Types of social supports predicting health-related quality of life among adult patients with CHD in the Institut Jantung Negara (National Heart Institute), Malaysia.

PubMed

Tye, Sue K; Kandavello, Geetha; Gan, Kah L

2017-01-01

The objectives of this study were to examine which types of social supports - emotional/informational support, tangible support, affectionate support, and positive interactions - are the predictors of health-related quality of life (HRQoL) in adult patients with CHD and to assess the influence of demographic variables and clinical factors on these variables. In total, 205 adult patients with CHD from the National Heart Institute, Malaysia, were recruited. Patients were first screened by cardiology consultants to ensure they fit the inclusion criteria before filling in questionnaires, which were medical outcome studies - social support survey and AQoL-8D. Results/conclusions All social supports and their subscales were found to have mild-to-moderate significant relationships with physical dimension, psychological dimension, and overall HRQoL; however, only positive interaction, marital status, and types of diagnosis were reported as predictors of HRQoL. Surprisingly, with regard to the physical dimension of quality of life, social supports were not significant predictors, but educational level, marital status, and types of diagnosis were significant predictors. Positive interaction, affectionate support, marital status, and types of diagnosis were again found to be predictors in the aspects of the psychological dimension of quality of life. In conclusion, positive interaction and affectionate support, which include elements of fun, relaxation, love, and care, should be included in the care of adult patients with CHD.

The metabolic syndrome: prevalence, CHD risk, and treatment.

PubMed

Sarti, Cinzia; Gallagher, John

2006-01-01

An increased risk of coronary heart disease (CHD) morbidity and mortality is associated with the metabolic syndrome, a condition characterized by the concomitant presence of several abnormalities, including abdominal obesity, dyslipidemia, hypertension, insulin resistance (with or without glucose intolerance or diabetes), microalbuminuria, prothrombotic, and proinflammatory states. Estimates of the prevalence of the metabolic syndrome indicate that this condition is now common and likely to increase dramatically over the coming decades, in parallel with greater rates of obesity and Type 2 diabetes. Risk factors for the metabolic syndrome are already present in obese children and adolescents. Thus, identifying and treating all affected individuals promptly and optimally are critical to ensure that this potentially challenging healthcare burden is minimized. Here, we review the prevalence of the metabolic syndrome, dyslipidemias, and CHD risk. Although changes in lifestyle are fundamental to reducing many of the CHD risk factors associated with the metabolic syndrome, pharmacologic interventions also play an important role. Retrospective subanalyses of the effects of statins on coronary event rates and lipid levels in patients with the metabolic syndrome included in clinical trials indicate that these agents are beneficial in correcting the extensive lipid abnormalities that are frequently present in these individuals. However, the optimal management of metabolic syndrome dyslipidemia will depend on the outcomes of future prospective clinical trials. This review examines the underlying causes and prevalence of the metabolic syndrome and its impact on CHD morbidity and mortality and discusses the role of statins in optimizing its management.

School-related adjustment in children and adolescents with CHD.

PubMed

Im, Yu-Mi; Lee, Sunhee; Yun, Tae-Jin; Choi, Jae Young

2017-09-01

Advancements in medical and surgical treatment have increased the life expectancy of patients with CHD. Many patients with CHD, however, struggle with the medical, psychosocial, and behavioural challenges as they transition from childhood to adulthood. Specifically, the environmental and lifestyle challenges in school are very important factors that affect children and adolescents with CHD. This study aimed to evaluate school-related adjustments depending on school level and disclosure of disease in children and adolescents with CHD. This was a descriptive and exploratory study with 205 children and adolescents, aged 7-18 years, who were recruited from two congenital heart clinics from 5 January to 27 February, 2015. Data were analysed using the Student's t-test, analysis of variance, and a univariate general linear model. School-related adjustment scores were significantly different according to school level and disclosure of disease (p<0.001) when age, religion, experience being bullied, and parents' educational levels were assigned as covariates. The school-related adjustment score of patients who did not disclose their disease dropped significantly in high school. This indicated that it is important for healthcare providers to plan developmentally appropriate educational transition programmes for middle-school students with CHD in order for students to prepare themselves before entering high school.

Genetic factors may play a prominent role in the development of coronary heart disease dependent on important environmental factors

PubMed Central

Song, C; Chang, Z; Magnusson, P K E; Ingelsson, E; Pedersen, N L

2014-01-01

Astract Song C, Chang Z, Magnusson PKE, Ingelsson E, Pedersen NL (Karolinska Institutet, Stockholm; Uppsala University, Uppsala; Sweden). Genetic factors may play a prominent role in the developmentofcoronary heart diseasedependenton important environmental factors. J InternMed2014; 275: 631–639. Objective The aim of the study was to examine whether various lifestyle factors modify genetic influences on coronary heart disease (CHD). Design The effect of lifestyle factors [including smoking, sedentary lifestyle, alcohol intake and body mass index (BMI)] on risk of CHD was evaluated via Cox regression models in a twin study of gene–environment interaction. Using structure equation modelling, we estimated genetic variance of CHD dependent on lifestyle factors. Subjects In total, 51 065 same-sex twins from 25 715 twin pairs born before 1958 and registered in the Swedish Twin Registry were eligible for this study. During the 40-year follow-up, 7264 incident CHD events were recorded. Results Smoking, sedentary lifestyle and above average BMI were significantly associated with increased CHD incidence. The heritability of CHD decreased with increasing age, as well as with increasing levels of BMI, in both men and women. Conclusions The difference in the genetic component of CHD as a function of BMI suggests that genetic factors may play a more prominent role for disease development in the absence of important environmental factors. Increased knowledge of gene–environment interactions will be important for a full understanding of the aetiology of CHD. PMID:24330166

Does maternal environmental tobacco smoke interact with social-demographics and environmental factors on congenital heart defects?

PubMed

Liu, Xiaoqing; Nie, Zhiqiang; Chen, Jimei; Guo, Xiaoling; Ou, Yanqiu; Chen, Guanchun; Mai, Jinzhuang; Gong, Wei; Wu, Yong; Gao, Xiangmin; Qu, Yanji; Bell, Erin M; Lin, Shao; Zhuang, Jian

2018-03-01

Congenital heart defects (CHDs) are a major cause of death in infancy and childhood. Major risk factors for most CHDs, particularly those resulting from the combination of environmental exposures with social determinants and behaviors, are still unknown. This study evaluated the main effect of maternal environmental tobacco smoke (ETS), and its interaction with social-demographics and environmental factors on CHDs in China. A population-based, matched case-control study of 9452 live-born infants and stillborn fetuses was conducted using the Guangdong Registry of Congenital Heart Disease data (2004-2014). The CHDs were evaluated by obstetrician, pediatrician, or cardiologist, and confirmed by cardia tomography/catheterization. Controls were randomly chosen from singleton newborns without any malformation, born in the same hospital as the cases and 1:1 matched by infant sex, time of conception, and parental residence (same city and town to ensure sufficient geographical distribution for analyses). Face-to-face interviews were conducted to collect information on demographics, behavior patterns, maternal disease/medication, and environmental exposures. Conditional logistic regression was used to estimate odds ratios and 95% confidence intervals of ETS exposure on CHDs while controlling for all risk factors. Interactive effects were evaluated using a multivariate delta method for maternal demographics, behavior, and environmental exposures on the ETS-CHD relationship. Mothers exposed to ETS during the first trimester of pregnancy were more likely to have infants with CHD than mothers who did not (aOR = 1.44, 95% CI 1.25-1.66). We also observed a significant dose-response relationship when mothers were exposed to ETS and an increasing number of risk factors and CHDs. There were greater than additive interactions for maternal ETS and migrant status, low household income and paternal alcohol consumption on CHDs. Maternal low education also modified the ETS-CHD

CHD5, a brain-specific paralog of Mi2 chromatin remodeling enzymes, regulates expression of neuronal genes.

PubMed

Potts, Rebecca Casaday; Zhang, Peisu; Wurster, Andrea L; Precht, Patricia; Mughal, Mohamed R; Wood, William H; Zhang, Yonqing; Becker, Kevin G; Mattson, Mark P; Pazin, Michael J

2011-01-01

CHD5 is frequently deleted in neuroblastoma and is a tumor suppressor gene. However, little is known about the role of CHD5 other than it is homologous to chromatin remodeling ATPases. We found CHD5 mRNA was restricted to the brain; by contrast, most remodeling ATPases were broadly expressed. CHD5 protein isolated from mouse brain was associated with HDAC2, p66ß, MTA3 and RbAp46 in a megadalton complex. CHD5 protein was detected in several rat brain regions and appeared to be enriched in neurons. CHD5 protein was predominantly nuclear in primary rat neurons and brain sections. Microarray analysis revealed genes that were upregulated and downregulated when CHD5 was depleted from primary neurons. CHD5 depletion altered expression of neuronal genes, transcription factors, and brain-specific subunits of the SWI/SNF remodeling enzyme. Expression of gene sets linked to aging and Alzheimer's disease were strongly altered by CHD5 depletion from primary neurons. Chromatin immunoprecipitation revealed CHD5 bound to these genes, suggesting the regulation was direct. Together, these results indicate that CHD5 protein is found in a NuRD-like multi-protein complex. CHD5 expression is restricted to the brain, unlike the closely related family members CHD3 and CHD4. CHD5 regulates expression of neuronal genes, cell cycle genes and remodeling genes. CHD5 is linked to regulation of genes implicated in aging and Alzheimer's disease.

CHD5, a Brain-Specific Paralog of Mi2 Chromatin Remodeling Enzymes, Regulates Expression of Neuronal Genes

PubMed Central

Potts, Rebecca Casaday; Zhang, Peisu; Wurster, Andrea L.; Precht, Patricia; Mughal, Mohamed R.; Wood, William H.; Zhang, Yonqing; Becker, Kevin G.; Mattson, Mark P.; Pazin, Michael J.

2011-01-01

CHD5 is frequently deleted in neuroblastoma and is a tumor suppressor gene. However, little is known about the role of CHD5 other than it is homologous to chromatin remodeling ATPases. We found CHD5 mRNA was restricted to the brain; by contrast, most remodeling ATPases were broadly expressed. CHD5 protein isolated from mouse brain was associated with HDAC2, p66ß, MTA3 and RbAp46 in a megadalton complex. CHD5 protein was detected in several rat brain regions and appeared to be enriched in neurons. CHD5 protein was predominantly nuclear in primary rat neurons and brain sections. Microarray analysis revealed genes that were upregulated and downregulated when CHD5 was depleted from primary neurons. CHD5 depletion altered expression of neuronal genes, transcription factors, and brain-specific subunits of the SWI/SNF remodeling enzyme. Expression of gene sets linked to aging and Alzheimer's disease were strongly altered by CHD5 depletion from primary neurons. Chromatin immunoprecipitation revealed CHD5 bound to these genes, suggesting the regulation was direct. Together, these results indicate that CHD5 protein is found in a NuRD-like multi-protein complex. CHD5 expression is restricted to the brain, unlike the closely related family members CHD3 and CHD4. CHD5 regulates expression of neuronal genes, cell cycle genes and remodeling genes. CHD5 is linked to regulation of genes implicated in aging and Alzheimer's disease. PMID:21931736

Adult CHD: the ongoing need for physician counselling about heredity and contraceptive options.

PubMed

Londono-Obregon, Camila; Goldmuntz, Elizabeth; Davey, Brooke T; Zhang, Xuemei; Slap, Gail B; Kim, Yuli Y

2017-05-01

Purpose Current guidelines recommend that patients with CHD receive age-appropriate counselling on reproduction, pregnancy, and risk of heredity. Our aim was to examine patient knowledge of reproductive health and explore the association between patient knowledge of CHD transmission risk and earlier physician counselling in adults with CHD. We performed a cross-sectional survey of patients with CHD aged 18 years and older in a paediatric hospital. Of the 100 patients who completed the questionnaire, most did not report counselling on heredity (66%) or contraception (71%). Of the 54 women, 25 (46%) identified their contraceptive options correctly; 42 (78%) women were classified as being at significantly increased risk for an adverse outcome during pregnancy, and of these 20 (48%) identified this risk correctly. Of all patients surveyed, 72% did not know that having CHD placed them at increased risk for having a child with CHD. On multivariate analysis, factors associated with correct knowledge about risk of recurrence were correct identification of CHD diagnosis (p=0.04) and patient-reported counselling (p=0.001). Knowledge about heredity, pregnancy risk, and contraceptive options is inadequate among adults with CHD followed-up in a paediatric subspecialty clinic. The majority of patients did not report a history of counselling about reproductive health. There is a strong correlation between history of counselling by the patient's cardiologist and correct knowledge about recurrence risk, suggesting that effective reproductive counselling can positively impact this knowledge gap.

Type 1 diabetes mellitus and associated risk factors in patients with or without CHD: a case-control study.

PubMed

Björk, Anna; Svensson, Ann-Marie; Fard, Mir Nabi Pirouzi; Eriksson, Peter; Dellborg, Mikael

2017-05-29

Approximately 1% of children are born with CHD, and 90-95% reach adulthood. Increased exposure to infections and stress-strain can contribute to an increased risk of developing type 1 diabetes mellitus. CHD may increase the risk of more serious infections, stress-strain, and increased risk of developing type 1 diabetes mellitus. We analysed the onset of and the risk of mortality and morbidity associated with concurrent CHD in patients with type 1 diabetes mellitus compared with patients with type 1 diabetes mellitus without CHD. The study combined data from the National Diabetes Register and the National Patient Register. A total of 104 patients with CHD and type 1 diabetes mellitus were matched with 520 controls. Patients with CHD and type 1 diabetes mellitus had an earlier onset of diabetes (13.9 versus 17.4 years, p<0.001), longer duration of diabetes (22.4 versus 18.1 years, p<0.001), higher prevalence of retinopathy (64.0 versus 43.0%, p=0.003), higher creatinine levels (83.5 versus 74.1 µmol/L, p=0.03), higher mortality (16 versus 5%, p=0.002), and after onset of type 1 diabetes mellitus higher rates of co-morbidity (5.28 versus 3.18, p⩽0.01), heart failure (9 versus 2%, p=0.02), and stroke (6 versus 2%, p=0.048) compared with controls. From a nationwide register of patients with type 1 diabetes mellitus, the coexistence of CHD and type 1 diabetes mellitus was associated with an earlier onset, a higher frequency of microvascular complications, co-morbidity, and mortality.

Different CHD chromatin remodelers are required for expression of distinct gene sets and specific stages during development of Dictyostelium discoideum

PubMed Central

Platt, James L.; Rogers, Benjamin J.; Rogers, Kelley C.; Harwood, Adrian J.; Kimmel, Alan R.

2013-01-01

Control of chromatin structure is crucial for multicellular development and regulation of cell differentiation. The CHD (chromodomain-helicase-DNA binding) protein family is one of the major ATP-dependent, chromatin remodeling factors that regulate nucleosome positioning and access of transcription factors and RNA polymerase to the eukaryotic genome. There are three mammalian CHD subfamilies and their impaired functions are associated with several human diseases. Here, we identify three CHD orthologs (ChdA, ChdB and ChdC) in Dictyostelium discoideum. These CHDs are expressed throughout development, but with unique patterns. Null mutants lacking each CHD have distinct phenotypes that reflect their expression patterns and suggest functional specificity. Accordingly, using genome-wide (RNA-seq) transcriptome profiling for each null strain, we show that the different CHDs regulate distinct gene sets during both growth and development. ChdC is an apparent ortholog of the mammalian Class III CHD group that is associated with the human CHARGE syndrome, and GO analyses of aberrant gene expression in chdC nulls suggest defects in both cell-autonomous and non-autonomous signaling, which have been confirmed through analyses of chdC nulls developed in pure populations or with low levels of wild-type cells. This study provides novel insight into the broad function of CHDs in the regulation development and disease, through chromatin-mediated changes in directed gene expression. PMID:24301467

Estimating CHD prevalence by small area: integrating information from health surveys and area mortality.

PubMed

Congdon, Peter

2008-03-01

The risk of coronary heart disease (CHD) is strongly linked both to deprivation and ethnicity and so prevalence will vary considerably between areas. Variations in prevalence are important in assessing health care needs and how far CHD service provision and surgical intervention rates match need. This paper uses a regression model of prevalence rates by age, sex, region and ethnicity from the 1999 and 2003 Health Surveys for England to estimate CHD prevalence for 354 English local authority areas. To allow for the impact of social factors on prevalence, survey information on the deprivation quintile in the respondents' micro-area of residence is also used. Allowance is also made for area CHD mortality rates (obtained from aggregated vital statistics data) which are positively correlated with, and hence a proxy for, CHD prevalence rates. An application involves assessment of surgical intervention rates in relation to prevalence at the level of 28 Strategic Health Authorities.

CHD3 and CHD4 recruitment and chromatin remodeling activity at DNA breaks is promoted by early poly(ADP-ribose)-dependent chromatin relaxation.

PubMed

Smith, Rebecca; Sellou, Hafida; Chapuis, Catherine; Huet, Sébastien; Timinszky, Gyula

2018-05-04

One of the first events to occur upon DNA damage is the local opening of the compact chromatin architecture, facilitating access of repair proteins to DNA lesions. This early relaxation is triggered by poly(ADP-ribosyl)ation by PARP1 in addition to ATP-dependent chromatin remodeling. CHD4 recruits to DNA breaks in a PAR-dependent manner, although it lacks any recognizable PAR-binding domain, and has the ability to relax chromatin structure. However, its role in chromatin relaxation at the site of DNA damage has not been explored. Using a live cell fluorescence three-hybrid assay, we demonstrate that the recruitment of CHD4 to DNA damage, while being poly(ADP-ribosyl)ation-dependent, is not through binding poly(ADP-ribose). Additionally, we show that CHD3 is recruited to DNA breaks in the same manner as CHD4 and that both CHD3 and CHD4 play active roles in chromatin remodeling at DNA breaks. Together, our findings reveal a two-step mechanism for DNA damage induced chromatin relaxation in which PARP1 and the PAR-binding remodeler activities of Alc1/CHD1L induce an initial chromatin relaxation phase that promotes the subsequent recruitment of CHD3 and CHD4 via binding to DNA for further chromatin remodeling at DNA breaks.

The nu sub 2 band CHD3; ground state parameters for CHD3 from combination differences

NASA Technical Reports Server (NTRS)

Jennings, D. E.; Blass, W. E.

1974-01-01

The nu sub 2 fundamental band of CHD3, centered near 2143/cm, was recorded at a resolution of 0.015-0.25/cm. Analysis of ground state combination differences yielded well-determined values for the ground state molecular parameters for CHD3. These parameters were used in the determination of the alpha and beta molecular parameters for nu sub 2.

Congenital Heart Disease (CHD) and Environmental Physical Activity, Kaunas, 1995-2005.

NASA Astrophysics Data System (ADS)

Stoupel, E.; Dulskiene, V.; Kuciene, R.; Abramson, E.; Israelevich, P.; Sulkes, J.

2009-12-01

Recent studies described a number of fetal development sides related to the environmental physical activity. The aim of this study was to check the possible links between congenital heart disease (CHD) born in a non-selected medical network and indices of environmental physical activity. Children born with CHD in Kaunas, Lithuania, in years 1995-2005 were analyzed at the end of the first year of life (including also those died after birth from this condition). Monthly distribution of CHD (total - 371, both gender (178 boys and 193 girls), 41435 births) were compared with parameters of solar (SA), geomagnetic (GMA) and cosmic ray (CRA) activity, as well as the year, at the month of birth, 9 months before and at year of birth and one year before. CRA was represented by neutron activity on the Earth's surface. Heliogeophysical data were obtained from space research centers in the USA, Russia and Finland. There was found a significant correlation between yearly number of births (r = - 0.9, p = 0.00012). Monthly number of CHD was correlated with SA and CRA often highly at the beginning of pregnancy both in monthly and yearly (r = - 0.7, p = 0.025 for SA, r = 0.8, p = 0.005 for CRA) comparison. For boys the correlation was stronger, but also it was significant for girls. GMA has not shown significant effects. It is concluded that the number of yearly and monthly CHD is connected with SA and CRA in pregnancy. Boys show high levels in these correlations. The mechanism of the cosmophysical effects on human development and temporal distribution of CHD deserve special studies.

Distinct cerebellar foliation anomalies in a CHD7 haploinsufficient mouse model of CHARGE syndrome.

PubMed

Whittaker, Danielle E; Kasah, Sahrunizam; Donovan, Alex P A; Ellegood, Jacob; Riegman, Kimberley L H; Volk, Holger A; McGonnell, Imelda; Lerch, Jason P; Basson, M Albert

2017-12-01

Mutations in the gene encoding the ATP dependent chromatin-remodeling factor, CHD7 are the major cause of CHARGE (Coloboma, Heart defects, Atresia of the choanae, Retarded growth and development, Genital-urinary anomalies, and Ear defects) syndrome. Neurodevelopmental defects and a range of neurological signs have been identified in individuals with CHARGE syndrome, including developmental delay, lack of coordination, intellectual disability, and autistic traits. We previously identified cerebellar vermis hypoplasia and abnormal cerebellar foliation in individuals with CHARGE syndrome. Here, we report mild cerebellar hypoplasia and distinct cerebellar foliation anomalies in a Chd7 haploinsufficient mouse model. We describe specific alterations in the precise spatio-temporal sequence of fissure formation during perinatal cerebellar development responsible for these foliation anomalies. The altered cerebellar foliation pattern in Chd7 haploinsufficient mice show some similarities to those reported in mice with altered Engrailed, Fgf8 or Zic1 gene expression and we propose that mutations or polymorphisms in these genes may modify the cerebellar phenotype in CHARGE syndrome. Our findings in a mouse model of CHARGE syndrome indicate that a careful analysis of cerebellar foliation may be warranted in patients with CHARGE syndrome, particularly in patients with cerebellar hypoplasia and developmental delay. © 2017 The Authors. American Journal of Medical Genetics Part C Published by Wiley Periodicals, Inc.

Distinct cerebellar foliation anomalies in a CHD7 haploinsufficient mouse model of CHARGE syndrome

PubMed Central

Whittaker, Danielle E.; Kasah, Sahrunizam; Donovan, Alex P. A.; Ellegood, Jacob; Riegman, Kimberley L. H.; Volk, Holger A.; McGonnell, Imelda; Lerch, Jason P.

2017-01-01

Mutations in the gene encoding the ATP dependent chromatin‐remodeling factor, CHD7 are the major cause of CHARGE (Coloboma, Heart defects, Atresia of the choanae, Retarded growth and development, Genital‐urinary anomalies, and Ear defects) syndrome. Neurodevelopmental defects and a range of neurological signs have been identified in individuals with CHARGE syndrome, including developmental delay, lack of coordination, intellectual disability, and autistic traits. We previously identified cerebellar vermis hypoplasia and abnormal cerebellar foliation in individuals with CHARGE syndrome. Here, we report mild cerebellar hypoplasia and distinct cerebellar foliation anomalies in a Chd7 haploinsufficient mouse model. We describe specific alterations in the precise spatio‐temporal sequence of fissure formation during perinatal cerebellar development responsible for these foliation anomalies. The altered cerebellar foliation pattern in Chd7 haploinsufficient mice show some similarities to those reported in mice with altered Engrailed, Fgf8 or Zic1 gene expression and we propose that mutations or polymorphisms in these genes may modify the cerebellar phenotype in CHARGE syndrome. Our findings in a mouse model of CHARGE syndrome indicate that a careful analysis of cerebellar foliation may be warranted in patients with CHARGE syndrome, particularly in patients with cerebellar hypoplasia and developmental delay. PMID:29168327

Prevalence and risk factors associated with non-attendance in neurodevelopmental follow-up clinic among infants with CHD.

PubMed

Loccoh, Eméfah C; Yu, Sunkyung; Donohue, Janet; Lowery, Ray; Butcher, Jennifer; Pasquali, Sara K; Goldberg, Caren S; Uzark, Karen

2018-04-01

Neurodevelopmental impairment is increasingly recognised as a potentially disabling outcome of CHD and formal evaluation is recommended for high-risk patients. However, data are lacking regarding the proportion of eligible children who actually receive neurodevelopmental evaluation, and barriers to follow-up are unclear. We examined the prevalence and risk factors associated with failure to attend neurodevelopmental follow-up clinic after infant cardiac surgery. Survivors of infant (<1 year) cardiac surgery at our institution (4/2011-3/2014) were included. Socio-demographic and clinical characteristics were evaluated in neurodevelopmental clinic attendees and non-attendees in univariate and multivariable analyses. A total of 552 patients were included; median age at surgery was 2.4 months, 15% were premature, and 80% had moderate-severe CHD. Only 17% returned for neurodevelopmental evaluation, with a median age of 12.4 months. In univariate analysis, non-attendees were older at surgery, had lower surgical complexity, fewer non-cardiac anomalies, shorter hospital stay, and lived farther from the surgical center. Non-attendee families had lower income, and fewer were college graduates or had private insurance. In multivariable analysis, lack of private insurance remained independently associated with non-attendance (adjusted odds ratio 1.85, p=0.01), with a trend towards significance for distance from surgical center (adjusted odds ratio 2.86, p=0.054 for ⩾200 miles). The majority of infants with CHD at high risk for neurodevelopmental dysfunction evaluated in this study are not receiving important neurodevelopmental evaluation. Efforts to remove financial/insurance barriers, increase access to neurodevelopmental clinics, and better delineate other barriers to receipt of neurodevelopmental evaluation are needed.

Pregnancy in complex CHD: focus on patients with Fontan circulation and patients with a systemic right ventricle.

PubMed

Khan, Abigail; Kim, Yuli Y

2015-12-01

The majority of children with congenital heart disease (CHD) now survive into adulthood, and many women with CHD want to pursue pregnancy. Pregnancy represents a complex issue for the CHD care provider. It requires balancing the interests of the woman against the risk to her health during pregnancy, while also factoring in the long-term risks to her health and the risk to her fetus. Our knowledge about this subject has been historically limited by lack of data regarding the outcome of pregnancy in CHD; however, in recent years, more data have begun to emerge. In this review, we will summarise what is known about risk assessment in pregnant CHD patients. We provide a framework for healthcare providers managing pregnancy in this population, with focus on the systemic right ventricle and the Fontan operation.

Relation of family history and reversible risk factors to coronary heart disease prevalence in an Afrikaner community.

PubMed

Rossouw, J E; Thompson, M L; Jooste, P L; Swanepoel, A S; Jordaan, P C

1991-01-01

In a cross-sectional study of an Afrikaner community (n = 2,722 men and n = 3,173 women aged 25-64 years), family history of coronary heart disease (CHD) was associated with an adverse risk factor profile and with prevalent CHD. Men with myocardial infarction (MI) and a family history of CHD had higher total minus high density lipoprotein cholesterol (TC-HDLC) levels than men with MI but no CHD family history. In preliminary multiple regression analyses, family history of CHD appeared to exert its effect partly independently of known risk factors and partly dependently through age, TC minus HDLC, and HDLC. Even though their association with MI was weakened after entering family history into the models, the reversible risk factors (particularly TC minus HDLC, HDLC, and uric acid levels) continued to contribute to CHD. For MI in men, there was an interaction between family history of CHD and TC minus HDLC, to the extent that raised TC minus HDLC levels were adverse only in the presence of a positive CHD family history. The findings suggest coinheritance of high blood cholesterol and increased susceptibility to CHD. If confirmed in prospective studies, the interaction between family history and TC minus HDLC will have implications for cholesterol screening and management.

Retinoic acid-induced CHD5 upregulation and neuronal differentiation of neuroblastoma.

PubMed

Higashi, Mayumi; Kolla, Venkatadri; Iyer, Radhika; Naraparaju, Koumudi; Zhuang, Tiangang; Kolla, Sriharsha; Brodeur, Garrett M

2015-08-07

Chromodomain-helicase DNA binding protein 5 (CHD5) is an important tumor suppressor gene deleted from 1p36.31 in neuroblastomas (NBs). High CHD5 expression is associated with a favorable prognosis, but deletion or low expression is frequent in high-risk tumors. We explored the role of CHD5 expression in the neuronal differentiation of NB cell lines. NB cell lines SH-SY5Y (SY5Y), NGP, SK-N-DZ, IMR5, LAN5, SK-N-FI, NB69 and SH-EP were treated with 1-10 μM 13-cis-retinoic acid (13cRA) for 3-12 days. qRT-PCR and Western blot analyses were performed to measure mRNA and protein expression levels, respectively. Morphological differences were examined by both phase contrast and immunofluorescence studies. Treatment of SY5Y cells with 13cRA caused upregulation of CHD5 expression in a time- and dose-dependent manner (1, 5, or 10 μM for 7 or 12 days) and also induced neuronal differentiation. Furthermore, both NGP and SK-N-DZ cells showed CHD5 upregulation and neuronal differentiation after 13cRA treatment. In contrast, 13cRA treatment of IMR5, LAN5, or SK-N-FI induced neither CHD5 expression nor neuronal differentiation. NB69 cells showed two different morphologies (neuronal and substrate adherent) after 12 days treatment with 10 μM of 13cRA. CHD5 expression was high in the neuronal cells, but low/absent in the flat, substrate adherent cells. Finally, NGF treatment caused upregulation of CHD5 expression and neuronal differentiation in SY5Y cells transfected to express TrkA (SY5Y-TrkA) but not in TrkA-null parental SY5Y cells, and both changes were blocked by a pan-TRK inhibitor. Treatment with 13cRA induces neuronal differentiation only in NB cells that upregulate CHD5. In addition, NGF induced CHD5 upregulation and neuronal differentiation only in TrkA expressing cells. Together, these results suggest that CHD5 is downstream of TrkA, and CHD5 expression may be crucial for neuronal differentiation induced by either 13cRA or TrkA/NGF signaling.

Longer Sleep Duration and Midday Napping Are Associated with a Higher Risk of CHD Incidence in Middle-Aged and Older Chinese: the Dongfeng-Tongji Cohort Study.

PubMed

Yang, Liangle; Yang, Handong; He, Meian; Pan, An; Li, Xiulou; Min, Xinwen; Zhang, Ce; Xu, Chengwei; Zhu, Xiaoyan; Yuan, Jing; Wei, Sheng; Miao, Xiaoping; Hu, Frank B; Wu, Tangchun; Zhang, Xiaomin

2016-03-01

To analyze the independent and combined relations of sleep duration and midday napping with coronary heart diseases (CHD) incidence along with the underlying changes of cardiovascular disease (CVD) risk factors among Chinese adults. We included 19,370 individuals aged 62.8 years at baseline from September 2008 to June 2010, and they were followed until October 2013. Cox proportional hazards models and general linear models were used for multivariate longitudinal analyses. Compared with sleeping 7- < 8 h/night, the hazard ratio (HR) of CHD incidence was 1.33 (95% CI = 1.10 to 1.62) for sleeping ≥ 10 h/night. The association was particularly evident among individuals who were normal weight and without diabetes. Similarly, the HR of incident CHD was 1.25 (95% CI = 1.05 to 1.49) for midday napping > 90 min compared with 1-30 min. When sleep duration and midday napping were combined, individuals having sleep duration ≥ 10 h and midday napping > 90 min were at a greater risk of CHD than those with sleeping 7- < 8 h and napping 1-30 min: the HR was 1.67 (95% CI = 1.04 to 2.66; P for trend = 0.017). In addition, longer sleep duration ≥ 10 h was significantly associated with increases in triglycerides and waist circumference, and a reduction in HDL-cholesterol; while longer midday napping > 90 min was related to increased waist circumference. Both longer sleep duration and midday napping were independently and jointly associated with a higher risk of CHD incidence, and altered lipid profile and waist circumference may partially explain the relationships. © 2016 Associated Professional Sleep Societies, LLC.

CHR729 Is a CHD3 Protein That Controls Seedling Development in Rice.

PubMed

Ma, Xiaoding; Ma, Jian; Zhai, Honghong; Xin, Peiyong; Chu, Jinfang; Qiao, Yongli; Han, Longzhi

2015-01-01

CHD3 is one of the chromatin-remodeling factors that contribute to controlling the expression of genes associated with plant development. Loss-of-function mutants display morphological and growth defects. However, the molecular mechanisms underlying CHD3 regulation of plant development remain unclear. In this study, a rice CHD3 protein, CHR729, was identified. The corresponding mutant line (t483) exhibited late seed germination, low germination rate, dwarfism, low tiller number, root growth inhibition, adaxial albino leaves, and short and narrow leaves. CHR729 encoded a nuclear protein and was expressed in almost all organs. RNA-sequencing analysis showed that several plant hormone-related genes were up- or down-regulated in t483 compared to wild type. In particular, expression of the gibberellin synthetase gibberellin 20 oxidase 4 gene was elevated in the mutant. Endogenous gibberellin assays demonstrated that the content of bioactive GA3 was reduced in t483 compared to wild type. Moreover, the seedling dwarfism, late seed germination, and short root length phenotypes of t483 were partially rescued by treatment with exogenous GA3. These results suggest that the rice CHD3 protein CHR729 plays an important role in many aspects of seedling development and controls this development via the gibberellin pathway.

Longer Sleep Duration and Midday Napping Are Associated with a Higher Risk of CHD Incidence in Middle-Aged and Older Chinese: the Dongfeng-Tongji Cohort Study

PubMed Central

Yang, Liangle; Yang, Handong; He, Meian; Pan, An; Li, Xiulou; Min, Xinwen; Zhang, Ce; Xu, Chengwei; Zhu, Xiaoyan; Yuan, Jing; Wei, Sheng; Miao, Xiaoping; Hu, Frank B.; Wu, Tangchun; Zhang, Xiaomin

2016-01-01

Study Objectives: To analyze the independent and combined relations of sleep duration and midday napping with coronary heart diseases (CHD) incidence along with the underlying changes of cardiovascular disease (CVD) risk factors among Chinese adults. Methods: We included 19,370 individuals aged 62.8 years at baseline from September 2008 to June 2010, and they were followed until October 2013. Cox proportional hazards models and general linear models were used for multivariate longitudinal analyses. Results: Compared with sleeping 7– < 8 h/night, the hazard ratio (HR) of CHD incidence was 1.33 (95% CI = 1.10 to 1.62) for sleeping ≥ 10 h/night. The association was particularly evident among individuals who were normal weight and without diabetes. Similarly, the HR of incident CHD was 1.25 (95% CI = 1.05 to 1.49) for midday napping > 90 min compared with 1–30 min. When sleep duration and midday napping were combined, individuals having sleep duration ≥ 10 h and midday napping > 90 min were at a greater risk of CHD than those with sleeping 7– < 8 h and napping 1–30 min: the HR was 1.67 (95% CI = 1.04 to 2.66; P for trend = 0.017). In addition, longer sleep duration ≥ 10 h was significantly associated with increases in triglycerides and waist circumference, and a reduction in HDL-cholesterol; while longer midday napping > 90 min was related to increased waist circumference. Conclusions: Both longer sleep duration and midday napping were independently and jointly associated with a higher risk of CHD incidence, and altered lipid profile and waist circumference may partially explain the relationships. Citation: Yang L, Yang H, He M, Pan A, Li X, Min X, Zhang C, Xu C, Zhu X, Yuan J, Wei S, Miao X, Hu FB, Wu T, Zhang X. Longer sleep duration and midday napping are associated with a higher risk of CHD incidence in middle-aged and older Chinese: the Dongfeng-Tongji Cohort Study. SLEEP 2016;39(3):645–652. PMID:26564127

CHD1 regulates cell fate determination by activation of differentiation-induced genes

PubMed Central

Baumgart, Simon J.; Najafova, Zeynab; Hossan, Tareq; Xie, Wanhua; Nagarajan, Sankari; Kari, Vijayalakshmi; Ditzel, Nicholas; Kassem, Moustapha

2017-01-01

Abstract The coordinated temporal and spatial activation of gene expression is essential for proper stem cell differentiation. The Chromodomain Helicase DNA-binding protein 1 (CHD1) is a chromatin remodeler closely associated with transcription and nucleosome turnover downstream of the transcriptional start site (TSS). In this study, we show that CHD1 is required for the induction of osteoblast-specific gene expression, extracellular-matrix mineralization and ectopic bone formation in vivo. Genome-wide occupancy analyses revealed increased CHD1 occupancy around the TSS of differentiation-activated genes. Furthermore, we observed that CHD1-dependent genes are mainly induced during osteoblast differentiation and are characterized by higher levels of CHD1 occupancy around the TSS. Interestingly, CHD1 depletion resulted in increased pausing of RNA Polymerase II (RNAPII) and decreased H2A.Z occupancy close to the TSS, but not at enhancer regions. These findings reveal a novel role for CHD1 during osteoblast differentiation and provide further insights into the intricacies of epigenetic regulatory mechanisms controlling cell fate determination. PMID:28475736

Factor VIII, Protein C and Cardiovascular Disease Risk: The REasons for Geographic and Racial Differences in Stroke Study (REGARDS).

PubMed

Zakai, Neil A; Judd, Suzanne E; Kissela, Brett; Howard, George; Safford, Monika M; Cushman, Mary

2018-06-11

 Haemostatic balance represented by low protein C (PC) and elevated factor VIII (FVIII) has been inconsistently associated with stroke and coronary heart disease (CHD) risk.  This article assesses whether an elevated FVIII and a low PC would increase cardiovascular risk more than either individually.  REGARDS recruited 30,239 black and white U.S. participants aged ≥ 45 years between 2003 and 2007. FVIII and PC were measured in a case-cohort sample of 646 stroke, 654 CHD, and a 1,104-person random sample with follow-up for approximately 4.5 years. Hazard ratios (HRs) were estimated using Cox models adjusted for demographic and cardiovascular risk factors.  Elevated FVIII (per standard deviation [SD] increase) was associated with increased risk of both stroke (HR, 1.26; 95% confidence interval [CI], 1.08, 1.46) and CHD (HR, 1.52; 95% CI, 1.29, 1.79), while there was no association of PC per SD decrease. For PC, there was a trend towards increased cardiovascular disease risk in the lowest values (bottom 5%). For stroke, there was no interaction between FVIII and low PC ( p interaction  = 0.55). For CHD, the adjusted HR of FVIII per SD increase was significantly greater with PC in the bottom 5% (HR, 3.59; 95% CI, 1.39, 8.29) than PC in the upper 95% (HR, 1.45; 95% CI, 1.23, 1.71; p interaction  = 0.07).  Higher FVIII was associated with both CHD and stroke risk and the risk potentiated by low PC for CHD. Findings demonstrate that risks for cardiovascular diseases conferred by adverse levels of haemostasis biomarkers may be augmented by levels of other biomarkers. Schattauer GmbH Stuttgart.

The relationship between the effect of pravastatin and risk factors for coronary heart disease in Japanese patients with hypercholesterolemia.

PubMed

Ishikawa, Toshitsugu; Mizuno, Kyoichi; Nakaya, Noriaki; Ohashi, Yasuo; Tajima, Naoko; Kushiro, Toshio; Teramoto, Tamio; Uchiyama, Shinichiro; Nakamura, Haruo

2008-10-01

Several epidemiologic studies in Japan have shown the risk factors for coronary heart disease (CHD) in the general population. The present analysis determined the risk factors for CHD in the MEGA Study, a large primary prevention trial with pravastatin in Japanese with hypercholesterolemia. The relationship between each baseline characteristic and the risk of CHD for the 5-year study period were evaluated using the Cox proportional hazard model. The multivariable predictors of CHD were sex, age, high-density lipoprotein-cholesterol (HDL-C), diabetes mellitus (DM), hypertension (HT), and history of smoking. Serum total and low-density lipoprotein-cholesterol were not independent risk factors for CHD in the current analysis. In addition, the effect of pravastatin was evaluated by subgroups in each risk factor using the interaction in a Cox model. Diet plus pravastatin treatment reduced CHD risk by 14-43% compared with diet alone, regardless of the presence or absence of risk factors. The risk factors for CHD were sex, age, DM, HT, smoking, and low HDL-C in the MEGA Study. The pravastatin treatment was effective for reducing the risk of CHD, regardless of the presence of risk factors.

CHD1 regulates cell fate determination by activation of differentiation-induced genes.

PubMed

Baumgart, Simon J; Najafova, Zeynab; Hossan, Tareq; Xie, Wanhua; Nagarajan, Sankari; Kari, Vijayalakshmi; Ditzel, Nicholas; Kassem, Moustapha; Johnsen, Steven A

2017-07-27

The coordinated temporal and spatial activation of gene expression is essential for proper stem cell differentiation. The Chromodomain Helicase DNA-binding protein 1 (CHD1) is a chromatin remodeler closely associated with transcription and nucleosome turnover downstream of the transcriptional start site (TSS). In this study, we show that CHD1 is required for the induction of osteoblast-specific gene expression, extracellular-matrix mineralization and ectopic bone formation in vivo. Genome-wide occupancy analyses revealed increased CHD1 occupancy around the TSS of differentiation-activated genes. Furthermore, we observed that CHD1-dependent genes are mainly induced during osteoblast differentiation and are characterized by higher levels of CHD1 occupancy around the TSS. Interestingly, CHD1 depletion resulted in increased pausing of RNA Polymerase II (RNAPII) and decreased H2A.Z occupancy close to the TSS, but not at enhancer regions. These findings reveal a novel role for CHD1 during osteoblast differentiation and provide further insights into the intricacies of epigenetic regulatory mechanisms controlling cell fate determination. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

CHD chromatin remodelers and the transcription cycle

PubMed Central

Murawska, Magdalena

2011-01-01

It is well established that ATP-dependent chromatin remodelers modulate DNA access of transcription factors and RNA polymerases by “opening” or “closing” chromatin structure. However, this view is far too simplistic. Recent findings have demonstrated that these enzymes not only set the stage for the transcription machinery to act but also are actively involved at every step of the transcription process. As a consequence, they affect initiation, elongation, termination and RNA processing. In this review we will use the CHD family as a paradigm to illustrate the progress that has been made in revealing these new concepts. PMID:22223048

Midlife moderation-quantified healthy diet and 40-year mortality risk from CHD: the prospective National Heart, Lung, and Blood Institute Twin Study

PubMed Central

Dai, Jun; Krasnow, Ruth E.; Reed, Terry

2018-01-01

It is unknown whether influences of midlife whole diet on the long-term CHD mortality risk are independent of genetic and common environmental factors or familial predisposition. We addressed this question prospectively using data from the National Heart, Lung, and Blood Institute Twin Study. We included 910 male twins who were middle-aged and had usual diet assessed with nutritionist-administered, crosschecked dietary history interview at baseline (1969–1973). Moderation-quantified healthy diet (MQHD), a dietary pattern, was created to evaluate a whole diet. Primary outcome was time-to-CHD death. Hazard ratios (HR) were estimated using frailty survival model. Known CHD risk factors were controlled. During the follow-up of 40 years through 31 December 2009, 113 CHD deaths, 198 total cardiovascular deaths and 610 all-cause deaths occurred. In the entire cohort, the multivariable-adjusted HR for the overall association (equivalent to a general population association) was 0·76 (95 % CI 0·66, 0·88) per 10-unit increment in the MQHD score for CHD, and the multivariable-adjusted HR for a twin with a MQHD score ten units higher than his co-twin brother was 0·79 (95 % CI 0·64, 0·96, P = 0·02) for CHD independent of familial predisposition. Similar results were found for a slightly more food-specified alternative moderation-quantified healthy diet (aMQHD). The between-pair association (reflecting familial influence) was significant for CHD for both MQHD and aMQHD. It is concluded that associations of MQHD and aMQHD with a lower long-term CHD mortality risk are both nutritionally and familially affected, supporting their use for dietary planning to prevent CHD mortality. PMID:27188259

Midlife moderation-quantified healthy diet and 40-year mortality risk from CHD: the prospective National Heart, Lung, and Blood Institute Twin Study.

PubMed

Dai, Jun; Krasnow, Ruth E; Reed, Terry

2016-07-01

It is unknown whether influences of midlife whole diet on the long-term CHD mortality risk are independent of genetic and common environmental factors or familial predisposition. We addressed this question prospectively using data from the National Heart, Lung, and Blood Institute Twin Study. We included 910 male twins who were middle-aged and had usual diet assessed with nutritionist-administered, cross-checked dietary history interview at baseline (1969-1973). Moderation-quantified healthy diet (MQHD), a dietary pattern, was created to evaluate a whole diet. Primary outcome was time-to-CHD death. Hazard ratios (HR) were estimated using frailty survival model. Known CHD risk factors were controlled. During the follow-up of 40 years through 31 December 2009, 113 CHD deaths, 198 total cardiovascular deaths and 610 all-cause deaths occurred. In the entire cohort, the multivariable-adjusted HR for the overall association (equivalent to a general population association) was 0·76 (95 % CI 0·66, 0·88) per 10-unit increment in the MQHD score for CHD, and the multivariable-adjusted HR for a twin with a MQHD score ten units higher than his co-twin brother was 0·79 (95 % CI 0·64, 0·96, P=0·02) for CHD independent of familial predisposition. Similar results were found for a slightly more food-specified alternative moderation-quantified healthy diet (aMQHD). The between-pair association (reflecting familial influence) was significant for CHD for both MQHD and aMQHD. It is concluded that associations of MQHD and aMQHD with a lower long-term CHD mortality risk are both nutritionally and familially affected, supporting their use for dietary planning to prevent CHD mortality.

CHD7 Expression Predicts Survival Outcomes in Patients with Resected Pancreatic Cancer

PubMed Central

Colbert, Lauren E.; Petrova, Aleksandra V.; Fisher, Sarah B.; Pantazides, Brooke G.; Madden, Matthew Z.; Hardy, Claire W.; Warren, Matthew D.; Pan, Yunfeng; Nagaraju, Ganji P.; Liu, Elaine A.; Saka, Burcu; Hall, William A.; Shelton, Joseph W.; Gandhi, Khanjan; Pauly, Rini; Kowalski, Jeanne; Kooby, David A.; El-Rayes, Bassel F.; Staley, Charles A.; Adsay, N. Volkan; Curran, Walter J.; Landry, Jerome C.; Maithel, Shishir K.; Yu, David S.

2014-01-01

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with poor outcomes with current therapies. Gemcitabine is the primary adjuvant drug used clinically, but its effectiveness is limited. In this study, our objective was to utilize a rationale-driven approach to identify novel biomarkers for outcome in patients with early-stage resected PDAC treated with adjuvant gemcitabine. Using a synthetic lethal screen in human PDAC cells, we identified 93 genes including 55 genes linked to DNA damage responses (DDR) that demonstrated gemcitabine sensitization when silenced, including CHD7 which functions in chromatin remodeling. CHD7 depletion sensitized PDAC cells to gemcitabine and delayed their growth in tumor xenografts. Moreover, CHD7 silencing impaired ATR-dependent phosphorylation of CHK1 and increased DNA damage induced by gemcitabine. CHD7 was dysregulated, ranking above the 90th percentile in differential expression in a panel of PDAC clinical specimens, highlighting its potential as a biomarker. Immunohistochemical analysis of specimens from 59 resected PDAC patients receiving adjuvant gemcitabine revealed that low CHD7 expression was associated with increased recurrence-free survival (RFS) and overall survival (OS), in univariate and multivariate analyses. Notably, CHD7 expression was not associated with RFS or OS for patients not receiving gemcitabine. Thus, low CHD7 expression was correlated selectively with gemcitabine sensitivity in this patient population. These results supported our rationale-driven strategy to exploit dysregulated DDR pathways in PDAC to identify genetic determinants of gemcitabine sensitivity, identifying CHD7 as a novel biomarker candidate to evaluate further for individualizing PDAC treatment. PMID:24626090

Reproductive Risk Factors and Coronary Heart Disease in the Women’s Health Initiative Observational Study

PubMed Central

Parikh, Nisha I.; Jeppson, Rebecca P.; Berger, Jeffrey S.; Eaton, Charles B.; Kroenke, Candyce H.; LeBlanc, Erin S.; Lewis, Cora E.; Loucks, Eric B.; Parker, Donna R.; Rillamas-Sun, Eileen; Ryckman, Kelli K; Waring, Molly E.; Schenken, Robert S.; Johnson, Karen C; Edstedt-Bonamy, Anna-Karin; Allison, Matthew A.; Howard, Barbara V.

2016-01-01

Background Reproductive factors provide an early window into a woman’s coronary heart disease (CHD) risk, however their contribution to CHD risk stratification is uncertain. Methods and Results In the Women’s Health Initiative Observational Study, we constructed Cox proportional hazards models for CHD including age, pregnancy status, number of live births, age at menarche, menstrual irregularity, age at first birth, stillbirths, miscarriages, infertility ≥ 1 year, infertility cause, and breastfeeding. We next added each candidate reproductive factor to an established CHD risk factor model. A final model was then constructed with significant reproductive factors added to established CHD risk factors. Improvement in C-statistic, net reclassification index (or NRI with risk categories of <5%, 5–<10%, and ≥10% 10-year risk of CHD) and integrated discriminatory index (IDI) were assessed. Among 72,982 women [n=4607 CHD events, median follow-up=12.0 (IQR=8.3–13.7) years, mean (SD) age 63.2 (7.2) years], an age-adjusted reproductive risk factor model had a C-statistic of 0.675 for CHD. In a model adjusted for established CHD risk factors, younger age at first birth, number of still births, number of miscarriages and lack of breastfeeding were positively associated with CHD. Reproductive factors modestly improved model discrimination (C-statistic increased from 0.726 to 0.730; IDI=0.0013, p-value < 0.0001). Net reclassification for women with events was not improved (NRI events=0.007, p-value=0.18); and for women without events was marginally improved (NRI non-events=0.002, p-value=0.04) Conclusions Key reproductive factors are associated with CHD independently of established CHD risk factors, very modestly improve model discrimination and do not materially improve net reclassification. PMID:27143682

hs-CRP is strongly associated with coronary heart disease (CHD): A data mining approach using decision tree algorithm.

PubMed

Tayefi, Maryam; Tajfard, Mohammad; Saffar, Sara; Hanachi, Parichehr; Amirabadizadeh, Ali Reza; Esmaeily, Habibollah; Taghipour, Ali; Ferns, Gordon A; Moohebati, Mohsen; Ghayour-Mobarhan, Majid

2017-04-01

Coronary heart disease (CHD) is an important public health problem globally. Algorithms incorporating the assessment of clinical biomarkers together with several established traditional risk factors can help clinicians to predict CHD and support clinical decision making with respect to interventions. Decision tree (DT) is a data mining model for extracting hidden knowledge from large databases. We aimed to establish a predictive model for coronary heart disease using a decision tree algorithm. Here we used a dataset of 2346 individuals including 1159 healthy participants and 1187 participant who had undergone coronary angiography (405 participants with negative angiography and 782 participants with positive angiography). We entered 10 variables of a total 12 variables into the DT algorithm (including age, sex, FBG, TG, hs-CRP, TC, HDL, LDL, SBP and DBP). Our model could identify the associated risk factors of CHD with sensitivity, specificity, accuracy of 96%, 87%, 94% and respectively. Serum hs-CRP levels was at top of the tree in our model, following by FBG, gender and age. Our model appears to be an accurate, specific and sensitive model for identifying the presence of CHD, but will require validation in prospective studies. Copyright © 2017 Elsevier B.V. All rights reserved.

Molecular and phenotypic aspects of CHD7 mutation in CHARGE syndrome

PubMed Central

Zentner, Gabriel E.; Layman, Wanda S.; Martin, Donna M.; Scacheri, Peter C.

2010-01-01

CHARGE syndrome (Coloboma of the eye, Heart defects, Atresia of the choanae, Retardation of growth and/or development, Genital and/or urinary abnormalities, and Ear abnormalities (including deafness) is a genetic disorder characterized by a specific and a recognizable pattern of anomalies. De novo mutations in the gene encoding chromodomain helicase DNA binding protein 7 (CHD7) are the major cause of CHARGE syndrome. Here, we review the clinical features of 379 CHARGE patients who tested positive or negative for mutations in CHD7. We found that CHARGE individuals with CHD7 mutations more commonly have ocular colobomas, temporal bone anomalies (semicircular canal hypoplasia/dysplasia), and facial nerve paralysis compared with mutation negative individuals. We also highlight recent genetic and genomic studies that have provided functional insights into CHD7 and the pathogenesis of CHARGE syndrome. PMID:20186815

The prevalence of insulin resistance and other cardiovascular disease risk factors in healthy elderly southwestern Nigerians.

PubMed

Ezenwaka, C E; Akanji, A O; Akanji, B O; Unwin, N C; Adejuwon, C A

1997-02-10

We assessed the prevalence of coronary heart disease (CHD) risk factors including insulin resistance in 500 (205 males, 295 females) healthy elderly (age > 55 years) indigenous, low socioeconomic group Yorubas residents in either an urban slum (n = 240) or a rural town (n = 260) in southwestern Nigeria. Anthropometric indices, blood pressure and fasting plasma levels of glucose, lipids, insulin and insulin resistance were measured. The results indicated that: (i) gross obesity (4.4%), diabetes (1.6%), hyperlipidaemia (0.2%) and cigarette smoking (4.8%) were relatively uncommon in the population, although the prevalence of hypertension (30%) was higher than previously reported from this population; (ii). the subjects had a relatively high prevalence of multiple CHD risk factors (about 20% had > 4 risk factors), an observation considered paradoxical in view of the reportedly low CHD prevalence in this population; (iii) these CHD risk factors (increased body mass and blood pressure (BP), hyperinsulinaemia and insulin resistance) were more prevalent in the women and in urban residents; (iv) hyperinsulinaemia (20%) and insulin resistance (35%) were common in the population, and were associated, on regression analyses, to such other CHD risk factors as BP and body mass, particularly in women, suggesting, as in Caucasians, that insulin resistance could be an important index of CHD risk; and (v) the excess of multiple CHD risk factors in the women, is due at least in part, to their increased tendency to obesity (8%) and reduced physical activity (83%). This study concludes that: (i) despite the high prevalence of multiple risk factors in this population, CHD prevalence is low, indicating the supremacy of such major risk factors as diabetes and hyperlipidaemia (relatively uncommon here) in the development of CHD; and (ii) potentially the greatest CHD risk is in the elderly women especially if relatively overweight, physically inactive and resident in an urban centre. While

Association of temporal trends in risk factors and treatment uptake with coronary heart disease mortality, 1994-2005.

PubMed

Wijeysundera, Harindra C; Machado, Márcio; Farahati, Farah; Wang, Xuesong; Witteman, William; van der Velde, Gabrielle; Tu, Jack V; Lee, Douglas S; Goodman, Shaun G; Petrella, Robert; O'Flaherty, Martin; Krahn, Murray; Capewell, Simon

2010-05-12

Coronary heart disease (CHD) mortality has declined substantially in Canada since 1994. To determine what proportion of this decline was associated with temporal trends in CHD risk factors and advancements in medical treatments. Prospective analytic study of the Ontario, Canada, population aged 25 to 84 years between 1994 and 2005, using an updated version of the validated IMPACT model, which integrates data on population size, CHD mortality, risk factors, and treatment uptake changes. Relative risks and regression coefficients from the published literature quantified the relationship between CHD mortality and (1) evidence-based therapies in 8 distinct CHD subpopulations (acute myocardial infarction [AMI], acute coronary syndromes, secondary prevention post-AMI, chronic coronary artery disease, heart failure in the hospital vs in the community, and primary prevention for hyperlipidemia or hypertension) and (2) population trends in 6 risk factors (smoking, diabetes mellitus, systolic blood pressure, plasma cholesterol level, exercise, and obesity). The number of deaths prevented or delayed in 2005; secondary outcome measures were improvements in medical treatments and trends in risk factors. Between 1994 and 2005, the age-adjusted CHD mortality rate in Ontario decreased by 35% from 191 to 125 deaths per 100,000 inhabitants, translating to an estimated 7585 fewer CHD deaths in 2005. Improvements in medical and surgical treatments were associated with 43% (range, 11% to 124%) of the total mortality decrease, most notably in AMI (8%; range, -5% to 40%), chronic stable coronary artery disease (17%; range, 7% to 35%), and heart failure occurring while in the community (10%; range, 6% to 31%). Trends in risk factors accounted for 3660 fewer CHD deaths prevented or delayed (48% of total; range, 28% to 64%), specifically, reductions in total cholesterol (23%; range, 10% to 33%) and systolic blood pressure (20%; range, 13% to 26%). Increasing diabetes prevalence and body

The chromatin remodeler chd5 is necessary for proper head development during embryogenesis of Danio rerio.

PubMed

Bishop, Brett; Ho, Kwok Ki; Tyler, Kim; Smith, Amanda; Bonilla, Sylvia; Leung, Yuk Fai; Ogas, Joe

2015-08-01

The chromatin remodeler CHD5 plays a critical role in tumor suppression and neurogenesis in mammals. CHD5 contributes to gene expression during neurogenesis, but there is still much to learn regarding how this class of remodelers contributes to differentiation and development. CHD5 remodelers are vertebrate-specific, raising the prospect that CHD5 plays one or more conserved roles in this phylum. Expression of chd5 in adult fish closely mirrors expression of CHD5 in adult mammals. Knockdown of Chd5 during embryogenesis suggests new roles for CHD5 remodelers based on resulting defects in craniofacial development including reduced head and eye size as well as reduced cartilage formation in the head. In addition, knockdown of Chd5 results in altered expression of neural markers in the developing brain and eye as well as a profound defect in differentiation of dopaminergic amacrine cells. Recombinant zebrafish Chd5 protein exhibits nucleosome remodeling activity in vitro, suggesting that it is the loss of this activity that contributes to the observed phenotypes. Our studies indicate that zebrafish is an appropriate model for functional characterization of CHD5 remodelers in vertebrates and highlight the potential of this model for generating novel insights into the role of this vital class of remodelers. Copyright © 2015. Published by Elsevier B.V.

Serum lipoprotein(a) concentration as a cardiovascular risk factor in Kuwaiti type 2 diabetic patients.

PubMed

Abdella, N A; Mojiminiyi, O A; Akanji, A O; Al Mohammadi, H; Moussa, M A

2001-01-01

Serum lipoprotein(a) [Lp(a)], a risk factor for coronary heart disease (CHD) in some nondiabetic populations, is largely under genetic control and varies among ethnic and racial groups. We evaluated serum Lp(a) concentration and its relationship with traditional CHD risk factors (age, sex, smoking, hypertension, dyslipidemia) as well as stage of diabetic nephropathy in 345 type 2 diabetic patients. Lp(a) concentration was skewed with median (2.5th, 97.5th percentiles) of 25.0 (8.1, 75.7) mg/dl. Twenty-three of 55 (41.8%) patients with CHD had increased (>30 mg/dl) Lp(a) compared with 102 of 290 (35.1%) patients without CHD (P=.35). Twelve of 27 (44.4%) female patients with CHD had increased Lp(a) compared to 11 of 28 (39.3%) males (P=.70). Lp(a) was significantly (P<.05) higher in females than males, but the logistic regression analysis showed significant association of Lp(a), LDL-C, and duration of diabetes mellitus (DM) with CHD in male patients only. Although female patients with CHD and macroalbuminuria had significantly (P<.05) higher Lp(a) than normoalbuminuric female patients without CHD, no such association was found in males and no significant association was found between Lp(a) and the degree of albuminuria. Partial correlation analysis controlling for age, sex, and BMI showed significant correlation of Lp(a) with total cholesterol only (P=.03) and no correlation was found with other lipid parameters. Multiple regression analysis did not show significant associations of Lp(a) with standard CHD risk factors, HbA(1c), and plasma creatinine. This study is in agreement with studies in other populations, which showed that Lp(a) may not be an independent risk factor for CHD in patients with DM. However, as Lp(a) could promote atherogenesis via several mechanisms, follow-up studies in our patients will confirm if increased Lp(a) concentration can partly account for the poorer prognosis when diabetic patients develop CHD.

Concerted action of the PHD, chromo and motor domains regulates the human chromatin remodelling ATPase CHD4.

PubMed

Morra, Rosa; Lee, Benjamin M; Shaw, Heather; Tuma, Roman; Mancini, Erika J

2012-07-30

CHD4, the core subunit of the Nucleosome Remodelling and Deacetylase (NuRD) complex, is a chromatin remodelling ATPase that, in addition to a helicase domain, harbors tandem plant homeo finger and chromo domains. By using a panel of domain constructs we dissect their roles and demonstrate that DNA binding, histone binding and ATPase activities are allosterically regulated. Molecular shape reconstruction from small-angle X-ray scattering reveals extensive domain-domain interactions, which provide a structural explanation for the regulation of CHD4 activities by intramolecular domain communication. Our results demonstrate functional interdependency between domains within a chromatin remodeller. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Adult CHD patients under clinical follow-up have a similar quality of life to the general population in Malta.

PubMed

Caruana, Maryanne; Grech, Victor

2017-08-01

The improved survival of patients born with CHD has led to increasing interest in research on quality of life of adult survivors. We report the findings of the first study in Malta carried out to investigate quality of life in adults with CHD under follow-up. A self-reporting questionnaire modelled on the basis of the European Health Interview Survey 2008, including questions on mental health and vitality, was administered to consecutive adult CHD outpatients, aged 16 years and over, between May, 2013 and May, 2014. Foreigners and patients with learning difficulties or cognitive impairment were excluded. Quality-of-life data were compared with that from 371 age- and sex-matched 2008 survey responders - general population cohort. The impact of congenital lesion complexity, hospitalisation in the preceding 12 months, arrhythmias, co-morbidities, and cardiac medication use on quality of life of the CHD cohort was also investigated. There were a total of 120 patient responders (63 males; mean age 30.53, SD 12.77 years). Overall, there were no significant differences in mental health and vitality between patient and general population cohorts, although older patients had better mental health scores compared with age-matched controls. Within the adult CHD cohort, hospitalisation in the preceding 12 months was the only factor associated with a poorer quality of life. Overall, CHD has no negative impact on mental health and vitality in Maltese adult patients under follow-up. Patients needing frequent hospitalisations might warrant closer attention by clinical psychologists.

Genetic Predisposition, Nongenetic Risk Factors, and Coronary Infarct

PubMed Central

Trichopoulou, Antonia; Yiannakouris, Nikos; Bamia, Christina; Benetou, Vassiliki; Trichopoulos, Dimitrios; Ordovas, Jose M.

2015-01-01

Background Using a genetic predisposition score (GPS), additively integrating the associations of 11 polymorphisms with coronary heart disease (CHD), we examined the consequences of the joint presence of a high GPS and nongenetic CHD risk factors. Methods Within the European Prospective Investigation Into Cancer and Nutrition, 202 case patients with medically confirmed incident coronary infarct and 197 control subjects were identified in Greece. Each polymorphism contributed 1 unit (high-risk homozygous), one-half unit (heterozygous), or no units (low-risk homozygous) to the GPS. Odds ratios of coronary infarction for those at high risk because of genetic predisposition and simultaneous presence of an established CHD risk factor were estimated, compared with subjects at low risk, for both GPS and each CHD risk factor. Results The joint presence of a high GPS (≥3.5) and each studied CHD risk factor was in all instances associated with a significantly increased risk of coronary infarction. The odds ratio (95% confidence interval) was 2.62 (1.14–6.02) for ever smoking, 2.88 (1.33–6.24) for hypertension, 3.50 (1.67–7.33) for low high-density lipoprotein (HDL) level, 3.05 (1.53–6.08) for high non-HDL level, and 3.66 (1.75–7.65) for poor adherence to the Mediterranean diet. The odds ratios were always lower and nonsignificant when the GPS was low. There was suggestive evidence for interaction of a high GPS with hypertension (P =.05) and non-HDL cholesterol level (P =.13). Conclusions Genetic predisposition may interact with hypertension and, perhaps, also with the level of non-HDL cholesterol, in the causation of CHD. Genetic predisposition and the other studied exposures seem to have converging effects. Thus, the GPS may identify individuals who could realize disproportional benefits by controlling their hypertension and, possibly, their non-HDL cholesterol level. PMID:18443266

Quantifying the contributions of behavioral and biological risk factors to socioeconomic disparities in coronary heart disease incidence: The MORGEN study

PubMed Central

Kershaw, Kiarri N.; Droomers, Mariël; Robinson, Whitney R.; Carnethon, Mercedes R.; Daviglus, Martha L.; Verschuren, W.M. Monique

2013-01-01

Quantifying the impact of different modifiable behavioral and biological risk factors on socioeconomic disparities in coronary heart disease (CHD) may help inform targeted, population-specific strategies to reduce the unequal distribution of the disease. Previous studies have used analytic approaches that limit our ability to disentangle the relative contributions of these risk factors to CHD disparities. The goal of this study was to assess mediation of the effect of low education on incident CHD by multiple risk factors simultaneously. Analyses are based on 15,067 participants of the Dutch Monitoring Project on Risk Factors for Chronic Diseases aged 20–65 years examined 1994–1997 and followed for events until January 1, 2008. Path analysis was used to quantify and test mediation of the low education-CHD association by behavioral (current cigarette smoking, heavy alcohol use, poor diet, and physical inactivity) and biological (obesity, hypertension, diabetes, and hypercholesterolemia) risk factors. Behavioral and biological risk factors accounted for 56.6% (95% CI: 42.6%–70.8%) of the low education-incident CHD association. Smoking was the strongest mediator, accounting for 27.3% (95% CI: 17.7%–37.4%) of the association, followed by obesity (10.2%; 95% CI: 4.5%–16.1%), physical inactivity (6.3%; 95% CI: 2.7%–10.0%), and hypertension (5.3%; 95% CI: 2.8%–8.0%). In summary, in a Dutch cohort, the majority of the relationship between low education and incident CHD was mediated by traditional behavioral and biological risk factors. Addressing barriers to smoking cessation, blood pressure and weight management, and physical activity may be the most effective approaches to eliminating socioeconomic inequalities in CHD. PMID:24037117

Increased Risk of the APOB rs11279109 Polymorphism for CHD among the Kuwaiti Population

PubMed Central

Ismael, Fatma G.; Al-Serri, Ahmad; Al-Rashdan, Ibrahim

2017-01-01

Background Coronary heart disease (CHD) is among the leading causes of death in Kuwait. This case-control study investigated the genetic association of APOB rs11279109 with CHD in Kuwaitis. Methods The polymorphism was genotyped in 734 Kuwaiti samples by direct amplification. Statistical analysis with genetic modeling was used to assess its association with CHD. Results A statistically significant association (P < 0.001) between the rs11279109 DD genotype (OR: 2.43, CI: 1.34–4.41) with CHD was observed. A codominant genetic model revealed a 2.69 risk increase (CI: 1.57–4.61) for the DD genotype (P = 0.009) independent of age, sex, BMI, smoking, hypercholesterolemia, and ethnicity suggesting APOB rs11279109 as an indicator for the increased risk of CHD. Conclusion The DD genotype may explain molecular mechanisms that underline increased LDL oxidation leading to arthrosclerosis. The findings emphasize the need to identify genetic markers specific to the CHD patient ethnic group in order to improve prognosis and help in early diagnosis and prevention. PMID:29362515

Psychosocial factors in the development of heart disease in women: current research and future directions.

PubMed

Low, Carissa A; Thurston, Rebecca C; Matthews, Karen A

2010-11-01

To review the recent (1995-2009) literature on psychosocial risk and protective factors for coronary heart disease (CHD) among women, including negative emotions, stress, social relationships, and positive psychological factors. Articles for the review were identified using PubMed and bibliographies of relevant articles. Eligible studies included at least 100 women and either focused on a) exclusively female participants or b) both men and women, conducting either gender-stratified analyses or examining interactions with gender. Sixty-seven published reports were identified that examined prospective associations with incident or recurrent CHD. In general, evidence suggests that depression, anxiety disorders, anger suppression, and stress associated with relationships or family responsibilities are associated with elevated CHD risk among women, that supportive social relationships and positive psychological factors may be associated with reduced risk, and that general anxiety, hostility, and work-related stress are less consistently associated with CHD among women relative to men. A growing literature supports the significance of psychosocial factors for the development of CHD among women. Consideration of both traditional psychosocial factors (e.g., depression) and factors that may be especially important for women (e.g., stress associated with responsibilities at home or multiple roles) may improve identification of women at elevated risk as well as the development of effective psychological interventions for women with or at risk for CHD.

Triglyceride-to-HDL cholesterol ratio. Predictive value for CHD severity and new-onset heart failure.

PubMed

Yunke, Z; Guoping, L; Zhenyue, C

2014-02-01

This study aimed to explore the association between the triglyceride-to-high-density lipoprotein cholesterol (TG/HDL-C) ratio and the severity of coronary heart disease (CHD). It also evaluated the clinical role of the TG/HDL-C ratio in predicting in-hospital CHD events and the long-term prognosis of CHD patients. According to the results of coronary angiography examinations, 317 patients were enrolled in the study and classified into a CHD group (n=233) and a control group (n=84). The TG/HDL-C ratio was calculated at baseline. The CHD group was then further classified into cases of single-branch stenosis (n=79), double-branch stenosis (n=73), and multi-branch stenosis (n=81). The Gensini score was calculated for each group to analyze the relationship between the TG/HDL-C ratio and the severity of CHD. The TG/HDL-C ratio in the CHD group was significantly higher than in the normal group (P < 0.001). The TG/HDL-C ratio was positively correlated with the Gensini score. The ratio was significantly higher in patients with new-onset heart failure than in those without heart failure events (P < 0.05). An average 3-year follow-up showed that the serum TG/HDL-C ratios of patients with adverse events were significantly higher than other patients (P <  0.01). The TG/HDL-C ratio is predictive of the severity of CHD. It could also help predict in-hospital new-onset heart failure incidents of CHD patients.

CHD associated with syndromic diagnoses: peri-operative risk factors and early outcomes

PubMed Central

Landis, Benjamin J.; Cooper, David S.; Hinton, Robert B.

2016-01-01

CHD is frequently associated with a genetic syndrome. These syndromes often present specific cardiovascular and non-cardiovascular co-morbidities that confer significant peri-operative risks affecting multiple organ systems. Although surgical outcomes have improved over time, these co-morbidities continue to contribute substantially to poor peri-operative mortality and morbidity outcomes. Peri-operative morbidity may have long-standing ramifications on neurodevelopment and overall health. Recognising the cardiovascular and non-cardiovascular risks associated with specific syndromic diagnoses will facilitate expectant management, early detection of clinical problems, and improved outcomes – for example, the development of syndrome-based protocols for peri-operative evaluation and prophylactic actions may improve outcomes for the more frequently encountered syndromes such as 22q11 deletion syndrome. PMID:26345374

Olive oil intake and CHD in the European Prospective Investigation into Cancer and Nutrition Spanish cohort.

PubMed

Buckland, Genevieve; Travier, Noemie; Barricarte, Aurelio; Ardanaz, Eva; Moreno-Iribas, Conchi; Sánchez, María-José; Molina-Montes, Esther; Chirlaque, María Dolores; Huerta, José María; Navarro, Carmen; Redondo, Maria Luisa; Amiano, Pilar; Dorronsoro, Miren; Larrañaga, Nerea; Gonzalez, Carlos A

2012-12-14

Olive oil is well known for its cardioprotective properties; however, epidemiological data showing that olive oil consumption reduces incident CHD events are still limited. Therefore, we studied the association between olive oil and CHD in the European Prospective Investigation into Cancer and Nutrition (EPIC) Spanish cohort study. The analysis included 40 142 participants (38 % male), free of CHD events at baseline, recruited from five EPIC-Spain centres from 1992 to 1996 and followed up until 2004. Baseline dietary and lifestyle information was collected using interview-administered questionnaires. Cox proportional regression models were used to assess the relationship between validated incident CHD events and olive oil intake (energy-adjusted quartiles and each 10 g/d per 8368 kJ (2000 kcal) increment), while adjusting for potential confounders. During a 10·4-year follow-up, 587 (79 % male) CHD events were recorded. Olive oil intake was negatively associated with CHD risk after excluding dietary mis-reporters (hazard ratio (HR) 0·93; 95 % CI 0·87, 1·00 for each 10 g/d per 8368 kJ (2000 kcal) and HR 0·78; 95 % CI 0·59, 1·03 for upper v. lower quartile). The inverse association between olive oil intake (per 10 g/d per 8368 kJ (2000 kcal)) and CHD was more pronounced in never smokers (11 % reduced CHD risk (P = 0·048)), in never/low alcohol drinkers (25 % reduced CHD risk (P < 0·001)) and in virgin olive oil consumers (14 % reduced CHD risk (P = 0·072)). In conclusion, olive oil consumption was related to a reduced risk of incident CHD events. This emphasises the need to conserve the traditional culinary use of olive oil within the Mediterranean diet to reduce the CHD burden.

Regulation of nucleosome positioning by a CHD Type III chromatin remodeler and its relationship to developmental gene expression in Dictyostelium.

PubMed

Platt, James L; Kent, Nicholas A; Kimmel, Alan R; Harwood, Adrian J

2017-04-01

Nucleosome placement and repositioning can direct transcription of individual genes; however, the precise interactions of these events are complex and largely unresolved at the whole-genome level. The Chromodomain-Helicase-DNA binding (CHD) Type III proteins are a subfamily of SWI2/SNF2 proteins that control nucleosome positioning and are associated with several complex human disorders, including CHARGE syndrome and autism. Type III CHDs are required for multicellular development of animals and Dictyostelium but are absent in plants and yeast. These CHDs can mediate nucleosome translocation in vitro, but their in vivo mechanism is unknown. Here, we use genome-wide analysis of nucleosome positioning and transcription profiling to investigate the in vivo relationship between nucleosome positioning and gene expression during development of wild-type (WT) Dictyostelium and mutant cells lacking ChdC, a Type III CHD protein ortholog. We demonstrate major nucleosome positional changes associated with developmental gene regulation in WT. Loss of chdC caused an increase of intragenic nucleosome spacing and misregulation of gene expression, affecting ∼50% of the genes that are repositioned during WT development. These analyses demonstrate active nucleosome repositioning during Dictyostelium multicellular development, establish an in vivo function of CHD Type III chromatin remodeling proteins in this process, and reveal the detailed relationship between nucleosome positioning and gene regulation, as cells transition between developmental states. © 2017 Platt et al.; Published by Cold Spring Harbor Laboratory Press.

Splicing Factor Prp8 Interacts With NES(AR) and Regulates Androgen Receptor in Prostate Cancer Cells.

PubMed

Wang, Dan; Nguyen, Minh M; Masoodi, Khalid Z; Singh, Prabhpreet; Jing, Yifeng; O'Malley, Katherine; Dar, Javid A; Dhir, Rajiv; Wang, Zhou

2015-12-01

Androgen receptor (AR) plays a pivotal role in the development of primary as well as advanced castration-resistant prostate cancer. Previous work in our lab identified a novel nuclear export signal (NES) (NES(AR)) in AR ligand-binding domain essential for AR nucleocytoplasmic trafficking. By characterizing the localization of green fluorescence protein (GFP)-tagged NES(AR), we designed and executed a yeast mutagenesis screen and isolated 7 yeast mutants that failed to display the NES(AR) export function. One of those mutants was identified as the splicing factor pre-mRNA processing factor 8 (Prp8). We further showed that Prp8 could regulate NES(AR) function using short hairpin RNA knockdown of Prp8 coupled with a rapamycin export assay in mammalian cells and knockdown of Prp8 could induce nuclear accumulation of GFP-tagged AR in PC3 cells. Prp8 expression was decreased in castration-resistant LuCaP35 xenograft tumors as compared with androgen-sensitive xenografts. Laser capture microdissection and quantitative PCR showed Prp8 mRNA levels were decreased in human prostate cancer specimens with high Gleason scores. In prostate cancer cells, coimmunoprecipitation and deletion mutagenesis revealed a physical interaction between Prp8 and AR mainly mediated by NES(AR). Luciferase assay with prostate specific antigen promoter-driven reporter demonstrated that Prp8 regulated AR transcription activity in prostate cancer cells. Interestingly, Prp8 knockdown also increased polyubiquitination of endogenous AR. This may be 1 possible mechanism by which it modulates AR activity. These results show that Prp8 is a novel AR cofactor that interacts with NES(AR) and regulates AR function in prostate cancer cells.

Modifiable risk factor levels of coronary heart disease survivors in a middle-aged workforce.

PubMed

Metcalf, P A; Scragg, R K; Swinburn, B

1999-06-01

Coronary heart disease (CHD) is common in New Zealand. Risk factors for CHD are modifiable or non-modifiable. Modifiable risk factor levels of CHD survivors were compared with those without such a history (non-CHD). Participants were from a cross-sectional survey of 5,656 workers aged > or = 40. CHD survivors were 73 general practitioner (GP)-confirmed participants with a history of hospitalisation for CHD. There were no significant differences in mean blood pressure levels between CHD survivors and non-CHD workers after adjusting for age, gender and ethnicity, but current use of antihypertensive medications was higher in CHD survivors (34.2%) than non-CHD workers (8.1%); p < 0.001. CHD survivors had higher, similarly adjusted, mean serum total cholesterol, triglyceride and lower HDL-cholesterol levels, and their reported carbohydrate, fibre, polyunsaturated fat intakes and ratio of polyunsaturated to saturated fat intakes were higher and total fat, saturated fat and monounsaturated fat intakes were lower. CHD survivors ate fewer servings of red meats per month and more servings of fruit, and cereal, and number of cups of milk. Salt added to meals was lower and margarine use higher in CHD survivors. There were no significant differences in the proportions of those who exercised regularly, or were current cigarette smokers. However, more CHD survivors (57.5%) than non-CHD workers (33.1%) were ex-smokers p < 0.001, who had stopped smoking at a higher mean (se) age (41.1 (1.36) vs 37.6 (0.20) years respectively; p = 0.012). A large proportion of CHD survivors were dyslipidaemic, despite consuming a lower fat, higher fibre and carbohydrate diet. More than 50% of CHD survivors were ex-cigarette smokers, who had given up smoking at a later age than non-CHD workers. These high-risk CHD survivors would benefit from more aggressive measures aimed at correcting their dyslipidaemias.

Genetics Home Reference: CHD2 myoclonic encephalopathy

MedlinePlus

... Møller RS, Linnankivi T, Dimova P, Striano P, Zara F, Marini C, Guerrini R, Depienne C, Baulac S, ... M, Accorsi P, Cappelletti S, Claps DJ, Vigevano F, Zara F, Specchio N. CHD2 mutations are a rare ...

21 CFR 101.82 - Health claims: Soy protein and risk of coronary heart disease (CHD).

Code of Federal Regulations, 2010 CFR

2010-04-01

... risk of CHD. (1) Cardiovascular disease means diseases of the heart and circulatory system. CHD is one of the most common and serious forms of cardiovascular disease and refers to diseases of the heart... heart disease (CHD). 101.82 Section 101.82 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF...

Additive influence of genetic predisposition and conventional risk factors in the incidence of coronary heart disease: a population-based study in Greece

PubMed Central

Yiannakouris, Nikos; Katsoulis, Michail; Trichopoulou, Antonia; Ordovas, Jose M; Trichopoulos, Dimitrios

2014-01-01

Objectives An additive genetic risk score (GRS) for coronary heart disease (CHD) has previously been associated with incident CHD in the population-based Greek European Prospective Investigation into Cancer and nutrition (EPIC) cohort. In this study, we explore GRS-‘environment’ joint actions on CHD for several conventional cardiovascular risk factors (ConvRFs), including smoking, hypertension, type-2 diabetes mellitus (T2DM), body mass index (BMI), physical activity and adherence to the Mediterranean diet. Design A case–control study. Setting The general Greek population of the EPIC study. Participants and outcome measures 477 patients with medically confirmed incident CHD and 1271 controls participated in this study. We estimated the ORs for CHD by dividing participants at higher or lower GRS and, alternatively, at higher or lower ConvRF, and calculated the relative excess risk due to interaction (RERI) as a measure of deviation from additivity. Results The joint presence of higher GRS and higher risk ConvRF was in all instances associated with an increased risk of CHD, compared with the joint presence of lower GRS and lower risk ConvRF. The OR (95% CI) was 1.7 (1.2 to 2.4) for smoking, 2.7 (1.9 to 3.8) for hypertension, 4.1 (2.8 to 6.1) for T2DM, 1.9 (1.4 to 2.5) for lower physical activity, 2.0 (1.3 to 3.2) for high BMI and 1.5 (1.1 to 2.1) for poor adherence to the Mediterranean diet. In all instances, RERI values were fairly small and not statistically significant, suggesting that the GRS and the ConvRFs do not have effects beyond additivity. Conclusions Genetic predisposition to CHD, operationalised through a multilocus GRS, and ConvRFs have essentially additive effects on CHD risk. PMID:24500614

Extension of the millimeter- and submillimeter-wave spectral databases of deuterated methyl cyanides (CH2DCN and CHD2CN)

NASA Astrophysics Data System (ADS)

Nguyen, L.; Walters, A.; Margulès, L.; Motiyenko, R. A.; Guillemin, J.-C.; Kahane, C.; Ceccarelli, C.

2013-05-01

Context. The study of deuterated abundant molecules is recognized as important in understanding molecular complexity in star-forming regions. Aims: We seek to assign the laboratory millimeter and submillimeter wave rotational spectra of the CHD2CN and CH2DCN deuterated isotopologues of methyl cyanide over a wide frequency range in order to provide precise spectral predictions for observations. Methods: Using the solid-state submillimeter-wave spectrometer in Lille, we measured and assigned 723 new lines for CHD2CN and 307 new lines for CH2DCN. The observed rotational transition frequencies were fitted with the ASFIT program to determine the spectroscopic parameters. The prediction of transition frequencies was performed using the SPCAT program. Results: Measurements for both isotoplogues were taken up to 945 GHz and are made available at the CDS. For CHD2CN this is significantly higher than the previous range of measurement up to 40 GHz. For CH2DCN many more lines of high Ka have been measured than previously. Conclusions: Our work confirms the recent analysis for CHD2CN given in the CDMS database and extends the number of determined molecular parameters from 10 to 19. For CH2DCN, 3 new parameters including DK have been determined, and the uncertainty on parameters has been decreased by a factor of approximately 2. For both isotopologues the measured data show shifts in the frequency of some high Ka transitions that are attributed to interactions with a low-lying vibrational state. The availability of more directly measured data and the increase in confidence of the predictions to higher quantum numbers and frequencies will be helpful for the radio astronomical detection of deuterated isotopologues of methyl cyanide in the interstellar medium. Full Tables B.1 and B.2 are only available in electronic form at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/553/A84

Is having a job a protective factor? Employment status and state of medical care as subjectively perceived by adults with CHD in Germany.

PubMed

Helm, Paul C; Sticker, Elisabeth J; Keuchen, Roland; Koerten, Marc-André; Diller, Gerhard-Paul; Tutarel, Oktay; Bauer, Ulrike M M

2017-08-01

Most patients born with CHD nowadays reach adulthood, and thus quality of life, life situation, and state of medical care aspects are gaining importance in the current era. The present study aimed to investigate whether patients' assessment depends on their means of occupation. The findings are expected to be helpful in optimising care and for developing individual treatment plans. The present study was based on an online survey conducted in cooperation with patient organisations. Participants were recruited from the database of the German National Register for Congenital Heart Defects. In total, 1828 individuals (777 males, 1051 females) took part. Participants were asked to rate aspects such their state of health on a six-tier scale (1=worst specification). Response behaviour was measured against the background of occupational details. Training for or pursuing a profession was found to be significantly associated with participants' rating of five of the six examined aspects (p<0.05). Sex seemed to play an important part in four of the six aspects. An optimal treatment plan for adults with CHD should always consider aspects such as sex and employment status. To work out such an optimal and individual treatment plan for each adult CHD patient, an objective tool to measure patients' actual CHD-specific knowledge precluding socially accepted response bias would be very useful.

A novel frameshift mutation of CHD7 in a Japanese patient with CHARGE syndrome.

PubMed

Kohmoto, Tomohiro; Shono, Miki; Naruto, Takuya; Watanabe, Miki; Suga, Ken-Ichi; Nakagawa, Ryuji; Kagami, Shoji; Masuda, Kiyoshi; Imoto, Issei

2016-01-01

CHARGE syndrome is a rare autosomal dominant developmental disorder involving multiple organs. CHD7 is a major causative gene of CHARGE syndrome. We performed targeted-exome sequencing using a next-generation sequencer for molecular diagnosis of a 4-month-old male patient who was clinically suspected to have CHARGE syndrome, and report a novel monoallelic mutation in CHD7, NM_017780.3(CHD7_v001):c.2966del causing a reading frameshift [p.(Cys989Serfs*3)].

A novel frameshift mutation of CHD7 in a Japanese patient with CHARGE syndrome

PubMed Central

Kohmoto, Tomohiro; Shono, Miki; Naruto, Takuya; Watanabe, Miki; Suga, Ken-ichi; Nakagawa, Ryuji; Kagami, Shoji; Masuda, Kiyoshi; Imoto, Issei

2016-01-01

CHARGE syndrome is a rare autosomal dominant developmental disorder involving multiple organs. CHD7 is a major causative gene of CHARGE syndrome. We performed targeted-exome sequencing using a next-generation sequencer for molecular diagnosis of a 4-month-old male patient who was clinically suspected to have CHARGE syndrome, and report a novel monoallelic mutation in CHD7, NM_017780.3(CHD7_v001):c.2966del causing a reading frameshift [p.(Cys989Serfs*3)]. PMID:27081570

Oral-health-related background factors and dental service utilisation among Sudanese children with and without a congenital heart defects.

PubMed

Ali, H M; Mustafa, M; Nasir, E F; Lie, S A; Hasabalrasol, S; Elshazali, O H; Ali, R W; Skeie, M S

2016-11-15

Sudanese children with congenital heart defects (CHDs) were found to have poorer oral health than those without CHDs. The aims of this study were to: describe the patterns of oral-health-related background factors in children with and without CHD and explore any differences, and to evaluate the effects of background factors on caries and gingivitis prevalence and dental services utilisation. In this analytical cross-sectional study, caregivers of children aged 3-12 years with (CHD cases n = 111) and without CHDs (Controls n = 182), underwent face-to-face interviews using a structured questionnaire. The questionnaire items covered several oral health background factors (independent variables) including: child's health status, oral hygiene practices, dental services utilization, mother's level of education, and caregiver's perception and awareness of their child's oral health. The relationship between these factors and occurrence of 'caries' and 'gingivitis' as well as 'child's dental services utilisation' (dependent variables) were explored using multiple adjusted and hierarchal logistic regression analyses. Compared with controls, CHD cases had lower frequencies of brushing and use of fluoridated toothpaste, and their caregivers were less knowledgeable about caries. Among CHD cases, the variables (brushing and fluoridated toothpaste use) had significant impacts on caries prevalence (odd ratio (OR) =5.6, 95% confidence interval (CI): 1.4-22.8 and OR = 0.3, 95% CI: 0.1-0.8 for infrequent compared to frequent ones, respectively) as well as the mother's level of education (OR = 2.6, 95% CI: 1.0-6.4). When differences in background factors were controlled for, the adjusted ORs for caries and gingivitis prevalence in CHD cases compared with controls were 1.8, (95% CI: 1.1-3.2) and 5.3 (95% CI: 2.9-9.4), respectively. Among CHD cases, the child's age (8-12 years: OR = 11.9, 95% CI: 1.9-71.6), and the mother's level of education (lower education: OR�

Communication: Reactivity borrowing in the mode selective chemistry of H + CHD3 → H2 + CD3

NASA Astrophysics Data System (ADS)

Ellerbrock, Roman; Manthe, Uwe

2017-12-01

Quantum state-resolved reaction probabilities for the H + CHD3 → H2 + CD3 reaction are calculated by accurate full-dimensional quantum dynamics calculations using the multi-layer multi-configurational time-dependent Hartree approach and the quantum transition state concept. Reaction probabilities of various ro-vibrational states of the CHD3 reactant are investigated for vanishing total angular momentum. While the reactivity of the different vibrational states of CHD3 mostly follows intuitive patterns, an unusually large reaction probability is found for CHD3 molecules triply excited in the CD3 umbrella-bending vibration. This surprising reactivity can be explained by a Fermi resonance-type mixing of the single CH-stretch excited and the triple CD3 umbrella-bend excited vibrational states of CHD3. These findings show that resonant energy transfer can significantly affect the mode-selective chemistry of CHD3 and result in counter-intuitive reactivity patterns.

Comparative Genomics Reveals Chd1 as a Determinant of Nucleosome Spacing in Vivo.

PubMed

Hughes, Amanda L; Rando, Oliver J

2015-07-14

Packaging of genomic DNA into nucleosomes is nearly universally conserved in eukaryotes, and many features of the nucleosome landscape are quite conserved. Nonetheless, quantitative aspects of nucleosome packaging differ between species because, for example, the average length of linker DNA between nucleosomes can differ significantly even between closely related species. We recently showed that the difference in nucleosome spacing between two Hemiascomycete species-Saccharomyces cerevisiae and Kluyveromyces lactis-is established by trans-acting factors rather than being encoded in cis in the DNA sequence. Here, we generated several S. cerevisiae strains in which endogenous copies of candidate nucleosome spacing factors are deleted and replaced with the orthologous factors from K. lactis. We find no change in nucleosome spacing in such strains in which H1 or Isw1 complexes are swapped. In contrast, the K. lactis gene encoding the ATP-dependent remodeler Chd1 was found to direct longer internucleosomal spacing in S. cerevisiae, establishing that this remodeler is partially responsible for the relatively long internucleosomal spacing observed in K. lactis. By analyzing several chimeric proteins, we find that sequence differences that contribute to the spacing activity of this remodeler are dispersed throughout the coding sequence, but that the strongest spacing effect is linked to the understudied N-terminal end of Chd1. Taken together, our data find a role for sequence evolution of a chromatin remodeler in establishing quantitative aspects of the chromatin landscape in a species-specific manner. Copyright © 2015 Hughes and Rando.

The Mi-2-like Smed-CHD4 gene is required for stem cell differentiation in the planarian Schmidtea mediterranea.

PubMed

Scimone, M Lucila; Meisel, Joshua; Reddien, Peter W

2010-04-01

Freshwater planarians are able to regenerate any missing part of their body and have extensive tissue turnover because of the action of dividing cells called neoblasts. Neoblasts provide an excellent system for in vivo study of adult stem cell biology. We identified the Smed-CHD4 gene, which is predicted to encode a chromatin-remodeling protein similar to CHD4/Mi-2 proteins, as required for planarian regeneration and tissue homeostasis. Following inhibition of Smed-CHD4 with RNA interference (RNAi), neoblast numbers were initially normal, despite an inability of the animals to regenerate. However, the proliferative response of neoblasts to amputation or growth stimulation in Smed-CHD4(RNAi) animals was diminished. Smed-CHD4(RNAi) animals displayed a dramatic reduction in the numbers of certain neoblast progeny cells. Smed-CHD4 was required for the formation of these neoblast progeny cells. Together, these results indicate that Smed-CHD4 is required for neoblasts to produce progeny cells committed to differentiation in order to control tissue turnover and regeneration and suggest a crucial role for CHD4 proteins in stem cell differentiation.

Do pre-employment influences explain the association between psychosocial factors at work and coronary heart disease? The Whitehall II study.

PubMed

Hintsa, Taina; Shipley, Martin J; Gimeno, David; Elovainio, Marko; Chandola, Tarani; Jokela, Markus; Keltikangas-Järvinen, Liisa; Vahtera, Jussi; Marmot, Michael G; Kivimäki, Mika

2010-05-01

To examine whether the association between psychosocial factors at work and incident coronary heart disease (CHD) is explained by pre-employment factors, such as family history of CHD, education, paternal education and social class, number of siblings and height. A prospective cohort study of 6435 British men aged 35-55 years at phase 1 (1985-1988) and free from prevalent CHD at phase 2 (1989-1990) was conducted. Psychosocial factors at work were assessed at phases 1 and 2 and mean scores across the two phases were used to determine long-term exposure. Selected pre-employment factors were assessed at phase 1. Follow-up for coronary death, first non-fatal myocardial infarction or definite angina between phase 2 and 1999 was based on clinical records (250 events, follow-up 8.7 years). The selected pre-employment factors were associated with risk for CHD: HRs (95% CI) were 1.33 (1.03 to 1.73) for family history of CHD, 1.18 (1.05 to 1.32) for each quartile decrease in height and 1.16 (0.99 to 1.35) for each category increase in number of siblings. Psychosocial work factors also predicted CHD: 1.72 (1.08 to 2.74) for low job control and 1.72 (1.10 to 2.67) for low organisational justice. Adjustment for pre-employment factors changed these associations by 4.1% or less. In this occupational cohort of British men, the association between psychosocial factors at work and CHD was largely independent of family history of CHD, education, paternal educational attainment and social class, number of siblings and height.

The single-nucleotide polymorphisms in CHD5 affect the prognosis of patients with hepatocellular carcinoma

PubMed Central

Zhu, Xiao; Kong, Qingming; Xie, Liwei; Chen, Zhihong; Li, Hongmei; Zhu, Zhu; Huang, Yongmei; Lan, Feifei; Luo, Haiqing; Zhan, Jingting; Ding, Hongrong; Lei, Jinli; Xiao, Qin; Fu, Weiming; Fan, Wenguo; Zhang, Jinfang; Luo, Hui

2018-01-01

Previous studies showed that the low expressions of chromodomain-helicase-DNA-binding protein 5 (CHD5) were intensively associated with deteriorative biologic and clinical characteristics as well as outcomes in many tumors. The aim of this study is to determine whether CHD5 single nucleotide polymorphisms (SNPs) contribute to the prognosis of hepatocellular carcima (HCC). The SNPs were selected according to their linkage disequilibrium (LD) in the targeted next-generation sequencing (NGS) and then genotyped with TaqMan probers. We revealed a rare haplotype AG in CHD5 (SNPs: rs12564469-rs9434711) was markedly associated with HCC prognosis. The univariate and multivariate regression analyses revealed the patients with worse overall survival time were those with tumor metastasis and haplotype AG, as well as cirrhosis, poor differentiation and IV-TNM stage. Based on the available public databases, we discovered the significant association between haplotype AG and CHD5 mRNA expressions only existed in Chinese. These data proposed that the potentially genetic haplotype might functionally contribute to HCC prognosis and CHD5 mRNA expressions. PMID:29568352

Radiation Dose-Response Relationship for Risk of Coronary Heart Disease in Survivors of Hodgkin Lymphoma.

PubMed

van Nimwegen, Frederika A; Schaapveld, Michael; Cutter, David J; Janus, Cècile P M; Krol, Augustinus D G; Hauptmann, Michael; Kooijman, Karen; Roesink, Judith; van der Maazen, Richard; Darby, Sarah C; Aleman, Berthe M P; van Leeuwen, Flora E

2016-01-20

Cardiovascular diseases are increasingly recognized as late effects of Hodgkin lymphoma (HL) treatment. The purpose of this study was to identify the risk factors for coronary heart disease (CHD) and to quantify the effects of radiation dose to the heart, chemotherapy, and other cardiovascular risk factors. We conducted a nested case-control study in a cohort of 2,617 5-year HL survivors, treated between 1965 and 1995. Cases were patients diagnosed with CHD as their first cardiovascular event after HL. Detailed treatment information was collected from medical records of 325 cases and 1,204 matched controls. Radiation charts and simulation radiographs were used to estimate in-field heart volume and mean heart dose (MHD). A risk factor questionnaire was sent to patients still alive. The median interval between HL and CHD was 19.0 years. Risk of CHD increased linearly with increasing MHD (excess relative risk [ERR]) per Gray, 7.4%; 95% CI, 3.3% to 14.8%). This results in a 2.5-fold increased risk of CHD for patients receiving a MHD of 20 Gy from mediastinal radiotherapy, compared with patients not treated with mediastinal radiotherapy. ERRs seemed to decrease with each tertile of age at treatment (ERR/Gy(<27.5years), 20.0%; ERR/Gy(27.5-36.4years), 8.8%; ERR/Gy(36.5-50.9years), 4.2%; P(interaction) = .149). Having ≥ 1 classic CHD risk factor (diabetes mellitus, hypertension, or hypercholesterolemia) independently increased CHD risk (rate ratio, 1.5; 95% CI, 1.1 to 2.1). A high level of physical activity was associated with decreased CHD risk (rate ratio, 0.5; 95% CI, 0.3 to 0.8). The linear radiation dose-response relationship identified can be used to predict CHD risk for future HL patients and survivors. Appropriate early management of CHD risk factors and stimulation of physical activity may reduce CHD risk in HL survivors. © 2015 by American Society of Clinical Oncology.

Constraint of gene expression by the chromatin remodelling protein CHD4 facilitates lineage specification

PubMed Central

O'Shaughnessy-Kirwan, Aoife; Signolet, Jason; Costello, Ita; Gharbi, Sarah; Hendrich, Brian

2015-01-01

Chromatin remodelling proteins are essential for different aspects of metazoan biology, yet functional details of why these proteins are important are lacking. Although it is possible to describe the biochemistry of how they remodel chromatin, their chromatin-binding profiles in cell lines, and gene expression changes upon loss of a given protein, in very few cases can this easily translate into an understanding of how the function of that protein actually influences a developmental process. Here, we investigate how the chromatin remodelling protein CHD4 facilitates the first lineage decision in mammalian embryogenesis. Embryos lacking CHD4 can form a morphologically normal early blastocyst, but are unable to successfully complete the first lineage decision and form functional trophectoderm (TE). In the absence of a functional TE, Chd4 mutant blastocysts do not implant and are hence not viable. By measuring transcript levels in single cells from early embryos, we show that CHD4 influences the frequency at which unspecified cells in preimplantation stage embryos express lineage markers prior to the execution of this first lineage decision. In the absence of CHD4, this frequency is increased in 16-cell embryos, and by the blastocyst stage cells fail to properly adopt a TE gene expression programme. We propose that CHD4 allows cells to undertake lineage commitment in vivo by modulating the frequency with which lineage-specification genes are expressed. This provides novel insight into both how lineage decisions are made in mammalian cells, and how a chromatin remodelling protein functions to facilitate lineage commitment. PMID:26116663

Chd7 Collaborates with Sox2 to Regulate Activation of Oligodendrocyte Precursor Cells after Spinal Cord Injury.

PubMed

Doi, Toru; Ogata, Toru; Yamauchi, Junji; Sawada, Yasuhiro; Tanaka, Sakae; Nagao, Motoshi

2017-10-25

Oligodendrocyte precursor cells (OPCs) act as a reservoir of new oligodendrocytes (OLs) in homeostatic and pathological conditions. OPCs are activated in response to injury to generate myelinating OLs, but the underlying mechanisms remain poorly understood. Here, we show that chromodomain helicase DNA binding protein 7 (Chd7) regulates OPC activation after spinal cord injury (SCI). Chd7 is expressed in OPCs in the adult spinal cord and its expression is upregulated with a concomitant increase in Sox2 expression after SCI. OPC-specific ablation of Chd7 in injured mice leads to reduced OPC proliferation, the loss of OPC identity, and impaired OPC differentiation. Ablation of Chd7 or Sox2 in cultured OPCs shows similar phenotypes to those observed in Chd7 knock-out mice. Chd7 and Sox2 form a complex in OPCs and bind to the promoters or enhancers of the regulator of cell cycle ( Rgcc ) and protein kinase C θ ( PKC θ) genes, thereby inducing their expression. The expression of Rgcc and PKCθ is reduced in the OPCs of the injured Chd7 knock-out mice. In cultured OPCs, overexpression and knock-down of Rgcc or PKCθ promote and suppress OPC proliferation, respectively. Furthermore, overexpression of both Rgcc and PKCθ rescues the Chd7 deletion phenotypes. Chd7 is thus a key regulator of OPC activation, in which it cooperates with Sox2 and acts via direct induction of Rgcc and PKCθ expression. SIGNIFICANCE STATEMENT Spinal cord injury (SCI) leads to oligodendrocyte (OL) loss and demyelination, along with neuronal death, resulting in impairment of motor or sensory functions. Oligodendrocyte precursor cells (OPCs) activated in response to injury are potential sources of OL replacement and are thought to contribute to remyelination and functional recovery after SCI. However, the molecular mechanisms underlying OPC activation, especially its epigenetic regulation, remain largely unclear. We demonstrate here that the chromatin remodeler chromodomain helicase DNA binding

Determinants of quality of life in adults with CHD: an Australian cohort.

PubMed

Eaton, Sarah L; Wang, QiFeng; Menahem, Samuel

2017-10-01

Following improved survival rates in children with CHD, their quality of life and its determinants have become increasingly important. As part of a multicentre study entitled "Assessment of Patterns of Patient-Reported Outcomes in Adults with Congenital Heart Disease - International Study", this article reviews the relationships among quality of life, anxiety and depression, sense of coherence, and severity of disease in an Australian cohort of adults with CHD. Methods and results Adults with CHD were recruited from a single, community-based cardiology practice. All patients completed a self-reported questionnaire. A total of 135 patients, 71 males and 64 females, were recruited with a mean age of 26 years. The median quality of life in this cohort was 90; one-fifth of the patients experienced symptoms of anxiety. There was a significant negative correlation between quality of life and symptoms of anxiety and depression and a positive correlation between quality of life and sense of coherence. The quality of life of this cohort was generally excellent; however, one-fifth of them experienced symptoms of anxiety. Those with less anxiety and depression symptoms appeared to have a better quality of life, as did those who reported a higher sense of coherence. Interestingly, there was no significant relationship between complexity of CHD and quality of life.

The Mi-2-like Smed-CHD4 gene is required for stem cell differentiation in the planarian Schmidtea mediterranea

PubMed Central

Scimone, M. Lucila; Meisel, Joshua; Reddien, Peter W.

2010-01-01

Freshwater planarians are able to regenerate any missing part of their body and have extensive tissue turnover because of the action of dividing cells called neoblasts. Neoblasts provide an excellent system for in vivo study of adult stem cell biology. We identified the Smed-CHD4 gene, which is predicted to encode a chromatin-remodeling protein similar to CHD4/Mi-2 proteins, as required for planarian regeneration and tissue homeostasis. Following inhibition of Smed-CHD4 with RNA interference (RNAi), neoblast numbers were initially normal, despite an inability of the animals to regenerate. However, the proliferative response of neoblasts to amputation or growth stimulation in Smed-CHD4(RNAi) animals was diminished. Smed-CHD4(RNAi) animals displayed a dramatic reduction in the numbers of certain neoblast progeny cells. Smed-CHD4 was required for the formation of these neoblast progeny cells. Together, these results indicate that Smed-CHD4 is required for neoblasts to produce progeny cells committed to differentiation in order to control tissue turnover and regeneration and suggest a crucial role for CHD4 proteins in stem cell differentiation. PMID:20223763

Five-factor model personality traits as predictors of incident coronary heart disease in the community: a 10.5-year cohort study based on the Baltimore epidemiologic catchment area follow-up study.

PubMed

Lee, Hochang Benjamin; Offidani, Emanuela; Ziegelstein, Roy C; Bienvenu, Oscar Joseph; Samuels, Jack; Eaton, William W; Nestadt, Gerald

2014-01-01

Certain personality and behavioral traits (e.g., type A and type D) have been reported to be associated with development and progression of coronary heart disease (CHD), but few have examined the relationship using a comprehensive assessment of personality along with a structured assessment of psychiatric disorders. Based on participants (age: 47.3 ± 12.8; female: 62.6%) of the Baltimore Epidemiologic Catchment Area follow-up study, we examined the relationship between the 5 major domains of personality traits (neuroticism, extraversion, openness, agreeableness, and conscientiousness) and incident CHD between Wave III (1993-1996) and Wave IV (2004-2005). Incident CHD developed in 65 participants during the follow-up. Those with incident CHD had lower on openness (44.06 ± 9.29 vs. 47.18 ± 8.80; p = 0.007) and extraversion (45.98 ± 9.25 vs. 49.12 ± 8.92; p = 0.007) scores than those without. Logistic regression models revealed an inverse association (OR = 0.73; 95% CI = 0.54-0.98) between openness factor z-scores and incident CHD after adjusting for putative confounding factors, including DSM III-R Major Depressive Disorder. High openness appears to be an independent protective factor for incident CHD in the community. Future studies should examine behavioral and pathophysiologic mechanisms underlying this association. Copyright © 2014 Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.

Mature middle and inner ears express Chd7 and exhibit distinctive pathologies in a mouse model of CHARGE syndrome

PubMed Central

Hurd, Elizabeth A.; Adams, Meredith E.; Layman, Wanda S.; Swiderski, Donald L.; Beyer, Lisa A.; Halsey, Karin E.; Benson, Jennifer M.; Gong, Tzy-Wen; Dolan, David F.; Raphael, Yehoash; Martin, Donna M.

2011-01-01

Heterozygous mutations in the gene encoding chromodomain-DNA-binding-protein 7 (CHD7) cause CHARGE syndrome, a multiple anomaly condition which includes vestibular dysfunction and hearing loss. Mice with heterozygous Chd7 mutations exhibit semicircular canal dysgenesis and abnormal inner ear neurogenesis, and are an excellent model of CHARGE syndrome. Here we characterized Chd7 expression in mature middle and inner ears, analyzed morphological features of mutant ears and tested whether Chd7 mutant mice have altered responses to noise exposure and correlated those responses to inner and middle ear structure. We found that Chd7 is highly expressed in mature inner and outer hair cells, spiral ganglion neurons, vestibular sensory epithelia and middle ear ossicles. There were no obvious defects in individual hair cell morphology by Prestin immunostaining or scanning electron microscopy, and cochlear innervation appeared normal in Chd7Gt/+ mice. Hearing thresholds by auditory brainstem response (ABR) testing were elevated at 4 and 16 kHz in Chd7Gt/+ mice, and there were reduced distortion product otoacoustic emissions (DPOAE). Exposure of Chd7Gt/+ mice to broadband noise resulted in variable degrees of hair cell loss which inversely correlated with severity of stapedial defects. The degrees of hair cell loss and threshold shifts after noise exposure were more severe in wild type mice than in mutants. Together, these data indicate that Chd7Gt/+ mice have combined conductive and sensorineural hearing loss, correlating with changes in both middle and inner ears. PMID:21875659

Reversible Congenital Hypogonadotropic Hypogonadism in Patients with CHD7, FGFR1 or GNRHR Mutations

PubMed Central

Laitinen, Eeva-Maria; Tommiska, Johanna; Sane, Timo; Vaaralahti, Kirsi; Toppari, Jorma; Raivio, Taneli

2012-01-01

Background Congenital hypogonadotropic hypogonadism (HH) is a rare cause for delayed or absent puberty. These patients may recover from HH spontaneously in adulthood. To date, it is not possible to predict who will undergo HH reversal later in life. Herein we investigated whether Finnish patients with reversal of congenital hypogonadotropic hypogonadism (HH) have common phenotypic or genotypic features. Methods and Findings Thirty-two male HH patients with anosmia/hyposmia (Kallmann Syndrome, KS; n = 26) or normal sense of smell (nHH; n = 6) were enrolled (age range, 18–61 yrs). The patients were clinically examined, and reversal of HH was assessed after treatment withdrawal. KAL1, FGFR1, FGF8, PROK2, PROKR2, CHD7, WDR11, GNRHR, GNRH1, KISS1R, KISS1, TAC3, TACR3, and LHβ were screened for mutations. Six HH patients (2 KS, 4 nHH) were verified to have reversal of HH. In the majority of cases, reversal occurred early in adulthood (median age, 23 yrs; range, 21–39 yrs). All had spontaneous testicular growth while on testosterone replacement therapy (TRT). One nHH subject was restarted on TRT due to a decline in serum T. Two reversal variants had a same GNRHR mutation (R262Q), which was accompanied by another GNRHR mutation (R139H or del309F). In addition, both of the KS patients had a mutation in CHD7 (p.Q51X) or FGFR1 (c.91+2T>A). Conclusions Considerable proportion of patients with HH (8% of KS probands) may recover in early adulthood. Spontaneous testicular enlargement during TRT was highly suggestive for reversal of HH. Those with the GNRHR mutation R262Q accompanied by another GNRHR mutation may be prone to reversal, although even patients with a truncating mutation in CHD7 or a splice-site mutation in FGFR1 can recover. We recommend that all adolescents and young adults with congenital HH should be informed on the possibility of reversal. PMID:22724017

Mature middle and inner ears express Chd7 and exhibit distinctive pathologies in a mouse model of CHARGE syndrome.

PubMed

Hurd, Elizabeth A; Adams, Meredith E; Layman, Wanda S; Swiderski, Donald L; Beyer, Lisa A; Halsey, Karin E; Benson, Jennifer M; Gong, Tzy-Wen; Dolan, David F; Raphael, Yehoash; Martin, Donna M

2011-12-01

Heterozygous mutations in the gene encoding chromodomain-DNA-binding-protein 7 (CHD7) cause CHARGE syndrome, a multiple anomaly condition which includes vestibular dysfunction and hearing loss. Mice with heterozygous Chd7 mutations exhibit semicircular canal dysgenesis and abnormal inner ear neurogenesis, and are an excellent model of CHARGE syndrome. Here we characterized Chd7 expression in mature middle and inner ears, analyzed morphological features of mutant ears and tested whether Chd7 mutant mice have altered responses to noise exposure and correlated those responses to inner and middle ear structure. We found that Chd7 is highly expressed in mature inner and outer hair cells, spiral ganglion neurons, vestibular sensory epithelia and middle ear ossicles. There were no obvious defects in individual hair cell morphology by prestin immunostaining or scanning electron microscopy, and cochlear innervation appeared normal in Chd7(Gt)(/+) mice. Hearing thresholds by auditory brainstem response (ABR) testing were elevated at 4 and 16 kHz in Chd7(Gt)(/+) mice, and there were reduced distortion product otoacoustic emissions (DPOAE). Exposure of Chd7(Gt)(/+) mice to broadband noise resulted in variable degrees of hair cell loss which inversely correlated with severity of stapedial defects. The degrees of hair cell loss and threshold shifts after noise exposure were more severe in wild type mice than in mutants. Together, these data indicate that Chd7(Gt)(/+) mice have combined conductive and sensorineural hearing loss, correlating with changes in both middle and inner ears. Copyright © 2011 Elsevier B.V. All rights reserved.

Dietary patterns within educational groups and their association with CHD and stroke in the European Prospective Investigation into Cancer and Nutrition-Netherlands cohort.

PubMed

Biesbroek, Sander; Kneepkens, Mirjam C; van den Berg, Saskia W; Fransen, Heidi P; Beulens, Joline W; Peeters, Petra H M; Boer, Jolanda M A

2018-04-01

Higher-educated people often have healthier diets, but it is unclear whether specific dietary patterns exist within educational groups. We therefore aimed to derive dietary patterns in the total population and by educational level and to investigate whether these patterns differed in their composition and associations with the incidence of fatal and non-fatal CHD and stroke. Patterns were derived using principal components analysis in 36 418 participants of the European Prospective Investigation into Cancer and Nutrition-Netherlands cohort. Self-reported educational level was used to create three educational groups. Dietary intake was estimated using a validated semi-quantitative FFQ. Hazard ratios were estimated using Cox Proportional Hazard analysis after a mean follow-up of 16 years. In the three educational groups, similar 'Western', 'prudent' and 'traditional' patterns were derived as in the total population. However, with higher educational level a lower population-derived score for the 'Western' and 'traditional' patterns and a higher score on the 'prudent' pattern were observed. These differences in distribution of the factor scores illustrate the association between education and food consumption. After adjustments, no differences in associations between population-derived dietary patterns and the incidence of CHD or stroke were found between the educational groups (P interaction between 0·21 and 0·98). In conclusion, although in general population and educational groups-derived dietary patterns did not differ, small differences between educational groups existed in the consumption of food groups in participants considered adherent to the population-derived patterns (Q4). This did not result in different associations with incident CHD or stroke between educational groups.

The Role of CHD7 Mutations in Patients with Idiopathic Hypogonadotropic Hypogonadism and Kallmann Syndrome

PubMed Central

Kim, Hyung-Goo; Layman, Lawrence C.

2013-01-01

Mutations in the chromodomain helicase DNA binding protein-7 (CHD7) cause CHARGE syndrome, which includes eye coloboma, heart malformations, atresia of the choanae, retardation of growth/development, genital anomalies, and ear abnormalities. CHARGE syndrome is usually sporadic, but is also autosomal dominant. CHD7 encodes a large protein that participates in chromatin remodeling and transcription. Findings from studies of mouse models employing ENU-mutagenesis or gene-trap methods recapitulate human CHARGE syndrome. CHARGE patients may manifest anosmia and/or hypogonadism, features that overlap with idiopathic hypogonadotropic hypogonadism (IHH) and Kallmann syndrome (KS). Similarly, IHH/KS patients may also display partial CHARGE features. Therefore, it has been hypothesized that IHH/KS represents a milder allelic variant of CHARGE syndrome, which has been supported by the identification of heterozygous CHD7 mutations in both normosmic IHH and KS. Developmental expression within the hypothalamus and the presence of human mutations indicate that CHD7 has an important role in puberty and reproduction. PMID:21856375

Development and validation of the coronary heart disease scale under the system of quality of life instruments for chronic diseases QLICD-CHD: combinations of classical test theory and Generalizability Theory.

PubMed

Wan, Chonghua; Li, Hezhan; Fan, Xuejin; Yang, Ruixue; Pan, Jiahua; Chen, Wenru; Zhao, Rong

2014-06-04

Quality of life (QOL) for patients with coronary heart disease (CHD) is now concerned worldwide with the specific instruments being seldom and no one developed by the modular approach. This paper is aimed to develop the CHD scale of the system of Quality of Life Instruments for Chronic Diseases (QLICD-CHD) by the modular approach and validate it by both classical test theory and Generalizability Theory. The QLICD-CHD was developed based on programmed decision procedures with multiple nominal and focus group discussions, in-depth interview, pre-testing and quantitative statistical procedures. 146 inpatients with CHD were used to provide the data measuring QOL three times before and after treatments. The psychometric properties of the scale were evaluated with respect to validity, reliability and responsiveness employing correlation analysis, factor analyses, multi-trait scaling analysis, t-tests and also G studies and D studies of Genralizability Theory analysis. Multi-trait scaling analysis, correlation and factor analyses confirmed good construct validity and criterion-related validity when using SF-36 as a criterion. The internal consistency α and test-retest reliability coefficients (Pearson r and Intra-class correlations ICC) for the overall instrument and all domains were higher than 0.70 and 0.80 respectively; The overall and all domains except for social domain had statistically significant changes after treatments with moderate effect size SRM (standardized response mea) ranging from 0.32 to 0.67. G-coefficients and index of dependability (Ф coefficients) confirmed the reliability of the scale further with more exact variance components. The QLICD-CHD has good validity, reliability, and moderate responsiveness and some highlights, and can be used as the quality of life instrument for patients with CHD. However, in order to obtain better reliability, the numbers of items for social domain should be increased or the items' quality, not quantity, should be

Crystal Structure of the Chromodomain Helicase DNA-binding Protein 1 (Chd1) DNA-binding Domain in Complex with DNA*

PubMed Central

Sharma, Amit; Jenkins, Katherine R.; Héroux, Annie; Bowman, Gregory D.

2011-01-01

Chromatin remodelers are ATP-dependent machines that dynamically alter the chromatin packaging of eukaryotic genomes by assembling, sliding, and displacing nucleosomes. The Chd1 chromatin remodeler possesses a C-terminal DNA-binding domain that is required for efficient nucleosome sliding and believed to be essential for sensing the length of DNA flanking the nucleosome core. The structure of the Chd1 DNA-binding domain was recently shown to consist of a SANT and SLIDE domain, analogous to the DNA-binding domain of the ISWI family, yet the details of how Chd1 recognized DNA were not known. Here we present the crystal structure of the Saccharomyces cerevisiae Chd1 DNA-binding domain in complex with a DNA duplex. The bound DNA duplex is straight, consistent with the preference exhibited by the Chd1 DNA-binding domain for extranucleosomal DNA. Comparison of this structure with the recently solved ISW1a DNA-binding domain bound to DNA reveals that DNA lays across each protein at a distinct angle, yet contacts similar surfaces on the SANT and SLIDE domains. In contrast to the minor groove binding seen for Isw1 and predicted for Chd1, the SLIDE domain of the Chd1 DNA-binding domain contacts the DNA major groove. The majority of direct contacts with the phosphate backbone occur only on one DNA strand, suggesting that Chd1 may not strongly discriminate between major and minor grooves. PMID:22033927

Fish consumption and CHD mortality: an updated meta-analysis of seventeen cohort studies.

PubMed

Zheng, Jusheng; Huang, Tao; Yu, Yinghua; Hu, Xiaojie; Yang, Bin; Li, Duo

2012-04-01

Results of studies on fish consumption and CHD mortality are inconsistent. The present updated meta-analysis was conducted to investigate the up-to-date pooling effects. A random-effects model was used to pool the risk estimates. Generalized least-squares regression and restricted cubic splines were used to assess the possible dose-response relationship. Subgroup analyses were conducted to examine the sources of heterogeneity. PubMed and ISI Web of Science databases up to September 2010 were searched and secondary referencing qualified for inclusion in the study. Seventeen cohorts with 315,812 participants and average follow-up period of 15·9 years were identified. Compared with the lowest fish intake (<1 serving/month or 1-3 servings/month), the pooled relative risk (RR) of fish intake on CHD mortality was 0·84 (95% CI 0·75, 0·95) for low fish intake (1 serving/week), 0·79 (95% CI 0·67, 0·92) for moderate fish intake (2-4 servings/week) and 0·83 (95% CI 0·68, 1·01) for high fish intake (>5 servings/week). The dose-response analysis indicated that every 15 g/d increment of fish intake decreased the risk of CHD mortality by 6% (RR = 0·94; 95% CI 0·90, 0·98). The method of dietary assessment, gender and energy adjustment affected the results remarkably. Our results indicate that either low (1 serving/week) or moderate fish consumption (2-4 servings/week) has a significantly beneficial effect on the prevention of CHD mortality. High fish consumption (>5 servings/week) possesses only a marginally protective effect on CHD mortality, possibly due to the limited studies included in this group.

Cardiac MRI in patients with complex CHD following primary or secondary implantation of MRI-conditional pacemaker system.

PubMed

Al-Wakeel, Nadya; O h-Ici, Darach; Schmitt, Katharina R; Messroghli, Daniel R; Riesenkampff, Eugénie; Berger, Felix; Kuehne, Titus; Peters, Bjoern

2016-02-01

In patients with CHD, cardiac MRI is often indicated for functional and anatomical assessment. With the recent introduction of MRI-conditional pacemaker systems, cardiac MRI has become accessible for patients with pacemakers. The present clinical study aims to evaluate safety, susceptibility artefacts, and image reading of cardiac MRI in patients with CHD and MRI-conditional pacemaker systems. Material and methods CHD patients with MRI-conditional pacemaker systems and a clinical need for cardiac MRI were examined with a 1.5-T MRI system. Lead function was tested before and after MRI. Artefacts and image readings were evaluated using a four-point grading scale. A total of nine patients with CHD (mean age 34.0 years, range 19.5-53.6 years) received a total of 11 cardiac MRI examinations. Owing to clinical indications, seven patients had previously been converted from conventional to MRI-conditional pacemaker systems. All MRI examinations were completed without adverse effects. Device testing immediately after MRI and at follow-up showed no alteration of pacemaker device and lead function. Clinical questions could be addressed and answered in all patients. Cardiac MRI can be performed safely with high certainty of diagnosis in CHD patients with MRI-conditional pacemaker systems. In case of clinically indicated lead and box changing, CHD patients with non-MRI-conditional pacemaker systems should be considered for complete conversion to MRI-conditional systems.

De Novo Mutations in CHD4, an ATP-Dependent Chromatin Remodeler Gene, Cause an Intellectual Disability Syndrome with Distinctive Dysmorphisms.

PubMed

Weiss, Karin; Terhal, Paulien A; Cohen, Lior; Bruccoleri, Michael; Irving, Melita; Martinez, Ariel F; Rosenfeld, Jill A; Machol, Keren; Yang, Yaping; Liu, Pengfei; Walkiewicz, Magdalena; Beuten, Joke; Gomez-Ospina, Natalia; Haude, Katrina; Fong, Chin-To; Enns, Gregory M; Bernstein, Jonathan A; Fan, Judith; Gotway, Garrett; Ghorbani, Mohammad; van Gassen, Koen; Monroe, Glen R; van Haaften, Gijs; Basel-Vanagaite, Lina; Yang, Xiang-Jiao; Campeau, Philippe M; Muenke, Maximilian

2016-10-06

Chromodomain helicase DNA-binding protein 4 (CHD4) is an ATP-dependent chromatin remodeler involved in epigenetic regulation of gene transcription, DNA repair, and cell cycle progression. Also known as Mi2β, CHD4 is an integral subunit of a well-characterized histone deacetylase complex. Here we report five individuals with de novo missense substitutions in CHD4 identified through whole-exome sequencing and web-based gene matching. These individuals have overlapping phenotypes including developmental delay, intellectual disability, hearing loss, macrocephaly, distinct facial dysmorphisms, palatal abnormalities, ventriculomegaly, and hypogonadism as well as additional findings such as bone fusions. The variants, c.3380G>A (p.Arg1127Gln), c.3443G>T (p.Trp1148Leu), c.3518G>T (p.Arg1173Leu), and c.3008G>A, (p.Gly1003Asp) (GenBank: NM_001273.3), affect evolutionarily highly conserved residues and are predicted to be deleterious. Previous studies in yeast showed the equivalent Arg1127 and Trp1148 residues to be crucial for SNF2 function. Furthermore, mutations in the same positions were reported in malignant tumors, and a de novo missense substitution in an equivalent arginine residue in the C-terminal helicase domain of SMARCA4 is associated with Coffin Siris syndrome. Cell-based studies of the p.Arg1127Gln and p.Arg1173Leu mutants demonstrate normal localization to the nucleus and HDAC1 interaction. Based on these findings, the mutations potentially alter the complex activity but not its formation. This report provides evidence for the role of CHD4 in human development and expands an increasingly recognized group of Mendelian disorders involving chromatin remodeling and modification. Published by Elsevier Inc.

Infective endocarditis: call for education of adults with CHD: review of the evidence.

PubMed

Hays, Laura H

2016-03-01

Advanced surgical repair procedures have resulted in the increased survival rate to adulthood of patients with CHD. The resulting new chronic conditions population is greater than one million in the United States of America and >1.2 million in Europe. This review describes the risks and effects of infective endocarditis - a systemic infectious process with high morbidity and mortality - on this population and examines the evidence to determine whether greater patient education on recognition of symptoms and preventative measures is warranted. The literature search included the terms "infective endocarditis" and "adult congenital heart disease". Search refinement, the addition of articles cited by included articles, as well as addition of supporting articles, resulted in utilisation of 24 articles. Infective endocarditis, defined by the modified Duke Criteria, occurs at a significantly higher rate in the CHD population due to congenitally or surgically altered cardiac anatomies and placement of prosthetic valves. This literature review returned no studies in the past five years assessing knowledge of the definition, recognition of symptoms, and preventative measures of infective endocarditis in the adult CHD population. Existing data are more than 15 years old and show significant knowledge deficits. Studies have consistently shown the need for improved CHD patient knowledge with regard to infective endocarditis, and there is no recent evidence that these knowledge deficits have decreased. It is important to address and decrease knowledge deficits in order to improve patient outcomes and decrease healthcare utilisation and costs.

Socioeconomic factors and use of secondary preventive therapies for cardiovascular diseases in South Asia: The PURE study.

PubMed

Gupta, Rajeev; Islam, Shofiqul; Mony, Prem; Kutty, V Raman; Mohan, Viswanathan; Kumar, Rajesh; Thakur, J S; Shankar, V Kiruba; Mohan, Deepa; Vijayakumar, K; Rahman, Omar; Yusuf, Rita; Iqbal, Romaina; Shahid, Mohammed; Mohan, Indu; Rangarajan, Sumathy; Teo, Koon K; Yusuf, Salim

2015-10-01

The purpose of this study was to determine the association of socioeconomic factors on use of cardioprotective medicines in known coronary heart disease (CHD) or stroke in South Asia. We enrolled 33,423 subjects aged 35-70 years (women 56%, rural 53%, low education 51%, low household wealth 25%) in 150 communities in India, Pakistan and Bangladesh during 2003-2009. Information regarding socioeconomic status, disease conditions and treatments was recorded. We studied influence of rural location, educational status and household wealth on use of drug therapies. Odds ratios (ORs) and 95% confidence intervals were calculated. CHD was reported in 683 (2.0%), stroke 316 (0.9%), and CHD/stroke in 970 (2.9%). Median duration since diagnosis was four years. Participants with CHD/stroke were older with greater prevalence of smoking, overweight, hypertension and diabetes (p < 0.01). In patients with CHD, stroke and CHD/stroke, respectively, use (%) of antiplatelets was 11.6, 3.8 and 9.3, beta-blockers 11.9, 7.0 and 10.4, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers 6.4, 1.9 and 5.3 and statins 4.8, 0.6 and 3.5. In CHD/stroke patients any one of these drugs was used in 18.1%, any two in 7.2%, any three in 2.8% and none in 81.5%. Details of drug dose were not available. Use of drugs was significantly lower in rural low education and low wealth index participants (all p < 0.01). Low wealth index participants had the lowest use of these therapies with no attenuation after multiple adjustments. The use of secondary preventive drug therapies in patients with known CHD or stroke in South Asia is low with over 80% receiving none of the effective drug treatments. Low household wealth is the most important determinant. © The European Society of Cardiology 2014.

Defeating EpCAM(+) liver cancer stem cells by targeting chromatin remodeling enzyme CHD4 in human hepatocellular carcinoma.

PubMed

Nio, Kouki; Yamashita, Taro; Okada, Hikari; Kondo, Mitsumasa; Hayashi, Takehiro; Hara, Yasumasa; Nomura, Yoshimoto; Zeng, Sha Sha; Yoshida, Mariko; Hayashi, Tomoyuki; Sunagozaka, Hajime; Oishi, Naoki; Honda, Masao; Kaneko, Shuichi

2015-11-01

Hepatocellular carcinoma is composed of a subset of cells with enhanced tumorigenicity and chemoresistance that are called cancer stem (or stem-like) cells. We explored the role of chromodomain-helicase-DNA-binding protein 4, which is encoded by the CHD4 gene and is known to epigenetically control gene regulation and DNA damage responses in EpCAM(+) liver cancer stem cells. Gene and protein expression profiles were determined by microarray and immunohistochemistry in 245 and 144 hepatocellular carcinoma patients, respectively. The relationship between gene/protein expression and prognosis was examined. The functional role of CHD4 was evaluated in primary hepatocellular carcinoma cells and in cell lines in vitro and in vivo. CHD4 was abundantly expressed in EpCAM(+) hepatocellular carcinoma with expression of hepatic stem cell markers and poor prognosis in two independent cohorts. In cell lines, CHD4 knockdown increased chemosensitivity and CHD4 overexpression induced epirubicin chemoresistance. To inhibit the functions of CHD4 that are mediated through histone deacetylase and poly (ADP-ribose) polymerase, we evaluated the effect of the histone deacetylase inhibitor suberohydroxamic acid and the poly (ADP-ribose) polymerase inhibitor AG-014699. Treatment with either suberohydroxamic acid or AG-014699 reduced the number of EpCAM(+) liver cancer stem cells in vitro, and suberohydroxamic acid and AG-014699 in combination successfully inhibited tumor growth in a mouse xenograft model. CHD4 plays a pivotal role in chemoresistance and the maintenance of stemness in liver cancer stem cells and is therefore a good target for the eradication of hepatocellular carcinoma. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Mode-specific multi-channel dynamics of the F- + CHD2Cl reaction on a global ab initio potential energy surface

NASA Astrophysics Data System (ADS)

Szabó, István; Czakó, Gábor

2016-10-01

We report a detailed quasiclassical trajectory study for the dynamics of the ground-state and CH/CD stretching-excited F- + CHD2Cl(vCH/CD = 0, 1) → Cl- + CHD2F, HF + CD2Cl-, and DF + CHDCl- SN2, proton-, and deuteron-abstraction reactions using a full-dimensional global ab initio analytical potential energy surface. The simulations show that (a) CHD2Cl(vCH/CD = 1), especially for vCH = 1, maintains its mode-specific excited character prior to interaction, (b) the SN2 reaction is vibrationally mode-specific, (c) double inversion can occur and is enhanced upon CH/CD stretching excitations, (d) in the abstraction reactions the HF channel is preferred and the vCH/CD = 1 excitations significantly promote the HF/DF channels, (e) back-side rebound, back-side stripping, and front-side stripping are the dominant direct abstraction mechanisms based on correlated scattering- and attack-angle distributions, (f) the exact classical vibrational energy-based Gaussian binning (1GB) provides realistic mode-specific polyatomic product state distributions, (g) in the abstraction reactions CH and CD stretchings are not pure spectator modes and mainly ground-state products are produced, thus most of the initial energy transfers into product translation, and (h) the HF and DF product molecules are rotationally cold without any significant dependence on the reactant's and HF/DF vibrational states.

Apolipoproteins E and CIII interact to regulate HDL metabolism and coronary heart disease risk

PubMed Central

Morton, Allyson M.; Koch, Manja; Mendivil, Carlos O.; Furtado, Jeremy D.; Tjønneland, Anne; Overvad, Kim; Wang, Liyun; Jensen, Majken K.; Sacks, Frank M.

2018-01-01

BACKGROUND. Subspecies of HDL contain apolipoprotein E (apoE) and/or apoCIII. Both proteins have properties that could affect HDL metabolism. The relation between HDL metabolism and risk of coronary heart disease (CHD) is not well understood. METHODS. Eighteen participants were given a bolus infusion of [D3]L-leucine to label endogenous proteins on HDL. HDL was separated into subspecies containing apoE and/or apoCIII and then into 4 sizes. Metabolic rates for apoA-I in HDL subspecies and sizes were determined by interactive modeling. The concentrations of apoE in HDL that contain or lack apoCIII were measured in a prospective study in Denmark including 1,949 incident CHD cases during 9 years. RESULTS. HDL containing apoE but not apoCIII is disproportionately secreted into the circulation, actively expands while circulating, and is quickly cleared. These are key metabolic steps in reverse cholesterol transport, which may protect against atherosclerosis. ApoCIII on HDL strongly attenuates these metabolic actions of HDL apoE. In the epidemiological study, the relation between HDL apoE concentration and CHD significantly differed depending on whether apoCIII was present. HDL apoE was associated significantly with lower risk of CHD only in the HDL subspecies lacking apoCIII. CONCLUSIONS. ApoE and apoCIII on HDL interact to affect metabolism and CHD. ApoE promotes metabolic steps in reverse cholesterol transport and is associated with lower risk of CHD. ApoCIII, when coexisting with apoE on HDL, abolishes these benefits. Therefore, differences in metabolism of HDL subspecies pertaining to reverse cholesterol transport are reflected in differences in association with CHD. TRIAL REGISTRATION. Clinicaltrials.gov NCT01399632. FUNDING. This work was supported by NIH grant R01HL095964 to FMS and by a grant to the Harvard Clinical and Translational Science Center (8UL1TR0001750) from the National Center for Advancing Translational Science. PMID:29467335

The association of 83 plasma proteins with CHD mortality, BMI, HDL-, and total-cholesterol in men: applying multivariate statistics to identify proteins with prognostic value and biological relevance.

PubMed

Heidema, A Geert; Thissen, Uwe; Boer, Jolanda M A; Bouwman, Freek G; Feskens, Edith J M; Mariman, Edwin C M

2009-06-01

In this study, we applied the multivariate statistical tool Partial Least Squares (PLS) to analyze the relative importance of 83 plasma proteins in relation to coronary heart disease (CHD) mortality and the intermediate end points body mass index, HDL-cholesterol and total cholesterol. From a Dutch monitoring project for cardiovascular disease risk factors, men who died of CHD between initial participation (1987-1991) and end of follow-up (January 1, 2000) (N = 44) and matched controls (N = 44) were selected. Baseline plasma concentrations of proteins were measured by a multiplex immunoassay. With the use of PLS, we identified 15 proteins with prognostic value for CHD mortality and sets of proteins associated with the intermediate end points. Subsequently, sets of proteins and intermediate end points were analyzed together by Principal Components Analysis, indicating that proteins involved in inflammation explained most of the variance, followed by proteins involved in metabolism and proteins associated with total-C. This study is one of the first in which the association of a large number of plasma proteins with CHD mortality and intermediate end points is investigated by applying multivariate statistics, providing insight in the relationships among proteins, intermediate end points and CHD mortality, and a set of proteins with prognostic value.

Evaluation of Carbohydrate-Derived Fulvic Acid (CHD-FA) as a Topical Broad-Spectrum Antimicrobial for Drug-Resistant Wound Infections

DTIC Science & Technology

2016-10-01

restored from day 3 till day 6 in the cutaneous wound infection model. Although we have previously confirmed the broad-spectrum activity of CHD-FA in...vitro, CHD-FA may be less active against Gram-positive pathogens in vivo. The exact molecular mechanisms of the antibiotic activity of CHD-FA are still...not clear, and will be further investigated to address the discrepancy in its activity against Gram-positive and Gram-negative pathogens in our

Latent Constructs in Psychosocial Factors Associated with Cardiovascular Disease: An Examination by Race and Sex

PubMed Central

Clark, Cari Jo; Henderson, Kimberly M.; de Leon, Carlos F. Mendes; Guo, Hongfei; Lunos, Scott; Evans, Denis A.; Everson-Rose, Susan A.

2012-01-01

This study examines race and sex differences in the latent structure of 10 psychosocial measures and the association of identified factors with self-reported history of coronary heart disease (CHD). Participants were 4,128 older adults from the Chicago Health and Aging Project. Exploratory factor analysis (EFA) with oblique geomin rotation was used to identify latent factors among the psychosocial measures. Multi-group comparisons of the EFA model were conducted using exploratory structural equation modeling to test for measurement invariance across race and sex subgroups. A factor-based scale score was created for invariant factor(s). Logistic regression was used to test the relationship between the factor score(s) and CHD adjusting for relevant confounders. Effect modification of the relationship by race–sex subgroup was tested. A two-factor model fit the data well (comparative fit index = 0.986; Tucker–Lewis index = 0.969; root mean square error of approximation = 0.039). Depressive symptoms, neuroticism, perceived stress, and low life satisfaction loaded on Factor I. Social engagement, spirituality, social networks, and extraversion loaded on Factor II. Only Factor I, re-named distress, showed measurement invariance across subgroups. Distress was associated with a 37% increased odds of self-reported CHD (odds ratio: 1.37; 95% confidence intervals: 1.25, 1.50; p-value < 0.0001). This effect did not differ by race or sex (interaction p-value = 0.43). This study identified two underlying latent constructs among a large range of psychosocial variables; only one, distress, was validly measured across race–sex subgroups. This construct was robustly related to prevalent CHD, highlighting the potential importance of latent constructs as predictors of cardiovascular disease. PMID:22347196

Risk factors of coronary heart disease among medical students in King Abdulaziz University, Jeddah, Saudi Arabia.

PubMed

Ibrahim, Nahla Khamis; Mahnashi, Morooj; Al-Dhaheri, Amal; Al-Zahrani, Borooj; Al-Wadie, Ebtihal; Aljabri, Mydaa; Al-Shanketi, Rajaa; Al-Shehri, Rawiah; Al-Sayes, Fatin M; Bashawri, Jamil

2014-04-28

Nowadays, Cardiovascular Diseases (CVDs) represents an escalating worldwide public health problem. Providing consistent data on the magnitude and risk factors of CVDs among young population will help in controlling the risks and avoiding their consequences. The objective was to estimate the prevalence of risk factors of Coronary Heart Disease (CHD) among medical students during their clinical clerkship (4th - 6th years). A cross-sectional study was done during the educational year 2012-2013 at King Abdulaziz University (KAU), Jeddah. Ethical standards were followed and a multistage stratified random sample method was used for selection of 214 medical students. Data was collected through an interviewing questionnaire, measurements and laboratory investigations. Both descriptive and analytical statistics were done by SPSS version 21. CHD risk percent in thirty years was calculated using Framingham algorithm for each student, then the risk among all students was determined. The commonest risk factors of CHDs were daily intake of high fat diet (73.4%), physical inactivity (57.9%), overweight/or obesity (31.2%) and daily consumption of fast food (13.1%). Hyper-cholesterolemia (17.2%) and hypertension (9.3%) were also prevalent risk factors. Smoking prevalence was low (2.8%). Males had significantly higher mean scores for most of CHD risk factors compared to females (p < 0.05). Systolic Blood pressure was higher among males (119.47 ± 11.17) compared to females (112.26 ± 9.06). A highly statistical significant difference was present (Students't test = 4.74, p < 0.001). Framingham Risk Score revealed that CHD risk percent in thirty-years among all students was 10.7%, 2.3% and 0.5% for mild, moderate and severe risk, respectively. An alarmingly high prevalence of CHD risk factors was prevailed among medical students, especially among males. However, a low prevalence of smoking may indicate the success of "Smoke-free Campus" program. Screening risk

LDL-cholesterol Predicts a First CHD Event in Senior Citizens, Especially So in Those With Elevated Lipoprotein(a): Dubbo Study of the Elderly.

PubMed

Simons, Leon A; Simons, Judith; Friedlander, Yechiel; McCallum, John

2018-03-01

The analysis was designed to explore the combined effects of LDL-cholesterol and lipoprotein(a) (Lp(a)) in predicting incident coronary heart disease (CHD) in senior citizens without prior CHD. This is a prospective cohort study in Dubbo NSW which has followed 2805 men and women 60 years and older for 16 years since 1988-1989. Subjects with prior CHD (n=607) were excluded from this analysis. Incident CHD events were identified by hospital record linkage. The contributions of LDL and Lp(a) to CHD events and their combined effects were evaluated in proportional hazards regression models. There were 689 CHD events over 16 years in a cohort of 2198 men and women without prior CHD. LDL-cholesterol (corrected for cholesterol content of Lp(a)) and Lp(a) modelled in quartile categories each independently predicted CHD, but exclusively in Quartile 4 (Q4) for each parameter. Using the combination of LDL Q1 and Lp(a) Q1 as a reference group, LDL Q4 (>4.90mmol/L) most clearly predicted CHD in combination with Lp(a) Q4 (>276mg/L), hazard ratio 1.95 (95%CI 1.31-2.90). The present findings may have important practical implications in clinical management. If Lp(a) is assessed in senior citizens without prior CHD and found to be genuinely low, elevated LDL-cholesterol may not require active intervention. Copyright © 2017 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

21 CFR 101.83 - Health claims: plant sterol/stanol esters and risk of coronary heart disease (CHD).

Code of Federal Regulations, 2010 CFR

2010-04-01

.... (1) Cardiovascular disease means diseases of the heart and circulatory system. Coronary heart disease (CHD) is one of the most common and serious forms of cardiovascular disease and refers to diseases of... of coronary heart disease (CHD). 101.83 Section 101.83 Food and Drugs FOOD AND DRUG ADMINISTRATION...

Defects in neural stem cell proliferation and olfaction in Chd7 deficient mice indicate a mechanism for hyposmia in human CHARGE syndrome

PubMed Central

Layman, W.S.; McEwen, D.P.; Beyer, L.A.; Lalani, S.R.; Fernbach, S.D.; Oh, E.; Swaroop, A.; Hegg, C.C.; Raphael, Y.; Martens, J.R.; Martin, D.M.

2009-01-01

Mutations in CHD7, a chromodomain gene, are present in a majority of individuals with CHARGE syndrome, a multiple anomaly disorder characterized by ocular Coloboma, Heart defects, Atresia of the choanae, Retarded growth and development, Genital hypoplasia and Ear anomalies. The clinical features of CHARGE syndrome are highly variable and incompletely penetrant. Olfactory dysfunction is a common feature in CHARGE syndrome and has been potentially linked to primary olfactory bulb defects, but no data confirming this mechanistic link have been reported. On the basis of these observations, we hypothesized that loss of Chd7 disrupts mammalian olfactory tissue development and function. We found severe defects in olfaction in individuals with CHD7 mutations and CHARGE, and loss of odor evoked electro-olfactogram responses in Chd7 deficient mice, suggesting reduced olfaction is due to a dysfunctional olfactory epithelium. Chd7 expression was high in basal olfactory epithelial neural stem cells and down-regulated in mature olfactory sensory neurons. We observed smaller olfactory bulbs, reduced olfactory sensory neurons, and disorganized epithelial ultrastructure in Chd7 mutant mice, despite apparently normal functional cilia and sustentacular cells. Significant reductions in the proliferation of neural stem cells and regeneration of olfactory sensory neurons in the mature Chd7Gt/+ olfactory epithelium indicate critical roles for Chd7 in regulating neurogenesis. These studies provide evidence that mammalian olfactory dysfunction due to Chd7 haploinsufficiency is linked to primary defects in olfactory neural stem cell proliferation and may influence olfactory bulb development. PMID:19279158

Role of Circulating Fibroblast Growth Factor 21 Measurement in Primary Prevention of Coronary Heart Disease Among Chinese Patients With Type 2 Diabetes Mellitus.

PubMed

Lee, Chi Ho; Woo, Yu Cho; Chow, Wing Sun; Cheung, Chloe Yu Yan; Fong, Carol Ho Yi; Yuen, Michele Mae Ann; Xu, Aimin; Tse, Hung Fat; Lam, Karen Siu Ling

2017-06-06

Fibroblast growth factor 21 (FGF21) has demonstrated beneficial effects on lipid and carbohydrate metabolism. In cross-sectional studies, an association of raised circulating FGF21 levels with coronary heart disease (CHD) was found in some but not all studies. Here we investigated prospectively whether baseline serum FGF21 levels could predict incident CHD in subjects with type 2 diabetes mellitus and no known cardiovascular diseases. Baseline serum FGF21 levels were measured in 3528 Chinese subjects with type 2 diabetes mellitus recruited from the Hong Kong West Diabetes Registry. The role of baseline serum FGF21 levels in predicting incident CHD over a median follow-up of 3.8 years was analyzed using Cox regression analysis. Among 3528 recruited subjects without known cardiovascular diseases, 147 (4.2%) developed CHD over a mean follow-up of 4 years. Baseline serum log-transformed FGF21 levels were significantly higher in those who had incident CHD than those who did not (222.7 pg/mL [92.8-438.4] versus 151.1 pg/mL [75.6-274.6]; P <0.001). On multivariable Cox regression analysis, baseline serum FGF21 levels, using an optimal cutoff of 206.22 pg/mL derived from our study, independently predicted incident CHD (hazard ratio, 1.55; 95% CI, 1.10-2.19; P =0.013) and significantly improved net reclassification index and integrated discrimination improvement after adjustment for conventional cardiovascular risk factors. We have demonstrated, for the first time, that serum FGF21 level is an independent predictor of incident CHD and might be usefully utilized as a biomarker for identifying type 2 diabetes mellitus subjects with raised CHD risk, for primary prevention. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Pulmonary hypertension in children with congenital heart disease (PAH-CHD, PPHVD-CHD). Expert consensus statement on the diagnosis and treatment of paediatric pulmonary hypertension. The European Paediatric Pulmonary Vascular Disease Network, endorsed by ISHLT and DGPK.

PubMed

Kozlik-Feldmann, Rainer; Hansmann, Georg; Bonnet, Damien; Schranz, Dietmar; Apitz, Christian; Michel-Behnke, Ina

2016-05-01

Pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD) is a complex disease that presents with a broad spectrum of morphological and haemodynamic findings of varying severity. Recently, the aspect of paediatric pulmonary hypertensive vascular disease (PPHVD) has been introduced to expand the understanding of the full spectrum of pulmonary hypertension and increased pulmonary vascular resistance. Evaluation and treatment of PAH-CHD/PPHVD-CHD can be divided into in different topics. First, defining criteria for operability and initiation of advanced therapies preoperatively and postoperatively is an unresolved issue. Second, management of Eisenmenger syndrome is still an important question, with recent evidence on the severity of the disease and a more rapidly progressive course than previously described. Third, the Fontan circulation with no subpulmonary ventricle requires a distinct discussion, definition and classification since even a mild rise in pulmonary vascular resistance may lead to the so-called failing Fontan situation. Patients with CHD and single-ventricle physiology (Fontan/total cavopulmonary anastomosis) require a particularly stepwise and individualised approach. This consensus statement is on the current evidence for the most accurate evaluation and treatment of increased pulmonary artery pressure and resistance, as well as ventricular dysfunction, in children with congenital heart defects, and provides according practical recommendations. To optimise preoperative and postoperative management in patients with PAH-CHD, diagnostic and treatment algorithms are provided. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Serum uric acid as prognostic marker of coronary heart disease (CHD).

PubMed

Purnima, Samudrala; El-Aal, Bahiga Galal Abd

A substantial body of epidemiological and experimental evidence suggests the significance of serum uric acid as an important and independent risk factor of cardio vascular and renal diseases especially in patients with diabetes mellitus, hypertension. Hyperuricemia is a risk factor of coronary heart disease. Several studies showed positive association between hyperuricemia and CHD risk factors. To analyze the serum uric acid levels in patients with diabetes and hypertension, which helps in understanding its role as prognostic marker of coronary heart disease. The study was conducted in population of Wadi-Al Dawasir (K.S.A.) aged 20-80 years through random sampling from October 2012 to June 2013. It included 250 samples and the cases were categorized into diabetic and hypertensive. In the cases, purely hypertensive were 52, diabetic were 57 and mixed group included both diabetic and hypertensive patients 65. Fasting blood was collected to analyze lipid profile which included (total cholesterol, triglycerides, high density lipoprotein, low density lipoprotein) and serum uric acid in association with age and heredity was also studied. Patient demographics were recorded. The study revealed significant association of serum uric acid (p<0.014*) and total cholesterol (p<0.007**) triglycerides (p<0.009**) low density lipoprotein (p<0.044*) in hypertensive group. Serum uric acid levels in the mixed group patients with diabetes and hypertension reported serum uric acid (p<0.0037), total cholesterol (p<0.089+) proved to have increased risk of coronary heart disease. When compared to controls (non-diabetic p<0.529) and (non-hypertensive p<0.021*) with respect to serum uric acid levels show the magnitude of risk to coronary heart disease. With progressing age the association of lipid profile and serum uric acid reported (p<0.001**) in diabetics. Significant correlations were found between serum uric acid and risk factors for CHD. This is first study of its kind in this region

CTCF-KDM4A complex correlates with histone modifications that negatively regulate CHD5 gene expression in cancer cell lines

PubMed Central

Guerra-Calderas, Lissania; González-Barrios, Rodrigo; Patiño, Carlos César; Alcaraz, Nicolás; Salgado-Albarrán, Marisol; de León, David Cantú; Hernández, Clementina Castro; Sánchez-Pérez, Yesennia; Maldonado-Martínez, Héctor Aquiles; De la Rosa-Velazquez, Inti A.; Vargas-Romero, Fernanda; Herrera, Luis A.; García-Carrancá, Alejandro; Soto-Reyes, Ernesto

2018-01-01

Histone demethylase KDM4A is involved in H3K9me3 and H3K36me3 demethylation, which are epigenetic modifications associated with gene silencing and RNA Polymerase II elongation, respectively. KDM4A is abnormally expressed in cancer, affecting the expression of multiple targets, such as the CHD5 gene. This enzyme localizes at the first intron of CHD5, and the dissociation of KDM4A increases gene expression. In vitro assays showed that KDM4A-mediated demethylation is enhanced in the presence of CTCF, suggesting that CTCF could increase its enzymatic activity in vivo, however the specific mechanism by which CTCF and KDM4A might be involved in the CHD5 gene repression is poorly understood. Here, we show that CTCF and KDM4A form a protein complex, which is recruited into the first intron of CHD5. This is related to a decrease in H3K36me3/2 histone marks and is associated with its transcriptional downregulation. Depletion of CTCF or KDM4A by siRNA, triggered the reactivation of CHD5 expression, suggesting that both proteins are involved in the negative regulation of this gene. Furthermore, the knockout of KDM4A restored the CHD5 expression and H3K36me3 and H3K36me2 histone marks. Such mechanism acts independently of CHD5 promoter DNA methylation. Our findings support a novel mechanism of epigenetic repression at the gene body that does not involve promoter silencing. PMID:29682202

CHD risk equivalents and the metabolic syndrome. Trial evidence supports aggressive management.

PubMed

Thompson, Paul D

2003-08-01

Updated guidelines issued by the National Cholesterol Education Program's 2001 Adult Treatment Panel III (ATP III) reaffirm the importance of intensive management of low density lipoprotein cholesterol (LDL-C) in patients with established coronary heart disease (CHD). Clinical studies also show that diabetes, peripheral arterial disease, abdominal aortic aneurysm, and symptomatic carotid artery disease are CHD risk equivalents that require intensive therapeutic lifestyle changes and drug therapy to prevent associated morbidity and mortality. Likewise, the metabolic syndrome is a secondary target of treatment. Drug therapy usually starts with an LDL-C-lowering agent, such as a statin. If LDL-C and non-high-density lipoprotein cholesterol goals are not achieved, statin therapy should be intensified or a fibrate or niacin should be added.

eHealth literacy and preferences for eHealth resources in parents of children with complex CHD.

PubMed

Kasparian, Nadine A; Lieu, Nathan; Winlaw, David S; Cole, Andrew; Kirk, Edwin; Sholler, Gary F

2017-05-01

Introduction This study aimed to (a) examine eHealth literacy, beliefs, and behaviours in parents of children with complex CHD, and (b) identify parents' preferences for the content, format, features, and functions of eHealth resources for CHD. Materials and methods Families (n=198) of children born between 2008 and 2011 and diagnosed with CHD requiring surgery were mailed a survey assessing a range of variables including eHealth literacy, beliefs, and behaviours as well as preferences for the format, functions, features, and content of eHealth resources for CHD. A total of 132 parents (83 mothers, 49 fathers) completed the survey (response rate: 50%). Mothers (96%) were more likely to access eHealth resources than fathers (83%, χ2=6.74, p=0.009). Despite high eHealth resource use, eHealth literacy was relatively low, with results demonstrating considerable and widespread gaps in awareness of, access to, and communication about eHealth resources. Over 50% of parents reported that decisions regarding their child's healthcare were influenced, to some extent, by web-based resources. Barriers to doctor-patient communication about eHealth included limited consultation time and concern about doctors' disapproval. Participants demonstrated a strong desire for "eHealth prescriptions" from their child's healthcare team, and perceived a wide range of eHealth topics as highly important, including treatment-related complications as well as physical, cognitive, and emotional development in children with CHD. Discussion Results suggest a need for stronger, more proactive partnerships between clinicians, researchers, educators, technologists, and patients and families to bring about meaningful innovations in the development and implementation of eHealth interventions in paediatric cardiology.

21 CFR 101.81 - Health claims: Soluble fiber from certain foods and risk of coronary heart disease (CHD).

Code of Federal Regulations, 2010 CFR

2010-04-01

... cholesterol and that include soluble fiber from certain foods and the risk of CHD. (1) Cardiovascular disease... common and serious forms of cardiovascular disease and refers to diseases of the heart muscle and... and risk of coronary heart disease (CHD). 101.81 Section 101.81 Food and Drugs FOOD AND DRUG...

Infrared absorption spectra of partially deuterated methoxy radicals CH2DO and CHD2O isolated in solid para-hydrogen.

PubMed

Haupa, Karolina A; Johnson, Britta A; Sibert, Edwin L; Lee, Yuan-Pern

2017-10-21

The investigation of partially deuterated methoxy radicals is important because the symmetry lowering from C 3v to C s provides new insights into the couplings between rovibronic states via Jahn-Teller and spin-orbit interactions. The vibrational spectrum of the partially deuterated methoxy radical CH 2 DO in a matrix of p-H 2 has been recorded. This species was prepared by irradiating a p-H 2 matrix containing deuterated d 1 -nitritomethane (CH 2 DONO) at 3.3 K with laser light at 355 nm. The identification of the radical is based on the photochemical behavior of the precursor and comparison of observed vibrational wavenumbers and infrared (IR) intensities with those predicted from a refined quartic, curvilinear, internal coordinate force field calculated with the coupled-cluster singles and doubles with perturbative triples/cc-pVTZ method. CH 2 DO reacts with H 2 with a rate coefficient (3.5 ± 1.0) × 10 -3 s -1 . Predominantly c-CHDOH and a negligibly small amount of t-CHDOH were produced. This stereoselectivity results from the reaction H + C s -CH 2 DOH, which was demonstrated by an additional experiment on irradiation of a CH 2 DOH/Cl 2 /p-H 2 matrix with ultraviolet and IR light to induce the H + CH 2 DOH reaction; only c-CHDOH was observed from this experiment. Even though the energies of transition states and products for the formation of c-CHDOH and t-CHDOH differ by only ∼10 cm -1 , the selective formation of c-CHDOH can be explained by tunneling of the hydrogen atom via an optimal tunneling path. Similarly, the vibronic spectrum for the partially deuterated specie d 2 -methoxy radical (CHD 2 O) was obtained upon irradiation of d 2 -nitritomethane (CHD 2 ONO) at 355 nm. Lines associated with the fundamental vibrational modes were observed and assigned; line positions agree with theoretically predicted vibrational wavenumbers. CHD 2 O reacts with H 2 with a rate coefficient (6.0 ± 1.4) × 10 -3 s -1 ; CD 2 OH was produced as a major product because

Infrared absorption spectra of partially deuterated methoxy radicals CH2DO and CHD2O isolated in solid para-hydrogen

NASA Astrophysics Data System (ADS)

Haupa, Karolina A.; Johnson, Britta A.; Sibert, Edwin L.; Lee, Yuan-Pern

2017-10-01

The investigation of partially deuterated methoxy radicals is important because the symmetry lowering from C3v to Cs provides new insights into the couplings between rovibronic states via Jahn-Teller and spin-orbit interactions. The vibrational spectrum of the partially deuterated methoxy radical CH2DO in a matrix of p-H2 has been recorded. This species was prepared by irradiating a p-H2 matrix containing deuterated d1-nitritomethane (CH2DONO) at 3.3 K with laser light at 355 nm. The identification of the radical is based on the photochemical behavior of the precursor and comparison of observed vibrational wavenumbers and infrared (IR) intensities with those predicted from a refined quartic, curvilinear, internal coordinate force field calculated with the coupled-cluster singles and doubles with perturbative triples/cc-pVTZ method. CH2DO reacts with H2 with a rate coefficient (3.5 ± 1.0) × 10-3 s-1. Predominantly c-CHDOH and a negligibly small amount of t-CHDOH were produced. This stereoselectivity results from the reaction H + Cs-CH2DOH, which was demonstrated by an additional experiment on irradiation of a CH2DOH/Cl2/p-H2 matrix with ultraviolet and IR light to induce the H + CH2DOH reaction; only c-CHDOH was observed from this experiment. Even though the energies of transition states and products for the formation of c-CHDOH and t-CHDOH differ by only ˜10 cm-1, the selective formation of c-CHDOH can be explained by tunneling of the hydrogen atom via an optimal tunneling path. Similarly, the vibronic spectrum for the partially deuterated specie d2-methoxy radical (CHD2O) was obtained upon irradiation of d2-nitritomethane (CHD2ONO) at 355 nm. Lines associated with the fundamental vibrational modes were observed and assigned; line positions agree with theoretically predicted vibrational wavenumbers. CHD2O reacts with H2 with a rate coefficient (6.0 ± 1.4) × 10-3 s-1; CD2OH was produced as a major product because the barrier for the formation of CHDOH from H

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gompers, Andrea L.; Su-Feher, Linda; Ellegood, Jacob

The chromatin remodeling gene CHD8 represents a central node in neurodevelopmental gene networks implicated in autism. In this paper, we examined the impact of germline heterozygous frameshift Chd8 mutation on neurodevelopment in mice. Chd8 +/ del5 mice displayed normal social interactions with no repetitive behaviors but exhibited cognitive impairment correlated with increased regional brain volume, validating that phenotypes of Chd8 +/ del5 mice overlap pathology reported in humans with CHD8 mutations. We applied network analysis to characterize neurodevelopmental gene expression, revealing widespread transcriptional changes in Chd8 +/ del5 mice across pathways disrupted in neurodevelopmental disorders, including neurogenesis, synaptic processes andmore » neuroimmune signaling. We identified a co-expression module with peak expression in early brain development featuring dysregulation of RNA processing, chromatin remodeling and cell-cycle genes enriched for promoter binding by Chd8, and we validated increased neuronal proliferation and developmental splicing perturbation in Chd8 +/ del5 mice. Finally, this integrative analysis offers an initial picture of the consequences of Chd8 haploinsufficiency for brain development.« less

Multidisciplinary family-centred psychosocial care for patients with CHD: consensus recommendations from the AEPC Psychosocial Working Group.

PubMed

Utens, Elisabeth M W J; Callus, Edward; Levert, Eveline M; Groote, Katya De; Casey, Frank

2018-02-01

Because of the enormous advances in the medical treatment of CHD, the long-term survival of patients suffering from this disease has increased significantly. Currently, about 90% of patients reach adulthood, which entails many new challenges both for patients and their families and for healthcare professionals. The main objective of family-centred psychosocial care is to strengthen the emotional resilience of chronically ill patients and their families by adopting a holistic approach. During the biannual meeting of the psychosocial working group in 2012, participants expressed the need for general European guidelines. The present recommendations were written to support medical staff and psychosocial healthcare professionals to provide the best care for children and adolescents with CHD as well as for their families. This article describes in detail how the integrated family-centred psychological care modules work, involving different healthcare specialists, including a paediatric/congenital cardiologist or a general paediatrician. The different clinical implications and specific needs have been taken into account and recommendations have been provided on the following: structured follow-up screening; identification of stressful periods related to cardiac surgery or invasive medical procedures; evidence-based, disease-specific, and family-oriented psychosocial interventions; and interactive media links to medical and psychosocial information.

MEDication reminder APPs to improve medication adherence in Coronary Heart Disease (MedApp-CHD) Study: a randomised controlled trial protocol

PubMed Central

Chow, Clara K; Thiagalingam, Aravinda; Rogers, Kris; Chalmers, John; Redfern, Julie

2017-01-01

Introduction The growing number of smartphone health applications available in the app stores makes these apps a promising tool to help reduce the global problem of non-adherence to long-term medications. However, to date, there is limited evidence that available medication reminder apps are effective. This study aims to determine the impact of medication reminder apps on adherence to cardiovascular medication when compared with usual care for people with coronary heart disease (CHD) and to determine whether an advanced app compared with a basic app is associated with higher adherence. Methods and analysis Randomised controlled trial with follow-up at 3 months to evaluate the feasibility and effectiveness of medication reminder apps on medication adherence compared with usual care. An estimated sample size of 156 patients with CHD will be randomised to one of three groups (usual care group, basic medication reminder app group and advanced medication reminder app group). The usual care group will receive standard care for CHD with no access to a medication reminder app. The basic medication reminder app group will have access to a medication reminder app with a basic feature of providing simple daily reminders with no interactivity. The advanced medication reminder app group will have access to a medication reminder app with additional interactive and customisable features. The primary outcome is medication adherence measured by the eight-item Morisky Medication Adherence Scale at 3 months. Secondary outcomes include clinical measurements of blood pressure and cholesterol levels, and medication knowledge. A process evaluation will also be performed to assess the feasibility of the intervention by evaluating the acceptability, utility and engagement with the apps. Ethics and dissemination Ethical approval has been obtained from the Western Sydney Local Health Network Human Research Ethics Committee (AU/RED/HREC/1/WMEAD/3). Study findings will be disseminated via

MEDication reminder APPs to improve medication adherence in Coronary Heart Disease (MedApp-CHD) Study: a randomised controlled trial protocol.

PubMed

Santo, Karla; Chow, Clara K; Thiagalingam, Aravinda; Rogers, Kris; Chalmers, John; Redfern, Julie

2017-10-08

The growing number of smartphone health applications available in the app stores makes these apps a promising tool to help reduce the global problem of non-adherence to long-term medications. However, to date, there is limited evidence that available medication reminder apps are effective. This study aims to determine the impact of medication reminder apps on adherence to cardiovascular medication when compared with usual care for people with coronary heart disease (CHD) and to determine whether an advanced app compared with a basic app is associated with higher adherence. Randomised controlled trial with follow-up at 3 months to evaluate the feasibility and effectiveness of medication reminder apps on medication adherence compared with usual care. An estimated sample size of 156 patients with CHD will be randomised to one of three groups (usual care group, basic medication reminder app group and advanced medication reminder app group). The usual care group will receive standard care for CHD with no access to a medication reminder app. The basic medication reminder app group will have access to a medication reminder app with a basic feature of providing simple daily reminders with no interactivity. The advanced medication reminder app group will have access to a medication reminder app with additional interactive and customisable features. The primary outcome is medication adherence measured by the eight-item Morisky Medication Adherence Scale at 3 months. Secondary outcomes include clinical measurements of blood pressure and cholesterol levels, and medication knowledge. A process evaluation will also be performed to assess the feasibility of the intervention by evaluating the acceptability, utility and engagement with the apps. Ethical approval has been obtained from the Western Sydney Local Health Network Human Research Ethics Committee (AU/RED/HREC/1/WMEAD/3). Study findings will be disseminated via usual scientific forums. ACTRN12616000661471; Pre-results. �

Patients' Adherence to Healthy Behavior in Coronary Heart Disease: Risk Factor Management Among Jordanian Patients.

PubMed

Mosleh, Sultan M; Darawad, Muhammad

2015-01-01

Poor adherence to risk factor management behaviors for coronary heart disease (CHD) patients increases the risk for a further cardiac event. There is a scarcity of literature about the level of adherence to risk factor management behaviors after CHD diagnosis in Jordan. The aim of this study was to explore which demographic, psychosocial, and clinical factors predict better adherence to risk factor management behaviors, particularly smoking cessation, physical activity, healthy diet, and medication adherence. In addition, we sought to explore the association of poor adherence to hospital readmission. A cross-sectional survey was performed using a sample of 350 patients who visited the outpatient clinics in 4 hospitals in Jordan. Data were obtained from 254 patients (response rate, 73%). Most were overweight (47.8%) or obese (28.5%), and 30% remained smokers after CHD diagnosis; 53 (21.5%) described themselves as ex-smokers. One-third of participants (88, 34.8%) performed regular walking exercise. Only 16% of participants reported that they had been instructed to perform regular activity. Stepwise multiple regressions revealed younger age and lower body mass index as independent predictors for more physical activity. Only 51 (20.9%) reported always following a low-fat dietary regimen, and participants who received dietary recommendation advice were significantly more likely to be on a healthy diet (odds ratio, 10.3; 95% confidence interval, 3.79-30.80; P < .001). Most of the participants (183, 72%) reported low medication adherence (score ≤6), based on the Morisky scale, and only 5 (2%) reported a high adherence score (score = 8). Male gender and having chronic back pain were independent predictors for better medication adherence. About one-third of participants had been hospitalized for cardiac reason at last 2 times in the past 12 months. Rehospitalization was significantly more common among patients who were not following a dietary regimen (Mann-Whitney Z = -2

Gender differences in risk factors for coronary heart disease.

PubMed

Tan, Yen Y; Gast, Gerrie-Cor M; van der Schouw, Yvonne T

2010-02-01

Coronary heart disease (CHD), traditionally considered a male disease, is also a major threat to women. This review article addresses independent risk factors for CHD that are specific for women as well as non-gender-specific risk factors and how their effects differ between men and women. Although polycystic ovary syndrome (PCOS) in women is associated with an adverse metabolic risk profile, current evidence regarding future risk of CHD is conflicting. Preeclampsia is consistently associated with higher risk of CHD later in life. Menopause is associated with an increased risk of CHD, and the earlier the onset of menopause, the larger the risk. Existing data on postmenopausal hormone therapy (HT) was inconclusive with regard to possible protection when HT is initiated close to menopause in young peri- or postmenopausal women. Evidence on use of low-dose oral contraceptives strongly suggests no increased risk of CHD. Although levels of physical inactivity are similar for men and women, the higher prevalences of hypertension, diabetes, and obesity in older women portends a greater risk in women than in men. Additionally, risk factors like smoking, hypertriglyceridemia and low high-density lipoprotein cholesterol levels have greater impact in women than in men. This review indicates that acknowledgement of non-gender-specific risk factors in addition to those that are unique to women would help optimize diagnosis, treatment and earlier prevention of CHD in women. Further research is needed to ascertain if incorporating these gender-specific risks into a clinically used risk stratification model would change outcome in women. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

The Burden of Cardiovascular Disease Attributable to Major Modifiable Risk Factors in Indonesia.

PubMed

Hussain, Mohammad Akhtar; Al Mamun, Abdullah; Peters, Sanne Ae; Woodward, Mark; Huxley, Rachel R

2016-10-05

In Indonesia, coronary heart disease (CHD) and stroke are estimated to cause more than 470 000 deaths annually. In order to inform primary prevention policies, we estimated the sex- and age-specific burden of CHD and stroke attributable to five major and modifiable vascular risk factors: cigarette smoking, hypertension, diabetes, elevated total cholesterol, and excess body weight. Population attributable risks for CHD and stroke attributable to these risk factors individually were calculated using summary statistics obtained for prevalence of each risk factor specific to sex and to two age categories (<55 and ≥55 years) from a national survey in Indonesia. Age- and sex-specific relative risks for CHD and stroke associated with each of the five risk factors were derived from prospective data from the Asia-Pacific region. Hypertension was the leading vascular risk factor, explaining 20%-25% of all CHD and 36%-42% of all strokes in both sexes and approximately one-third of all CHD and half of all strokes across younger and older age groups alike. Smoking in men explained a substantial proportion of vascular events (25% of CHD and 17% of strokes). However, given that these risk factors are likely to be strongly correlated, these population attributable risk proportions are likely to be overestimates and require verification from future studies that are able to take into account correlation between risk factors. Implementation of effective population-based prevention strategies aimed at reducing levels of major cardiovascular risk factors, especially blood pressure, total cholesterol, and smoking prevalence among men, could reduce the growing burden of CVD in the Indonesian population.

Subgroup differences in psychosocial factors relating to coronary heart disease in the UK South Asian population☆

PubMed Central

Williams, Emily D.; Nazroo, James Y.; Kooner, Jaspal S.; Steptoe, Andrew

2010-01-01

Objectives To explore the differences in psychosocial risk factors related to coronary heart disease (CHD) between South Asian subgroups in the UK. South Asian people suffer significantly higher rates of CHD than other ethnic groups, but vulnerability varies between South Asian subgroups, in terms of both CHD rates and risk profiles. Psychosocial factors may contribute to the excess CHD propensity that is observed; however, subgroup heterogeneity in psychosocial disadvantage has not previously been systematically explored. Methods With a cross-sectional design, 1065 healthy South Asian and 818 white men and women from West London, UK, completed psychosocial questionnaires. Psychosocial profiles were compared between South Asian religious groups and the white sample, using analyses of covariance and post hoc tests. Results Of the South Asian sample, 50.5% was Sikh, 28.0% was Hindu, and 15.8% was Muslim. Muslim participants were more socioeconomically deprived and experienced higher levels of chronic stress, including financial strain, low social cohesion, and racial discrimination, compared with other South Asian religious groups. In terms of health behaviors, Muslim men smoked more than Sikhs and Hindus, and Muslims also reported lower alcohol consumption and were less physically active than other groups. Conclusion This study found that Muslims were exposed to more psychosocial and behavioral adversity than Sikhs and Hindus, and highlights the importance of investigating subgroup heterogeneity in South Asian CHD risk. PMID:20846539

Can breast cancer patients use soyafoods to help reduce risk of CHD?

PubMed

Messina, Mark; Messina, Virginia; Jenkins, David J A

2012-09-01

Over the past 20 years, the popularity of soyafoods has increased in part because of research suggesting that these foods convey health benefits independent of their nutrient content. For example, in 1999, the US Food and Drug Administration approved a health-claim for soyafoods and CHD based on the hypocholesterolaemic effects of soya protein. However, soyafoods have become controversial in recent years because of concerns that their uniquely rich phyto-oestrogen (isoflavone) content may cause untoward effects in some individuals. Most notable in this regard is the concern that soyafoods are contraindicated for breast cancer patients and women at high risk of developing this disease. Furthermore, the hypocholesterolaemic effects of soya protein have been challenged. However, the results of recently published meta-analyses indicate that soya protein directly lowers circulating LDL-cholesterol levels by approximately 4 %. There is also intriguing evidence that soyafoods reduce CHD risk independent of their effects on lipid levels. In regard to the breast cancer controversy, recently published clinical and epidemiological data do not support observations in rodents that soyabean isoflavones increase breast cancer risk. In postmenopausal women, isoflavone exposure does not adversely affect breast tissue density or breast cell proliferation. Furthermore, both US and Chinese prospective epidemiological studies show that post-diagnosis soya consumption is associated with an improved prognosis. Therefore, soyafoods should be considered by women as healthy foods to include in diets aimed at reducing the risk of CHD regardless of their breast cancer status.

Can an Internet-based health risk assessment highlight problems of heart disease risk factor awareness? A cross-sectional analysis.

PubMed

Dickerson, Justin B; McNeal, Catherine J; Tsai, Ginger; Rivera, Cathleen M; Smith, Matthew Lee; Ohsfeldt, Robert L; Ory, Marcia G

2014-04-18

Health risk assessments are becoming more popular as a tool to conveniently and effectively reach community-dwelling adults who may be at risk for serious chronic conditions such as coronary heart disease (CHD). The use of such instruments to improve adults' risk factor awareness and concordance with clinically measured risk factor values could be an opportunity to advance public health knowledge and build effective interventions. The objective of this study was to determine if an Internet-based health risk assessment can highlight important aspects of agreement between respondents' self-reported and clinically measured CHD risk factors for community-dwelling adults who may be at risk for CHD. Data from an Internet-based cardiovascular health risk assessment (Heart Aware) administered to community-dwelling adults at 127 clinical sites were analyzed. Respondents were recruited through individual hospital marketing campaigns, such as media advertising and print media, found throughout inpatient and outpatient facilities. CHD risk factors from the Framingham Heart Study were examined. Weighted kappa statistics were calculated to measure interrater agreement between respondents' self-reported and clinically measured CHD risk factors. Weighted kappa statistics were then calculated for each sample by strata of overall 10-year CHD risk. Three samples were drawn based on strategies for treating missing data: a listwise deleted sample, a pairwise deleted sample, and a multiple imputation (MI) sample. The MI sample (n=16,879) was most appropriate for addressing missing data. No CHD risk factor had better than marginal interrater agreement (κ>.60). High-density lipoprotein cholesterol (HDL-C) exhibited suboptimal interrater agreement that deteriorated (eg, κ<.30) as overall CHD risk increased. Conversely, low-density lipoprotein cholesterol (LDL-C) interrater agreement improved (eg, up to κ=.25) as overall CHD risk increased. Overall CHD risk of the sample was lower than

[Risk factors and coronary heart disease prevention in selected Lódź population--part II].

PubMed

Kowalski, Jan; Kos, Małgorzata; Gburek, Jolanta; Wrocławski, Witold; Pawlicki, Lucjan

2005-12-01

Evaluation of the knowledge on CHD risk factors in selected Lódź population was made. Realization of primary and secondary CHD prevention principles was assessed. Over 20% of patients with CHD and over 38% of subjects without CHD did not realize the prevention principles. Hypolipemic therapy was effective only in 44.21% of patients with CHD and 35.9% of subjects without CHD. Antihypertensive therapy was successful in about 55% of patients with CHD and 35% of subjects without CHD. The results of our study have shown low effectiveness of both CHD prevention principles realization and hipolipemic and antihypertensive therapy in selected Lódź population.

Comparison of electrocardiographic findings and associated risk factors between Taiwan Chinese and US White adults.

PubMed

Wu, Chih-Cheng; Yeh, Wen-Ting; Crow, Richard S; Bai, Chyi-Huey; Pan, Wen-Harn

2008-08-18

Electrocardiographic (ECG) findings are known to differ by race, however, systematic comparisons of findings between eastern and western countries are rare. To compare the ECG findings and associated coronary heart disease (CHD) risk factors between Taiwan Chinese and US White adults aged >or=40 years. We compared the prevalence rate of Minnesota Code criteria based ECG findings and associated CHD risk factors by using data from the third National Health and Nutrition Examination Survey (NHANES III) and the Nutrition and Health Survey in Taiwan (NAHSIT, 1993-1996). Examining all the ECG findings collectively, we observed a higher prevalence of major Minnesota Code findings in Taiwan Chinese women than in US White women (15.0% vs. 10.5%), particularly ST segment depression (5.4% vs. 2.4%) and T wave abnormalities (10.8% vs. 4.8%). The prevalence of major Minnesota Code findings was similar in both Taiwan Chinese and US White men (22.7% vs. 19.6%). Taiwan Chinese men had a higher prevalence of ST segment elevation (13.7% vs. 0.9%). Taiwan Chinese also had a higher prevalence of left ventricular hypertrophy with repolarization change than US Whites in both sexes (2.7% vs. 1.4% for men, 4.3% vs. 1.3% for women). Taiwan Chinese had more favorable CHD risk factor profiles than US Whites, including lipid profile, obesity, central obesity, and smoking status. The prevalence of hypertension was similar between the two groups, however, a lower percentage of Taiwan Chinese received treatment. Taiwan Chinese men had a lower prevalence of diabetes mellitus than US White men, whereas Taiwan Chinese women had a higher prevalence than US White women. These results suggest that substantial differences in ECG findings exist between Taiwan Chinese and US Whites which cannot be entirely explained by CHD risk factors alone.

Advancing the Hypothesis that Geographic Variations in Risk Factors Contribute Relatively Little to Observed Geographic Variations in Heart Disease and Stroke Mortality

PubMed Central

Howard, George; Cushman, Mary; Prineas, Ronald J.; Howard, Virginia J.; Moy, Claudia S.; Sullivan, Lisa M.; D’Agostino, Ralph B.; McClure, Leslie A.; Pulley, Lea Vonne; Safford, Monika M.

2009-01-01

Purpose Geographic variation in risk factors may underlie geographic disparities in coronary heart disease (CHD) and stroke mortality. Methods Framingham CHD Risk Score (FCRS) and Stroke Risk Score (FSRS) were calculated for 25,770 stroke-free and 22,247 CHD-free participants from the REasons for Geographic And Racial Differences in Stroke cohort. Vital statistics provided age-adjusted CHD and stroke mortality rates. In an ecologic analysis, the age-adjusted, race-sex weighted, average state-level risk factor levels were compared to state-level mortality rates. Results There was no relationship between CHD and stroke mortality rates (r = 0.04; p = 0.78), but there was between CHD and stroke risk scores at the individual (r = 0.68; p < 0.0001) and state (r = 0.64, p < 0.0001) level. There was a stronger (p < 0.0001) association between state-level FCRS and state-level CHD mortality (r = 0.28, p = 0.18), than between FSRS and stroke mortality (r = 0.12, p = 0.56). Conclusions Weak associations between CHD and stroke mortality and strong associations between CHD and stroke risk scores suggest geographic variation in risk factors may not underlie geographic variations in stroke and CHD mortality. The relationship between risk factor scores and mortality was stronger for CHD than stroke. PMID:19285103

Evidence for the interaction of the regulatory protein Ki-1/57 with p53 and its interacting proteins

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nery, Flavia C.; Departamento de Genetica e Evolucao, Universidade Estadual de Campinas, Campinas, SP; Rui, Edmilson

Ki-1/57 is a cytoplasmic and nuclear phospho-protein of 57 kDa and interacts with the adaptor protein RACK1, the transcription factor MEF2C, and the chromatin remodeling factor CHD3, suggesting that it might be involved in the regulation of transcription. Here, we describe yeast two-hybrid studies that identified a total of 11 proteins interacting with Ki-1/57, all of which interact or are functionally associated with p53 or other members of the p53 family of proteins. We further found that Ki-1/57 is able to interact with p53 itself in the yeast two-hybrid system when the interaction was tested directly. This interaction could bemore » confirmed by pull down assays with purified proteins in vitro and by reciprocal co-immunoprecipitation assays from the human Hodgkin analogous lymphoma cell line L540. Furthermore, we found that the phosphorylation of p53 by PKC abolishes its interaction with Ki-1/57 in vitro.« less

Coronary Heart Disease and Stroke Attributable to Major Risk Factors is Similar in Argentina and the United States: the Coronary Heart Disease Policy Model

PubMed Central

Moran, Andrew; DeGennaro, Vincent; Ferrante, Daniel; Coxson, Pamela G.; Palmas, Walter; Mejia, Raul; Perez-Stable, Eliseo J.; Goldman, Lee

2011-01-01

Background Cardiovascular disease is the leading cause of death in Argentina and the U.S. Argentina is 92% urban, with cardiovascular disease risk factor levels approximating the U.S. Methods The Coronary Heart Disease (CHD) Policy Model is a national-scale computer model of CHD and stroke. Risk factor data were obtained from the Cardiovascular Risk Factor Multiple Evaluation in Latin America Study (2003–04), Argentina National Risk Factor Survey (2005) and U.S. national surveys. Proportions of cardiovascular events over 2005–2015 attributable to risk factors were simulated by setting risk factors to optimal exposure levels [systolic blood pressure (SBP) 115 mm Hg, low-density lipoprotein cholesterol (LDL) 2.00 mmol/l (78 mg/dl), high-density lipoprotein cholesterol (HDL) 1.03 mmol/l (60 mg/dl), absence of diabetes, and smoking]. Cardiovascular disease attributable to body mass index (BMI) > 21 kg/m2 was assumed mediated through SBP, LDL, HDL, and diabetes. Results Cardiovascular disease attributable to major risk factors was similar between Argentina and the U.S., except for elevated SBP in men (CHD 8 % points higher in Argentine men, 6% higher for stroke). CHD attributable to BMI > 21 kg/m2 was substantially higher in the U.S. (men 10–11 % points higher; women CHD 13–14% higher). Conclusions Projected cardiovascular disease attributable to major risk factors appeared similar in Argentina and the U.S., though elevated BMI may be responsible for more of U.S. cardiovascular disease. A highly urbanized middle-income nation can have cardiovascular disease rates and risk factor levels comparable to a high income nation, but fewer resources for fighting the epidemic. PMID:21550675

Sleep duration and chronic diseases among U.S. adults age 45 years and older: evidence from the 2010 Behavioral Risk Factor Surveillance System.

PubMed

Liu, Yong; Wheaton, Anne G; Chapman, Daniel P; Croft, Janet B

2013-10-01

To examine the effects of obesity and frequent mental distress (FMD) on the relationship of sleep duration with coronary heart disease (CHD), stroke, and diabetes. Cross-sectional study. Population-based surveillance. There were 54,269 adults age 45 y or older who completed the 2010 Behavioral Risk Factor Surveillance System survey in 14 states. Nearly one third (31.1% or an estimated 11.1 million) of respondents age 45 y and older reported being short sleepers (≤ 6 h), 64.8% being optimal sleepers (7-9 h), and 4.1% being long sleepers (≥ 10 h) in a 24-h period. Compared with the optimal sleep duration, both short and long sleep durations were significantly associated with obesity, FMD (mental health was not good ≥ 14 days during the past 30 days), CHD, stroke, and diabetes after controlling for sex, age, race/ethnicity, and education. The U-shaped relationships of sleep duration with CHD, stroke, and diabetes were moderately attenuated by FMD. The relationship between sleep duration and diabetes was slightly attenuated by obesity. Sleep duration had U-shaped relationships with leading chronic diseases. Further prospective studies are needed to determine how mental health and maintenance of a normal weight may interact with sleep duration to prevent chronic diseases.

Organizational Justice and Physiological Coronary Heart Disease Risk Factors in Japanese Employees: a Cross-Sectional Study.

PubMed

Inoue, Akiomi; Kawakami, Norito; Eguchi, Hisashi; Miyaki, Koichi; Tsutsumi, Akizumi

2015-12-01

Growing evidence has shown that lack of organizational justice (i.e., procedural justice and interactional justice) is associated with coronary heart disease (CHD) while biological mechanisms underlying this association have not yet been fully clarified. The purpose of the present study was to investigate the cross-sectional association of organizational justice with physiological CHD risk factors (i.e., blood pressure, high-density lipoprotein [HDL] cholesterol, low-density lipoprotein [LDL] cholesterol, and triglyceride) in Japanese employees. Overall, 3598 male and 901 female employees from two manufacturing companies in Japan completed self-administered questionnaires measuring organizational justice, demographic characteristics, and lifestyle factors. They completed health checkup, which included blood pressure and serum lipid measurements. Multiple logistic regression analyses and trend tests were conducted. Among male employees, multiple logistic regression analyses and trend tests showed significant associations of low procedural justice and low interactional justice with high triglyceride (defined as 150 mg/dL or greater) after adjusting for demographic characteristics and lifestyle factors. Among female employees, trend tests showed significant dose-response relationship between low interactional justice and high LDL cholesterol (defined as 140 mg/dL or greater) while multiple logistic regression analysis showed only marginally significant or insignificant odds ratio of high LDL cholesterol among the low interactional justice group. Neither procedural justice nor interactional justice was associated with blood pressure or HDL cholesterol. Organizational justice may be an important psychosocial factor associated with increased triglyceride at least among Japanese male employees.

Heart Disease and Depression: Is Culture a Factor?

PubMed

Gholizadeh, Leila; Davidson, Patricia M; Heydari, Mehrdad; Salamonson, Yenna

2014-07-01

This article seeks to review and discuss the evidence linking depression, coronary heart disease (CHD), and culture. PsychInfo, CINAHL, PubMed, and Google were searched for pertinent evidence linking depression, culture, and CHD, and retrieved articles were analyzed using thematic content analysis. Identified themes were the followings: depression is a factor in development and prognosis of CHD and affects the capacity to self-manage and adhere to treatment recommendations; culture mediates mental health/illness representations and treatment-seeking behaviors; screening and assessment of depression can be affected by cultural factors; and there is a need for culturally appropriate screening and therapeutic strategies. As depression is a predictor and moderating variable in the genesis and progression of CHD, understanding how factors such as culture affect screening and management of the disease is important to inform the development of culturally and linguistically competent strategies that ensure accurate screening, detection, and treatment of depression in cardiac patients in clinical practice. © The Author(s) 2014.

Subgroup differences in psychosocial factors relating to coronary heart disease in the UK South Asian population.

PubMed

Williams, Emily D; Nazroo, James Y; Kooner, Jaspal S; Steptoe, Andrew

2010-10-01

To explore the differences in psychosocial risk factors related to coronary heart disease (CHD) between South Asian subgroups in the UK. South Asian people suffer significantly higher rates of CHD than other ethnic groups, but vulnerability varies between South Asian subgroups, in terms of both CHD rates and risk profiles. Psychosocial factors may contribute to the excess CHD propensity that is observed; however, subgroup heterogeneity in psychosocial disadvantage has not previously been systematically explored. With a cross-sectional design, 1065 healthy South Asian and 818 white men and women from West London, UK, completed psychosocial questionnaires. Psychosocial profiles were compared between South Asian religious groups and the white sample, using analyses of covariance and post hoc tests. Of the South Asian sample, 50.5% was Sikh, 28.0% was Hindu, and 15.8% was Muslim. Muslim participants were more socioeconomically deprived and experienced higher levels of chronic stress, including financial strain, low social cohesion, and racial discrimination, compared with other South Asian religious groups. In terms of health behaviors, Muslim men smoked more than Sikhs and Hindus, and Muslims also reported lower alcohol consumption and were less physically active than other groups. This study found that Muslims were exposed to more psychosocial and behavioral adversity than Sikhs and Hindus, and highlights the importance of investigating subgroup heterogeneity in South Asian CHD risk. Crown Copyright © 2010. Published by Elsevier Inc. All rights reserved.

Risk factors for ischaemic heart disease in a Cretan rural population: a twelve year follow-up study.

PubMed

Karalis, Ioannis K; Alegakis, Athanasios K; Kafatos, Antonios G; Koutis, Antonios D; Vardas, Panos E; Lionis, Christos D

2007-12-18

Crete has been of great epidemiological interest ever since the publication of the Seven Countries Study. In 1988 a well-defined area of rural Crete was studied, with only scarce signs of coronary heart disease (CHD) despite the unfavorable risk profile. The same population was re-examined twelve years later aiming to describe the trends of CHD risk factors over time and discuss some key points on the natural course of coronary heart disease in a rural population of Crete. We re-examined 200 subjects (80.7% of those still living in the area, 62.4 +/- 17.0 years old). The prevalence of risk factors for CHD was high with 65.9% of men and 65.1% of women being hypertensive, 14.3% of men and 16.5% of women being diabetic, 44% of men being active smokers and more than 40% of both sexes having hyperlipidaemia. Accordingly, 77.5% of the population had a calculated Framingham Risk Score (FRS) > or = 15%, significantly higher compared to baseline (p < 0.001). The overall occurrence rate for CHD events was calculated at 7.1 per 1000 person-years (95% confidence interval: 6.8-7.3). The study confirms the unfavorable risk factor profile of a well defined rural population in Crete. Its actual effect on the observed incidence of coronary events in Cretans remains yet to be defined.

Multiple Interacting Risk Factors: On Methods for Allocating Risk Factor Interactions.

PubMed

Price, Bertram; MacNicoll, Michael

2015-05-01

A persistent problem in health risk analysis where it is known that a disease may occur as a consequence of multiple risk factors with interactions is allocating the total risk of the disease among the individual risk factors. This problem, referred to here as risk apportionment, arises in various venues, including: (i) public health management, (ii) government programs for compensating injured individuals, and (iii) litigation. Two methods have been described in the risk analysis and epidemiology literature for allocating total risk among individual risk factors. One method uses weights to allocate interactions among the individual risk factors. The other method is based on risk accounting axioms and finding an optimal and unique allocation that satisfies the axioms using a procedure borrowed from game theory. Where relative risk or attributable risk is the risk measure, we find that the game-theory-determined allocation is the same as the allocation where risk factor interactions are apportioned to individual risk factors using equal weights. Therefore, the apportionment problem becomes one of selecting a meaningful set of weights for allocating interactions among the individual risk factors. Equal weights and weights proportional to the risks of the individual risk factors are discussed. © 2015 Society for Risk Analysis.

The effect of a smartphone-based coronary heart disease prevention (SBCHDP) programme on awareness and knowledge of CHD, stress, and cardiac-related lifestyle behaviours among the working population in Singapore: a pilot randomised controlled trial.

PubMed

Zhang, Hui; Jiang, Ying; Nguyen, Hoang D; Poo, Danny Chiang Choon; Wang, Wenru

2017-03-14

Coronary heart disease (CHD) is the most prevalent type of cardiac disease among adults worldwide, including those in Singapore. Most of its risk factors, such as smoking, physical inactivity and high blood pressure, are preventable. mHealth has improved in the last decade, showing promising results in chronic disease prevention and health promotion worldwide. Our aim was to develop and examine the effect of a 4-week Smartphone-Based Coronary Heart Disease Prevention (SBCHDP) programme in improving awareness and knowledge of CHD, perceived stress as well as cardiac-related lifestyle behaviours in the working population of Singapore. The smartphone app "Care4Heart" was developed as the main component of the programme. App content was reviewed and validated by a panel of experts, including two cardiologists and two experienced cardiology-trained nurses. A pilot randomised controlled trial was conducted. Eighty working people were recruited and randomised to either the intervention group (n = 40) or the control group (n = 40). The intervention group underwent a 4-week SBCHDP programme, whereas the control group were offered health promotion websites only. The participants' CHD knowledge, perceived stress and behavioural risk factors were measured at baseline and on the 4th week using the Heart Disease Fact Questionnaire-2, Perceived Stress Scale, and Behavioural Risk Factor Surveillance System. After the SBCHDP programme, participants in the intervention group had a better awareness of CHD being the second leading cause of death in Singapore (X 2   = 6.486, p = 0.039), a better overall CHD knowledge level (t = 3.171, p = 0.002), and better behaviour concerning blood cholesterol control (X 2  = 4.54, p = 0.033) than participants in the control group. This pilot study partially confirmed the positive effects of the SBCHDP programme in improving awareness and knowledge of CHD among the working population. Due to the small sample size and

The Chd1 Chromatin Remodeler Shifts Nucleosomal DNA Bidirectionally as a Monomer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qiu, Yupeng; Levendosky, Robert F.; Chakravarthy, Srinivas

Chromatin remodelers catalyze dynamic packaging of the genome by carrying out nucleosome assembly/disassembly, histone exchange, and nucleosome repositioning. Remodeling results in evenly spaced nucleosomes, which requires probing both sides of the nucleosome, yet the way remodelers organize sliding activity to achieve this task is not understood. Here, we show that the monomeric Chd1 remodeler shifts DNA back and forth by dynamically alternating between different segments of the nucleosome. During sliding, Chd1 generates unstable remodeling intermediates that spontaneously relax to a pre-remodeled position. We demonstrate that nucleosome sliding is tightly controlled by two regulatory domains: the DNA-binding domain, which interferes withmore » sliding when its range is limited by a truncated linking segment, and the chromodomains, which play a key role in substrate discrimination. We propose that active interplay of the ATPase motor with the regulatory domains may promote dynamic nucleosome structures uniquely suited for histone exchange and chromatin reorganization during transcription.« less

Interaction between nonsynonymous polymorphisms in PLA2G7 gene and smoking on the risk of coronary heart disease in a Chinese population.

PubMed

Chi, Yunpeng; Shi, Conghong; Zhang, Xiaojiang; Xi, Yang

2018-05-04

To investigate the impact of PLA2G7 polymorphism, and additional their interactions with smoking and drinking on coronary heart disease (CHD) risk based on Chinese population. GMDR model was used to screen the best gene-smoking and gene-drinking interaction combinations. Logistic regression was performed to investigate association between 4 SNPs and CHD, and the interaction effect between rs1805017 and smoking. For CHD patient-control haplotype analyses, the SHEsis online haplotype analysis software ( http://analysis.bio-x.cn/myAnalysis.php ) was employed. CHD risks were higher in carriers of homozygous mutant of rs1805017 and rs1805018 than those with wild-type homozygotes, OR (95% CI) were 1.45 (1.16-1.92) and 1.51 (1.23-1.97), respectively, but the other two SNPs, rs16874954 and rs1051931 were not significant associated with CHD risks. GMDR analysis indicated that there was a significant two-locus model (p = 0.0107) involving rs1805017 and smoking, indicating a potential gene-environment interaction between rs1805017 and smoking. But we did not found any gene-drinking and gene-gene interaction combinations in GMDR models. The haplotype R-I was observed most frequently in two groups, with 47.43 and 54.38% in the case and control group of the population, respectively. The results also indicated that the haplotype containing the rs1805017-H and rs1805018-T alleles were associated with a statistically increased CHD risk, OR (95% CI) 1.43 (1.10-1.86), p = 0.0021. Polymorphisms in rs1805017 and rs1805018, additional interaction between rs1805017 and smoking, and haplotype containing the rs1805017-H and rs1805018-T alleles were associated with increased CHD risk.

Differences in Risk Factors for Coronary Heart Disease among Diabetic and Nondiabetic Individuals from a Population with High Rates of Diabetes: The Strong Heart Study

PubMed Central

Lee, Elisa T.; Peterson, Leif E.; Devereux, Richard B.; Rhoades, Everett R.; Umans, Jason G.; Best, Lyle G.; Howard, William J.; Paranilam, Jaya; Howard, Barbara V.

2012-01-01

Context: Coronary heart disease (CHD) is the leading cause of death in the United States. Objective: This study compares differences in risk factors for CHD in diabetic vs. nondiabetic Strong Heart Study participants. Design: This was an observational study. Setting: The study was conducted at three centers in Arizona, Oklahoma, and North and South Dakota. Participants: Data were obtained from 3563 of 4549 American Indians free of cardiovascular disease at baseline. Intervention(s): CHD events were ascertained during follow-up. Main Outcome Measure: CHD events were classified using standardized criteria. Results: In diabetic and nondiabetic participants, 545 and 216 CHD events, respectively, were ascertained during follow-up (21,194 and 22,990 person-years); age- and sex-adjusted incidence rates of CHD were higher for the diabetic group (27.5 vs. 12.1 per 1,000 person-years). Risk factors for incident CHD common to both groups included older age, male sex, prehypertension or hypertension, and elevated low-density lipoprotein cholesterol. Risk factors specific to the diabetic group were lower high-density lipoprotein cholesterol, current smoking, macroalbuminuria, lower estimated glomerular filtration rate, use of diabetes medication, and longer duration of diabetes. Higher body mass index was a risk factor only for the nondiabetic group. The association of male sex and CHD was greater in those without diabetes than in those with diabetes. Conclusions: In addition to higher incidence rates of CHD events in persons with diabetes compared with those without, the two groups differed in CHD risk factors. These differences must be recognized in estimating CHD risk and managing risk factors. PMID:22802089

Is maternal transmission of coronary heart disease risk stronger than paternal transmission?

PubMed

Kinra, S; Davey Smith, G; Okasha, M; McCarron, P; McEwen, J

2003-08-01

To test whether intergenerational transmission of coronary heart disease (CHD) to offspring is greater from the mother than from the father, the association between parental history of CHD and coronary mortality in male offspring was examined. Prospective cohort study with 43 years of follow up. University of Glasgow. Male students (n = 8402) aged 16-30 years when examined in 1948 to 1968. Fatal CHD. Of the 8402 men studied, 615 (7.3%) reported a history of CHD in at least one of the parents: 479 (5.8%) for fathers only, 124 (1.6%) for mothers only, and a further 12 (0.2%) for both their parents. During follow up, 373 (4.4%) men died of CHD. Parental history of disease was associated with fatal CHD and controlling for personal risk factors such as cigarette smoking, body mass index, systolic blood pressure, and father's social class did not attenuate this relation. The fully adjusted hazard ratios were 1.53 (95% confidence interval (CI) 1.08 to 2.18), 1.19 (95% CI 0.61 to 2.32), and 8.65 (95% CI 2.65 to 28.31) for father only, mother only, and both parents with CHD, respectively, compared with men whose parents did not have CHD. There was some evidence for interaction between parental histories (p = 0.049), with particularly high risk if both parents reported a history of CHD. This study found no differential transmission of CHD. Paternal history of CHD was at least as important as maternal history. Data from other comparable cohorts provide no consistent evidence of differential transmission. Intergenerational transmission of CHD does not appear to have differential effects between mothers and fathers.

Hepatocyte growth factor demonstrates racial heterogeneity as a biomarker for coronary heart disease.

PubMed

Bielinski, Suzette J; Berardi, Cecilia; Decker, Paul A; Larson, Nicholas B; Bell, Elizabeth J; Pankow, James S; Sale, Michele M; Tang, Weihong; Hanson, Naomi Q; Wassel, Christina L; de Andrade, Mariza; Budoff, Matthew J; Polak, Joseph F; Sicotte, Hugues; Tsai, Michael Y

2017-08-01

To determine if hepatocyte growth factor (HGF), a promising biomarker of coronary heart disease (CHD) given its release into circulation in response to endothelial damage, is associated with subclinical and clinical CHD in a racial/ethnic diverse population. HGF was measured in 6738 participants of the Multi-Ethnic Study of Atherosclerosis (MESA). Highest mean HGF values (pg/mL) were observed in Hispanic, followed by African, non-Hispanic white, then Chinese Americans. In all races/ethnicities, HGF levels were associated with older age, higher systolic blood pressure (SBP) and body mass index, lower high-density lipoprotein, diabetes and current smoking. In fully adjusted models, each SD higher HGF was associated with an average increase in coronary artery calcium (CAC) of 55 Agatston units for non-Hispanic whites (p<0.001) and 51 Agatston units for African-Americans (p=0.007) but was not in the other race/ethnic groups (interaction p=0.02). There were 529 incident CHD events, and CHD risk was 41% higher in African (p<0.001), 17% in non-Hispanic white (p=0.026) and Chinese (p=0.36), and 6% in Hispanic Americans (p=0.56) per SD increase in HGF. In a large and diverse population-based cohort, we report that HGF is associated with subclinical and incident CHD. We demonstrate evidence of racial/ethnic heterogeneity within these associations, as the results are most compelling in African-Americans and non-Hispanic white Americans. We provide evidence that HGF is a biomarker of atherosclerotic disease that is independent of traditional risk factors. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The ISW1 and CHD1 ATP-dependent chromatin remodelers compete to set nucleosome spacing in vivo.

PubMed

Ocampo, Josefina; Chereji, Răzvan V; Eriksson, Peter R; Clark, David J

2016-06-02

Adenosine triphosphate-dependent chromatin remodeling machines play a central role in gene regulation by manipulating chromatin structure. Most genes have a nucleosome-depleted region at the promoter and an array of regularly spaced nucleosomes phased relative to the transcription start site. In vitro, the three known yeast nucleosome spacing enzymes (CHD1, ISW1 and ISW2) form arrays with different spacing. We used genome-wide nucleosome sequencing to determine whether these enzymes space nucleosomes differently in vivo We find that CHD1 and ISW1 compete to set the spacing on most genes, such that CHD1 dominates genes with shorter spacing and ISW1 dominates genes with longer spacing. In contrast, ISW2 plays a minor role, limited to transcriptionally inactive genes. Heavily transcribed genes show weak phasing and extreme spacing, either very short or very long, and are depleted of linker histone (H1). Genes with longer spacing are enriched in H1, which directs chromatin folding. We propose that CHD1 directs short spacing, resulting in eviction of H1 and chromatin unfolding, whereas ISW1 directs longer spacing, allowing H1 to bind and condense the chromatin. Thus, competition between the two remodelers to set the spacing on each gene may result in a highly dynamic chromatin structure. Published by Oxford University Press on behalf of Nucleic Acids Research 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

The CAA repeat polymorphism in the ZFHX3 gene is associated with risk of coronary heart disease in a Chinese population.

PubMed

Sun, Shunchang; Zhang, Wenwu; Chen, Xi; Song, Huiwen

2015-04-01

Coronary heart disease (CHD) is a disease resulting from the interaction between genetic variations and environmental factors. Zinc finger homeobox 3 (ZFHX3) is a transcription factor and contains a poly-glutamine tract in a compositionally biased region that is encoded by exon 9, containing a cluster of CAG and CAA triplets followed by the polymorphic CAA repeats: (CAG)2(CAA)2(CAG)3CAACAG(CAA)nGCA. Thus, nine successive glutamine residues precede the poly-glutamine tract, encoded by the polymorphic CAA repeats. The aim of this study was to investigate the association of the CAA repeat polymorphism in exon 9 of the ZFHX3 gene with the risk of CHD in a Chinese population. The CAA repeat polymorphism was determined by polymerase chain reaction followed by DNA sequencing in 321 CHD patients. Genotype frequencies were compared using the non-parametric mood median test. Four alleles of CAG(CAA)10GCA, CAG(CAA)8GCA, CAG(CAA)9GCA, and CAG(CAA)11GCA were found in Chinese CHD patients in exon 9 of the ZFHX3 gene. The CAG(CAA)10GCA was a major allele (95.95%), and the CAG(CAA)8GCA was a minor allele (3.58%). The CAG(CAA)9GCA and CAG(CAA)11GCA were rare alleles (0.31% and 0.16%). The CAG(CAA)10GCA allele encodes a poly-glutamine tract of 19 residues. Importantly, the CHD patients homozygous for the CAG(CAA)10GCA allele had a higher risk of CHD, compared to the heterozygous patients carrying a CAG(CAA)8GCA allele. Moreover, the CAG(CAA)10GCA allele was significantly associated with hypertension, diabetes mellitus, or dyslipidemia (P < 0.05). Thus, the CAA repeat polymorphism in exon 9 of the ZFHX3 gene contributes to the CHD susceptibility in the Chinese population.

Risk factors for clinical coronary heart disease in systemic lupus erythematosus: the lupus and atherosclerosis evaluation of risk (LASER) study.

PubMed

Haque, Sahena; Gordon, Caroline; Isenberg, David; Rahman, Anisur; Lanyon, Peter; Bell, Aubrey; Emery, Paul; McHugh, Neil; Teh, Lee Suan; Scott, David G I; Akil, Mohamed; Naz, Sophia; Andrews, Jacqueline; Griffiths, Bridget; Harris, Helen; Youssef, Hazem; McLaren, John; Toescu, Veronica; Devakumar, Vinodh; Teir, Jamal; Bruce, Ian N

2010-02-01

Accelerated atherosclerosis and premature coronary heart disease (CHD) are recognized complications of systemic lupus erythematosus (SLE), but the exact etiology remains unclear and is likely to be multifactorial. We hypothesized that SLE patients with CHD have increased exposure to traditional risk factors as well as differing disease phenotype and therapy-related factors compared to SLE patients free of CHD. Our aim was to examine risk factors for development of clinical CHD in SLE in the clinical setting. In a UK-wide multicenter retrospective case-control study we recruited 53 SLE patients with verified clinical CHD (myocardial infarction or angina pectoris) and 96 SLE patients without clinical CHD. Controls were recruited from the same center as the case and matched by disease duration. Charts were reviewed up to time of event for cases, or the same "dummy-date" in controls. SLE patients with clinical CHD were older at the time of event [mean (SD) 53 (10) vs 42 (10) yrs; p < 0.001], more likely to be male [11 (20%) vs 3 (7%); p < 0.001], and had more exposure to all classic CHD risk factors compared to SLE patients without clinical CHD. They were also more likely to have been treated with corticosteroids (OR 2.46; 95% CI 1.03, 5.88) and azathioprine (OR 2.33; 95% CI 1.16, 4.67) and to have evidence of damage on the pre-event SLICC damage index (SDI) (OR 2.20; 95% CI 1.09, 4.44). There was no difference between groups with regard to clinical organ involvement or autoantibody profile. Our study highlights the need for clinical vigilance to identify modifiable risk factors in the clinical setting and in particular with male patients. The pattern of organ involvement did not differ in SLE patients with CHD events. However, the higher pre-event SDI, azathioprine exposure, and pattern of damage items (disease-related rather than therapy-related) in cases suggests that a persistent active lupus phenotype contributes to CHD risk. In this regard, corticosteroids and

Preventable coronary heart disease events from control of cardiovascular risk factors in US adults with diabetes (projections from utilizing the UKPDS risk engine).

PubMed

Wong, Nathan D; Patao, Christopher; Malik, Shaista; Iloeje, Uchenna

2014-04-15

Type 2 diabetes mellitus (T2DM) carries significant risks for coronary heart disease (CHD). We examined the potential US population impact of single and composite risk factor control. Among US adults with diagnosed T2DM aged≥30 years in the National Health and Nutrition Examination Survey 2007 to 2012, we assessed CHD events preventable using the United Kingdom Prospective Diabetes Study CHD risk engine. We examined in all those not at goal the impact of statistical control of smoking, glycated hemoglobin, systolic blood pressure, and total and high-density lipoprotein cholesterol, according to the predefined criteria setting risk factors at different levels of control representing (1) "All to Goal," (2) at "Nominal Control," or (3) at "Aggressive Control." Preventable CHD events represented the difference between the number of events estimated from the control of these risk factors versus current levels of the risk factors. Of 606 men (representing 6.2 million) and 603 women (6.3 million) with DM and no previous CHD, 1.3 million men and 0.7 million women would develop a CHD event within 10 years if left uncontrolled. Controlling all risk factors to goal was projected to prevent 35% and 45% of CHD events in men and women, respectively. Nominal risk factor control was projected to prevent 36% and 38% and aggressive control 51% and 61% of CHD events, respectively. In conclusion, a significant proportion of CHD events in adults with T2DM could be prevented from composite control of risk factors often not at goal. Copyright © 2014 Elsevier Inc. All rights reserved.

Coronary Artery Calcium Volume and Density: Potential Interactions and Overall Predictive Value: The Multi-Ethnic Study of Atherosclerosis.

PubMed

Criqui, Michael H; Knox, Jessica B; Denenberg, Julie O; Forbang, Nketi I; McClelland, Robyn L; Novotny, Thomas E; Sandfort, Veit; Waalen, Jill; Blaha, Michael J; Allison, Matthew A

2017-08-01

This study sought to determine the possibility of interactions between coronary artery calcium (CAC) volume or CAC density with each other, and with age, sex, ethnicity, the new atherosclerotic cardiovascular disease (ASCVD) risk score, diabetes status, and renal function by estimated glomerular filtration rate, and, using differing CAC scores, to determine the improvement over the ASCVD risk score in risk prediction and reclassification. In MESA (Multi-Ethnic Study of Atherosclerosis), CAC volume was positively and CAC density inversely associated with cardiovascular disease (CVD) events. A total of 3,398 MESA participants free of clinical CVD but with prevalent CAC at baseline were followed for incident CVD events. During a median 11.0 years of follow-up, there were 390 CVD events, 264 of which were coronary heart disease (CHD). With each SD increase of ln CAC volume (1.62), risk of CHD increased 73% (p < 0.001) and risk of CVD increased 61% (p < 0.001). Conversely, each SD increase of CAC density (0.69) was associated with 28% lower risk of CHD (p < 0.001) and 25% lower risk of CVD (p < 0.001). CAC density was inversely associated with risk at all levels of CAC volume (i.e., no interaction was present). In multivariable Cox models, significant interactions were present for CAC volume with age and ASCVD risk score for both CHD and CVD, and CAC density with ASCVD risk score for CVD. Hazard ratios were generally stronger in the lower risk groups. Receiver-operating characteristic area under the curve and Net Reclassification Index analyses showed better prediction by CAC volume than by Agatston, and the addition of CAC density to CAC volume further significantly improved prediction. The inverse association between CAC density and incident CHD and CVD events is robust across strata of other CVD risk factors. Added to the ASCVD risk score, CAC volume and density provided the strongest prediction for CHD and CVD events, and the highest correct reclassification

[Independent risk factors for severe cardiovascular events in male patients with gout: Results of a 7-year prospective study].

PubMed

Eliseev, M S; Denisov, I S; Markelova, E I; Glukhova, S I; Nasonov, E L

To determine risk factors for severe cardiovascular (CV) events (CVEs) in male patients with crystal-verified gout. 251 male patients with crystal-verified gout were prospectively followed up in 2003 to 2013. The mean follow-up period was 6.9±2.0 years. New severe CVE cases and deaths were recorded. Logistic regression was used to analyze the impact of traditional and other risk factors and allopurinol use on the risk for severe CVEs. 32 patients died during the follow-up period. Severe CVEs were recorded in 58 (23.1%) patients; CVE deaths were notified in 22 (8.8%) patients. The risk of all severe CVEs was high for hypertension, increased serum high-sensitivity C-reactive protein (hs-CRP) level (>5 mg/l), ≥ stage III chronic kidney disease (CKD) (glomerular filtration rate, <60 ml/min/1.73 m2), alcohol intake (>20 g/day), coronary heart disease (CHD), and a family history of premature CHD. The risk of fatal CVEs was highest for elevated serum hs-CRP level, ≥ stage III CKD, a family history of premature CHD, hypercholesterolemia, upper quartile of serum uric acid levels (>552 µmol/l), and regular intake of allopurinol. In addition to the traditional risk factors of CV catastrophes, the presence of chronic inflammation and the impact of high serum uric acid levels may explain the high frequency of CV catastrophes.

Expression, purification, and characterization of recombinant human and murine milk fat globule-epidermal growth factor-factor 8.

PubMed

Castellanos, Erick R; Ciferri, Claudio; Phung, Wilson; Sandoval, Wendy; Matsumoto, Marissa L

2016-08-01

Milk fat globule-epidermal growth factor-factor 8 (MFG-E8), as its name suggests, is a major glycoprotein component of milk fat globules secreted by the mammary epithelium. Although its role in milk fat production is unclear, MFG-E8 has been shown to act as a bridge linking apoptotic cells to phagocytes for removal of these dying cells. MFG-E8 is capable of bridging these two very different cell types via interactions through both its epidermal growth factor (EGF)-like domain(s) and its lectin-type C domains. The EGF-like domain interacts with αVβ3 and αVβ5 integrins on the surface of phagocytes, whereas the C domains bind phosphatidylserine found on the surface of apoptotic cells. In an attempt to purify full-length, recombinant MFG-E8 expressed in either insect cells or CHO cells, we find that it is highly aggregated. Systematic truncation of the domain architecture of MFG-E8 indicates that the C domains are mainly responsible for the aggregation propensity. Addition of Triton X-100 to the conditioned cell culture media allowed partial recovery of non-aggregated, full-length MFG-E8. A more comprehensive detergent screen identified CHAPS as a stabilizer of MFG-E8 and allowed purification of a significant portion of non-aggregated, full-length protein. The CHAPS-stabilized recombinant MFG-E8 retained its natural ability to bind both αVβ3 and αVβ5 integrins and phosphatidylserine suggesting that it is properly folded and active. Herein we describe an efficient purification method for production of non-aggregated, full-length MFG-E8. Copyright © 2016 Elsevier Inc. All rights reserved.

The development of a consensus-based nutritional pathway for infants with CHD before surgery using a modified Delphi process.

PubMed

Marino, Luise V; Johnson, Mark J; Hall, Nigel J; Davies, Natalie J; Kidd, Catherine S; Daniels, M Lowri; Robinson, Julia E; Richens, Trevor; Bharucha, Tara; Darlington, Anne-Sophie E

2018-04-29

IntroductionDespite improvements in the medical and surgical management of infants with CHD, growth failure before surgery in many infants continues to be a significant concern. A nutritional pathway was developed, the aim of which was to provide a structured approach to nutritional care for infants with CHD awaiting surgery.Materials and methodsThe modified Delphi process was development of a nutritional pathway; initial stakeholder meeting to finalise draft guidelines and develop questions; round 1 anonymous online survey; round 2 online survey; regional cardiac conference and pathway revision; and final expert meeting and pathway finalisation. Paediatric Dietitians from all 11 of the paediatric cardiology surgical centres in the United Kingdom contributed to the guideline development. In all, 33% of participants had 9 or more years of experience working with infants with CHD. By the end of rounds 1 and 2, 76 and 96% of participants, respectively, were in agreement with the statements. Three statements where consensus was not achieved by the end of round 2 were discussed and agreed at the final expert group meeting. Nutrition guidelines were developed for infants with CHD awaiting surgery, using a modified Delphi process, incorporating the best available evidence and expert opinion with regard to nutritional support in this group.

Associations of coagulation factors IX and XI levels with incident coronary heart disease and ischemic stroke: the REGARDS study.

PubMed

Olson, N C; Cushman, M; Judd, S E; Kissela, B M; Safford, M M; Howard, G; Zakai, N A

2017-06-01

Essentials Coagulation factors (F) IX and XI have been implicated in cardiovascular disease (CVD) risk. We studied associations of FIX and FXI with incident coronary heart disease (CHD) and stroke. Higher FIX antigen was associated with incident CHD risk in blacks but not whites. Higher levels of FIX antigen may be a CHD risk factor among blacks. Background Recent studies have suggested the importance of coagulation factor IX and FXI in cardiovascular disease (CVD) risk. Objectives To determine whether basal levels of FIX or FXI antigen were associated with the risk of incident coronary heart disease (CHD) or ischemic stroke. Patients/Methods The REasons for Geographic And Racial Differences in Stroke (REGARDS) study recruited 30 239 participants across the contiguous USA between 2003 and 2007. In a case-cohort study within REGARDS, FIX and FXI antigen were measured in participants with incident CHD (n = 609), in participants with incident ischemic stroke (n = 538), and in a cohort random sample (n = 1038). Hazard ratios (HRs) for CHD and ischemic stroke risk were estimated with Cox models per standard deviation higher FIX or FXI level, adjusted for CVD risk factors. Results In models adjusting for CHD risk factors, higher FIX levels were associated with incident CHD risk (HR 1.19; 95% confidence interval [CI] 1.01-1.40) and the relationship of higher FXI levels was slightly weaker (HR 1.15; 95% CI 0.97-1.36). When stratified by race, the HR of FIX was higher in blacks (HR 1.39; 95% CI 1.10-1.75) than in whites (HR 1.06; 95% CI 0.86-1.31). After adjustment for stroke risk factors, there was no longer an association of FIX levels with ischemic stroke, whereas the association of FXI levels with ischemic stroke was slightly attenuated. Conclusions Higher FIX antigen levels were associated with incident CHD in blacks but not in whites. FIX levels may increase CHD risk among blacks. © 2017 International Society on Thrombosis and Haemostasis.

Characteristics of metabolic and lifestyle risk factors in young Japanese patients with coronary heart disease: a comparison with older patients.

PubMed

Azegami, Masako; Hongo, Minoru; Yanagisawa, Setsuko; Yamazaki, Akie; Sakaguchi, Kesami; Yazaki, Yoshikazu; Imamura, Hiroshi

2006-05-01

Coronary heart disease (CHD) is recognized as a lifestyle-related disease and is the second leading cause of death in Japan. However, the cardiac risk factor profile of young patients with CHD has not been clarified in suburban areas of Japan. Our study aimed to determine metabolic and lifestyle risk factors in young patients and compare them with older patients living in suburban areas of Nagano Prefecture. A multicenter study was conducted in 86 young (aged less than 40 years) and 91 older (aged 50 years and over) patients diagnosed with CHD from 1992 to 2002. There was a strong association between obesity and the occurrence of CHD events in young patients (odds ratio = 3.61, P = 0.006). Lifestyle in the young patients was characterized by a lack of physical activity and regular physical activity was found to decrease the risk of the CHD events in these patients (odds ratio = 0.31, P = 0.030). In older patients, hypertension was identified as an independent risk factor for CHD events. The results of the present study have demonstrated that obesity and a lack of regular physical exercise are independent risk factors for CHD events in younger patients. Thus, the data may be useful for the effective screening of high-risk individuals and the development of educational programs for the prevention of CHD, especially in younger Japanese.

Large-Scale Description of Interacting One-Dimensional Bose Gases: Generalized Hydrodynamics Supersedes Conventional Hydrodynamics

NASA Astrophysics Data System (ADS)

Doyon, Benjamin; Dubail, Jérôme; Konik, Robert; Yoshimura, Takato

2017-11-01

The theory of generalized hydrodynamics (GHD) was recently developed as a new tool for the study of inhomogeneous time evolution in many-body interacting systems with infinitely many conserved charges. In this Letter, we show that it supersedes the widely used conventional hydrodynamics (CHD) of one-dimensional Bose gases. We illustrate this by studying "nonlinear sound waves" emanating from initial density accumulations in the Lieb-Liniger model. We show that, at zero temperature and in the absence of shocks, GHD reduces to CHD, thus for the first time justifying its use from purely hydrodynamic principles. We show that sharp profiles, which appear in finite times in CHD, immediately dissolve into a higher hierarchy of reductions of GHD, with no sustained shock. CHD thereon fails to capture the correct hydrodynamics. We establish the correct hydrodynamic equations, which are finite-dimensional reductions of GHD characterized by multiple, disjoint Fermi seas. We further verify that at nonzero temperature, CHD fails at all nonzero times. Finally, we numerically confirm the emergence of hydrodynamics at zero temperature by comparing its predictions with a full quantum simulation performed using the NRG-TSA-abacus algorithm. The analysis is performed in the full interaction range, and is not restricted to either weak- or strong-repulsion regimes.

Routine intra-operative trans-oesophageal echocardiography yields better outcomes in surgical repair of CHD.

PubMed

Madriago, Erin J; Punn, Rajesh; Geeter, Natalie; Silverman, Norman H

2016-02-01

Trans-oesophageal echocardiographic imaging is valuable in the pre- and post-operative evaluation of children and adults with CHD; however, the frequency by which trans-oesophageal echocardiography guides the intra-operative course of patients is unknown. We retrospectively reviewed 1748 intra-operative trans-oesophageal echocardiograms performed between 1 October, 2005 and 31 December, 2010, and found 99 cases (5.7%) that required return to bypass, based in part upon the intra-operative echocardiographic findings. The diagnoses most commonly requiring further repair and subsequent imaging were mitral valve disease (20.9%), tricuspid valve disease (16.0%), atrioventricular canal defects (12.0%), and pulmonary valve disease (14.1%). The vast majority of those requiring immediate return to bypass benefited by avoiding subsequent operations and longer lengths of hospital stay. A total of 14 patients (0.8%) who received routine imaging required further surgical repair within 1 week, usually due to disease that developed over ensuing days. Patients who had second post-operative trans-oesophageal echocardiograms in the operating room rarely required re-operations, confirming the benefit of routine intra-operative imaging. This study represents a large single institutional review of intra-operative trans-oesophageal echocardiography, and confirms its applicability in the surgical repair of patients with CHD. Routine imaging accurately identifies patients requiring further intervention, does not confer additional risk of mortality or prolonged length of hospital stay, and prevents subsequent operations and associated sequelae in a substantial subset of patients. This study demonstrates the utility of echocardiography in intra-operative monitoring of surgical repair and highlights patients who are most likely to require return to bypass, as well as the co-morbidities of such manipulations.

Thermodynamic analysis of the interaction of factor VIII with von Willebrand factor.

PubMed

Dimitrov, Jordan D; Christophe, Olivier D; Kang, Jonghoon; Repessé, Yohann; Delignat, Sandrine; Kaveri, Srinivas V; Lacroix-Desmazes, Sébastien

2012-05-22

Factor VIII (FVIII) is a glycoprotein that plays an important role in the intrinsic pathway of coagulation. In circulation, FVIII is protected upon binding to von Willebrand factor (VWF), a chaperone molecule that regulates its half-life, distribution, and activity. Despite the biological significance of this interaction, its molecular mechanisms are not fully characterized. We determined the equilibrium and activation thermodynamics of the interaction between FVIII and VWF. The equilibrium affinity determined by surface plasmon resonance was temperature-dependent with a value of 0.8 nM at 35 °C. The FVIII-VWF interaction was characterized by very fast association (8.56 × 10(6) M(-1) s(-1)) and fast dissociation (6.89 × 10(-3) s(-1)) rates. Both the equilibrium association and association rate constants, but not the dissociation rate constant, were dependent on temperature. Binding of FVIII to VWF was characterized by favorable changes in the equilibrium and activation entropy (TΔS° = 89.4 kJ/mol, and -TΔS(++) = -8.9 kJ/mol) and unfavorable changes in the equilibrium and activation enthalpy (ΔH° = 39.1 kJ/mol, and ΔH(++) = 44.1 kJ/mol), yielding a negative change in the equilibrium Gibbs energy. Binding of FVIII to VWF in solid-phase assays demonstrated a high sensitivity to acidic pH and a sensitivity to ionic strength. Our data indicate that the interaction between FVIII and VWF is mediated mainly by electrostatic forces, and that it is not accompanied by entropic constraints, suggesting the absence of conformational adaptation but the presence of rigid "pre-optimized" binding surfaces.

[The role of remodeling complexes CHD1 and ISWI in spontaneous and UV-induced mutagenesis control in yeast Saccharomyces cerevisiae].

PubMed

Evstiukhina, T A; Alekseeva, E A; Fedorov, D V; Peshekhonov, V T; Korolev, V G

2017-02-01

Chromatin remodulators are special multiprotein machines capable of transforming the structure, constitution, and positioning of nucleosomes on DNA. Biochemical activities of remodeling complexes CHD1 and ISWI from the SWI2/SNF2 family are well established. They ensure correct positioning of nucleosomes along the genome, which is probably critical for genome stability, in particular, after action of polymerases, repair enzymes, and transcription. In this paper, we show that single mutations in genes ISW1, ISW2, and CHD1 weakly affect repair and mutagenic processes in yeast cells. At the same time, there are differences in the effect of these mutations on spontaneous mutation levels, which indicates certain specificity of action of protein complexes ISW1, ISW2, and CHD1 on expression of different genes that control repair and mutation processes in yeast.

Short-term exposure to ambient air pollution and coronary heart disease mortality in 8 Chinese cities.

PubMed

Li, Huichu; Chen, Renjie; Meng, Xia; Zhao, Zhuohui; Cai, Jing; Wang, Cuicui; Yang, Changyuan; Kan, Haidong

2015-10-15

Coronary heart disease (CHD) accounted for a large fraction of death globally. The association between air pollution and CHD has been reported, but evidence from highly-polluted regions was scarce. We aimed to estimate the acute effects of outdoor air pollution on daily CHD mortality in China. We collected daily CHD deaths in 8 large Chinese cities from 1996 to 2008. We firstly obtained the city-specific effect estimates of air pollution using generalized additive models with quasi-Poisson regression, controlling for time trends, meteorological indicators and day of the week. The random-effect model in meta-analysis was used to pool the exposure-response relationships. We identified a total of 0.13 million CHD deaths. On average, an increase of 10μg/m(3) in 2-day moving average concentrations of particulate matter≤10μm in aerodynamic diameter (PM10), sulfur dioxide (SO2) and nitrogen dioxide (NO2) was significantly associated with increases of 0.36% [95% confidence intervals (CIs): 0.12%, 0.61%], 0.86% (95% CIs: 0.30%,1.41%) and 1.30% (95% CIs: 0.45%, 2.14%) in daily CHD mortality over the 8 Chinese cities, respectively. The pooled exposure-response curves were almost linear and no apparent thresholds were identified. The effects were more pronounced in cities with lower levels of air pollution. The effects of PM10 and NO2 were more robust than SO2. Our findings contributed to the very limited evidence regarding the hazardous effects of ambient air pollution on CHD mortality in highly-polluted regions such as China. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Regional body composition changes exhibit opposing effects on coronary heart disease risk factors.

PubMed

Okura, Tomohiro; Nakata, Yoshio; Yamabuki, Keisuke; Tanaka, Kiyoji

2004-05-01

We investigated how regional body composition measured by dual-energy X-ray absorptiometry (DXA) is associated with risk factors for coronary heart disease (CHD) during weight reduction in obese women. Data were gathered from 128 overweight and obese women, aged 34 to 66 years, during a 14-week intervention study with diet and exercise. Regional (arms, legs, and trunk) fat tissue (FT) and lean soft tissue (LST) were measured by DXA. The FT change in legs correlated negatively with changes in diastolic blood pressure, low-density lipoprotein cholesterol (LDL-C), fasting plasma glucose (FPG), and the number of CHD risk factors per subject (r=-0.17, P<0.05 to -0.26, P<0.01) in response to weight reduction, whereas truncal FT change had positive correlations with changes in triglycerides, LDL-C, FPG, and the number of CHD risk factors per subject (r=0.17, P<0.05 to 0.25, P<0.01). LST change in legs correlated negatively with changes in systolic blood pressure, FPG, and the number of risk factors (r=-0.20 to -0.21, P<0.05). Regional body composition information is important for evaluating improvement of CHD risk factors during weight-reduction treatment for obesity; differential FTs had opposing effects on CHD risk factors during weight reduction in obese women.

Born-Oppenheimer and Renner-Teller Quantum Dynamics of CH(X(2)Π) + D((2)S) Reactions on Three CHD Potential Surfaces.

PubMed

Gamallo, Pablo; Akpinar, Sinan; Defazio, Paolo; Petrongolo, Carlo

2015-11-19

The quantum dynamics of three CH(X(2)Π) + D((2)S) reactions is studied by means of the coupled-channel time-dependent real-wavepacket (WP) and flux methods at collision energy Ecol ≤ 0.6 eV and on three potential energy surfaces (PESs): the Born-Oppenheimer (BO) ground PES X̃(3)A″ and the excited ones ã(1)A' and b̃(1)A″, coupled by nonadiabatic (NA) Renner-Teller (RT) effects. This three-state model is suitable for obtaining initial-state-resolved observables, is based on a complete analysis of the correlation diagram of the lowest electronic states of the CHD intermediate and of their NA interactions, and neglects the smaller coupling effects due to the asymptotic electronic angular momenta that become important in state-to-state dynamics. WPs are propagated on each PES at total angular momentum values J ≤ 70, with CH in the two lowest vibrational states v0 and in the ground rotational state j0 = 1. Reaction probabilities are obtained for three possible final products (f): (dP) CH decay and C((3)P) + HD(X(1)Σ(+)) formation that occurs on the uncoupled ground PES, (dD) CH decay and C((1)D) + HD(X(1)Σ(+)) formation that depends on the RT-coupled singlet species, and (ex) exchange to CD(X(2)Π) + H((2)S) available adiabatically from the X̃(3)A″ PES and nonadiabatically from ã(1)A' and b̃(1)A″. Observable cross sections σf,v0j0 and rate constants kf,v0j0 in the temperature range T = 100-2000 K are obtained for (dP), (dD), and (ex) channels. Comparing BO with RT probabilities, we show that NA effects are important at high J values for the (ex) channel at v0 = 1. Real time mechanisms on the three PESs show that RT couplings are opened after some time and clearly point out the formation of the product channels. Both cross sections and rate constants present the same sequence, for example σex,11 > σdP,01 ∼ σex,01 > σdP,11 ≫ σdD,11 ≫ σdD,01, and the CH vibrational excitation enhances the total removal CH+D reactivity by a factor of ∼1

Multiple risk factor interventions for primary prevention of coronary heart disease

PubMed Central

Ebrahim, Shah; Beswick, Andrew; Burke, Margaret; Smith, George Davey

2014-01-01

Background Primary prevention programmes in many countries attempt to reduce mortality and morbidity due to coronary heart disease (CHD) through risk factor modification. It is widely believed that multiple risk factor intervention using counselling and educational methods is efficacious and cost-effective and should be expanded. Recent trials examining risk factor changes have cast considerable doubt on the effectiveness of these multiple risk factor interventions. Objectives To assess the effects of multiple risk factor intervention for reducing cardiovascular risk factors, total mortality, and mortality from CHD among adults without clinical evidence of established cardiovascular disease. Search strategy MEDLINE was searched for the original review to 1995. This was updated by searching the Cochrane Central Register of Controlled Trials on The Cochrane Library Issue 3 2001, MEDLINE(2000 to September 2001) and EMBASE (1998 to September 2001). Selection criteria Intervention studies using counselling or education to modify more than one cardiovascular risk factor in adults from general populations, occupational groups, or high risk groups. Trials of less than 6 months duration were excluded. Data collection and analysis Data were extracted by two reviewers independently. Investigators were contacted to obtain missing information. Main results A total of 39 trials were found of which ten reported clinical event data. In the ten trials with clinical event end-points, the pooled odds ratios for total and CHD mortality were 0.96 (95% confidence intervals (CI) 0.92 to 1.01) and 0.96 (95% CI 0.89 to 1.04) respectively. Net changes in systolic and diastolic blood pressure, and blood cholesterol were (weighted mean differences) −3.6 mmHg (95% CI −3.9 to −3.3 mmHg), −2.8 mmHg (95% CI −2.9 to −2.6 mmHg) and −0.07 mMol/l (95% CI −0.8 to −0.06 mMol/l) respectively. Odds of reduction in smoking prevalence was 20% (95% CI 8% to 31%). Statistical heterogeneity

Cardiovascular risk goes up as your mood goes down: Interaction of depression and socioeconomic status in determination of cardiovascular risk in the CONSTANCES cohort.

PubMed

Wiernik, Emmanuel; Meneton, Pierre; Empana, Jean-Philippe; Siemiatycki, Jack; Hoertel, Nicolas; Vulser, Hélène; Nabi, Hermann; Limosin, Frédéric; Czernichow, Sébastien; Goldberg, Marcel; Ozguler, Anna; Zins, Marie; Lemogne, Cédric

2018-07-01

Recent evidence suggests that the association of psychological variables with the risk of coronary heart disease (CHD) might depend upon socioeconomic status (SES). However, it is unclear whether the association between depressive symptoms and CHD risk might differ according to three SES indicators (education, occupational status and household monthly income). Among 34,836 working participants of the French CONSTANCES cohort (16,221 men, mean age [SD]: 44.0 [10.4] years) without history of cardiovascular disease, depressive symptoms were assessed with the Center of Epidemiologic Studies Depression scale (CES-D). The Framingham risk equation calibrated to the French population estimated the participant's 10-year risk of CHD. Associations between depressive symptoms and CHD risk were estimated using linear regression models in SES strata. The estimated 10-year risk of CHD was 16.9% in men and 1.8% in women. In men, the increased CHD risk in those with (versus without) depressive symptoms was more pronounced as occupational status decreased, being 0.65% (-0.57; 1.88), 1.58% (0.50; 2.66) and 3.19% (1.30; 5.07) higher in individuals of high, medium and low occupational status, respectively (p for interaction: 0.01). In contrast, effect modification by education or household income was less evident, despite similar trends. In women, no effect modification was found whatever the SES indicator. Depressive symptoms and 10-year estimated CHD risk were more tightly linked in individuals of lower SES, at least in men. Occupational status was the SES indicator that displays the most obvious effect modification on this association. Copyright © 2018 Elsevier B.V. All rights reserved.

Independent and combined effects of environmental factors and miR-126, miR-143, and miR-145 on the risk of coronary heart disease.

PubMed

Lin, Da-Cen; Lin, Jia-Bing; Chen, Zhou; Chen, Rong; Wan, Chun-Yu; Lin, Shao-Wei; Ruan, Qi-Shuang; Li, Huang-Yuan; Wu, Si-Ying

2017-11-01

To evaluate the effects of environmental factors and microRNAs (miRNAs) (miR-126, miR-143, and miR-145) on the risk of coronary heart disease (CHD). A frequency-matched case-control study (450 patients, 450 controls) was conducted from April 2014 to December 2016 in Fuzhou City, China. Environmental factors were investigated using a self-administered questionnaire, and the expression levels of miR-126, miR-143, and miR-145 were determined by quantitative real-time Polymerase Chain Reaction (PCR) in peripheral blood mononuclear cells. Unconditional logistic regression models were used for statistical evaluation. Alcohol consumption, high-salt diets, high-intensity work, and lack of physical activity were significantly associated with increased CHD risk, whereas light diet was significantly associated with decreased risk. MiR-126, miR-143, and miR-145 were highly expressed in the CHD group compared with the control group. After adjustment for other environmental factors, unconditional logistic regression results revealed that miR-126, miR-143, and depression were the independent risk factors of CHD, and light diet was the independent protective factor of CHD. Our data suggest that a family history of CHD, anxiety, and alcohol consumption was significantly associated with increased CHD risk, whereas light diet was significantly associated with decreased risk. Furthermore, miR-126 and miR-143 in combination with several risk factors, could play a joint role in the development of CHD. Therefore, it is necessary to manage patients with CHD in all directions and multiple level.

Knowledge of Coronary Heart Disease Risk Factors among a Community Sample in Oman: Pilot study.

PubMed

Ammouri, Ali A; Tailakh, Ayman; Isac, Chandrani; Kamanyire, Joy K; Muliira, Joshua; Balachandran, Shreedevi

2016-05-01

The aim of this study was to assess the knowledge of Omani adults regarding conventional coronary heart disease (CHD) risk factors and to identify demographic variables associated with these knowledge levels. This descriptive cross-sectional pilot study was carried out among a convenience sample of 130 adults attending a health awareness fair held in a local shopping mall in Muscat, Oman, in November 2012. A modified version of the Heart Disease Facts Questionnaire in both English and Arabic was used to assess knowledge of CHD risk factors. Scores were calculated by summing the correct answers for each item (range: 0-21). Inadequate knowledge was indicated by a mean score of <70%. Descriptive and multivariate logistic regression analyses were performed to establish the participants' knowledge levels and identify associated demographic variables. A total of 114 subjects participated in the study (response rate: 87.7%). Of these, 69 participants (60.5%) had inadequate mean CHD knowledge scores. Knowledge of CHD risk factors was significantly associated with body mass index (odds ratio [OR] = 0.739; P = 0.023), marital status (OR = 0.057; P = 0.036) and education level (OR = 9.243; P = 0.006). Low knowledge levels of CHD risk factors were observed among the studied community sample in Oman; this is likely to limit the participants' ability to engage in preventative practices. These findings support the need for education programmes to enhance awareness of risk factors and prevention of CHD in Oman.

Obesity is associated with fatal coronary heart disease independently of traditional risk factors and deprivation.

PubMed

Logue, Jennifer; Murray, Heather M; Welsh, Paul; Shepherd, James; Packard, Chris; Macfarlane, Peter; Cobbe, Stuart; Ford, Ian; Sattar, Naveed

2011-04-01

The effect of body mass index (BMI) on coronary heart disease (CHD) risk is attenuated when mediators of this risk (such as diabetes, hypertension and hyperlipidaemia) are accounted for. However, there is now evidence of a differential effect of risk factors on fatal and non-fatal CHD events, with markers of inflammation more strongly associated with fatal than non-fatal events. To describe the association with BMI separately for both fatal and non-fatal CHD risk after accounting for classical risk factors and to assess any independent effects of obesity on CHD risk. In the West of Scotland Coronary Prevention Study BMI in 6082 men (mean age 55 years) with hypercholesterolaemia, but no history of diabetes or CVD, was related to the risk of fatal and non-fatal CHD events. After excluding participants with any event in the first 2 years, 1027 non-fatal and 214 fatal CHD events occurred during 14.7 years of follow-up. A minimally adjusted model (age, sex, statin treatment) and a maximally adjusted model (including known CVD risk factors and deprivation) were compared, with BMI 25-27.4 kg/m² as referent. The risk of non-fatal events was similar across all BMI categories in both models. The risk of fatal CHD events was increased in men with BMI 30.0-39.9 kg/m² in both the minimally adjusted model (HR = 1.75 (95% CI 1.12 to 2.74)) and the maximally adjusted model (HR = 1.60 (95% CI 1.02 to 2.53)). These hypothesis generating data suggest that obesity is associated with fatal, but not non-fatal, CHD after accounting for known cardiovascular risk factors and deprivation. Clinical trial registration WOSCOPS was carried out and completed before the requirement for clinical trial registration.

Turkish assessment of SURF (SUrvey of Risk Factor Management) study: Control rates of cardiovascular risk factors derived from databases of 15 different levels of health centers in Turkey.

PubMed

Tokgözoğlu, Lale; Oğuz, Aytekin; Balcı, Mustafa Kemal; Temizhan, Ahmet; Güldal Altunoğlu, Esma; Bektaş, Osman; Aslan, Güler; Iyigün, Özgün; Kara, Ahmet; Tanrıverdi Pınar, Handan; Yavuz, Saffet; Tekin, Murat; Ercan, Saffet; Çelik, Selda; Sezgin Meriçliler, Özlem; Bozkurt Çakır, İrem

2017-07-01

The aim of this study was to evaluate the adherence to recommendations for secondary prevention and the achievement of treatment targets for the control of risk factors in patients with established coronary heart disease (CHD) who were followed-up at various healthcare facilities in Turkey. According to the protocol of the international Survey of Risk Factor Management study, questionnaire forms were completed and demographic, anthropometric, and laboratory data of CHD patients who were followed-up at a total of 15 selected primary, secondary, and tertiary healthcare centers were recorded. Among a total of 724 CHD patients (69.8% male; mean age: 63.3±10.7 years) included in the study, 18.4% were current smokers, only 19.1% had normal body mass index, and 22.1% had waist circumference below the limit of abdominal obesity. Physical activity was insufficient in 53% of the patients, 47.3% had low high-density lipoprotein cholesterol value, 46% had triglyceride level above 150 mg/dL, and 67% had glycated hemoglobin value of 6.5% or above. Of all the patients, 88.1% were using antiplatelet drugs, 71.4% were using beta-blockers, 55.7% were using statins, and 41.9% were using angiotensin-converting enzyme inhibitors/angiotensin receptor blockers. Blood pressure was under control in 56.7% of the hypertensive patients using antihypertensive drugs, and the proportion of diabetic patients who reached glycemic control targets using antidiabetic drugs was 35.9%. Low-density lipoprotein cholesterol was below 70 mg/dL in 12.2% of the patients using statins. According to the data obtained, among Turkish CHD patients, the control rate of cardiovascular risk factors is low, and implementation of the recommendations regarding lifestyle modification and medication use for secondary prevention in the current guidelines are insufficient.

Trends in risk factors for coronary heart disease in the Netherlands.

PubMed

Koopman, C; Vaartjes, I; Blokstra, A; Verschuren, W M M; Visser, M; Deeg, D J H; Bots, M L; van Dis, I

2016-08-19

Favourable trends in risk factor levels in the general population may partly explain the decline in coronary heart disease (CHD) morbidity and mortality. Our aim was to present long-term national trends in established risk factors for CHD. Data were obtained from five data sources including several large scale population based surveys, cohort studies and general practitioner registers between 1988 and 2012. We applied linear regression models to age-standardized time trends to test for statistical significant trends. Analyses were stratified by sex and age (younger <65 and older ≥65 years adults). The results demonstrated favourable trends in smoking (except in older women) and physical activity (except in older men). Unfavourable trends were found for body mass index (BMI) and diabetes mellitus prevalence. Although systolic blood pressure (SBP) and total cholesterol trends were favourable for older persons, SBP and total cholesterol remained stable in younger persons. Four out of six risk factors for CHD showed a favourable or stable trend. The rise in diabetes mellitus and BMI is worrying with respect to CHD morbidity and mortality.

Coronary Heart Disease Risk Factors in Young People of Differing Socio-Economic Status

ERIC Educational Resources Information Center

Thomas, Non-Eleri; Cooper, Stephen-Mark; Williams, Simon P.; Baker, Julien S.; Davies, Bruce

2005-01-01

This study determined the prevalence of coronary heart disease (CHD) risk factors in young people of differing socio-economic status (SES). A cohort of 100 boys and 108 girls, aged 12.9, SD 0.3 years drawn of differing SES were assessed for CHD risk factors. Measurements included indices of obesity, blood pressure, aerobic fitness, diet, blood…

Social and Behavioral Risk Marker Clustering Associated with Biological Risk Factors for Coronary Heart Disease: NHANES 2001–2004

PubMed Central

Everage, Nicholas J.; Linkletter, Crystal D.; Gjelsvik, Annie; McGarvey, Stephen T.; Loucks, Eric B.

2014-01-01

Background. Social and behavioral risk markers (e.g., physical activity, diet, smoking, and socioeconomic position) cluster; however, little is known whether clustering is associated with coronary heart disease (CHD) risk. Objectives were to determine if sociobehavioral clustering is associated with biological CHD risk factors (total cholesterol, HDL cholesterol, systolic blood pressure, body mass index, waist circumference, and diabetes) and whether associations are independent of individual clustering components. Methods. Participants included 4,305 males and 4,673 females aged ≥20 years from NHANES 2001–2004. Sociobehavioral Risk Marker Index (SRI) included a summary score of physical activity, fruit/vegetable consumption, smoking, and educational attainment. Regression analyses evaluated associations of SRI with aforementioned biological CHD risk factors. Receiver operator curve analyses assessed independent predictive ability of SRI. Results. Healthful clustering (SRI = 0) was associated with improved biological CHD risk factor levels in 5 of 6 risk factors in females and 2 of 6 risk factors in males. Adding SRI to models containing age, race, and individual SRI components did not improve C-statistics. Conclusions. Findings suggest that healthful sociobehavioral risk marker clustering is associated with favorable CHD risk factor levels, particularly in females. These findings should inform social ecological interventions that consider health impacts of addressing social and behavioral risk factors. PMID:24719858

Age-dependent interaction of apolipoprotein E gene with eastern birthplace in Finland affects severity of coronary atherosclerosis and risk of fatal myocardial infarction--Helsinki Sudden Death Study.

PubMed

Tyynelä, Petri; Goebeler, Sirkka; Ilveskoski, Erkki; Mikkelsson, Jussi; Perola, Markus; Lehtimäki, Terho; Karhunen, Pekka J

2013-05-01

Mortality from coronary heart disease (CHD) has been constantly higher in eastern late settlement regions compared to western early settlements in Finland, unrelated to classical risk factors. In line with this, eastern birthplace was an age-dependent predictor of severe coronary atherosclerosis and pre-hospital sudden coronary death among male residents of Helsinki. We investigated a possible interaction of apolipoprotein E (APOE) gene with birthplace on the risk of myocardial infarction (MI) and coronary atherosclerosis. APOE genotypes were analyzed in the Helsinki Sudden Death Study series comprising out-of-hospital deaths among males aged 33-70 years (n = 577), who were born in high (east, n = 273) or low (west, n = 304) CHD mortality area. Eastern-born men ≤ 55 years carried 30% more often (P = 0.017) and older men 40% less often (P = 0.022) the APOE ϵ4 allele compared to western-born men (P = 0.003 for birthplace-by-age interaction). In multivariate analysis, the ϵ4 allele associated with the risk of out-of-hospital MI (odds ratio 2.58; 95% CI 1.20-5.55; P = 0.016) only in eastern-born men and with advanced atherosclerosis in both regions of origin, respectively. Birthplace-bound risk of CHD was age-dependently modified by APOE ϵ4 allele, suggesting genetic differences in CHD susceptibility between early and late settlement regions in Finland and providing one explanation for the eastern high mortality.

Trends in Cardiovascular Risk Factor Levels in the Minnesota Heart Survey (1980–2002) as Compared With the National Health and Nutrition Examination Survey (1976–2002): A Partial Explanation for Minnesota's Low Cardiovascular Disease Mortality?

PubMed Central

Wang, Huifen; Steffen, Lyn M.; Jacobs, David R.; Zhou, Xia; Blackburn, Henry; Berger, Alan K.; Filion, Kristian B.; Luepker, Russell V.

2011-01-01

The authors compared trends in and levels of coronary heart disease (CHD) risk factors between the Minneapolis-St. Paul, Minnesota, metropolitan area (Twin Cities) and the entire US population to help explain the ongoing decline in US CHD mortality rates. The study populations for risk factors were adults aged 25–74 years enrolled in 2 population-based surveillance studies: the Minnesota Heart Survey (MHS) in 1980–1982, 1985–1987, 1990–1992, 1995–1997, and 2000–2002 and the National Health and Nutrition Examination Survey (NHANES) in 1976–1980, 1988–1994, 1999–2000, and 2001–2002. The authors found a continuous decline in CHD mortality rates in the Twin Cities and nationally between 1980 and 2000. Similar decreasing rates of change in risk factors across survey years, parallel to the CHD mortality rate decline, were observed in MHS and in NHANES. Adults in MHS had generally lower levels of CHD risk factors than NHANES adults, consistent with the CHD mortality rate difference. Approximately 47% of women and 44% of men in MHS had no elevated CHD risk factors, including smoking, hypertension, high cholesterol, and obesity, versus 36% of women and 34% of men in NHANES. The better CHD risk factor profile in the Twin Cities may partly explain the lower CHD death rate there. PMID:21273396

Accurate diagnosis of CHD by Paediatricians with Expertise in Cardiology.

PubMed

Jacob, Hannah C; Massey, Hannah; Yates, Robert W M; Kelsall, A Wilfred

2017-08-01

Introduction Paediatricians with Expertise in Cardiology assess children with a full history, examination, and often perform an echocardiogram. A minority are then referred to an outreach clinic run jointly with a visiting paediatric cardiologist. The accuracy of the echocardiography diagnosis made by the Paediatrician with Expertise in Cardiology is unknown. Materials and methods We conducted a retrospective review of clinic letters for children seen in the outreach clinic for the first time between March, 2004 and March, 2011. Children with CHD diagnosed antenatally or elsewhere were excluded. We recorded the echocardiography diagnosis made by the paediatric cardiologist and previously by the Paediatrician with Expertise in Cardiology. The Paediatrician with Expertise in Cardiology referred 317/3145 (10%) children seen in the local cardiac clinics to the outreach clinic over this period, and among them 296 were eligible for inclusion. Their median age was 1.5 years (range 1 month-15.1 years). For 244 (82%) children, there was complete diagnostic agreement between the Paediatrician with Expertise in Cardiology and the paediatric cardiologist. For 29 (10%) children, the main diagnosis was identical with additional findings made by the paediatric cardiologist. The abnormality had resolved in 17 (6%) cases by the time of clinic attendance. In six (2%) patients, the paediatric cardiologist made a different diagnosis. In total, 138 (47%) patients underwent a surgical or catheter intervention. Discussion Paediatricians with Expertise in Cardiology can make accurate diagnoses of CHD in children referred to their clinics. This can allow effective triage of children attending the outreach clinic, making best use of limited specialist resources.

Current status of coronary risk factors among rural Malays in Malaysia.

PubMed

Nawawi, Hapizah M; Nor, Idris M; Noor, Ismail M; Karim, Norimah A; Arshad, Fatimah; Khan, Rahmattullah; Yusoff, Khalid

2002-02-01

Coronary heart disease (CHD) is the leading cause of death in Malaysia, despite its status as a developing country. The rural population is thought to be at low risk. To investigate the prevalence of risk factors and global risk profile among rural Malays in Malaysia. We studied 609 rural Malay subjects (346 females, 263 males; age range 30-65 years). Blood pressure (BP), body mass index (BMI), waist-hip ratio (WHR), smoking habits and family history of premature CHD were documented. Fasting blood samples were analysed for serum lipids, lipoprotein (a), plasma glucose and fibrinogen. Oral glucose tolerance tests were performed using 75 g anhydrous glucose. The prevalence of hypercholesterolaemia for total cholesterol concentrations of > or = 5.2, > or =6.5 and > or =7.8 mmol/l were 67.3, 30.5 and 11.8% respectively. There was a high prevalence of low serum high-density lipoprotein cholesterol (13.1%), hypertension (30.3%), smokers (24.4%), diabetes (6.4%), impaired fasting glucose or glucose tolerance (13.9%), overweight or obesity (44.7%) and increased WHR (48.5%). Global risk assessment showed that 67.3% of the study population were at risk, with 15.9, 18.9 and 32.5% in the mild, moderate and high risk categories respectively. Prevalence of risk factors was high in the rural population. Global risk assessment showed a high-risk profile with two-thirds being at risk, and one-third being categorized into the high-risk group. Although rural communities were considered at low risk of developing CHD, this is changing fast, possibly due to the rapid socio-economic development, in addition to underlying genetic predisposition.

Chd1 remodelers maintain open chromatin and regulate the epigenetics of differentiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Persson, Jenna; Ekwall, Karl, E-mail: karl.ekwall@ki.se; School of Life Sciences, University College Sodertorn, NOVUM, Huddinge

Eukaryotic DNA is packaged around octamers of histone proteins into nucleosomes, the basic unit of chromatin. In addition to enabling meters of DNA to fit within the confines of a nucleus, the structure of chromatin has functional implications for cell identity. Covalent chemical modifications to the DNA and to histones, histone variants, ATP-dependent chromatin remodelers, small noncoding RNAs and the level of chromatin compaction all contribute to chromosomal structure and to the activity or silencing of genes. These chromatin-level alterations are defined as epigenetic when they are heritable from mother to daughter cell. The great diversity of epigenomes that canmore » arise from a single genome permits a single, totipotent cell to generate the hundreds of distinct cell types found in humans. Two recent studies in mouse and in fly have highlighted the importance of Chd1 chromatin remodelers for maintaining an open, active chromatin state. Based on evidence from fission yeast as a model system, we speculate that Chd1 remodelers are involved in the disassembly of nucleosomes at promoter regions, thus promoting active transcription and open chromatin. It is likely that these nucleosomes are specifically marked for disassembly by the histone variant H2A.Z.« less

Armadillo Repeat Containing 8α Binds to HRS and Promotes HRS Interaction with Ubiquitinated Proteins

PubMed Central

Tomaru, Koji; Ueda, Atsuhisa; Suzuki, Takeyuki; Kobayashi, Nobuaki; Yang, Jun; Yamamoto, Masaki; Takeno, Mitsuhiro; Kaneko, Takeshi; Ishigatsubo, Yoshiaki

2010-01-01

Recently, we reported that a complex with an essential role in the degradation of Fructose-1,6-bisphosphatase in yeast is well conserved in mammalian cells; we named this mammalian complex C-terminal to the Lissencephaly type-1-like homology (CTLH) complex. Although the function of the CTLH complex remains unclear, here we used yeast two-hybrid screening to isolate Hepatocyte growth factor-regulated tyrosine kinase substrate (HRS) as a protein binding to a key component of CTLH complex, Armadillo repeat containing 8 (ARMc8) α. The association was confirmed by a yeast two-hybrid assay and a co-immunoprecipitation assay. The proline-rich domain of HRS was essential for the association. As demonstrated through immunofluorescence microscopy, ARMc8α co-localized with HRS. ARMc8α promoted the interaction of HRS with various ubiquitinated proteins through the ubiquitin-interacting motif. These findings suggest that HRS mediates protein endosomal trafficking partly through its interaction with ARMc8α. PMID:20224683

Coronary Heart Disease Knowledge and Risk Factors among Tri-Ethnic College Students

ERIC Educational Resources Information Center

Koutoubi, Samer; Huffman, Fatma G.; Ciccazzo, Michele W.; Himburg, Susan P.; Johnson, Paulette

2005-01-01

Objectives: Coronary heart disease (CHD) is the leading cause of death in the United States and Europe. This study identified and compared nutritional knowledge associated with CHD risk factors among tri-ethnic college students. Design: A quantitative, cross-sectional, observational study using questionnaires. Setting: University laboratory.…

A Systems Biology Framework Identifies Molecular Underpinnings of Coronary Heart Disease

PubMed Central

Huan, Tianxiao; Zhang, Bin; Wang, Zhi; Joehanes, Roby; Zhu, Jun; Johnson, Andrew D.; Ying, Saixia; Munson, Peter J.; Raghavachari, Nalini; Wang, Richard; Liu, Poching; Courchesne, Paul; Hwang, Shih-Jen; Assimes, Themistocles L.; McPherson, Ruth; Samani, Nilesh J.; Schunkert, Heribert; Meng, Qingying; Suver, Christine; O'Donnell, Christopher J.; Derry, Jonathan; Yang, Xia; Levy, Daniel

2013-01-01

Objective Genetic approaches have identified numerous loci associated with coronary heart disease (CHD). The molecular mechanisms underlying CHD gene-disease associations, however, remain unclear. We hypothesized that genetic variants with both strong and subtle effects drive gene subnetworks that in turn affect CHD. Approach and Results We surveyed CHD-associated molecular interactions by constructing coexpression networks using whole blood gene expression profiles from 188 CHD cases and 188 age- and sex-matched controls. 24 coexpression modules were identified including one case-specific and one control-specific differential module (DM). The DMs were enriched for genes involved in B-cell activation, immune response, and ion transport. By integrating the DMs with altered gene expression associated SNPs (eSNPs) and with results of GWAS of CHD and its risk factors, the control-specific DM was implicated as CHD-causal based on its significant enrichment for both CHD and lipid eSNPs. This causal DM was further integrated with tissue-specific Bayesian networks and protein-protein interaction networks to identify regulatory key driver (KD) genes. Multi-tissue KDs (SPIB and TNFRSF13C) and tissue-specific KDs (e.g. EBF1) were identified. Conclusions Our network-driven integrative analysis not only identified CHD-related genes, but also defined network structure that sheds light on the molecular interactions of genes associated with CHD risk. PMID:23539213

Identification of susceptible genes for complex chronic diseases based on disease risk functional SNPs and interaction networks.

PubMed

Li, Wan; Zhu, Lina; Huang, Hao; He, Yuehan; Lv, Junjie; Li, Weimin; Chen, Lina; He, Weiming

2017-10-01

Complex chronic diseases are caused by the effects of genetic and environmental factors. Single nucleotide polymorphisms (SNPs), one common type of genetic variations, played vital roles in diseases. We hypothesized that disease risk functional SNPs in coding regions and protein interaction network modules were more likely to contribute to the identification of disease susceptible genes for complex chronic diseases. This could help to further reveal the pathogenesis of complex chronic diseases. Disease risk SNPs were first recognized from public SNP data for coronary heart disease (CHD), hypertension (HT) and type 2 diabetes (T2D). SNPs in coding regions that were classified into nonsense and missense by integrating several SNP functional annotation databases were treated as functional SNPs. Then, regions significantly associated with each disease were screened using random permutations for disease risk functional SNPs. Corresponding to these regions, 155, 169 and 173 potential disease susceptible genes were identified for CHD, HT and T2D, respectively. A disease-related gene product interaction network in environmental context was constructed for interacting gene products of both disease genes and potential disease susceptible genes for these diseases. After functional enrichment analysis for disease associated modules, 5 CHD susceptible genes, 7 HT susceptible genes and 3 T2D susceptible genes were finally identified, some of which had pleiotropic effects. Most of these genes were verified to be related to these diseases in literature. This was similar for disease genes identified from another method proposed by Lee et al. from a different aspect. This research could provide novel perspectives for diagnosis and treatment of complex chronic diseases and susceptible genes identification for other diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

Mortality from Congenital Heart Disease in Mexico: A Problem on the Rise

PubMed Central

Torres-Cosme, José Luis; Rolón-Porras, Constanza; Aguinaga-Ríos, Mónica; Acosta-Granado, Pedro Manuel; Reyes-Muñoz, Enrique; Murguía-Peniche, Teresa

2016-01-01

Background and Objectives Temporal trends in mortality from congenital heart disease (CHD) vary among regions. It is therefore necessary to study this problem in each country. In Mexico, congenital anomalies were responsible for 24% of infant mortality in 2013 and CHD represented 55% of total deaths from congenital anomalies among children under 1 year of age. The objectives of this study were to analyze the trends in infant mortality from CHD in Mexico (1998 to 2013), its specific causes, age at death and associated socio-demographic factors. Methods Population-based study which calculated the compounded annual growth rate of death rom CHD between 1998 and 2013. Specific causes, age at which death from CHD occurred and risk factors associated with mortality were analyzed for the year 2013. Results Infant mortality from CHD increased 24.8% from 1998 to 2013 (114.4 to 146.4/ 100,000 live births). A total of 3,593 CHD deaths occurred in 2013; the main causes were CHD with left-to-right shunt (n = 487; 19.8/100,000 live births) and cyanotic heart disease (n = 410; 16.7/100,000). A total of 1,049 (29.2%) deaths from CHD occurred during the first week of life. Risk factors associated with mortality from CHD were, in order of magnitude: non-institutional birth, rural area, birth in a public hospital and male sex. Conclusions Mortality from CHD has increased in Mexico. The main causes were CHD with left-to-right shunt, which are not necessarily fatal if treated promptly. Populations vulnerable to death from CHD were identified. Approximately one-third of the CHD occurred during the first week of life. It is important to promote early diagnosis, especially for non-institutional births. PMID:26937635

Red flags: a case series of clinician-family communication challenges in the context of CHD.

PubMed

Sekar, Priya; Marcus, Katie L; Williams, Erin P; Boss, Renee D

2017-07-01

We describe three cases of newborns with complex CHD characterised by communication challenges. These communication challenges were categorised as patient, family, or system-related red flags. Strategies for addressing these red flags were proposed, for the goal of optimising care and improving quality of life in this vulnerable population.

Demographic and cardiovascular risk factors modify association of fasting insulin with incident coronary heart disease and ischemic stroke (from the Atherosclerosis Risk In Communities Study).

PubMed

Rasmussen-Torvik, Laura J; Yatsuya, Hiroshi; Selvin, Elizabeth; Alonso, Alvaro; Folsom, Aaron R

2010-05-15

Previous studies have reported an association between circulating insulin and incident cardiovascular disease, but limited knowledge is available on the association across subgroups. We examined the associations of fasting insulin with incident coronary heart disease (CHD) and ischemic stroke in multiple subgroups of a biracial, middle-age cohort. A total of 12,323 subjects were included in the analysis. The incidence of CHD (n = 960) and ischemic stroke (n = 445) through 2005 was determined through annual interviews, repeat examinations, and community surveillance. Serum insulin was measured at baseline. Cox regression analysis was used to estimate the hazard ratios by quintile of fasting insulin at baseline and to determine the significance of effect modification. In the minimally adjusted models (age, gender, race, and field center), the baseline fasting insulin quintile was positively associated with both incident CHD (hazard ratio per quintile insulin = 1.12, p-trend <0.0001) and ischemic stroke (hazard ratio per quintile insulin = 1.11, p = 0.0018). The adjustment for high-density lipoprotein completely attenuated the association of insulin with CHD but not with stroke. The associations of insulin with CHD were stronger in nonsmokers (p-interaction = 0.018) and in those without hypertension (p-interaction = 0.0087). The associations of insulin with stroke were stronger in women (p-interaction = 0.037), whites (compared to blacks; p-interaction = 0.036), and those without hypertension (p-interaction = 0.0027). Copyright 2010 Elsevier Inc. All rights reserved.

Kalirin and CHD7: novel endothelial dysfunction indicators in circulating extracellular vesicles from hypertensive patients with albuminuria

PubMed Central

de la Cuesta, Fernando; Baldan-Martin, Montserrat; Moreno-Luna, Rafael; Alvarez-Llamas, Gloria; Gonzalez-Calero, Laura; Mourino-Alvarez, Laura; Sastre-Oliva, Tamara; López, Juan A.; Vázquez, Jesús; Ruiz-Hurtado, Gema; Segura, Julian; Vivanco, Fernando; Ruilope, Luis M.; Barderas, Maria G.

2017-01-01

Despite of the great advances in anti-hypertensive therapies, many patients under Renin-Angiotensin- System (RAS) suppression develop albuminuria, which is a clear indicator of therapeutic inefficiency. Hence, indicators of vascular function are needed to assess patients’ condition and help deciding future therapies. Proteomic analysis of circulating extracellular vesicles (EVs) showed two proteins, kalirin and chromodomain-helicase-DNA-binding protein 7 (CHD7), increased in albuminuric patients. A positive correlation of both with the expression of the endothelial activation marker E-selectin was found in EVs. In vitro analysis using TNFα-treated adult human endothelial cells proved their involvement in endothelial cell activation. Hence, we propose protein levels of kalirin and CHD7 in circulating EVs as novel endothelial dysfunction markers to monitor vascular condition in hypertensive patients with albuminuria. PMID:28152519

HIV and Ischemic Heart Disease.

PubMed

Vachiat, Ahmed; McCutcheon, Keir; Tsabedze, Nqoba; Zachariah, Don; Manga, Pravin

2017-01-03

The association of coronary heart disease (CHD) and human immunodeficiency virus (HIV) infection has been well recognized for many years. The etiology of the increased prevalence of CHD in HIV-infected populations is the result of complex interactions among the viral infection, host factors, traditional risk factors, and therapies for HIV. As the HIV population is living longer, largely attributable to combination antiretroviral therapy, there is concern about the effect of the rising prevalence of CHD on morbidity and mortality, as well its effect on health systems around the world. This review will highlight the epidemiological evidence linking HIV infection and CHD. It will also focus on our current understanding of the pathogenesis and factors associated with HIV infection and CHD. In addition, the review will highlight modes of presentation and management strategies for mitigating risk and treatment of HIV-positive patients presenting with CHD. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Studying the determinant factors leading to congenital heart disease in newborns.

PubMed

Arjmandnia, Mohammadhossein; Besharati, Mahsa; Rezvan, Sajad

2018-01-01

Congenital heart disease (CHD) is an important cause of death during the 1 st year of life and includes a special group of cardiac diseases that exist from birth. These conditions arise due to the abnormal development of an embryo's normal structures. A case-control study was conducted to investigate the determinant factors leading to CHD. All newborns who have been diagnosed with CHD upon echocardiography in 2013 were considered as cases. The number of samples required was randomly selected from the newborns who lacked CHD on cardiography. The mothers of both groups were handed the questionnaires. SPSS 23 was employed to analyze the data. A statistically significant association was seen between CHD and a positive family history (FH) ( P < 0.001), consanguinity ( P < 0.001), maternal diabetes ( P = 0.004), the use of antiepileptics during the first 45 days of gestation ( P = 0.002), and the mother's education status ( P > 0.001). No significant association was observed between CHD in the newborn and the age below 20 and above 35 years and ( P = 0.11), maternal body mass index (BMI) ( P = 0.44), smoking during the first 45 days of gestation ( P = 0.017), and maternal rheumatologic diseases ( P = 0.4). Newborns are at a greater risk of having CHD born from mothers with a FH of CHD, from consanguineous marriages, history of diabetes, antiepileptic use, and lack of folic acid use. However, no significant associations were found between newborn CHD and maternal age, BMI, or cigarette smoking.

Disparity in management of diabetes and coronary heart disease risk factors by sex in DCCT/EDIC.

PubMed

Larkin, M E; Backlund, J-Y; Cleary, P; Bayless, M; Schaefer, B; Canady, J; Nathan, D M

2010-04-01

Coronary heart disease (CHD) is a major cause of morbidity and mortality in patients with diabetes. Sex disparity in the treatment of modifiable CHD risk factors in patients with Type 2 diabetes has been reported previously; however, there is little comparable information in Type 1 diabetes. We performed a cross-sectional analysis of 1153 subjects with Type 1 diabetes in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) cohort to compare achievement of metabolic and CHD risk factor goals and use of recommended risk factor interventions between the sexes. Women were less likely than men to achieve glycated haemoglobin (HbA1c)<7.0% [adjusted odds ratio (AOR) 0.76, 95% confidence interval (CI) 0.57-0.995] or<8.0% (AOR 0.74, 95% CI 0.58-0.95). Achievement of target lipid levels was not significantly different between the sexes. As in the non-diabetic population, men had higher blood pressure. Women were significantly less likely than men to report using aspirin (AOR 0.77, 0.60-0.99) and angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) (AOR 0.62, 0.49-0.80) and statins (AOR 0.56, 0.43-0.73), even after adjusting for blood pressure and lipid levels, respectively. Reported use of statins was also lower in women than men in the subset that developed a low-density lipoprotein (LDL) cholesterol level>3.4 mmol/l (39% vs. 60%, P<0.05). In Type 1 diabetes, women report lower frequency than men in the use of interventions that decrease CHD risk. These findings are consistent with reports in the Type 2 diabetic population, showing that risk-reducing measures are underused in women with diabetes.

21 CFR 101.82 - Health claims: Soy protein and risk of coronary heart disease (CHD).

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 2 2011-04-01 2011-04-01 false Health claims: Soy protein and risk of coronary... HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION FOOD LABELING Specific Requirements for Health Claims § 101.82 Health claims: Soy protein and risk of coronary heart disease (CHD). (a...

Long-term Effects of Large-volume Liposuction on Metabolic Risk Factors for Coronary Heart Disease

PubMed Central

Mohammed, B. Selma; Cohen, Samuel; Reeds, Dominic; Young, V. Leroy; Klein, Samuel

2009-01-01

Abdominal obesity is associated with metabolic risk factors for coronary heart disease (CHD). Although we previously found that using liposuction surgery to remove abdominal subcutaneous adipose tissue (SAT) did not result in metabolic benefits, it is possible that postoperative inflammation masked the beneficial effects. Therefore, this study provides a long-term evaluation of a cohort of subjects from our original study. Body composition and metabolic risk factors for CHD, including oral glucose tolerance, insulin resistance, plasma lipid profile, and blood pressure were evaluated in seven obese (39 ± 2 kg/m2) women before and at 10, 27, and 84–208 weeks after large-volume liposuction. Liposuction surgery removed 9.4 ± 1.8 kg of body fat (16 ± 2% of total fat mass; 6.1 ± 1.4 kg decrease in body weight), primarily from abdominal SAT; body composition and weight remained the same from 10 through 84–208 weeks. Metabolic endpoints (oral glucose tolerance, homeostasis model assessment of insulin resistance, blood pressure and plasma triglyceride (TG), high-density lipoprotein (HDL)-cholesterol, and low-density lipoprotein (LDL)-cholesterol concentrations) obtained at 10 through 208 weeks were not different from baseline and did not change over time. These data demonstrate that removal of a large amount of abdominal SAT by using liposuction does not improve CHD metabolic risk factors associated with abdominal obesity, despite a long-term reduction in body fat. PMID:18820648

Traditional Cardiovascular Risk Factors as Predictors of Cardiovascular Events in the U.S. Astronaut Corps

NASA Technical Reports Server (NTRS)

Halm, M. K.; Clark, A.; Wear, M. L.; Murray, J. D.; Polk, J. D.; Amirian, E.

2009-01-01

Risk prediction equations from the Framingham Heart Study are commonly used to predict the absolute risk of myocardial infarction (MI) and coronary heart disease (CHD) related death. Predicting CHD-related events in the U.S. astronaut corps presents a monumental challenge, both because astronauts tend to live healthier lifestyles and because of the unique cardiovascular stressors associated with being trained for and participating in space flight. Traditional risk factors may not hold enough predictive power to provide a useful indicator of CHD risk in this unique population. It is important to be able to identify individuals who are at higher risk for CHD-related events so that appropriate preventive care can be provided. This is of special importance when planning long duration missions since the ability to provide advanced cardiac care and perform medical evacuation is limited. The medical regimen of the astronauts follows a strict set of clinical practice guidelines in an effort to ensure the best care. The purpose of this study was to evaluate the utility of the Framingham risk score (FRS), low-density lipoprotein (LDL) and high-density lipoprotein levels, blood pressure, and resting pulse as predictors of CHD-related death and MI in the astronaut corps, using Cox regression. Of these factors, only two, LDL and pulse at selection, were predictive of CHD events (HR(95% CI)=1.12 (1.00-1.25) and HR(95% CI)=1.70 (1.05-2.75) for every 5-unit increase in LDL and pulse, respectively). Since traditional CHD risk factors may lack the specificity to predict such outcomes in astronauts, the development of a new predictive model, using additional measures such as electron-beam computed tomography and carotid intima-media thickness ultrasound, is planned for the future.

A pilot Croatian survey of risk factor (CRO-SURF) management in patients with cardiovascular disease.

PubMed

Pećin, Ivan; Milicić, Davor; Jurin, Hrvoje; Reiner, Zeljko

2012-06-01

A pilot survey was performed to determine the presence of known risk factors for cardiovascular disease in Croatian patients with diagnosed coronary heart disease (CHD) using a new questionnaire. The idea was to test this new and very simple questionnaire but also to compare the data collected in this pilot survey with the results of the last Croatian national survey (TASPIC-CRO V) and so to obtain the information whether secondary prevention has improved between 2003 and 2010. 122 patients with established CHD (88 men, 34 women, mean age 66.3 years) treated in Zagreb University Hospital Center were included. Data collection was based on filling the SURF questionnaire right after the clinical exam or later using review of medical records. Patients were hospitalized because of CABG (1%), PCI (8%), ACS (35%) or chronic stable angina (56%). The history of arterial hypertension had 95%patients (however, on admission mean systolic pressure was 130.1 mmHg, diastolic 76.8 mmHg), 90% had dyslipidaemia (total cholesterol <4.5 mmol/L had 43%; <4.0 mmol/L 33%; LDL-cholesterol <2.5 mmol/L 49%; <2.0 mmol/L 32%; HDL>1.2 mmol/L (women) or >1.0 mmol/L (men) had 67%), 25% had diabetes which was poorly regulated (mean HbA1c 8.2%), 18% were active smokers. After discharge only 24% performed cardiac rehabilitation. Mean body mass index of the patients was 28.3 kg/m2 (32% were obese, 72% overweight). Compared to TASPIC-CRO V there was lower usage of aspirin than recommended on discharge. This was also true for statin therapy. More patients were taking beta blockers, calcium antagonists and diuretics than 7 years ago. This pilot survey showed that CRO-SURF questionnaire is short, quick, effective and simple to use. It is a good and cost effective tool to collect data on CVD risk factors and their management. The results obtained by using it indicate that there is still a high prevalence of modifiable risk factors in Croatian patients with CHD.

Smad7 Protein Induces Interferon Regulatory Factor 1-dependent Transcriptional Activation of Caspase 8 to Restore Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL)-mediated Apoptosis

PubMed Central

Hong, Suntaek; Kim, Hye-Youn; Kim, Jooyoung; Ha, Huyen Trang; Kim, Young-Mi; Bae, Eunjin; Kim, Tae Hyung; Lee, Kang Choon; Kim, Seong-Jin

2013-01-01

Smad7 has been known as a negative regulator for the transforming growth factor-β (TGF-β) signaling pathway through feedback regulation. However, Smad7 has been suspected to have other biological roles through the regulation of gene transcription. By screening differentially regulated genes, we found that the caspase 8 gene was highly up-regulated in Smad7-expressing cells. Smad7 was able to activate the caspase 8 promoter through recruitment of the interferon regulatory factor 1 (IRF1) transcription factor to the interferon-stimulated response element (ISRE) site. Interaction of Smad7 on the caspase 8 promoter was confirmed with electrophoretic mobility shift assay and chromatin immunoprecipitation experiment. Interestingly, Smad7 did not directly interact with the ISRE site, but it increased the binding activity of IRF1 with ISRE. These results support that Smad7 recruits IRF1 protein on the caspase 8 promoter and functions as a transcriptional coactivator. To confirm the biological significance of caspase 8 up-regulation, we tested tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-mediated cell death assay in breast cancer cells. Smad7 in apoptosis-resistant MCF7 cells markedly sensitized the cells to TRAIL-induced cell death by restoring the caspase cascade. Furthermore, restoration of caspase 8-mediated apoptosis pathway repressed the tumor growth in the xenograft model. In conclusion, we suggest a novel role for Smad7 as a transcriptional coactivator for caspase 8 through the interaction with IRF1 in regulation of the cell death pathway. PMID:23255602

Did it fall or was it pushed? The contribution of trends in established risk factors to the decline in premature coronary heart disease mortality in New Zealand.

PubMed

Tobias, Martin; Taylor, Richard; Yeh, Li-Chia; Huang, Ken; Mann, Stewart; Sharpe, Norman

2008-04-01

To estimate the contribution of trends in three risk factors--systolic blood pressure (SBP), total blood cholesterol (TBC) and cigarette smoking--to the decline in premature coronary heart disease (CHD) mortality in New Zealand from 1980-2004. Risk factor prevalence data by 10-year age group (35-64 years) and sex was sourced from six national or Auckland regional health surveys and three population censuses (the latter only for smoking). The data were smoothed using two-point moving averages, then further smoothed by fitting quadratic regression equations (SBP and TBC) or splines (smoking). Risk factor/CHD mortality hazard ratios estimated by expert working groups for the World Health Organization Global Burden of Disease Study 2001 were used to translate average annual changes in risk factor prevalences to the corresponding percentage changes in premature CHD mortality. The expected trends in CHD mortality were then compared with the observed trend to estimate the contribution of each risk factor to the decline. Approximately 80% (73% for males, 87% for females) of the decline in premature CHD mortality from 1980 to 2004 is estimated to have resulted from the joint trends in population SBP and TBC distributions and smoking prevalence. Overall, approximately 42%, 36% and 22% of the joint risk factor effect was contributed by trends in SBP, TBC and smoking respectively. Our estimate for the joint risk factor contribution to the CHD mortality decline of 80% exceeds those of two earlier New Zealand studies, but agrees closely with a similar Australian study. This provides an indicator of the scope that still remains for further reduction in CHD mortality through primary and secondary prevention.

Generation of Mice Deficient in both KLF3/BKLF and KLF8 Reveals a Genetic Interaction and a Role for These Factors in Embryonic Globin Gene Silencing

PubMed Central

Funnell, Alister P. W.; Mak, Ka Sin; Twine, Natalie A.; Pelka, Gregory J.; Norton, Laura J.; Radziewic, Tania; Power, Melinda; Wilkins, Marc R.; Bell-Anderson, Kim S.; Fraser, Stuart T.; Perkins, Andrew C.; Tam, Patrick P.; Pearson, Richard C. M.

2013-01-01

Krüppel-like factors 3 and 8 (KLF3 and KLF8) are highly related transcriptional regulators that bind to similar sequences of DNA. We have previously shown that in erythroid cells there is a regulatory hierarchy within the KLF family, whereby KLF1 drives the expression of both the Klf3 and Klf8 genes and KLF3 in turn represses Klf8 expression. While the erythroid roles of KLF1 and KLF3 have been explored, the contribution of KLF8 to this regulatory network has been unknown. To investigate this, we have generated a mouse model with disrupted KLF8 expression. While these mice are viable, albeit with a reduced life span, mice lacking both KLF3 and KLF8 die at around embryonic day 14.5 (E14.5), indicative of a genetic interaction between these two factors. In the fetal liver, Klf3 Klf8 double mutant embryos exhibit greater dysregulation of gene expression than either of the two single mutants. In particular, we observe derepression of embryonic, but not adult, globin expression. Taken together, these results suggest that KLF3 and KLF8 have overlapping roles in vivo and participate in the silencing of embryonic globin expression during development. PMID:23716600

Psychological Factors and Cardiac Risk And Impact of Exercise Training Programs—A Review of Ochsner Studies

PubMed Central

Lavie, Carl J.; Milani, Richard V.; Artham, Surya M.; Gilliland, Yvonne

2007-01-01

Although under-emphasized, substantial evidence indicates that psychological distress, especially depression, hostility, and anxiety, are risk factors for coronary heart disease (CHD) and affect recovery following major coronary heart disease events. We review several major studies from Ochsner Medical Center demonstrating the high prevalence of psychological distress in CHD patients and the marked benefits that occur following formal cardiac rehabilitation and exercise training programs. These benefits include reductions in psychological stress, improvements in CHD risk factors that accompany high stress, and reduced all-cause mortality. These data support the benefits of exercise training and increased levels of fitness to improve psychological stress and subsequent prognosis. PMID:21603539

Transcription factor 19 interacts with histone 3 lysine 4 trimethylation and controls gluconeogenesis via the nucleosome-remodeling-deacetylase complex.

PubMed

Sen, Sabyasachi; Sanyal, Sulagna; Srivastava, Dushyant Kumar; Dasgupta, Dipak; Roy, Siddhartha; Das, Chandrima

2017-12-15

Transcription factor 19 (TCF19) has been reported as a type 1 diabetes-associated locus involved in maintenance of pancreatic β cells through a fine-tuned regulation of cell proliferation and apoptosis. TCF19 also exhibits genomic association with type 2 diabetes, although the precise molecular mechanism remains unknown. It harbors both a plant homeodomain and a forkhead-associated domain implicated in epigenetic recognition and gene regulation, a phenomenon that has remained unexplored. Here, we show that TCF19 selectively interacts with histone 3 lysine 4 trimethylation through its plant homeodomain finger. Knocking down TCF19 under high-glucose conditions affected many metabolic processes, including gluconeogenesis. We found that TCF19 overexpression represses de novo glucose production in HepG2 cells. The transcriptional repression of key genes, induced by TCF19, coincided with NuRD (nucleosome-remodeling-deacetylase) complex recruitment to the promoters of these genes. TCF19 interacted with CHD4 (chromodomain helicase DNA-binding protein 4), which is a part of the NuRD complex, in a glucose concentration-independent manner. In summary, our results show that TCF19 interacts with an active transcription mark and recruits a co-repressor complex to regulate gluconeogenic gene expression in HepG2 cells. Our study offers critical insights into the molecular mechanisms of transcriptional regulation of gluconeogenesis and into the roles of chromatin readers in metabolic homeostasis. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Possible Common Aetiology behind Maternal Preeclampsia and Congenital Heart Defects in the Child: a Cardiovascular Diseases in Norway Project Study.

PubMed

Brodwall, Kristoffer; Leirgul, Elisabeth; Greve, Gottfried; Vollset, Stein Emil; Holmstrøm, Henrik; Tell, Grethe S; Øyen, Nina

2016-01-01

The aetiology of congenital heart defects (CHD) is mostly unknown, but maternal factors may modify the infant risk of CHD. We investigated the association between maternal preeclampsia and offspring risk of severe CHD in a nation-wide cohort study. Information on all births registered in the Medical Birth Registry of Norway, 1994-2009, was completed with information on CHD diagnoses from national health registries and the Cardiovascular Diseases in Norway Project (CVDNOR). Among 914 703 singleton births without chromosomal abnormalities, 32 864 (3.6%) were born after a pregnancy with preeclampsia. The preeclampsia was diagnosed before the 34th week of pregnancy (early-onset preeclampsia) in 2618 (8.0% of preeclamptic pregnancies). CHDs were diagnosed in 10 691 infants; of these, 2473 had severe CHD. The risk of severe CHD was compared between births with and without maternal preeclampsia and estimated with binomial log-linear regression. When adjusting for year of birth, maternal age, parity, and pregestational diabetes, the risk ratio (RR) for severe CHD in offspring of mothers with any preeclampsia was 1.3 [95% confidence interval (CI) 1.1, 1.5], and in pregnancies with early-onset preeclampsia, the RR was 2.8 (95% CI 1.8, 4.4). The association between early-onset preeclampsia and specific types of severe CHD was stronger for atrioventricular septal defects (AVSD), with adjusted RR 13.5 (95% CI 6.8, 26.8). Early-onset preeclampsia was strongly associated with infant risk of severe CHD, specifically; the risk of AVSD was 15-fold higher if the mother was diagnosed with early-onset preeclampsia, suggesting common aetiological factors for early-onset preeclampsia and erroneous fetal heart development. © 2015 John Wiley & Sons Ltd.

The role of exercise in reducing coronary heart disease and associated risk factors.

PubMed

Leclerc, K M

1992-06-01

Despite public health efforts, heart disease remains a leading cause of death and disease in the United States. There is sufficient evidence to justify the inclusion of regular exercise in efforts to reduce overall coronary heart disease (CHD) morbidity and mortality. This paper reviews the supportive evidence for this stance as well as the role of exercise in managing the major CHD risk factors of atherogenic serum lipids, hypertension, and obesity. Recognition of exercise as a lifestyle behavior is addressed and recommendations for prescribing exercise for adults interested in preventing CHD are presented.

Maintenance of Genome Integrity by Mi2 Homologs CHD-3 and LET-418 in Caenorhabditis elegans.

PubMed

Turcotte, Carolyn A; Sloat, Solomon A; Rigothi, Julia A; Rosenkranse, Erika; Northrup, Alexandra L; Andrews, Nicolas P; Checchi, Paula M

2018-03-01

Meiotic recombination depends upon the tightly coordinated regulation of chromosome dynamics and is essential for the production of haploid gametes. Central to this process is the formation and repair of meiotic double-stranded breaks (DSBs), which must take place within the constraints of a specialized chromatin architecture. Here, we demonstrate a role for the nucleosome remodeling and deacetylase (NuRD) complex in orchestrating meiotic chromosome dynamics in Caenorhabditis elegans Our data reveal that the conserved Mi2 homologs Chromodomain helicase DNA-binding protein (CHD-3) and its paralog LET-418 facilitate meiotic progression by ensuring faithful repair of DSBs through homologous recombination. We discovered that loss of either CHD-3 or LET-418 results in elevated p53-dependent germ line apoptosis, which relies on the activation of the conserved checkpoint kinase CHK-1 Consistent with these findings, chd-3 and let-418 mutants produce a reduced number of offspring, indicating a role for Mi2 in forming viable gametes. When Mi2 function is compromised, persisting recombination intermediates are detected in late pachytene nuclei, indicating a failure in the timely repair of DSBs. Intriguingly, our data indicate that in Mi2 mutant germ lines, a subset of DSBs are repaired by nonhomologous end joining, which manifests as chromosomal fusions. We find that meiotic defects are exacerbated in Mi2 mutants lacking CKU-80, as evidenced by increased recombination intermediates, corpses, and defects in chromosomal integrity. Taken together, our findings support a model wherein the C. elegans Mi2 complex maintains genomic integrity through reinforcement of a chromatin landscape suitable for homology-driven repair mechanisms. Copyright © 2018 by the Genetics Society of America.

Do Differences in Risk Factors Explain the Lower Rates of Coronary Heart Disease in Japanese Versus U.S. Women?

PubMed Central

Willcox, Bradley J.; Usui, Takeshi; Carr, John Jeffrey; Barinas-Mitchell, Emma J.M.; Masaki, Kamal H.; Watanabe, Makoto; Tracy, Russell P.; Bertolet, Marianne H.; Evans, Rhobert W.; Nishimura, Kunihiko; Sutton-Tyrrell, Kim; Kuller, Lewis H.; Miyamoto, Yoshihiro

2013-01-01

Abstract Background Mortality from coronary heart disease (CHD) in women in Japan is one of the lowest in developed countries. In an attempt to shed some light on possible reasons of lower CHD in women in Japan compared with the United States, we extensively reviewed and analyzed existing national data and recent literature. Methods We searched recent epidemiological studies that reported incidence of acute myocardial infarction (AMI) and examined risk factors for CHD in women in Japan. Then, we compared trends in risk factors between women currently aged 50–69 years in Japan and the United States, using national statistics and other available resources. Results Recent epidemiological studies have clearly shown that AMI incidence in women in Japan is lower than that reported from other countries, and that lipids, blood pressure (BP), diabetes, smoking, and early menopause are independent risk factors. Comparing trends in risk factors between women in Japan and the United States, current levels of serum total cholesterol are higher in women in Japan and levels have been similar at least since 1990. Levels of BP have been higher in in Japan for the past 3 decades. Prevalence of type 2 diabetes has been similar in Japanese and white women currently aged 60–69 for the past 2 decades. In contrast, rates of cigarette smoking, although low in women in both countries, have been lower in women in Japan. Conclusions Differences in risk factors and their trends are unlikely to explain the difference in CHD rates in women in Japan and the United States. Determining the currently unknown factors responsible for low CHD mortality in women in Japan may lead to new strategy for CHD prevention. PMID:24073782

Psychosocial risk factors for coronary heart disease in UK South Asian men and women.

PubMed

Williams, E D; Steptoe, A; Chambers, J C; Kooner, J S

2009-12-01

South Asian people in the UK and other western countries have elevated rates of coronary heart disease (CHD). Psychosocial factors contribute to CHD risk, but information about psychosocial risk profiles in UK South Asians is limited. This study aimed to examine the profile of conventional and novel psychosocial risk factors in South Asian compared with white men and women. Using a cross-sectional population study design, psychosocial profiles were assessed in 1130 South Asian and 818 white European healthy men and women aged between 35 and 75 years, who had previously participated in a cardiovascular risk assessment programme in West London. Psychosocial factors potentially contributing to CHD risk were assessed using standardised questionnaires. UK South Asians reported significantly higher psychosocial adversity compared with UK whites. South Asian men and women experienced greater chronic stress, in the form of financial strain, residential crowding, family conflict, social deprivation and discrimination, than white Europeans. They had larger social networks, but reported lower social support and greater depression and hostility. These effects were largely independent of socioeconomic status. UK South Asians experience significant psychosocial adversity compared with UK white Europeans. This is consistent with the heightened vulnerability to CHD observed in this population.

Temporal variation of birth prevalence of congenital heart disease in the United States.

PubMed

Egbe, Alexander; Uppu, Santosh; Lee, Simon; Stroustrup, Annemarie; Ho, Deborah; Srivastava, Shubhika

2015-01-01

This is a longitudinal analysis of the largest and most comprehensive inpatient care database in the United States to determine temporal variation of birth prevalence of congenital heart disease (CHD) diagnosis, adjusting for potentially confounding factors. We compared all entries of CHD diagnoses in the Nationwide Inpatient Sample (NIS) database in 1998 and 2008 to determine differences in birth prevalence of overall CHD and specific CHD phenotypes stratified by race, gender, socioeconomic status, and geographical location. CHD prevalence was 10.2/1000 in 1998 and 10.8/1000 live births in 2008, without significant changes in prevalence (P = .09). Prevalence of isolated patent ductus arteriosus increased from 1.9 to 2.8 per 1000 (P < .001), and this temporal increase remained statistically significant after stratification by race, income status, and geographic location. Prevalence of mild CHD increased from 8.0 to 9.1 per 1000 (P = .01), with most of this increase occurring among Caucasians and the upper socioeconomic class. There was a decrease in prevalence of severe CHD from 1.5 to 0.9 (P = .03), while prevalence of moderate CHD and all other specific CHD phenotypes remained unchanged in both cohorts. We report increased prevalence of isolated patent ductus arteriosus and mild CHD; decreased prevalence of severe CHD; and unchanged prevalence of overall CHD and all other specific CHD phenotype. We speculate that increased prevalence of mild CHD was due to increased case detection because of improvement in echocardiography. Decrease in diagnosis of severe CHD could be due to the impact of pregnancy termination. © 2014 Wiley Periodicals, Inc.

[Correlation between polymorphisms in the coagulation factor VII gene hypervariable region 4 site and the risk of coronary heart disease in population with different ethnic backgrounds: a Meta-analysis].

PubMed

Wang, Li-li; Ma, Bin; Qian, Dun; Pang, Jun; Yao, Ya-li

2013-12-01

To assess the correlation between polymorphisms in the coagulation factor VII (F VII)gene hypervariable region 4 (HVR4)site and risk related to coronary heart disease (CHD)in different ethnic populations, especially the Asian populations. Publications up to April 2013, from CBM, CNKI, Wanfang Database,VIP, PubMed, Cochrane Library and Embase were searched to collect data from case-control studies related to F VII gene HVR4 site and CHD in populations from different ethnicities. Quality of studies was evaluated, available data extracted and both RevMan 5.1 and Stata 11.0 softwares were used for Meta-analysis. Fifteen case-control studies were included, involving 3167 cases with CHD group and 3168 cases in the control group. on this Meta-analysis showed that:a)polymorphism of the F VII gene HVR4 site H7/H6+H5 and CHD, b)H7H7/H6H6 + H7H6 and CHD were both slightly correlated between people with different ethnic backgrounds. However, the H6 allele versus H7+H5 allele and CHD showed different results-a high correlation seen in different ethnic groups. H5 allele versus H6+H7 allele and CHD did not appear significant difference(OR = 1.20, 95%CI:0.76-1.90, P = 0.43). Both F VII gene HVR4 polymorphisms H7 allele and the H7H7 genotype might have served as protective factors for CHD in different ethnic groups, H6 allele might serve as a risk factor for CHD, but H5 allele was likely not to be associated with CHD in different ethnic groups.

Overweight is an independent risk factor for cardiovascular disease in Chinese populations.

PubMed

Zhou, Beifan; Wu, Yangfeng; Yang, Jun; Li, Ying; Zhang, Hongye; Zhao, Liancheng

2002-08-01

In the last decade of the 20th century, cardiovascular disease was the leading cause of death in China, accounting for one-third of the total deaths. In comparison with western populations, the mean body weight or body mass index (BMI) of the Chinese population was lower, but showed an increasing trend. Whether the variation within lower levels of BMI or waist circumference was associated with other risk factors of cardiovascular disease, and whether they contribute independently to the risk of cardiovascular disease in the Chinese population, was investigated in this study. In keeping with a uniform study design, in each of 14 study populations at different geographical locations and with different characteristics, the incidence rates of stroke, coronary heart disease (CHD) and the causes of death were monitored in approximately/= 100000 residents from 1991 to 1995 using the MONICA procedure. Risk factors were surveyed in a random cluster sample of 1000 subjects (35-59 years of age) from each population under surveillance using internationally standardized methods and a centralized system to ensure quality control. Among the risk factors, body weight, height, and waist and hip circumferences were measured. Cross-sectional stratified analyses were used to analyse the relationship of BMI (kg m(-2)) or waist circumference to other metabolic risk factors. Ten cohorts among the 14 study populations with 24734 participants were surveyed from 1982 to 1985 as a baseline for further study and were followed-up for 9 years taking the events of stroke, CHD and different causes of death as end-points. Cox regression models were used to explore the association of BMI with the relative risks of stroke, CHD and total death. The survey in 14 random samples with a total number of 19 741 subjects showed that the mean BMI (20.8-25.1) and waist circumference (67.8-86.7 cm) were much lower than those of western populations. There was, however, variation in the anthropometric

Depressive symptoms are associated with incident coronary heart disease or revascularization among Blacks but not among Whites in the Reasons for Geographical and Racial Differences in Stroke (REGARDS) Study

PubMed Central

Sims, Mario; Redmond, Nicole; Khodneva, Yulia; Durant, Raegan W.; Halanych, Jewell; Safford, Monika M.

2015-01-01

Purpose To examine the association of depressive symptoms with coronary heart disease (CHD) endpoints by race and income. Methods Study participants were Blacks and Whites (n=24,443) without CHD at baseline from the national REasons for Geographical and Racial Differences in Stroke (REGARDS) cohort. Outcomes included acute CHD and CHD or revascularization. We estimated race-stratified multivariable Cox proportional hazards models of incident CHD and incident CHD or revascularization with the 4-item Center for Epidemiological Studies-Depression scale, adjusting for risk factors. Results Mean follow-up was 4.2+1.5 years, CHD incidence was 8.3 events per 1000 person years (n=366) among Blacks and 8.8 events per 1000 person years (n=613) among Whites. After adjustment for age, sex, marital status, region, and socioeconomic status, depressive symptoms were significantly associated with incident CHD among Blacks [HR 1.39 (95%CI 1.00-1.91)], but not among Whites [HR 1.10 (95%CI 0.74-1.64)]. In the fully-adjusted model, compared to Blacks who reported no depressive symptoms, those reporting depressive symptoms had greater risk for the composite endpoint of CHD or revascularization [HR 1.36 (95%CI 1.01-1.81)]. Depressive symptoms were not associated with incident CHD endpoints among Whites. Conclusions High depressive symptoms were associated with higher risk of CHD or revascularization for Blacks but not Whites. PMID:25891100

Contrasting cardiovascular mortality trends in Eastern Mediterranean populations: Contributions from risk factor changes and treatments.

PubMed

Critchley, Julia; Capewell, Simon; O'Flaherty, Martin; Abu-Rmeileh, Niveen; Rastam, Samer; Saidi, Olfa; Sözmen, Kaan; Shoaibi, Azza; Husseini, Abdullatif; Fouad, Fouad; Ben Mansour, Nadia; Aissi, Wafa; Ben Romdhane, Habiba; Unal, Belgin; Bandosz, Piotr; Bennett, Kathleen; Dherani, Mukesh; Al Ali, Radwan; Maziak, Wasim; Arık, Hale; Gerçeklioğlu, Gül; Altun, Deniz Utku; Şimşek, Hatice; Doganay, Sinem; Demiral, Yücel; Aslan, Özgür; Unwin, Nigel; Phillimore, Peter; Achour, Nourredine; Aissi, Waffa; Allani, Riadh; Arfa, Chokra; Abu-Kteish, Heidar; Abu-Rmeileh, Niveen; Al Ali, Radwan; Altun, Deniz; Ahmad, Balsam; Arık, Hale; Aslan, Özgür; Beltaifa, Latifa; Ben Mansour, Nadia; Bennett, Kathleen; Ben Romdhane, Habiba; Ben Salah, Nabil; Collins, Marissa; Critchley, Julia; Capewell, Simon; Dherani, Mukesh; Demiral, Yücel; Doganay, Sinem; Elias, Madonna; Ergör, Gül; Fadhil, Ibtihal; Fouad, Fouad; Gerçeklioğlu, Gül; Ghandour, Rula; Göğen, Sibel; Husseini, Abdullatif; Jaber, Samer; Kalaca, Sibel; Khatib, Rana; Khatib, Rasha; Koudsie, Saer; Kilic, Bülent; Lassoued, Olfa; Mason, Helen; Maziak, Wasim; Mayaleh, Maher Abou; Mikki, Nahed; Moukeh, Ghmaez; Flaherty, Martin O; Phillimore, Peter; Rastam, Samer; Roglic, Gojka; Saidi, Olfa; Saatli, Gül; Satman, Ilhan; Shoaibi, Azza; Şimşek, Hatice; Soulaiman, Nesrien; Sözmen, Kaan; Tlili, Faten; Unal, Belgin; Unwin, Nigel; Yardim, Nazan; Zaman, Shahaduz

2016-04-01

Middle income countries are facing an epidemic of non-communicable diseases, especially coronary heart disease (CHD). We used a validated CHD mortality model (IMPACT) to explain recent trends in Tunisia, Syria, the occupied Palestinian territory (oPt) and Turkey. Data on populations, mortality, patient numbers, treatments and risk factor trends from national and local surveys in each country were collated over two time points (1995-97; 2006-09); integrated and analysed using the IMPACT model. Risk factor trends: Smoking prevalence was high in men, persisting in Syria but decreasing in Tunisia, oPt and Turkey. BMI rose by 1-2 kg/m(2) and diabetes prevalence increased by 40%-50%. Mean systolic blood pressure and cholesterol levels increased in Tunisia and Syria. Mortality trends: Age-standardised CHD mortality rates rose by 20% in Tunisia and 62% in Syria. Much of this increase (79% and 72% respectively) was attributed to adverse trends in major risk factors, occurring despite some improvements in treatment uptake. CHD mortality rates fell by 17% in oPt and by 25% in Turkey, with risk factor changes accounting for around 46% and 30% of this reduction respectively. Increased uptake of community treatments (drug treatments for chronic angina, heart failure, hypertension and secondary prevention after a cardiac event) accounted for most of the remainder. CHD death rates are rising in Tunisia and Syria, whilst oPt and Turkey demonstrate clear falls, reflecting improvements in major risk factors with contributions from medical treatments. However, smoking prevalence remains very high in men; obesity and diabetes levels are rising dramatically. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Erythrocyte stearidonic acid and other n-3 fatty acids and CHD in the Physicians’ Health Study

USDA-ARS?s Scientific Manuscript database

Intake of marine-based n-3 fatty acids (EPA, docosapentaenoic acid and DHA) is recommended to prevent CHD. Stearidonic acid (SDA), a plant-based n-3 fatty acid, is a precursor of EPA and may be more readily converted to EPA than a-linolenic acid (ALA). While transgenic soyabeans might supply SDA at ...

[Identification of the interacting proteins with S100A8 or S100A9 by affinity purification and mass spectrometry].

PubMed

Wang, Jing; Zhang, Xuemei; Li, Zheng; Li, Xiayu; Ma, Jian; Shen, Shourong

2017-04-28

To identify the interacting proteins with S100A8 or S100A9 in HEK293 cell line by flag-tag affinity purification and liquid chromatography mass spectrometry/mass spectrometry (LC-MS/MS).
 Methods: The p3×Flag-CMV-S100A8 and p3×Flag-CMV-S100A9 expression vectors were constructed by inserting S100A8 or S100A9 coding sequence. The recombinant plasmids were then transfected into HEK293 cells. Affinity purification and LC-MS/MS were applied to identify the proteins interacting with S100A8 or S100A9. Bioinformatics analysis was used to seek the gene ontology of the interacting proteins. Co-immunoprecipitation (Co-IP) was applied to confirm the proteins interacted with S100A8 or S100A9.
 Results: Fourteen proteins including pyruvate kinase, muscle (PKM), nucleophosmin (NPM1) and eukaryotic translation initiation factor 5A (EIF5A), which potentially interacted with S100A8, were successfully identified by Flag-tag affinity purification followed by LC-MS/MS analysis. Six proteins, such as tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon (14-3-3ε) and PKM, which potentially interacted with S100A9, were successfully identified. Gene ontology analysis of the identified proteins suggested that proteins interacted with S100A8 or S100A9 were involved in several biological pathways, including canonical glycolysis, positive regulation of NF-κB transcription factor activity, negative regulation of apoptotic process, cell-cell adhesion, etc. Co-IP experiment confirmed that PKM2 can interact with both S100A8 and S100A9, and 14-3-3ε can interact with S100A8.
 Conclusion: PKM2 is identified to interact with both S100A8 and S100A9, while 14-3-3ε can interact with S100A9. These results may provide a new clue for the role of S100A8 or S100A9 in the progression of colitis-associated colorectal cancer.

"Missing pieces": exploring cardiac risk perceptions in older women.

PubMed

Lefler, Leanne L; McSweeney, Jean C; Garner, Kimberly K

2013-04-01

Approximately 95% of older women have factors that put them at risk for developing cardiovascular disease, but research indicates many do not perceive themselves to be at risk. We examined older women's perceived risk for coronary heart disease (CHD) and the factors influencing their perceptions. We conducted a descriptive, qualitative study using in-depth, individual interviews and quantitative measures to assess perceived risk and risk factors. Twenty-four older African American and Caucasian women had a mean 4.46 cardiac risk factors but perceived their own CHD risk as unrealistically low at 1.95 cm (SD = 1.57, on 0-to-8 cm visual analogue scale). Narrative data clustered in themes that represented a lack of fact-based information and multiple misconceptions about CHD and prevention. Major improvements in CHD health are only achievable if risk factors are prevented. This research suggests older women have substantial needs for consistent CHD information and prevention guidance. Copyright 2013, SLACK Incorporated.

"What I Wish You Knew": Social Barriers toward Physical Activity in Youth with Congenital Heart Disease (CHD)

ERIC Educational Resources Information Center

Moola, Fiona; Fusco, Caroline; Kirsh, Joel A.

2011-01-01

Despite the benefits of physical activity for youth with congenital heart disease (CHD), most patients are inactive. Although literature has addressed medical and psychological barriers to participation, little is known about the social barriers that youth encounter. This qualitative study explored sociocultural barriers to physical activity from…

Pre-Exercise Screening and Health Coaching in CHD Secondary Prevention: A Qualitative Study of the Patient Experience

ERIC Educational Resources Information Center

Shaw, R.; Gillies, M.; Barber, J.; MacIntyre, K.; Harkins, C.; Findlay, I. N.; McCloy, K.; Gillie, A.; Scoular, A.; MacIntyre, P. D.

2012-01-01

Secondary prevention programmes can be effective in reducing morbidity and mortality from coronary heart disease (CHD). In particular, UK guidelines, including those from the Department of Health, emphasize physical activity. However, the effects of secondary prevention programmes with an exercise component are moderate and uptake is highly…

Features of coronary heart disease development in emergency workers of the Chornobyl accident depending on the action of radiation and non radiation risk factors and genotypes of single nucleotide polymorphism rs966221 of phosphodiesterase 4D gene.

PubMed

Belyi, D; Pleskach, G; Nastina, O; Sidorenko, G; Kursina, N; Bazyka, O; Kovalev, O; Chumak, A; Abramenko, I

2016-12-01

This study devoted to specific features of coronary heart disease (CHD) development in emergency work ers (EW) of the accident at the Chernobyl nuclear power plant (ChNPP) based on analysis the interaction between radiation and non radiation risk factors and single nucleotide polymorphism (SNP) rs966221 of phosphodiesterase (PDE) 4D gene. It was examined 397 men with CHD, including 274 EW of 1986-1987 and 123 non irradiated persons (con trol group) who were 66±10 and 69±11 years old relatively. The program studies included clinical examination, elec trocardiography (ECG), ECG daily monitoring, ECG stress testing, echo doppler cardiography, analysis of serum lipid spectrum, polymerase chain reaction with restriction of reaction products, retrospective analysis of case histories. Diagnosis of CHD or its approval was carried out in accordance with the standards of diagnosis, accepted in Ukraine. All EW before their taking part in cleaning ChNPP territory did not suffered from CHD. According to the analysis of contingency tables, carriers of the TT genotype of rs966221 increased the risk of myocardial infarction (MI) in 2.538 times compared with carriers of genotypes CC and CT. The use of Kaplan Meier method showed that a half of EW with the TT genotype developed MI before 64 years old, while with the other geno types up to 78.7 years old. In the control group statistically significant increase of cumulative proportion of patients with MI, carriers of the TT genotype, began from 60 years old. Compared to the non irradiated patients EW fell ill with CHD on 9.4 years earlier. Using proportional hazards analysis (Cox regression), it was found that EW had 3.9 times higher risk of CHD than in non irradiated individuals. Smoking and overweight brought three times less but significant risk - 1.37 and 1.33 respectively. The TT genotype unlike genotypes CC and CT gene PDE4D increased risk of MI in 1.757 times more both in EW and control group. The risk of CHD development was

The impact of obesity on risk factors and prevalence and prognosis of coronary heart disease-the obesity paradox.

PubMed

De Schutter, Alban; Lavie, Carl J; Milani, Richard V

2014-01-01

Obesity is associated with a host of cardiovascular risk factors and its prevalence is rising rapidly. Despite strong evidence that obesity predisposes to the development and progression of coronary heart disease (CHD), numerous studies have shown an inverse relationship between various measures of obesity (most commonly body mass index) and outcomes in established CHD. In this article we review the evidence surrounding the ≪obesity paradox≫ in the secondary care of CHD patients and the CHD presentations where a paradox has been found. Finally we discuss the impact of cardiorespiratory fitness and a number of mechanisms which may offer potential explanations for this puzzling phenomenon. © 2014.

Stock volatility as a risk factor for coronary heart disease death.

PubMed

Ma, Wenjuan; Chen, Honglei; Jiang, Lili; Song, Guixiang; Kan, Haidong

2011-04-01

The volatility of financial markets may cause substantial emotional and physical stress among investors. We hypothesize that this may have adverse effects on cardiovascular health. The Chinese stock markets were extremely volatile between 2006 and 2008. We, therefore, examined the relationship between daily change of the Shanghai Stock Exchange (SSE) Composite Index (referred as the Index) and coronary heart disease (CHD) deaths from 1 January 2006 to 31 December 2008 in Shanghai, the financial capital of China. Daily death and stock performance data were collected from the Shanghai Center for Disease Control and Prevention and SSE, respectively. Data were analysed with over-dispersed generalized linear Poisson models, controlling for long-term and seasonal trends of CHD mortality, day of the week, Index closing value, weather conditions, and air pollution levels. We observed a U-shaped relationship between the Index change and CHD deaths: both rising and falling of the Index were associated with more deaths and the fewest deaths coincided with little or no change of the index. We also examined the absolute daily change of the Index in relation to CHD deaths: in a 1-day lag model, each 100-point change of the Index corresponded to 5.17% (95% confidence interval: 1.71, 8.63%) increase in CHD deaths. Further analysis showed that the association was stronger for out-of-hospital CHD death than for in-hospital death. We found that CHD deaths fluctuated with daily stock changes in Shanghai, suggesting that stock volatility may adversely affect cardiovascular health.

Cutaneous Uptake of 14C-HD Vapor by the Hairless Guinea Pig.

DTIC Science & Technology

1996-10-01

guinea pig (HGP) is used by our laboratory to model the human cutaneous response to sulfur mustard (HD) exposure. We have determined the HD content in the skin of HOP after 7-minute exposures to vapors saturated with a mixture of HD and 14C-HD. Concentration/time (C1) values in the range of 2 mg/sq cm/min were determined by counting skin 14C disintegrations per minute (dpm) in animals euthanized immediately after exposure. These values are similar to human penetration rates obtained by other investigators. A direct relationship between C1 and relative humidity was

A Genome-wide Regulatory Network Identifies Key Transcription Factors for Memory CD8+ T Cell Development

PubMed Central

Hu, Guangan; Chen, Jianzhu

2014-01-01

Memory CD8+ T cell development is defined by the expression of a specific set of memory signature genes (MSGs). Despite recent progress, many components of the transcriptional control of memory CD8+ T cell development are still unknown. To identify transcription factors (TFs) and their interactions in memory CD8+ T cell development, we construct a genome-wide regulatory network and apply it to identify key TFs that regulate MSGs. Most of the known TFs in memory CD8+ T cell development are rediscovered and about a dozen new TFs are also identified. Sox4, Bhlhe40, Bach2 and Runx2 are experimentally verified and Bach2 is further shown to promote both development and recall proliferation of memory CD8+ T cells through Prdm1 and Id3. Gene perturbation study identifies the mode of interactions among the TFs with Sox4 as a hub. The identified TFs and insights into their interactions should facilitate further dissection of molecular mechanisms underlying memory CD8+ T cell development. PMID:24335726

Qualitative evaluation of a local coronary heart disease treatment pathway: practical implications and theoretical framework.

PubMed

Kramer, Lena; Schlößler, Kathrin; Träger, Susanne; Donner-Banzhoff, Norbert

2012-05-14

Coronary heart disease (CHD) is a common medical problem in general practice. Due to its chronic character, shared care of the patient between general practitioner (GP) and cardiologist (C) is required. In order to improve the cooperation between both medical specialists for patients with CHD, a local treatment pathway was developed. The objective of this study was first to evaluate GPs' opinions regarding the pathway and its practical implications, and secondly to suggest a theoretical framework of the findings by feeding the identified key factors influencing the pathway implementation into a multi-dimensional model. The evaluation of the pathway was conducted in a qualitative design on a sample of 12 pathway developers (8 GPs and 4 cardiologists) and 4 pathway users (GPs). Face-to face interviews, which were aligned with previously conducted studies of the department and assumptions of the theory of planned behaviour (TPB), were performed following a semi-structured interview guideline. These were audio-taped, transcribed verbatim, coded, and analyzed according to the standards of qualitative content analysis. We identified 10 frequently mentioned key factors having an impact on the implementation success of the CHD treatment pathway. We thereby differentiated between pathway related (pathway content, effort, individual flexibility, ownership), behaviour related (previous behaviour, support), interaction related (patient, shared care/colleagues), and system related factors (context, health care system). The overall evaluation of the CHD pathway was positive, but did not automatically lead to a change of clinical behaviour as some GPs felt to have already acted as the pathway recommends. By providing an account of our experience creating and implementing an intersectoral care pathway for CHD, this study contributes to our knowledge of factors that may influence physicians' decisions regarding the use of a local treatment pathway. An improved adaptation of the

[Influences of environmental factors and interaction of several chemokines gene-environmental on systemic lupus erythematosus].

PubMed

Ye, Dong-qing; Hu, Yi-song; Li, Xiang-pei; Huang, Fen; Yang, Shi-gui; Hao, Jia-hu; Yin, Jing; Zhang, Guo-qing; Liu, Hui-hui

2004-11-01

To explore the impact of environmental factors, daily lifestyle, psycho-social factors and the interactions between environmental factors and chemokines genes on systemic lupus erythematosus (SLE). Case-control study was carried out and environmental factors for SLE were analyzed by univariate and multivariate unconditional logistic regression. Interactions between environmental factors and chemokines polymorphism contributing to systemic lupus erythematosus were also analyzed by logistic regression model. There were nineteen factors associated with SLE when univariate unconditional logistic regression was used. However, when multivariate unconditional logistic regression was used, only five factors showed having impacts on the disease, in which drinking well water (OR=0.099) was protective factor for SLE, and multiple drug allergy (OR=8.174), over-exposure to sunshine (OR=18.339), taking antibiotics (OR=9.630) and oral contraceptives were risk factors for SLE. When unconditional logistic regression model was used, results showed that there was interaction between eating irritable food and -2518MCP-1G/G genotype (OR=4.387). No interaction between environmental factors was found that contributing to SLE in this study. Many environmental factors were related to SLE, and there was an interaction between -2518MCP-1G/G genotype and eating irritable food.

Healthy lifestyle factors in the primary prevention of coronary heart disease among men: benefits among users and nonusers of lipid-lowering and antihypertensive medications.

PubMed

Chiuve, Stephanie E; McCullough, Marjorie L; Sacks, Frank M; Rimm, Eric B

2006-07-11

Healthy lifestyle choices such as eating a prudent diet, exercising regularly, managing weight, and not smoking may substantially reduce coronary heart disease (CHD) risk by improving lipids, blood pressure, and other risk factors. The burden of CHD that could be avoided through adherence to these modifiable lifestyle factors has not been assessed among middle-aged and older US men, specifically men taking medications for hypertension or hypercholesterolemia. We prospectively monitored 42 847 men in the Health Professionals Follow-up Study, 40 to 75 years of age and free of disease in 1986. Lifestyle factors were updated through self-reported questionnaires. Low risk was defined as (1) absence of smoking, (2) body mass index <25 kg/m2, (3) moderate-to-vigorous activity > or = 30 min/d, (4) moderate alcohol consumption (5 to 30 g/d), and (5) the top 40% of the distribution for a healthy diet score. Over 16 years, we documented 2183 incident cases of CHD (nonfatal myocardial infarction and fatal CHD). In multivariate-adjusted Cox proportional hazards models, men who were at low risk for 5 lifestyle factors had a lower risk of CHD (relative risk: 0.13; 95% confidence interval [CI]: 0.09, 0.19) compared with men who were at low risk for no lifestyle factors. Sixty-two percent (95% CI: 49%, 74%) of coronary events in this cohort may have been prevented with better adherence to these 5 healthy lifestyle practices. Among men taking medication for hypertension or hypercholesterolemia, 57% (95% CI: 32%, 79%) of all coronary events may have been prevented with a low-risk lifestyle. Compared with men who did not make lifestyle changes during follow-up, those who adopted > or = 2 additional low-risk lifestyle factors had a 27% (95% CI: 7%, 43%) lower risk of CHD. A majority of CHD events among US men may be preventable through adherence to healthy lifestyle practices, even among those taking medications for hypertension or hypercholesterolemia.

Interactive effects of global change factors on soil respiration and its components: a meta-analysis.

PubMed

Zhou, Lingyan; Zhou, Xuhui; Shao, Junjiong; Nie, Yuanyuan; He, Yanghui; Jiang, Liling; Wu, Zhuoting; Hosseini Bai, Shahla

2016-09-01

As the second largest carbon (C) flux between the atmosphere and terrestrial ecosystems, soil respiration (Rs) plays vital roles in regulating atmospheric CO2 concentration ([CO2 ]) and climatic dynamics in the earth system. Although numerous manipulative studies and a few meta-analyses have been conducted to determine the responses of Rs and its two components [i.e., autotrophic (Ra) and heterotrophic (Rh) respiration] to single global change factors, the interactive effects of the multiple factors are still unclear. In this study, we performed a meta-analysis of 150 multiple-factor (≥2) studies to examine the main and interactive effects of global change factors on Rs and its two components. Our results showed that elevated [CO2 ] (E), nitrogen addition (N), irrigation (I), and warming (W) induced significant increases in Rs by 28.6%, 8.8%, 9.7%, and 7.1%, respectively. The combined effects of the multiple factors, EN, EW, DE, IE, IN, IW, IEW, and DEW, were also significantly positive on Rs to a greater extent than those of the single-factor ones. For all the individual studies, the additive interactions were predominant on Rs (90.6%) and its components (≈70.0%) relative to synergistic and antagonistic ones. However, the different combinations of global change factors (e.g., EN, NW, EW, IW) indicated that the three types of interactions were all important, with two combinations for synergistic effects, two for antagonistic, and five for additive when at least eight independent experiments were considered. In addition, the interactions of elevated [CO2 ] and warming had opposite effects on Ra and Rh, suggesting that different processes may influence their responses to the multifactor interactions. Our study highlights the crucial importance of the interactive effects among the multiple factors on Rs and its components, which could inform regional and global models to assess the climate-biosphere feedbacks and improve predictions of the future states of the

Novel coronary heart disease risk factors at 60–64 years and life course socioeconomic position: The 1946 British birth cohort

PubMed Central

Jones, Rebecca; Hardy, Rebecca; Sattar, Naveed; Deanfield, John E.; Hughes, Alun; Kuh, Diana; Murray, Emily T.; Whincup, Peter H.; Thomas, Claudia

2015-01-01

Social disadvantage across the life course is associated with a greater risk of coronary heart disease (CHD) and with established CHD risk factors, but less is known about whether novel CHD risk factors show the same patterns. The Medical Research Council National Survey of Health and Development was used to investigate associations between occupational socioeconomic position during childhood, early adulthood and middle age and markers of inflammation (C-reactive protein, interleukin-6), endothelial function (E-selectin, tissue-plasminogen activator), adipocyte function (leptin, adiponectin) and pancreatic beta cell function (proinsulin) measured at 60–64 years. Life course models representing sensitive periods, accumulation of risk and social mobility were compared with a saturated model to ascertain the nature of the relationship between social class across the life course and each of these novel CHD risk factors. For interleukin-6 and leptin, low childhood socioeconomic position alone was associated with high risk factor levels at 60–64 years, while for C-reactive protein and proinsulin, cumulative effects of low socioeconomic position in both childhood and early adulthood were associated with higher (adverse) risk factor levels at 60–64 years. No associations were observed between socioeconomic position at any life period with either endothelial marker or adiponectin. Associations for C-reactive protein, interleukin-6, leptin and proinsulin were reduced considerably by adjustment for body mass index and, to a lesser extent, cigarette smoking. In conclusion, socioeconomic position in early life is an important determinant of several novel CHD risk factors. Body mass index may be an important mediator of these relationships. PMID:25437893

Qualitative evaluation of a local coronary heart disease treatment pathway: practical implications and theoretical framework

PubMed Central

2012-01-01

Background Coronary heart disease (CHD) is a common medical problem in general practice. Due to its chronic character, shared care of the patient between general practitioner (GP) and cardiologist (C) is required. In order to improve the cooperation between both medical specialists for patients with CHD, a local treatment pathway was developed. The objective of this study was first to evaluate GPs’ opinions regarding the pathway and its practical implications, and secondly to suggest a theoretical framework of the findings by feeding the identified key factors influencing the pathway implementation into a multi-dimensional model. Methods The evaluation of the pathway was conducted in a qualitative design on a sample of 12 pathway developers (8 GPs and 4 cardiologists) and 4 pathway users (GPs). Face-to face interviews, which were aligned with previously conducted studies of the department and assumptions of the theory of planned behaviour (TPB), were performed following a semi-structured interview guideline. These were audio-taped, transcribed verbatim, coded, and analyzed according to the standards of qualitative content analysis. Results We identified 10 frequently mentioned key factors having an impact on the implementation success of the CHD treatment pathway. We thereby differentiated between pathway related (pathway content, effort, individual flexibility, ownership), behaviour related (previous behaviour, support), interaction related (patient, shared care/colleagues), and system related factors (context, health care system). The overall evaluation of the CHD pathway was positive, but did not automatically lead to a change of clinical behaviour as some GPs felt to have already acted as the pathway recommends. Conclusions By providing an account of our experience creating and implementing an intersectoral care pathway for CHD, this study contributes to our knowledge of factors that may influence physicians’ decisions regarding the use of a local treatment

21 CFR 101.81 - Health claims: Soluble fiber from certain foods and risk of coronary heart disease (CHD).

Code of Federal Regulations, 2011 CFR

2011-04-01

...) of LDL-cholesterol. The scientific evidence establishes that diets high in saturated fat and..., and then removal by centrifugation of the insoluble components consisting of a high portion of protein... of coronary heart disease (CHD). (a) Relationship between diets that are low in saturated fat and...

21 CFR 101.81 - Health claims: Soluble fiber from certain foods and risk of coronary heart disease (CHD).

Code of Federal Regulations, 2014 CFR

2014-04-01

...) of LDL-cholesterol. The scientific evidence establishes that diets high in saturated fat and..., and then removal by centrifugation of the insoluble components consisting of a high portion of protein... of coronary heart disease (CHD). (a) Relationship between diets that are low in saturated fat and...

21 CFR 101.81 - Health claims: Soluble fiber from certain foods and risk of coronary heart disease (CHD).

Code of Federal Regulations, 2013 CFR

2013-04-01

...) of LDL-cholesterol. The scientific evidence establishes that diets high in saturated fat and..., and then removal by centrifugation of the insoluble components consisting of a high portion of protein... of coronary heart disease (CHD). (a) Relationship between diets that are low in saturated fat and...

21 CFR 101.81 - Health claims: Soluble fiber from certain foods and risk of coronary heart disease (CHD).

Code of Federal Regulations, 2012 CFR

2012-04-01

...) of LDL-cholesterol. The scientific evidence establishes that diets high in saturated fat and..., and then removal by centrifugation of the insoluble components consisting of a high portion of protein... of coronary heart disease (CHD). (a) Relationship between diets that are low in saturated fat and...

The future impact of population growth and aging on coronary heart disease in China: projections from the Coronary Heart Disease Policy Model-China

PubMed Central

Moran, Andrew; Zhao, Dong; Gu, Dongfeng; Coxson, Pamela; Chen, Chung-Shiuan; Cheng, Jun; Liu, Jing; He, Jiang; Goldman, Lee

2008-01-01

Background China will experience an overall growth and aging of its adult population in coming decades. We used a computer model to forecast the future impact of these demographic changes on coronary heart disease (CHD) in China. Methods The CHD Policy Model is a validated state-transition, computer simulation of CHD on a national scale. China-specific CHD risk factor, incidence, case-fatality, and prevalence data were incorporated, and a CHD prediction model was generated from a Chinese cohort study and calibrated to age-specific Chinese mortality rates. Disability-adjusted life years (DALYs) due to CHD were calculated using standard methods. The projected population of China aged 35–84 years was entered, and CHD events, deaths, and DALYs were simulated over 2000–2029. CHD risk factors other than age and case-fatality were held at year 2000 levels. Sensitivity analyses tested uncertainty regarding CHD mortality coding, the proportion of total deaths attributable to CHD, and case-fatality. Results We predicted 7.8 million excess CHD events (a 69% increase) and 3.4 million excess CHD deaths (a 64% increase) in the decade 2020–2029 compared with 2000–2009. For 2030, we predicted 71% of almost one million annual CHD deaths will occur in persons ≥65 years old, while 67% of the growing annual burden of CHD death and disability will weigh on adults <65 years old. Substituting alternate CHD mortality assumptions led to 17–20% more predicted CHD deaths over 2000–2029, though the pattern of increases in CHD events and deaths over time remained. Conclusion We forecast that absolute numbers of CHD events and deaths will increase dramatically in China over 2010–2029, due to a growing and aging population alone. Recent data suggest CHD risk factor levels are increasing, so our projections may underestimate the extent of the potential CHD epidemic in China. PMID:19036167

Polycystic ovary syndrome (PCOS) and the risk of coronary heart disease (CHD): a meta-analysis.

PubMed

Zhao, Luqian; Zhu, Zhigang; Lou, Huiling; Zhu, Guodong; Huang, Weimin; Zhang, Shaogang; Liu, Feng

2016-06-07

Some studies reported a significant association between polycystic ovary syndrome (PCOS) and risk of cardiovascular disease (CVD). However, the results are controversial. A systematic search was conducted in the PubMed, Science Direct, EMBASE, and Cochrane Library databases. Five case-control studies and 5 cohort studies were selected, involving a total of 104392 subjects in this meta-analysis. PCOS was significantly associated with the increased risk of CVD (OR = 1.30; 95% CI 1.09 - 1.56; P = 0.004). In the subgroup analysis of study design, both case-control studies and prospective cohort studies showed significant results (OR = 1.79; 95% CI 1.16 - 2.77; P = 0.009; OR = 1.20; 95% CI 1.06 - 1.37; P = 0.005), while retrospective cohort studies did not show positive result (OR = 0.91; 95% CI 0.60 - 1.40; P = 0.68). In a further stratified analysis by type of CVD, a significant association was found between PCOS and coronary heart disease (CHD) (OR = 1.44; 95% CI 1.13 - 1.84; P = 0.004). However, no significant association was observed between PCOS and myocardial infarction (MI) (OR = 1.01; 95% CI 0.68 - 1.51; P = 0.95). In conclusion, this meta-analysis suggested that PCOS is significantly associated with increased CHD risk.

Studies on adsorption, reaction mechanisms and kinetics for photocatalytic degradation of CHD, a pharmaceutical waste.

PubMed

Sarkar, Santanu; Bhattacharjee, Chiranjib; Curcio, Stefano

2015-11-01

The photocatalytic degradation of chlorhexidine digluconate (CHD), a disinfectant and topical antiseptic and adsorption of CHD catalyst surface in dark condition has been studied. Moreover, the value of kinetic parameters has been measured and the effect of adsorption on photocatalysis has been investigated here. Substantial removal was observed during the photocatalysis process, whereas 40% removal was possible through the adsorption route on TiO2 surface. The parametric variation has shown that alkaline pH, ambient temperature, low initial substrate concentration, high TiO2 loading were favourable, though at a certain concentration of TiO2 loading, photocatalytic degradation efficiency was found to be maximum. The adsorption study has shown good confirmation with Langmuir isotherm and during the reaction at initial stage, it followed pseudo-first-order reaction, after that Langmuir Hinshelwood model was found to be appropriate in describing the system. The present study also confirmed that there is a significant effect of adsorption on photocatalytic degradation. The possible mechanism for adsorption and photocatalysis has been shown here and process controlling step has been identified. The influences of pH and temperature have been explained with the help of surface charge distribution of reacting particles and thermodynamic point of view respectively. Copyright © 2015 Elsevier Inc. All rights reserved.

Increased Risk of Coronary Heart Disease in Patients with Primary Fibromyalgia and Those with Concomitant Comorbidity—A Taiwanese Population-Based Cohort Study

PubMed Central

Su, Chia-Hsien; Chen, Jiunn-Horng; Lan, Joung-Liang; Wang, Yu-Chiao; Tseng, Chun-Hung; Hsu, Chung-Yi; Huang, Lichi

2015-01-01

Objectives Fibromyalgia has seldom been associated with coronary heart disease (CHD). The aim of this study was to evaluate the risk of CHD in patients with fibromyalgia. Methods We used a dataset of one million participants, systemically scrambled from the Taiwanese national insurance beneficiaries, to identify 61,612 patients with incident fibromyalgia (ICD-9-CM 729.0–729.1) and 184,834 reference subjects matched by sex, age and index date of diagnosis in a 1:3 ratio from 2000 to 2005, with a mean 8.86 ± 2.68 years of follow-up until 2011. Risk of CHD was analyzed by Cox proportional hazard modeling. Results Patients with fibromyalgia had a mean age of 44.1 ± 16.5 years. CHD events developed in fibromyalgia patients (n = 8,280; 15.2 per 103 person-years) and reference subjects (n = 15,162; 9.26 per 103 person-years) with a significant incidence rate ratio of 1.64 (95% confidence interval: 1.61–1.68). The adjusted hazard ratio for CHD in fibromyalgia patients relative to reference subjects was 1.47 (1.43–1.51), after adjusting for age, gender, occupation, monthly income, traditional cardiovascular comorbidities, depression and anxiety. We noted that fibromyalgia and cardiovascular comorbidities had a significant interaction effect on CHD risk (p for interaction <0.01), which was markedly enhanced in fibromyalgia patients with concomitant comorbidities relative to patients with primary fibromyalgia and reference subjects (no fibromyalgia, no comorbidity). Conclusions Our report shows that fibromyalgia patients have an independent risk for CHD development. Fibromyalgia patients with concomitant comorbidities have markedly increased CHD risk relative to those with primary fibromyalgia. PMID:26366998

The role of health-related behavioural factors in accounting for inequalities in coronary heart disease risk by education and area deprivation: prospective study of 1.2 million UK women.

PubMed

Floud, Sarah; Balkwill, Angela; Moser, Kath; Reeves, Gillian K; Green, Jane; Beral, Valerie; Cairns, Benjamin J

2016-10-13

Some recent research has suggested that health-related behaviours, such as smoking, might explain much of the socio-economic inequalities in coronary heart disease (CHD) risk. In a large prospective study of UK women, we investigated the associations between education and area deprivation and CHD risk and assessed the contributions of smoking, alcohol consumption, physical activity and body mass index (BMI) to these inequalities. After excluding women with heart disease, stroke or cancer at recruitment, 1,202,983 women aged 56 years (SD 5 years) on average, were followed for first coronary event (hospital admission or death) and for CHD mortality. Relative risks of CHD were estimated by Cox regression, and the extent to which any association could be accounted for by smoking, alcohol, physical inactivity, and BMI was assessed by calculating the percentage reduction in the relevant likelihood-ratio (LR) statistic after adjustment for these factors, separately and together. A total of 71,897 women had a first CHD event (hospital admission or death) and 6032 died from CHD during 12 years follow-up. In analyses adjusted by age, birth cohort and region of residence only, lower levels of education and greater deprivation were associated with higher risks of CHD (P heterogeneity  < 0.0001 for each); associations for education were found within every level of deprivation and for deprivation were found within every level of education. Smoking, alcohol consumption, physical inactivity and BMI accounted for most of the associations (adjustment for all four factors together reduced the LR statistics for education and for deprivation by 76 % and 71 %, respectively, for first CHD event; and by 87 % and 79 %, respectively, for CHD mortality). Of these four factors, adjustment for smoking resulted in the largest reduction in the LR statistic. Given the large reduction in the predictive values of education and deprivation after adjustment for only four health

The effects of TLR3, TRIF and TRAF3 SNPs and interactions with environmental factors on type 2 diabetes mellitus and vascular complications in a Han Chinese population.

PubMed

Zhou, Zixing; Zeng, Chengli; Nie, Lihong; Huang, Shiqi; Guo, Congcong; Xiao, Di; Han, Yajing; Ye, Xiaohong; Ou, Meiling; Huang, Chuican; Ye, Xingguang; Wen, Zihao; Yang, Guang; Jing, Chunxia

2017-08-30

Toll-like receptor 3 (TLR3) is involved in type I interferon-β (IFN-β) via TIR-domain-containing adapter-inducing interferon-β (TRIF) and Tumor necrosis factor receptor-associated factor 3 (TRAF3), culminating in inflammation and immunity reactions. TLR3 is implicated in insulin resistance and type 2 diabetes mellitus (T2DM). Eight SNPs of these genes were detected in 552 T2DM patients and 552 matched healthy control subjects. Gene-gene and gene-environment interactions and haplotype associations were also evaluated. We identified a 21% increased risk of T2DM for the T allele of rs12435483 in the TRAF3 gene (OR: 1.21; 95% CI: 1.01-1.44; P=0.036). The GA genotype and GA+AA genotype of TRAF3 rs12147254 were found to increase the risk of coronary heart disease (CHD) among T2DM patients (GA vs. GG: OR=4.17, 95% CI: 1.04-16.79, P=0.045; GA+AA vs. GG: OR=3.97, 95% CI: 1.02-15.48, P=0.047). However, the GACGAC haplotype in TRAF3 had a protective effect on T2DM micro-macrovascular complications (OR=0.33, 95% CI: 0.13-0.85, P=0.017). Two-factor (TRAF3 rs12435483 and LDL) and three-factor (TRAF3 rs12435483, BMI and HDL) interactions of the risk of T2DM were identified. In conclusion, the genetic variants in the TLR3-TRIF-TRAF3-INF-β signaling pathway and interactions with some particular environmental factors (LDL, BMI and HDL) may contribute to susceptibility to T2DM and vascular complications in the Han Chinese population. Copyright © 2017. Published by Elsevier B.V.

Risk Factors for Coronary Heart Disease Among Inpatients Who Have Mild Intellectual Disability and Mental Illness

ERIC Educational Resources Information Center

Merriman, S.; Haw, C.; Kirk, J.; Stubbs, J.

2005-01-01

Coronary heart disease (CHD) is a major cause of morbidity and mortality in the UK. The aim of this study was to screen inpatients with mild or borderline intellectual disability, many of whom also have mental illness, for risk factors for CHD. Participants were interviewed, measured and had blood samples taken. Of the 53 participants, 20 (37.7%)…

Cardiovascular risk factors associated with the metabolic syndrome are more prevalent in people reporting chronic pain: results from a cross-sectional general population study.

PubMed

Goodson, Nicola J; Smith, Blair H; Hocking, Lynne J; McGilchrist, Mark M; Dominiczak, Anna F; Morris, Andrew; Porteous, David J; Goebel, Andreas

2013-09-01

To explore whether chronic pain is associated with cardiovascular risk factors and identify whether increased distribution or intensity of pain is associated with cardiovascular risk, participants in Generation Scotland: The Scottish Family Health study completed pain questionnaires recording the following: presence of chronic pain, distribution of pain, and intensity of chronic pain. Blood pressure, lipids, blood glucose, smoking history, waist-hip ratio, and body mass index were recorded; Framingham 10-year coronary heart disease (CHD) risk scores were calculated and a diagnosis of metabolic syndrome derived. Associations between chronic pain and cardiovascular risk were explored. Of 13,328 participants, 1100 (8.3%) had high CHD risk. Chronic pain was reported by 5209 (39%), 1294 (9.7%) reported widespread chronic pain, and 707 (5.3%) reported high-intensity chronic pain. In age- and gender-adjusted analyses, chronic pain was associated with elevated CHD risk scores (odds ratio 1.11, 95% confidence interval 1.01-1.23) and the metabolic syndrome (odds ratio 1.42, 95% confidence interval 1.24-1.62). Multivariate analyses identified dyslipidaemia, age, gender, smoking, obesity, and high waist-hip ratio as independently associated with chronic pain. Within the chronic pain subgroup, widespread pain did not confer any additional cardiovascular disease risk. However, cardiovascular disease risk factors contributing to metabolic syndrome were more prevalent in those reporting high-intensity chronic pain. This large population-based study has demonstrated that chronic pain, and in particular high-intensity chronic pain, is associated with an increased prevalence of cardiovascular risk factors and metabolic syndrome. The 10-year CHD risk score and metabolic syndrome correlate well with increased pain intensity, but not with widespread pain. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Insulin-like growth factor (IGF)-I, IGF-II and IGF-binding protein (IGFBP)-3 levels in Arab subjects with coronary heart disease.

PubMed

Akanji, A O; Suresh, C G; Al-Radwan, R; Fatania, H R

2007-01-01

Insulin-like growth factors (IGF-I, IGF-II) and their binding protein (IGFBP-3) may be risk markers for coronary heart disease (CHD). This study aimed to assess the levels and determinants of the serum levels of IGF-I, IGF-II and IGFBP-3 in Arab patients with established CHD. Two groups of subjects were matched for age, gender, BMI and waist-hip ratio (WHR): (i) CHD (n = 105), median age 51.0 (range 40.0-60.0) years; (ii) controls (n = 97) aged 49.0 (range 37.0-60.0) years. We measured fasting serum levels of glucose and lipoproteins (total cholesterol, triglycerides, LDL, HDL, apo B), insulin, HOMA-IR, IGF-I, IGF-II and IGFBP-3 and compared the results between groups. The effects of body mass and the metabolic syndrome (MS) on IGF levels were also examined, and linear correlations were sought between the various parameters. The levels of IGF-I, IGF-II and IGFBP-3 were significantly lower (all p<0.01) for the CHD group than for the control group. These differences were not influenced by BMI or with the presence of MS. In CHD, there were no significant correlations between levels of IGF-I and IGF-II and age, BMI, WHR, lipoprotein concentrations and insulin sensitivity, although IGFBP-3 had weakly significant relationships with some of the lipoproteins. Levels of IGF-I, IGF-II and IGFBP3 are reduced in male Arab patients with CHD, and did not appear influenced by traditional CHD risk factors such as age, BMI, insulin sensitivity and presence of MS. Perturbations in the IGF/IGFBP-3 axis may be potential additional targets for pharmacological manipulation in CHD.

Tumor Necrosis Factor-Alpha Gene Promoter Region Polymorphism and the Risk of Coronary Heart Disease

PubMed Central

Asifa, Gul Zareen; Kazmi, Syed Ali Raza; Javed, Qamar

2013-01-01

Background. Tumor necrosis factor-alpha (TNF-α) gene polymorphisms have been implicated in the manifestation of atherosclerosis. Controversy exists regarding the link between the cytokine's variant genotype and CHD among different ethnic groups. There have been fewer studies on the TNF-α gene −1031T>C and −863C>A polymorphisms in relation to CHD. Therefore, the current study was designed to investigate the association of the TNF-α gene −1031T>C and −863C>A polymorphisms with CHD in a Pakistani population. Methods. Patients with CHD (n = 310) and healthy individuals (n = 310) were enrolled in this study. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results. A significant difference was observed in the −863C>A polymorphism between patients with CHD and control subjects (P < 0.0001). CHD risk was positively associated with the variant allele −863A (P < 0.0001) in the study subjects. There was no significant link between the −1031T>C polymorphism and CHD risk in the study population. Haplotypes A-T and A-C of the TNF-alpha gene loci at −863 and −1031 showed higher frequency in the patient group compared with controls (P < 0.05). Conclusion. The TNF-α  −863C>A gene polymorphism was associated with the pathogenesis of CHD while the −1031T>C polymorphism did not show any link with the disease in a Pakistani population. PMID:24381514

Characterization of the primary interaction between the mating pheromone, alpha-factor, and its receptor in Saccharomyces cerevisiae

DOE Office of Scientific and Technical Information (OSTI.GOV)

Raths, S.K.

1987-01-01

Alpha-factor is a peptide of thirteen amino acids which is required for mating between the haploid mating types, a and ..cap alpha.., in Saccharomyces cerevisiae. An analogue of alpha-factor, DHP/sup 8/ DHP/sup 11/ Nle/sup 12/ tridecapeptide, was catalytically reduced in the presence of /sup 3/H gas for production of a radiolabeled pheromone suitable for use in binding studies. Incorporation of tritium resulted in /sup 3/H-alpha-factor with high specific activity, purity, biological activity and long shelf-life. Binding studies revealed that alpha-factor interacts with its receptor via a simple, reversible process which obeys the law of mass action. Association and dissociation kineticsmore » indicate values of 2.92 x 10/sup 6/ M/sup /minus/1/ min/sup -1/ for k/sub 1/ and between 4 and 7 x 10/sup /minus/2/ min/sup /minus/1/ for k/sub /minus/1/. Saturation binding studies reveal an equilibrium dissociation constant equal to 2.32 x 10/sup /minus/8/ M which approximate the kinetically-derived K/sub D/ of 2.12 x 10/sup /minus/8/ M. Scatchard and Hill analyses as well as dissociation behavior in the presence of excess unlabeled ligand indicate alpha-factor interacts with a homogeneous population of binding sites which do not interact and exhibit one affinity for the alpha-factor pheromone.« less

NF-κB p65 Subunit Mediates Lipopolysaccharide-Induced Na+/I− Symporter Gene Expression by Involving Functional Interaction with the Paired Domain Transcription Factor Pax8

PubMed Central

Nicola, Juan Pablo; Nazar, Magalí; Mascanfroni, Iván Darío; Pellizas, Claudia Gabriela; Masini-Repiso, Ana María

2010-01-01

The Gram-negative bacterial endotoxin lipopolysaccharide (LPS) elicits a variety of biological responses. Na+/I− symporter (NIS)-mediated iodide uptake is the main rate-limiting step in thyroid hormonogenesis. We have recently reported that LPS stimulates TSH-induced iodide uptake. Here, we further analyzed the molecular mechanism involved in the LPS-induced NIS expression in Fisher rat thyroid cell line 5 (FRTL-5) thyroid cells. We observed an increase in TSH-induced NIS mRNA expression in a dose-dependent manner upon LPS treatment. LPS enhanced the TSH-stimulated NIS promoter activity denoting the NIS-upstream enhancer region (NUE) as responsible for the stimulatory effects. We characterized a novel putative conserved κB site for the transcription factor nuclear factor-κB (NF-κB) within the NUE region. NUE contains two binding sites for the transcription factor paired box 8 (Pax8), main regulator of NIS transcription. A physical interaction was observed between the NF-κB p65 subunit and paired box 8 (Pax8), which appears to be responsible for the synergic effect displayed by these transcription factors on NIS gene transcription. Moreover, functional blockage of NF-κB signaling and site-directed mutagenesis of the κB cis-acting element abrogated LPS stimulation. Silencing expression of p65 confirmed its participation as an effector of LPS-induced NIS stimulation. Furthermore, chromatin immunoprecipitation corroborated that NIS is a novel target gene for p65 transactivation in response to LPS. Moreover, we were able to corroborate the LPS-stimulatory effect on thyroid cells in vivo in LPS-treated rats, supporting that thyrocytes are capable of responding to systemic infections. In conclusion, our results reveal a new mechanism involving p65 in the LPS-induced NIS expression, denoting a novel aspect in thyroid cell differentiation. PMID:20667985

A systematic review of the evidence supporting a causal link between dietary factors and coronary heart disease.

PubMed

Mente, Andrew; de Koning, Lawrence; Shannon, Harry S; Anand, Sonia S

2009-04-13

Although a wealth of literature links dietary factors and coronary heart disease (CHD), the strength of the evidence supporting valid associations has not been evaluated systematically in a single investigation. We conducted a systematic search of MEDLINE for prospective cohort studies or randomized trials investigating dietary exposures in relation to CHD. We used the Bradford Hill guidelines to derive a causation score based on 4 criteria (strength, consistency, temporality, and coherence) for each dietary exposure in cohort studies and examined for consistency with the findings of randomized trials. Strong evidence supports valid associations (4 criteria satisfied) of protective factors, including intake of vegetables, nuts, and "Mediterranean" and high-quality dietary patterns with CHD, and associations of harmful factors, including intake of trans-fatty acids and foods with a high glycemic index or load. Among studies of higher methodologic quality, there was also strong evidence for monounsaturated fatty acids and "prudent" and "western" dietary patterns. Moderate evidence (3 criteria) of associations exists for intake of fish, marine omega-3 fatty acids, folate, whole grains, dietary vitamins E and C, beta carotene, alcohol, fruit, and fiber. Insufficient evidence (< or =2 criteria) of association is present for intake of supplementary vitamin E and ascorbic acid (vitamin C); saturated and polyunsaturated fatty acids; total fat; alpha-linolenic acid; meat; eggs; and milk. Among the dietary exposures with strong evidence of causation from cohort studies, only a Mediterranean dietary pattern is related to CHD in randomized trials. The evidence supports a valid association of a limited number of dietary factors and dietary patterns with CHD. Future evaluation of dietary patterns, including their nutrient and food components, in cohort studies and randomized trials is recommended.

Implantable cardiac devices: the utility of remote monitoring in a paediatric and CHD population.

PubMed

Olen, Melissa M; Dechert-Crooks, Brynn

2017-01-01

Remote monitoring in the modern era has improved outcomes for patients with cardiac implantable electronic devices. There are many advantages to remote monitoring, including improved quality of life for patients, decreased need for in-office interrogation, and secondary reduced costs. Patient safety and enhanced survival remain the most significant benefit. With most of the published literature on this topic being focussed on adults, paediatric outcomes continue to be defined. This is a review of the benefits of remote monitoring in paediatrics and in patients with CHD.

7Be(p,gamma)8B S-factor from Ab Initio Wave Functions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Navratil, P; Bertulani, C A; Caurier, E

2006-10-12

There has been a significant progress in ab initio approaches to the structure of light nuclei. Starting from realistic two- and three-nucleon interactions the ab initio no-core shell model (NCSM) predicts low-lying levels in p-shell nuclei. It is a challenging task to extend ab initio methods to describe nuclear reactions. We present here a brief overview of the first steps taken toward nuclear reaction applications. In particular, we discuss our calculation of the {sup 7}Be(p,{gamma}){sup 8}B S-factor. We also present our first results of the {sup 3}He({alpha},{gamma}){sup 7}Be S-factor and of the S-factor of the mirror reaction {sup 3}H({alpha},{gamma}){sup 7}Li.more » The {sup 7}Be(p,{gamma}){sup 8}B and {sup 3}He({alpha},{gamma}){sup 7}Be reactions correspond to the most important uncertainties in solar model predictions of neutrino fluxes.« less

p62/Sequestosome-1, Autophagy-related Gene 8, and Autophagy in Drosophila Are Regulated by Nuclear Factor Erythroid 2-related Factor 2 (NRF2), Independent of Transcription Factor TFEB.

PubMed

Jain, Ashish; Rusten, Tor Erik; Katheder, Nadja; Elvenes, Julianne; Bruun, Jack-Ansgar; Sjøttem, Eva; Lamark, Trond; Johansen, Terje

2015-06-12

The selective autophagy receptor p62/sequestosome 1 (SQSTM1) interacts directly with LC3 and is involved in oxidative stress signaling in two ways in mammals. First, p62 is transcriptionally induced upon oxidative stress by the NF-E2-related factor 2 (NRF2) by direct binding to an antioxidant response element in the p62 promoter. Second, p62 accumulation, occurring when autophagy is impaired, leads to increased p62 binding to the NRF2 inhibitor KEAP1, resulting in reduced proteasomal turnover of NRF2. This gives chronic oxidative stress signaling through a feed forward loop. Here, we show that the Drosophila p62/SQSTM1 orthologue, Ref(2)P, interacts directly with DmAtg8a via an LC3-interacting region motif, supporting a role for Ref(2)P in selective autophagy. The ref(2)P promoter also contains a functional antioxidant response element that is directly bound by the NRF2 orthologue, CncC, which can induce ref(2)P expression along with the oxidative stress-associated gene gstD1. However, distinct from the situation in mammals, Ref(2)P does not interact directly with DmKeap1 via a KEAP1-interacting region motif; nor does ectopically expressed Ref(2)P or autophagy deficiency activate the oxidative stress response. Instead, DmAtg8a interacts directly with DmKeap1, and DmKeap1 is removed upon programmed autophagy in Drosophila gut cells. Strikingly, CncC induced increased Atg8a levels and autophagy independent of TFEB/MitF in fat body and larval gut tissues. Thus, these results extend the intimate relationship between oxidative stress-sensing NRF2/CncC transcription factors and autophagy and suggest that NRF2/CncC may regulate autophagic activity in other organisms too. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Regulation of fibroblast growth factor receptor signalling and trafficking by Src and Eps8.

PubMed

Auciello, Giulio; Cunningham, Debbie L; Tatar, Tulin; Heath, John K; Rappoport, Joshua Z

2013-01-15

Fibroblast growth factor receptors (FGFRs) mediate a wide spectrum of cellular responses that are crucial for development and wound healing. However, aberrant FGFR activity leads to cancer. Activated growth factor receptors undergo stimulated endocytosis, but can continue to signal along the endocytic pathway. Endocytic trafficking controls the duration and intensity of signalling, and growth factor receptor signalling can lead to modifications of trafficking pathways. We have developed live-cell imaging methods for studying FGFR dynamics to investigate mechanisms that coordinate the interplay between receptor trafficking and signal transduction. Activated FGFR enters the cell following recruitment to pre-formed clathrin-coated pits (CCPs). However, FGFR activation stimulates clathrin-mediated endocytosis; FGF treatment increases the number of CCPs, including those undergoing endocytosis, and this effect is mediated by Src and its phosphorylation target Eps8. Eps8 interacts with the clathrin-mediated endocytosis machinery and depletion of Eps8 inhibits FGFR trafficking and immediate Erk signalling. Once internalized, FGFR passes through peripheral early endosomes en route to recycling and degredative compartments, through an Src- and Eps8-dependent mechanism. Thus Eps8 functions as a key coordinator in the interplay between FGFR signalling and trafficking. This work provides the first detailed mechanistic analysis of growth factor receptor clustering at the cell surface through signal transduction and endocytic trafficking. As we have characterised the Src target Eps8 as a key regulator of FGFR signalling and trafficking, and identified the early endocytic system as the site of Eps8-mediated effects, this work provides novel mechanistic insight into the reciprocal regulation of growth factor receptor signalling and trafficking.

NT-proBNP is associated with coronary heart disease risk in healthy older women but fails to enhance prediction beyond established risk factors: results from the British Women's Heart and Health Study.

PubMed

Sattar, Naveed; Welsh, Paul; Sarwar, Nadeem; Danesh, John; Di Angelantonio, Emanuele; Gudnason, Vilmundur; Davey Smith, George; Ebrahim, Shah; Lawlor, Debbie A

2010-03-01

Limited evidence suggests NT-proBNP improves prediction of coronary heart disease (CHD) events but further data are needed, especially in people without pre-existing CHD and in women. We measured NT-proBNP in serum from 162 women with incident CHD events and 1226 controls (60-79 years) in a case-control study nested within the prospective British Women's Heart and Health Study. All cases and controls were free from CHD at baseline. We related NT-proBNP to CHD event risk, and determined to what extent NT-proBNP enhanced CHD risk prediction beyond established risk factors. The odds ratio for CHD per 1 standard deviation increase in log(e)NT-proBNP was 1.37 (95% CI: 1.13-1.68) in analyses adjusted for established CHD risk factors, social class, CRP and insulin. However, addition of log(e)NT-proBNP did not improve the discrimination of a prediction model including age, social class, smoking, physical activity, lipids, fasting glucose, waist:hip ratio, hypertension, statin and aspirin use, nor a standard Framingham risk score model; area under the receiver operator curve for the former model increased from 0.676 to 0.687 on inclusion of NT-proBNP (p=0.3). Furthermore, adding NT-proBNP did not improve calibration of a prediction model containing established risk factors, nor did inclusion more appropriately re-classify participants in relation to their final outcome. Findings were similar (independent associations, but no prediction improvement) for fasting insulin and CRP. These results caution against use of NT-proBNP for CHD risk prediction in healthy women and suggest a need for larger studies in both genders to resolve outstanding uncertainties.

Thyroid antibody status, subclinical hypothyroidism, and the risk of coronary heart disease: an individual participant data analysis.

PubMed

Collet, Tinh-Hai; Bauer, Douglas C; Cappola, Anne R; Asvold, Bjørn O; Weiler, Stefan; Vittinghoff, Eric; Gussekloo, Jacobijn; Bremner, Alexandra; den Elzen, Wendy P J; Maciel, Rui M B; Vanderpump, Mark P J; Cornuz, Jacques; Dörr, Marcus; Wallaschofski, Henri; Newman, Anne B; Sgarbi, José A; Razvi, Salman; Völzke, Henry; Walsh, John P; Aujesky, Drahomir; Rodondi, Nicolas

2014-09-01

Subclinical hypothyroidism has been associated with increased risk of coronary heart disease (CHD), particularly with thyrotropin levels of 10.0 mIU/L or greater. The measurement of thyroid antibodies helps predict the progression to overt hypothyroidism, but it is unclear whether thyroid autoimmunity independently affects CHD risk. The objective of the study was to compare the CHD risk of subclinical hypothyroidism with and without thyroid peroxidase antibodies (TPOAbs). A MEDLINE and EMBASE search from 1950 to 2011 was conducted for prospective cohorts, reporting baseline thyroid function, antibodies, and CHD outcomes. Individual data of 38 274 participants from six cohorts for CHD mortality followed up for 460 333 person-years and 33 394 participants from four cohorts for CHD events. Among 38 274 adults (median age 55 y, 63% women), 1691 (4.4%) had subclinical hypothyroidism, of whom 775 (45.8%) had positive TPOAbs. During follow-up, 1436 participants died of CHD and 3285 had CHD events. Compared with euthyroid individuals, age- and gender-adjusted risks of CHD mortality in subclinical hypothyroidism were similar among individuals with and without TPOAbs [hazard ratio (HR) 1.15, 95% confidence interval (CI) 0.87-1.53 vs HR 1.26, CI 1.01-1.58, P for interaction = .62], as were risks of CHD events (HR 1.16, CI 0.87-1.56 vs HR 1.26, CI 1.02-1.56, P for interaction = .65). Risks of CHD mortality and events increased with higher thyrotropin, but within each stratum, risks did not differ by TPOAb status. CHD risk associated with subclinical hypothyroidism did not differ by TPOAb status, suggesting that biomarkers of thyroid autoimmunity do not add independent prognostic information for CHD outcomes.

Thyroid Antibody Status, Subclinical Hypothyroidism, and the Risk of Coronary Heart Disease: An Individual Participant Data Analysis

PubMed Central

Collet, Tinh-Hai; Bauer, Douglas C.; Cappola, Anne R.; Åsvold, Bjørn O.; Weiler, Stefan; Vittinghoff, Eric; Gussekloo, Jacobijn; Bremner, Alexandra; den Elzen, Wendy P. J.; Maciel, Rui M. B.; Vanderpump, Mark P. J.; Cornuz, Jacques; Dörr, Marcus; Wallaschofski, Henri; Newman, Anne B.; Sgarbi, José A.; Razvi, Salman; Völzke, Henry; Walsh, John P.; Aujesky, Drahomir

2014-01-01

Context: Subclinical hypothyroidism has been associated with increased risk of coronary heart disease (CHD), particularly with thyrotropin levels of 10.0 mIU/L or greater. The measurement of thyroid antibodies helps predict the progression to overt hypothyroidism, but it is unclear whether thyroid autoimmunity independently affects CHD risk. Objective: The objective of the study was to compare the CHD risk of subclinical hypothyroidism with and without thyroid peroxidase antibodies (TPOAbs). Data Sources and Study Selection: A MEDLINE and EMBASE search from 1950 to 2011 was conducted for prospective cohorts, reporting baseline thyroid function, antibodies, and CHD outcomes. Data Extraction: Individual data of 38 274 participants from six cohorts for CHD mortality followed up for 460 333 person-years and 33 394 participants from four cohorts for CHD events. Data Synthesis: Among 38 274 adults (median age 55 y, 63% women), 1691 (4.4%) had subclinical hypothyroidism, of whom 775 (45.8%) had positive TPOAbs. During follow-up, 1436 participants died of CHD and 3285 had CHD events. Compared with euthyroid individuals, age- and gender-adjusted risks of CHD mortality in subclinical hypothyroidism were similar among individuals with and without TPOAbs [hazard ratio (HR) 1.15, 95% confidence interval (CI) 0.87–1.53 vs HR 1.26, CI 1.01–1.58, P for interaction = .62], as were risks of CHD events (HR 1.16, CI 0.87–1.56 vs HR 1.26, CI 1.02–1.56, P for interaction = .65). Risks of CHD mortality and events increased with higher thyrotropin, but within each stratum, risks did not differ by TPOAb status. Conclusions: CHD risk associated with subclinical hypothyroidism did not differ by TPOAb status, suggesting that biomarkers of thyroid autoimmunity do not add independent prognostic information for CHD outcomes. PMID:24915118

Fibulin-1 Binds to Fibroblast Growth Factor 8 with High Affinity: EFFECTS ON EMBRYO SURVIVAL.

PubMed

Fresco, Victor M; Kern, Christine B; Mohammadi, Moosa; Twal, Waleed O

2016-09-02

Fibulin-1 (FBLN1) is a member of a growing family of extracellular matrix glycoproteins that includes eight members and is involved in cellular functions such as adhesion, migration, and differentiation. FBLN1 has also been implicated in embryonic heart and valve development and in the formation of neural crest-derived structures, including aortic arch, thymus, and cranial nerves. Fibroblast growth factor 8 (FGF8) is a member of a large family of growth factors, and its functions include neural crest cell (NCC) maintenance, specifically NCC migration as well as patterning of structures formed from NCC such as outflow tract and cranial nerves. In this report, we sought to investigate whether FBLN1 and FGF8 have cooperative roles in vivo given their influence on the development of the same NCC-derived structures. Surface plasmon resonance binding data showed that FBLN1 binds tightly to FGF8 and prevents its enzymatic degradation by ADAM17. Moreover, overexpression of FBLN1 up-regulates FGF8 gene expression, and down-regulation of FBLN1 by siRNA inhibits FGF8 expression. The generation of a double mutant Fbln1 and Fgf8 mice (Fbln1(-/-) and Fgf8(-/-)) showed that haplo-insufficiency (Fbln1(+/-) and Fgf8(+/-)) resulted in increased embryonic mortality compared with single heterozygote crosses. The mortality of the FGF8/Fbln1 double heterozygote embryos occurred between 14.5 and 16.5 days post-coitus. In conclusion, FBLN1/FGF8 interaction plays a role in survival of vertebrate embryos, and reduced levels of both proteins resulted in added mortality in utero The FBLN1/FGF8 interaction may also be involved in the survival of neural crest cell population during development. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Direct Interactions Between Gli3, Wnt8b, and Fgfs Underlie Patterning of the Dorsal Telencephalon.

PubMed

Hasenpusch-Theil, Kerstin; Watson, Julia A; Theil, Thomas

2017-02-01

A key step in the development of the cerebral cortex is a patterning process, which subdivides the telencephalon into several molecularly distinct domains and is critical for cortical arealization. This process is dependent on a complex network of interactions between signaling molecules of the Fgf and Wnt gene families and the Gli3 transcription factor gene, but a better knowledge of the molecular basis of the interplay between these factors is required to gain a deeper understanding of the genetic circuitry underlying telencephalic patterning. Using DNA-binding and reporter gene assays, we here investigate the possibility that Gli3 and these signaling molecules interact by directly regulating each other's expression. We show that Fgf signaling is required for Wnt8b enhancer activity in the cortical hem, whereas Wnt/β-catenin signaling represses Fgf17 forebrain enhancer activity. In contrast, Fgf and Wnt/β-catenin signaling cooperate to regulate Gli3 expression. Taken together, these findings indicate that mutual interactions between Gli3, Wnt8b, and Fgf17 are crucial elements of the balance between these factors thereby conferring robustness to the patterning process. Hence, our study provides a framework for understanding the genetic circuitry underlying telencephalic patterning and how defects in this process can affect the formation of cortical areas. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Effects of reagent rotational excitation on the H + CHD{sub 3} → H{sub 2} + CD{sub 3} reaction: A seven dimensional time-dependent wave packet study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Zhaojun; Zhang, Dong H., E-mail: zhangdh@dicp.ac.cn

Seven-dimensional time-dependent wave packet calculations have been carried out for the title reaction to obtain reaction probabilities and cross sections for CHD{sub 3} in J{sub 0} = 1, 2 rotationally excited initial states with k{sub 0} = 0 − J{sub 0} (the projection of CHD{sub 3} rotational angular momentum on its C{sub 3} axis). Under the centrifugal sudden (CS) approximation, the initial states with the projection of the total angular momentum on the body fixed axis (K{sub 0}) equal to k{sub 0} are found to be much more reactive, indicating strong dependence of reactivity on the orientation of the reagentmore » CHD{sub 3} with respect to the relative velocity between the reagents H and CHD{sub 3}. However, at the coupled-channel (CC) level this dependence becomes much weak although in general the K{sub 0} specified cross sections for the K{sub 0} = k{sub 0} initial states remain primary to the overall cross sections, implying the Coriolis coupling is important to the dynamics of the reaction. The calculated CS and CC integral cross sections obtained after K{sub 0} averaging for the J{sub 0} = 1, 2 initial states with all different k{sub 0} are essentially identical to the corresponding CS and CC results for the J{sub 0} = 0 initial state, meaning that the initial rotational excitation of CHD{sub 3} up to J{sub 0} = 2, regardless of its initial k{sub 0}, does not have any effect on the total cross sections for the title reaction, and the errors introduced by the CS approximation on integral cross sections for the rotationally excited J{sub 0} = 1, 2 initial states are the same as those for the J{sub 0} = 0 initial state.« less

Women's Heart Disease: Heart Disease Risk Factors

MedlinePlus

... this page please turn JavaScript on. Feature: Women's Heart Disease Heart Disease Risk Factors Past Issues / Winter 2014 Table ... or habits may raise your risk for coronary heart disease (CHD). These conditions are known as risk ...

Coronary heart disease events in Aboriginal Australians: incidence in an urban population.

PubMed

Bradshaw, Pamela J; Alfonso, Helman S; Finn, Judith C; Owen, Julie; Thompson, Peter L

2009-05-18

To determine the incidence of coronary heart disease (CHD) events in an urban Aboriginal population. Cohort study of 906 Aboriginal people without CHD from 998 who had undergone risk-factor assessment in the Perth Aboriginal Atherosclerosis Risk Study (PAARS) in 1998-1999. PAARS cohort data were electronically linked to a range of databases that included Western Australian hospital morbidity data and death registry data. We analysed data from January 1980 to December 2006 to identify previous admissions for CHD from 1980 to baseline (1998-1999) and new events from baseline to 2006. First CHD event (hospital admission or death). There were 891 linked records for the 906 participants without previous CHD. The event rate was 12.6/1000 person-years (95% CI, 10.2-15.6/1000 person-years). Annual CHD event rates ranged from 8 to 18/1000 person-years. After adjustment for age (sex was not associated with the risk factors assessed), factors associated with risk of a CHD event in the PAARS cohort were a history of diabetes, overweight or obesity (indicated by body mass index), smoking, and hypertension, but not waist circumference. People with these risk factors were 1.9-2.7 times more likely to experience a CHD event. Compared with previously published information from a remote Aboriginal community in the Northern Territory, the incidence of CHD events among urban-dwelling Aboriginal people was not significantly different (P > 0.05 overall and for subgroups defined by age and sex). City-dwelling Aboriginal Australians have an incidence of CHD events comparable to that of Aboriginal people living in remote northern Australia.

Relationships between coronary heart disease risk factors and serum ionized calcium in Kennedy Space Center Cohort

NASA Technical Reports Server (NTRS)

Goodwin, Lisa Ann; Frey, Mary Anne Bassett; Merz, Marion P.; Alford, William R.

1987-01-01

Kennedy Space Center (KSC) employees are reported to be at high risk for coronary heart disease (CHD). Risk factors for CHD include high serum total cholesterol levels, low levels of high-density lipoprotein cholesterol (HDLC), elevated triglyceride, smoking, inactivity, high blood pressure, being male, and being older. Higher dietary and/or serum calcium Ca(++) may be related to a lower risk for CHD. Fifty men and 37 women participated. Subjects were tested in the morning after fasting 12 hours. Information relative to smoking and exercise habits was obtained; seated blood pressures were measured; and blood drawn. KCS men had higher risk values than KCS women as related to HDLC, triglycerides, systolic blood pressure, and diastolic blood pressure. Smoking and nonsmoking groups did not differ for other risk factors or for serum Ca(++) levels. Exercise and sedentary groups differed in total cholesterol and triglyceride levels. Serum Ca(++) levels were related to age, increasing with age in the sedentary group and decreasing in the exercisers, equally for men and women. It is concluded that these relationships may be significant to the risk of CHD and/or the risk of bone demineralization in an aging population.

What Makes Sports Fans Interactive? Identifying Factors Affecting Chat Interactions in Online Sports Viewing

PubMed Central

Yeo, Jaeryong; Lee, Juyeong

2016-01-01

Sports fans are able to watch games from many locations using TV services while interacting with other fans online. In this paper, we identify the factors that affect sports viewers’ online interactions. Using a large-scale dataset of more than 25 million chat messages from a popular social TV site for baseball, we extract various game-related factors, and investigate the relationships between these factors and fans’ interactions using a series of multiple regression analyses. As a result, we identify several factors that are significantly related to viewer interactions. In addition, we determine that the influence of these factors varies according to the user group; i.e., active vs. less active users, and loyal vs. non-loyal users. PMID:26849568

Psychosocial needs of children undergoing an invasive procedure for a CHD and their parents.

PubMed

Levert, Eveline M; Helbing, Willem A; Dulfer, Karolijn; van Domburg, Ron T; Utens, Elisabeth M W J

2017-03-01

The aim of this study was to investigate the psychosocial needs of both parents of children with CHD (aged 0-18 years) and patients themselves (aged 8-18 years) in the week before cardiac surgery or a catheter intervention. Patients Eligible participants included all consecutive patients (0-18 years) scheduled to undergo cardiac surgery or a catheter intervention in our hospital between March, 2012 and July, 2013. Psychosocial needs were assessed using a disease-specific questionnaire designed for this study, consisting of a 83-item parent version and a 59-item child version (for children ⩾8 years), each covering five domains: physical/medical, emotional, social, educational/occupational, and health behaviour; two items assessed from whom and in what format psychosocial care was preferred. Quality of life was also assessed. Interventions If parents/patients reported a need for psychosocial care, referral to adequate mental health-care professionals was arranged. More than 40% of participating parents and >50% of participating children reported a need for psychosocial care on each of the five domains. Needs for psychosocial care for parents themselves were highest for those with children aged 0-12 years. Parents and patients report clear preferences when asked from whom and in what format they would like to receive psychosocial care. Quality of life was relatively high for both parents and patients. Psychosocial care interventions in our hospital increased significantly after the implementation of this study. Results show that psychosocial care is rated as (very) important by both parents and children during an extremely stressful period of their life.

Metformin-diet ameliorates coronary heart disease risk factors and facilitates resumption of regular menses in adolescents with polycystic ovary syndrome.

PubMed

Glueck, Charles J; Goldenberg, Naila; Wang, Ping

2009-09-01

In 20 adolescents age < or = 17 (16 +/- 1 yr) with polycystic ovary syndrome (PCOS), we assessed efficacy and safety of metformin-diet for 1 year in treatment of endocrinopathy and coronary heart disease (CHD) risk factors. Calories were targeted to 1,500-1,800/ day if body mass index (BMI) was < 25 or to 1,200-1,500/day if BMI was > or = 25, along with 2,550 mg metformin. Median weight fell from 85.5 to 78.4 kg (p = 0.004), waist circumference from 91 to 84 cm (p = 0.017), triglyceride from 108 to 71 mg/dl (p = 0.008), insulin from 20.5 to 15 microU/ml (p = 0.018), HOMA-IR from 2.0 to 1.5 (p = 0.026), and testosterone from 45.5 to 31.5 ng/dl (p = 0.03). The percentage of cycles with normal menses rose from a pre-treatment median of 8% to 100%, p < 0.0001. In adolescents (< or = age 17 yr) with PCOS, metformin-diet safely ameliorates CHD risk factors and endocrinopathy while facilitating resumption of regular menses.

Identifying factors associated with experiences of coronary heart disease patients receiving structured chronic care and counselling in European primary care

PubMed Central

2012-01-01

Background Primary care for chronic illness varies across European healthcare systems. In patients suffering from coronary heart disease (CHD), factors associated with patients’ experiences of receiving structured chronic care and counselling at the patient and practice level were investigated. Methods In an observational study comprising 140 general practices from five European countries (Austria, Germany, the Netherlands, Switzerland and the United Kingdom), 30 patients with Coronary Heart Disease (CHD) per practice were chosen at random to partake in this research. Patients were provided with a questionnaire and the Patient Assessment of Chronic Illness Care (PACIC-5A) - instrument. Practice characteristics were assessed through a practice questionnaire and face to face interviews. Data were aggregated to obtain two practice scores representing quality management and CHD care, respectively. A hierarchical multilevel analysis was performed to examine the impact of patient and practice characteristics on PACIC scores. Results The final sample included 1745 CHD-patients from 131 general practices with a mean age of 67.8 (SD 9.9) years. The overall PACIC score was 2.84 (95%CI: 2.79; 2.89) and the 5A score reflecting structured lifestyle counselling was 2.75 (95% CI: 2.69; 2.79). At the patient level, male gender, more frequent practice contact and fewer related or unrelated conditions were associated with higher PACIC scores. At the practice level, performance scores reflecting quality management (p = 0.013) and CHD care (p = 0.009) were associated with improved assessment of the structured chronic care and counselling received. Conclusions Patients’ perceived quality of care varies. However, good practice management and organisation of care were positively reflected in patients’ assessments of receiving structured chronic illness care. This highlights the importance of integrating patient experiences into quality measurements to provide feedback to

Congenital heart disease protein 5 associates with CASZ1 to maintain myocardial tissue integrity.

PubMed

Sojka, Stephen; Amin, Nirav M; Gibbs, Devin; Christine, Kathleen S; Charpentier, Marta S; Conlon, Frank L

2014-08-01

The identification and characterization of the cellular and molecular pathways involved in the differentiation and morphogenesis of specific cell types of the developing heart are crucial to understanding the process of cardiac development and the pathology associated with human congenital heart disease. Here, we show that the cardiac transcription factor CASTOR (CASZ1) directly interacts with congenital heart disease 5 protein (CHD5), which is also known as tryptophan-rich basic protein (WRB), a gene located on chromosome 21 in the proposed region responsible for congenital heart disease in individuals with Down's syndrome. We demonstrate that loss of CHD5 in Xenopus leads to compromised myocardial integrity, improper deposition of basement membrane, and a resultant failure of hearts to undergo cell movements associated with cardiac formation. We further report that CHD5 is essential for CASZ1 function and that the CHD5-CASZ1 interaction is necessary for cardiac morphogenesis. Collectively, these results establish a role for CHD5 and CASZ1 in the early stages of vertebrate cardiac development. © 2014. Published by The Company of Biologists Ltd.

The cardiac TBX5 interactome reveals a chromatin remodeling network essential for cardiac septation

PubMed Central

Waldron, Lauren; Steimle, Jeffrey D.; Greco, Todd M.; Gomez, Nicholas C.; Dorr, Kerry M.; Kweon, Junghun; Temple, Brenda; Yang, Xinan Holly; Wilczewski, Caralynn M.; Davis, Ian J.; Cristea, Ileana M.; Moskowitz, Ivan P.; Conlon, Frank L.

2016-01-01

SUMMARY Human mutations in the cardiac transcription factor gene TBX5 cause Congenital Heart Disease (CHD), however the underlying mechanism is unknown. We report characterization of the endogenous TBX5 cardiac interactome and demonstrate that TBX5, long considered a transcriptional activator, interacts biochemically and genetically with the Nucleosome Remodeling and Deacetylase (NuRD) repressor complex. Incompatible gene programs are repressed by TBX5 in the developing heart. CHD missense mutations that disrupt the TBX5-NuRD interaction cause depression of a subset of repressed genes. Furthermore, the TBX5-NuRD interaction is required for heart development. Phylogenetic analysis showed that the TBX5-NuRD interaction domain evolved during early diversification of vertebrates, simultaneous with the evolution of cardiac septation. Collectively, this work defines a TBX5-NuRD interaction essential to cardiac development and the evolution of the mammalian heart, and when altered may contribute to human CHD. PMID:26859351

Stroke symptoms and risk for incident coronary heart disease in the REasons for Geographic And Racial Differences in Stroke (REGARDS) Study

PubMed Central

Colantonio, Lisandro D.; Gamboa, Christopher M.; Kleindorfer, Dawn O.; Carson, April P.; Howard, Virginia J.; Muntner, Paul; Cushman, Mary; Howard, George; Safford, Monika M.

2016-01-01

Background Many adults without cerebrovascular disease report a history of stroke symptoms, which is associated with higher risk for stroke. Because stroke and coronary heart disease (CHD) share many risk factors, we examined the association between a history of stroke symptoms and incident CHD. Methods We analyzed data from 8,999 black and 12,499 white REasons for Geographic And Racial Differences in Stroke (REGARDS) study participants without a prior myocardial infarction, stroke or transitory ischemic attack enrolled in 2003-2007 (total participants=21,498, all ≥45 years of age). A history of stroke symptoms (i.e., unilateral weakness, unilateral numbness, full-field vision loss, half-field vision loss, understanding problems and communication problems) was assessed at baseline using the Questionnaire for Verifying Stroke-Free Status. Participants were followed for incident CHD and CHD death through December 2011. Results Overall, 3,432 (16.0%) participants reported a history of stroke symptoms (1,771 [19.7%] blacks and 1,661 [13.3%] whites). There were 701 incident CHD events including 209 CHD deaths over a median follow-up of 5.8 years. After adjustment for CHD risk factors, hazard ratios (95% confidence interval [95%CI]) for incident CHD associated with reporting any versus no stroke symptoms were 1.26 (1.04-1.51) in the overall population, 1.28 (0.99-1.65) among blacks and 1.23 (0.94-1.61) among whites. Multivariable-adjusted hazard ratios (95%CI) for CHD death associated with any versus no stroke symptoms were 1.50 (1.10-2.06) overall, 1.58 (1.07-2.32) among blacks and 1.41 (0.82-2.43) among whites. Conclusion A history of stroke symptoms is associated with a higher incidence of CHD among black and white adults. PMID:27376567

Functional Analyses of a Novel Splice Variant in the CHD7 Gene, Found by Next Generation Sequencing, Confirm Its Pathogenicity in a Spanish Patient and Diagnose Him with CHARGE Syndrome.

PubMed

Villate, Olatz; Ibarluzea, Nekane; Fraile-Bethencourt, Eugenia; Valenzuela, Alberto; Velasco, Eladio A; Grozeva, Detelina; Raymond, F L; Botella, María P; Tejada, María-Isabel

2018-01-01

Mutations in CHD7 have been shown to be a major cause of CHARGE syndrome, which presents many symptoms and features common to other syndromes making its diagnosis difficult. Next generation sequencing (NGS) of a panel of intellectual disability related genes was performed in an adult patient without molecular diagnosis. A splice donor variant in CHD7 (c.5665 + 1G > T) was identified. To study its potential pathogenicity, exons and flanking intronic sequences were amplified from patient DNA and cloned into the pSAD ® splicing vector. HeLa cells were transfected with this construct and a wild-type minigene and functional analysis were performed. The construct with the c.5665 + 1G > T variant produced an aberrant transcript with an insert of 63 nucleotides of intron 28 creating a premature termination codon (TAG) 25 nucleotides downstream. This would lead to the insertion of 8 new amino acids and therefore a truncated 1896 amino acid protein. As a result of this, the patient was diagnosed with CHARGE syndrome. Functional analyses underline their usefulness for studying the pathogenicity of variants found by NGS and therefore its application to accurately diagnose patients.

Socioeconomic Status and Coronary Heart Disease Risk: The Role of Social Cognitive Factors

PubMed Central

Phillips, Jennifer E.; Klein, William M. P.

2011-01-01

The aim of this study is to examine existing research on social cognitive factors that may, in part, mediate the relationship between socioeconomic status (SES) and coronary heart disease (CHD). We focus on how social status is ‘carried’ in the mental systems of individuals, and how these systems differentially affect CHD risk and associated behaviors. To this end, literatures documenting the association of various social cognitive factors (e.g., social comparison, perceived discrimination, and self-efficacy) with cardiovascular disease are reviewed as are literatures regarding the relationship of these factors to SES. Possible mechanisms through which social cognitions may affect health are addressed. In addition, directions for future research are discussed, and a model identifying the possible associations between social cognitive factors, SES, and coronary disease is provided. PMID:21785652

Prevalence and predictors of complementary and alternative medicine use among people with coronary heart disease or at risk for this in the sixth Tromsø study: a comparative analysis using protection motivation theory.

PubMed

Kristoffersen, Agnete E; Sirois, Fuschia M; Stub, Trine; Hansen, Anne Helen

2017-06-19

Engagement in healthy lifestyle behaviors, such as healthy diet and regular physical activity, are known to reduce the risk of developing coronary heart disease (CHD). Complementary and alternative medicine (CAM) is known to be associated with having a healthy lifestyle. The primary aim of this study was to examine the prevalence and predictors of CAM use in CHD patients, and in those without CHD but at risk for developing CHD, using Protection Motivation Theory (PMT) as a guiding conceptual framework. Questionnaire data were collected from 12,981 adult participants in the cross-sectional sixth Tromsø Study (2007-8). Eligible for analyses were 11,103 participants who reported whether they had used CAM or not. Of those, 830 participants reported to have or have had CHD (CHD group), 4830 reported to have parents, children or siblings with CHD (no CHD but family risk), while 5443 reported no CHD nor family risk of CHD. We first compared the patterns of CAM use in each group, and then examined the PMT predictors of CAM use. Health vulnerability from the threat appraisal process of PMT was assessed by self-rated health and expectations for future health. Response efficacy from the coping appraisal process of PMT was assessed as preventive health beliefs and health behavior frequency. Use of CAM was most commonly seen in people with no CHD themselves, but family risk of developing CHD (35.8%), compared to people already diagnosed with CHD (30.2%) and people with no CHD nor family risk (32.1%). All four of the PMT factors; self-rated health, expectations for future health, preventive health beliefs, and the health behavior index - were predictors for CAM use in the no CHD but family risk group. These findings suggest that people use CAM in response to a perceived risk of developing CHD, and to prevent disease and to maintain health.

How predictive is breast arterial calcification of cardiovascular disease and risk factors when found at screening mammography?

PubMed

Kataoka, Masako; Warren, Ruth; Luben, Robert; Camus, Joanna; Denton, Erika; Sala, Elvis; Day, Nicholas; Khaw, Kay-Tee

2006-07-01

The purpose of this study was to examine the relationship between breast arterial calcification (BAC), commonly found on mammography, and cardiovascular disease and its risk factors. The study population, nested within the European Prospective Investigation of Cancer-Norfolk (EPIC-Norfolk) cohort study, consisted of 1,590 women older than 55 years, not taking hormone replacement therapy, and with available screening mammograms. Mammograms were coded by three radiologists for presence or absence of BAC. History of coronary heart disease (CHD), stroke, and diabetes and risk factors for cardiovascular disease (including smoking status, body mass index [BMI], blood pressure, diabetes, and glycosylated hemoglobin [HbA1c]) were independently measured from health examinations in the EPIC study. The prevalence of BAC was 16.0%. Women with BAC were significantly older than those without it. BAC was associated with prevalent CHD, but not stroke. The odds ratio of having CHD was 2.54 (95% confidence interval, 1.03-6.30). The sensitivity and specificity were 32.4% and 85.5%, respectively. Except for smoking, which showed an inverse association, there was no consistent significant association of BAC with cardiovascular disease risk factors including BMI, diabetes, HbA1c, or lipids. BAC found on mammograms was associated with prevalent CHD after adjustment for age, but with low sensitivity. BAC may provide additional information toward identifying cardiovascular disease risk among otherwise healthy women.

EDUCATION AND CORONARY HEART DISEASE RISK: POTENTIAL MECHANISMS SUCH AS LITERACY, PERCEIVED CONSTRAINT AND DEPRESSIVE SYMPTOMS

PubMed Central

Loucks, Eric B.; Gilman, Stephen E.; Howe, Chanelle; Kawachi, Ichiro; Kubzansky, Laura D.; Rudd, Rima E.; Martin, Laurie T.; Nandi, Arijit; Wilhelm, Aude; Buka, Stephen L.

2015-01-01

OBJECTIVE Education is inversely associated with coronary heart disease (CHD) risk, however the mechanisms are poorly understood. The study objectives were to evaluate the extent to which rarely measured factors (literacy, time preference, sense of control) and more commonly measured factors (income, depressive symptomatology, body mass index) in the education-CHD literature explain the associations between education and CHD risk. METHOD The study sample included 346 participants, aged 38–47 years (59.5% women), of the New England Family Study birth cohort. Ten-year CHD risk was calculated using the validated Framingham risk algorithm that utilizes diabetes, smoking, blood pressure, total cholesterol, HDL cholesterol, age and gender. Multivariable regression and mediation analyses were performed. RESULTS Regression analyses adjusting for age, race/ethnicity and childhood confounders (e.g. parental socioeconomic status, intelligence) demonstrated that relative to those with ≥college education, men and women with 8) higher 10-year CHD risk, respectively. Mediation analyses demonstrated significant indirect effects for reading comprehension in women (7.2%; 95% CI: 0.7, 19.4) and men (7.2%; 95% CI: 0.8, 19.1), and depressive symptoms (11.8%; 95% CI: 2.5, 26.6) and perceived constraint (6.7%, 95% CI: 0.7, 19.1) in women. CONCLUSIONS Evidence suggested that reading comprehension in women and men, and depressive symptoms and perceived constraint in women, may mediate some of the association between education and CHD risk. If these mediated effects are interpreted causally, interventions targeting reading, depressive symptoms, and perceived constraint could reduce educational inequalities in CHD. PMID:25431228

Gender Differences in Genetic Risk Profiles for Cardiovascular Disease

PubMed Central

Silander, Kaisa; Saarela, Olli; Ripatti, Samuli; Auro, Kirsi; Karvanen, Juha; Kulathinal, Sangita; Niemelä, Matti; Ellonen, Pekka; Vartiainen, Erkki; Jousilahti, Pekka; Saarela, Janna; Kuulasmaa, Kari; Evans, Alun; Perola, Markus; Salomaa, Veikko; Peltonen, Leena

2008-01-01

Background Cardiovascular disease (CVD) incidence, complications and burden differ markedly between women and men. Although there is variation in the distribution of lifestyle factors between the genders, they do not fully explain the differences in CVD incidence and suggest the existence of gender-specific genetic risk factors. We aimed to estimate whether the genetic risk profiles of coronary heart disease (CHD), ischemic stroke and the composite end-point of CVD differ between the genders. Methodology/Principal Findings We studied in two Finnish population cohorts, using the case-cohort design the association between common variation in 46 candidate genes and CHD, ischemic stroke, CVD, and CVD-related quantitative risk factors. We analyzed men and women jointly and also conducted genotype-gender interaction analysis. Several allelic variants conferred disease risk for men and women jointly, including rs1801020 in coagulation factor XII (HR = 1.31 (1.08–1.60) for CVD, uncorrected p = 0.006 multiplicative model). Variant rs11673407 in the fucosyltransferase 3 gene was strongly associated with waist/hip ratio (uncorrected p = 0.00005) in joint analysis. In interaction analysis we found statistical evidence of variant-gender interaction conferring risk of CHD and CVD: rs3742264 in the carboxypeptidase B2 gene, p(interaction) = 0.009 for CHD, and rs2774279 in the upstream stimulatory factor 1 gene, p(interaction) = 0.007 for CHD and CVD, showed strong association in women but not in men, while rs2069840 in interleukin 6 gene, p(interaction) = 0.004 for CVD, showed strong association in men but not in women (uncorrected p-values). Also, two variants in the selenoprotein S gene conferred risk for ischemic stroke in women, p(interaction) = 0.003 and 0.007. Importantly, we identified a larger number of gender-specific effects for women than for men. Conclusions/Significance A false discovery rate analysis suggests that we may expect half of

Cardiac surgery in adults with high-surgical complexity CHD: results of a network collaborative programme.

PubMed

Gilad, Vered; Santoro, Francesco; Ribera, Elena; Calevo, Maria G; Cipriani, Adriano; Pasquè, Achille; Chierchia, Sergio L

2018-01-01

Adults with CHD often exhibit complex cardiac abnormalities, whose management requires specific clinical and surgical expertise. To enable easier access of these patients to highly specialised care, we implemented a collaborative programme that incorporates medical and surgical specialists belonging to both paediatric and adult cardiovascular institutions. The objective of this study was to review the experience gained and to analyse the surgical outcome of major cardiac surgery. We retrospectively reviewed all consecutive patients admitted for major cardiac surgery using our network between January, 2010 and December, 2013. Analysis of surgical outcome was performed in patients selected for major cardiac surgery with cardiopulmonary bypass. Early and late outcomes were evaluated. Out of a total of 433 inward patients, 86 were selected for surgery. The median age was 25.5 years, -64 patients (74.4%) had previously undergone heart surgery, and -55 patients (64%) had been subjected to at least one sternotomy. Abnormalities of the left ventricular and right ventricular outflow tract were the most frequent (37.2% and 30.2%, respectively), and despite high-surgical complexity only one death occurred (in-hospital mortality 1.1%). On a median follow-up time of 4 years no deaths and no heart-failure events have occurred; one patient underwent further cardiac surgery programmed at the time of discharge. Low mortality and morbidity rates can be obtained in high-surgical complexity adults with CHD populations when paediatric and adult cardiac specialists operate in the same multidisciplinary environment.

Comparison of 4- and 8-h dialysis sessions in thrice-weekly in-centre haemodialysis: a prospective, case-controlled study.

PubMed

Ok, Ercan; Duman, Soner; Asci, Gulay; Tumuklu, Murat; Onen Sertoz, Ozen; Kayikcioglu, Meral; Toz, Huseyin; Adam, Siddik M; Yilmaz, Mumtaz; Tonbul, Halil Zeki; Ozkahya, Mehmet

2011-04-01

Longer dialysis sessions may improve outcome in haemodialysis (HD) patients. We compared the clinical and laboratory outcomes of 8- and 4-h thrice-weekly HD. Two-hundred and forty-seven HD patients who agreed to participate in a thrice-weekly 8-h in-centre nocturnal HD (NHD) treatment and 247 age-, sex-, diabetes status- and HD duration-matched control cases to 4-h conventional HD (CHD) were enrolled in this prospective controlled study. Echocardiography and psychometric measurements were performed at baseline and at the 12th month. The primary outcome was 1-year overall mortality. Overall mortality rates were 1.77 (NHD) and 6.23 (CHD) per 100 patient-years (P = 0.01) during a mean 11.3 ± 4.7 months of follow-up. NHD treatment was associated with a 72% risk reduction for overall mortality compared to the CHD treatment (hazard ratio = 0.28, 95% confidence interval 0.09-0.85, P = 0.02). Hospitalization rate was lower in the NHD arm. Post-HD body weight and serum albumin levels increased in the NHD group. Use of antihypertensive medications and erythropoietin declined in the NHD group. In the NHD group, left atrium and left ventricular end-diastolic diameters decreased and left ventricular mass index regressed. Both use of phosphate binders and serum phosphate level decreased in the NHD group. Cognitive functions improved in the NHD group, and quality of life scores deteriorated in the CHD group. Eight-hour thrice-weekly in-centre NHD provides morbidity and possibly mortality benefits compared to conventional 4-h HD.

Knowledge of warning signs, presenting symptoms and risk factors of coronary heart disease among the population of Dubai and Northern Emirates in UAE: a cross-sectional study

PubMed Central

Shehnaz, Syed Ilyas; Guruswami, Gomathi Kadayam; Ibrahim, Salwa Abdelzaher Mabrouk; Mustafa, Sana Abdul Jabbar

2017-01-01

Background: To evaluate the level of knowledge regarding warning signs, presenting symptoms and risk factors associated with coronary heart disease (CHD) among population of Dubai and Northern Emirates in UAE. Materials and Methods: A cross sectional survey of 1367 residents of Dubai and Northern Emirates was conducted using a self-administered questionnaire. Results: Respondents were classified into two groups: Young Adult Population (YAP; 18-24 years of age) and General Population (GP; 25 years and older). Majority of participants were males (56.7%) and of South Asian (57.5%) or Middle-Eastern (30.8%) ethnicity. Regarding presenting symptoms of CHD, chest pain was identified by around 80% of population, whereas pain in the left shoulder was recognized by 61% of GP and 44% of YAP. Atypical symptoms were poorly identified. Regarding risk factors, only one-fourth population knew that males were at higher risk compared to premenopausal females. Few knew that the risk increases in females after menopause and that the risk is higher for females who smoke and use oral contraceptives. 62% knew that the survivors of a heart attack are at high risk of recurrences. Except for tobacco smoke, hypercholesterolemia and hypertension, knowledge of other risk factors was not satisfactory. Older adults and females had comparatively higher level of knowledge. Conclusion: Knowledge level of many of the symptoms and risk factors of CHD is unsatisfactory. There is, therefore, a need to increase the awareness in the population of UAE. The knowledge gaps identified through this study can be addressed through health campaigns to increase the awareness about warning signs, symptoms and modifiable risk factors. . PMID:29181228

CHARGE syndrome: a recurrent hotspot of mutations in CHD7 IVS25 analyzed by bioinformatic tools and minigene assays.

PubMed

Legendre, Marine; Rodriguez-Ballesteros, Montserrat; Rossi, Massimiliano; Abadie, Véronique; Amiel, Jeanne; Revencu, Nicole; Blanchet, Patricia; Brioude, Frédéric; Delrue, Marie-Ange; Doubaj, Yassamine; Sefiani, Abdelaziz; Francannet, Christine; Holder-Espinasse, Muriel; Jouk, Pierre-Simon; Julia, Sophie; Melki, Judith; Mur, Sébastien; Naudion, Sophie; Fabre-Teste, Jennifer; Busa, Tiffany; Stamm, Stephen; Lyonnet, Stanislas; Attie-Bitach, Tania; Kitzis, Alain; Gilbert-Dussardier, Brigitte; Bilan, Frédéric

2018-02-01

CHARGE syndrome is a rare genetic disorder mainly due to de novo and private truncating mutations of CHD7 gene. Here we report an intriguing hot spot of intronic mutations (c.5405-7G > A, c.5405-13G > A, c.5405-17G > A and c.5405-18C > A) located in CHD7 IVS25. Combining computational in silico analysis, experimental branch-point determination and in vitro minigene assays, our study explains this mutation hot spot by a particular genomic context, including the weakness of the IVS25 natural acceptor-site and an unconventional lariat sequence localized outside the common 40 bp upstream the acceptor splice site. For each of the mutations reported here, bioinformatic tools indicated a newly created 3' splice site, of which the existence was confirmed using pSpliceExpress, an easy-to-use and reliable splicing reporter tool. Our study emphasizes the idea that combining these two complementary approaches could increase the efficiency of routine molecular diagnosis.

The Brain in Congenital Heart Disease across the Lifespan: The Cumulative Burden of Injury

PubMed Central

Marelli, Ariane; Miller, Steven P.; Marino, Bradley Scott; Jefferson, Angela L.; Newburger, Jane W.

2017-01-01

The number of patients surviving with congenital heart disease (CHD) has soared over the last three decades. Adults constitute the fastest growing segment of the CHD population, now outnumbering children. Research to date on the heart-brain intersection in this population has largely been focused on neurodevelopmental outcomes in childhood and adolescence. Mutations in genes that are highly expressed in heart and brain may cause cerebral dysgenesis. Together with altered cerebral perfusion in utero, these factors are associated with abnormalities of brain structure and brain immaturity in a significant portion of neonates with critical CHD even before they undergo cardiac surgery. In infancy and childhood, the brain may be affected by risk factors related to heart disease itself or to its interventional treatments. As children with CHD become adults, they increasingly develop heart failure, atrial fibrillation, hypertension, diabetes and coronary disease. These acquired cardiovascular comorbidities can be expected to have effects similar to those in the general population on cerebral blood flow, brain volumes, and dementia. In both children and adults, cardiovascular disease may have adverse effects on achievement, executive function, memory, language, social interactions, and quality of life. In summary, against the backdrop of shifting demographics, risk factors for brain injury in the CHD population are cumulative and synergistic. As neurodevelopmental sequelae in children with CHD evolve to cognitive decline or dementia during adulthood, a growing population of CHD can be expected to require support services. We highlight evidence gaps and future research directions. PMID:27185022

Attitudes to lifestyle risk factors for coronary heart disease amongst South Asians in Leicester: a focus group study.

PubMed

Farooqi, A; Nagra, D; Edgar, T; Khunti, K

2000-08-01

South Asians have a significantly higher risk of mortality from coronary heart disease (CHD) compared with the general population in the UK. There is a lack of evidence on attitudes to and knowledge of risk factors for CHD amongst South Asians. Such information is important for the provision of effective health promotion services. The aim of the study was to identify key issues relating to knowledge of and attitudes to lifestyle risk factors for CHD amongst South Asians aged over 40 years in Leicester, UK. A qualitative focus group analysis was carried out using randomly selected South Asians from GP lists and South Asians attending community centres. Group discussions were taped, translated and transcribed. The transcripts were analysed using qualitative methodology to identify key issues and themes. Participants expressed a range of attitudes to and different levels of knowledge of lifestyle risk factors for CHD. Barriers to improving lifestyle with respect to diet and exercise were identified; these included lack of information (e.g. of how to cook traditional Indian food more healthily) and cultural barriers, such as lack of women-only exercise facilities. Participants perceived stress as an important cause of CHD, and stress directly related to ethnic minority status was described frequently. Language was identified as a key barrier to accessing health services. Health professionals need to provide individually tailored health promotion for South Asians which avoids stereotyping, but recognizes potential cultural obstacles to change. The issue of stress amongst South Asians requires more research and needs to be recognized as an important issue by health professionals. South Asians still face problems accessing health and leisure services due to language and cultural issues.

OSBP-related protein 8 (ORP8) interacts with Homo sapiens sperm associated antigen 5 (SPAG5) and mediates oxysterol interference of HepG2 cell cycle

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhong, Wenbin; Zhou, You; Li, Jiwei

We earlier identified OSBP-related protein 8 (ORP8) as an endoplasmic reticulum/nuclear envelope oxysterol-binding protein implicated in cellular lipid homeostasis, migration, and organization of the microtubule cytoskeleton. Here, a yeast two-hybrid screen identified Homo sapiens sperm associated antigen 5 (SPAG5)/Astrin as interaction partner of ORP8. The putative interaction was further confirmed by pull-down and co-immunoprecipitation assays. ORP8 did not colocalize with kinetochore-associated SPAG5 in mitotic HepG2 or HuH7 cells, but overexpressed ORP8 was capable of recruiting SPAG5 onto endoplasmic reticulum membranes in interphase cells. In our experiments, 25-hydroxycholesterol (25OHC) retarded the HepG2 cell cycle, causing accumulation in G2/M phase; ORP8 overexpressionmore » resulted in the same phenotype. Importantly, ORP8 knock-down dramatically inhibited the oxysterol effect on HepG2 cell cycle, suggesting a mediating role of ORP8. Furthermore, knock-down of SPAG5 significantly reduced the effects of both ORP8 overexpression and 25OHC on the cell cycle, placing SPAG5 downstream of the two cell-cycle interfering factors. Taken together, the present results suggest that ORP8 may via SPAG5 mediate oxysterol interference of the HepG2 cell cycle. - Highlights: • The oxysterol-binding protein ORP8 was found to interact with the mitotic regulator SPAG5/Astrin. • Treatment of HepG2 cells with 25-hydroxycholesterol caused cell cycle retardation in G2/M. • ORP8 overexpression caused a similar G2/M accumulation, and ORP8 knock-down reversed the 25-hydroxycholesterol effect. • Reduction of cellular of SPAG5/Astrin reversed the cell cycle effects of both 25-hydroxycholesterol and ORP8 overexpression. • Our results suggest that ORP8 mediates via SPAG5/Astrin the oxysterol interference of HepG2 cell cycle.« less

ANGPTL4 E40K and T266M: effects on plasma triglyceride and HDL levels, postprandial responses, and CHD risk.

PubMed

Talmud, Philippa J; Smart, Melissa; Presswood, Edward; Cooper, Jackie A; Nicaud, Viviane; Drenos, Fotios; Palmen, Jutta; Marmot, Michael G; Boekholdt, S Matthijs; Wareham, Nicholas J; Khaw, Kay-Tee; Kumari, Meena; Humphries, Steve E

2008-12-01

Angiopoietin-like 4 is a dual-function protein: an inhibitor of LPL, influencing plasma triglycerides (TGs), with angiogenic properties. We examined the association of common ANGPTL4 variants with CHD traits and risk in 5 studies (13,527 individuals). The effects on plasma lipids of 6 tagging SNPs and the recently identified E40K were examined in a study of 2772 men. Only T266M (rs1044250, MAF=30%) and E40K (MAF=2%) were significantly associated with TG-lowering (-10.4%, P<0.004 and -20.4%, P<0.0001), respectively. T266M no longer showed significant associations when K40 carriers (K40+) were excluded (P=0.2). Combining data from 5 studies confirmed the TG-lowering effect of K40+ (weighted mean difference: -0.12 [95% CI -0.18, -0.05] mmol/L TG P=0.0001). Surprisingly, in the 3 prospective studies, the combined OR for CHD was 1.48 (1.11 to 1.96, P=0.007), independent of TG. In individuals with a paternal history of MI (n=332) T266M, but not E40K, showed effects on postprandial AUC TG and glucose (P=0.009 and P=0.017, respectively) compared to controls (n=370). Although associated with an atheroprotective lipid profile, E40K was associated with increased CHD risk, suggesting Angptl4 influences parameters beyond lipid levels. T266M showed effects only under conditions of postprandial stress. The functionality of these potential "loss-of-function" variants needs validation.

Influence of interaction of environmental risk factors and sensitization in young asthmatic children.

PubMed

Lindfors, A; van Hage-Hamsten, M; Rietz, H; Wickman, M; Nordvall, S L

1999-10-01

The increasing prevalence of asthma and allergy in many countries demands evaluation of potential risk factors to improve the possibility of prevention. We studied the association between exposure to cat and dog allergen and allergic sensitization in young children with asthma and interactions with potential environmental risk factors. One hundred eighty-nine young children with asthma were evaluated. IgE antibodies to cat and dog were analyzed. Questionnaires were filled in focusing on exposure to cats and dogs, environmental tobacco smoke (ETS), and signs of home dampness as indicated by window pane condensation (WPC) during the first years of life. House dust was analyzed for content of cat (Fel d 1) and dog (Can f 1) allergen. There was a strong association between the degree of reported exposure to cat and dog and the concentration of the respective allergens in floor dust. A dose-response relationship was found between cat exposure, measured as either reported degree of cat exposure or cat allergen levels in dust, and sensitization both to cat and dog. No such relationship was found between exposure and sensitization to dog. WPC increased the risk for sensitization to cat (odds ratio = 2.6, 95% confidence interval 1.2-5.8), whereas ETS strongly tended to do so both to cat and dog. Interaction was found between exposure to ETS, WPC, and high levels of cat allergen (>8 microg/g dust). The presence of all 3 risk factors revealed a multiplicative interaction with a high risk of sensitization to cat (odds ratio = 42.0, 95% confidence interval 3.7-472.8). Keeping cats indoors may be a health hazard for infants and young children at risk for development of asthma, particularly when they live in a damp house and their parents smoke.

The gender gap in risk factor control: Effects of age and education on the control of cardiovascular risk factors in male and female coronary patients. The EUROASPIRE IV study by the European Society of Cardiology.

PubMed

De Smedt, Delphine; De Bacquer, Dirk; De Sutter, Johan; Dallongeville, Jean; Gevaert, Sofie; De Backer, Guy; Bruthans, Jan; Kotseva, Kornelia; Reiner, Željko; Tokgözoğlu, Lale; Clays, Els

2016-04-15

The aim of this study was to investigate gender related differences in the management and risk factor control of patients with coronary heart disease (CHD), taking into account their age and educational level. Analyses are based on the EUROASPIRE IV (EUROpean Action on Secondary and Primary Prevention through Intervention to Reduce Events) survey. Males and females between 18 and 80years of age, hospitalized for a first or recurrent coronary event were included in the study. Data were available for 7998 patients of which 75.6% were males. Overall, females had a worse risk factor profile compared to males and were more likely to have 3 or more risk factors (29.5% vs. 34.9%; p<0.001) across all age groups. A significant gender by education interaction (p<0.05) and gender by age interaction effect (p<0.05) was found. Furthermore, males were more likely to have a LDL-cholesterol on target (OR=1.50[1.28-1.76]), a HbA1c on target (OR=1.33[1.07-1.64]), to be non-obese (OR=1.45[1.30-1.62]) and perform adequate physical activity (OR=1.71[1.46-2.00]). In contrast males were less likely to be non-smokers (OR=0.71[0.60-0.83]). Furthermore, males were less likely to have made a dietary change (OR=0.78[0.64-0.95]) or a smoking cessation attempt (OR=0.70[0.50-0.96]) and more likely to have received smoking cessation advice if they were smokers (OR=1.52[1.10-2.09]). Whereas gender differences in CHD treatment are limited, substantial differences were found regarding target achievement. The largest gender difference was seen in less educated and elderly patients. The gender gap declined with decreasing age and higher education. Copyright © 2016. Published by Elsevier Ireland Ltd.

Crystal Structure of the C-terminal Domain of Splicing Factor Prp8 Carrying Retinitis Pigmentosa Mutants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang,L.; Shen, J.; Guarnieri, M.

2007-01-01

Prp8 is a critical pre-mRNA splicing factor. Prp8 is proposed to help form and stabilize the spliceosome catalytic core and to be an important regulator of spliceosome activation. Mutations in human Prp8 (hPrp8) cause a severe form of the genetic disorder retinitis pigmentosa, RP13. Understanding the molecular mechanism of Prp8's function in pre-mRNA splicing and RP13 has been hindered by its large size (over 2000 amino acids) and remarkably low-sequence similarity with other proteins. Here we present the crystal structure of the C-terminal domain (the last 273 residues) of Caenorhabditis elegans Prp8 (cPrp8). The core of the C-terminal domain ismore » an / structure that forms the MPN (Mpr1, Pad1 N-terminal) fold but without Zn{sup 2+} coordination. We propose that the C-terminal domain is a protein interaction domain instead of a Zn{sup 2+}-dependent metalloenzyme as proposed for some MPN proteins. Mapping of RP13 mutants on the Prp8 structure suggests that these residues constitute a binding surface between Prp8 and other partner(s), and the disruption of this interaction provides a plausible molecular mechanism for RP13.« less

Evaluation of Carbohydrate-Derived Fulvic Acid (CHD-FA) as a Topical Broad-Spectrum Antimicrobial for Drug-Resistant Wound Infections

DTIC Science & Technology

2015-10-01

resistant Klebsiella pneumoniae, Enterococcus faecium, Staphylococcus aureus, Methicillin- resistant Staphylococcus aureus (MRSA), Escherichia coli ...cutaneous wound model in rats with the drug resistant Gram negative bacteria Acinetobacter baumannii, Escherichia coli , Klebsiella pneumoniae and...bioburden reduction induced by CHD-FA was also observed in wounds infected with multidrug resistant E. coli and K. pneumoniae. To better assess wound

Coronary heart disease risk factors in adult premenopausal white women with polycystic ovary syndrome compared with a healthy female population.

PubMed

Glueck, Charles J; Morrison, John A; Goldenberg, Naila; Wang, Ping

2009-05-01

Our specific aim was to determine whether coronary heart disease (CHD) risk factors in polycystic ovary syndrome (PCOS) patients were independent of their higher body mass index (BMI) and centripetal obesity. In adult, premenopausal, white women, CHD risk factors were compared between 488 patients with well-defined PCOS and 351 healthy free-living population controls from the Princeton Follow-up Study (PFS). After excluding women with irregular menses (putative PCOS phenotypes), comparisons were also made between the 261 PFS women with a history of regular menses and the 488 women with PCOS. Fasting lipids, insulin, glucose, homeostasis model assessment of insulin resistance (HOMA-IR), HOMA insulin secretion, blood pressure, BMI, and waist circumference were measured. Compared with both the full cohort of 351 PFS women and the subgroup of 261 PFS women with regular menses, women with PCOS had higher BMI, waist circumference, total and low-density lipoprotein cholesterol, triglyceride, systolic blood pressure, diastolic blood pressure, insulin, glucose, and HOMA-IR (all Ps < or = .005). After adjusting for age and BMI, women with PCOS, compared with the 351 and 261 PFS women, had lower high-density lipoprotein cholesterol (P < .0001, .0008) and higher systolic blood pressure (P = .0002, < .0001), insulin (P = .017, .039), HOMA-IR (P = .013, .032), and HOMA insulin secretion (P = .022, .037). The small subgroup of PCOS women with normal BMI (<25 kg/m(2)) (36/488, 7%) also had higher age-adjusted insulin, glucose, and HOMA-IR (all Ps < .005) than the subgroup of PFS women with BMI less than 25 kg/m(2) (123/261, 47%). Increased CHD risk factors and high HOMA-IR in PCOS cannot be exclusively attributed to their preponderant centripetal obesity. Identification of women with clinical features of PCOS should alert the clinician to potentially increased risk for CHD and prompt CHD risk factor testing.

[Analysis and follow-up study on 8 children with combined congenital heart disease treated with simultaneous trans-catheter therapy].

PubMed

Cheng, Sheng-Quan; Liu, Jian-Ping; Sun, Xin; Li, Jun; Zhang, Jun; Liu, Li-Wen; Deng, Yue-Lin; Niu, Yong-Chun

2008-10-01

Interventional treatment for childhood combined congenital heart disease (CHD) has developed very quickly and more new types of occluders have emerged in recent years. The aim of this study is to investigate the efficiency and safety of interventional treatment for combined CHD in children. Eight children with combined CHD (4 boys and 4 girls), aged 6.1+/-2.9 years, underwent simultaneous transcatheter therapy. Of the 8 children with CHD, 1 case had atrial septal defect (ASD), ventricular septal defect (VSD) and patent ductus arteriosus (PDA), 1 case had ASD, PDA and pulmonary stenosis (PS), 1 case had ASD and PDA, 1 case had patent foramen ovale (PFO) and PS, and 4 cases had ASD and PS. The methods of transcatheter intervention for these patients were as follows: in patients with ASD,VSD and PDA, the occlusion of VSD was performed first, followed by PDA and ASD occlusions; in patients with ASD, PDA and PS, the occlusion of percutaneous balloon pulmonary valvuloplasty (PBPV) was performed first, followed by PDA and ASD occlusions; in patients with PFO and PS, the occlusion of PBPV was performed first, and PFO occlusion followed; in patients with ASD and PS, the occlusion of PBPV was performed first, and ASD occlusion followed. The intervention operation was successfully performed in all of the 8 patients. No serious adverse events occurred during the operation. No residual shunt was found and all the occlusion devices were in the suitable sites shown by transthoracic echocardiography (TTE) and X-ray right after the operation. In the 6 patients with PS, the systolic pressure across the pulmonary valve decreased from 75.3+/-15.6 mmHg (before operation) to 14.0+/-5.6 mmHg after operation (P<0.05).A 3.4+/-1.2 years follow-up demonstrated that no residual shunt occurred and gradients across valve or coarctation sites were within the limit of satisfactory results. No complications were observed during the follow-up. Transcatheter interventional therapy for childhood

Screening and identification of host factors interacting with UL14 of herpes simplex virus 1.

PubMed

Wu, Fuqing; Xing, Junji; Wang, Shuai; Li, Meili; Zheng, Chunfu

2011-08-01

The UL14 protein of herpes simplex virus type 1 (HSV-1) is highly conserved in herpesvirus family. However, its exact function during the HSV-1 replication cycle is little known. In the present study, a high throughput yeast two-hybrid system was employed to screen the cellular factors interacting with UL14, and five target candidates were yielded: (1) TSC22 domain family protein 3 (TSC22D3); (2) Mediator of RNA polymerase II transcription subunit 8 isoform 1(MED8); (3) Runt-related transcription factor 3 (RUNX3); (4) Arrestin beta-2 (ARRB2); (5) Cereblon (CRBN). Indirect immunofluorescent assay showed that both TSC22D3 and MED8 co-localized with UL14. Co-immunoprecipitation assay demonstrated that UL14 could be immunoprecipitated by TSC22D3, suggesting that UL14 interacted with TSC22D3 under physiological condition. In summary, this study opened up new avenues toward delineating the function and physiological significance of UL14 during the HSV-1 replication cycle.

Effective Factors in Interactions within Japanese EFL Classrooms

ERIC Educational Resources Information Center

Maftoon, Parviz; Ziafar, Meisam

2013-01-01

Classroom interactional patterns depend on some contextual, cultural and local factors in addition to the methodologies employed in the classroom. In order to delineate such factors, the focus of classroom interaction research needs to shift from the observables to the unobservables like teachers' and learners' psychological states and cultural…

Omega-3 Index of Canadian adults.

PubMed

Langlois, Kellie; Ratnayake, Walisundera M N

2015-11-01

Cardioprotective properties have been associated with two fatty acids-eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The Omega-3 Index indicates the percentage of EPA+DHA in red blood cell fatty acids. Omega-3 Index levels of the Canadian population have not been directly measured. Data for respondents aged 20 to 79 from cycle 3 (2012/2013) of the Canadian Health Measures Survey were used to calculate means and the prevalence of Omega-3 Index coronary heart disease (CHD) risk cut-offs-high (4% or less), moderate (more than 4% to less than 8%), and low (8% or more)-by sociodemographic and lifestyle characteristics, including fish consumption and use of omega-3 supplements. Associations between the Omega-3 Index and CHD-related factors including biomarkers, risk factors, and previous CHD events, were examined in multivariate regression models. The mean Omega-3 Index level of Canadians aged 20 to 79 was 4.5%. Levels were higher for women, older adults, Asians and other non-white Canadians, omega-3 supplement users, and fish consumers; levels were lower for smokers and people who were obese. Fewer than 3% of adults had levels associated with low CHD risk; 43% had levels associated with high risk. No CHD-related factor was associated with the Omega-3 Index when control variables were taken into account. Omega-3 Index levels among Canadian adults were strongly related to age, race, supplement use, fish consumption, smoking status and obesity. Fewer than 3% of adults had Omega-3 Index levels associated with low risk for CHD.

Exercise frequency, health risk factors, and diseases of the elderly.

PubMed

Kemmler, Wolfgang; von Stengel, Simon

2013-11-01

To determine the effect of exercise frequency on various diseases and risk factors of the elderly. Retrospective analysis of a randomized controlled 18-month exercise trial. University ambulatory group setting. Community-dwelling women aged ≥65 years (N=162) in the area of Northern Bavaria. Mixed, intense aerobic, resistance, and balance protocol for 18 months. Subjects were retrospectively subdivided into 2 groups according to their effective attendance over 18 months (>1-<2 vs ≥2-4 sessions/wk). Bone mineral density (BMD), lean body mass, appendicular skeletal muscle mass by dual-energy x-ray absorptiometry, Framingham study-based 10-year coronary heart disease (CHD) risk, and number of falls by calendar method. Significant differences between the low-frequency exercise group (LF-EG) and the high-frequency exercise group (HF-EG) were observed for lumbar spine BMD (HF-EG, 2.4%±2.8% vs LF-EG, 0.3%±2.2%; P<.001) and proximal femur BMD (HF-EG, 2.4%±2.8% vs LF-EG, -0.5%±1.6%; P=.014), lean body mass (1.6%±3.4% vs 0.3%±2.6%, P=.053), and appendicular skeletal muscle mass (0.9%±4.5% vs -1.3%±3.2%, P=.011). No differences between both exercise groups were observed for 10-year CHD risk (-1.94%±4.14% vs -2.00%±3.13%; P=.943) and number of falls (0.95±1.36 vs 1.03±1.21 falls/person). Comparing the LF-EG with the less active control group (n=47), only nonsignificant effects for fall number (P=.065) and 10-year CHD risk (P=.178) were evaluated. Although this result might not be generalizable across all exercise types and cohorts, it indicates that an overall exercise frequency of at least 2 sessions/wk may be crucial for impacting bone and muscle mass of elderly subjects. Copyright © 2013 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Association of ACE and FACTOR VII gene variability with the risk of coronary heart disease in north Indian population.

PubMed

Sobti, R C; Maithil, Nishi; Thakur, Hitender; Sharma, Yashpaul; Talwar, K K

2010-08-01

The angiotensin converting enzyme (ACE) is a key factor in the production of angiotensin II and in the degradation of bradykinin. Chronic exposure to high levels of circulating and tissue ACE predispose to vascular wall thickening and atherosclerosis. Factor VII (FACTOR VII) is the first enzyme in the extrinsic pathway of the blood coagulation system and plays a key role in hemostasis; it also contributes to the occurrence of thrombotic events. In this study, we have examined the association of ACE and FACTOR VII gene in coronary heart disease patients (n = 300) and their age-matched controls (n = 300). Genotyping was done by PCR-RFLP method. No significant difference was observed in the distribution of I/D genotypes of ACE between cases and controls. In case of FACTOR VII R353Q polymorphism, there was not much difference in the distribution of alleles. AA genotype had protective effect for CHD (OR 0.56, 95% CI 0.37-0.83, P = 0.001). In case of FACTOR VII VNTR, there was difference in the distribution of alleles, H6 (73.5) and H7 (25.5) in cases, and H6 (70.5) and H7 (30.5) in controls. H6H7 and H7H7 genotypes had a protective effect for CHD with OR 0.27, 95% CI 0.18-0.41, P < 0.001, and OR 0.18, 95% CI 0.09-0.36, P < 0.001. Our study showed D allele of ACE to be associated with marginal risk of CHD, AA genotype of FACTOR VII R353Q and H6H7 and H7H7 genotypes of FACTOR VII VNTR showed protective effect for CHD.

Ebola Virus VP35 Interaction with Dynein LC8 Regulates Viral RNA Synthesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Luthra, Priya; Jordan, David S.; Leung, Daisy W.

2015-03-04

Ebola virus VP35 inhibits alpha/beta interferon production and functions as a viral polymerase cofactor. Previously, the 8-kDa cytoplasmic dynein light chain (LC8) was demonstrated to interact with VP35, but the functional consequences were unclear. Here we demonstrate that the interaction is direct and of high affinity and that binding stabilizes the VP35 N-terminal oligomerization domain and enhances viral RNA synthesis. Mutational analysis demonstrates that VP35 interaction is required for the functional effects of LC8.

A cross-sectional study of the relationship between job demand-control, effort-reward imbalance and cardiovascular heart disease risk factors.

PubMed

Söderberg, Mia; Rosengren, Annika; Hillström, Jenny; Lissner, Lauren; Torén, Kjell

2012-12-21

This cross-sectional study explored relationships between psychosocial work environment, captured by job demand-control (JDC) and effort-reward imbalance (ERI), and seven cardiovascular heart disease (CHD) risk factors in a general population. The sampled consists of randomly-selected men and women from Gothenburg, Sweden and the city's surrounding metropolitan areas. Associations between psychosocial variables and biomarkers were analysed with multiple linear regression adjusted for age, smoking, education and occupational status. The study included 638 men and 668 women aged 24-71. Analysis between JDC and CHD risk factors illustrated that, for men, JDC was associated with impaired scores in several biomarkers, especially among those in high strain jobs. For women, there were no relationships between JDC and biomarkers. In the analysis of links between ERI and CHD risk factors, most associations tested null. The only findings were raised triglycerides and BMI among men in the fourth quartile of the ERI-ratio distribution, and lowered LDL-cholesterol for women. An complementary ERI analysis, combining high/low effort and reward into categories, illustrated lowered triglycerides and elevated HDL-cholesterol values among women reporting high efforts and high rewards, compared to women experiencing low effort and high reward. There were some associations between psychosocial stressors and CHD risk factors. The cross-sectional design did not allow conclusions about causality but some results indicated gender differences regarding sensitivity to work stressors and also how the models might capture different psychosocial dimensions.

A cross-sectional study of the relationship between job demand-control, effort-reward imbalance and cardiovascular heart disease risk factors

PubMed Central

2012-01-01

Background This cross-sectional study explored relationships between psychosocial work environment, captured by job demand-control (JDC) and effort-reward imbalance (ERI), and seven cardiovascular heart disease (CHD) risk factors in a general population. Method The sampled consists of randomly-selected men and women from Gothenburg, Sweden and the city’s surrounding metropolitan areas. Associations between psychosocial variables and biomarkers were analysed with multiple linear regression adjusted for age, smoking, education and occupational status. Results The study included 638 men and 668 women aged 24–71. Analysis between JDC and CHD risk factors illustrated that, for men, JDC was associated with impaired scores in several biomarkers, especially among those in high strain jobs. For women, there were no relationships between JDC and biomarkers. In the analysis of links between ERI and CHD risk factors, most associations tested null. The only findings were raised triglycerides and BMI among men in the fourth quartile of the ERI-ratio distribution, and lowered LDL-cholesterol for women. An complementary ERI analysis, combining high/low effort and reward into categories, illustrated lowered triglycerides and elevated HDL-cholesterol values among women reporting high efforts and high rewards, compared to women experiencing low effort and high reward. Conclusions There were some associations between psychosocial stressors and CHD risk factors. The cross-sectional design did not allow conclusions about causality but some results indicated gender differences regarding sensitivity to work stressors and also how the models might capture different psychosocial dimensions. PMID:23259757

Risk factors for infective endocarditis in children with congenital heart diseases - A nationwide population-based case control study.

PubMed

Sun, Li-Chuan; Lai, Chih-Cheng; Wang, Cheng-Yi; Wang, Ya-Hui; Wang, Jen-Yu; Hsu, Yo-Ling; Hu, Yin-Lan; Wu, En-Ting; Lin, Ming-Tai; Sy, Leticia B; Chen, Likwang

2017-12-01

Infective endocarditis (IE) is uncommon in childhood. Its associated epidemiological characteristics in patients with congenital heart disease (CHD) remain unclear. The study population included children born in Taiwan during the years 1997 to 2005 who were diagnosed as having CHD before 3years of age. All children were followed up until the end year of 2010, the diagnosis of infective endocarditis, or death. The demographic characteristics of patients with and without IE, the invasive procedures performed during 6months before the index date, the prophylactic antibiotics related to dental procedures, and in-hospital mortality were collected. Information of 24,729 children with CHD were retrieved for our analysis and 237 patients with newly diagnosed IE were identified. The incidence rate of IE in all CHD lesions was 11.13 per 10,000person-years. Taking ASD for reference, the following CHD lesions were at risk for IE: cyanotic CHD (adjusted OR, 9.58; 95% confidence interval, 5.38-17.05), endocardial cushion defect (ECD) (8.01; 2.73-23.50), Left-sided lesions (4.36; 1.90-10.01) and VSD (2.93; 1.64-5.23). Patients who underwent procedures have a higher risk of acquiring IE which include central venous catheter (CVC) insertion (3.17; 2.36-4.27), cardiac catheterization (3.74; 2.67-5.22), open-heart surgery (2.47; 1.61-3.77), valve surgery (3.20; 1.70-6.02), and shunt surgery (7.43; 2.36-23.41). However, dental procedures did not increase the risk of IE, irrespective of antibiotic usage. The risk of IE varies markedly among CHD lesions in our study. Invasive heart procedures but not dental procedures, are more significantly associated with IE among children with CHD. Copyright © 2017. Published by Elsevier B.V.

Neonatal antecedents for cerebral palsy in extremely preterm babies and interaction with maternal factors.

PubMed

Tran, Uyen; Gray, Peter H; O'Callaghan, Michael J

2005-06-01

Preterm delivery is associated with an increased risk of cerebral palsy (CP). The greatest risk is for infants born <28 weeks' gestation. To identify significant neonatal risk factors for CP and explore the interactions between antenatal and neonatal risk factors, among extremely preterm infants of 27 weeks' gestation or less. Nested case control design. Infants born between 1989 and 1996, at 24-27 weeks' gestation, were evaluated: 30 with CP at 2 years corrected age and 120 control infants matched for gestation age. Neonatal variables were compared using matched analyses with the interaction between antenatal and neonatal factors being examined using logistic regression analyses. Risk factors for CP on matched analyses included patent ductus arteriosus requiring surgical ligation, peri-intraventricular haemorrhage, moderate to severe ventricular dilatation, periventricular leukomalacia (PVL) and need for home oxygen. Independent neonatal predictors were ventricular dilatation (OR 7.3; 95% CI 1.6, 32.3), PVL (OR 29.8; 95% CI 5.6, 159.1) and home oxygen use (OR 3.4; 95% CI 1.2, 9.4). No interaction terms in the logistic models were significant between the previously identified pregnancy risk factors of absence of antenatal steroids and intrauterine growth restriction and the neonatal risk factors. PVL is the most powerful independent predictor of CP in extremely preterm infants of 27 weeks' gestation or less and appears to be uninfluenced by antenatal factors.

Prevalence of chronic kidney disease and its determinants in coronary heart disease patients in 24 European countries: Insights from the EUROASPIRE IV survey of the European Society of Cardiology.

PubMed

Wagner, Martin; Wanner, Christoph; Kotseva, Kornelia; Wood, David; De Bacquer, Dirk; Rydén, Lars; Störk, Stefan; Heuschmann, Peter U

2017-07-01

Aims Chronic kidney disease (CKD) is associated with the development and progression of coronary heart disease (CHD), in addition to classic cardiovascular risk factors. We analysed the prevalence of CKD in CHD patients from 24 European countries in the ambulatory setting and in a preceding hospital stay for CHD (index). Methods and results A total of 7998 EUROASPIRE IV participants (median 65 years of age, 76% male) attended a study visit 6-36 months after the index hospitalisation. CKD was classified according to stages of estimated glomerular filtration rate (eGFR) and albuminuria (urinary albumin/creatinine ratio). In stable CHD conditions (study visit), 17.3% had CKD (eGFR <60 mL/min/1.73 m 2 ) with variation among participating countries (range 13.1-26.4%). A further 12% presented with preserved eGFR but significant albuminuria. During the hospital stay due to a coronary event, impaired kidney function was observed in 17.6% (range 7.5-38.2%). Risk factors for impaired kidney function included older age, female gender, classic cardiovascular (CV) risk factors, details of CHD history and congestive heart failure (multivariate regression). Of all patients, 38.9% had declined, 31.3% were stable and 29.8% had improved kidney function between hospital discharge and the study visit, dependent on age, gender, CV risk factors, CHD history and cardiac dysfunction (multivariate regression). Conclusions Every fifth CHD patient had CKD, while every tenth exhibited albuminuria as the sole indicator of kidney damage. These subjects are at increased risk of progression of CKD and CHD complications. After hospital stays due to CHD, there is potential of recovery of kidney function, but our findings underline the importance of identifying patients who are at high risk of developing CKD in order to counteract disease progression.

Solution NMR characterization of chemokine CXCL8/IL-8 monomer and dimer binding to glycosaminoglycans: structural plasticity mediates differential binding interactions

PubMed Central

Joseph, Prem Raj B.; Mosier, Philip D.; Desai, Umesh R.; Rajarathnam, Krishna

2015-01-01

Chemokine CXCL8/interleukin-8 (IL-8) plays a crucial role in directing neutrophils and oligodendrocytes to combat infection/injury and tumour cells in metastasis development. CXCL8 exists as monomers and dimers and interaction of both forms with glycosaminoglycans (GAGs) mediate these diverse cellular processes. However, very little is known regarding the structural basis underlying CXCL8–GAG interactions. There are conflicting reports on the affinities, geometry and whether the monomer or dimer is the high-affinity GAG ligand. To resolve these issues, we characterized the binding of a series of heparin-derived oligosaccharides [heparin disaccharide (dp2), heparin tetrasaccharide (dp4), heparin octasaccharide (dp8) and heparin 14-mer (dp14)] to the wild-type (WT) dimer and a designed monomer using solution NMR spectroscopy. The pattern and extent of binding-induced chemical shift perturbation (CSP) varied between dimer and monomer and between longer and shorter oligosaccharides. NMR-based structural models show that different interaction modes coexist and that the nature of interactions varied between monomer and dimer and oligosaccharide length. MD simulations indicate that the binding interface is structurally plastic and provided residue-specific details of the dynamic nature of the binding interface. Binding studies carried out under conditions at which WT CXCL8 exists as monomers and dimers provide unambiguous evidence that the dimer is the high-affinity GAG ligand. Together, our data indicate that a set of core residues function as the major recognition/binding site, a set of peripheral residues define the various binding geometries and that the structural plasticity of the binding interface allows multiplicity of binding interactions. We conclude that structural plasticity most probably regulates in vivo CXCL8 monomer/dimer–GAG interactions and function. PMID:26371375

The effects of vitamin D, K and calcium co-supplementation on carotid intima-media thickness and metabolic status in overweight type 2 diabetic patients with CHD.

PubMed

Asemi, Zatollah; Raygan, Fariba; Bahmani, Fereshteh; Rezavandi, Zohreh; Talari, Hamid Reza; Rafiee, Motahereh; Poladchang, Somayyeh; Darooghegi Mofrad, Manijeh; Taheri, Sara; Mohammadi, Ali Akbar; Esmaillzadeh, Ahmad

2016-07-01

This study was conducted to examine the effects of vitamin D, K and Ca co-supplementation on carotid intima-media thickness (CIMT) and metabolic status in overweight diabetic patients with CHD. This randomised, double-blind, placebo-controlled trial was conducted among sixty-six diabetic patients with CHD. Participants were randomly allocated into two groups to take either 5µg vitamin D, 90 µg vitamin K plus 500 mg Ca supplements (n 33) or placebo (n 33) twice a day for 12 weeks. Fasting blood samples were obtained at the beginning of the study and after the 12-week intervention period to determine related markers. Vitamin D, K and Ca co-supplementation resulted in a significant reduction in maximum levels of left CIMT (-0·04 (sd 0·22) v. +0·04 (sd 0·09) mm, P=0·02). Changes in serum vitamin D (+6·5 (sd 7·8) v. +0·4 (sd 2·2) ng/ml, P<0·001), Ca (+0·6 (sd 0·3) v. +0·1 (sd 0·1) mg/dl, P<0·001) and insulin concentrations (-0·9 (sd 3·1) v. +2·6 (sd 7·2) µIU/ml, P=0·01), homoeostasis model for assessment of estimated insulin resistance (-0·4 (sd 1·2) v. +0·7 (sd 2·3), P=0·01), β-cell function (-2·1 (sd 9·0) v. +8·9 (sd 23·7), P=0·01) and quantitative insulin sensitivity check index (+0·007 (sd 0·01) v. -0·006 (sd 0·02), P=0·01) in supplemented patients were significantly different from those in patients in the placebo group. Supplementation resulted in significant changes in HDL-cholesterol (+2·7 (sd 7·0) v. -2·5 (sd 5·7) mg/dl, P=0·002), high-sensitivity C-reactive protein (-1320·1 (sd 3758·3) v. +464·0 (sd 3053·3) ng/ml, P=0·03) and plasma malondialdehyde concentrations (-0·4 (sd 0·5) v. -1·0 (sd 1·1) µmol/l, P=0·007) compared with placebo. Overall, vitamin D, K and Ca co-supplementation for 12 weeks among diabetic patients with CHD had beneficial effects on maximum levels of left CIMT and metabolic status. The effect of vitamin D, K and Ca co-supplementation on maximum levels of left CIMT could be a chance

Position paper on the importance of psychosocial factors in cardiology: Update 2013

PubMed Central

Ladwig, Karl-Heinz; Lederbogen, Florian; Albus, Christian; Angermann, Christiane; Borggrefe, Martin; Fischer, Denise; Fritzsche, Kurt; Haass, Markus; Jordan, Jochen; Jünger, Jana; Kindermann, Ingrid; Köllner, Volker; Kuhn, Bernhard; Scherer, Martin; Seyfarth, Melchior; Völler, Heinz; Waller, Christiane; Herrmann-Lingen, Christoph

2014-01-01

Background: The rapid progress of psychosomatic research in cardiology and also the increasing impact of psychosocial issues in the clinical daily routine have prompted the Clinical Commission of the German Heart Society (DGK) to agree to an update of the first state of the art paper on this issue which was originally released in 2008. Methods: The circle of experts was increased, general aspects were implemented and the state of the art was updated. Particular emphasis was dedicated to coronary heart diseases (CHD), heart rhythm diseases and heart failure because to date the evidence-based clinical knowledge is most advanced in these particular areas. Differences between men and women and over the life span were considered in the recommendations as were influences of cognitive capability and the interactive and synergistic impact of classical somatic risk factors on the affective comorbidity in heart disease patients. Results: A IA recommendation (recommendation grade I and evidence grade A) was given for the need to consider psychosocial risk factors in the estimation of coronary risks as etiological and prognostic risk factors. Furthermore, for the recommendation to routinely integrate psychosocial patient management into the care of heart surgery patients because in these patients, comorbid affective disorders (e.g. depression, anxiety and post-traumatic stress disorder) are highly prevalent and often have a malignant prognosis. A IB recommendation was given for the treatment of psychosocial risk factors aiming to prevent the onset of CHD, particularly if the psychosocial risk factor is harmful in itself (e.g. depression) or constrains the treatment of the somatic risk factors. Patients with acute and chronic CHD should be offered anti-depressive medication if these patients suffer from medium to severe states of depression and in this case medication with selective reuptake inhibitors should be given. In the long-term course of treatment with implanted

Lifestyle Risk Factors and Cardiovascular Disease in Cubans and Cuban Americans

PubMed Central

Burroughs Peña, Melissa S.; Patel, Dhaval; Rodríguez Leyva, Delfin; Khan, Bobby V.; Sperling, Laurence

2012-01-01

Cardiovascular disease is the leading cause of mortality in Cuba. Lifestyle risk factors for coronary heart disease (CHD) in Cubans have not been compared to risk factors in Cuban Americans. Articles spanning the last 20 years were reviewed. The data on Cuban Americans are largely based on the Hispanic Health and Nutrition Examination Survey (HHANES), 1982–1984, while more recent data on epidemiological trends in Cuba are available. The prevalence of obesity and type 2 diabetes mellitus remains greater in Cuban Americans than in Cubans. However, dietary preferences, low physical activity, and tobacco use are contributing to the rising rates of obesity, type 2 diabetes mellitus, and CHD in Cuba, putting Cubans at increased cardiovascular risk. Comprehensive national strategies for cardiovascular prevention that address these modifiable lifestyle risk factors are necessary to address the increasing threat to public health in Cuba. PMID:22203917

Association Between a Genetic Variant Related to Glutamic Acid Metabolism and Coronary Heart Disease in Type 2 Diabetes

PubMed Central

Qi, Qibin; Prudente, Sabrina; Mendonca, Christine; Andreozzi, Francesco; di Pietro, Natalia; Sturma, Mariella; Novelli, Valeria; Mannino, Gaia Chiara; Formoso, Gloria; Gervino, Ernest V.; Hauser, Thomas H.; Muehlschlegel, Jochen D.; Niewczas, Monika A.; Krolewski, Andrzej S.; Biolo, Gianni; Pandolfi, Assunta; Rimm, Eric; Sesti, Giorgio; Trischitta, Vincenzo; Hu, Frank

2013-01-01

IMPORTANCE Diabetes is associated with an elevated risk of coronary heart disease (CHD). Previous studies have suggested that the genetic factors predisposing to excess cardiovascular risk may be different in diabetic and non-diabetic participants. OBJECTIVE To identify genetic determinants of CHD that are specific to diabetic patients. DESIGN, SETTING, AND PARTICIPANTS We studied five independent sets of CHD cases and CHD-negative controls from the Nurses Health Study (NHS; enrolled in 1976 and followed through 2008), Health Professionals Follow-up Study (HPFS; enrolled in 1986 and followed through 2008), Joslin Heart Study (enrolled in 2001-2008), Gargano Heart Study (enrolled in 2001-2008), and Catanzaro Study (enrolled in 2004-2010). Included were a total of 1,517 CHD cases and 2,671 CHD-negative controls, all with type 2 diabetes. Results in diabetic patients were compared with those in 737 non-diabetic CHD cases and 1,637 non-diabetic CHD-negative controls from the NHS and HPFS cohorts. EXPOSURE 2,543,016 common genetic variants occurring throughout the genome. MAIN OUTCOME CHD defined as fatal or non-fatal myocardial infarction, coronary artery bypass grafting, percutaneous transluminal coronary angioplasty, or angiographic evidence of significant stenosis of the coronary arteries. RESULTS We identified a variant on chromosome 1q25 (rs10911021) consistently associated with CHD risk among diabetic participants with an odds ratio of 1.36 (95% confidence interval [CI] 1.22-1.51, P=2×10−8). No association between this variant and CHD was detected among non-diabetic participants (OR=0.99, P=0.89), consistent with a significant gene-by-diabetes interaction on CHD risk (P=2×10−4). As compared to protective allele homozygotes, rs10911021 risk allele homozygotes were characterized by a 32% decrease in the expression of the neighboring glutamate-ammonia ligase (GLUL) gene in human endothelial cells (P=0.0048). They also showed a decreased ratio between plasma

Global Quantitative Modeling of Chromatin Factor Interactions

PubMed Central

Zhou, Jian; Troyanskaya, Olga G.

2014-01-01

Chromatin is the driver of gene regulation, yet understanding the molecular interactions underlying chromatin factor combinatorial patterns (or the “chromatin codes”) remains a fundamental challenge in chromatin biology. Here we developed a global modeling framework that leverages chromatin profiling data to produce a systems-level view of the macromolecular complex of chromatin. Our model ultilizes maximum entropy modeling with regularization-based structure learning to statistically dissect dependencies between chromatin factors and produce an accurate probability distribution of chromatin code. Our unsupervised quantitative model, trained on genome-wide chromatin profiles of 73 histone marks and chromatin proteins from modENCODE, enabled making various data-driven inferences about chromatin profiles and interactions. We provided a highly accurate predictor of chromatin factor pairwise interactions validated by known experimental evidence, and for the first time enabled higher-order interaction prediction. Our predictions can thus help guide future experimental studies. The model can also serve as an inference engine for predicting unknown chromatin profiles — we demonstrated that with this approach we can leverage data from well-characterized cell types to help understand less-studied cell type or conditions. PMID:24675896

MeWRKY20 and its interacting and activating autophagy-related protein 8 (MeATG8) regulate plant disease resistance in cassava.

PubMed

Yan, Yu; Wang, Peng; He, Chaozu; Shi, Haitao

2017-12-09

As a highly conserved mechanism, autophagy is responsible for the transport of cytoplasmic constituents in the vacuoles or lysosomes. Moreover, autophagy is essential for plant development and various stress responses. In this study, 34 MeATGs were systematically identified in cassava, and their transcripts were commonly regulated by Xanthomonas axonopodis pv manihotis (Xam). Through transient expression in Nicotiana benthamiana, the subcellular locations of 4 MeATG8s were revealed. Notably, MeWRKY20 was identified as physical interacting protein of MeATG8a/8f/8h and upstream transcriptional activator of MeATG8a. Through virus-induced gene silencing (VIGS) in cassava, we found that MeATG8-silenced and MeWRKY20-silenced plants resulted in disease sensitive, with less callose depositions and lower autophagic activity. This study may facilitate our understanding of the upstream MeWRKY20 and underlying target as well as interacting proteins of MeATG8s in immune response. Taken together, MeWRKY20 and MeATG8a/8f/8h are essential for disease resistance against bacterial blight by forming various transcriptional modules and interacting complex in cassava. Copyright © 2017 Elsevier Inc. All rights reserved.

Otitis Media in a New Mouse Model for CHARGE Syndrome with a Deletion in the Chd7 Gene

PubMed Central

Tian, Cong; Yu, Heping; Yang, Bin; Han, Fengchan; Zheng, Ye; Bartels, Cynthia F.; Schelling, Deborah; Arnold, James E.; Scacheri, Peter C.; Zheng, Qing Yin

2012-01-01

Otitis media is a middle ear disease common in children under three years old. Otitis media can occur in normal individuals with no other symptoms or syndromes, but it is often seen in individuals clinically diagnosed with genetic diseases such as CHARGE syndrome, a complex genetic disease caused by mutation in the Chd7 gene and characterized by multiple birth defects. Although otitis media is common in human CHARGE syndrome patients, it has not been reported in mouse models of CHARGE syndrome. In this study, we report a mouse model with a spontaneous deletion mutation in the Chd7 gene and with chronic otitis media of early onset age accompanied by hearing loss. These mice also exhibit morphological alteration in the Eustachian tubes, dysregulation of epithelial proliferation, and decreased density of middle ear cilia. Gene expression profiling revealed up-regulation of Muc5ac, Muc5b and Tgf-β1 transcripts, the products of which are involved in mucin production and TGF pathway regulation. This is the first mouse model of CHARGE syndrome reported to show otitis media with effusion and it will be valuable for studying the etiology of otitis media and other symptoms in CHARGE syndrome. PMID:22539951

The contribution of changes in diet, exercise, and stress management to changes in coronary risk in women and men in the multisite cardiac lifestyle intervention program.

PubMed

Daubenmier, Jennifer J; Weidner, Gerdi; Sumner, Michael D; Mendell, Nancy; Merritt-Worden, Terri; Studley, Joli; Ornish, Dean

2007-02-01

The relative contribution of health behaviors to coronary risk factors in multicomponent secondary coronary heart disease (CHD) prevention programs is largely unknown. Our purpose is to evaluate the additive and interactive effects of 3-month changes in health behaviors (dietary fat intake, exercise, and stress management) on 3-month changes in coronary risk and psychosocial factors among 869 nonsmoking CHD patients (34% female) enrolled in the health insurance-based Multisite Cardiac Lifestyle Intervention Program. Analyses of variance for repeated measures were used to analyze health behaviors, coronary risk factors, and psychosocial factors at baseline and 3 months. Multiple regression analyses evaluated changes in dietary fat intake and hours per week of exercise and stress management as predictors of changes in coronary risk and psychosocial factors. Significant overall improvement in coronary risk was observed. Reductions in dietary fat intake predicted reductions in weight, total cholesterol, low-density lipoprotein cholesterol, and interacted with increased exercise to predict reductions in perceived stress. Increases in exercise predicted improvements in total cholesterol and exercise capacity (for women). Increased stress management was related to reductions in weight, total cholesterol/high-density lipoprotein cholesterol (for men), triglycerides, hemoglobin A1c (in patients with diabetes), and hostility. Improvements in dietary fat intake, exercise, and stress management were individually, additively and interactively related to coronary risk and psychosocial factors, suggesting that multicomponent programs focusing on diet, exercise, and stress management may benefit patients with CHD.

Cardiac diseases as a risk factor for stroke in Saudi children.

PubMed

Salih, Mustafa A; Al-Jarallah, Abdullah S; Abdel-Gader, Abdel-Galil M; Al-Jarallah, Ahmed A; Al-Saadi, Muslim M; Kentab, Amal Y; Alorainy, Ibrahim A; Hassan, Hamdy H

2006-03-01

To ascertain the role of cardiac diseases as a risk factor for stroke in a cohort of Saudi children who were evaluated in a retrospective and prospective study. Children with cardiac diseases were identified from within a cohort of 104 Saudi children who presented with stroke. They were seen as inpatients in the Pediatric Wards or evaluated at the Outpatient Clinics of the Division of Pediatric Neurology (DPN), and the Division of Pediatric Cardiology at King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia during the periods July 1992 to February 2001 (retrospective study) and February 2001 to March 2003 (prospective study). A comprehensive form for clinical, neuroimaging, neurophysiological and laboratory data retrieval was designed and completed for each patient. Cardiac evaluation included 12-lead ECG and serial echocardiograms. Cardiac catheterization and 24-hour ambulatory ECG (Holter) were conducted on clinical discretion. Cardiac diseases were the underlying risk factor for stroke in 6 (5.8%) of the 104 children (aged one month to 12 years). The patients (4 males and 2 females) were evaluated at the DPN at a mean age of 5.3 years (range = 1-8 years; median 6.5 years). Onset of stroke was at a mean age of 34 months (range = 4 months-8 years; median = 30 months). Five patients had stroke in association with congenital heart disease (CHD), whereas the sixth had restrictive cardiomyopathy. The identified CHD consisted of membranous ventricular septal defect in a 5-year-old boy who had moyamoya syndrome and sickle cell beta(0)-thalassemia, asymptomatic patent ductus arteriosus (PDA) in a 17-month-old girl, atrioventricular canal defect and PDA in an 8-year-old boy who also had Down syndrome, partial anomalous pulmonary venous drainage in a one-year-old boy, and Tetralogy of Fallot in an 8-year-old boy. The latter patient developed hemiparesis secondary to a septic embolus, which evolved into brain abscess involving the right fronto-parietal region

Urban-rural differences in the prevalence of non-communicable diseases risk factors among 25-74 years old citizens in Yangon Region, Myanmar: a cross sectional study.

PubMed

Htet, Aung Soe; Bjertness, Marius B; Sherpa, Lhamo Y; Kjøllesdal, Marte Karoline; Oo, Win Myint; Meyer, Haakon E; Stigum, Hein; Bjertness, Espen

2016-12-05

Recent societal and political reforms in Myanmar may upturn the socio-economy and, thus, contribute to the country's health transition. Baseline data on urban-rural disparities in non-communicable disease (NCD) risk factors are not thoroughly described in this country which has been relatively closed for more than five decades. We aim to investigate urban-rural differences in mean values and the prevalence of selected behavioral and metabolic risk factors for non-communicable diseases and 10-years risk in development of coronary heart diseases (CHD). Two cross-sectional studies were conducted in urban and rural areas of Yangon Region in 2013 and 2014 respectively, using the WHO STEPwise approach to surveillance of risk factors of NCDs. Through a multi-stage cluster sampling method, 1486 participants were recruited. Age-standardized prevalence of the behavioral risk factors tended to be higher in the rural than urban areas for all included factors and significantly higher for alcohol drinking (19.9% vs. 13.9%; p = 0.040) and low fruit & vegetable consumption (96.7% vs. 85.1%; p = 0.001). For the metabolic risk factors, the tendency was opposite, with higher age-standardized prevalence estimates in urban than rural areas, significantly for overweight and obesity combined (40.9% vs. 31.2%; p = 0.023), obesity (12.3% vs.7.7%; p = 0.019) and diabetes (17.2% vs. 9.2%; p = 0.024). In sub-group analysis by gender, the prevalence of hypercholesterolemia and hypertriglyceridemia were significantly higher in urban than rural areas among males, 61.8% vs. 40.4%; p = 0.002 and 31.4% vs. 20.7%; p = 0.009, respectively. Mean values of age-standardized metabolic parameters showed higher values in urban than rural areas for both male and female. Based on WHO age-standardized Framingham risk scores, 33.0% (95% CI = 31.7-34.4) of urban dwellers and 27.0% (95% CI = 23.5-30.8) of rural dwellers had a moderate to high risk of developing CHD in the next

Analyzing Recent Coronary Heart Disease Mortality Trends in Tunisia between 1997 and 2009

PubMed Central

Saidi, Olfa; Ben Mansour, Nadia; O’Flaherty, Martin; Capewell, Simon; Critchley, Julia A.; Romdhane, Habiba Ben

2013-01-01

Background In Tunisia, Cardiovascular Diseases are the leading causes of death (30%), 70% of those are coronary heart disease (CHD) deaths and population studies have demonstrated that major risk factor levels are increasing. Objective To explain recent CHD trends in Tunisia between 1997 and 2009. Methods Data Sources: Published and unpublished data were identified by extensive searches, complemented with specifically designed surveys. Analysis Data were integrated and analyzed using the previously validated IMPACT CHD policy model. Data items included: (i)number of CHD patients in specific groups (including acute coronary syndromes, congestive heart failure and chronic angina)(ii) uptake of specific medical and surgical treatments, and(iii) population trends in major cardiovascular risk factors (smoking, total cholesterol, systolic blood pressure (SBP), body mass index (BMI), diabetes and physical inactivity). Results CHD mortality rates increased by 11.8% for men and 23.8% for women, resulting in 680 additional CHD deaths in 2009 compared with the 1997 baseline, after adjusting for population change. Almost all (98%) of this rise was explained by risk factor increases, though men and women differed. A large rise in total cholesterol level in men (0.73 mmol/L) generated 440 additional deaths. In women, a fall (−0.43 mmol/L), apparently avoided about 95 deaths. For SBP a rise in men (4 mmHg) generated 270 additional deaths. In women, a 2 mmHg fall avoided 65 deaths. BMI and diabetes increased substantially resulting respectively in 105 and 75 additional deaths. Increased treatment uptake prevented about 450 deaths in 2009. The most important contributions came from secondary prevention following Acute Myocardial Infarction (AMI) (95 fewer deaths), initial AMI treatments (90), antihypertensive medications (80) and unstable angina (75). Conclusions Recent trends in CHD mortality mainly reflected increases in major modifiable risk factors, notably SBP and

Phosphorylation of the Nicotiana benthamiana WRKY8 Transcription Factor by MAPK Functions in the Defense Response[C][W][OA

PubMed Central

Ishihama, Nobuaki; Yamada, Reiko; Yoshioka, Miki; Katou, Shinpei; Yoshioka, Hirofumi

2011-01-01

Mitogen-activated protein kinase (MAPK) cascades have pivotal roles in plant innate immunity. However, downstream signaling of plant defense-related MAPKs is not well understood. Here, we provide evidence that the Nicotiana benthamiana WRKY8 transcription factor is a physiological substrate of SIPK, NTF4, and WIPK. Clustered Pro-directed Ser residues (SP cluster), which are conserved in group I WRKY proteins, in the N-terminal region of WRKY8 were phosphorylated by these MAPKs in vitro. Antiphosphopeptide antibodies indicated that Ser residues in the SP cluster of WRKY8 are phosphorylated by SIPK, NTF4, and WIPK in vivo. The interaction of WRKY8 with MAPKs depended on its D domain, which is a MAPK-interacting motif, and this interaction was required for effective phosphorylation of WRKY8 in plants. Phosphorylation of WRKY8 increased its DNA binding activity to the cognate W-box sequence. The phospho-mimicking mutant of WRKY8 showed higher transactivation activity, and its ectopic expression induced defense-related genes, such as 3-hydroxy-3-methylglutaryl CoA reductase 2 and NADP-malic enzyme. By contrast, silencing of WRKY8 decreased the expression of defense-related genes and increased disease susceptibility to the pathogens Phytophthora infestans and Colletotrichum orbiculare. Thus, MAPK-mediated phosphorylation of WRKY8 has an important role in the defense response through activation of downstream genes. PMID:21386030

The M235T Polymorphism in the AGT Gene and CHD Risk: Evidence of a Hardy-Weinberg Equilibrium Violation and Publication Bias in a Meta-Analysis

PubMed Central

Zafarmand, Mohammad Hadi; van der Schouw, Yvonne T.; Grobbee, Diederick E.; de Leeuw, Peter W.; Bots, Michiel L.

2008-01-01

Background The M235T polymorphism in the AGT gene has been related to an increased risk of hypertension. This finding may also suggest an increased risk of coronary heart disease (CHD). Methodology/Principal Findings A case-cohort study was conducted in 1,732 unrelated middle-age women (210 CHD cases and 1,522 controls) from a prospective cohort of 15,236 initially healthy Dutch women. We applied a Cox proportional hazards model to study the association of the polymorphism with acute myocardial infarction (AMI) (n = 71) and CHD. In the case-cohort study, no increased risk for CHD was found under the additive genetic model (hazard ratio [HR] = 1.20; 95% confidence interval [CI], 0.86 to 1.68; P = 0.28). This result was not changed by adjustment (HR = 1.17; 95% CI, 0.83 to 1.64; P = 0.38) nor by using dominant, recessive and pairwise genetic models. Analyses for AMI risk under the additive genetic model also did not show any statistically significant association (crude HR = 1.14; 95% CI, 0.93 to 1.39; P = 0.20). To evaluate the association, a comprehensive systematic review and meta-analysis were undertaken of all studies published up to February 2007 (searched through PubMed/MEDLINE, Web of Science and EMBASE). The meta-analysis (38 studies with 13284 cases and 18722 controls) showed a per-allele odds ratio (OR) of 1.08 (95% CI, 1.01 to 1.15; P = 0.02). Moderate to large levels of heterogeneity were identified between studies. Hardy-Weinberg equilibrium (HWE) violation and the mean age of cases were statistically significant sources of the observed variation. In a stratum of non-HWE violation studies, there was no effect. An asymmetric funnel plot, the Egger's test (P = 0.066), and the Begg-Mazumdar test (P = 0.074) were all suggestive of the presence of publication bias. Conclusions/Significance The pooled OR of the present meta-analysis, including our own data, presented evidence that there is an increase in the risk of CHD

Human Atg8-cardiolipin interactions in mitophagy: Specific properties of LC3B, GABARAPL2 and GABARAP.

PubMed

Antón, Zuriñe; Landajuela, Ane; Hervás, Javier H; Montes, L Ruth; Hernández-Tiedra, Sonia; Velasco, Guillermo; Goñi, Felix M; Alonso, Alicia

2016-12-01

The phospholipid cardiolipin (CL) has been proposed to play a role in selective mitochondrial autophagy, or mitophagy. CL externalization to the outer mitochondrial membrane would act as a signal for the human Atg8 ortholog subfamily, MAP1LC3 (LC3). The latter would mediate both mitochondrial recognition and autophagosome formation, ultimately leading to removal of damaged mitochondria. We have applied quantitative biophysical techniques to the study of CL interaction with various Atg8 human orthologs, namely LC3B, GABARAPL2 and GABARAP. We have found that LC3B interacts preferentially with CL over other di-anionic lipids, that CL-LC3B binding occurs with positive cooperativity, and that the CL-LC3B interaction relies only partially on electrostatic forces. CL-induced increased membrane fluidity appears also as an important factor helping LC3B to bind CL. The LC3B C terminus remains exposed to the hydrophilic environment after protein binding to CL-enriched membranes. In intact U87MG human glioblastoma cells rotenone-induced autophagy leads to LC3B translocation to mitochondria and subsequent delivery of mitochondria to lysosomes. We have also observed that GABARAP, but not GABARAPL2, interacts with CL in vitro. However neither GABARAP nor GABARAPL2 were translocated to mitochondria in rotenone-treated U87MG cells. Thus the various human Atg8 orthologs might play specific roles in different autophagic processes.

Hot flushes, coronary heart disease, and hormone therapy in postmenopausal women

PubMed Central

Huang, Alison J.; Sawaya, George F.; Vittinghoff, Eric; Lin, Feng; Grady, Deborah

2010-01-01

Objective The aim of this study was to examine interactions between hot flushes, estrogen plus progestogen therapy (EPT), and coronary heart disease (CHD) events in postmenopausal women with CHD. Methods We analyzed data from the Heart and Estrogen/Progestin Replacement Study, a randomized, placebo-controlled trial of 0.625 mg conjugated equine estrogens plus 2.5 mg medroxyprogesterone acetate in 2,763 postmenopausal women with CHD. Hot flushes were assessed at baseline using self-administered questionnaires; women reporting bothersome hot flushes “some” to ”all” of the time were considered to have clinically significant flushing. Cox regression models were used to examine the effect of EPT on risk of CHD events among women with and without significant flushing at baseline. Results The mean age of participants was 66.7 ± 6.8 years, and 89% (n = 2,448) were white. Sixteen percent (n = 434) of participants reported clinically significant hot flushes at baseline. Among women with baseline flushing, EPT increased risk of CHD events nine-fold in the first year compared with placebo (hazard ratio = 9.01; 95% CI, 1.15-70.35); among women without baseline flushing, treatment did not significantly affect CHD event risk in the first year (hazard ratio = 1.32; 95% CI, 0.86-2.03; P = 0.07 for interaction of hot flushes with treatment). The trend toward differential effects of EPT on risk for CHD among women with and without baseline flushing did not persist after the first year of treatment. Conclusions Among older postmenopausal women with CHD, EPT may increase risk of CHD events substantially in the first year of treatment among women with clinically significant hot flushes but not among those without hot flushes. PMID:19325499

Three job stress models/concepts and oxidative DNA damage in a sample of workers in Japan.

PubMed

Inoue, Akiomi; Kawakami, Norito; Ishizaki, Masao; Tabata, Masaji; Tsuchiya, Masao; Akiyama, Miki; Kitazume, Akiko; Kuroda, Mitsuyo; Shimazu, Akihito

2009-04-01

Three job stress models/concepts (the job demands-control [DC] model, the effort-reward imbalance [ERI] model, and organizational justice) have been linked to coronary heart disease (CHD) at work. In recent years, oxidative DNA damage has been identified as a new risk factor for CHD. However, evidence for the association between these job stressors and oxidative DNA damage is limited. The present cross-sectional study investigated the association between these job stress models/concepts and oxidative DNA damage as a possible mediator of the adverse health effects of job stress. A total of 166 male and 51 female workers of a manufacturing factory in Japan were surveyed using a mailed questionnaire regarding job stressors and demographic, occupational, and lifestyle variables. Urinary concentrations of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of oxidative DNA damage, were also measured. In male subjects, the urinary concentrations of 8-OHdG were significantly higher among the group with lower interactional justice, one of the two components of organizational justice; however, no association was observed with the DC model or the ERI model. In female subjects, high job demands/control ratio was significantly and positively associated with the urinary concentrations of 8-OHdG. Interactional justice among male workers and the DC model-based strain among female workers may be associated with increased urinary concentrations of 8-OHdG which possibly reflects oxidative DNA damage.

Association of Coronary Artery Calcium in Adults Aged 32 to 46 Years With Incident Coronary Heart Disease and Death

PubMed Central

Jacobs, David R.; Terry, James G.; Shay, Christina M.; Sidney, Stephen; Liu, Kiang; Schreiner, Pamela J.; Lewis, Cora E.; Shikany, James M.; Reis, Jared P.; Goff, David C.

2017-01-01

Importance Coronary artery calcium (CAC) is associated with coronary heart disease (CHD) and cardiovascular disease (CVD); however, prognostic data on CAC are limited in younger adults. Objective To determine if CAC in adults aged 32 to 46 years is associated with incident clinical CHD, CVD, and all-cause mortality during 12.5 years of follow-up. Design, Setting, and Participants The Coronary Artery Risk Development in Young Adults (CARDIA) Study is a prospective community-based study that recruited 5115 black and white participants aged 18 to 30 years from March 25, 1985, to June 7, 1986. The cohort has been under surveillance for 30 years, with CAC measured 15 (n = 3043), 20 (n = 3141), and 25 (n = 3189) years after recruitment. The mean follow-up period for incident events was 12.5 years, from the year 15 computed tomographic scan through August 31, 2014. Main Outcomes and Measures Incident CHD included fatal or nonfatal myocardial infarction, acute coronary syndrome without myocardial infarction, coronary revascularization, or CHD death. Incident CVD included CHD, stroke, heart failure, and peripheral arterial disease. Death included all causes. The probability of developing CAC by age 32 to 56 years was estimated using clinical risk factors measured 7 years apart between ages 18 and 38 years. Results At year 15 of the study among 3043 participants (mean [SD] age, 40.3 [3.6] years; 1383 men and 1660 women), 309 individuals (10.2%) had CAC, with a geometric mean Agatston score of 21.6 (interquartile range, 17.3-26.8). Participants were followed up for 12.5 years, with 57 incident CHD events and 108 incident CVD events observed. After adjusting for demographics, risk factors, and treatments, those with any CAC experienced a 5-fold increase in CHD events (hazard ratio [HR], 5.0; 95% CI, 2.8-8.7) and 3-fold increase in CVD events (HR, 3.0; 95% CI, 1.9-4.7). Within CAC score strata of 1-19, 20-99, and 100 or more, the HRs for CHD were 2.6 (95% CI, 1

Molecular biology of human herpesvirus 8: novel functions and virus-host interactions implicated in viral pathogenesis and replication.

PubMed

Cousins, Emily; Nicholas, John

2014-01-01

Human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus (KSHV), is the second identified human gammaherpesvirus. Like its relative Epstein-Barr virus, HHV-8 is linked to B-cell tumors, specifically primary effusion lymphoma and multicentric Castleman's disease, in addition to endothelial-derived KS. HHV-8 is unusual in its possession of a plethora of "accessory" genes and encoded proteins in addition to the core, conserved herpesvirus and gammaherpesvirus genes that are necessary for basic biological functions of these viruses. The HHV-8 accessory proteins specify not only activities deducible from their cellular protein homologies but also novel, unsuspected activities that have revealed new mechanisms of virus-host interaction that serve virus replication or latency and may contribute to the development and progression of virus-associated neoplasia. These proteins include viral interleukin-6 (vIL-6), viral chemokines (vCCLs), viral G protein-coupled receptor (vGPCR), viral interferon regulatory factors (vIRFs), and viral antiapoptotic proteins homologous to FLICE (FADD-like IL-1β converting enzyme)-inhibitory protein (FLIP) and survivin. Other HHV-8 proteins, such as signaling membrane receptors encoded by open reading frames K1 and K15, also interact with host mechanisms in unique ways and have been implicated in viral pathogenesis. Additionally, a set of micro-RNAs encoded by HHV-8 appear to modulate expression of multiple host proteins to provide conditions conducive to virus persistence within the host and could also contribute to HHV-8-induced neoplasia. Here, we review the molecular biology underlying these novel virus-host interactions and their potential roles in both virus biology and virus-associated disease.

Serum level of triglycerides is a potent risk factor comparable to LDL cholesterol for coronary heart disease in Japanese patients with type 2 diabetes: subanalysis of the Japan Diabetes Complications Study (JDCS).

PubMed

Sone, Hirohito; Tanaka, Sachiko; Tanaka, Shiro; Iimuro, Satoshi; Oida, Koji; Yamasaki, Yoshimitsu; Oikawa, Shinichi; Ishibashi, Shun; Katayama, Shigehiro; Ohashi, Yasuo; Akanuma, Yasuo; Yamada, Nobuhiro

2011-11-01

Risk factors for cardiovascular complications in Japanese patients with diabetes have not been fully elucidated. Our objective was to determine incidence of and risk factors for coronary heart disease (CHD) and stroke in Japanese diabetic patients. We conducted a prospective study at 59 hospitals throughout Japan. Patients included 940 men and 831 women with type 2 diabetes (mean age, 58.2 yr) without a history of cardiovascular complications who were followed for a median of 7.86 yr. This was an observational study. Incidence of CHD and stroke was evaluated. Incidences of CHD and stroke per 1000 person-years were 9.59 and 7.45, respectively, whereas those of myocardial and brain infarctions were 3.84 and 6.29, respectively. Multivariate Cox analysis revealed that the serum log-transformed triglyceride level was a potent and independent predictor of CHD [hazard ratio (HR) = 1.54; 95% confidence interval (CI) = 1.22-1.94 per 1 sd increase), comparable to low-density lipoprotein (LDL) cholesterol (HR = 1.49; 95% CI = 1.25-1.78 per 1 sd increase). Triglycerides and LDL cholesterol linearly and continuously increased CHD risk, and subjects in the top third for both had markedly high risks of CHD, and their effects were possibly additive. However, serum triglycerides worked independently of blood pressure levels. Systolic blood pressure was the only significant predictor for stroke except for age (HR = 1.31; 95% CI = 1.04-1.65, per 1 sd increase). In Japanese patients with type 2 diabetes, the serum triglyceride level was a leading predictor of CHD, comparable to LDL cholesterol. Because the serum triglyceride level is not a leading predictor of CHD in diabetic subjects in Western countries, ethnic group-specific strategies for prevention of diabetic macroangiopathy may be indicated.

Protein-protein interactions in the regulation of WRKY transcription factors.

PubMed

Chi, Yingjun; Yang, Yan; Zhou, Yuan; Zhou, Jie; Fan, Baofang; Yu, Jing-Quan; Chen, Zhixiang

2013-03-01

It has been almost 20 years since the first report of a WRKY transcription factor, SPF1, from sweet potato. Great progress has been made since then in establishing the diverse biological roles of WRKY transcription factors in plant growth, development, and responses to biotic and abiotic stress. Despite the functional diversity, almost all analyzed WRKY proteins recognize the TTGACC/T W-box sequences and, therefore, mechanisms other than mere recognition of the core W-box promoter elements are necessary to achieve the regulatory specificity of WRKY transcription factors. Research over the past several years has revealed that WRKY transcription factors physically interact with a wide range of proteins with roles in signaling, transcription, and chromatin remodeling. Studies of WRKY-interacting proteins have provided important insights into the regulation and mode of action of members of the important family of transcription factors. It has also emerged that the slightly varied WRKY domains and other protein motifs conserved within each of the seven WRKY subfamilies participate in protein-protein interactions and mediate complex functional interactions between WRKY proteins and between WRKY and other regulatory proteins in the modulation of important biological processes. In this review, we summarize studies of protein-protein interactions for WRKY transcription factors and discuss how the interacting partners contribute, at different levels, to the establishment of the complex regulatory and functional network of WRKY transcription factors.

Ile-1781-Leu and Asp-2078-Gly Mutations in ACCase Gene, Endow Cross-resistance to APP, CHD, and PPZ in Phalaris minor from Mexico

PubMed Central

Cruz-Hipolito, Hugo; Fernandez, Pablo; Alcantara, Ricardo; Gherekhloo, Javid; Osuna, Maria Dolores; De Prado, Rafael

2015-01-01

Herbicides that inhibit acetyl coenzyme A carboxylase (ACCase) are commonly used in Mexico to control weedy grasses such as little seed canarygrass (Phalaris minor). These herbicides are classified into three major families (ariloxyphenoxypropionates (APP), cyclohexanodiones (CHD), and, recently, phenylpyrazolines (PPZ)). In this work, the resistance to ACCase (APP, CHD, and PPZ) inhibiting herbicides was studied in a biotype of Phalaris minor (P. minor) from Mexico, by carrying out bioassays at the whole-plant level and investigating the mechanism behind this resistance. Dose-response and ACCase in vitro activity assays showed cross-resistance to all ACCase herbicides used. There was no difference in the absorption, translocation, and metabolism of the 14C-diclofop-methyl between the R and S biotypes. The PCR generated CT domain fragments of ACCase from the R biotype and an S reference were sequenced and compared. The Ile-1781-Leu and Asp-2078-Gly point mutations were identified. These mutations could explain the loss of affinity for ACCase by the ACCase-inhibing herbicides. This is the first report showing that this substitution confers resistance to APP, CHD, and PPZ herbicides in P. minor from Mexico. The mutations have been described previously only in a few cases; however, this is the first study reporting on a pattern of cross-resistance with these mutations in P. minor. The findings could be useful for better management of resistant biotypes carrying similar mutations. PMID:26370967

Suboptimal management of cardiovascular risk factors in coronary heart disease patients in primary care occurs particularly in women.

PubMed

Driscoll, A; Beauchamp, A; Lyubomirsky, G; Demos, L; McNeil, J; Tonkin, A

2011-10-01

Patients with established coronary heart disease (CHD) are at the highest risk of further events. Despite proven therapies, secondary prevention is often suboptimal. General practitioners (GPs) are in an ideal position to improve secondary prevention. To contrast management of cardiovascular risk factors in patients with established CHD in primary care to those in clinical guidelines and according to gender. GPs throughout Australia were approached to participate in a programme incorporating a disease management software (mdCare) program. Participating practitioners (1258 GPs) recruited individual patients whose cardiovascular risk factor levels were measured. The mdCare programme included 12,509 patients (58% male) diagnosed with CHD. Their mean age was 71.7years (intra-quartile range 66-78) for men and 74years (intra-quartile range 68-80) for women. Low-density-lipoprotein cholesterol was above target levels in 69% (2032) of women compared with 58% (2487) in men (P < 0.0001). There was also a higher proportion of women with total cholesterol above target levels (76%, 3592) compared with men (57%, 3787) (P < 0.0001). In patients who were prescribed lipid-lowering medication, 53% (2504) of men and 72% (2285) of women continued to have a total cholesterol higher than recommended target levels (P < 0.0001). Overall, over half (52%, 6538) had at least five cardiovascular risk factors (55% (2914) in women and 50% (3624) in men, P < 0.0001). This study found less intensive management of cardiovascular risk factors in CHD patients, particularly among women, despite equivalent cardiovascular risk. This study has shown that these patients have multiple risk factors where gender also plays a role. © 2011 The Authors. Internal Medicine Journal © 2011 Royal Australasian College of Physicians.

IL-8 interacts with metadherin promoting proliferation and migration in gastric cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Wenfeng; Lin, Shuangming; Li, Wenhuan

It has been reported that IL-8 was involved in the promotion of invasion of Gastric Cancer (GC), however the underlying mechanism by which IL-8 was observed to be able to promote invasion remains unknown. Here, in our study, IL-8 was shown to be significantly up-regulated in GC compared with paired normal control tissues whose expression was markedly associated with inferior overall prognosis; and IL-8 was displayed to be capable of directly interacting with metadherin (MTDH), which in turn can up-regulate IL-8 expression. Blockage of IL-8/MTDH using specific mono-antibody can abolish the invasion IL-8 mediated. Taken together, our results may providemore » a novel explanation of working mechanism of IL-8 in the invasion of GC. - Highlights: • IL-8 was commonly observed to be significantly up-regulated in gastric cancer. • IL-8 was found to be able to be directly interacted with MTDH. • MTDH can up-regulate IL-8 promoting EMT process. • Blockage of IL-8-MTDH complex can abrogate the growth of gastric cancer cells in vitro and in vivo.« less

Incidence and Risk Factors for Perioperative Cardiovascular and Respiratory Adverse Events in Pediatric Patients With Congenital Heart Disease Undergoing Noncardiac Procedures.

PubMed

Lee, Sandra; Reddington, Elise; Koutsogiannaki, Sophia; Hernandez, Michael R; Odegard, Kirsten C; DiNardo, James A; Yuki, Koichi

2018-04-27

While mortality and adverse perioperative events after noncardiac surgery in children with a broad range of congenital cardiac lesions have been investigated using large multiinstitutional databases, to date single-center studies addressing adverse outcomes in children with congenital heart disease (CHD) undergoing noncardiac surgery have only included small numbers of patients with significant heart disease. The primary objective of this study was to determine the incidences of perioperative cardiovascular and respiratory events in a large cohort of patients from a single institution with a broad range of congenital cardiac lesions undergoing noncardiac procedures and to determine risk factors for these events. We identified 3010 CHD patients presenting for noncardiac procedures in our institution over a 5-year period. We collected demographic information, including procedure performed, cardiac diagnosis, ventricular function as assessed by echocardiogram within 6 months of the procedure, and classification of CHD into 3 groups (minor, major, or severe CHD) based on residual lesion burden and cardiovascular functional status. Characteristics related to conduct of anesthesia care were also collected. The primary outcome variables for our analysis were the incidences of intraoperative cardiovascular and respiratory events. Univariable and multivariable logistic regressions were used to determine risk factors for these 2 outcomes. The incidence of cardiovascular events was 11.5% and of respiratory events was 4.7%. Univariate analysis and multivariable analysis demonstrated that American Society of Anesthesiologists (≥3), emergency cases, major and severe CHD, single-ventricle physiology, ventricular dysfunction, orthopedic surgery, general surgery, neurosurgery, and pulmonary procedures were associated with perioperative cardiovascular events. Respiratory events were associated with American Society of Anesthesiologists (≥4) and otolaryngology, gastrointestinal

Serum brain-derived neurotrophic factor and stability of depressive symptoms in coronary heart disease patients: A prospective study.

PubMed

Kuhlmann, Stella L; Tschorn, Mira; Arolt, Volker; Beer, Katja; Brandt, Julia; Grosse, Laura; Haverkamp, Wilhelm; Müller-Nordhorn, Jacqueline; Rieckmann, Nina; Waltenberger, Johannes; Warnke, Katharina; Hellweg, Rainer; Ströhle, Andreas

2017-03-01

Brain-derived neurotrophic factor (BDNF) supports neurogenesis, angiogenesis, and promotes the survival of various cell types in the brain and the coronary system. Moreover, BDNF is associated with both coronary heart disease (CHD) and depression. The current study aims to investigate whether serum BDNF levels are associated with the course of depressive symptoms in CHD patients. At baseline, N=225 CHD patients were enrolled while hospitalized. Of these, N=190 (84%) could be followed up 6 months later. Depressive symptoms were assessed both at baseline and at the 6-months follow-up using the Patient Health Questionnaire (PHQ-9). Serum BDNF concentrations were measured using fluorometric Enzyme-linked immunosorbent assays (ELISA). Logistic regression models showed that lower BDNF levels were associated with persistent depressive symptoms, even after adjustment for age, sex, smoking and potential medical confounders. The incidence of depressive symptoms was not related to lower BDNF levels. However, somatic comorbidity (as measured by the Charlson Comorbidity Index) was significantly associated with the incidence of depressive symptoms. Our findings suggest a role of BDNF in the link between CHD and depressive symptoms. Particularly, low serum BDNF levels could be considered as a valuable biomarker for the persistence of depressive symptoms among depressed CHD patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

Lower Circulating Folate Induced by a Fidgetin Intronic Variant Is Associated With Reduced Congenital Heart Disease Susceptibility.

PubMed

Wang, Dan; Wang, Feng; Shi, Kai-Hu; Tao, Hui; Li, Yang; Zhao, Rui; Lu, Han; Duan, Wenyuan; Qiao, Bin; Zhao, Shi-Min; Wang, Hongyan; Zhao, Jian-Yuan

2017-05-02

Folate deficiency is an independent risk factor for congenital heart disease (CHD); however, the maternal plasma folate level is paradoxically not a good diagnostic marker. Genome-wide surveys have identified variants of nonfolate metabolic genes associated with the plasma folate level, suggesting that these genetic polymorphisms are potential risk factors for CHD. To examine the effects of folate concentration-related variations on CHD risk in the Han Chinese population, we performed 3 independent case-control studies including a total of 1489 patients with CHD and 1745 control subjects. The expression of the Fidgetin (FIGN) was detected in human cardiovascular and decidua tissue specimens with quantitative real-time polymerase chain reaction and Western blotting. The molecular mechanisms were investigated by luciferase reporter assays, surface plasmon resonance, and chromatin immunoprecipitation. FIGN-interacting proteins were confirmed by tandem affinity purification and coimmunoprecipitation. Proteasome activity and metabolite concentrations in the folate pathway were quantified with a commercial proteasome activity assay and immunoassays, respectively. The +94762G>C (rs2119289) variant in intron 4 of the FIGN gene was associated with significant reduction in CHD susceptibility ( P =5.1×10 -14 for the allele, P =8.5×10 --13 for the genotype). Analysis of combined samples indicated that CHD risks in individuals carrying heterozygous (GC) or homozygous (CC) genotypes were reduced by 44% (odds ratio [OR]=0.56; 95% confidence interval [CI]=0.47-0.67) and 66% (OR=0.34; 95% CI=0.23-0.50), respectively, compared with those with the major GG genotype. Minor C allele carriers who had decreased plasma folate levels exhibited significantly increased FIGN expression because the transcription suppressor CREB1 did not bind the alternative promoter of FIGN isoform X3. Mechanistically, increased FIGN expression led to the accumulation of both reduced folate carrier 1 and

Are Cardiovascular Risk Factors also Associated with the Incidence of Atrial Fibrillation?

PubMed Central

Allan, Victoria; Honarbakhsh, Shohreh; Casas, Juan-Pablo; Wallace, Joshua; Hunter, Ross; Schilling, Richard; Perel, Pablo; Morley, Katherine; Banerjee, Amitava

2017-01-01

Summary Established primary prevention strategies of cardiovascular diseases are based on understanding of risk factors, but whether the same risk factors are associated with atrial fibrillation (AF) remains unclear. We conducted a systematic review and field synopsis of the associations of 23 cardiovascular risk factors and incident AF, which included 84 reports based on 28 consented and four electronic health record cohorts of 20,420,175 participants and 576,602 AF events. We identified 3-19 reports per risk factor and heterogeneity in AF definition, quality of reporting, and adjustment. We extracted relative risks (RR) and 95 % confidence intervals [CI] and visualised the number of reports with inverse (RR [CI]<1.00), or direct (RR [CI]>1.00) associations. For hypertension (13/17 reports) and obesity (19/19 reports), there were direct associations with incident AF, as there are for coronary heart disease (CHD). There were inverse associations for non-White ethnicity (5/5 reports, with RR from 0.35 to 0.84 [0.82–0.85]), total cholesterol (4/13 reports from 0.76 [0.59–0.98] to 0.94 [0.90–0.97]; 8/13 reports with non-significant inverse associations), and diastolic blood pressure (2/11 reports from 0.87 [0.78–0.96] to 0.92 [0.85–0.99]; 5/11 reports with non-significant inverse associations), and direct associations for taller height (7/10 reports from 1.03 [1.02–1.05] to 1.92 [1.38–2.67]), which are in the opposite direction of known associations with CHD. A systematic evaluation of the available evidence suggests similarities as well as important differences in the risk factors for incidence of AF as compared with other cardiovascular diseases, which has implications for the primary prevention strategies for atrial fibrillation. PMID:28229164

Factor XIII Val34Leu polymorphism and the risk of myocardial infarction under the age of 36 years.

PubMed

Rallidis, Loukianos S; Politou, Marianna; Komporozos, Christoforos; Panagiotakos, Demosthenes B; Belessi, Chrisoula I; Travlou, Anthi; Lekakis, John; Kremastinos, Dimitrios T

2008-06-01

There are limited and controversial data regarding the impact of factor XIII (FXIII) Val34Leu polymorphism in the pathogenesis of premature myocardial infarction (MI). We examined whether FXIII Val34Leu polymorphism is associated with the development of early MI. We recruited 159 consecutive patients who had survived their first acute MI under the age of 36 years (mean age = 32.1 +/- 3.6 years, 138 were men). The control group consisted of 121 healthy individuals matched with cases for age and sex, without a family history of premature coronary heart disease (CHD). FXIII Val34Leu polymorphism was tested with polymerase chain reaction and reverse hybridization. There was a lower prevalence of carriers of the Leu34 allele in patients than in controls (30.2 vs. 47.1%, p = 0.006). FXIII Val34Leu polymorphism was associated with lower risk for acute MI after adjusting for major cardiovascular risk factors (odds ratio [OR] = 0.51, 95% confidence interval [CI] 0.27-0.95, p = 0.03). Subgroup analysis according to angiographic findings ("normal" coronary arteries [n = 29] or significant CHD [n = 130]) showed that only patients with MI and significant CHD had lower prevalence of carriers of the Leu34 allele compared to controls after adjusting for major cardiovascular risk factors (OR = 0.42, 95% CI 0.22-0.83, p = 0.01). Our data indicate that FXIII Val34Leu polymorphism has a protective effect against the development of MI under the age of 36 years, particularly in the setting of significant CHD.

DNA repair goes hip-hop: SMARCA and CHD chromatin remodellers join the break dance.

PubMed

Rother, Magdalena B; van Attikum, Haico

2017-10-05

Proper signalling and repair of DNA double-strand breaks (DSB) is critical to prevent genome instability and diseases such as cancer. The packaging of DNA into chromatin, however, has evolved as a mere obstacle to these DSB responses. Posttranslational modifications and ATP-dependent chromatin remodelling help to overcome this barrier by modulating nucleosome structures and allow signalling and repair machineries access to DSBs in chromatin. Here we recap our current knowledge on how ATP-dependent SMARCA- and CHD-type chromatin remodellers alter chromatin structure during the signalling and repair of DSBs and discuss how their dysfunction impacts genome stability and human disease.This article is part of the themed issue 'Chromatin modifiers and remodellers in DNA repair and signalling'. © 2017 The Authors.

NFI Transcription Factors Interact with FOXA1 to Regulate Prostate-Specific Gene Expression

PubMed Central

Elliott, Amicia D.; DeGraff, David J.; Anderson, Philip D.; Anumanthan, Govindaraj; Yamashita, Hironobu; Sun, Qian; Friedman, David B.; Hachey, David L.; Yu, Xiuping; Sheehan, Jonathan H.; Ahn, Jung-Mo; Raj, Ganesh V.; Piston, David W.; Gronostajski, Richard M.; Matusik, Robert J.

2014-01-01

Androgen receptor (AR) action throughout prostate development and in maintenance of the prostatic epithelium is partly controlled by interactions between AR and forkhead box (FOX) transcription factors, particularly FOXA1. We sought to identity additional FOXA1 binding partners that may mediate prostate-specific gene expression. Here we identify the nuclear factor I (NFI) family of transcription factors as novel FOXA1 binding proteins. All four family members (NFIA, NFIB, NFIC, and NFIX) can interact with FOXA1, and knockdown studies in androgen-dependent LNCaP cells determined that modulating expression of NFI family members results in changes in AR target gene expression. This effect is probably mediated by binding of NFI family members to AR target gene promoters, because chromatin immunoprecipitation (ChIP) studies found that NFIB bound to the prostate-specific antigen enhancer. Förster resonance energy transfer studies revealed that FOXA1 is capable of bringing AR and NFIX into proximity, indicating that FOXA1 facilitates the AR and NFI interaction by bridging the complex. To determine the extent to which NFI family members regulate AR/FOXA1 target genes, motif analysis of publicly available data for ChIP followed by sequencing was undertaken. This analysis revealed that 34.4% of peaks bound by AR and FOXA1 contain NFI binding sites. Validation of 8 of these peaks by ChIP revealed that NFI family members can bind 6 of these predicted genomic elements, and 4 of the 8 associated genes undergo gene expression changes as a result of individual NFI knockdown. These observations suggest that NFI regulation of FOXA1/AR action is a frequent event, with individual family members playing distinct roles in AR target gene expression. PMID:24801505

An examination of social interaction profiles based on the factors measured by the screen for social interaction.

PubMed

Mahoney, Emery B; Breitborde, Nicholas J K; Leone, Sarah L; Ghuman, Jaswinder Kaur

2014-10-01

Deficits in the capacity to engage in social interactions are a core deficit associated with Autistic Disorder (AD) and Pervasive Developmental Disorder-Not Otherwise Specified (PDD-NOS). These deficits emerge at a young age, making screening for social interaction deficits and interventions targeted at improving capacity in this area important for early identification and intervention. Screening and early intervention efforts are particularly important given the poor short and long term outcomes for children with Autism Spectrum Disorders (ASDs) who experience social interaction deficits. The Screen for Social Interaction (SSI) is a well-validated screening measure that examines a child's capacity for social interaction using a developmental approach. The present study identified four underlying factors measured by the SSI, namely, Connection with Caregiver, Interaction/Imagination, Social Approach/Interest, and Agreeable Nature. The resulting factors were utilized to compare social interaction profiles across groups of children with AD, PDD-NOS, children with non-ASD developmental and/or psychiatric conditions and typically developing children. The results indicate that children with AD and those with PDD-NOS had similar social interaction profiles, but were able to be distinguished from typically developing children on every factor and were able to be distinguished from children with non-ASD psychiatric conditions on every factor except the Connection with Caregiver factor. In addition, children with non-ASD developmental and/or psychiatric conditions could be distinguished from typically developing children on the Connection with Caregiver factor and the Social Approach/Interest factor. These findings have implications for screening and intervention for children with ASDs and non-ASD psychiatric conditions. Copyright © 2014 Elsevier Ltd. All rights reserved.

Are cardiovascular risk factors also associated with the incidence of atrial fibrillation? A systematic review and field synopsis of 23 factors in 32 population-based cohorts of 20 million participants.

PubMed

Allan, Victoria; Honarbakhsh, Shohreh; Casas, Juan-Pablo; Wallace, Joshua; Hunter, Ross; Schilling, Richard; Perel, Pablo; Morley, Katherine; Banerjee, Amitava; Hemingway, Harry

2017-05-03

Established primary prevention strategies of cardiovascular diseases are based on understanding of risk factors, but whether the same risk factors are associated with atrial fibrillation (AF) remains unclear. We conducted a systematic review and field synopsis of the associations of 23 cardiovascular risk factors and incident AF, which included 84 reports based on 28 consented and four electronic health record cohorts of 20,420,175 participants and 576,602 AF events. We identified 3-19 reports per risk factor and heterogeneity in AF definition, quality of reporting, and adjustment. We extracted relative risks (RR) and 95 % confidence intervals [CI] and visualised the number of reports with inverse (RR [CI]<1.00), or direct (RR [CI]>1.00) associations. For hypertension (13/17 reports) and obesity (19/19 reports), there were direct associations with incident AF, as there are for coronary heart disease (CHD). There were inverse associations for non-White ethnicity (5/5 reports, with RR from 0.35 to 0.84 [0.82-0.85]), total cholesterol (4/13 reports from 0.76 [0.59-0.98] to 0.94 [0.90-0.97]; 8/13 reports with non-significant inverse associations), and diastolic blood pressure (2/11 reports from 0.87 [0.78-0.96] to 0.92 [0.85-0.99]; 5/11 reports with non-significant inverse associations), and direct associations for taller height (7/10 reports from 1.03 [1.02-1.05] to 1.92 [1.38-2.67]), which are in the opposite direction of known associations with CHD. A systematic evaluation of the available evidence suggests similarities as well as important differences in the risk factors for incidence of AF as compared with other cardiovascular diseases, which has implications for the primary prevention strategies for atrial fibrillation.

Explaining the increase in coronary heart disease mortality in Syria between 1996 and 2006.

PubMed

Rastam, Samer; Al Ali, Radwan; Maziak, Wasim; Mzayek, Fawaz; Fouad, Fouad M; O'Flaherty, Martin; Capewell, Simon

2012-09-09

Despite advances made in treating coronary heart disease (CHD), mortality due to CHD in Syria has been increasing for the past two decades. This study aims to assess CHD mortality trends in Syria between 1996 and 2006 and to investigate the main factors associated with them. The IMPACT model was used to analyze CHD mortality trends in Syria based on numbers of CHD patients, utilization of specific treatments, trends in major cardiovascular risk factors in apparently healthy persons and CHD patients. Data sources for the IMPACT model included official statistics, published and unpublished surveys, data from neighboring countries, expert opinions, and randomized trials and meta-analyses. Between 1996 and 2006, CHD mortality rate in Syria increased by 64%, which translates into 6370 excess CHD deaths in 2006 as compared to the number expected had the 1996 baseline rate held constant. Using the IMPACT model, it was estimated that increases in cardiovascular risk factors could explain approximately 5140 (81%) of the CHD deaths, while some 2145 deaths were prevented or postponed by medical and surgical treatments for CHD. Most of the recent increase in CHD mortality in Syria is attributable to increases in major cardiovascular risk factors. Treatments for CHD were able to prevent about a quarter of excess CHD deaths, despite suboptimal implementation. These findings stress the importance of population-based primary prevention strategies targeting major risk factors for CHD, as well as policies aimed at improving access and adherence to modern treatments of CHD.

Prevalence and Risk Factors Among Minors for Online Sexual Solicitations and Interactions With Adults.

PubMed

de Santisteban, Patricia; Gámez-Guadix, Manuel

2017-11-02

The research on online child sexual victimization has mainly focused on the sexual solicitation of minors (i.e., sexual requests by an adult), with scarce information available on sexual interactions (e.g., cybersex or meeting in person) in which a minor is exploited by an adult. In the present study, we analyzed the prevalence and risk factors associated with both sexual solicitations and interactions of minors with adults. The sample included 2,731 minors between 12 and 15 years old (50.6% female). The minors completed several self-report questionnaires about sexual solicitations and interactions with adults, including possible risk factors (e.g., sociodemographic variables, Internet use, and psychological adjustment). Of the participants, 15.6% of girls and 9.3% of boys reported sexual solicitations, and 8.2% of girls and 7.4% of boys reported sexualized interactions with adults. Among the variables studied, several appeared related to both sexual solicitations and interactions: older age, having been involved in sexting, being a victim of cyberbullying, having unknown people in friends list, using chat, time spent online on a weekday, and depression symptoms. Gender (being female), using video chat, and instant messaging by computer were significant variables for sexual solicitation but not for sexual interaction; participation in online games was significant only for sexual interactions. Finally, minors reporting sexual interactions presented a higher risk profile than those reporting only sexual solicitations. These findings highlight the relevance of distinguishing between sexual solicitations and sexual interactions and suggest important avenues for prevention programs.

Factors in Client–Clinician Interaction That Influence Hearing Aid Adoption

PubMed Central

Jennings, Mary Beth; Shaw, Lynn; Meston, Christine N.; Cheesman, Margaret F.

2011-01-01

The influence of client–clinician interactions has not been emphasized in hearing health care, despite the extensive evidence of the impact of the provider–patient interaction on health outcomes. The purpose of this study was to identify factors in the client–clinician interaction that may influence hearing aid adoption. Thirteen adults who had received a hearing aid recommendation within the previous 3 months and 10 audiologists participated in a study to generate, sort, and rate the importance of factors in client–clinician interaction that may influence the hearing aid purchase decision. A concept mapping approach was used to define meaningful clusters of factors. Quantitative analysis and qualitative interpretation of the statements resulted in eight concepts. The concepts in order of their importance are (a) Ensuring client comfort, (b) Understanding and meeting client needs, (c) Client-centered traits and actions, (d) Acknowledging client as an individual, (e) Imposing undue pressure and discomfort, (f) Conveying device information by clinician, (g) Supporting choices and shared decision making, and (h) Factors in client readiness. Two overarching themes of client-centered interaction and client empowerment were identified. Results highlight the influence of the client–clinician interaction in hearing aid adoption and suggest the possibility of improving hearing aid adoption by empowering clients through a client-centered interaction. PMID:22155784

Growth factor transgenes interactively regulate articular chondrocytes.

PubMed

Shi, Shuiliang; Mercer, Scott; Eckert, George J; Trippel, Stephen B

2013-04-01

Adult articular chondrocytes lack an effective repair response to correct damage from injury or osteoarthritis. Polypeptide growth factors that stimulate articular chondrocyte proliferation and cartilage matrix synthesis may augment this response. Gene transfer is a promising approach to delivering such factors. Multiple growth factor genes regulate these cell functions, but multiple growth factor gene transfer remains unexplored. We tested the hypothesis that multiple growth factor gene transfer selectively modulates articular chondrocyte proliferation and matrix synthesis. We tested the hypothesis by delivering combinations of the transgenes encoding insulin-like growth factor I (IGF-I), fibroblast growth factor-2 (FGF-2), transforming growth factor beta1 (TGF-β1), bone morphogenetic protein-2 (BMP-2), and bone morphogenetic protien-7 (BMP-7) to articular chondrocytes and measured changes in the production of DNA, glycosaminoglycan, and collagen. The transgenes differentially regulated all these chondrocyte activities. In concert, the transgenes interacted to generate widely divergent responses from the cells. These interactions ranged from inhibitory to synergistic. The transgene pair encoding IGF-I and FGF-2 maximized cell proliferation. The three-transgene group encoding IGF-I, BMP-2, and BMP-7 maximized matrix production and also optimized the balance between cell proliferation and matrix production. These data demonstrate an approach to articular chondrocyte regulation that may be tailored to stimulate specific cell functions, and suggest that certain growth factor gene combinations have potential value for cell-based articular cartilage repair. Copyright © 2012 Wiley Periodicals, Inc.

Interaction between physical and psychosocial work risk factors for low back symptoms and its consequences amongst Indonesian coal mining workers.

PubMed

Widanarko, Baiduri; Legg, Stephen; Devereux, Jason; Stevenson, Mark

2015-01-01

This study assessed the interaction between physical and psychosocial factors for low back symptoms (LBS) and its consequences (reduced activities and absenteeism) in a developing country. A sample of 1294 Indonesian coal mining workers reported occupational exposures, LBS and its consequences using a self-administered questionnaire. Respondents were placed into one of four combination exposure groups: high physical and high psychosocial (HPhyHPsy); high physical and low psychosocial (HPhyLPsy); low physical and high psychosocial (LPhyHPsy), and; low physical and low psychosocial (LPhyLPsy). The attributable proportion due to interaction between physical and psychosocial factors was examined. Individuals in the HPhyHPsy group were most likely to report LBS (OR 5.42, 95% CI 3.30-8.89), reduced activities (OR 4.89, 95% CI 3.09-7.74), and absenteeism (OR 4.96, 95% CI 3.05-8.06). Interactions between physical and psychosocial factors were present for LBS, reduced activities, and absenteeism; although for LBS and absenteeism the interactions were not significant. Current smokers were more likely to report LBS consequences. Permanent employment and night shift work increased the odds of LBS and its consequences. We conclude that interventions aimed at reducing LBS and its consequences should address both physical and psychosocial factors, with a focus on smokers, permanent employment and night shift work. Copyright © 2014 Elsevier Ltd and The Ergonomics Society. All rights reserved.

Explaining the increase in coronary heart disease mortality in Syria between 1996 and 2006

PubMed Central

2012-01-01

Background Despite advances made in treating coronary heart disease (CHD), mortality due to CHD in Syria has been increasing for the past two decades. This study aims to assess CHD mortality trends in Syria between 1996 and 2006 and to investigate the main factors associated with them. Methods The IMPACT model was used to analyze CHD mortality trends in Syria based on numbers of CHD patients, utilization of specific treatments, trends in major cardiovascular risk factors in apparently healthy persons and CHD patients. Data sources for the IMPACT model included official statistics, published and unpublished surveys, data from neighboring countries, expert opinions, and randomized trials and meta-analyses. Results Between 1996 and 2006, CHD mortality rate in Syria increased by 64%, which translates into 6370 excess CHD deaths in 2006 as compared to the number expected had the 1996 baseline rate held constant. Using the IMPACT model, it was estimated that increases in cardiovascular risk factors could explain approximately 5140 (81%) of the CHD deaths, while some 2145 deaths were prevented or postponed by medical and surgical treatments for CHD. Conclusion Most of the recent increase in CHD mortality in Syria is attributable to increases in major cardiovascular risk factors. Treatments for CHD were able to prevent about a quarter of excess CHD deaths, despite suboptimal implementation. These findings stress the importance of population-based primary prevention strategies targeting major risk factors for CHD, as well as policies aimed at improving access and adherence to modern treatments of CHD. PMID:22958443

[The influence of certain meteorological factors on mortality from complications of arterial hypertension].

PubMed

Afanas'eva, G N; Panova, T N; Dedova, A V; Dzhuvaliakov, P G

2010-01-01

The weather may influence the clinical course of many diseases. The objective of the present study was to evaluate effects of certain meteorological factors on the mortality rate associated with complications of arterial hypertension (cerebral stroke and myocardial infarction) in the city of Astrakhan during the period from 1983 to 2005. The analysis included 17,198 cases of death from cardiovascular disorders (CVD). An original software program was used for the purpose that made it possible to estimate the influence of meteorological factors (air temperature, velocity of wind and precipitation) on the mortality rate among subjects with and without AH. It was shown that mortality due to coronary heart disease (CHD) and cerebrovascular disease positively correlated with the air temperature and amount of precipitation but inversely correlated with the velocity of wind. Correlations between mortality from CVD and meteorological factors among subjects presenting with CHD, cerebrovascular disease, and AH were more pronounced and statistically significant compared with patients of the same groups without AH.

Integrative Analysis of Transcription Factor Combinatorial Interactions Using a Bayesian Tensor Factorization Approach

PubMed Central

Ye, Yusen; Gao, Lin; Zhang, Shihua

2017-01-01

Transcription factors play a key role in transcriptional regulation of genes and determination of cellular identity through combinatorial interactions. However, current studies about combinatorial regulation is deficient due to lack of experimental data in the same cellular environment and extensive existence of data noise. Here, we adopt a Bayesian CANDECOMP/PARAFAC (CP) factorization approach (BCPF) to integrate multiple datasets in a network paradigm for determining precise TF interaction landscapes. In our first application, we apply BCPF to integrate three networks built based on diverse datasets of multiple cell lines from ENCODE respectively to predict a global and precise TF interaction network. This network gives 38 novel TF interactions with distinct biological functions. In our second application, we apply BCPF to seven types of cell type TF regulatory networks and predict seven cell lineage TF interaction networks, respectively. By further exploring the dynamics and modularity of them, we find cell lineage-specific hub TFs participate in cell type or lineage-specific regulation by interacting with non-specific TFs. Furthermore, we illustrate the biological function of hub TFs by taking those of cancer lineage and blood lineage as examples. Taken together, our integrative analysis can reveal more precise and extensive description about human TF combinatorial interactions. PMID:29033978

Integrative Analysis of Transcription Factor Combinatorial Interactions Using a Bayesian Tensor Factorization Approach.

PubMed

Ye, Yusen; Gao, Lin; Zhang, Shihua

2017-01-01

Transcription factors play a key role in transcriptional regulation of genes and determination of cellular identity through combinatorial interactions. However, current studies about combinatorial regulation is deficient due to lack of experimental data in the same cellular environment and extensive existence of data noise. Here, we adopt a Bayesian CANDECOMP/PARAFAC (CP) factorization approach (BCPF) to integrate multiple datasets in a network paradigm for determining precise TF interaction landscapes. In our first application, we apply BCPF to integrate three networks built based on diverse datasets of multiple cell lines from ENCODE respectively to predict a global and precise TF interaction network. This network gives 38 novel TF interactions with distinct biological functions. In our second application, we apply BCPF to seven types of cell type TF regulatory networks and predict seven cell lineage TF interaction networks, respectively. By further exploring the dynamics and modularity of them, we find cell lineage-specific hub TFs participate in cell type or lineage-specific regulation by interacting with non-specific TFs. Furthermore, we illustrate the biological function of hub TFs by taking those of cancer lineage and blood lineage as examples. Taken together, our integrative analysis can reveal more precise and extensive description about human TF combinatorial interactions.

Detecting regulatory gene-environment interactions with unmeasured environmental factors.

PubMed

Fusi, Nicoló; Lippert, Christoph; Borgwardt, Karsten; Lawrence, Neil D; Stegle, Oliver

2013-06-01

Genomic studies have revealed a substantial heritable component of the transcriptional state of the cell. To fully understand the genetic regulation of gene expression variability, it is important to study the effect of genotype in the context of external factors such as alternative environmental conditions. In model systems, explicit environmental perturbations have been considered for this purpose, allowing to directly test for environment-specific genetic effects. However, such experiments are limited to species that can be profiled in controlled environments, hampering their use in important systems such as human. Moreover, even in seemingly tightly regulated experimental conditions, subtle environmental perturbations cannot be ruled out, and hence unknown environmental influences are frequent. Here, we propose a model-based approach to simultaneously infer unmeasured environmental factors from gene expression profiles and use them in genetic analyses, identifying environment-specific associations between polymorphic loci and individual gene expression traits. In extensive simulation studies, we show that our method is able to accurately reconstruct environmental factors and their interactions with genotype in a variety of settings. We further illustrate the use of our model in a real-world dataset in which one environmental factor has been explicitly experimentally controlled. Our method is able to accurately reconstruct the true underlying environmental factor even if it is not given as an input, allowing to detect genuine genotype-environment interactions. In addition to the known environmental factor, we find unmeasured factors involved in novel genotype-environment interactions. Our results suggest that interactions with both known and unknown environmental factors significantly contribute to gene expression variability. and implementation: Software available at http://pmbio.github.io/envGPLVM/. Supplementary data are available at Bioinformatics online.

Stroke symptoms and risk for incident coronary heart disease in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study.

PubMed

Colantonio, Lisandro D; Gamboa, Christopher M; Kleindorfer, Dawn O; Carson, April P; Howard, Virginia J; Muntner, Paul; Cushman, Mary; Howard, George; Safford, Monika M

2016-10-01

Many adults without cerebrovascular disease report a history of stroke symptoms, which is associated with higher risk for stroke. Because stroke and coronary heart disease (CHD) share many risk factors, we examined the association between a history of stroke symptoms and incident CHD. We analyzed data from 8999 black and 12,499 white REasons for Geographic And Racial Differences in Stroke (REGARDS) study participants without a prior myocardial infarction, stroke or transitory ischemic attack enrolled in 2003-2007 (total participants=21,498, all ≥45years of age). A history of stroke symptoms (i.e., unilateral weakness, unilateral numbness, full-field vision loss, half-field vision loss, understanding problems and communication problems) was assessed at baseline using the Questionnaire for Verifying Stroke-Free Status. Participants were followed for incident CHD and CHD death through December 2011. Overall, 3432 (16.0%) participants reported a history of stroke symptoms (1771 [19.7%] blacks and 1661 [13.3%] whites). There were 701 incident CHD events including 209 CHD deaths over a median follow-up of 5.8years. After adjustment for CHD risk factors, hazard ratios (95% confidence interval [95% CI]) for incident CHD associated with reporting any versus no stroke symptoms were 1.26 (1.04-1.51) in the overall population, 1.28 (0.99-1.65) among blacks and 1.23 (0.94-1.61) among whites. Multivariable-adjusted hazard ratios (95% CI) for CHD death associated with any versus no stroke symptoms were 1.50 (1.10-2.06) overall, 1.58 (1.07-2.32) among blacks and 1.41 (0.82-2.43) among whites. A history of stroke symptoms is associated with a higher incidence of CHD among black and white adults. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Socio-demographic characteristics, lifestyle factors and burden of morbidity associated with self-reported hearing and vision impairments in older British community-dwelling men: a cross-sectional study.

PubMed

Liljas, A E M; Wannamethee, S G; Whincup, P H; Papacosta, O; Walters, K; Iliffe, S; Lennon, L T; Carvalho, L A; Ramsay, S E

2016-06-01

Hearing and vision problems are common in older adults. We investigated the association of self-reported sensory impairment with lifestyle factors, chronic conditions, physical functioning, quality of life and social interaction. A population-based cross-sectional study of participants of the British Regional Heart Study aged 63-85 years. A total of 3981 men (82% response rate) provided data. Twenty-seven per cent (n = 1074) reported hearing impairment including being able to hear with aid (n = 482), being unable to hear (no aid) (n = 424) and being unable to hear despite aid (n = 168). Three per cent (n = 124) reported vision impairment. Not being able to hear, irrespective of use of hearing aid, was associated with poor quality of life, poor social interaction and poor physical functioning. Men who could not hear despite hearing aid were more likely to report coronary heart disease (CHD) [age-adjusted odds ratios (ORs) 1.89 (95% confidence interval 1.36-2.63)]. Vision impairment was associated with symptoms of CHD including breathlessness [OR 2.06 (1.38-3.06)] and chest pain [OR 1.58 (1.07-2.35)]. Vision impairment was also associated with poor quality of life, poor social interaction and poor physical functioning. Sensory impairment is associated with poor physical functioning, poor health and poor social interaction in older men. Further research is warranted on pathways underlying these associations. © The Author 2015. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Post-traumatic stress disorder and incidence of coronary heart disease: a twin study.

PubMed

Vaccarino, Viola; Goldberg, Jack; Rooks, Cherie; Shah, Amit J; Veledar, Emir; Faber, Tracy L; Votaw, John R; Forsberg, Christopher W; Bremner, J Douglas

2013-09-10

The aim of this study was to determine whether post-traumatic stress disorder (PTSD) is associated with coronary heart disease (CHD) using a prospective twin study design and objective measures of CHD. It has long been hypothesized that PTSD increases the risk of CHD, but empirical evidence using objective measures is limited. We conducted a prospective study of middle-aged male twins from the Vietnam Era Twin Registry. Among twin pairs without self-reported CHD at baseline, we selected pairs discordant for a lifetime history of PTSD, pairs discordant for a lifetime history of major depression, and pairs without either condition. All underwent a clinic visit after a median follow-up of 13 years. Outcomes included clinical events (myocardial infarction, other hospitalizations for CHD and coronary revascularization) and quantitative measures of myocardial perfusion by [(13)N] ammonia positron emission tomography, including a stress total severity score and coronary flow reserve. A total of 562 twins (281 pairs) with a mean age of 42.6 years at baseline were included in this study. The incidence of CHD was more than double in twins with PTSD (22.6%) than in those without PTSD (8.9%; p < 0.001). The association remained robust after adjusting for lifestyle factors, other risk factors for CHD, and major depression (odds ratio: 2.2; 95% confidence interval: 1.2 to 4.1). Stress total severity score was significantly higher (+95%, p = 0.001) and coronary flow reserve was lower (-0.21, p = 0.02) in twins with PTSD than in those without PTSD, denoting worse myocardial perfusion. Associations were only mildly attenuated in 117 twin pairs discordant for PTSD. Among Vietnam-era veterans, PTSD is a risk factor for CHD. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Depression, anxiety, and risk factor control in patients after hospitalization for coronary heart disease: the EUROASPIRE III Study.

PubMed

Pająk, Andrzej; Jankowski, Piotr; Kotseva, Kornelia; Heidrich, Jan; de Smedt, Delphine; De Bacquer, Dirk

2013-04-01

To assess in coronary heart disease (CHD) patients: (1) differences in the prevalence of depression and anxiety between samples selected from 22 countries; (2) the association of depression and anxiety with age, education, diagnostic category, favourable behaviours, use of cardioprotective drugs, and reaching the secondary prevention treatment targets. Cross-sectional study. The study group consisted of 8580 patients from 22 European countries examined at least 6 months after hospitalization due to CHD. Depression and anxiety were assessed using Hospital Anxiety and Depression Scale (HADS). Prevalence of depression (HADS depression score ≥ 8) varied from 8.2% to 35.7% in men and from 10.3% to 62.5% in women. Prevalence of anxiety (HADS anxiety score ≥ 8) varied from 12.0% to 41.8% in men and from 21.5% to 63.7% in women. Older age, female sex, low education, and no history of invasive treatment were associated with more frequent depression and anxiety. Depression and anxiety were associated with less frequent modification of lifestyle. Depression was related with body mass index, waist circumference, fasting glucose, and more frequent self-reported diabetes but not with reaching the treatment targets for blood pressure and lipids. High prevalence of depression and anxiety in CHD patients, and relation with less frequent lifestyle modification, call to integrate methods of identification and minimizing unfavourable effects of depression and anxiety into the cardiac rehabilitation and prevention programmes.

[Relationship between Ghrelin polymorphism and serum lipoprotein levels in Han Chinese with or without coronary heart disease risk factors].

PubMed

Xie, Xuan; Zhang, Jing; Wang, Yu-huan; Wang, Jun-hong; Zhang, Chun-hong; Ni, Hong-yan; Yuan, Xiao-hong

2008-04-01

To investigate the relationship between polymorphism of Ghrelin gene and serum levels of lipoprotein in Han Chinese with or without coronary heart disease (CHD) risk factors. PCR restriction fragment length polymorphism assay was used to detect the distribution of genotypes of Ghrelin gene in 225 Han Chinese (40 to 69 years-old) with CHD risk factors, 78 subjects without CHD risk factors served as normal controls. Serum levels of total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C) and very low-density lipoprotein (VLDL) were measured to analyze the relationship with the polymorphism of Ghrelin gene. Ghrelin genotype frequencies of AA, AG, GG (0.975, 0.025, 0.00 in control group and 0.956, 0.040, 0.004 in the high-risk group, all P > 0.05) as well as the allele frequencies of A, G (0.987, 0.013 in control group and 0.976, 0.024 in the high-risk group, all P > 0.05) were similar between the groups. HDL-C levels of the Arg/Gln carriers were significantly lower than those of Arg/Arg carriers in control group and in the high-risk group (all P < 0.05). Arg/Gln carriers were associated lower HDL-C levels in Han Chinese.

Overweight Status, Obesity, and Risk Factors for Coronary Heart Disease in Adults with Intellectual Disability

ERIC Educational Resources Information Center

Henderson, C. Michael; Robinson, Laura M.; Davidson, Philip W.; Haveman, Meindert; Janicki, Matthew P.; Albertini, Giorgio

2008-01-01

Research indicates that adults with intellectual disabilities (ID) have high rates of overweight status/obesity (OSO). OSO is associated with several important risk factors for coronary heart disease (CHD). This study focused on assessing whether such risk factors are being identified in adults with ID who are receiving their healthcare in…

Dose-expanded study in the reinforcement of efficacy of simvastatin.

PubMed

Vichayanrat, Apichati

2002-04-01

Two hundred and twenty two hyperlipidemic patients were recruited for a 12-week prospective, multicenter, open-label, titrate-to-goal study to evaluate the efficacy and safety of 20 to 40 mg per day of simvastatin in a Thai population. The efficacy on lipid lowering was evaluated at 4 weeks and 8 weeks after medication. Based on NCEP ATP II guideline and ADA position statement, subjects were categorized into three groups according to LDL-C goals; group I: patients without CHD and with < 2 CHD risk factors, group II: patients without CHD and with > or = 2 CHD risk factors and group III: CHD patients or diabetic patients with > or = 1 risk factors. Significant changes of all lipid parameters from baselines were noted at 4 weeks after medication except for HDL-C levels. Reduction of serum LDL-C, TC and TG by 40 per cent, 29 per cent and 16 per cent respectively and increase of serum HDL-C by 5 per cent were observed at 8 weeks of therapy (p<0.05). At 4 weeks after taking simvastatin 20 mg/day, 78.9 per cent of patients in group I, 67.4 per cent in group II and 40.9 per cent in group III achieved LDL-C goals. Seventeen per cent of the patients who were evaluated at 8 weeks increased the simvastatin dosage to 40 mg per day in the second month of treatment. At 8 weeks of therapy with simvastatin 20-40 mg/day, 90.1 per cent of patients in group I, 77.4 per cent in group II and 66.7 per cent in group III achieved LDL-C goals. Adverse symptoms during therapy, mostly mild, developed in 6.3 per cent of the 222 patients. Simvastatin 20-40 mg/day was effective and well tolerated in managing lipid parameters in Thai patients similar to other ethnic populations.

Electrostatic Forces as Dominant Interactions Between Proteins and Polyanions: an ESI MS Study of Fibroblast Growth Factor Binding to Heparin Oligomers

NASA Astrophysics Data System (ADS)

Minsky, Burcu Baykal; Dubin, Paul L.; Kaltashov, Igor A.

2017-04-01

The interactions between fibroblast growth factors (FGFs) and their receptors (FGFRs) are facilitated by heparan sulfate (HS) and heparin (Hp), highly sulfated biological polyelectrolytes. The molecular basis of FGF interactions with these polyelectrolytes is highly complex due to the structural heterogeneity of HS/Hp, and many details still remain elusive, especially the significance of charge density and minimal chain length of HS/Hp in growth factor recognition and multimerization. In this work, we use electrospray ionization mass spectrometry (ESI MS) to investigate the association of relatively homogeneous oligoheparins (octamer, dp8, and decamer, dp10) with acidic fibroblast growth factor (FGF-1). This growth factor forms 1:1, 2:1, and 3:1 protein/heparinoid complexes with both dp8 and dp10, and the fraction of bound protein is highly dependent on protein/heparinoid molar ratio. Multimeric complexes are preferentially formed on the highly sulfated Hp oligomers. Although a variety of oligomers appear to be binding-competent, there is a strong correlation between the affinity and the overall level of sulfation (the highest charge density polyanions binding FGF most strongly via multivalent interactions). These results show that the interactions between FGF-1 and Hp oligomers are primarily directed by electrostatics, and also demonstrate the power of ESI MS as a tool to study multiple binding equilibria between proteins and structurally heterogeneous polyanions.

Physical activity in patients with stable coronary heart disease: an international perspective.

PubMed

Stewart, Ralph; Held, Claes; Brown, Rebekkah; Vedin, Ola; Hagstrom, Emil; Lonn, Eva; Armstrong, Paul; Granger, Christopher B; Hochman, Judith; Davies, Richard; Soffer, Joseph; Wallentin, Lars; White, Harvey

2013-11-01

Despite the known benefits of regular exercise, the reasons why many coronary heart disease (CHD) patients engage in little physical activity are not well understood. This study identifies factors associated with low activity levels in individuals with chronic CHD participating in the STABILITY study, a global clinical outcomes trial evaluating the lipoprotein phospholipaseA2 inhibitor darapladib. Prior to randomization, 15 486 (97.8%) participants from 39 countries completed a lifestyle questionnaire. Total physical activity was estimated from individual subject self-reports of hours spend each week on mild, moderate, and vigorous exercise, corresponding approximately to 2, 4, and 8 METS, respectively. Multivariate logistic regression evaluated clinical and demographic variables for the lowest compared with higher overall exercise levels, and for individuals who decreased rather than maintained or increased activity since diagnosis of CHD. The least active 5280 subjects (34%) reported exercise of ≤ 24 MET.h/week. A total of 7191 subjects (46%) reported less exercise compared with before diagnosis of CHD. The majority of participants were either 'not limited' or 'limited a little' walking 100 m (84%), climbing one flight of stairs (82%), or walking 1 km/1/2; mile (68%), and <10% were limited 'a lot' by dyspnoea or angina. Variables independently associated with both low physical activity and decreasing exercise after diagnosis of CHD included more co-morbid conditions, poorer general health, fewer years of education, race, and country (P < 0.001 for all). In this international study, low physical activity was only partly explained by cardiovascular symptoms. Potentially modifiable societal and health system factors are important determinants of physical inactivity in patients with chronic CHD.

Intervening on risk factors for coronary heart disease: an application of the parametric g-formula.

PubMed

Taubman, Sarah L; Robins, James M; Mittleman, Murray A; Hernán, Miguel A

2009-12-01

Estimating the population risk of disease under hypothetical interventions--such as the population risk of coronary heart disease (CHD) were everyone to quit smoking and start exercising or to start exercising if diagnosed with diabetes--may not be possible using standard analytic techniques. The parametric g-formula, which appropriately adjusts for time-varying confounders affected by prior exposures, is especially well suited to estimating effects when the intervention involves multiple factors (joint interventions) or when the intervention involves decisions that depend on the value of evolving time-dependent factors (dynamic interventions). We describe the parametric g-formula, and use it to estimate the effect of various hypothetical lifestyle interventions on the risk of CHD using data from the Nurses' Health Study. Over the period 1982-2002, the 20-year risk of CHD in this cohort was 3.50%. Under a joint intervention of no smoking, increased exercise, improved diet, moderate alcohol consumption and reduced body mass index, the estimated risk was 1.89% (95% confidence interval: 1.46-2.41). We discuss whether the assumptions required for the validity of the parametric g-formula hold in the Nurses' Health Study data. This work represents the first large-scale application of the parametric g-formula in an epidemiologic cohort study.

pH-Dependent Interactions in Dimers Govern the Mechanics and Structure of von Willebrand Factor.

PubMed

Müller, Jochen P; Löf, Achim; Mielke, Salomé; Obser, Tobias; Bruetzel, Linda K; Vanderlinden, Willem; Lipfert, Jan; Schneppenheim, Reinhard; Benoit, Martin

2016-07-26

Von Willebrand factor (VWF) is a multimeric plasma glycoprotein that is activated for hemostasis by increased hydrodynamic forces at sites of vascular injury. Here, we present data from atomic force microscopy-based single-molecule force measurements, atomic force microscopy imaging, and small-angle x-ray scattering to show that the structure and mechanics of VWF are governed by multiple pH-dependent interactions with opposite trends within dimeric subunits. In particular, the recently discovered strong intermonomer interaction, which induces a firmly closed conformation of dimers and crucially involves the D4 domain, was observed with highest frequency at pH 7.4, but was essentially absent at pH values below 6.8. However, below pH 6.8, the ratio of compact dimers increased with decreasing pH, in line with a previous transmission electron microscopy study. These findings indicated that the compactness of dimers at pH values below 6.8 is promoted by other interactions that possess low mechanical resistance compared with the strong intermonomer interaction. By investigating deletion constructs, we found that compactness under acidic conditions is primarily mediated by the D4 domain, i.e., remarkably by the same domain that also mediates the strong intermonomer interaction. As our data suggest that VWF has the highest mechanical resistance at physiological pH, local deviations from physiological pH (e.g., at sites of vascular injury) may represent a means to enhance VWF's hemostatic activity where needed. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Risk Factors of Congenital Heart Diseases: A Case-Control Study inNorthwest Iran.

PubMed

Naghavi-Behzad, Mohammad; Alizadeh, Mahasti; Azami, Saber; Foroughifar, Shirin; Ghasempour-Dabbaghi, Khazar; Karzad, Nazila; Ahadi, Hamid-Reza; Naghavi-Behzad, Ali

2013-01-01

Congenital heart diseases are of immense importance and also a high prevalence. Contributing factors to developing these defects have not been abundantly studied. Therefore, the current study was conducted aiming at determining the effective factors on Congenital Heart Disease (CHD) in newborn infants of Northwest Iran. A case-control study was carried out in North-West of Iran from 2002 to 2012 and a total of 473 infants entered the study. Required data were obtained through check lists completed by the information of hospital records and interview with mothers of 267 newborn infants with CHD together with medical records of mothers as the case group, and 206 medical records of healthy infants at the same period all together with those of their mothers as the control group. The obtained data were statistically analyzed using descriptive statistical methods, T-test, Spearman's correlation coefficient, and Multi-variable Logistic Regression Model (OR with 95% CI), using SPSS.19. In the present study, P value less than 0.05 was considered statistically significant. Based on the results of univariable analyses, the number of previous cesarean sections, past medical history of diseases, gestational age (GA), fetal weight at birth, diastolic blood pressure, fetal heart rate, pulse rate, fetal hemoglobin and hematocrit levels, and fetal head circumference at birth have significant relationship with incidence of congenital abnormalities (P<0.05). Family history, past cesarean sections history, past medical history and GA had significant relationship with CHD incidence. Based on the results of present study, in order to control and reduce the cases of CHD, it is crucial to make proper decisions and implement policies for reducing cesarean cases, lowering consanguineous marriages, providing proper pre-marriage counseling, prompt treatment of mothers' illnesses, improving pregnancy health care and mothers' health status for the purpose of better well-being of newborn infants.

Serum levels of ghrelin, tumor necrosis factor-alpha and interleukin-6 in infants and children with congenital heart disease.

PubMed

Afify, Mohamed Farouk; Mohamed, Gamal B; El-Maboud, Mohamed Abd; Abdel-Latif, Esmat A

2009-12-01

To estimate serum levels of ghrelin, tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in infants and children with congenital heart disease (CHD), compared with levels in age-matched controls, and to correlate the levels of ghrelin with TNF-alpha and IL-6. Case-control study. Suzan Moubarak Hospital of Al-Minya University, Egypt. We measured serum ghrelin, TNF-alpha and IL-6 levels using ELISA in 60 patients with CHD (40 acyanotic and 20 cyanotic) and in 20 control subjects. Our results showed that patients with CHD, regardless of the presence or absence of cyanosis, had significantly higher serum ghrelin, TNF-alpha and IL-6 than controls (p = 0.000). Serum levels of ghrelin and TNF-alpha in the acyanotic patients were significantly higher than in the cyanotic patients (p = 0.000). On the other hand, there was no significant difference in serum levels of IL-6 between the acyanotic and the cyanotic patients (p = 0.126). In acyanotic and cyanotic patients with CHD, there was a positive correlation between ghrelin and TNF-alpha (r = 0.424; p = 0.006 and r = 0.577; p = 0.008, respectively). Ghrelin levels were not correlated to IL-6 in the acyanotic and cyanotic patients with CHD (r = -0.211; p = 0.216 and r = -0.341; p = 0.08, respectively). Serum ghrelin, TNF-alpha and IL-6 levels are elevated in patients with CHD whether acyanotic or cyanotic. Increased ghrelin levels represent malnutrition and growth retardation in these patients. The relation of ghrelin with TNF-alpha may be explained by the possible effect of chronic congestive heart failure and chronic shunt hypoxemia.

Total cholesterol as a risk factor for coronary heart disease and stroke in women compared with men: A systematic review and meta-analysis.

PubMed

Peters, Sanne A E; Singhateh, Yankuba; Mackay, Diana; Huxley, Rachel R; Woodward, Mark

2016-05-01

Raised total cholesterol is a strong risk factor for cardiovascular disease (CVD). It remains unknown whether sex differences exist in the relationship between total cholesterol and CVD outcomes. PubMed was searched in December 2014 for cohort studies reporting on the relationship between total cholesterol and coronary heart disease (CHD) and total stroke, separately in men and women. Random effects meta-analyses with inverse variance weighting were used to obtain adjusted pooled sex-specific relative risks (RR) and women-to-men ratio of RRs (RRRs). Data from 97 cohorts, 1,022,276 individuals, and 20,176 CHD and 13,067 stroke cases were included. The pooled RR (95% confidence interval) for CHD associated with a 1-mmol/L increase in total cholesterol was 1.20 (1.16; 1.24) in women and 1.24 (1.20; 1.28) in men, resulting in a RRR of 0.96 (0.93; 0.99). Corresponding RRs for the risk of total stroke were 1.01 (0.98; 1.05) in women, and 1.03 (1.00; 1.05) in men, with a pooled RRR of 0.99 (0.93; 1.04). Pooled RRRs (95% CI) comparing individuals in the highest TC category to those in the lowest, such as the highest versus lowest third, were 0.87 (0.79; 0.96) for CHD and 0.86 (0.76; 0.97) for total stroke. Raised total cholesterol is a strong risk factor for CHD, with evidence of a small, but significantly stronger, effect in men compared to women. Raised total cholesterol had little effect on the risk of total stroke in both sexes. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Arabidopsis TCP Transcription Factors Interact with the SUMO Conjugating Machinery in Nuclear Foci

PubMed Central

Mazur, Magdalena J.; Spears, Benjamin J.; Djajasaputra, André; van der Gragt, Michelle; Vlachakis, Georgios; Beerens, Bas; Gassmann, Walter; van den Burg, Harrold A.

2017-01-01

In Arabidopsis more than 400 proteins have been identified as SUMO targets, both in vivo and in vitro. Among others, transcription factors (TFs) are common targets for SUMO conjugation. Here we aimed to exhaustively screen for TFs that interact with the SUMO machinery using an arrayed yeast two-hybrid library containing more than 1,100 TFs. We identified 76 interactors that foremost interact with the SUMO conjugation enzyme SCE1 and/or the SUMO E3 ligase SIZ1. These interactors belong to various TF families, which control a wide range of processes in plant development and stress signaling. Amongst these interactors, the TCP family was overrepresented with several TCPs interacting with different proteins of the SUMO conjugation cycle. For a subset of these TCPs we confirmed that the catalytic site of SCE1 is essential for this interaction. In agreement, TCP1, TCP3, TCP8, TCP14, and TCP15 were readily SUMO modified in an E. coli sumoylation assay. Strikingly, these TCP-SCE1 interactions were found to redistribute these TCPs into nuclear foci/speckles, suggesting that these TCP foci represent sites for SUMO (conjugation) activity. PMID:29250092

Factors associated with social interaction anxiety among Chinese adolescents.

PubMed

Peng, Z W; Lam, L T; Jin, J

2011-12-01

To investigate potential risk factors for social anxiety, particularly social interaction anxiety among the Chinese adolescents. A cross-sectional health survey was conducted in Guangzhou city of the Guangdong Province where high school students aged 13 to 18 years were recruited. The sample was selected from all high schools in the city using a 2-stage random cluster sampling technique. Social interaction anxiety was assessed using the Social Interaction Anxiety Scale. Information collected in the survey included: demographics, self-perception on school performance, relationship with teachers and peers, satisfaction with self-image, achievements, and parenting style of the mother. The parent-child relationship, specifically the relationship between respondents and their mothers, was assessed using the mother attachment subscale of the Inventory of Parent and Peer Attachment. Self-esteem was assessed using the Rosenberg Self-Esteem Scale. The multiple linear regression technique was applied to investigate associations between selected potential risk factors and social interaction anxiety, with adjustments for cluster sampling. Lower family income, lower self-esteem, and hostility were significantly associated with social interaction anxiety among adolescents. Variables identified as risk factors of anxiety disorder in the literature, such as gender, were not associated with social interaction anxiety in this sample. These results were consistent with those of other studies conducted mainly in the United States and Europe. Regarding non-significant results related to gender, they need viewing in the context of parenting styles of Chinese mothers.

Congenital heart diseases in a reference service: clinical evolution and associated illnesses.

PubMed

Huber, Janaína; Peres, Vivian Catarino; Santos, Tiago Jeronimo dos; Beltrão, Lauro da Fontoura; Baumont, Angélica Cerveira de; Cañedo, Andrés Delgado; Schaan, Beatriz D'Agord; Pellanda, Lucia Campos

2010-03-01

Several factors, which include prenatal diagnosis and availability of new therapeutic procedures, have contributed to change the profile of patients with congenital heart disease (CHD). Knowing these changes is important to a better health care. Description of profile of patients with CHD in a reference service in the State of Rio Grande do Sul, Brazil. It is a cross-sectional study including 684 patients with CHD in a service of pediatric cardiology from January 2007 to May 2008. We interviewed the patients (and/or their parents) and examined these patients (congenital malformations, anthropometric measures). Moreover, their charts were reviewed in order to detail heart diseases, procedures and echocardiography. Patients were from 16 days to 66 years old, 51.8% were female, and 93.7% were Caucasian. The mean age at diagnosis was 15.8 +/- 46.8 months. Ventricular septal defect, patent ductus arteriosus and Tetralogy of Fallot were the most prevalent CHD. 59.1% of examined patients, whose average age was 44.3 +/- 71.2 months, have been undergoing therapeutic procedures; 30.4% had congenital extracardiac malformations; and 12 patients had genetic syndrome. Regarding development, 46.6% had low weight and height gain, and 13.7% had neuropsychomotor delay. Furthermore, 18.4% had family history of congenital heart disease. Neuropsychomotor delay and low weight and height gain may be related to CHD. Establishing a profile of patients with CHD, who were treated at an institution of reference, may function as a basis in which health care of this population can be planed appropriately.

The InterAct Project: An Examination of the Interaction of Genetic and Lifestyle Factors on the Incidence of Type 2 Diabetes in the EPIC Study

PubMed Central

Langenberg, C; Sharp, S; Forouhi, NG; Franks, P; Schulze, MB; Kerrison, N; Ekelund, U; Barroso, I; Panico, S; Tormo, M; Spranger, J; Griffin, S; van der Schouw, YT; Amiano, P; Ardanaz, E; Arriola, L; Balkau, B; Barricarte, A; Beulens, JWJ; Boeing, H; Bueno-de-Mesquita, HB; Buijsse, BB; Chirlaque Lopez, MD; Clavel-Chapelon, F; Crowe, FL; de Lauzon-Guillan, B; Deloukas, P; Dorronsoro, M; Drogan, DD; Froguel, P; Gonzalez, C; Grioni, S; Groop, L; Groves, C; Hainaut, P; Halkjaer, J; Hallmans, G; Hansen, T; Kaaks, R; Key, TJ; Khaw, K; Koulman, A; Mattiello, A; Navarro, C; Nilsson, P; Norat, T; Overvad, K; Palla, L; Palli, D; Pedersen, O; Peeters, PH; Quirós, JR; Ramachandran, A; Rodriguez-Suarez, L; Rolandsson, O; Romaguera, D; Romieu, I; Sacerdote, C; Sánchez, M; Sandbaek, A; Slimani, N; Sluijs, I; Spijkerman, AMW; Teucher, B; Tjonneland, A; Tumino, R; van der A, DL; Verschuren, WMM; Tuomilehto, J; Feskens, E; McCarthy, M; Riboli, E; Wareham, NJ

2014-01-01

Background Studying gene-lifestyle interaction may help to identify lifestyle factors that modify genetic susceptibility and uncover genetic loci exerting important subgroup effects. Adequately powered studies with prospective, unbiased, standardised assessment of key behavioural factors for gene-lifestyle studies are lacking. Objective To establish a type 2 diabetes case-cohort study designed to investigate how genetic and potentially modifiable lifestyle and behavioral factors, particularly diet and physical activity, interact in their influence on the risk of developing type 2 diabetes. Methods Funded by the Sixth European Framework Programme, InterAct consortium partners ascertained and verified incident cases of type 2 diabetes occurring in European Prospective Investigation into Cancer and Nutrition (EPIC) cohorts between 1991 and 2007 from 8 of the 10 EPIC countries. A pragmatic, high sensitivity approach was used for case ascertainment including multiple sources at each EPIC centre, followed by diagnostic verification. Prentice-weighted Cox regression and random effects meta-analyses were used to investigate differences in diabetes incidence by age and sex. Results A total of 12,403 verified incident cases of type 2 diabetes occurred during 3.99 million person-years of follow-up of 340,234 EPIC participants eligible for InterAct. We defined a centre stratified subcohort of 16,154 individuals for comparative analyses. Individuals with incident diabetes that were randomly selected into the subcohort (n=778) were included as cases in the analyses. All prevalent diabetes cases were excluded from the study. InterAct cases were followed-up for an average of 6.9 years, 49.7% were men. Mean baseline age and age at diagnosis were 55.6 and 62.5 years, mean BMI and waist were 29.4 kg/m2 and 102.7 cm in men, and 30.1 kg/m2 and 92.8 cm in women, respectively. Risk of type 2 diabetes increased linearly with age, with an overall hazard ratio (95% CI) of 1.56 (1.48; 1

Demonstrating Interactions of Transcription Factors with DNA by Electrophoretic Mobility Shift Assay.

PubMed

Yousaf, Nasim; Gould, David

2017-01-01

Confirming the binding of a transcription factor with a particular DNA sequence may be important in characterizing interactions with a synthetic promoter. Electrophoretic mobility shift assay is a powerful approach to demonstrate the specific DNA sequence that is bound by a transcription factor and also to confirm the specific transcription factor involved in the interaction. In this chapter we describe a method we have successfully used to demonstrate interactions of endogenous transcription factors with sequences derived from endogenous and synthetic promoters.

Carotid arterial wall characteristics are associated with incident ischemic stroke but not coronary heart disease in the ARIC Study

PubMed Central

Yang, Eric Y.; Chambless, Lloyd; Sharrett, A. Richey; Virani, Salim S.; Liu, Xiaoxi; Tang, Zhengzheng; Boerwinkle, Eric; Ballantyne, Christie M.; Nambi, Vijay

2011-01-01

Background and Purpose Ultrasound measurements of arterial stiffness are associated with atherosclerosis risk factors, but limited data exist on their association with incident cardiovascular events. We evaluated the association of carotid ultrasound derived arterial stiffness measures with incident coronary heart disease (CHD) and ischemic stroke in the ARIC study. Methods Carotid arterial strain (CAS) and compliance (AC), distensibility (AD) and stiffness indices (SI), pressure-strain (Ep) and Young’s elastic moduli (YEM) were measured in 10,407 individuals using ultrasound. Hazard ratios for incident CHD (myocardial infarction [MI], fatal CHD, coronary revascularization) and stroke in minimally adjusted (age, sex, center, race) and fully adjusted models (minimally adjusted model + diabetes, height, weight, total cholesterol, high-density lipoprotein cholesterol, tobacco use, systolic blood pressure, antihypertensive medication use, and carotid intima-media thickness (CIMT) were calculated. Results The mean age was 55.3 years. Over a mean follow up of 13.8 years, 1,267 incident CHD and 383 ischemic stroke events occurred. After full adjustment for risk factors and CIMT, all arterial stiffness parameters [CAS HR (95% confidence interval [CI]) =1.14 (1.02, 1.28); AD HR=1.19 (1.02, 1.39); SI HR=1.14 (1.04, 1.25); Ep HR=1.17 (1.06, 1.28); YEM HR=1.13 (1.03, 1.24)], except arterial compliance HR=1.02 (0.90, 1.16), were significantly associated with incident stroke but not with CHD. Conclusions After adjusting for cardiovascular risk factors, ultrasound measures of carotid arterial stiffness are associated with incident ischemic stroke but not incident CHD events, despite that the 2 outcomes sharing similar risk factors. PMID:22033999

The integrated effect of moderate exercise on coronary heart disease.

PubMed

Mathews, Marc J; Mathews, Edward H; Mathews, George E

Moderate exercise is associated with a lower risk for coronary heart disease (CHD). A suitable integrated model of the CHD pathogenetic pathways relevant to moderate exercise may help to elucidate this association. Such a model is currently not available in the literature. An integrated model of CHD was developed and used to investigate pathogenetic pathways of importance between exercise and CHD. Using biomarker relative-risk data, the pathogenetic effects are representable as measurable effects based on changes in biomarkers. The integrated model provides insight into higherorder interactions underlying the associations between CHD and moderate exercise. A novel 'connection graph' was developed, which simplifies these interactions. It quantitatively illustrates the relationship between moderate exercise and various serological biomarkers of CHD. The connection graph of moderate exercise elucidates all the possible integrated actions through which risk reduction may occur. An integrated model of CHD provides a summary of the effects of moderate exercise on CHD. It also shows the importance of each CHD pathway that moderate exercise influences. The CHD risk-reducing effects of exercise appear to be primarily driven by decreased inflammation and altered metabolism.

Should Antihypertensive Treatment Recommendations Differ in Patients With and Without Coronary Heart Disease? (From the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial [ALLHAT])

PubMed Central

Alderman, Michael H.; Davis, Barry R.; Piller, Linda B.; Ford, Charles E.; Baraniuk, M. Sarah; Pressel, Sara L.; Assadi, Mahshid A.; Einhorn, Paula T.; Haywood, L. Julian; Ilamathi, Ekambaram; Oparil, Suzanne; Retta, Tamrat M.

2015-01-01

Thiazide-type diuretics have been recommended for initial treatment of hypertension in most patients, but should this recommendation differ for patients with and without coronary heart disease (CHD)? The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) was a randomized, double-blind hypertension treatment trial in 42,418 participants with high risk of combined cardiovascular disease (CVD) (25% with pre-existing CHD). This post-hoc analysis compares long-term major clinical outcomes in those assigned amlodipine (n=9048) or lisinopril (n=9054) with those assigned chlorthalidone (n=15,255), stratified by CHD status. After 4–8 years, randomized treatment was discontinued. Total follow-up (active treatment + passive surveillance using national databases for deaths and hospitalizations) was 8–13 years. For most CVD outcomes, ESRD, and total mortality, there were no differences across randomized treatment arms regardless of baseline CHD status. In-trial rates of CVD were significantly higher for lisinopril compared with chlorthalidone, and rates of heart failure were significantly higher for amlodipine compared with chlorthalidone in those with and without CHD (overall HRs: 1.10, p<0.001 and 1.38, p<0.001, respectively). During extended follow-up, significant outcomes according to CHD status interactions (p=0.012) were noted in amlodipine versus chlorthalidone comparison for CVD and CHD mortality, HR=0.88, p=0.04 and 0.84, p=0.04, respectively, in those with CHD at baseline and 1.06, p=0.15 and 1.08, p=0.17 in those without. The results of the overall increased stroke mortality in lisinopril compared to chlorthalidone (HR=1.2; p=0.03) and hospitalized heart failure in amlodipine compared to chlorthalidone (HR=1.12; p=0.01) during extended follow-up did not differ by baseline CHD status. In conclusion, these results provide no reason to alter our previous recommendation to include a properly dosed diuretic (such as chlorthalidone 12

Prevalence and Pattern of Executive Dysfunction in School Age Children with Congenital Heart Disease

PubMed Central

Sanz, Jacqueline H.; Berl, Madison M.; Armour, Anna C.; Wang, Jichuan; Cheng, Yao I.; Donofrio, Mary T.

2016-01-01

Objective Executive Function, a set of cognitive skills important to social and academic outcomes, is a specific area of cognitive weakness in children with congenital heart disease (CHD). We evaluated the prevalence and profile of executive dysfunction in a heterogeneous sample of school aged children with CHD, examined whether children with executive dysfunction are receiving school services and support, and identified risk factors for executive dysfunction at school age. Design 91 school aged patients completed questionnaires, including the Behavior Rating Inventory of Executive Function (BRIEF) and a medical history questionnaire. An age and gender matched control sample was drawn from a normativedatabase. Results CHD patients had a higher rate of parent reported executive dysfunction (OR=4.37, p<0.0001), especially for working memory (OR=8.22, p<0.0001) and flexibility (OR=8.05, p<0.0001). Those with executive dysfunction were not more likely to be receiving school services (p>0.05). Gender, premature birth (≤37 weeks), and CHD with aortic obstruction were predictive of executive dysfunction, especially for behavior regulation skills. Conclusions School aged children with CHD have an increased prevalence of executive dysfunction, especially problems with working memory and flexibility, and are underserved by the school system. The increased risk for executive dysfunction in those with CHD and prematurity or CHD with aortic obstruction suggests an etiology of delayed brain development in the fetal and neonatal periods, while male gender may increase susceptibility to brain injury. This study highlights the need for regular neurodevelopmental follow up in children with CHD, and a need to better understand mechanisms that contribute to adverse neurodevelopmental outcomes. PMID:27863079

Prevalence and pattern of executive dysfunction in school age children with congenital heart disease.

PubMed

Sanz, Jacqueline H; Berl, Madison M; Armour, Anna C; Wang, Jichuan; Cheng, Yao I; Donofrio, Mary T

2017-03-01

Executive function, a set of cognitive skills important to social and academic outcomes, is a specific area of cognitive weakness in children with congenital heart disease (CHD). We evaluated the prevalence and profile of executive dysfunction in a heterogeneous sample of school aged children with CHD, examined whether children with executive dysfunction are receiving school services and support, and identified risk factors for executive dysfunction at school age. Ninety-one school aged patients completed questionnaires, including the Behavior Rating Inventory of Executive Function (BRIEF) and a medical history questionnaire. An age- and gender- matched control sample was drawn from a normative database. Children with CHD had a higher rate of parent reported executive dysfunction (OR = 4.37, P < .0001), especially for working memory (OR = 8.22, P < .0001) and flexibility (OR = 8.05, P < .0001). Those with executive dysfunction were not more likely to be receiving school services (P > .05). Gender, premature birth (≤37 weeks), and CHD with aortic obstruction were predictive of executive dysfunction, especially for behavior regulation skills. School aged children with CHD have an increased prevalence of executive dysfunction, especially problems with working memory and flexibility, and are underserved by the school system. The increased risk for executive dysfunction in those with CHD and prematurity or CHD with aortic obstruction suggests an etiology of delayed brain development in the fetal and neonatal periods, while male gender may increase susceptibility to brain injury. This study highlights the need for regular neurodevelopmental follow up in children with CHD, and a need to better understand mechanisms that contribute to adverse neurodevelopmental outcomes. © 2016 Wiley Periodicals, Inc.

Are Pain-Related Temporomandibular Disorders the Product of an Interaction Between Psychological Factors and Self-Reported Bruxism?

PubMed

van Selms, Maurits Ka; Muzalev, Konstantin; Visscher, Corine M; Koutris, Michail; Bulut, Melike; Lobbezoo, Frank

2017-01-01

To investigate whether pain-related temporomandibular disorders (TMD) are the product of an interaction between psychological factors and self-reported bruxism activities. Patients referred to a specialized clinic for complaints of orofacial pain and dysfunction completed a digital questionnaire prior to the first clinical visit. The patient sample was then split into a case group consisting of 268 patients diagnosed with TMD pain according to the Diagnostic Criteria for Temporomandibular Disorders (85.8% women; mean ± standard deviation [SD] age = 40.1 ± 14.5 years) and a control group consisting of 254 patients without any pain in the orofacial area (50.8% women; 46.9 ± 13.6 years). The possible moderating roles of six psychological factors (depression, somatic symptoms, anxiety, stress, optimism, and prior psychological treatment) on the relationship between self-reported bruxism and the clinical presence of TMD pain were examined. Patients with TMD pain reported significantly more bruxism than patients without any report of orofacial pain. Furthermore, bruxism intensity was associated with a variety of psychological factors; however, there were no significant interactions between any of the psychological factors and bruxism with respect to the clinical presence of TMD pain. These findings do not support the view that the effect of bruxism on TMD pain is stronger in patients who experience higher levels of psychological distress compared to those with lower levels of distress.

Probabilistic Multi-Factor Interaction Model for Complex Material Behavior

NASA Technical Reports Server (NTRS)

Chamis, Christos C.; Abumeri, Galib H.

2008-01-01

The Multi-Factor Interaction Model (MFIM) is used to evaluate the divot weight (foam weight ejected) from the launch external tanks. The multi-factor has sufficient degrees of freedom to evaluate a large number of factors that may contribute to the divot ejection. It also accommodates all interactions by its product form. Each factor has an exponent that satisfies only two points, the initial and final points. The exponent describes a monotonic path from the initial condition to the final. The exponent values are selected so that the described path makes sense in the absence of experimental data. In the present investigation the data used was obtained by testing simulated specimens in launching conditions. Results show that the MFIM is an effective method of describing the divot weight ejected under the conditions investigated.

Probabilistic Multi-Factor Interaction Model for Complex Material Behavior

NASA Technical Reports Server (NTRS)

Chamis, Christos C.; Abumeri, Galib H.

2008-01-01

The Multi-Factor Interaction Model (MFIM) is used to evaluate the divot weight (foam weight ejected) from the launch external tanks. The multi-factor has sufficient degrees of freedom to evaluate a large number of factors that may contribute to the divot ejection. It also accommodates all interactions by its product form. Each factor has an exponent that satisfies only two points the initial and final points. The exponent describes a monotonic path from the initial condition to the final. The exponent values are selected so that the described path makes sense in the absence of experimental data. In the present investigation, the data used was obtained by testing simulated specimens in launching conditions. Results show that the MFIM is an effective method of describing the divot weight ejected under the conditions investigated.

Effort-reward imbalance at work and recurrent coronary heart disease events: a 4-year prospective study of post-myocardial infarction patients.

PubMed

Aboa-Éboulé, Corine; Brisson, Chantal; Maunsell, Elizabeth; Bourbonnais, Renée; Vézina, Michel; Milot, Alain; Dagenais, Gilles R

2011-01-01

Prospective studies have shown that effort-reward imbalance (ERI) at work is associated with the incidence of a first coronary heart disease (CHD) event. However, it is unknown whether ERI at work increases the risk of recurrent CHD events. The objective of this study was to determine whether ERI at work and its components (effort and reward) increase the risk of recurrent CHD in post-myocardial infarction (post-MI) workers. We carried out a prospective cohort study of 669 men and 69 women who returned to work after a first MI. ERI at work was assessed by telephone interview using validated scales of reward and psychological demands. The outcome was a composite of fatal CHD, nonfatal MI, and unstable angina. CHD risk factors were documented in medical files and by interview. The participants were followed up for a mean period of 4.0 years (1998-2005). During the follow-up, 96 CHD events were documented. High ERI and low reward were associated with recurrent CHD (respective adjusted hazard ratios [HRs] = 1.75, 95% confidence interval [CI] = 0.99-3.08, and HR = 1.77, 95% CI = 1.16-2.71). There was a gender interaction showing stronger effects among women (respective adjusted HRs for high ERI and low reward: HR = 3.95, 95% CI = 0.93-16.79, and HR = 9.53, 95% CI = 1.15-78.68). Post-MI workers holding jobs that involved ERI or low reward had increased risk of recurrent CHD.

Coronary artery disease: the role of lipids, hypertension and smoking.

PubMed

Keil, U

2000-01-01

Pioneering epidemiological projects such as the Seven Countries study, and the Framingham Heart study established the classical risk factor concept for coronary heart disease (CAD). These landmark studies showed that a raised serum total cholesterol, high blood pressure (systolic and diastolic) and smoking increase the risk of developing CHD in men and women in a graded fashion. Women develop CHD about 10 years later than men and women's risk is smaller. In the years and decades following these early studies many more prospective cohort studies primarily in the US and Europe have confirmed the early findings. In Germany two occupational and one population based cohort studies have contributed further information on this topic. In addition interactions between the three classical risk factors have been quantified, demonstrating for example that smoking carries a much higher risk for CHD in persons with high cholesterol values. Most cohort studies have confirmed that the relative risks for the classical risk factors are very similar. However, the respective absolute risks can differ tremendously, indicating that many more factors such as socio-economic conditions, nutrition, physical activity and others are of importance for the development of CHD. The scientific community, however, did not accept the consistent findings from the many observational studies as proof of causality. They required evidence that the risk for CHD could be reduced when the respective risk factor(s) was (were) diminished or eliminated. The late 1960s early 1970s thus saw the beginning of the era of randomized controlled trials (RCTs) following the advice of Archibald Cochrane who once wrote "we have to find that point on the distribution curve where therapy does more good than harm". We now know from meta-analyses of RCTs that a 1% reduction in serum cholesterol produces a 2-3% decline in risk for CHD and we can achieve reductions in total cholesterol of 20% or more. Regarding treatment of

Gene-environment interaction study for BMI reveals interactions between genetic factors and physical activity, alcohol consumption and socioeconomic status

PubMed Central

Karlsson, Torgny; Ek, Weronica E.

2017-01-01

Previous genome-wide association studies (GWAS) have identified hundreds of genetic loci to be associated with body mass index (BMI) and risk of obesity. Genetic effects can differ between individuals depending on lifestyle or environmental factors due to gene-environment interactions. In this study, we examine gene-environment interactions in 362,496 unrelated participants with Caucasian ancestry from the UK Biobank resource. A total of 94 BMI-associated SNPs, selected from a previous GWAS on BMI, were used to construct weighted genetic scores for BMI (GSBMI). Linear regression modeling was used to estimate the effect of gene-environment interactions on BMI for 131 lifestyle factors related to: dietary habits, smoking and alcohol consumption, physical activity, socioeconomic status, mental health, sleeping patterns, as well as female-specific factors such as menopause and childbirth. In total, 15 lifestyle factors were observed to interact with GSBMI, of which alcohol intake frequency, usual walking pace, and Townsend deprivation index, a measure of socioeconomic status, were all highly significant (p = 1.45*10−29, p = 3.83*10−26, p = 4.66*10−11, respectively). Interestingly, the frequency of alcohol consumption, rather than the total weekly amount resulted in a significant interaction. The FTO locus was the strongest single locus interacting with any of the lifestyle factors. However, 13 significant interactions were also observed after omitting the FTO locus from the genetic score. Our analyses indicate that many lifestyle factors modify the genetic effects on BMI with some groups of individuals having more than double the effect of the genetic score. However, the underlying causal mechanisms of gene-environmental interactions are difficult to deduce from cross-sectional data alone and controlled experiments are required to fully characterise the causal factors. PMID:28873402

Neighborhood socioeconomic status and the prevalence of stroke and coronary heart disease in rural China: a population-based study

PubMed Central

Tang, Xun; Laskowitz, Daniel T.; He, Liu; Østbye, Truls; Bettger, Janet Prvu; Cao, Yang; Li, Na; Li, Jingrong; Zhang, Zongxin; Liu, Jianjiang; Yu, Liping; Xu, Haitao; Hu, Yonghua; Goldstein, Larry B.

2014-01-01

Background Lower neighborhood-level socioeconomic status (SES) is associated with an increased risk of vascular disease in developed countries. Aims This study aims to identify village- and individual-level determinants of stroke and coronary heart disease (CHD) in a rural Chinese population. Methods We analyzed data from a population-based survey of 14,424 rural Chinese adults aged over 40-years from 54 villages. Primary outcomes were stroke and CHD prevalence. Village-level SES was determined from the Chinese government's official statistical yearbook. Individual-level characteristics were obtained by in-person interviews. Prevalence rate ratios (RR) and 95% confidence intervals (95% CI) were calculated using generalized linear mixed models with log link function to explore associations of village-level SES and individual social, demographic, and cardiovascular risk factors with stroke or CHD. Variance was expressed using the median rate ratio (MRR) and interval rate ratio (IRR). Results Villages accounted for significant variability in the prevalence of stroke (MRR=1.70; 95% CI:1.42-1.94; P<0.05) and CHD (MRR=1.59; 95% CI:1.35-1.78, P<0.05) with village-level income alone accounted for 10% and 13.5% of between-village variation in stroke and CHD, respectively. High-income villages were at higher risk of both stroke (RR=1.69, 95% CI:1.09∼2.62) and CHD (RR=1.63, 95% CI:1.13∼2.34) than lower-income villages. Among individual-level risk factors, hypertension was associated with a higher prevalence of stroke (RR=2.33, 95% CI:1.93-2.80) than CHD (RR=1.58, 95% CI:1.38-1.82), whereas obesity was only associated with CHD (RR=1.43, 95% CI:1.23-1.66). In addition, there was an interaction between age and income; residents of higher income villages age<60 had a higher prevalence of CHD (RR=1.58, 95% CI:1.15-2.18), but not stroke. Conclusions There were differences in vascular risk across rural villages in China, with higher lifetime stroke and CHD prevalence in higher

Methodological and conceptual issues regarding occupational psychosocial coronary heart disease epidemiology.

PubMed

Burr, Hermann; Formazin, Maren; Pohrt, Anne

2016-05-01

limited focus on investigating occupational psychosocial factors outside of these two models (1, 2). In this letter, we would like to raise some conceptual and methodological issues which are inherent to these two stress models but also which arise from the heavy emphasis placed on them. Conceptual issues The conceptual issues we discuss below are empirical confirmation of the assumptions of these models and to what extent the focus on the demand-control and ERI models is warranted. Investigating the assumptions of the models Both the demand-control and the ERI models are based on assumptions which have only been tested empirically to a limited extent (1, 2). We pose three specific questions: (i) Does the interaction of demands and control constitute a risk factor for CHD? (ii) Does the imbalance between effort and reward explain more variance in CHD risk than high effort and low reward alone? (iii) Do the sub-dimensions of the scales in these models have common health effects? Regarding the interaction of demands and control. The concept of the demand-control model is useful when the health risk of being exposed to job strain (simultaneous high demands and low control) differs greatly from the sum of individual health risks of being exposed solely to high demands and low control. If this interaction were not present, it would be warranted to look separately at high demands and low control. This would for instance counteract overlooking those persons exposed to low control but not high demands (known as "passive work"; 3, 4). It should be emphasized that the interaction of demands and control has only been tested in very few - underpowered - cases (1, 2). Initial support for an interaction within the demand-control model can be tentatively derived from the work of the IPD-Work Consortium (7): In a reanalysis of an earlier study (8), it was shown that while neither demands nor job control alone (appendix to 8) predicted CHD, job strain did when controlling for sex, age and

C-terminal region of the UV-B photoreceptor UVR8 initiates signaling through interaction with the COP1 protein

PubMed Central

Cloix, Catherine; Kaiserli, Eirini; Heilmann, Monika; Baxter, Katherine J.; Brown, Bobby A.; O’Hara, Andrew; Smith, Brian O.; Christie, John M.; Jenkins, Gareth I.

2012-01-01

UV-B light initiates photomorphogenic responses in plants. Arabidopsis UV RESISTANCE LOCUS8 (UVR8) specifically mediates these responses by functioning as a UV-B photoreceptor. UV-B exposure converts UVR8 from a dimer to a monomer, stimulates the rapid accumulation of UVR8 in the nucleus, where it binds to chromatin, and induces interaction of UVR8 with CONSTITUTIVELY PHOTOMORPHOGENIC1 (COP1), which functions with UVR8 to control photomorphogenic UV-B responses. Although the crystal structure of UVR8 reveals the basis of photoreception, it does not show how UVR8 initiates signaling through interaction with COP1. Here we report that a region of 27 amino acids from the C terminus of UVR8 (C27) mediates the interaction with COP1. The C27 region is necessary for UVR8 function in the regulation of gene expression and hypocotyl growth suppression in Arabidopsis. However, UVR8 lacking C27 still undergoes UV-B–induced monomerization in both yeast and plant protein extracts, accumulates in the nucleus in response to UV-B, and interacts with chromatin at the UVR8-regulated ELONGATED HYPOCOTYL5 (HY5) gene. The UV-B–dependent interaction of UVR8 and COP1 is reproduced in yeast cells and we show that C27 is both necessary and sufficient for the interaction of UVR8 with the WD40 domain of COP1. Furthermore, we show that C27 interacts in yeast with the REPRESSOR OF UV-B PHOTOMORPHOGENESIS proteins, RUP1 and RUP2, which are negative regulators of UVR8 function. Hence the C27 region has a key role in UVR8 function. PMID:22988111

Reducing the H0 and σ8 tensions with dark matter-neutrino interactions

NASA Astrophysics Data System (ADS)

Di Valentino, Eleonora; Bœhm, Céline; Hivon, Eric; Bouchet, François R.

2018-02-01

The introduction of dark matter-neutrino interactions modifies the cosmic microwave background (CMB) angular power spectrum at all scales, thus affecting the reconstruction of the cosmological parameters. Such interactions can lead to a slight increase of the value of H0 and a slight decrease of S8≡σ8√{Ωm/0.3 } , which can help reduce somewhat the tension between the CMB and weak lensing or Cepheids data sets. Here we show that it is impossible to solve both tensions simultaneously. While the 2015 Planck temperature and low multipole polarization data combined with the Cepheids data sets prefer large values of the Hubble rate (up to H0=72.1-1.7+1.5 km /s /Mpc , when Neff is free to vary), the σ8 parameter remains too large to reduce the σ8 tension. Adding high multipole Planck polarization data does not help since this data shows a strong preference for low values of H0, thus worsening current tensions, even though they also prefer smaller value of σ8.

Fluorescent Oxidation Products and Risk of Coronary Heart Disease: A Prospective Study in Women

PubMed Central

Jensen, Majken K.; Wang, Yushan; Rimm, Eric B.; Townsend, Mary K.; Willett, Walter; Wu, Tianying

2013-01-01

Background Oxidative stress is implicated in the etiology of coronary heart disease (CHD). New measures to capture oxidative stress are warranted. Fluorescent oxidation products (FlOPs) can be measured in plasma and have been shown to reflect levels of oxidative stress and to predict risk of CHD in men over 6 years of follow‐up. The objective of this study is to determine whether measures of FlOPs are associated with risk of CHD in women over an extended follow‐up period. Methods and Results We measured FlOP by spectrofluorometer in a nested case–control study within the Nurses' Health Study, with baseline blood collection in 1990 and follow‐up of 397 incident CHD cases through 2004 matched 1:2 with controls. Level of FlOPs was independently associated with CHD. The relative risk across extreme quintiles was 1.64 (95% confidence interval [CI], 1.06 to 2.53) when adjusted for lifestyle factors, lipids and C‐reactive protein (P trend across quintiles=0.01). A slightly stronger association was observed when analyses were restricted to women fasting >8 hours at blood draw (RR, 1.91; 95% CI, 1.16 to 3.15). In exploratory time to event analyses, high levels of FlOPs measured ≥5 years before the CHD event, but not closer to the CHD event, were associated with the risk of CHD. Conclusions Higher levels of FlOPs were associated with the risk of CHD in women. The association appeared strongest for long‐term prediction of CHD events. PMID:24103570

Fluorescent oxidation products and risk of coronary heart disease: a prospective study in women.

PubMed

Jensen, Majken K; Wang, Yushan; Rimm, Eric B; Townsend, Mary K; Willett, Walter; Wu, Tianying

2013-10-08

Oxidative stress is implicated in the etiology of coronary heart disease (CHD). New measures to capture oxidative stress are warranted. Fluorescent oxidation products (FlOPs) can be measured in plasma and have been shown to reflect levels of oxidative stress and to predict risk of CHD in men over 6 years of follow-up. The objective of this study is to determine whether measures of FlOPs are associated with risk of CHD in women over an extended follow-up period. We measured FlOP by spectrofluorometer in a nested case-control study within the Nurses' Health Study, with baseline blood collection in 1990 and follow-up of 397 incident CHD cases through 2004 matched 1:2 with controls. Level of FlOPs was independently associated with CHD. The relative risk across extreme quintiles was 1.64 (95% confidence interval [CI], 1.06 to 2.53) when adjusted for lifestyle factors, lipids and C-reactive protein (P trend across quintiles = 0.01). A slightly stronger association was observed when analyses were restricted to women fasting > 8 hours at blood draw (RR, 1.91; 95% CI, 1.16 to 3.15). In exploratory time to event analyses, high levels of FlOPs measured ≥ 5 years before the CHD event, but not closer to the CHD event, were associated with the risk of CHD. Higher levels of FlOPs were associated with the risk of CHD in women. The association appeared strongest for long-term prediction of CHD events.

35 GHz ENDOR characterization of the "very rapid" signal of xanthine oxidase reacted with 2-hydroxy-6-methylpurine (13C8): evidence against direct Mo-C8 interaction.

PubMed

Manikandan, P; Choi, E Y; Hille, R; Hoffman, B M

2001-03-21

Xanthine oxidase is a molybdenum-containing enzyme that catalyzes the hydroxylation of xanthine and a wide variety of other aromatic heterocycles. In the course of the reaction with xanthine and substrates such as 2-hydroxy-6-methylpurine (HMP), the enzyme gives rise to a Mo(V) EPR signal, denoted "very rapid", that arises from an authentic catalytic intermediate. The two alternative catalytic mechanisms proposed for this enzyme differ critically in whether the distance between Mo and C8 of the purine nucleus in this intermediate is short enough to admit a direct bonding interaction. To examine this distance, we have performed 13C ENDOR measurements of the "very rapid" EPR signal generated by xanthine oxidase during reaction with 13C8-HMP. The resulting (13)C8 hyperfine tensor, A = [10.2(1), 7.0(1), 6.5(1)] MHz, is discussed in the framework of a detailed consideration of factors involved in extracting metrical parameters from an anisotropic hyperfine interaction composed of contributions from multiple sources, in particular, the effect of the local contributions from spin density on (13)C8. The analysis presented here gives a Mo...C distance whose value is expected to be ca. 2.7-2.9 A in the "very rapid" intermediates formed with both xanthine and HMP, consistent with plausible bond lengths for a Mo-O-C8 fragment where C8 is a trigonal-planar aromatic carbon. The difference from earlier conclusions is explained. The data thus do not support the existence of a direct Mo-C bond in the signal-giving species. This conclusion supports a mechanism that does not involve such an interaction and which begins with base-assisted nucleophilic attack of the Mo(VI)-OH group on the C-8 of substrate, with concomitant hydride transfer to the Mo=S group to give Mo(IV)-SH; the EPR-active "very rapid" species then forms by one-electron oxidation and deprotonation to yield the EPR-detectable Mo(V)OS(OR) species. We further discuss the complexities and limitations of the semiempirical

Clinical Utility of Multimarker Genetic Risk Scores for Prediction of Incident Coronary Heart Disease: A Cohort Study Among Over 51 Thousand Individuals of European Ancestry.

PubMed

Iribarren, Carlos; Lu, Meng; Jorgenson, Eric; Martínez, Manuel; Lluis-Ganella, Carla; Subirana, Isaac; Salas, Eduardo; Elosua, Roberto

2016-12-01

We evaluated whether including multilocus genetic risk scores (GRSs) into the Framingham Risk Equation improves the predictive capacity, discrimination, and reclassification of asymptomatic individuals with respect to coronary heart disease (CHD) risk. We performed a cohort study among 51 954 European-ancestry members of a Northern California integrated healthcare system (67% female; mean age 59) free of CHD at baseline (2007-2008). Four GRSs were constructed using between 8 and 51 previously identified genetic variants. After a mean (±SD) follow-up of 5.9 (±1.5) years, 1864 incident CHD events were documented. All GRSs were linearly associated with CHD in a model adjusted by individual risk factors: hazard ratio (95% confidence interval) per SD unit: 1.21 (1.15-1.26) for GRS_8, 1.20 (1.15-1.26) for GRS_12, 1.23 (1.17-1.28) for GRS_36, and 1.23 (1.17-1.28) for GRS_51. Inclusion of the GRSs improved the C statistic (ΔC statistic =0.008 for GRS_8 and GRS_36; 0.007 for GRS_12; and 0.009 for GRS_51; all P<0.001). The net reclassification improvement was 5% for GRS_8, GRS_12, and GRS_36 and 4% for GRS_51 in the entire cohort and was (after correcting for bias) 9% for GRS_8 and GRS_12 and 7% for GRS_36 and GRS_51 when analyzing those classified as intermediate Framingham risk (10%-20%). The number required to treat to prevent 1 CHD after selectively treating with statins up-reclassified subjects on the basis of genetic information was 36 for GRS_8 and GRS_12, 41 for GRS_36, and 43 for GRS_51. Our results demonstrate significant and clinically relevant incremental discriminative/predictive capability of 4 multilocus GRSs for incident CHD among subjects of European ancestry. © 2016 American Heart Association, Inc.

Self rated health as a predictor of coronary heart disease in Copenhagen, Denmark.

PubMed Central

Møller, L; Kristensen, T S; Hollnagel, H

1996-01-01