Does sticky blood predict a sticky end? Associations of blood viscosity, haematocrit and fibrinogen with mortality in the West of Scotland

There is increasing evidence that blood viscosity and its major determinants (haematocrit, plasma viscosity and fibrinogen) are associated with an increased risk of incident cardiovascular events; however, their associations with mortality are not established. We therefore studied the associations of these variables with cardiovascular events and total mortality in 1238 men and women aged 25-64 years, followed for 13 years in the first North Glasgow MONICA (MONItoring CArdiovascular disease) survey and West of Scotland centres in the Scottish Heart Health Study. After adjustment for age and sex, increasing whole blood viscosity, plasma viscosity, haematocrit and fibrinogen (analysed by both von Clauss and heat precipitation assays) were significantly associated with mortality. Only the association for fibrinogen (von Clauss assay) remained significant after adjustment for major cardiovascular risk factors. We conclude that clottable fibrinogen may be independently associated with mortality. However, the significance of this association, and the extent to which viscosity is associated with mortality, remain to be established in larger studies and meta-analyses

N-terminal pro-B-type natriuretic peptide and the prediction of primary cardiovascular events: results from 15-year follow-up of WOSCOPS

<b>Aims:</b>To test whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) was independently associated with, and improved the prediction of, cardiovascular disease (CVD) in a primary prevention cohort. <b>Methods and results:</b> In the West of Scotland Coronary Prevention Study (WOSCOPS), a cohort of middle-aged men with hypercholesterolaemia at a moderate risk of CVD, we related the baseline NT-proBNP (geometric mean 28 pg/mL) in 4801 men to the risk of CVD over 15 years during which 1690 experienced CVD events. Taking into account the competing risk of non-CVD death, NT-proBNP was associated with an increased risk of all CVD [HR: 1.17 (95% CI: 1.11–1.23) per standard deviation increase in log NT-proBNP] after adjustment for classical and clinical cardiovascular risk factors plus C-reactive protein. N-terminal pro-B-type natriuretic peptide was more strongly related to the risk of fatal [HR: 1.34 (95% CI: 1.19–1.52)] than non-fatal CVD [HR: 1.17 (95% CI: 1.10–1.24)] (P= 0.022). The addition of NT-proBNP to traditional risk factors improved the C-index (+0.013; P < 0.001). The continuous net reclassification index improved with the addition of NT-proBNP by 19.8% (95% CI: 13.6–25.9%) compared with 9.8% (95% CI: 4.2–15.6%) with the addition of C-reactive protein. N-terminal pro-B-type natriuretic peptide correctly reclassified 14.7% of events, whereas C-reactive protein correctly reclassified 3.4% of events. Results were similar in the 4128 men without evidence of angina, nitrate prescription, minor ECG abnormalities, or prior cerebrovascular disease. <b>Conclusion:</b> N-terminal pro-B-type natriuretic peptide predicts CVD events in men without clinical evidence of CHD, angina, or history of stroke, and appears related more strongly to the risk for fatal events. N-terminal pro-B-type natriuretic peptide also provides moderate risk discrimination, in excess of that provided by the measurement of C-reactive protein

Escoliose: triagem em escolares de 10 a 15 anos

O proposito deste estudo foi o de verificar a prevalência de casos suspeitos de escoliose e sua associação com peso do material escolar e em alunos de uma escola pública do município de Jequié - BA. Fizeram parte deste estudo descritivo e transversal, 143 escolares (13,26 ± 1,52 anos), 40 meninos e 103 meninas. A triagem dos casos suspeitos de escoliose foi feita através do teste de Adam: presença de gibosidade (suspeita de escoliose); ausência de gibosidade. A verificação da adequação do peso do material escolar (PME) foi feita a partir da relação entre PME e massa corporal (MC), utilizando-se a seguinte classificação: 10 % da MC = adequado e; > 10% da MC = inadequado. As associações foram feitas com teste qui-quadrado. Foram detectados 71 (49,7%) casos suspeitos de escoliose, 40 do sexo masculino e 103 do sexo feminino. Em ambos os sexos, a freqüência de casos suspeitos foi maior no grupo etário de 13-15 anos. O peso de material adequado foi observado em 91,6% dos escolares. Foram observadas associações estatisticamente significativas entre suspeita de escoliose e PME para meninos de 10-12 anos e meninas de 10-12 e 13-15 anos. Os resultados do permitem concluir, para este grupo de escolares, que a prevalência de casos suspeitos de escoliose é maior no sexo feminino, no grupo etário mais velho e nos indivíduos com peso do material escolar inadequado

C-reactive protein: associations with haematological variables, cardiovascular risk factors and prevalent cardiovascular disease

C-reactive protein (CRP) has been proposed as a risk factor for cardiovascular disease; however, this association is confounded by mutual relationships with both classical and haematological cardiovascular risk factors. We, therefore, measured CRP with a high-sensitivity assay in stored plasma samples from 414 men and 515 women in the north Glasgow MONICA (MONItoring trends in CArdiovascular diseases) survey, to study its correlation with haematological variables, classical risk factors and prevalent cardiovascular disease. CRP correlated with age, oral contraceptive use, menopause and most classical cardiovascular risk factors (except blood pressure). CRP also correlated with plasma levels of the pro-inflammatory cytokine interleukin 6, and haematocrit, viscosity, red cell aggregation, white cell count, and coagulation factors [fibrinogen, factor (F) VII in women, FVIII, FIX] and inhibitors (antithrombin and protein C in women; protein S) but not coagulation activation markers. CRP was significantly associated with prevalent cardiovascular disease in both men (P = 0.03) and women (P = 0.009), however, the association became non-significant after adjustment for firstly classical risk factors, then fibrinogen. We conclude that correlations with classical and haematological risk factors account for a substantial component of the association of CRP with prevalent cardiovascular disease, but there is evidence of a residual, independent effect among women

Obesity dysregulates the pulmonary antiviral immune response

Obesity is a well-recognized risk factor for severe influenza infections but the mechanisms underlying susceptibility are poorly understood. Here, we identify that obese individuals have deficient pulmonary antiviral immune responses in bronchoalveolar lavage cells but not in bronchial epithelial cells or peripheral blood dendritic cells. We show that the obese human airway metabolome is perturbed with associated increases in the airway concentrations of the adipokine leptin which correlated negatively with the magnitude of ex vivo antiviral responses. Exogenous pulmonary leptin administration in mice directly impaired antiviral type I interferon responses in vivo and ex vivo in cultured airway macrophages. Obese individuals hospitalised with influenza showed dysregulated upper airway immune responses. These studies provide insight into mechanisms driving propensity to severe influenza infections in obesity and raise the potential for development of leptin manipulation or interferon administration as novel strategies for conferring protection from severe infections in obese higher risk individuals

Stroke risk estimation across nine European countries in the MORGAM project.

Previous tools for stroke risk assessment have either been developed for specific populations or lack data on non-fatal events or uniform data collection. The purpose of this study was to develop a stepwise model for the estimation of 10 year risk of stroke in nine different countries across Europe.Using data from the MOnica Risk, Genetics, Archiving and Monograph (MORGAM) Project, sex-specific models estimating 10 year risk of stroke were developed using a Cox regression model stratified by country and including modelling of competing risks. Models were developed in a stepwise manner first using only data from questionnaires, and then adding data from physical examinations and finally data from blood samples.During 1,176,296 years of observation, 2928 incident fatal and non-fatal events of stroke were registered. The developed model showed good calibration and accuracy of prediction. The discrimination of the model varied between sex and country but increased with increasing number of variables used (area under the receiver operating characteristic curve between 0.77 and 0.79 in men and between 0.75 and 0.80 in women).The present study shows that using a large multicountry cohort from nine European countries it is possible to develop a stepwise risk estimation model for 10 year risk of stroke tailored to different availability of risk factors and still obtain valid measures of risk even in the simplest form of the model, with increasing performance of the model following increasing complexity. The methods chosen which separate this model from previous models (competing risk and stepwise approach) should be considered for future risk estimation models

The GATA1s isoform is normally down-regulated during terminal haematopoietic differentiation and over-expression leads to failure to repress MYB, CCND2 and SKI during erythroid differentiation of K562 cells

Background: Although GATA1 is one of the most extensively studied haematopoietic transcription factors little is currently known about the physiological functions of its naturally occurring isoforms GATA1s and GATA1FL in humans—particularly whether the isoforms have distinct roles in different lineages and whether they have non-redundant roles in haematopoietic differentiation. As well as being of general interest to understanding of haematopoiesis, GATA1 isoform biology is important for children with Down syndrome associated acute megakaryoblastic leukaemia (DS-AMKL) where GATA1FL mutations are an essential driver for disease pathogenesis. <p/>Methods: Human primary cells and cell lines were analyzed using GATA1 isoform specific PCR. K562 cells expressing GATA1s or GATA1FL transgenes were used to model the effects of the two isoforms on in vitro haematopoietic differentiation. <p/>Results: We found no evidence for lineage specific use of GATA1 isoforms; however GATA1s transcripts, but not GATA1FL transcripts, are down-regulated during in vitro induction of terminal megakaryocytic and erythroid differentiation in the cell line K562. In addition, transgenic K562-GATA1s and K562-GATA1FL cells have distinct gene expression profiles both in steady state and during terminal erythroid differentiation, with GATA1s expression characterised by lack of repression of MYB, CCND2 and SKI. <p/>Conclusions: These findings support the theory that the GATA1s isoform plays a role in the maintenance of proliferative multipotent megakaryocyte-erythroid precursor cells and must be down-regulated prior to terminal differentiation. In addition our data suggest that SKI may be a potential therapeutic target for the treatment of children with DS-AMKL

Foot pain and foot health in an educated population of adults: results from the Glasgow Caledonian University Alumni Foot Health Survey

Abstract Background Foot pain is common amongst the general population and impacts negatively on physical function and quality of life. Associations between personal health characteristics, lifestyle/behaviour factors and foot pain have been studied; however, the role of wider determinants of health on foot pain have received relatively little attention. Objectives of this study are i) to describe foot pain and foot health characteristics in an educated population of adults; ii) to explore associations between moderate-to-severe foot pain and a variety of factors including gender, age, medical conditions/co-morbidity/multi-morbidity, key indicators of general health, foot pathologies, and social determinants of health; and iii) to evaluate associations between moderate-to-severe foot pain and foot function, foot health and health-related quality-of-life. Methods Between February and March 2018, Glasgow Caledonian University Alumni with a working email address were invited to participate in the cross-sectional electronic survey (anonymously) by email via the Glasgow Caledonian University Alumni Office. The survey was constructed using the REDCap secure web online survey application and sought information on presence/absence of moderate-to-severe foot pain, patient characteristics (age, body mass index, socioeconomic status, occupation class, comorbidities, and foot pathologies). Prevalence data were expressed as absolute frequencies and percentages. Multivariate logistic and linear regressions were undertaken to identify associations 1) between independent variables and moderate-to-severe foot pain, and 2) between moderate-to-severe foot pain and foot function, foot health and health-related quality of life. Results Of 50,228 invitations distributed, there were 7707 unique views and 593 valid completions (median age [inter-quartile range] 42 [31–52], 67.3% female) of the survey (7.7% response rate). The sample was comprised predominantly of white Scottish/British (89.4%) working age adults (95%), the majority of whom were overweight or obese (57.9%), and in either full-time or part-time employment (82.5%) as professionals (72.5%). Over two-thirds (68.5%) of the sample were classified in the highest 6 deciles (most affluent) of social deprivation. Moderate-to-severe foot pain affected 236/593 respondents (39.8%). High body mass index, presence of bunions, back pain, rheumatoid arthritis, hip pain and lower occupation class were included in the final multivariate model and all were significantly and independently associated with moderate-to-severe foot pain (p < 0.05), except for rheumatoid arthritis (p = 0.057). Moderate-to-severe foot pain was significantly and independently associated lower foot function, foot health and health-related quality of life scores following adjustment for age, gender and body mass index (p < 0.05). Conclusions Moderate-to-severe foot pain was highly prevalent in a university-educated population and was independently associated with female gender, high body mass index, bunions, back pain, hip pain and lower occupational class. Presence of moderate-to-severe foot pain was associated with worse scores for foot function, foot health and health-related quality-of-life. Education attainment does not appear to be protective against moderate-to-severe foot pain