric hypertrophy group, there is a significant impairment in all the studied parameters (P < 0.05). CONCLUSIONS: LV adaptative response to hypertension is accompanied by a modification or even impairment, in LV myocardial deformation evaluated by 3D-WMT. This assessment might be useful to detect early and subtle deformation impairments in hypertensive patients and it could help optimize their clinical management.


Assuntos
Ecocardiografia Tridimensional/métodos , Técnicas de Imagem por Elasticidade/métodos , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/fisiopatologia , Hipertensão/diagnóstico por imagem , Hipertensão/fisiopatologia , Adaptação Fisiológica , Idoso , Módulo de Elasticidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
12.
Mech Ageing Dev ; 185: 111189, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31759995

RESUMO

INTRODUCTION: Huntington´s disease (HD) is a neurodegenerative disorder characterized by neuropsychiatric, motor and cognitive manifestations. It is caused by expansion of the trinucleotide CAG on HTT. The molecular bases are not completely understood, DNA damage, such as double and single strand breaks and oxidative stress (OS) have been implicated. At telomeres, DNA breaks are less efficiently repaired. Double strand breaks evoke the break induced replication (BIR) mechanism. BIR, plus inefficient repair can produce telomere shortening and cellular senescence. Our aim was to investigate the correlation between leukocyte relative telomeric length (RTL) and HD. METHODS: 206 samples were analyzed, 71 patients with molecular diagnosis and symptomatology (HD), 29 individuals with positive molecular test but asymptomatic (PP) and 106 healthy individuals (NP). RESULTS: We found a significant difference in RTL between HD patients compared with both, PP and NP, independently of subjects' age. DISCUSSION: Here we present evidence supporting an association between telomere shortening and HD. Telomere shortening could be related to DNA damage caused by ROS and defective DNA repair mechanism. Both events have been probed to occur in the presence of a mutant Huntingtin. This study contributes with current evidence suggesting a potential role of telomere shortening as HD biomarker.


Assuntos
Biomarcadores , Proteína Huntingtina/genética , Doença de Huntington , Encurtamento do Telômero , Doenças Assintomáticas , Senescência Celular , Correlação de Dados , Dano ao DNA , Feminino , Humanos , Doença de Huntington/diagnóstico , Doença de Huntington/genética , Doença de Huntington/metabolismo , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Avaliação de Sintomas/métodos , Expansão das Repetições de Trinucleotídeos
13.
J Clin Lipidol ; 12(4): 948-957, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29753733

RESUMO

BACKGROUND: Familial hypercholesterolemia (FH) confers an increased risk of premature atherosclerotic disease. Coronary computed tomographic angiography (CTA) can assess preclinical coronary atherosclerosis. OBJECTIVES: To describe coronary CTA findings in asymptomatic molecularly defined FH individuals, to identify those factors related to its presence and extension, and to assess the impact of these results in patients' care and estimated risk. METHODS: Four hundred and forty individuals with FH, without clinical cardiovascular disease, were consecutively enrolled and underwent a coronary CTA that was used to analyze coronary atherosclerosis based on coronary calcium score (CCS), sum of stenosis severity, and plaque composition sum (PCS). For FH patients, cardiovascular risk was estimated using the specific SAFEHEART risk equation. Follow-up was performed using a standardized protocol. RESULTS: Mean age was 46.4 years (231 women, 52%). Coronary calcium was present in 55%, mean CCS was 130.9, 46% had a plaque with lumen involvement, and mean PCS was 1.1. During follow-up, there were 17 (4%) nonfatal events and 2 (1%) fatal events. CCS was independently associated to the estimated risk and low-density lipoprotein-cholesterol life-years, sum of stenosis severity to the estimated risk, and PCS to the estimated risk and low-density lipoprotein-cholesterol life-years. CTA findings induced a positive change in patients' care and in their estimated risk. CONCLUSION: Coronary artery atherosclerosis is highly prevalent in asymptomatic patients with FH and it is independently associated to cardiovascular risk. More advanced disease on CTA was associated with subsequent intensification of therapy and reduction of estimated risk. Further longitudinal studies are required to know if these findings might improve the risk stratification in patients with FH.


Assuntos
Angiografia Coronária , Hiperlipoproteinemia Tipo II/diagnóstico , Adulto , Idoso , Cálcio/metabolismo , LDL-Colesterol/sangue , Constrição Patológica , Feminino , Seguimentos , Humanos , Hiperlipoproteinemia Tipo II/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/complicações , Placa Aterosclerótica/diagnóstico , Fatores de Risco , Tomografia Computadorizada por Raios X , Adulto Jovem
14.
Rev Esp Cardiol (Engl Ed) ; 70(6): 444-450, 2017 Jun.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-27913073

RESUMO

INTRODUCTION AND OBJECTIVES: Little is known about the characteristics of persons with familial hypercholesterolemia (FH) younger than 18 years, the lipid-lowering therapy used in these patients, and the lipid goals reached in real life. Our aim was to evaluate the achievement of low-density lipoprotein cholesterol (LDL-C) treatment goals in FH patients younger than 18 years enrolled in a large national registry. METHODS: We analyzed patients younger than 18 years enrolled in a large ongoing registry of molecularly-defined patients with FH in Spain. The attainment of guideline-recommended plasma LDL-C goals at entry and follow-up was analyzed in relation to the use of lipid-lowering therapy. RESULTS: We enrolled 392 individuals younger than 18 years. Of these, 217 were molecularly-diagnosed FH patients and had a complete follow-up. The median follow-up time was 4.69 years (interquartile range, 2.48-6.38 years), 68.2% of FH patients were on statins, and 41.5% patients had LDL-C < 130mg/dL. Statin use was the only predictor of LDL-C goal attainment. CONCLUSIONS: This study shows that a high proportion of FH patients younger than 18 years have high LDL-C levels and fail to achieve recommended LDL-C targets. Statin use was the only independent predictor of LDL-C goal achievement. No safety concerns were detected during follow-up. These results indicate that many FH patients are not adequately controlled and that there is still room for treatment improvement.


Assuntos
Anticolesterolemiantes/uso terapêutico , LDL-Colesterol/sangue , Fidelidade a Diretrizes , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Sistema de Registros , Adolescente , Criança , LDL-Colesterol/efeitos dos fármacos , Feminino , Seguimentos , Humanos , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/epidemiologia , Incidência , Masculino , Estudos Prospectivos , Espanha/epidemiologia , Resultado do Tratamento
15.
Eur J Prev Cardiol ; 23(17): 1903-1908, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27486159

RESUMO

BACKGROUND: Vascular age is a concept that represents the hypothetical age of the cardiovascular system and might be an alternative way of expressing the cardiovascular risk of a patient. The Data Collection on Adverse Effects of Anti-HIV Drugs Study (D:A:D) developed a cardiovascular risk equation from a population of HIV-infected patients, incorporating exposure to individual antiretroviral therapy drugs and traditional classic cardiovascular risk factors. OBJECTIVES: The aim of this study was to determine the vascular age calculated from the D:A:D equation, for HIV infected patients. METHODS: Vascular age was calculated according to its definition by using the D:A:D equation. The Poisson regression model used in the D:A:D equation is an exponential model to calculate the vascular age to match the exponent of the equation with the factors of a patient with the exponent of a subject with controlled risk factors. RESULTS: We obtained an equation that allows calculating the vascular age of a patient considering cardiovascular risk factors listed in the same D:A:D equation. From the equation, we have built a table for easy calculation of the vascular age and a table of cardiovascular risk equivalents. CONCLUSIONS: Vascular age is a new concept derived from Framingham risk tables that can be calculated with other risk scales, such as D:A:D for HIV patients. The calculation of vascular age in HIV patients could be a useful tool for communicating cardiovascular risk and to improve the control of modifiable risk factors.


Assuntos
Envelhecimento , Vasos Sanguíneos , Doenças Cardiovasculares/etiologia , Infecções por HIV/complicações , Modelos Teóricos , Medição de Risco , Adulto , Doenças Cardiovasculares/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Espanha/epidemiologia
16.
Mol Clin Oncol ; 3(4): 820-824, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26171188

RESUMO

Certain chemotherapy drugs for breast cancer may induce cardiotoxicity and these patients should be echocardiographically monitored. The performance of a focused echocardiographic evaluation (echoscopy) at the patient's location by a non-cardiologist appears to be feasible. The aim of the present study was to assess the accuracy of echoscopy performed by medical oncologists in an outpatient clinic using hand-held echocardiography devices. The study cohort comprised consecutive unselected patients who attended an oncology outpatient clinic. Two medical oncologists attended a one-week training period, which included theoretical and practical teaching by an expert cardiologist. Every subject underwent two echo examinations. The first examination was performed by an oncologist using a hand-held echo device and the second was performed by a cardiologist using a 'premium' device. Out of the 101 enrolled patients, 32 were men (31.7%) and the mean age was 56.03±16.88 years. There was a good global agreement [intra-class correlation coefficient (ICC): 0.65 for left ventricular ejection fraction (LVEF)]. When the results were analyzed depending on the period of time when the echo studies were performed, a clear and short learning curve was observed: LVEF started at ICC=0.58 and increased to 0.66 and 0.77 in the second and third period, respectively. There were extremely few clinically significant differences and a learning curve was also evident. In conclusion, cardiac echoscopy performed by an oncologist with a hand-held device may lead to a similar clinical management as a study performed by an expert cardiologist with a 'premium' system in patients under chemotherapy following a short training period.

17.
Eur Heart J Cardiovasc Imaging ; 15(7): 793-9, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24480243

RESUMO

BACKGROUND: Left atrium (LA) size assessment is clinically relevant, but the accuracy of two-dimensional echocardiographic (2D-echo) methods is limited. Three-dimensional (3D) echocardiography is an excellent alternative but is far from being used in daily clinical practice. Three-dimensional-wall motion tracking (3D-WMT) allows us to obtain volumes in a very simple and rapid manner. The aims of this study were to evaluate the accuracy of 3D-WMT technology to assess LA volume using cardiac magnetic resonance (CMR) as a reference method, to evaluate its reproducibility, and to determine its added clinical value to classify the LA enlargement severity. METHODS AND RESULTS: Seventy consecutive patients referred for a CMR study were prospectively enrolled. They underwent LA volume assessment by means of 2D-echo, 3D-WMT, and CMR. Inter-methods agreement was assessed. The mean age was 56 ± 18 years and 42 patients (60%) were males. Average maximal LA volume obtained by 2D-echo, 3D-WMT, and CMR were 63.33 ± 26.82, 79.80 ± 29.0, and 79.80 ± 28.99 mL, respectively. Univariate linear regression analysis showed a good correlation between 3D-WMT and CMR (r = 0.83; P < 0.001). The agreement analysis showed a similar result (ICC = 0.83; 95% CI = 0.74-0.89; P < 0.001). Furthermore, the LA enlargement degree was better evaluated with 3D-WMT than with 2D-echo. CONCLUSION: This study validates LA volume measurements obtained using the new and fast 3D-WMT technology, compared with CMR. This method is fast, accurate, and reproducible, and it allows a better classification of left LA enlargement severity compared with 2D-echo.


Assuntos
Ecocardiografia Tridimensional , Átrios do Coração/diagnóstico por imagem , Átrios do Coração/patologia , Imagem Cinética por Ressonância Magnética/métodos , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Função Atrial/fisiologia , Estudos de Coortes , Ecocardiografia/métodos , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Estudos Prospectivos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Fatores Sexuais
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